The Impact of a Stochastic Parameterization Scheme on Climate Sensitivity in EC-Earth.

Stochastic schemes, designed to represent unresolved subgrid-scale variability, are frequently used in short and medium-range weather forecasts, where they are found to improve several aspects of the model. In recent years, the impact of stochastic physics has also been found to be beneficial for the model's long-term climate. In this paper, we demonstrate for the first time that the inclusion of a stochastic physics scheme can notably affect a model's projection of global warming, as well as its historical climatological global temperature. Specifically, we find that when including the "stochastically perturbed parametrization tendencies" (SPPT) scheme in the fully coupled climate model EC-Earth v3.1, the predicted level of global warming between 1850 and 2100 is reduced by 10% under an RCP8.5 forcing scenario. We link this reduction in climate sensitivity to a change in the cloud feedbacks with SPPT. In particular, the scheme appears to reduce the positive low cloud cover feedback and increase the negative cloud optical feedback. A key role is played by a robust, rapid increase in cloud liquid water with SPPT, which we speculate is due to the scheme's nonlinear interaction with condensation.

Intrinsic material property differences in bone tissue from patients suffering low-trauma osteoporotic fractures, compared to matched non-fracturing women.

Osteoporotic (low-trauma) fractures are a significant public health problem. Over 50% of women over 50yrs. of age will suffer an osteoporotic fracture in their remaining lifetimes. While current therapies reduce skeletal fracture risk by maintaining or increasing bone density, additional information is needed that includes the intrinsic material strength properties of bone tissue to help develop better treatments, since measurements of bone density account for no more than ~50% of fracture risk. The hypothesis tested here is that postmenopausal women who have sustained osteoporotic fractures have reduced bone quality, as indicated with measures of intrinsic material properties compared to those who have not fractured. Transiliac biopsies (N=120) were collected from fracturing (N=60, Cases) and non-fracturing postmenopausal women (N=60, age- and BMD-matched Controls) to measure intrinsic material properties using the nano-indentation technique. Each biopsy specimen was embedded in epoxy resin and then ground, polished and used for the nano-indentation testing. After calibration, multiple indentations were made using quasi-static (hardness, modulus) and dynamic (storage and loss moduli) testing protocols. Multiple indentations allowed the median and variance to be computed for each type of measurement for each specimen. Cases were found to have significantly lower median values for cortical hardness and indentation modulus. In addition, cases showed significantly less within-specimen variability in cortical modulus, cortical hardness, cortical storage modulus and trabecular hardness, and more within-specimen variability in trabecular loss modulus. Multivariate modeling indicated the presence of significant independent mechanical effects of cortical loss modulus, along with variability of cortical storage modulus, cortical loss modulus, and trabecular hardness. These results suggest mechanical heterogeneity of bone tissue may contribute to fracture resistance. Although the magnitudes of differences in the intrinsic properties were not overwhelming, this is the first comprehensive study to investigate, and compare the intrinsic properties of bone tissue in fracturing and non-fracturing postmenopausal women.

Relationship of CD146 expression to activation of circulating T cells: exploratory studies in healthy donors and patients with connective tissue diseases.

The endothelial cell adhesion molecule, CD146, is expressed on ≈ 2% of normal circulating T cells, correlating with T cell activation, endothelial interactions and T helper type 17 (Th17) effector functions. In this study, we have characterized CD146 expression in circulating T cells from healthy controls and patients with stable, well-controlled autoimmune connective tissue diseases (CTDs). In vitro, anti-CD3/anti-CD28 stimulation induced CD146 expression in both CD4 and CD8 T cells. In healthy controls and CTD patients, CD146 was associated with expression of recent and chronic activation markers (CD25(+), OX-40(+), CD69(+), CD27(-)) and was confined to CD45RO(+)/RA(-)/CD28(+) populations within the CD4 subset. Except for CD69, these markers were not associated with CD146 in the CD8 subset. Surprisingly, most CTD patients exhibited no T cell hyperactivation ex vivo. In five of five patients with secondary Sjögren's syndrome circulating T cells appeared activated despite therapy, and CD146 up-regulation, associated with activation markers, was observed both on CD4 and CD8 T cells. There was no association between CD146 and putative pro-atherogenic T cell subsets. In conclusion, the relationship of CD146 expression to T cell activation differs between T cell subsets in healthy subjects and correlates with systemic hyperactivity, where present, in patients with CTDs, as exemplified by the patients with secondary Sjögren's syndrome in this study.

cAMP response element-binding protein content is a molecular determinant of smooth muscle cell proliferation and migration.

We hypothesized that cAMP response element-binding protein (CREB) could function as a molecular determinant of smooth muscle cell fate. In arterial sections from the systemic and pulmonary circulation, CREB content was high in proliferation-resistant medial subpopulations of smooth muscle cells and low in proliferation-prone regions. In vessels from neonatal calves exposed to chronic hypoxia, CREB content was depleted and smooth muscle cell (SMC) proliferation was accelerated. Induction of quiescence by serum deprivation in culture led to increased CREB content. Highly proliferative SMC in culture were observed to have low CREB content. Exposure to proliferative stimuli such as hypoxia or platelet-derived growth factor decreased SMC CREB content. Assessment of CREB gene transcription by nuclear run-on analysis and transcription from a CREB promoter-luciferase construct indicate that CREB levels in SMC are in part controlled at the level of transcription. Overexpression of wild type or constitutively active CREB in primary cultures of SMC arrested cell cycle progression. Additionally, expression of constitutively active CREB decreased both proliferation and chemokinesis. Consistent with these functional properties, active CREB decreased the expression of multiple cell cycle regulatory genes, as well as genes encoding growth factors, growth factor receptors, and cytokines. Our data suggest a unique mode of cellular phenotype determination at the level of the nuclear content of CREB.

Diabetes-related changes in cAMP response element-binding protein content enhance smooth muscle cell proliferation and migration.

We hypothesized that diabetes and glucose-induced reactive oxygen species lead to depletion of cAMP response element-binding protein (CREB) content in the vasculature. In primary cultures of smooth muscle cells (SMC) high medium glucose decreased CREB function but increased SMC chemokinesis and entry into the cell cycle. These effects were blocked by pretreatment with the antioxidants. High glucose increased intracellular reactive oxygen species detected by CM-H(2)DCFA. SMC exposed to oxidative stress (H(2)O(2)) demonstrated a 3.5-fold increase in chemokinesis (p < 0.05) and accelerated entry into cell cycle, accompanied by a significant decrease in CREB content. Chronic oxidative challenge similar to the microenvironment in diabetes (glucose oxidase treatment) decreases CREB content (40-50%). Adenoviral-mediated expression of constitutively active CREB abolished the increase in chemokinesis and cell cycle progression induced by either high glucose or oxidative stress. Analysis of vessels from insulin resistant or diabetic animals indicates that CREB content is decreased in the vascular stroma. Treatment of insulin-resistant animals with the insulin sensitizer rosiglitazone restores vessel wall CREB content toward that observed in normal animals. In summary, high glucose and oxidative stress decrease SMC CREB content increase chemokinesis and entry into the cell cycle, which is blocked by antioxidants or restoration of CREB content. Thus, decreased vascular CREB content could be one of the molecular mechanisms leading to increased atherosclerosis in diabetes.

Gas chromatography-mass spectrometry method for the simultaneous determination of wood extractive compounds in quaking aspen.

We have developed a rapid gas chromatography-mass spectrometry (GC-MS) method for the detailed compositional analysis of 70 underivatized wood extractive components present in quaking aspen (Populus tremuloides Michx.). Forty-four compounds were unequivocally identified by retention time and mass spectral comparison with standards. An additional 26 chromatographic peaks were assigned to broad chemical classes using retention time and mass spectra features. The results were compared to the respective tert.-butyldimethylsilyl derivatized wood extractives profile, and it was determined that derivatization was unnecessary for the GC-MS analysis of the target compounds.

A prospective human clinical trial of Endopore dental implants in restoring the partially edentulous maxilla using fixed prostheses.

This is the first report of a group of 50 partially edentulous patients who received a total of 151 Endopore dental implants in the maxilla. A mean implant length of 8.7 mm was used, and 76.8% of implants were placed in the posterior maxilla. At re-entry, all implants appeared to be osseointegrated and were used to support fixed prostheses. Approximately half of the crowns (57%) in these prostheses were splinted to one another, while the remainder (43%) were not. At the time of this report, the mean functional time was 34.6 months and the cumulative survival rate was 97.3% (4 implants had failed). Analysis of carefully standardized sequential radiographs indicated no significant changes in mean crestal bone levels between baseline and any of the examination times (after 6 months, 1 year, and 2 years in function). There were no detectable correlations between crestal bone loss and the factors implant length (7, 9, or 12 mm); implant diameter (3.5, 4.1, or 5.0 mm); implant position anteriorly or posteriorly in the maxilla; or whether or not the implant-supported crowns were splinted.

Transoral, flexible endoscopic suturing for treatment of GERD: a multicenter trial.

BACKGROUND: A totally transoral outpatient procedure for the treatment of GERD would be appealing. METHODS: A multicenter trial was initiated that included 64 patients with GERD treated with an endoscopic suturing device. Inclusion criteria were 3 or more heartburn episodes per week while not taking medication, dependency on antisecretory medicine, and documented acid reflux by pH monitoring. Exclusion criteria were dysphagia, grade 3 or 4 esophagitis, obesity, and hiatus hernia greater than 2 cm in length. Patients underwent manometry, endoscopy, 24-hour pH monitoring, and symptom severity scoring before and after the procedure. Patients were randomized to a linear or circumferential plication configuration. Adverse procedural events were recorded. RESULTS: Mean 6-month symptom score changes demonstrated procedural efficacy. Heartburn severity and frequency as well as regurgitation all improved (p > 0.0001 for each). Twenty-four-hour pH monitoring showed improvement in number of episodes below pH of 4 at 3 and 6 months (p < 0.0007 and 0.0002) and percentage of total time the pH was less than 4 at 6 months (p < 0.011). Plication configuration did not affect symptoms or pH monitoring results. One patient had a self-contained suture perforation that was successfully treated with antibiotics. CONCLUSION: Endoscopic gastroplasty is safe. It is associated with reduced symptoms and medication use at 6 month follow-up in patients with uncomplicated GERD.

Role of cyclin-dependent kinase inhibitors in the growth arrest at senescence in human prostate epithelial and uroepithelial cells.

Cellular senescence has been proposed to be an in vitro and in vivo block that cells must overcome in order to immortalize and become tumorigenic. To characterize these pathways, we focused on changes in the cyclin-dependent kinase inhibitors and their binding partners that underlie the cell cycle arrest at senescence. As a model, we utilized normal human prostate epithelial cell (HPEC) and human uroepithelial cell (HUC) cultures. After 30-40 population doublings cells became growth-arrested in G0/1 with a threefold decrease in Cdk2-associated activity, a point defined as pre-senescence. Temporally following this growth arrest, the cells develop a senescence morphology and express senescence-associated beta-galactosidase (SA-beta-gal). Levels of p16(INK4a) and p57(KIP2) rise in HUCs during progressive passages, whereas only p16 increases in HPEC cultures. The induced expression of p57, similar to p16, produces a senescent-like phenotype. pRB, cyclin D, p19(INK4d) and p27(KIP1) decrease in both cell types. We find that p53, p21(CIP1) and p15(INK4b) are transiently elevated in HPECs and HUCs at the pre-senescent growth arrest, then return to low proliferating levels at terminal senescence. Analysis of p53, p21(CIP1), p15(INK4b), p16(INK4a), and p57(KIP2) reveals altered expression in immortalized, non-tumorigenic HPV16 E6 and E7 prostate lines and in tumorigenic prostate cancer cells. These results indicate: (i) the existence of a subset of growth inhibiting genes elevated at the onset of the senescence, (ii) a distinct class of genes involved in the maintenance of senescence, and (iii) the frequent inactivation of these pathways during immortalization.

Adhesion of bonded orthodontic attachments to dental amalgam: In vitro study.

Bonding orthodontic attachments to molars is difficult in the presence of extensive buccal amalgam restorations. The purposes of this study were (1) to examine different amalgam surface preparations, (2) to examine properties of adhesive cements to amalgam, (3) to determine the most shear-resistant bonding technique and (4) to discuss whether these shear bond strengths were of adequate magnitude to be of clinical acceptability. The sample consisted of 108 standardized amalgam cylinders divided into 9 groups of 12 based on surface treatment technique and resin type. SPEED brackets (Strite Industries, Cambridge, Ontario) were bonded to amalgam surfaces that were either polished, sandblasted with 50 microm aluminium oxide, or chemically corroded. Adhesives used were Phase II (Reliance Orthodontic Products Inc, Itasca, Ill), Panavia EX (J Morita USA Inc, Tustin, Calif), or C & B Metabond (Parkell, Farmingdale, NY). After thermocycling from 10 degrees C to 50 degrees C 10,000 times, all samples were tested for shear bond strength with the Universal Testing Machine (Instron Corporation, Canton, Mass). The results show significantly higher bond strengths for all of the resin systems when sandblasting of the amalgam surface is used (P <.0001). Only Panavia EX bonded strongly to polished samples, suggesting the presence of a chemical bond. Laboratory acceptable bond strengths to amalgam are possible. The surface characteristics of the amalgam appear to be more influential in the strength of the bond than does the nature of the resin.

Entrapment of the index flexor digitorum profundus tendon after fracture of both forearm bones in a child.

Entrapment of the index FDP tendon in a radius fracture callus occurred after fracture of both forearm bones in a 4-year-old boy. Surgical release of the FDP tendon, three months after fracture, resulted in normal index finger motion. This clinical problem can be avoided by a detailed physical examination of children with forearm fractures, verifying full passive range-of-motion of the hand after cast immobilization. Prompt supervised active range-of-motion should be done to prevent adhesions at the fracture site.

The Endopore implant-enhanced osseointegration with a sintered porous-surfaced design.

The Endopore implant provides a novel method for reliable fixation of endosseous dental implants within the bone. Through the use of a porous-surfaced zone formed by sintering Ti alloy particles of the appropriate size and under appropriate processing conditions to a sold Ti alloy core of desired shape (tapered truncated cone), an implant is now available that can be placed using a relatively simple surgical procedure using either surgical burs or hand osteotomes. Of even greater value is the suitability of this implant design for treatment of cases that because of minimal bone height cannot be treated routinely using other currently-available implants. The high success rates experienced with significantly shorter implant lengths compared with other designs indicate the appropriateness of this system for difficult-to-treat cases. The Endopore system represents the next generation of endosseous dental implants characterized by uncomplicated and reliable treatment for a wider range of dentally-compromised patients. Its history is founded on extensive and fully-documented research at the human preclinical stage as well as human use experiences. The results during the past nine years have confirmed the high expectations that those early studies suggested.

Use of the Endopore dental implant to restore single teeth in the maxilla: protocol and early results.

This report outlines the experimental, surgical, and prosthodontic protocols for a prospective clinical trial using the Endopore dental implant to replace single maxillary teeth. Twenty patients (10 male, 10 female) ranging in age from 30 to 60 years each received one implant (mean length 10.1 mm), which, after an initial healing period of 4 months, was restored with a single crown. Records collected included radiographs, Periotest mobility measurements, supragingival Plaque Index, and an assessment of peri-implant soft tissue health using pocket probing depths, sulcular bleeding following probing, and probing attachment levels. Radiographs were exposed at predetermined intervals following crown placement (1 and 6 months, and then yearly) in a standardized procedure using a specialized filmholder that attaches to each implant after removal of the crown. At the time of this preliminary report, all of the 20 implants placed had been uncovered and were in function; 16 of the implants had been in function for 6 months or more, 14 had passed 1 year of function, and 3 had passed the 2-year function point. There have been no failures to date.

Comparison of a rapid dipstick test and thick blood films for detecting parasites of plasmodium falciparum used under typical conditions at a semi-rural hospital in Cote d'Ivoire.

This prospective study compares a rapid dipstick test (ParaSight-F) with thick blood films for the detection of parasites of P falciparum, under 'typical' conditions and constraints to be found in a semi-rural hospital in a tropical developing country in Africa. Eighty-two samples were tested using the two techniques and found to concur in 95.1% of cases. However, in four of the samples the results differed. The thick blood films of 60 samples were later re-read by a local reference laboratory. Of these 98.3% were in agreement with the reading performed at the hospital. Only one of the 60 slides differed. The rapid dipstick test proved to be both easy to use and free from many of the usual constraints such as a need for formally trained or experienced laboratory staff, laboratory equipment, and reliable water and electricity supplies. In an holoendemic area for P falciparum transmission, it would appear to be eminently suitable, in technical terms and ease of handling as well as on the basis of rapid results, for wider distribution within this region. Its main drawback remains financial.

Modifications to the National Dental Examining Board of Canada's certification process.

Following a lengthy and intense consultation with stakeholders, and an analysis of the present certification process, the National Dental Examining Board of Canada (NDEB) and the 10 provincial licensing authorities recently approved major changes to the certification process for dental licensure in Canada. As of January 1997, graduates of dental programs accredited by the American Dental Association's Commission on Dental Accreditation (ADA Commission) must complete successfully the same examinations as graduates of programs accredited by the Commission on Dental Accreditation of Canada (CDAC) to be licensed to practice in Canada. In addition, NDEB's examination system for graduates of dental programs that are not accredited by CDAC or the ADA Commission (i.e. international programs) will be discontinued on December 31, 1999. As of January 1, 2000, graduates of non-accredited programs will be required to complete a CDAC accredited, university-based qualifying program to be eligible to participate in the same certification process as graduates of ADA Commission and CDAC accredited dental programs.

Development and manufacture of prosthodontic components: do we need changes?

PURPOSE: Prosthodontic components for implant treatment have been developed with minimal reported scientific investigation. This paper aims to highlight a number of problems caused by this approach to the development and marketing of prosthodontic components and to suggest solutions. CONCLUSION: Prosthodontic components must be developed with a scientific approach that involves both laboratory and clinical testing so as to optimize treatment outcomes in the future.

Isozyme-dependent sensitivity of adenylyl cyclases to P-site-mediated inhibition by adenine nucleosides and nucleoside 3'-polyphosphates.

Recombinant adenylyl cyclase isozyme Types I, II, VI, VII, and three splice variants of Type VIII were compared for their sensitivity to P-site-mediated inhibition by several adenine nucleoside derivatives and by the family of recently synthesized adenine nucleoside 3'-polyphosphates (Désaubry, L., Shoshani, I., and Johnson, R. A. (1996) J. Biol. Chem. 271, 14028-14034). Inhibitory potencies were dependent on isozyme type, the mode of activation of the respective isozymes, and on P-site ligand. For the nucleoside derivatives potency typically followed the order 2',5'-dideoxyadenosine (2',5'-ddAdo) > beta-adenosine > 9-(cyclopentyl)-adenine (9-CP-Ade) >/= 9-(tetrahydrofuryl)-adenine (9-THF-Ade; SQ 22,536), with the exception of Type II adenylyl cyclase, which was essentially insensitive to inhibition by 9-CP-Ade. For the adenine nucleoside 3'-polyphosphates inhibitory potency followed the order Ado < 2'-dAdo < 2',5'-ddAdo and 3'-mono- < 3'-di- < 3'-triphosphate. Differences in potency of these ligands were noted between isozymes. The most potent ligand was 2',5'-dd-3'-ATP with IC50 values of 40-300 nM. The data demonstrate isozyme selectivity for some ligands, suggesting the possibility of isozyme-selective inhibitors to take advantage of differences in P-site domains among adenylyl cyclase isozymes. Differential expression of adenylyl cyclase isozymes may dictate the physiological sensitivity and hence importance of this regulatory mechanism in different cells or tissues.

Septic arthritis caused by chronic osteomyelitis.

We have treated four cases of previously quiescent osteomyelitis which presented as septic arthritis in an adjacent joint. The osteomyelitic focus was in the bone proximal to the involved joints (zero to ten centimeters above the joint line). Based on the presenting history, physical findings, laboratory tests and cultures of joint fluids, the joint sepsis was low grade in all patients which led to delays in diagnosis and treatment. Aggressive surgical debridement of both bone and joint, followed by a prolonged course of antibiotics led to resolution in all patients. A high index of suspicion combined with adequate radiographs of the surrounding bones should lead to the appropriate diagnosis and treatment.