text:
Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus
DOI: 10.1186/ar4399
© Bäck et al.; licensee BioMed Central Ltd. 2013
Received: 25 July 2013
Accepted: 12 November 2013
Published: 4 December 2013
Patients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE.
Fibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters.
Fibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT.
Activation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.
Patients with the autoimmune disease systemic lupus erythematosus (SLE) have a drastically increased risk of thrombotic events, which are a major cause of morbidity and mortality in these patients. Despite the improved overall survival in patients with SLE over the last few decades, the risk of death in vascular disease (VD) has not decreased[1]. Traditional cardiovascular risk factors can only partly explain this increased risk of VD in SLE[2], and it is likely that inflammatory mechanisms are also involved. The fact that the pathogenic mechanisms involved are not fully understood has contributed to a lack of reliable laboratory parameters for evaluating the risk of thrombotic events.
The contact system, which consists of factor (F) XII, FXI, prekallikrein, and high molecular weight kininogen (HK), is a plasma protease cascade that, when activated, initiates the intrinsic pathway of coagulation (Additional file1: Figure S1). It has been considered to be of lesser importance for hemostasis, since a deficiency in FXII does not cause any bleeding disorders[3]. Instead, a pathophysiological role for FXII in thrombosis was proposed after FXII-deficient mice were shown to be defective in thrombus formation in arterial beds[4]. FXII and HK have also been shown to bind to and initiate contact activation on endothelial cells via the C1q receptor for globular heads, the urokinase plasminogen activator receptor, and cytokeratin 1[5–7].
Recently, we demonstrated that activated human platelets trigger FXII-mediated contact activation[8]. These results, combined with the observation that patients with SLE have persistent platelet activation[9–11], led us to hypothesize that the contact system is involved in inflammation and thrombotic conditions associated with SLE. Kallikrein genes have been shown to be associated with glomerular basement membrane-specific, antibody-induced nephritis in mice and with lupus nephritis in humans[12, 13], supporting the possible involvement of the contact system. A reduction in FXII plasma levels occurs in SLE patients, concomitant with the appearance of anti-FXII antibodies[14, 15], further corroborating a role for the contact system in SLE.
The proteases of the contact system circulate in the blood as zymogens, and after contact activation have been initiated and enzyme activity has occurred, the enzymes quickly form complexes with their inhibitors, making it very difficult to measure free contact enzymes in plasma (Additional file1: Figure S1). Antithrombin (AT) and C1 inhibitor (C1INH) are members of the serpin protein family[16]. AT is the main inhibitor of the coagulation cascade and inhibits thrombin, FXa, FIXa, et cetera. Its activity is regulated by the glycosaminoglycan (GAG) heparin, which contains a pentasaccharide with a specific sequence of sulfated monosaccharides that upon binding to AT augments the antithrombin activity up to 300-fold. Heparin is present in mast cells and basophilic granulocytes and in the form of heparan sulfate on endothelial cells, but heparin is not available in blood or during blood clotting. In contrast to previous reports stating that FXIIa is mainly inhibited by C1INH, we have shown that the FXII activation triggered by activated platelets and during clot formation is regulated by AT. Only FXII activated by other surfaces (such as artificial material surfaces) is regulated by C1INH[17], which suggests that there is a physiological heparin-like mechanism by which AT is regulated during blood clotting.
In the present study, we investigated the contact system activation in SLE patients by quantifying complexes formed between contact activation enzymes and the serpins AT and C1INH in blood plasma. These complexes were evaluated with regard to their potential correlation with clinical data and with markers of platelet, coagulation, and complement activation. Our primary objective was to determine whether the contact system is activated in SLE patients and, based on our previous studies, to determine whether FXIIa-AT complexes might serve as a new potential biomarker for platelet activation and VD in SLE.
During routine clinical visits to the Department of Rheumatology at Skåne University Hospital (Lund, Sweden), 69 SLE patients were recruited for blood sampling and laboratory analyses. All patients fulfilled at least four American College of Rheumatology (ACR) classification criteria for SLE[18]. Patients with a known history of VD were preferentially selected, such that 45% of the 69 SLE patients had a history of VD, defined in this study as one or more previous episodes of either myocardial infarction, arterial thrombosis (12/13 with cerebrovascular incidents), or venous thrombosis (pulmonary embolism or deep venous thrombosis), as defined by the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index[19]. The median time between blood sampling and the last VD event was 8 years. An overview of the clinical characteristics at the time of blood sampling is presented in Additional file2: Table S1[20]. Healthy age- and sex-matched volunteers with no history of VD served as controls (n = 68). All of the patients and the controls were Caucasians, except for two individuals of Asian origin among the controls and one individual of Asian and two of Hispanic origin among the SLE patients. Autoantibodies and complement levels in serum were measured according to routine analytic protocols used at the Department of Clinical Immunology, Skåne University Hospital, Lund, Sweden.
Ethical permission
The study was approved by the regional ethics board at Lund University (LU 378–02). All patients have given written consent to the study.
Preparation of blood
Fresh human blood, obtained from healthy volunteers who had received no medication for at least 10 days, was collected in vacutainer tubes containing either citrate, ethylenediaminetetraacetic acid (EDTA) (BD Biosciences, San Jose, CA, USA) or lepirudin (added to a final concentration of 50 μg/mL; Schering AG, Berlin, Germany). Blood was centrifuged at 150 × g for 15 minutes at room temperature (RT) to produce platelet-rich plasma (PRP) and twice at 2200 × g for 15 min to produce platelet-poor plasma (PPP). The plasma was stored at -70°C.
Detection of P-selectin, platelet intracellular proteins, and platelet-leukocyte complexes
P-selectin (CD62P) exposed on the surface of platelets, IFN-induced transmembrane protein 1 (IFITM1) and protein kinase, IFN-inducible double stranded RNA dependent activator (PRKRA), and platelet-leukocyte complexes were detected by flow cytometry as previously described by Lood et al.[20].
The following parameters were measured in EDTA plasma as previously described: FXIIa-C1INH, FXIa-C1INH, FXIIa-AT, FXIa-AT[21], thrombospondin-1 (TSP-1), and thrombin-antithrombin (TAT)[17].
Plasma protein concentration
C1q, C3 and C4 were measured by nephelometry (Immage, Beckman-Coulter Inc, Hialeach, FL, USA).
Activation of FXII by fibrin clots
Fifty mIU of thrombin (Hoffmann-La Roche, Basel, Switzerland) was incubated with 0.09, 0.4, or 0.7 μg of fibrinogen (Haemochrom Diagnostica, Mölndal, Sweden) for 10 minutes at 37°C at the bottom of polypropylene tubes. The resulting clots were referred to as having high (H), intermediate (I), and low (L) thrombin/fibrinogen ratios.
Quantification of purified FXIIa activity by chromogenic assays
The fibrin clots were immediately incubated with 20 μL of the specific thrombin inhibitor, lepirudin (Schering AG, Berlin, Germany, 2.5 mg/mL) for 10 minutes at 37°C. Thereafter, 1 μg of purified FXII (Enzyme Research Laboratories, Swansea, UK) in 100 μL Tris buffer (50 mM Tris, 175 mM NaCl, 7.5 mM EDTA, pH 8.4) was added to the fibrin clots and incubated for an additional 10 minutes at 37°C: 100 μL of S-2302 (2.5 mM) and S-2238 (1 mM) (both from Haemochrom Diagnostica) was added separately and incubated for 5 minutes at 37°C. The reaction was stopped by adding 100 μL of 20% citric acid, and the absorbance at 405 nm was measured in the supernatant after centrifugation at 2200 × g for 2 minutes.
Quantification of FXIIa-serpin complexes in whole blood
Lepirudin-anticoagulated whole blood (700 μL), PRP (350 μL), or PPP (350 μL) from five different donors were added to the fibrin clots. The PPP samples were incubated for 30 minutes, and the others were incubated for 15 minutes, all at 37°C. The experiments with whole lepuridin-anticoagulated blood were also repeated in the presence of 5 μM (final blood concentration) of the low molecular weight thrombin inhibitor Melagatran (Astra Zeneca, Gothenburg, Sweden), which was added to the fibrin clots 5 minutes before the addition of the blood.
Activation of FXII induced by glass
Citrate anti-coagulated PPP (350 μL) from six different donors was incubated in glass tubes (borosilicate glass 10 × 75 mm, Kimble-Kontes, Vineland, NJ, USA), with and without the addition of calcium chloride (CaCl2) at a final concentration of 10 mM, for 30 minutes at 37°C. The reaction was blocked by adding EDTA to the samples to give a final plasma concentration of 10 mM. All samples were centrifuged at 2200 × g for 15 minutes at 4°C, and the plasma obtained was stored at -70°C until analyzed for FXII- and FXI-serpin complexes.
Electrophoresis and western blotting
Fibrinogen (Haemochrom Diagnostica) or increasing concentrations (0.025 to 33.0 μg/mL) of thrombin (Hoffmann-La Roche) were incubated with purified human FXII (Enzyme Research Laboratories, 2.5 μg/mL) for 15 minutes at 37°C. The proteins were analyzed by SDS-PAGE (10% gels) under reducing conditions followed by either staining with Coomassie brilliant blue or western blotting as previously described[22]. The polyvinylidene fluoride (PVDF) membranes were incubated with sheep anti-human FXII (the binding site) diluted 1:250. The membranes were then incubated with horseradish peroxidase (HRP)-conjugated anti-sheep Ig (Dako, Glostrup, Denmark) diluted 1:500 and developed with diaminobenzidine (Sigma-Aldrich, St Louis, MO, USA).
Statistical analyses
Non-parametric statistical analyses as indicated in the figure legends were performed using the commercial program GraphPad Prism Version 4 (GraphPad Software, Inc., San Diego, CA, USA). Data in the text section are presented as medians and interquartile ranges. P-values <0.05 were considered significant and in the figures are presented as * = P <0.05, ** = P <0.01 or *** = P <0.0001.
Fibrin activates FXII into FXIIa
Fibrin clots were produced at the bottom of plastic tubes, and these pre-made clots were incubated with purified FXII or with blood containing lepirudin. In the purified system, we observed significant FXII activation induced by the fibrin network as assessed by the chromogenic substrate S-2302 (Figure 1A). As the sensitivity and specificity of substrate S-2238 for thrombin is considerably higher than that of S-2302 for FXIIa, the low enzymatic thrombin activity detected with the chromogenic substrate S-2238 is overestimated, and confirmed that the cleavage of S-2302 originated from activated FXII.
The fibrin clots caused a significant generation of FXIIa-AT and FXIa-AT in PPP, PRP, and whole blood, with the highest levels in whole blood (Figure 1B-C), whereas the corresponding C1INH complexes were not detectable (not shown). The generation of AT complexes demonstrated that activation of FXII occurred in the blood/plasma systems and that AT was the preferred regulator. It also indicated that the activation proceeded to FXI, as thrombin in the presence of lepirudin could not contribute to FXI activation. Fibrinogen alone did not induce AT complexes, and purified thrombin alone triggered only a minor generation in whole blood.
To further certify that any remaining thrombin did not lead to FXII activation, lepirudin inhibition was complemented with the low molecular weight thrombin-inhibitor Melagatran, which is able to better penetrate the fibrin clots. Still, no difference in FXIIa generation was observed (data not shown). We also incubated purified human FXII in the presence of increasing concentrations of thrombin without observing any cleavage of FXII by SDS-PAGE and/or western blot analysis (data not shown).
Fibrin promotes AT inhibition of activated FXII
Levels of FXIIa-serpin complexes in SLE patients and healthy controls
Altered levels of FXIIa-serpin complexes are associated with previous thrombotic events in SLE patients
We also compared patients with a history of anti-phospholipid antibody syndrome (APS) to those without APS[23]. Patients with APS exhibited a tendency toward lower levels of FXIIa-C1INH and higher levels of FXIIa-AT than did those without APS (not significant).
The generation of FXIIa-AT is strongly linked with activated platelets
The plasma levels of C1q, C3, and C4, which are an indirect and insensitive mirror of complement activation and immune complex disease, were not correlated to any of the FXIIa-AT or FXIIa-C1INH complexes. No association was found between the FXIIa-serpin complexes and the systemic lupus erythematosus disease activity index (SLEDAI) at the time the samples were drawn.
Except for patients treated with warfarin, which tended to exhibit the highest levels of FXIIa-AT, we observed no association between any of the AT and C1INH complexes and any of the other most frequently used treatments or with other disease manifestations, such as glomerulonephritis or arthritis (data not shown). It should be noted that all of the warfarin-treated patients exhibited previous thrombosis except for six patients who all had very low levels of FXIIa-AT, which reflects that warfarin lowers the risk of thrombosis, and thereby decreases the FXIIa-AT levels.
The alterations in the levels of FXIIa-serpin complexes points to new biomarkers for VD risk evaluation in SLE patients
FXIIa-serpin complexes and aCL antibodies in association with VD in SLE patients
VD-, n (%)
VD+, n (%)
P-value a
38 (55)
31 (45)
FXIIa-C1INH <0.01 nMb
14 (37)
24 (77)
8.9 (2.8, 28.5)
FXIIa-AT >0.40 nMc
4 (11)
13 (42)
6.1 (1.7, 21.6)
Both low FXIIa-C1INH
1 (3)
12 (39)
23.4 (2.8, 194)
and high FXIIa-AT
aCL antibodies
12 (32)
15 (48)
2.0 (0.8, 5.4)
We have previously shown that activation of platelets induces activation of FXII that is regulated by AT, which is reflected by the formation of large amounts of FXIIa-AT and FXIa-AT complexes in clotted blood[8, 17]. In the present work, we demonstrate that fibrin formation is an essential mechanism that drives the activation of FXII and the subsequent formation of FXIIa-AT complexes. We also found that an SLE patient group enriched in patients with previous VD exhibited altered levels of FXIIa-complexes when compared with healthy controls and that increased levels of FXIIa-AT and decreased levels of FXIIa-C1INH were associated with VD and previous thrombotic events. These results are in line with recent data indicating an important role of FXII in thrombus formation.
In the present study, we asked whether fibrin clots could trigger FXII activation and if so, how it was regulated. Preformed fibrin clots were shown to activate purified FXII, and when incubated in blood, there was a substantial generation of both FXIIa-AT and FXIa-AT complexes, similar to what we previously have shown to occur in clotting blood. Thrombin cannot activate FXII, and with the simultaneous use of the antithrombin compounds melagatran and lepirudin, we verified that activation of FXII was not mediated by thrombin. These findings are consistent with a recent study demonstrating that fibrin binds FXII and α-FXIIa[24]. Complementing these findings, our data obtained using chromogenic substrates and measuring FXIIa-AT complexes, demonstrate that FXII is specifically activated by the preformed fibrin clots.
We also observed a reciprocal relationship between the generation of FXIIa-AT and FXIIa-C1INH complexes in plasma if fibrin generation and clotting were triggered in vitro. Fibrin formation promoted the generation of AT complexes and seemed to increase the affinity, or the accessibility, of AT for FXIIa and FXIa, competing out C1INH and leading to the generation of FXIIa-AT and FXIa-AT complexes. Thus, fibrin seems to act as a physiological heparin-like co-factor.
In previous studies, we and others, have shown that platelet activation and an increased generation of fibrin continuously occurs in vivo in SLE, particularly in those patients with a history of VD[9, 22, 25, 26]. Given the strong association between FXIIa-AT levels in plasma and platelet activation in vitro[8, 17], we expected to find increased levels of these complexes in SLE patients, with the highest levels in those with VD. When SLE patients with and without a history of VD were compared, we found significantly increased levels of FXIIa-AT in those who had VD. Higher levels of FXIIa-AT were found particularly in those patients with previous venous and arterial thrombosis. With the exception of the previously reported IFITM1 and PRKRA in platelets[20], none of the other markers of platelet activation that we examined allowed us to differentiate between the patients with previous VD and those without. A history of previous anti-cardiolipin antibodies was also uninformative.
Similar to the situation in the in vitro experiments, the high FXIIa-AT levels in vivo were reciprocal to those of FXIIa-C1INH, which were decreased in the SLE patients and particularly in those with a history of thrombotic events, where in many cases no FXIIa-C1INH could be detected. The decrease in FXIIa-C1INH was corroborated by a report of a study that investigated patients with coronary heart disease and stroke[27]. In that study, patients with VD exhibited significantly lower levels of FXIIa-C1INH complexes, particularly in the case of smokers, than did controls. Based on our in vitro experiments where fibrin gave rise to a switch from FXIIa-C1INH to FXIIa-AT complexes (see above), the generation of soluble fibrin and microthrombi, which preferentially promote AT regulation of FXIIa, is a possible cause of the decreased FXIIa-C1INH levels.
Further support for a link between platelet-induced fibrin generation and the generation of AT complexes was that both FXII-AT and FXIa-AT but none of the C1INH complexes were correlated with several platelet parameters, for example, TSP-1, P-selectin exposure, platelet count, and platelet-leukocyte complexes. Moreover, FXIIa-AT levels were correlated with the two type I IFN-regulated proteins, IFITM1 and PRKRA, detected in platelets. The up-regulation of these two proteins in platelets has previously been shown to be associated with platelet activation and VD in SLE[20].
The levels of FXIIa-AT were strongly correlated with those of FXIa-AT in the SLE patients. This was also the case for the corresponding C1INH complexes. These results suggest that the regulation of the protease with AT or C1INH occurred under different circumstances. The results may indicate that the initial activation of FXII occurred at different sites, where clot formation may represent the milieu where AT complexes are formed. Similar to our in vitro experiments, we also observed a negative correlation between FXIIa-AT and FXIIa-C1INH complexes in the SLE patients. This further emphasizes different mechanisms of FXII activation and complex formation, and the likelihood that soluble fibrin or microthrombi may be the explanation for the altered ratios of FXIIa complexes. Furthermore, these in vivo data corroborate that fibrin possesses heparin-like AT co-factor activity.
Today, assessment of anti-cardiolipin antibodies and lupus anticoagulants is the state-of-the-art approach to evaluate the risk of thrombotic events in SLE patients[23]. Anti-phospholipid antibodies are linked to, but not strictly correlated with VD and thrombotic events, as is also reflected in the present but limited study. By itself, our analytic approach is not sufficiently specific and needs to be complemented with other analyses to produce an accurate assessment of the risk of future thrombotic events. FXIIa-serpin complexes, which were strongly associated with VD, may be emerging analyses for the future evaluation of the risk of thrombotic events in SLE patients. However, these analyses need to be validated in prospective studies before they can be used alone or in combination as a means for gauging the risk of thrombotic events in SLE.
This study shows that activation of the contact system is involved in the pathophysiology of SLE and that the activation of the contact system is likely to be triggered by fibrin. We show that the formation of FXIIa-AT complexes is associated with thrombotic events and that generation of these complexes represents a promising potential biomarker for evaluation of the risk of thrombotic events in SLE.
Antiphospholipid antibody syndrome
C1 inhibitor
Ethylenediaminetetraacetic acid
Enzyme-linked immunosorbent assay: F, Factor
High molecular-weight kininogen
Immune complex
Type I interferon-induced transmembrane protein 1
Type I interferon
Myocardial infarction
Odds ratio
Platelet-poor plasma
Protein kinase IFN-inducible double-stranded RNA dependent activator
Platelet-rich plasma
Systemic lupus erythematosus
Systemic lupus erythematosus disease activity index
Vascular disease.
This study was supported by grants from the Swedish Research Council (2008–2201, 2009–4675 and 2013-65x-05647-34-4), the Swedish Rheumatism Association, the Gustav V foundation, the Medical Faculty at Lund University, Greta and Johan Kock's Foundation, King Gustaf V's 80th Birthday Foundation, Lund University Hospital, the Swedish Society of Medicine, and the Foundation of the National Board of Health and Welfare. We thank Graciela Elgue and Lillemor Funke-Stenbeck for their technical assistance and Deborah McClellan for editing the text.
Authors' Affiliations
- Bernatsky S, Boivin JF, Joseph L, Manzi S, Ginzler E, Gladman DD, Urowitz M, Fortin PR, Petri M, Barr S, Gordon C, Bae SC, Isenberg D, Zoma A, Aranow C, Dooley MA, Nived O, Sturfelt G, Steinsson K, Alarcón G, Senécal JL, Zummer M, Hanly J, Ensworth S, Pope J, Edworthy S, Rahman A, Sibley J, El-Gabalawy H, McCarthy T: Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006, 54: 2550-2557. 10.1002/art.21955.View ArticlePubMedGoogle Scholar
- Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, Côte R, Grover SA, Fortin PR, Clarke AE, Senécal JL: Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001, 44: 2331-2337. 10.1002/1529-0131(200110)44:10<2331::AID-ART395>3.0.CO;2-I.View ArticlePubMedGoogle Scholar
- Ratnoff OD, Margolius A: Hageman trait: an asymptomatic disorder of blood coagulation. Trans Assoc Am Physicians. 1955, 68: 149-154.PubMedGoogle Scholar
- Renne T, Pozgajova M, Gruner S, Schuh K, Pauer HU, Burfeind P, Gailani D, Nieswandt B: Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med. 2005, 202: 271-281. 10.1084/jem.20050664.PubMed CentralView ArticlePubMedGoogle Scholar
- Joseph K, Shibayama Y, Ghebrehiwet B, Kaplan AP: Factor XII-dependent contact activation on endothelial cells and binding proteins gC1qR and cytokeratin 1. Thromb Haemost. 2001, 85: 119-124.PubMedGoogle Scholar
- Joseph K, Shibayama Y, Nakazawa Y, Peerschke EI, Ghebrehiwet B, Kaplan AP: Interaction of factor XII and high molecular weight kininogen with cytokeratin 1 and gC1qR of vascular endothelial cells and with aggregated Abeta protein of Alzheimer's disease. Immunopharmacology. 1999, 43: 203-210. 10.1016/S0162-3109(99)00136-8.View ArticlePubMedGoogle Scholar
- Mahdi F, Madar ZS, Figueroa CD, Schmaier AH: Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranes. Blood. 2002, 99: 3585-3596. 10.1182/blood.V99.10.3585.View ArticlePubMedGoogle Scholar
- Back J, Sanchez J, Elgue G, Ekdahl KN, Nilsson B: Activated human platelets induce factor XIIa-mediated contact activation. Biochem Biophys Res Commun. 2010, 391: 11-17. 10.1016/j.bbrc.2009.10.123.View ArticlePubMedGoogle Scholar
- Ekdahl KN, Bengtsson AA, Andersson J, Elgue G, Ronnblom L, Sturfelt G, Nilsson B: Thrombotic disease in systemic lupus erythematosus is associated with a maintained systemic platelet activation. Br J Haematol. 2004, 125: 74-78. 10.1111/j.1365-2141.2004.04858.x.View ArticlePubMedGoogle Scholar
- Joseph JE, Harrison P, Mackie IJ, Isenberg DA, Machin SJ: Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis. Br J Haematol. 2001, 115: 451-459. 10.1046/j.1365-2141.2001.03101.x.View ArticlePubMedGoogle Scholar
- Nagahama M, Nomura S, Ozaki Y, Yoshimura C, Kagawa H, Fukuhara S: Platelet activation markers and soluble adhesion molecules in patients with systemic lupus erythematosus. Autoimmunity. 2001, 33: 85-94. 10.3109/08916930108995993.View ArticlePubMedGoogle Scholar
- Liu K, Li QZ, Delgado-Vega AM, Abelson AK, Sánchez E, Kelly JA, Li L, Liu Y, Zhou J, Yan M, Ye Q, Liu S, Xie C, Zhou XJ, Chung SA, Pons-Estel B, Witte T, de Ramón E, Bae SC, Barizzone N, Sebastiani GD, Merrill JT, Gregersen PK, Gilkeson GG, Kimberly RP, Vyse TJ, Kim I, D'Alfonso S, Martin J, Harley JB, Criswell LA: Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans. J Clin Invest. 2009, 119: 911-923. 10.1172/JCI36728.PubMed CentralView ArticlePubMedGoogle Scholar
- Ponticelli C, Meroni PL: Kallikreins and lupus nephritis. J Clin Invest. 2009, 119: 768-771. 10.1172/JCI38786.PubMed CentralView ArticlePubMedGoogle Scholar
- Bertolaccini ML, Mepani K, Sanna G, Hughes GR, Khamashta MA: Factor XII autoantibodies as a novel marker for thrombosis and adverse obstetric history in patients with systemic lupus erythematosus. Ann Rheum Dis. 2007, 66: 533-536.PubMed CentralView ArticlePubMedGoogle Scholar
- Jones DW, Gallimore MJ, MacKie IJ, Harris SL, Winter M: Reduced factor XII levels in patients with the antiphospholipid syndrome are associated with antibodies to factor XII. Br J Haematol. 2000, 110: 721-726. 10.1046/j.1365-2141.2000.02251.x.View ArticlePubMedGoogle Scholar
- Abildgaard U: Antithrombin–early prophecies and present challenges. Thromb Haemost. 2007, 98: 97-104.PubMedGoogle Scholar
- Back J, Lang MH, Elgue G, Kalbitz M, Sanchez J, Ekdahl KN, Nilsson B: Distinctive regulation of contact activation by antithrombin and C1-inhibitor on activated platelets and material surfaces. Biomaterials. 2009, 30: 6573-6580. 10.1016/j.biomaterials.2009.07.052.View ArticlePubMedGoogle Scholar
- Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25: 1271-1277. 10.1002/art.1780251101.View ArticlePubMedGoogle Scholar
- Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, Bacon P, Bombardieri S, Hanly J, Hay E, Isenberg D, Jones J, Kalunian K, Maddison P, Nived O, Petri M, Richter M, Sanchez-Guerrero J, Snaith M, Sturfelt G, Symmons D, Zoma A: The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996, 39: 363-369. 10.1002/art.1780390303.View ArticlePubMedGoogle Scholar
- Lood C, Amisten S, Gullstrand B, Jonsen A, Allhorn M, Truedsson L, Sturfelt G, Erlinge D, Bengtsson AA: Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease. Blood. 2010, 116: 1951-1957. 10.1182/blood-2010-03-274605.View ArticlePubMedGoogle Scholar
- Sanchez J, Elgue G, Riesenfeld J, Olsson P: Studies of adsorption, activation, and inhibition of factor XII on immobilized heparin. Thromb Res. 1998, 89: 41-50. 10.1016/S0049-3848(97)00310-1.View ArticlePubMedGoogle Scholar
- Ekdahl KN, Ronnblom L, Sturfelt G, Nilsson B: Increased phosphate content in complement component C3, fibrinogen, vitronectin, and other plasma proteins in systemic lupus erythematosus: covariation with platelet activation and possible association with thrombosis. Arthritis Rheum. 1997, 40: 2178-2186. 10.1002/art.1780401212.View ArticlePubMedGoogle Scholar
- Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006, 4: 295-306. 10.1111/j.1538-7836.2006.01753.x.View ArticlePubMedGoogle Scholar
- Konings J, Govers-Riemslag JW, Philippou H, Mutch NJ, Borissoff JI, Allan P, Mohan S, Tans G, Ten Cate H, Ariens RA: Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin. Blood. 2011, 118: 3942-3951. 10.1182/blood-2011-03-339572.View ArticlePubMedGoogle Scholar
- de Pablo P, Ramirez A, Cortina E, de la Pena A, Zamora J, Izaguirre R, Amigo MC: Increased fibrin polymerization rate in patients with primary antiphospholipid syndrome and systemic lupus erythematosus. Clin Appl Thromb Hemost. 2003, 9: 221-225. 10.1177/107602960300900306.View ArticlePubMedGoogle Scholar
- Pereira J, Alfaro G, Goycoolea M, Quiroga T, Ocqueteau M, Massardo L, Pérez C, Sáez C, Panes O, Matus V, Mezzano D: Circulating platelet-derived microparticles in systemic lupus erythematosus, Association with increased thrombin generation and procoagulant state. Thromb Haemost. 2006, 95: 94-99.PubMedGoogle Scholar
- Govers-Riemslag JW, Smid M, Cooper JA, Bauer KA, Rosenberg RD, Hack CE, Hamulyak K, Spronk HM, Miller GJ, ten Cate H: The plasma kallikrein-kinin system and risk of cardiovascular disease in men. J Thromb Haemost. 2007, 5: 1896-1903. 10.1111/j.1538-7836.2007.02687.x.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
NodeJS Library for Facebook
With facebook-node-sdk you can now easily write the same code and share between your server (nodejs) and the client (Facebook Javascript SDK).
Author: Thuzi
Maintainer Daniel Friesen
License: Apache v2
npm install fb
// Using require() in ES5 var FB = ; // Using require() in ES2015 var FB FacebookApiException = ; // Using ES2015 import through Babel ; // or, ;
Libraries can isolate themselves from the options belonging to the default
FB by creating an instance of the
// ES5 var FB = fb = options; // ES2015 w/ require() var Facebook FacebookApiException = fb = options; // ES2015 w/ import through Babel ;var fb = options;
Applications that run on behalf of multiple apps with different Facebook appIds and secrets can use
.extend (on
FB or any
version your application is coded against).
FBoptionsversion: 'v2.4';var fooApp = FB barApp = FB;
appId and
appSecret in
npm installcd samples/scrumptiousnpm installnode app.js
Passing Parameters
FB; var body = 'My first post using facebook-node-sdk';FB;
FB; var postId = '1234567890';FB;
FB; var extractEtag;FB; { var etag header headerIndex; forheaderIndex in resheaders header = resheadersheaderIndex; ifheadername === 'ETag' etag = headervalue; return etag;};
FB; var message = 'Hi from facebook-node-js';FB;
This is a non-standard behavior and does not work in the official client side FB JS SDK.
facebook-node-sdk is capable of handling oauth requests which return non-json responses. You can use it by calling
api method.
You can safely extract the code from the url using the
url module. Always make sure to handle invalid oauth callback as
well as error.
var url = ; var urlToParse = 'http://yoururl.com/callback?code=.....#_=_';var result = url;ifresultqueryerror ifresultqueryerror_description console; else console; return; else if !resultquerycode console; return; var code = resultquerycode;
Although Legacy REST Api is supported by facebook-node-sdk, it is highly discouraged to be used, as Facebook is in the process of deprecating the Legacy REST Api.
FB; var message = 'Hi from facebook-node-sdk';FB;
FB; var postId = '.....';FB;
This is a non-standard api and does not exist in the official client side FB JS SDK.
Warning: Due to Node's asynchronous nature, you should not use
setAccessToken when
FB is used on behalf of for multiple users.
If you want to use the api compatible with FB JS SDK, pass
access_token as parameter.
This is a non-standard api and does not exist in the official client side FB JS SDK.
FB.extend this returns a new FB object that inherits the same options but has an accessToken specific to it set.
var fb = FB;
setAccessToken this is a standard api and exists in FB JS SDK.
FB;var accessToken = FB;
For improved security, as soon as you provide an app secret and an access token, the library automatically computes and adds the appsecret_proof parameter to your requests.
This is a non-standard api and does not exist in the official client side FB JS SDK.
When this method is called with no parameters it will return all of the current options.
var options = FBoptions;
When this method is called with a string it will return the value of the option if exists, null if it does not.
var timeout = FBoptions'timeout';
When this method is called with an object it will merge the object onto the previous options object.
FBoptionsaccessToken: 'abc'; //equivalent to calling setAccessToken('abc') FBoptionstimeout: 1000 accessToken: 'XYZ'; //will set timeout and accessToken options var timeout = FBoptions'timeout'; //will get a timeout of 1000 var accessToken = FBoptions'accessToken'; //will get the accessToken of 'XYZ'
The existing options are:
'accessToken' string representing the Facebook accessToken to be used for requests. This is the same option that is updated by the
setAccessToken and
getAccessToken methods.
'appId' The ID of your app, found in your app's dashboard.
'appSecret' string representing the Facebook application secret.
'version' [default=
'v2.0'] string representing the Facebook api version to use. Defaults to the oldest available version of the api.
'proxy' string representing an HTTP proxy to be used. Support proxy Auth with Basic Auth, embedding the auth info in the uri: 'http://[username:password@]proxy[:port]' (parameters in brackets are optional).
'timeout' integer number of milliseconds to wait for a response. Requests that have not received a response in X ms. If set to null or 0 no timeout will exist. On timeout an error object will be returned to the api callback with the error code of
'ETIMEDOUT' (example below).
'scope' string representing the Facebook scope to use in
'redirectUri' string representing the Facebook redirect_uri to use in
This is a non-standard api and does not exist in the official client side FB JS SDK.
Gets the string representation of the facebook-node-sdk library version.
var version = FBversion;
This is a non-standard api and does not exist in the official client side FB JS SDK.
var signedRequestValue = 'signed_request_value';var appSecret = 'app_secret'; var signedRequest = FB;ifsignedRequest var accessToken = signedRequestoauth_token; var userId = signedRequestuser_id; var userCountry = signedRequestusercountry;
Note: parseSignedRequest will return undefined if validation fails. Always remember to check the result of parseSignedRequest before accessing the result.
If you already set the appSecret in options, you can ignore the second parameter when calling parseSignedRequest. If you do pass the second parameter it will use the appSecret passed in parameter instead of using appSecret from options.
If appSecret is absent, parseSignedRequest will throw an error.
FBoptions'appSecret': 'app_secret'; var signedRequestValue = 'signed_request_value'; var signedRequest = FB;ifsignedRequest var accessToken = signedRequestoauth_token; var userId = signedRequestuser_id; var userCountry = signedRequestusercountry;
This is a non-standard api and does not exist in the official client side FB JS SDK.
This returns the redirect url for a manual login flow.
These options are accepted and all correspond to url parameters documented in Facebook's manual login flow documentation.
'client_id' [default=
FB.options('appId')] The ID of your app, found in your app's dashboard.
'redirect_uri' [default=
FB.options('redirectUri')] The URL that you want to redirect the person logging in back to. This URL will capture the response from the Login Dialog.
'scope' [default=
FB.options('scope')] A comma separated list of Permissions to request from the person using your app.
'display' Can be set to 'popup'.
'state' An arbitrary unique string created by your app to guard against Cross-site Request Forgery.
'response_type' [default=
'code'] Determines whether the response data included when the redirect back to the app occurs is in URL parameters or fragments.
Note: Facebook is not consistent with their error format, and different systems can fail causing different error formats
Some examples of various error codes you can check for:
'ECONNRESET' - connection reset by peer
'ETIMEDOUT' - connection timed out
'ESOCKETTIMEDOUT' - socket timed out
'JSONPARSE' - could not parse JSON response, happens when the FB API has availability issues. It sometimes returns HTML
FBoptionstimeout: 1 accessToken: 'access_token'; FB;
This is a non-standard api and does not exist in the official client side FB JS SDK.
FB.napi takes the same input as
FB.api. Only the callback parameters is different. In the original
FB.api, the callback expects one parameter which is the response. In
FB.napi the callback expects two
parameters instead of one and follows the node standards. The first parameter is an error which is always
of type
FB.FacebookApiException and the second parameter is the same response as in
Error response can be accessed using
error.response which is the same response as the response when using
FB.napi was added especially to make it easier to work with async control flow libraries.
Here are some examples of using facebook-node-sdk with Step.
You will need to install
npm install step
var FB = Step = ; ;
Simplified version of facebook-node-sdk async callbacks using
var FB = Step = ; ;

subset: commoncrawl


text:
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BOB: hey look ive got a suntan
ROB: you idiot you're burnt
BOB: next time ill use sun lotion
ROB: you idiot you're burnt
BOB: next time ill use sun lotion
by tee-pot April 16, 2014
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If there is a name that is synonymous with Swedish melodic death metal, it has to be the one and only AT THE GATES.
Known as one of the forefathers of what would become Swedish melodic death metal, AT THE GATES set a benchmark with their iconic 1995 album 'Slaughter Of The Soul' – a release that would be an inspiration for a myriad of acts to follow and try to replicate – yet seldom duplicated.
When they reformed in 2007 after an 11 year hiatus, they toured the world on a highly successful reunion tour (with a stop off in Australia in 2012) that culminated in the band writing and creating a new album in 2014 entitled 'At War With Reality' and we are proud to announce AT THE GATES will be returning to Australian shores in October!
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Time and time again, AT THE GATES prove why they are one of the undisputed kings of the genre and then some. Instead of wasting your money on one of the imitators, see the innovators lay waste once again.


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With a range of indulgent contemporary facilities and comfortable but practical spaces overlooking an unspoilt, picturesque bay, Sava Villa 2 offers an appealing blend of private in and outdoor luxury. It's easy to switch into holiday mode as you drift between the pool, outdoor pavillions and spacious air-conditioned indoor living spaces, constantly connected to the fabulous views. The villa comes with two maids, a private chef and an estate manager to deal with individual vacation queries and requests, meaning every need is easily catered for and total comfort is guaranteed. The pace of life soon slows down with personal and social time easily balanced thanks to the villa's multiple private spaces. With the beach just steps away, all the facilities of a five star hotel and a delectable choice of dishes on the in-villa menu, there's little need to leave the villa grounds, even on an extended holiday.


text: NJ Candidate for Governor: This is New Jersey By Kevin Tor If Tim James can take a stand on the English language in Alabama, this candidate... more »If Tim James can take a stand on the English language in Alabama, this candidate can take a stand for New Jersey. Thanks to YouTube User doriansol for the piano. To see Tim James video: http://www.youtube.com/watch?v=B9ohsvJHkbY « less Published April 30, 2010 139 views More Info » Full Credits Kevin Tor Uploader Stats & Data 6 Funny Votes 4 Die Votes 139 Views Published: April 30, 2010 Categories: Sketch Politics Parody Keywords: tim james kevin tor comedy parody alabama speak english new jersey bon jovi jersey shore the situation snooki Up Next: Lady GaG - Butterface AUTOPLAY Up Next In: 10 Lady GaG - Butterface St. Patrick and the Snakes My Buddy Now Verizon Fios Kid Follow Facebook Twitter Tumblr Instagram Browse Related Comments 20+ more View All ▶ Kevin Tor Vaguely Related Videos Vaguely Related Pics & Words Advertisement Tags: tim james kevin tor comedy parody alabama Advertisement


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Leader of the Opposition Sunil Jakhar on Monday accused the Punjab government of being "a mere puppet in the hands of the sand mafia" by not auctioning the 39 quarries in the state that were given the nod by the Centre in June.
In a statement here, Jakhar said that chief minister Parkash Singh Badal had met union environment minister Prakash Javadekar on June 13, when the latter informed the CM that the 39 quarries were given the goahead for functioning.
"As a consequence, sand remains costly and it appears that there are some vested interests in the government who do not want to end this artificial scarcity and high price cycle for sand and gravel," Jakhar said.
Jakhar dared the chief minister to call a one-day legislative session exclusively on the issue of high prices of sand and let it be publicly telecast, so that the people should know the truth behind the costly sand and artificial scarcity. "It is time to debate on this sensitive issue threadbare so that the role of governmentsupported vested players gets exposed," he added.


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|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Shane Curcuru <...@shanecurcuru.org>
|Re: [www] html instead of markdown (mdtext)?
|Fri, 12 Aug 2011 16:50:30 GMT
Hey, my only role with Apache infrastructure is as court jester, so I'm not the one to help here: folks will need to organize specific proposals and work with the Apache infra team. Note this is *not* about which is the fastest way to serve content. The real question is how the Apache infra team - working within a non-profit org, with limited physical and admin resources - can effectively and reliably manage all services our many projects ask for. Information about Apache infrastructure is available: https://www.apache.org/dev/machines.html https://people.apache.org/~henkp/ (lots of links) https://people.apache.org/~vgritsenko/stats/daily.html https://www.apache.org/mirrors/ - Shane P.S. the CMS by default stores both the mdtext and the final html output both in SVN. The mdtext is in your working SVN area, with diffs to the appropriate project lists, so that the team can see what changes are being made in terms of the content people develop. The final html is in the staging/production website SVN areas, mainly for backup recovery and security. If the server's lost, just install httpd somewhere, and then svn checkout the html tree. On 8/12/2011 12:19 PM, Terry Ellison wrote: > Rob, > > I support your general point. Using static HTML files to achieve might > have been a sound argument in the 1990s, but it isn't really credible > with today platform technologies. What are the transactional rates for > the Apache site? How many requests per second even just roughly? > > Taking your example of the MediaWiki engine, this is scaled to meet the > transactional and data volume demand of wikipedia.org, one of the > busiest websites on the planet. (There are typically ~100 updates per > second and goodness know how many pageviews.) See > http://www.mediawiki.org/wiki/Cache and the few dozen subsidiary pages. > There are many high performance caching products that address this issue > -- Apache even does one: http://trafficserver.apache.org/ -- and the > mediaWiki engine already integrates with a couple of the leaders: Squid > and Varnish. > > Apache's "heartland" is its "number one HTTP server on the Internet". > Are we rally saying that the best way to manage content is through > static HTML files? This is just daft IHMO. Has anyone ever heard of > current CMS technology. > > How many content editors and contributors can read HTML these days? > > One other point: yes SVN or any equivalent versioning repository can > store most types of content, but versioning should take place at the > highest level of abstraction and language that the content providers > work in. Take an extreme example to emphasise this point. svn can store > object modules, but does this mean that we should use these are the > master control and disassemble back to assembly code to update programs. > Of course not. But to many editors, HTML is little more that binary > machine code. > > Non-functional (infrastructure) requirements help drive the design and > implementation cycles but they shouldn't unnecessarily limit the true > functional requirements of the system. To do so is madness. Is is really > an approach Apache wants to advocate? > > Regards > Terry >> On Fri, Aug 12, 2011 at 10:10 AM, Shane Curcuru<email@example.com> >> wrote: >>> (To provide a little context while Gav may be asleep) >>> >>> On 8/12/2011 9:26 AM, Rob Weir wrote: >>>> On Fri, Aug 12, 2011 at 3:41 AM, Gavin McDonald<firstname.lastname@example.com> >>>> wrote: >>>>>> On Thu, Aug 11, 2011 at 12:12 PM, Kay Schenk<email@example.com> >>> ...snip snip snip... >>> >>>>>> Just a thought: Could you do the entire website in MediaWiki, with >>>>>> only >>>>>> exception cases (download page, etc.) done in HTML? >>>>> Just to put a blocker on this right away, we will not be using the >>>>> wiki >>>>> as the >>>>> main website or the main entrance into the OOo world. >>>>> >>>> Since it is not self-evident to me why a wiki would be a problem for >>>> the main website, could you explain this a little further? Is there a >>>> technical problem? Remember, the wiki already comprises several >>>> thousand pages of website content, so in a very real sense the "main" >>>> website is already the wiki. >>> Performance. As I understand it, the bulk of all apache.org content is >>> served statically as html files. Putting a major project's homepage >>> website >>> like the future office.a.o (or whatever name) up as a wiki would add a >>> significant amount of load to our servers, even for a highly >>> efficient wiki >>> engine. >>> >> Thanks, that gives some context. So "main" in this case is not >> necessarily only the top level page, i.e., an eventually >> openoffice.apache.org or the current www.openoffice.org. Certainly >> those pages would be some of the most highly-trafficked pages. But we >> probably have some others that are also, FAQ's, Release notes, >> download page, etc. >> >> But that still leaves the long tail of the thousands of other pages >> that are individually accessed rarely, but may add up to significant >> load. >> >> I'm surprised there is no caching mechanism for MediaWiki to simply >> write out up static versions of pages and then invalidate the cache >> for a particular page when it is changed. In theory you could have >> the rarely-changed pages be just as efficient as static HTML. Plugins >> exist that do this for WordPress, for example. >> >> >>> The beauty of the CMS is that while it's easy to work on the pages >>> (either >>> via SVN or browser), the final result is simply checked into SVN and >>> then >>> the resulting .html file is just stuck on the production webserver site. >>> Some projects use a wiki to manage their homepages (i.e. project.a.o, >>> separate from any community wiki they may have), but the physical >>> homepage >>> that end-users see is typically static html that's been exported from >>> their >>> wiki site. >>> >>> Gav or infra folk can provide more details, but you should plan on >>> adhering >>> to whatever performance restrictions the infra team requires for the >>> main >>> website. >>> >>> - Shane >>> >
|View raw message


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Our country faces no more important task right now than putting millions of unemployed people back to work. We know that many won't get there without intensive job training and placement programs connected to business demands. What isn't clear enough is how to do that most effectively.
The United States spends billions of dollars every year on workforce training programs funded by 12 federal agencies, 50 states and at least 240 large foundations. One of the challenges to understanding what works best is that most of the programs use different data and different benchmarks for success.
Many don't even agree on what constitutes a job. Does starting a temporary job count as a job placement? Nearly two thirds of job training programs say it does, according to a national survey, whose initial results were released today by Public/Private Ventures (P/PV). About 40 percent want to see a minimum number of hours or wage level before a job is considered a job.
Job retention is even trickier to define. Nearly a quarter of the 214 programs surveyed as part of P/PV's Benchmarking Project check with participants 90 days after the job started to see if they're working at that time (the "snapshot" approach). If so, they've hit the three-month retention mark considered crucial for success in some federal programs. Half the programs surveyed use continuous employment with any employer for the 90-day period. And another quarter look for continuous employment with the same employer in that time frame. Not surprisingly, the highest retention rates were among the programs taking the 90-day snapshot.
Another critical question is who gets counted in the placement rates: everyone who enrolls in a training program or everyone who finishes it? Then there's the question of who gets chosen for the program in the first place. Some select job seekers with relatively high skills levels, while others concentrate on harder-to-place applicants, including former inmates or high-school dropouts. Guess which programs have the highest placement rates?
But how a program defines "success" is rarely a matter of choice--definitions are often dictated by who's funding the work. To further complicate matters, most workforce development programs rely on more than one source of funding.
That invariably means different sets of metrics and reports for the same services. Right now, the Labor Department asks for different data than the Health and Human Services Department, which asks for different data than the Department of Education. Their databases don't talk to each other, and programs that submit information generally can't pull it back from the databases in ways that could inform and improve their services.
Add to that the myriad state, local and philanthropic groups that support workforce development and that often ask for different data. The picture that emerges is of harried staff members keeping different sets of books for different backers.We are left with no clear picture, however, of what approaches are most likely to help people secure and keep jobs with the wages and benefits that would support a family.
So what can be done? The first step is to move toward more consistent definitions. P/PV is already working with private foundations that support programs in New York City to help align their performance standards; funders in Baltimore have undertaken similar efforts. It's time for federal, state and local agencies to do the same.
The technology needs to follow, so that training programs can not only share data easily with their funders, but also get the information back with some value added: summary tables, year-to-year comparisons, and trends for demographic groups or targeted industries.
Finally, public and private programs need to continue evaluating what constitutes "good performance." What definitions of job placement and retention indicate actual success for job seekers? What strategies work best for the hard-to-place populations? How can we improve what we do?
With support from the Annie E. Casey Foundation, P/PV is continuing research that began in 2004 and working to expand the pool of programs it surveys to better understand the answers to these questions. The Benchmarking Project is has also created a learning community to help boost performance across the workforce field, using both the data collected and the experiences of participating organizations to discern effective program strategies.
Some commentators have questioned whether workforce training really works given the pervasive joblessness our country now faces. The answer is not to give up on these efforts, but rather to find a way to quantify their successes and ensure that programs across the spectrum adopt a consistent set of benchmarks for returning Americans to work.
The Morning Email helps you start your workday with everything you need to know: breaking news, entertainment and a dash of fun. Learn more


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This quiet neighborhood of houses on an oval street, was originally a popular racetrack. Established in the 1800s by former slave Cal Johnson, the oval was Knoxville's best-known horse-racing venue. Later, it became Knoxville's first automobileracing track, the scene of dramatic events. In the 1920s, the track was paved over and redeveloped as residential property, part of what's now known as Burlington.
Tennessee Vacation eGuide
The 2016 eGuide gives you instant access to Tennessee's irresistible attractions and destinations. Peruse venues online, then put in your order to get a free guide delivered to your doorstep.


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This is the January 25, 2013 news archive. View today's Mavericks rumors and news.
Dallas Mavericks
Dallas Mavericks News and Rumors
Spurs' Parker gets cut above eye vs. Mavsnba.com Updated Jan 25, 2013Tony Parker missed about a quarter of Friday's game against Dallas after taking three stitches for a cut above the left eye.Share Tweet
Texas Legends of D-League acquire guard Westnba.com Jan 25, 2013Guard Delonte West was acquired by the Texas Legends on Friday, setting him up in the NBA Development League three months after Dallas released him following a pair of suspensions.Share Tweet
Spurs Roll Without DuncanJan 25Tony Parker scores 23 points in Tim Ducan's absence to lead Spurs to 113-107 win over Mavericks.


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Commercial, Apartments,Restaurant/Bar - Tupper Lake, NY
Established, fully equipped and modernized 150 seat restaurant and 25 client bar/lounge in a prime location, on a busiest traffic route in town (NYS Route 3 & 30) that has operated for over 50 years. Oversized 5+ BR apartment on second floor a big bonus!
Data Provided by Adirondack Champlain Valley MLSMore Information for this listing


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In a message dated 3/11/01 7:47:28 PM Eastern Standard Time, firstname.lastname@example.com
<< Don't suppose anybody got an extra stepping stones this year???
Oh, Paula, I wish I had known that you wanted one. Didn't think about it, I
didn't see too many people buying them. Could have shipped it to you.
Didn't they ship them to people who wanted them last year? Betty Davis might
know or know who to ask. I am sure that they had extras left over. She is
B D Eyes firstname.lastname@example.com.
You should bring a big group next year, now are you going to the convention,
I guess living in the middle of the country makes it a little bit easier to
go to those things as it is close in all directions. Can't wait for that
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Bauer Rainstar Series Irrigation Reel Systems Are Used For Landscaping and Grounds Maintenance Of Golf Courses, Sports Facilities, Farms And More.
Bauer Rainstar Series Irrigation Reel Systems are made of galvanized steel for long lasting durability. Rainstar with special PE-pipe, 2-wheel undercarriage with crop friendly tires and mechanical machine supports provide user convenience. Hot-dip galvanizing for pipe drum and undercarriage with Bauer turbine TCN 18 and Bauer transmission gear/PTO rewind provide optimum performance. Also features mechanical speed control with automatic plan metric adjustment, power transmission via external chain drive and auto cart lift/ auto shut-off. Wheel cart has adjustable track width for ease of use and versatility. System does not include sprinkler. Pipe sizes range from 1.3-1.9 inches. GPM, nozzle range and dimensions vary per model.
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Ipswich Punch & JudyNo Real Ale
41 Grafton Way, Cardinal Park, IP1 1AX
grid reference TM 162 440
opened 1998
bar / diner
(details under review)Something we've got wrong about this establishment? Something more you think we should know about it? Please email us
View in Google Earth
Local licensing authority for Ipswich is Ipswich Borough Council
CAMRA Ipswich & East Suffolk branch.
last updated 21/12/2016
A family orientated restaurant / bar with a "Wacky Warehouse", on edge of Cardinal Park (a youthful urban meeting zone which is popular at weekends and includes a large car-park, various restaurants, a film theatre and nightclubs). It is also close to the town's historic docks.
Lunchtime meals (not just snacks)
Evening meals
Restaurant or separate dining area
Family friendly
Pub is accessible to disabled customers
Railway station about 0.4 mile away (see public transport tab for details)
(Most pub, location & historic details collated by Nigel, Tony or Keith - original sources are credited)


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Apps: SoundStudio, TaskTime, DropWaterMark
SoundStudio 3.5.2 ($80) digital audio recording and editing tool. Allows digitizing of tapes and vinyl records, recording live performances, addition of crossfades, application of digital effects and the ability to save in various major file formats. Requires Mac OS X v10.4 or later, PowerPC G3 500 MHz or faster and 512 MB RAM [Download - 14.5MB] DropWaterMark 3.7.3 ($17) protects digital photographs and art by applying a watermark to the image. It has two basic mode for either a single image or folder of images. You can setup two different one line text marks, an image (image on image), or set borders for your pictures. You can also set the font, font properties, rotation, position, transparency (or brightness and color) and now shadow, bevel, and emboss. [Download - 4.8MB] TaskTime 4.3.4 ($20) fortracking time spent on jobs you done for clients. It can generate invoices which can be emailed, printed, and saved to disk. Features include automatic calculation of total time spent on projects and total amount owing. The new release fixes a bug that occurred when printing a report. TaskTime requires Mac OS X 10.1 or later [Download - 5.8MB] MovieChapterizer 2 ($15) provides the ability to add chapters to videos and sound files that can be played in QuickTime Player, including formats such as mov, avi, mp3, H.264 (high-definition), AIFF, etc. In the new release you can use chapter project files to allow easy editing of previously saved chapters. [Download - 3.3MB] Audiocorder 5.1.1 ($20) allows your Mac to act as an audio recorder. In one mode, it operates as a volume operated (VOX) automated audio recorder, allowing you set the volume that the sound must reach to automatically begin recording. It can also be set with a recording schedule, to pick up audio at specific times, or as a manually operated recorder. The new release will buffer sound, so that audio from before the VOX trigger will also be written to the recorded sound file. [Download - 430KB]
AOL Radio for Mac adds screen saver module
America Online as released a new beta edition of AOL Radio for Mac that includes a newly devised screen saver module that displays various song information while music is streaming. The application allows AOL members to listen to AOL Radio streams, including stations from XM Satellite Radio, and offers integration with iChat and a desktop overlay for song changes. The new "Radio Help" feature is a a screen saver module that displays album art, better display of artist album, and song information and other changes. AOL Radio requires Mac OS X 10.2.8 or later and an AOL membership.
Bebo, Audible Magic work to axe piracy
Following this week's deal with Apple to bring iTunes to its social network, Bebo today announced its partnership with Audible Magic, a provider of content recognition technology designed to ensure all artists and the half million bands on Bebo have complete control over their music. Using Audible Magic's content identification and digital fingerprinting technology, Bebo aims to instantly identify unauthorized copyrighted content and remove it from its site. "Bebo Music was established to enable people to build direct relationships with the artists they love, and to enable these artists to make money from their art," said Michael Birch, CEO & founder, Bebo. "With Audible Magic we ensure that artists and the labels that represent them are the only ones who decide which songs they give away for free and which not."
Apple the winner in Microsoft/Google battle
While Microsoft and Google duke it out over alleged violations of trade commission policy, Apple is left free to nimbly establish leadership in certain areas of interest to all three companies, and steal away market share in others. Earlier this year, Microsoft complained that Google's purchase of DoubleClick was a possible anti-trust violation. Google responded by claiming that new search functionality built into Windows Vista unfairly hinders Google's ability to compete. While the two bicker, Apple has made tremendous forays into shared competitive space, delivering a version of the Safari Web browser for Windows and pushing its way into the living room, aided by the Apple TV and Google-owned YouTube.
O2 unveils distinctive Cocoon 2GB music phone
European cell carrier O2 today held a special event to reveal the Cocoon, its aggressive step into music phones. The phone earns its name through an all-white and completely rounded shell which hides extra features: LEDs underneath the outer lid light up for incoming calls and also serve as a unique display for the phone's exclusive clock radio feature, which is switched on by plugging the Cocoon into its custom dock. Music is supported even further by dedicated side controls, 2GB of built-in flash with microSD card expansion, and a native 3.5mm headphone jack for plugging in any set of headphones or desktop speakers.
Windows Safari tops 1m downloads in 48 hours
Leopard ranks #1 on Amazon as pre-order
Amazon is now taking pre-orders for Mac OS X 10.5 (Leopard), due to ship in October of this year. Already it has snagged the #1 product ranking in Software, besting Microsoft Office Home and Student 2007, Microsoft Office Student and Teacher Edition 2004 Macintosh and others. We previously posted an in-depth look at the new features in Leopard, which were discussed in further detail at this week's WWDC (Worldwide Developer Conference) in San Francisco.
Archos announces 5th-gen portable media players
Quickly following up on its teaser, Archos today launched a sweeping update to its media players with the Generation 5 series. Headlining the updates is the fully-unveiled 605 WiFi. Unlike the outgoing 604, the fifth iteration packs a crisper 800x480, 4.3-inch touch LCD to help play H.264, MPEG-2/4, and WMV clips at DVD resolution for up to 5.5 hours as well as to browse the web through an Opera browser. The 605 docks with a DVR attachment that lets it record NTSC-resolution TV or audio, and plays back AAC/MP3/WAV/WMA tracks for up to 17 hours.
Motorola ic902 offers push-to-talk, EVDO
Countering a slew of new phone announcements from Sony-Ericsson, Motorola has launched the Deluxe ic902 with Sprint. The new phone follows up on the ic502, offering walkie-talkie capabilities but adding access to Power Vision services through Sprint's EVDO network, a 2-megapixel camera, and an MP3 player with a 128MB microSD card included. The phone also sports Bluetooth stereo capabilities for wireless headphones and speakers. As one of the carrier's most advanced PowerSource phones, it runs on the iDEN network for walkie-talkie access but also includes CDMA phone calling with EVDO Internet access. The ic902 the first such device in its class to offer access to Power Vision streaming audio and video, Sprint says. GPS support is integrated and helps navigate using the TeleNav system.
XpertMart unlimited license debuts
XpertMart has announced unlimited single store license for its popular Point of Sale system for Mac OS X. Priced at $2500, the new license allows retailers to network together an unlimited number of workstations and is designed for large-scale retail environments where multiple users need to be accessing the same database concurrently. XpertMart's Universal Binary Mac POS system runs on the Firebird database manager, a robust relational SQL database backed by the open source Firebird Foundation. "If you need to have more than three people working together at the same time then the Unlimited Single Store license was created for you," says XpertMart CEO Stephen Searfoss. Firebird is currently used by the US Navy, UK Rail, the Moscow Interbank Currency Exchange Bank and thousands of other organizations.
Sony-Ericsson continues with Z320, Z250 clamshells
Rounding out a series of announcements on Thursday from Sony-Ericsson are two stylized fashion phones. The Z320 and Z250 both focus on basic camera phone photography with 1.3-megapixel and VGA-resolution cameras respectively with one-button access. Both are also consciously retro and include dotted icon displays that light up to indicate new calls and messages. Battery life is long despite the budget focus with average talk time rated at seven hours, according to estimates.
Mac BU: Office 2008 on track
In a brief interview with MacNN discussing the departure of general manager Roz Ho, the Macintosh Business Unit (MacBU) of Microsoft told us that the division is squarely focused on delivering Office 2008 in the second half of 2007, and the placement of new general manager Craig Eisler does not signal that the project is off track. Meanwhile, is still a mystery where exactly former MacBU GM Roz Ho is headed in Microsoft's Entertainment and Devices division.
Sony-Ericsson W910, W960 take on iPhone
More Sony-Ericsson phones have been launched late on Tuesday that rest at the very high-end of the company's music-minded Walkman range and will represent the company's main challengers to the iPhone. The pictured W910i slider is the first Walkman to include HSDPA -- absent from the Apple offering -- and specifically supports US networks such as AT&T to provide high-speed access for streaming audio, uploading images and videos from its 2-megapixel rear camera, or video chats through its smaller front camera. It also debuts a new Shake control mode that can switch music tracks or steer games by moving the phone itself. A 1GB Memory Stick Micro card is packed with the phone as is a copy of the Media Manager PC software found with the K850.
Final Print bolsters source clip printing
Digital Heaven today released Final Print 1.5, an update to its companion application for Final Cut Pro that enables users to print the contents of a bin and markers on source clips. Final Print is a standalone application that prints a list of clips in a bin or markers contained in a clip or sequence, providing workflow enhancement when handing off a project to someone else for further work. Final Print opens XML files exported from Final Cut Pro and displays up to 10 columns of information, allowing users to print or save the list in PDF format. Final Print 1.5 is priced at $100, and requires Final Cut Pro 4.1 or later to export XML files.
Sony-Ericsson intros 5-megapixel K850, GPS-ready K530
Sony-Ericsson tonight held a special press event in Berlin that launched several new phones, including multiple devices that will reach the US. The K850i (shown) is a long-awaited sequel to the popular K790/K800 that establishes a number of firsts for the company. At 5 megapixels, the onboard camera is Sony-Ericsson's sharpest to date and features both auto-focus as well as a xenon flash to focus in darker rooms. The bar phone is also one of Sony-Ericsson's first phones with 3G wireless through HSDPA and has the raw Internet speed needed to upload full-resolution photos as well as make video calls (when supported) through a smaller front-facing camera.
Corona 2.5 updates payroll/accounting solution
DesignersDomain has released Corona 2.5, a general ledger and payroll accounting application that features drag-and-drop accounting alongside on-the-fly account creation and click-style reconcilement. The latest revision adds an unpaid bills file for users who don't need formal accounts payable, allowing users to drag-and-drop to the check register when a check is issued. Corona's invoices and purchase forms now support unit prices to three decimals, while the software's import and export features are rewritten. Corona 2.5 also introduces support for SQL (Structured Query Language), and includes new topics on cash management as well as credit cards. Corona 2.5 is a free upgrade to all registered users, and is priced at $65 (system requirements were unavailable).
Sony-Ericsson intros Bluetooth watches with OLED
Sony-Ericsson today revealed the MBW-150, the latest in its recent watch line that pairs with most Bluetooth phones to ease call handling and music. In line with the Fossil-branded MBW-100 released last fall, the three new designs include a vibration alert and a a small OLED display that provide caller ID and notices of SMS texts; a quick button press can accept or dismiss voice calls. Owners of Walkman phones or other Bluetooth music phones also get basic track navigation so they can listen without fishing the phone out of a pocket.
NI offers 3 free drum kits for Battery 3
Native Instruments (NI) today released a free library add-on with three artist drum kits for its percussion sampler Battery 3. The new kits are designed by NI endorsees Gorillaz, Einstuerzende Neubauten, and Turntablerocker, and are based on exclusive custom sounds from these artists' own productions. The "Dracula Eastwood" kit by Gorillaz producer Curtis Lynch provides Battery 3 users with high-quality drum sounds destined for various kinds of urban grooves. The kit includes an assortment of over 60 bass drums, snares, toms, and hihats that all carry a distinctive vinyl character.
HyperResearch 2.8 comes to Intel Macs
ResearchWare today released HyperRESEARCH 2.8, a multi-platform software package designed for qualitative analysis research. The latest revision offers enhanced support for Microsoft Windows Vista, runs natively on Intel-based Macs as a Universal Binary, and includes improvements to reporting and printing features alongside broader support for contextual menus. The software is used by researchers in social science research, psychology, usability, and corporate marketing to identify as well as analyze patterns and trends among qualitative data from a variety of media file types, according to ResearchWare. HyperResearch 2.8 is priced at $370 for a single-user license, and requires Mac OS X 10.3 or later.
Archos hints at fifth-generation media players
Archos is about to announce its next-generation line, according to a teaser posted at its main website with an indefinite countdown. Although officially vague, recent details show that the company plans to revise most of its models all at once to include additional storage options and will likely include extras beyond those revealed in leaks. The Archos 605 (pictured) will lead the designs with integrated Wi-Fi and either 4GB of flash or varying sizes of hard drive up to 160GB with a new SDHC card slot supporting as much as 32GB of extra space; both will reportedly share a 4.3-inch touchscreen.
Impact Resistant sleeve for MacBooks
MaxUpgrades has announced MaxProtect, an impact resistant Sleeve for MacBooks and MacBook Pros.�The new case is made of Visco-Elastic Memory Foam, which is designed to resist impact and shock. The case features high impact resistance polyurethane foam for shock absorption from all sides; thick foam padding throughout the entire surface of the notebook; a two-zipper, pull apart design;protected zipper closure (zippers don�t come in contact with the laptop); and handles. The MaxProtect ranges in price from $24-$30 depending on the model of MacBook or MacBook Pro it is designed for.
First iPhone apps surface on Web
David Cann has created an alternate interface for Digg that will (theoretically) work well on the iPhone's interface. Matching the iPhone's screen size, the AJAX Web app allows users to scroll through different Digg categories, then click through to links which become embedded in the same sized box. The interface is built with the Yahoo! UI Library, PHP and the Digg API. Meanwhile, Wired Blogs notes another "iPhone app" -- OneTrip, "a quick (though very elegant) grocery list program put together over-night by Neven Mrgan. [...] I think the new Apple strategy of "the web is the new SDK" is actually a wonderful one. They're pretty unlikely to crash, and really powerful development is a possibility. Anyone want to lay money on how long it will be until Google issues a version of Reader optimized for the iPhone?"
June 29th shopping appointments cancelled?
Apple has reportedly cancelled at least one Personal Shopping appointment for June 29th -- the chosen date that its highly-anticipted iPhone is scheduled to hit shelves at 6:00 p.m. local time. A ZDNet blogger who made a Personal Shopping appointment on what AT&T is predicting to be the largest commercial product launch in the history of electronics received a phone call from the local Apple store to reschedule his appointment, following earlier personalized email notifications confirming the appointment.
Briefly: iPhone on sale at 6pm local
In brief: An AT&T memo has revealed that Apple's iPhone is set to go on sale at 6:00 p.m. local time on June 29th, Other World Computing (OWC) held its official groundbreaking for the company's new corporate headquarters on June 2nd, and CocoaLab has released a Japanese language version of its free eBook titled "Become an Xcoder." Attendees registering for the annual FileMaker Developer Conference can save $200 with "early-bird" pricing until June 29th, and Iconkits.com has added two new add-on collections titled "Candy Addon" 1 and 2. A memo has surfaced from AT&T revealin gthat the iPhone will be available at 6:00 p.m. local time in all respective timezones on June 29th.
MusicStation races to beat iPhone/iTunes combo
Omnifone today announced that its new mobile music service MusicStation service is now live, representing one of the first unlimited online music stores available through cellphones. As the company first revealed in its 3GSM unveiling, the now active service directly challenges both the iPhone and its iTunes Store companion by offering a universal player and a flat-rate store. Its software layers runs on top of virtually any music phone and bases its entire structure on an unlimited weekly subscription model. The approach allows any music phone to keep relevant music in rotation as long as the device is within coverage of an EDGE (2.5G) or HSDPA (3G) mobile Internet connection, according to the company: as many phones don't have enough storage to hold the user's entire library, the service will automatically cache as many favorites as possible and download the next track in sequence to effectively produce an unlimited library which still holds music when the phone wanders outside of service.
Cowon intros iAudio 7 player with 60-hour runtime
Cowon this morning overhauled one of its most popular players. The iAudio 7 adopts the same form as the earlier version 6 but switches from a micro hard drive to flash. This not only makes the system virtually skip-proof but triples battery life to a virtually unmatched 60 hours of continuous music. Format support is also as broad with AAC, FLAC, and OGG joining the more traditional MP3/WMA/WAV audio support. Owners can even watch some XviD-encoded videos on the 1.3-inch LCD, Cowon says. Similar to most devices of its kind, the iAudio 7 also packs FM radio tuning and voice recording.
New Kodak sensor tech promises 4X better camera light
Promising a revolution, Kodak on Thursday revealed a new sensor technology from its camera labs that could dramatically improve the quality of digital camera shots. The development extends the Bayer Pattern that forms the basis of virtually all camera sensors today to include panchromatic pixels that accept all colors in addition to the blue-, green-, and red-only pixels of the past. Software interprets the neutral light to produce the expected image. All the extra light results in as much as two to four times the same amount of light entering the camera as with traditional digital cameras, Kodak says; the difference amounts to one or two full F-stops in traditional photography terms.
Tom Bihn ships Zephyr notebook briefcase
Bag, pack, and briefcase manufacturer Tom Bihn has introduced its Zephyr medium-sized briefcase for Apple's MacBook Pro 15.4-inch notebook. The Zephyr features "smart" pockets, pouches, and dividers for quick access and organization alongside the ability to add the Tom Bihn Brain Cell hard-sided laptop case as a protective interior compartment for a notebook. The briefcase, which is made from 1050 denier ballistic nylon and 500 denier Cordura, comes in several color combinations which include black, "steel," olive green, "hunter" green, deep blue, crimson, and others. A horizontal zippered pocket is designed to store DVDs or small electronics, and a vertical zippered pocket aims to provide quick access to a cellular phone. Tom Bihn's Zephyr briefcase is available for $140.
Bang & Olufsen intros luxury BeoVision 7 40-inch LCD
Premium home theater builders Bang & Olufsen today launched the BeoVision 7, a 40-inch LCD designed to minimize the number of extra components for a full home theater. The 1080p-native display incorporates a DVD player as with some mainstream sets, but also includes its own 7.1-channel surround sound decoder and a center-channel speaker that can be had in one of two models depending on the audio environment. A basic BeoLab 7-2 speaker provides stereo for smaller areas; the vertical BeoLab 7-4 in turn is meant to fit into a larger surround setup and provides added treble to dialog and other sounds unlikely to remain exclusively in side channels.
Safari 3.01 for Windows fixes security flaws
Apple has released Safari 3.01 for Windows, an update to the public beta that was announced earlier this week. The browser, now available for Windows XP and Vista, is based on the same WebKit foundation as the Mac and iPhone version. Although specific details of the update were not provided via Apple's security website, the release comes on the heels of criticism of Apple by researchers who claim to have found more than 18 security flaws in the Safari browser within a few days of its release.
iTunes replaces Sony's Mora on Yahoo Japan
Apple's iTunes continues to expand its presence overseas, landing a high-profile deal to make iTunes the default music service of Yahoo Japan. On the heels of Apple's expansion into social networking, the iTunes deal with Yahoo Japan replaces the default Sony-affiliated music download service and now offers the portal's 40 million visitors a prominent link to iTunes in the menu bar and one-click access to the download service, according to Macworld UK. The report indicates that users still have the option of making Mora their preferred source for internet music purchases: Mora is a download service run by the Sony-affiliated LabelGate.
Samsung unleashes 70" LED TV with 500,000:1 contrast
Samsung today unveiled what should be not just the company's largest production LCD TV but also its highest-quality model to date. The as-yet unnamed 70-inch LCD achieves an unprecedented 500,000:1 dynamic contrast ratio through a particularly advanced LED backlighting system, the company says. Hundreds of individual LED backlights not only provide a far more evenly distributed backlight than cold cathodes but also selectively dim depending on the on-screen activity, creating truer black levels than would be possible for the older technology. The LEDs can also 'scan' the image by rapidly shutting down in sequence and from there eliminate the flickering or ghosting effects that occur only on particularly large sets, Samsung claims.
Diamond ships first 1GB Radeon HD 2900 XT card
Diamond today became the first card maker to launch a 1GB version of AMD's newest
Now AAPL Stock: 137.11 ( + 0.41 )
Cirrus creates Lightning-headphone dev kit
Apple supplier Cirrus Logic has introduced a MFi-compliant new development kit for companies interested in using Cirrus' chips to create Lightning-based headphones, which -- regardless of whether rumors about Apple dropping the analog headphone jack in its iPhone this fall -- can offer advantages to music-loving iOS device users. The kit mentions some of the advantages of an all-digital headset or headphone connector, including higher-bitrate support, a more customizable experience, and support for power and data transfer into headphone hardware. Several companies already make Lightning headphones, and Apple has supported the concept since June 2014. http://bit.ly/29giiZj
Apple Store app offers Procreate Pocket
The Apple Store app for iPhone, which periodically rewards users with free app gifts, is now offering the iPhone "Pocket" version of drawing app Procreate for those who have the free Apple Store app until July 28. Users who have redeemed the offer by navigating to the "Stores" tab of the app and swiping past the "iPhone Upgrade Program" banner to the "Procreate" banner have noted that only the limited Pocket (iPhone) version of the app is available free, even if the Apple Store app is installed and the offer redeemed on an iPad. The Pocket version currently sells for $3 on the iOS App Store. [32.4MB]
Porsche adds CarPlay to 2017 Panamera
Porsche has added a fifth model of vehicle to its CarPlay-supported lineup, announcing that the 2017 Panamera -- which will arrive in the US in January -- will include Apple's infotainment technology, and be seen on a giant 12.3-inch touchscreen as part of an all-new Porsche Communication Management system. The luxury sedan starts at $99,900 for the 4S model, and scales up to the Panamera Turbo, which sells for $146,900. Other vehicles that currently support CarPlay include the 2016 911 and the 2017 models of Macan, 718 Boxster, and 718 Cayman. The company did not mention support for Google's corresponding Android Auto in its announcement. http://bit.ly/295ZQ94
Apple employees testing wheelchair features
New features included in the forthcoming watchOS 3 are being tested by Apple retail store employees, including a new activity-tracking feature that has been designed with wheelchair users in mind. The move is slightly unusual in that, while retail employees have previously been used to test pre-release versions of OS X and iOS, this marks the first time they've been included in the otherwise developer-only watchOS betas. The company is said to have gone to great lengths to modify the activity tracker for wheelchair users, including changing the "time to stand" notification to "time to roll" and including two wheelchair-centric workout apps. http://bit.ly/2955JDa
SanDisk reveals two 256GB microSDXC cards
SanDisk has introduced two 256GB microSDXC cards. Arriving in August for $150, the Ultra microSDXC UHS-I Premium Edition card offers transfer speeds of up to 95MB/s for reading data. The Extreme microSDXC UHS-I card can read at a fast 100MB/s and write at up to 90MB/s, and will be shipping sometime in the fourth quarter for $200. http://bit.ly/294Q1If
Apple's third-quarter results due July 26
Apple has advised it will be issuing its third-quarter results on July 26, with a conference call to answer investor and analyst queries about the earnings set to take place later that day. The stream of the call will go live at 2pm PT (5pm ET) via Apple's investor site, with the results themselves expected to be released roughly 30 minutes before the call commences. Apple's guidance for the quarter put revenue at between $41 billion and $43 billion. http://apple.co/1oi1Pbm
Twitter stickers slowly roll out to users
Twitter has introduced "stickers," allowing users to add extra graphical elements to their photos before uploading them to the micro-blogging service. A library of hundreds of accessories, props, and emoji will be available to use as stickers, which can be resized, rotated, and placed anywhere on the photograph. Images with stickers will also become searchable with viewers able to select a sticker to see how others use the same graphic in their own posts. Twitter advises stickers will be rolling out to users over the next few weeks, and will work on both the mobile apps and through the browser. http://bit.ly/29bbwUE


text: Physician InformationLocations U of M Physical Medicine & Rehabilitation Burlington Office Center325 E Eisenhower Parkway, Suite 100Ann ArborMI48108 Phone: 734-936-7175 Fax: 734-764-9439 U of M Physical Medicine & Rehabilitation C.S. Mott Children's Hospital, Floor 61500 E Medical Center DrAnn ArborMI48109 Phone: 734-647-3863 Credentials Medical School or Training Medical College of Ohio/University of Toledo, 1991 Residency Medical College of Ohio/University of Toledo, Physical Med & Rehab, OH, 1995 Fellowship Physical Med & Rehab, University of Michigan Health System, 1997 Professional Organizations American Academy of Physical Medicine and Rehabilitation Board Certification Physical Medicine & Rehab Research Exercise in people with disabilities and molecular aspects of exercise. Video profile Joseph Hornyak


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Former Man City and Newcastle star Shay Given leaves Aston Villa to join Middlesbrough
ASTON VILLA goalkeeper Shay Given has joined Middlesbrough on a month's loan.
The former Manchester City and Newcastle United stopper has fallen out of favour under Villa boss Paul Lambert with American Brad Guzan preferred between the sticks.
Given, 37, will go straight into the Boro squad for Saturday's home match against Bolton Wanderers and should he play it will be his 600th club game.
Capped 125 times for the Republic of Ireland, Given will provide new manager Aitor Karanka will much needed experience.
Given made 43 appearances for Villa since making the £3.5m move to the Midlands from City in 2011.