text:
Dr. J. H. Stone has received consultancy fees, speaking fees, and/or honoraria (more than $10,000) from Roche.
Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica
Version of Record online: 27 OCT 2012
DOI: 10.1002/acr.21750
Copyright © 2012 by the American College of Rheumatology
Arthritis Care & Research
Volume 64, Issue 11, pages 1720–1729, November 2012
Additional Information
How to Cite
Unizony, S., Arias-Urdaneta, L., Miloslavsky, E., Arvikar, S., Khosroshahi, A., Keroack, B., Stone, J. R. and Stone, J. H. (2012), Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res, 64: 1720–1729. doi: 10.1002/acr.21750
Publication History
- Issue online: 27 OCT 2012
- Version of Record online: 27 OCT 2012
- Accepted manuscript online: 5 JUN 2012 10:35AM EST
- Manuscript Accepted: 23 MAY 2012
- Manuscript Received: 7 MAR 2012
- Abstract
- Article
- References
- Cited By
The interleukin-6 pathway is up-regulated in giant cell arteritis (GCA), Takayasu arteritis (TA), and polymyalgia rheumatica (PMR). We retrospectively assessed the outcomes of 10 patients with relapsing/refractory GCA, TA, or PMR treated with tocilizumab (TCZ).
Patients with GCA (n = 7), TA (n = 2), and PMR (n = 1) received TCZ. Seven subjects had failed at least 1 second-line agent. The outcomes evaluated were symptoms of disease activity, inflammatory markers, ability to taper glucocorticoids, and cross-sectional imaging when indicated clinically.
The mean followup time of this cohort since diagnosis was 27 months (range 16–60 months). The patients were treated with TCZ for a mean period of 7.8 months (range 4–12 months). Before TCZ therapy, the patients experienced an average of 2.4 flares/year. All patients entered and maintained clinical remission during TCZ therapy. The mean daily prednisone dosages before and after TCZ initiation were 20.8 mg/day (range 7–34.3 mg/day) and 4.1 mg/day (range 0–10.7 mg/day), respectively (P = 0.0001). The mean erythrocyte sedimentation rate declined from 41.5 mm/hour (range 11–68 mm/hour) to 7 mm/hour (range 2.2–11.3 mm/hour; P = 0.0001). The adverse effects of TCZ included mild neutropenia (n = 4) and transaminitis (n = 4). One patient flared 2 months after TCZ discontinuation. An autopsy on 1 patient who died from a postoperative myocardial infarction following elective surgery revealed persistent vasculitis of large and medium-sized arteries.
TCZ therapy led to clinical and serologic improvement in patients with refractory/relapsing GCA, TA, or PMR. The demonstration of persistent large-vessel vasculitis at autopsy of 1 patient who had shown a substantial response requires close scrutiny in larger studies.
Glucocorticoids (GCs) remain the principal therapy for large-vessel vasculitis (LVV; giant cell arteritis [GCA] and Takayasu arteritis [TA]) and polymyalgia rheumatica (PMR) (1, 2). Although these agents generally control clinical evidence of inflammation when administered in moderate to high doses, a sizeable subset of patients (27–85%) with these conditions experience recrudescence of disease activity upon GC tapering or discontinuation (3–7). Such patients require prolonged or repetitive GC courses that result in a host of undesirable side effects. In GCA, long-term GC therapy is associated with adverse effects in the majority of patients, including fractures, diabetes mellitus, infection, cataracts, hypertension, avascular necrosis, and gastrointestinal bleeding (4). Therefore, a major unmet need in this spectrum of disease exists for more specific drugs to induce remission, maintain remission, and reduce the cumulative adverse effects of long-term GC exposure.
Experience using conventional immunosuppressive drugs has been mixed in LVV and PMR, but a clearly effective GC-sparing alternative has not been identified (6–14). In the setting of conflicting results (6–8, 15), methotrexate (MTX) has shown a weak positive signal in terms of remission maintenance in GCA, but prevention of GC-related adverse events could not be demonstrated. In a study by Jover et al (6), despite the lower cumulative dose of prednisone used, 90% of patients in the MTX group had at least 1 adverse event that was definitely or probably related to GCs, and 45% of these patients flared at least once. Tumor necrosis factor α (TNFα) blockade in GCA and PMR failed in controlled studies (16, 17), and the reported beneficial effects of MTX and TNFα inhibitors in TA (18, 19) have not been subject to scrutiny in randomized trials.
Interleukin-6 (IL-6) is a pleiotropic cytokine with a myriad of metabolic, regenerative, and proinflammatory effects that vary according to the target cell (20). IL-6 participates in the regulation of immune responses, acute-phase reactions, hematopoiesis, and bone metabolism, and there is increasing evidence that this molecule is important in the pathogenesis of diverse inflammatory conditions, including LVV and PMR. Patients with GCA, TA, and PMR have elevated concentrations of IL-6 in both their peripheral circulation and their inflamed tissues, and serum levels of IL-6 correlate with disease activity (21–24). Therefore, the IL-6 pathway is an attractive target for therapy.
IL-6 exerts its biologic activity through 2 molecules, an IL-6–specific receptor (IL-6R) and a signal transducer, gp130. The IL-6R exists in transmembrane (mIL-6R) and soluble (sIL-6R) isoforms generated by alternative splicing or enzymatic cleavage. Most cells express gp130 and are able to respond to the complex IL-6/sIL-6R by a process called trans-signaling, but only certain cell types (particularly neutrophils, macrophages, hepatocytes, and some T cell subsets) carry the transmembrane form (mIL-6R) and are directly stimulated by this mediator (classic signaling) (20).
Tocilizumab (TCZ) is a humanized anti-human IL-6R antibody that inhibits both isoforms of IL-6R and has antiinflammatory effects in conditions such as rheumatoid arthritis (25), juvenile idiopathic arthritis (26), Crohn's disease (27), adult-onset Still's disease (28), and Castleman's disease (29). Although TCZ has been studied in large randomized clinical trials of rheumatoid arthritis and juvenile idiopathic arthritis and in smaller trials of inflammatory bowel disease, there are only few studies in the literature regarding its use in GCA, TA, or PMR. In this study, we assessed the clinical, serologic, and radiographic outcomes of 10 patients with LVV or PMR treated with TCZ.
Significance & Innovations
Interleukin-6 (IL-6) receptor blockade may maintain disease remission and decrease the cumulative glucocorticoid exposure in patients with the giant cell arteritis spectrum of disease.
Our experience is the largest reported to date and the only one to provide information on treatment for at least 6 months in the majority of cases.
The autopsied case that we report also provides an important cautionary note, indicating the possibility that large-vessel vasculitis may persist in some cases despite apparent clinical control with anti-IL-6 receptor therapy.
The institutional review board at our hospital approved the retrospective collection of the clinical data reported in this study. This retrospective investigation was intended to evaluate the potential utility of anti–IL-6R therapy in facilitating the induction of remission, the tapering of GCs, and the prevention of disease exacerbation (flare) in a group of patients with LVV or PMR. Ten patients (7 women and 3 men) met the American College of Rheumatology classification criteria for GCA (30) or TA (31), or had a clinical diagnosis of PMR by the Jones and Hazleman criteria (32). All cases were refractory to conventional therapies or included intolerable adverse effects from treatment with these agents. TCZ was offered as a compassionate off-label option after discussing the risk/benefit ratio of this strategy with each particular individual.
Eight patients were treated with TCZ 8 mg/kg/month and 2 (cases 9 and 10, both GCA patients) (Tables 1 and 2) received TCZ 4 mg/kg/month. The patients studied all had a history of refractory/relapsing disease; at the time of TCZ initiation, 8 patients had clinical signs or symptoms of active disease despite a median prednisone dosage of 15 mg/day (range 5–60 mg/day). A subject with TA (case 3) received TCZ, given the radiographic evidence of arterial inflammation by positron emission tomography–computed tomography angiography (PET-CTA), and pulmonary artery stent stenosis despite a previous course of prednisone (Figure 1). An individual with PMR who was previously treated with prednisone for 19 months (case 7) was offered TCZ after she declined further GC therapy for persistently active disease.
|Case no., diagnosis
|Historical disease features
|Cross-sectional imaging (CTA, MRA)
|Before TCZ treatment
|Followup, months
|No. of flares
|Mean prednisone dosage, mg/day
|Mean ESR, mm/hour
|Mean CRP level, mg/liter
|Mean IL-6, pg/ml
|Other specific treatments
|Headache, jaw claudication, amaurosis fugax, PMR
|Headache, fever, PMR
|Pulse deficit, upper extremity claudication, pulmonary hypertension
|Pulmonary, carotid, and subclavian artery stenosis
|Pulmonary stent stenosis
|Headache, jaw claudication, upper extremity claudication, PMR
|Carotid, subclavian, distal aorta, and iliac artery stenosis
|Infliximab, CYC
|Headache, jaw claudication, diplopia, PMR, peripheral neuropathy
|Pulse deficit, lower extremity claudication, hypertension
|Aorta (+)
|Aortic arch aneurysm and external iliac artery stenosis
|Active inflammation on biopsy
|Headache, jaw claudication
|Aorta (+)
|Aortic arch aneurysm
|Headache, jaw claudication, PMR
|MTX, adalimumab, etanercept
|Jaw claudication, fever of unknown etiology
|Case no., diagnosis
|At the time of TCZ initiation
|During TCZ treatment
|Active features
|Prednisone dosage, mg/day
|ESR, mm/hour
|CRP level, mg/liter
|Followup, months
|No. of flares
|Mean prednisone dosage, mg/day
|Prednisone dosage at end of followup, mg/day
|Mean ESR, mm/hour
|Mean CRP level, mg/liter
|Mean IL-6, pg/ml
|Other specific treatment
|Headache, PMR
|Pulmonary stent stenosis; bilateral subclavian, right carotid, and left lower lobe pulmonary artery FDG uptake
|0 (PET abnormalities resolved)
|Headache, jaw claudication
|0 (adrenal insufficiency)
|Headache, jaw claudication
|0 (postoperative myocardial infarction)
|Lower extremity claudication
|Jaw claudication, myalgias
Before treatment with TCZ, 7 of the patients had failed treatment with up to 3 cytotoxic, immunomodulatory, or biologic agents, including MTX (n = 3), azathioprine (n = 1), cyclophosphamide (n = 3), adalimumab (n = 1), etanercept (n = 1), and infliximab (n = 2). The GCA patients were all taking aspirin (81 mg/day) at baseline. None of the patients increased their GC dose or received steroid pulses at the time of TCZ administration.
Clinical improvement was assessed by evaluating signs and symptoms of disease activity, ability to taper prednisone, and serial cross-sectional imaging when clinically indicated before and during anti–IL-6R therapy. Remission was defined as the absence of any clinical sign or symptom of active disease. A flare or active disease was defined as the unequivocal presence of signs or symptoms of active GCA, PMR, or TA that required therapy augmentation in order to be controlled (i.e., the increment of the GC dose and/or addition of another immunomodulatory therapy). The signs and symptoms of active GCA included fever (temperature ≥38°C or ≥100.4°F) without alternative explanation (i.e., infection), localized headache, temporal artery or scalp tenderness, visual signs or symptoms (such as acute vision loss due to arteritic anterior ischemic optic neuropathy, transient blurry vision, amaurosis fugax, or diplopia), jaw claudication, new or worsened extremity claudication, new or worsened vascular lesions on cross-sectional imaging or conventional angiography, or evidence of active vascular inflammation on arterial biopsy (arterial wall mononuclear cell infiltrates with or without the presence of giant cells). Active PMR was defined as shoulder and hip girdle pain associated with significant morning stiffness lasting for >45 minutes. Active TA was considered to be present in the setting of new or worsened vascular lesions on cross-sectional imaging or conventional angiography, new or worsened transient and otherwise unexplained ischemic manifestations (i.e., extremity claudication), appearance of new bruits or new peripheral pulse asymmetries, fever without alternative explanation, or active inflammation seen on blood vessel biopsy.
The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level were measured serially, even though these acute-phase reactants are expected to normalize with adequate IL-6R blockade and therefore their utility in monitoring response to treatment is theoretically limited. Before TCZ therapy, ESR and CRP level were measured every 1–3 months in all cases. In order to account for missing data and to obtain monthly ESR and CRP level, gaps were completed by averaging the closest available values. Once TCZ was initiated, acute-phase reactants were assessed monthly. With these results, mean ESR and CRP level before and after TCZ therapy were calculated for each particular patient. In 8 patients, serum IL-6 concentrations were checked at baseline and before each monthly TCZ infusion thereafter. As an estimate of the cumulative GC exposure, the mean prednisone dose used during the course of the disease before and during TCZ therapy was calculated for each patient.
Baseline patient characteristics.
In total, 10 patients (7 with GCA, 2 with TA, and 1 with PMR) received TCZ. Their mean ages were 69 years (range 60–83 years) for the GCA/PMR patients and 41 years (range 35–48 years) for the TA patients. The mean duration of disease at the time of anti–IL-6R therapy initiation was 20 months (range 10–53 months), and the mean followup time during TCZ treatment was 7.8 months (range 4–12 months). The patients experienced an average of 2.4 disease flares in the year that preceded their TCZ treatment (range 1–8 flares). Other baseline clinical characteristics of the patients are shown in Table 1.
Clinical response.
Within 8–12 weeks, all patients had clinical improvement and were able to taper their daily dose of prednisone to ≤6 mg. The disease activity features in each individual patient by the time of the first TCZ infusion and their response to treatment are shown in Table 2. Clinical remission was achieved in all patients and was maintained throughout the duration of TCZ treatment. The mean ESR declined from 41.5 mm/hour (range 11–68 mm/hour, normal value <17) in the period before TCZ therapy to 7 mm/hour (range 2.2–11.3 mm/hour) during TCZ treatment (P = 0.0001) (Figure 2). The mean CRP concentration declined from 29 mg/liter (range 9.3–72 mg/liter, normal value <8.0) before anti–IL-6R therapy to 3.8 mg/liter (range 0.3–21.2 mg/liter) during IL-6R blockade (P = 0.0001) (Figure 2). PET scans before and at 4 months after the start of TCZ therapy in 1 patient with TA showed complete resolution of high 18-fluorodeoxyglucose uptake in the carotid, subclavian, and pulmonary arteries (Figure 1).
GC sparing.
All patients achieved substantial reductions in their daily prednisone doses once TCZ was initiated. To estimate the cumulative exposure to GCs, we calculated the average of the mean GC doses for each patient over their entire disease course prior to the initiation of TCZ, and calculated the same measurement during anti–IL-6R therapy. This calculation showed that the cohort had been exposed to a mean prednisone dosage of 20.8 mg/day (range 7–34.3 mg/day) before starting IL-6 blockade (Table 1 and Figure 2) and 4.1 mg/day (range 0–10.7 mg/day) during the time they received TCZ (P = 0.0001) (Table 2 and Figure 2). The 6 patientswho were taking the highest prednisone dosages at the time of the first TCZ administration (≥15 mg/day of prednisone) were able to taper their GC dose by 60–90% within 8–12 weeks. No patients needed an increase in the amount of prednisone to control their disease following the initiation of TCZ. Other immunosuppressants were discontinued in all cases. At the end of the followup, only 3 subjects remained on a low-dose prednisone taper at a mean followup time of 8 months after starting TCZ (Table 2). One of these patients received GCs for adrenal insufficiency rather than GCA.
Serum IL-6 concentrations.
Despite the patients' baseline treatments, serum IL-6 concentrations were elevated before TCZ therapy in all subjects except 1 GCA patient. The mean pretreatment IL-6 concentration was 12.9 pg/ml (range 2.8–34 pg/ml, normal range 0.31–5). The mean IL-6 level during anti–IL-6R treatment was 98.4 pg/ml (range 8.6–239 pg/ml). In 7 of 8 cases (5 GCA and 2 TA), the mean IL-6 level significantly increased after TCZ infusion to 116.4 pg/ml (range 30.9–308 pg/ml). In 6 cases, this increment was seen within 1 month; in 1 subject with TA, this increment was seen after 3 infusions. IL-6 levels remained elevated and demonstrated wide fluctuations that ranged from 4.8–530 pg/ml (data not shown). Except for a transient normal value in 1 TA patient, the IL-6 concentrations never normalized during the followup period of our cohort.
Adverse outcomes.
All patients tolerated the study medication without infusion reactions. No infectious complications or gastrointestinal perforations occurred. TCZ was associated with leukopenia and neutropenia in 4 patients. The total white blood cell count nadir in these cases was 2,100–3,400/mm3 (normal value >4,000), with a corresponding absolute neutrophil count of 940–1,300/mm3 (normal value >1,500). Four subjects developed mild transaminitis. The aspartate aminotrasferase peaked at values ranging from 43–92 units/liter (normal range 9–32), and the alanine aminotrasnferase peaked at values between 50 and 74 units/liter (normal value 7–30). None of these abnormalities led to a cessation of the medication or modification of the dose. One patient (case 4) developed adrenal insufficiency after the completion of her prednisone taper and had to resume low-dose GC replacement therapy. One GCA patient (case 2) had a disease flare after discontinuing TCZ therapy for 2 months. Case 7 (who had PMR) experienced a liver contusion during a motor vehicle accident, and TCZ therapy was stopped because of her hepatic injury.
Finally, we report the single death in this series (case 5) in detail. An 82-year-old woman with GCA and a history of diverticulitis underwent elective colostomy reversal and died following a postoperative myocardial infarction. A postmortem examination showed evidence of active vasculitis in the large and medium-sized vessels despite normal inflammatory markers. This patient had a history of temporal artery biopsy–proven GCA that had responded initially to prednisone therapy, but flared with an extensive vasculitic neuropathy when her prednisone taper reached 10 mg/day. Subsequent treatment with high doses of GCs and daily cyclophosphamide led to multiple complications, including osteoporosis, severe leukopenia, and multilobar pneumonia. After 2 years of relapsing disease despite immunosuppressive therapy, we elected to treat her with TCZ.
During TCZ therapy (6 months), her inflammatory markers normalized and she was able to taper the prednisone dose by 1 mg every 2 weeks without having an exacerbation of her symptoms. When the daily dose of 4 mg was reached, a reversal of her colostomy was performed. Two days after the elective surgery, she developed shortness of breath unaccompanied by chest pain and died of a myocardial infarction.
The autopsy revealed active GCA involving the brachiocephalic, subclavian, carotid, vertebral, and femoral arteries. The most severe involvement was in the right subclavian artery (Figure 3). The right superficial temporal artery also showed active GCA, as did both the thoracic and abdominal aorta. There was focal mild involvement of the coronary arteries by GCA. The coronary arteries also showed severe atherosclerosis with 80% stenosis. The cause of death, an acute myocardial infarction of the left ventricle, was attributed to the rupture of an atherosclerotic plaque.
We observed good clinical and serologic responses in this group of patients whose LVV and PMR had been severe and highly refractory to GCs and other conventional and biologic immunosuppressive agents. The response to TCZ in our patient cohort is consistent with the concept that IL-6 is an important mediator in the pathogenesis of disorders in this disease spectrum. Our experience is the largest reported to date and the only one to provide information on treatment for at least 6 months in the majority of cases (33–38). The autopsied case that we described also provides an important cautionary note, indicating the possibility that LVV may persist in some cases despite apparent clinical control.
Our results are in concordance with other small series and case reports using TCZ for the treatment of LVV and PMR, but histologic evidence of inflammation despite TCZ treatment has not been described before. Seitz et al (33) reported rapid and complete clinical improvement in a group of 7 patients with relapsing and newly diagnosed LVV (5 with GCA, 2 with TA) treated with TCZ 8 mg/kg for a mean period of 4.3 months. Two subjects received TCZ monotherapy and 5 patients were able to taper their GC dosage significantly from a mean of 26.5 mg/day at the first TCZ administration to 4.5 mg/day at 12 weeks. Evidence of active LVV on baseline magnetic resonance angiography entirely disappeared in 3 GCA patients and improved in 2 TA subjects after 3 months of treatment. Salvarani et al (38) published a pilot study of 4 patients with LVV (2 with GCA, 2 with TA) treated with TCZ 8 mg/kg for 6 months followed by MTX maintenance therapy. Three patients entered complete clinical remission and 1 case achieved a partial response. All cases had improvement of vascular fluorodeoxyglucose uptake seen on baseline PET-CT. In 2 relapsing patients who were taking GCs at the time of TCZ initiation, prednisone was tapered off or gradually decreased to 2.5 mg/day by the end of the study period. Beyer et al (34) successfully treated 3 refractory LVV patients with TCZ 8 mg/kg for 6 months. Radiographic signs of activity assessed in 2 cases by PET-CT resolved, and all individuals were able to taper their daily prednisone dose below 7.5 mg.
IL-6R blockade has a sound pathophysiologic basis for the treatment of LVV. Vascular inflammation in GCA is hypothesized to be driven primarily by 2 lineages of CD4-positive T cells: an interferon-γ–producing Th1 cell line, and IL-17–secreting Th17 lymphocytes (39, 40). These cells infiltrate large and medium-sized blood vessels in response to chemotactic stimuli produced by dendritic cells after recognition of unknown danger signals within the vascular wall (41). IL-6 appears to act in concert with IL-1, TNFα, IL-23, IL-21, and transforming growth factor β (TGFβ) to promote the differentiation of naive T helper cells toward a Th17 phenotype with autoimmune characteristics (39). IL-17, in turn, stimulates macrophages and other resident cells within the vascular wall (endothelium, fibroblasts, and smooth muscle cells) to produce proinflammatory cytokines, including IL-6, thereby creating a positive feedback loop. The blockade of the IL-17/IL-6 cycle is one putative mechanism whereby TCZ could exert beneficial effects in patients with GCA (42, 43).
A second (and not mutually exclusive) potential mechanism of IL-6R antagonism in this disorder is the generation of Treg cells that counterbalance the effects of autoreactive lymphocytes. Th17 and Treg cells share a reciprocal developmental pathway. FoxP3, the master transcription factor of Treg cells, is induced by TGFβ and inhibited by IL-6. Therefore, TCZ could shift the Th17/Treg balance in favor of regulatory cell commitment, leading to the amelioration of disease (44–47).
In 2001, Nishimoto et al successfully treated a patient with refractory TA in the context of ulcerative colitis with TCZ (36). In pulseless disease, early active vascular infiltrates mainly consist of γδ T lymphocytes, natural killer cells, macrophages, and cytotoxic (CD8+) and T helper cells. In contrast, late-stage lesions demonstrate extensive fibrosis, intimal hyperplasia, and luminal narrowing. Patients with TA have increased serum concentrations of IL-6 (48) and strong expression of IL-6 within their aortic tissue (49). Several effects of IL-6 might be relevant in the pathogenesis of TA. IL-6 is known for its ability to trigger T cell and fibroblast proliferation, as well as cytotoxic lymphocyte differentiation. Furthermore, IL-6 stimulates the endothelial expression of intercellular adhesion molecule 1 and monocyte chemotactic protein 1, which in turn regulates the extravasation and chemotaxis of monocytes into inflamed tissues. Suzuki et al demonstrated that the rate of monocyte (U937 cell) adhesion to human umbilical vessel endothelial cells (HUVEC) was increased by pretreating HUVEC with IL-6 + sIL-6R, and this process was inhibited by TCZ (50). Infliximab, an inhibitor of TNFα, has been reported in open-label studies to be effective in TA (19). Because TNFα is upstream of IL-6 in the inflammatory cascade, one potential mechanism of action of infliximab in this setting could be the indirect reduction of IL-6 production.
TCZ binds to either sIL-6R or mIL-6R with an affinity similar to that of IL-6 and competes with the cytokine for its receptor. The administration of TCZ to our cohort of patients increased serum IL-6 levels significantly, an effect previously reported in other conditions (51). This phenomenon is explained by the fact that IL-6 normally undergoes receptor-induced catabolism, and this process is inhibited by IL-6R blockade (52). Circulating TCZ saturates IL-6R active sites, delaying IL-6 clearance and leaving its synthesis unopposed. In this regard, during pathologic states, serum IL-6 concentrations immediately after TCZ administration might reflect the actual state of endogenous cytokine production more accurately than do the concentrations before the initiation of treatment. Conversely, as data from a recently reported study of rheumatoid arthritis patients in Japan suggest (53), it is possible that asymptomatic patients receiving TCZ whose IL-6 levels decline over time are good candidates for lengthening the TCZ dosing interval or even discontinuing this therapy altogether. At this time, the meaning of the IL-6 levels during TCZ treatment for LVV remains unclear. Long-term followup of a larger cohort is required to have a better insight into this problem.
The finding of active LVV in 1 patient at autopsy confirms that TCZ requires rigorous testing in larger trials before it can be regarded as efficacious in this disease spectrum. It is known that LVV can often have an asymptomatic course (54). Moreover, persistent vascular inflammation despite apparent clinical control of the disease with GCs is well described in GCA patients, and some experts believe that GCs do not fully suppress vascular inflammation, even at high doses (55). Deng et al obtained a second temporal artery biopsy in 8 GCA patients 3–9 months after the initiation of treatment with prednisone, and found that all second-side biopsies had vasculitis by histomorphology (mainly interferon-γ–producing Th1 cells) (39). In this regard, the impact of anti–IL-6R therapy on the different inflammatory cell populations in GCA and its pathophysiologic consequences will require further study. It is presumed that blocking IL-6 will impact the Th17 arm, but the effects of this strategy on the Th1 and Treg cell compartments are less predictable. On the other hand, the unreliability of traditional acute-phase reactants for disease monitoring while receiving anti–IL-6 therapy may provide evidence in favor of exploring new biomarkers (e.g., Th1/Th17 signatures, vascular imaging) in order to assess the degree of disease activity in patients receiving TCZ.
Our study has certain limitations. Our conclusions must be circumscribed because of the retrospective nature of this study, the small number of subjects treated, the absence of controls, and the short followup period on the study medication. All of these factors could have distorted the magnitude of the effects and introduced bias. Nevertheless, the swiftness with which our patients' previously refractory clinical manifestations were controlled and their ability to taper GCs clearly give a positive preliminary signal that needs further study.
In summary, our findings are consistent with the concept that IL-6 may be a key mediator in GCA, TA, and PMR. Treatment with TCZ led to prompt clinical, serologic, and radiologic improvement in a group of patients with highly refractory/relapsing disease despite treatment with GCs and second-line immunomodulatory agents. At this juncture, adequately powered randomized controlled trials are needed to properly evaluate the safety and efficacy of TCZ for this spectrum of disease.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. J. H. Stone had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Unizony, Arias-Urdaneta, Khosroshahi, Keroack, J. R. Stone, J. H. Stone.
Acquisition of data. Unizony, Arias-Urdaneta, Miloslavsky, Arvikar, Khosroshahi, Keroack, J. R. Stone, J. H. Stone.
Analysis and interpretation of data. Unizony, Arias-Urdaneta, Khosroshahi, Keroack, J. R. Stone, J. H. Stone.
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- 28Treatment of refractory adult-onset Still's disease with tocilizumab: report of two cases and review of the literature. Rheumatol Int 2011; 31: 1653–6., , , , , .
- 29Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease. Intern Med 2007; 46: 771–4., , , , , , et al.
- 30The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33: 1122–8., , , , , , et al.
- 31The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 1990; 33: 1129–34., , , , , , et al.
- 32Prognosis and management of polymyalgia rheumatica. Ann Rheum Dis 1981; 40: 1–5., .
- 33Rapid induction of remission in large vessel vasculitis by IL-6 blockade: a case series. Swiss Med Wkly 2011; 141: w13156., , , , , .
- 34Anti-interleukin 6 receptor therapy as rescue treatment for giant cell arteritis [letter]. Ann Rheum Dis 2011; 70: 1874–5., , , , , , et al.
- 35Tocilizumab ameliorates clinical symptoms in polymyalgia rheumatica [letter]. J Rheumatol 2010; 37: 1075–6., , , .
- 36Successful treatment of a patient with Takayasu arteritis using a humanized anti–interleukin-6 receptor antibody. Arthritis Rheum 2008; 58: 1197–200., , , .
- 37Interleukin 6 blockade as steroid-sparing treatment for 2 patients with giant cell arteritis [letter]. J Rheumatol 2011; 38: 2080–1., , .
- 38Tocilizumab: a novel therapy for patients with large-vessel vasculitis. Rheumatology (Oxford) 2012; 51: 151–6., , , , , , et al.
- 39Th17 and Th1 T-cell responses in giant cell arteritis. Circulation 2010; 121: 906–15., , , , .
- 40Interleukin-21 modulates Th1 and Th17 responses in giant cell arteritis. Arthritis Rheum 2012; 64: 2001–11., , , , , , et al.
- 41Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis. J Exp Med 2004; 199: 173–83., , , , , .
- 42Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses. Arthritis Rheum 2008; 58: 3710–9., , , , , , et al.
- 43Interleukin-17 and type 17 helper T cells. N Engl J Med 2009; 361: 888–98., , .
- 44Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 2010; 327: 1098–102., .
- 45Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441: 235–8., , , , , , et al.
- 46Blockade of interleukin-6 signaling suppresses not only Th17 but also interphotoreceptor retinoid binding protein-specific Th1 by promoting regulatory T cells in experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 2011; 52: 3264–71., , , , , , et al.
- 47IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into FoxP3+ regulatory T cells. Proc Natl Acad Sci U S A 2008; 105: 18460–5., , , , , , et al.
- 48Serum cytokine profiles and their correlations with disease activity in Takayasu's arteritis. Rheumatology (Oxford) 2006; 45: 545–8., , , .
- 49Restricted usage of T-cell receptor Vα-Vβ genes in infiltrating cells in aortic tissue of patients with Takayasu's arteritis. Circulation 1996; 93: 1788–90., , , , , , et al.
- 50Anti-inflammatory mechanism of tocilizumab, a humanized anti-IL-6R antibody: effect on the expression of chemokine and adhesion molecule. Rheumatol Int 2010; 30: 309–15., , , .
- 51Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 2008; 112: 3959–64., , , , , .
- 52Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade of IL-6 clearance, but not via the induction of IL-6 production. Int Immunopharmacol 2008; 8: 1595–601., , , , , , et al.
- 53Drug free remission after cessation of tocilizumab (actemra) monotherapy (DREAM Study) [abstract]. Arthritis Rheum 2010; 62 Suppl: S750..
- 54Study of 52 patients with idiopathic aortitis from a cohort of 1,204 surgical cases. Arthritis Rheum 2000; 43: 901–7., , , .
- 55Influence of previous corticosteroid therapy on temporal artery biopsy yield in giant cell arteritis. Semin Arthritis Rheum 2007; 37: 13–9., , , , , , et al.


text:
Asperger Syndrome Center - Palm Coast, FL
- WebMD Physician Directory of Palm Coast Developmental-Behavioral Pediatrician Doctors
- Related Asperger Syndrome Articles
- Palm Coast Emergency Contacts
- Nearby Palm Coast Hospitals
- Find a Local Pharmacy on RxList - Palm Coast
Palm Coast Developmental-Behavioral Pediatrician Doctors for Asperger Syndrome
Type of Physician: Developmental-Behavioral Pediatrician
What is a Developmental-Behavioral Pediatrician? A subspecialty certification by the Board of Pediatrics; practitioners have a special interest in the developmental, learning, and behavioral problems of children, and in the support of parents and children during normal development and illness.
Specialty: Developmental-Behavioral Pediatrics
Common Name:
Developmental-Behavioral Pediatrician Doctors in Palm Coast * results
Don't see your city? Use the WebMD Physician Directory to expand your search.
Asperger's Syndrome (Asperger Syndrome, Asperger Disorder)
Asperger's syndrome facts
- Asperger's syndrome was formerly characterized as a distinct autism spectrum disorder; the DSM-5 in May 2013 combined the diagnosis with autistic disorder into one condition called autism spectrum disord...
Read the Asperger's Syndrome (Asperger Syndrome, Asperger Disorder) article »
Other Related Asperger Syndrome Articles
Emergency Contact for Palm Coast
- In case of Emergency, call 911
Nearby Palm Coast Hospitals results
- 1Florida Hospital Flagler
60 Memorial Medical Pkwy
Palm Coast, Florida 32164
(386) 586-200
- 2Flagler Hospital
400 Health Park Blvd
Palm Coast, Florida 32086
(904) 829-515
- 3Flagler Psychiatric Center
400 Health Park Blvd
Palm Coast, Florida 32086
(904) 819-456
- 4Florida Hospital Oceanside
264 S Atlantic Ave
Palm Coast, Florida 32176
(386) 672-416
- 5Florida Hosp Mem Med Ctr
301 Memorial Medical Pkwy
Palm Coast, Florida 32117
(386) 676-600
- 6Halifax Behavioral Services
841 Jimmy Ann Dr
Palm Coast, Florida 32117
(386) 274-533
- 7Halifax Health Medical Center
303 N Clyde Morris Blvd
Palm Coast, Florida 32114
(386) 254-400
- 8Putnam Community Medical Center
Hwy 20 W
Palm Coast, Florida 32177
(386) 328-571
- 9Clyde E Lassen State Veteran NH
4650 State Road 16
Palm Coast, Florida 32092
(904) 940-219
- 10Halifax Health Med Ctr Prt Orng
1041 Dunlawton Ave
Palm Coast, Florida 32127
(386) 322-470
* Provider Directory Terms of Use:
The WebMD 'Provider Directory' is provided by WebMD for use by the general public as a quick reference of information about Providers. The Provider Directory is not intended as a tool for verifying the credentials, qualifications, or abilities of any Provider contained therein. Inclusion in the Provider Directory does not imply recommendation or endorsement nor does omission in the Provider Directory imply WebMD disapproval.
You are prohibited from using, downloading, republishing, selling, duplicating, or "scraping" for commercial or any other purpose whatsoever, the Provider Directory or any of the data listings or other information contained therein, in whole or in part, in any medium whatsoever.
The Provider Directory is provided on an "AS-IS" basis. WebMD disclaims all warranties, either express or implied, including but not limited to the implied warranties of merchantability and fitness for particular purpose. Without limiting the foregoing, WebMD does not warrant or represent that the Provider Directory or any part thereof is accurate or complete. You assume full responsibility for the communications with any Provider you contact through the Provider Directory. WebMD shall in no event be liable to you or to anyone for any decision made or action taken by you in the reliance on information provided in the Provider Directory.
The use of WebMD Provider Directory by any entity or individual to verify the credentials of Providers is prohibited. The database of Provider information which drives WebMD Provider Directory does not contain sufficient information with which to verify Provider credentials under the standards of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), National Committee for Quality Assurance (NCQA) of the Utilization Review Accreditation Committee (URAC).
By using the WebMD Provider Directory, you agree to these Terms and Conditions.

subset: commoncrawl


text:
Free shipping on orders of 3 or more. US only
JMX Running Socks
Unisex mini-crew
Designed for feet that hurt. Enjoying short but intense runs or going long distances on all terrains, in most weather conditions resulting in moderate to significant stress on the foot. Specifically engineered to deliver maximum protection and comfort in the critical strike zones for any runner prone to blisters, foot pain or discomfort.Product details below
You may also like
Unique padding specifically designed for Running
The Design of Thorlos Padded Running Socks
Insights into the design, development and testing of Thorlos activity-specific, clinically-tested padded running socks from David Varsik, THORLO's senior design engineer.
What Independent Clinical Studies Say About Thorlos
Thorlos padding has been the subject of eight independent clinical research studies that were published in peer-reviewed medical journals. The results showed the proprietary padding reduces foot pain, blisters and other foot conditions, pressures on the foot and moisture.
- Constructed with THOR•LON® fibers for superior softness, resilience, durability, and moisture-wicking for drier, better feeling feet.
- Cushioning over the toes to help protect against runner's toe.
- Flat knit instep and cushioning in arch for better fit, more support and less pressure on the feet for a more comfortable run.
- Low profile toe seam won't rub or irritate the feet.
- Unique padding specifically engineered for running, clinically shown to reduce blisters, pain, pressures and moisture for maximum protection.
Product Details
- Length: mini-crew
- Cushion: Thick Cushion
- Fiber Contents: 85% Exclusive THOR•LON® Acrylic , 12% Stretch nylon , 2% Spandex
- Care instructions: For longer product life, maximum protection and comfort, wash and dry inside out (to fluff up the pads) using liquid fabric softener after each use (to lubricate the fibers for longer life). For optimal benefits, liquid fabric softeners are always recommended. Do Not Bleach. Wash Normal: 105F/40C. Dry Normal Medium. Do Not Dry Clean. Do Not Iron.
- Proudly made in the USA
Thorlos Guarantee: Thorlos Brand Promise,
Your feet will feel better or your money back®.
885 Reviews
Best socks for hurting feet
I bought these socks for my husband and he swears they are the BEST socks for feet that hurt when running or even walking/standing for a long time. He can't believe how good his feet feel with them on!
Zumba feet!
I feel like I'm dancing on a cloud!
Best socks for everything! Running, walking, working on your feet all day.
My feet are cushioned and stay dry all day. I wouldn't work without this sock!
Improved Construction
I had ordered these socks in the past and really enjoy the added comfort they provide, but the top seam has started to unravel on some of them. I reordered the same socks recently and it appears Thorlo reinforced the top of the ankle seam to make it more durable. Nice improvement to an already superior sock. My only disappointment was that the version with the light-colored padded areas, as opposed to the blue, was sold out in my size.
The only six I wear
They take care of my feet.
Best overall socks
Very good! These socks are great. They are very soft inside. I have been wearing Thorlo for many years, and these are the most comfortable. I bought four pair and keep washing them regularly. So, I always have a clean pair to wear.
great product
Great product. Not cheap but worth the $$.
too hot for summer
thick and they last, but too hot for summer, need thinner
Great work out socks
Tried buying these from Dick's in Mount Pleasant SC but they were always out of them. I went to your web site and ordered them. Much easier
All Time Favorite
I have very bad feet and am on them all day long. These socks really help with preventing foot fatigue. I have been wearing these socks for years. I love them.


text:
tough one
It's either south east or central
SOUTHEAST!!! its got The Hawks, The Magic,The Heat, and The Wizards(i know they suck, but i still like watching them)
Central is pretty interesting too (Cavs,Bulls,Bucks)
Northwest, has my favorite team the Nuggets, along with Portland and Utah, all three teams winning 50 games this season.
ooo tough 1.. pacific is pretty cool the lakers and warriors are always fun to watch and the kings always put up a fight plus they got tyreke.... but the southwest is fun too with the spurs and mavs and rockets
You have gotta go with the Northwest They got playoff teams in everyone except the t-wolves who just suck in general. Plus you gotta love watching Durant do his thing.
ACTIVE is the leader in online event registrations from 5k running races and marathons to softball leagues and local events. ACTIVE also makes it easy to learn and prepare for all the things you love to do with expert resources, training plans and fitness calculators.


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The Challenge Of Intermarriage
Regarding your "Raising Catholic Kids" symposium [1] (December 6, 2013): I am a practicing Catholic father married to a non-Catholic. I am the child of a Catholic mother and a Jewish father. I have some knowledge of the results of surveys documenting very high rates (over 50 percent) of intermarriage among non-Orthodox U.S. Jews. There is a negative correlation between levels of observant activity (in Judaism and probably all religions) and rates of intermarriage—those most intensely interested in their faith are less likely to marry outside it.
Forty years ago, I married a Jewish woman. The ceremony had to be conducted on "neutral territory" by both a priest and a rabbi, under multiple dispensations. Partly because of my own experience, I'd hoped to educate my children as Catholics, but I underestimated both the strength of my wife's commitment to her faith and the depth of her hostility to most things Catholic. We ultimately agreed that the children would be sent to a Reform Jewish Sunday school—I would drop them off on my way to church and pick them up afterward. I naïvely hoped that they would thereby acquire a belief in "the God of the Book," and I would have opportunities to advance their religious education by eventually informing them...
Links[1] https://www.commonwealmagazine.org/symposium-raising-catholic-kids
[2] https://www.commonwealmagazine.org/user/login?destination=print/35494
[3] https://www.commonwealmagazine.org/subscribe-Commonweal


text:
Lebo's Soweto Backpackers
Real Reviews
Real reviews from fellow travellers
These are trusted reviews from guests who have actually stayed here. We hope you find them helpful.
Note: we only give a property a rating once it has received a minimum of 3 reviews.
- Page:1/1
- " Quite a nice place to stay, in the heart of Soweto with acceptable facilities. Unfortunately, the night staff person, a woman, invited at least 2 men to have an extremely loud party with her; after complaining directly to her at 10:30 pm to please be quiet, she apologized only to continue even more loudly until after 1 am. I could not sleep at all and had to change accommodation the next morning. It is quite sad for Lebo's Soweto Backpackers to lose business because of one bad employee! "
- 22 Oct 2013 Anonymous Canada


text:
Former Fed Monetary Chief Madigan Hired by Barclays Capital
Brian Madigan, the Federal Reserve's former top staff adviser on interest-rate policy, was hired by Barclays Capital to provide counsel on economic research and regulation.
Madigan, who ended a three-decade Fed career last year and served from 2007 to 2010 as director of the monetary-affairs division, will be senior policy adviser and based in New York, Head of Research Larry Kantor said today in an internal memo obtained by Bloomberg News. Erica Chase, a Barclays spokeswoman, declined to comment.
The 57-year-old Madigan is a marquee name for a Barclays Plc division where Dean Maki, a former Fed researcher, is chief U.S. economist and two other former researchers, Troy Davig and Michael Gapen, were hired in the past year. Madigan and Federal Reserve Bank of New York President William C. Dudley were the main architects of many emergency-lending programs implemented by the central bank in 2008.
Barclays is the U.K.'s third-largest bank by assets, and Barclays Capital is the investment-banking division. At the Fed, Madigan was succeeded in July, by William English, a former top deputy, ahead of the decision to buy $600 billion of Treasuries in a second round of asset purchases. Madigan retired from the central bank on Sept. 1, said David Skidmore, a Fed spokesman.


text: Oga is only concerned with making the demon mark on his hand revert. These plans go straight to hell, thanks to Hilda and some toys from the demon world. This sends the episode into WTF mode. This anime has been consistently funny for me, but this is the best type of funny, it's random and absurd. Oga's and Furuichi's nurse outfits are wrong on so many levels! Shoulder-pads, why would any self-respecting nurse need those? Oga's idea of curing someone needs a serious evaluation, unless he's living in bizarro world. In short, I love episode 6, I haven't laughed this hard since episode 10 of Arakawa Under the Bridge x Bridge.


text:
The Romance in Paradise Package includes:
Package rates are quoted in US Dollars based on double occupancy and are subject to a 10% service charge and a 10% VAT.
Total Package Price: US$7,834.00 , excluding tax and service charge.
Ladera St Lucia Resort offers a unique design in luxury guest accommodations. The Caribbean resort villas & suites all have an
"open wall" - the west side of each unit is left open to expose the breathtaking views overlooking the Pitons and Caribbean Sea.


text:
Administrative and Educational Support Assessment
All Academic Departments and designated Administrative and Educational Support (AES) departments develop assessment plans. While the plans from the academic areas address student learning, those of the AES departments generally are more oriented towards assessing services the college provides. This institutional assessment evaluates the overall effectiveness with which the college is achieving its goals. It allows the College to better prioritize its resources, identify challenges and opportunities, improve efficiency and enhance student outcomes and stakeholder information. There is a CIE Fellow who works with the AES areas to help in the development and implementation of assessment plans.


text:
Re: Child Support Woes
My suggestions would be
* file the grievance with CS
* file a complaint with the BBB - CS has an obligation to provide proof that they have the right to collect.
* go to court and change the court order. No one has provided proof of actively attending school. And you want a limit on how long this game of going to school can be played/paid. Suggest a limit of 8 semesters total?
(1,535 Views)


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Why this course?
This unique course – the first of its kind in Europe – meets the needs of graduate students who want to contribute to environmental improvement and the circular economy, and learn how to identify and evaluate business opportunities. It's a collaboration between:
- Department of Civil & Environmental Engineering
- Hunter Centre for Entrepreneurship
The course also has contributions from eight other engineering departments, the Business School and the Law School.
Throughout the course, you'll develop skills that'll allow you to launch new ventures, strategies, products, and technologies that address society's environmental and natural resource problems.
Although this course is offered by an engineering department, it is unique as it accepts students from all backgrounds (social sciences, arts, engineering, law, chemistry, maths, physics, geology, biology and business). Students are able to select class options from a wide range of subjects to suit their background.
The course is suitable for anyone who'd like to refocus their career on environmental or sustainable entrepreneurship.
You'll study
You'll follow a curriculum of five core modules and a wide range of optional modules. Each module is taught for two to three hours per week over eight to 12 weeks. MSc students also undertake a dissertation.
Following successful completion of the taught component, you'll undertake a dissertation from June to August.
Work Placement
The Client-Based Environmental Entrepreneurship in Practice class has been developed for this MSc. This class has no formal teaching and instead sees you carry out a four month project of interest to a client, while at the same contributing to ecopreneurship in practice.
Our £6 million state-of-the-art laboratory facilities are well-equipped with high-technological instrumentation and available space to investigate:
- environmental & molecular microbiology
- environmental chemistry
- analytical chemistry
- geomechanics & soil quality
- structural design & material science
Teaching staff
The delivery team is made up of leading academics from the Department of Civil & Environmental Engineering and the Hunter Centre for Entrepreneurship.
- Dr Elsa João - Course Leader
- Mr Dominic Chalmers - Hunter Centre for Entrepreneurship
The course also has contributions from eight other engineering and business school departments as well as The Law School.
Flexible Learning
Home students can also choose to study through Flexible Learning. This is initially a non-graduating route. You register for one module at a time and have the option to build up credits eventually leading to a Postgraduate Certificate, Postgraduate Diploma or MSc. You can take up to five years to achieve the qualification.
This option is popular with students in employment, who may wish to undertake modules for Continuing Professional Development purposes.
Home students who do not meet the normal MSc entry requirements for this programme are welcome to apply through the Flexible Learning route.


text:
- OSI-Approved Open Source (15)
- Windows (15)
- Linux (14)
- Mac (11)
- Android (8)
- Grouping and Descriptive Categories (6)
- Modern (5)
- Embedded Operating Systems (1)
File Sharing Software
- BitTorrent
- Direct Connect
Hot topics in File Sharing Softwaresearch engine javascript yandex dumper and jumper jumper i2p portuble ares plus driver i2p os web sound} gnutella
Emu10k1 sound driver
Emu10k1 sound driver37 weekly downloads
ApexKB (Formerly Jumper)
ApexKB is a collaborative search engine that is powered by social bookmarking. It uses peer and social-networking principles to tag and link distributed content, media, or data to make valuable information more easily discoverable.7 weekly downloads
i2psuite is a suite of applications for Windows and Linux and is aimed to make use of the I2P network much easier. The suite contains many applications useful to I2P in an easy to install and easy to use suite. READ HOWTO ON DOWNLOAD PAGE OF WEBSITE16 weekly downloads
AMIGIFT is a FileSharing Application for AmigaOS compatible systems. It is mainly a User Interface to the giFT daemon, plus the distribution includes everything ready to run. Currently supported networks are FastTrack, Gnutella, OpenFT, and Ares.6 weekly downloads
pup2p is a remaster of the Puppy Linux livecd distro and is aimed at use with the anonymous network I2P. It includes I2P as well as a number of I2P related apps. NOTE: The ISO is currently VERY out of date! Sorry for my absence. I may try to update the project soon. The SFS file IS up to date as of this change. 03/20132 weekly downloads
A Chatting software in java implementing the concept of Peer to Peer architecture. The software facilitates the following:: 1.Private Chat 2.Conference Chat 3.File Transfer 4.Implementation of system tray icon along with user defined personal icon1 weekly downloads
Aeonserv is an authority grade package of the latest in Apache, MySQL, PHP, PERL, AWStats, phpMyAdmin & Geeklog builds. Designed to easily be customized and deployed within a matter of minutes it proves to be professional and ahead of its class.1 weekly downloads
Very simple script to download files from rapidshare in automatic mode. It supports only the 'free' method of downloading files. There is win32 version avalible, unix bash script and python source1 weekly downloads
Andalus- The Open Source Islamic Library
Andalus is a high availability, fully featured Islamic library written entirely in Java. It is a technology suitable for nearly any application that requires to make use of integrable Islamic resources. http://openandalus.wordpress.com/
Free Cell Phone Ring Tones
Do you pay for ring tones on your cellphone? Well the idea here is to make a web based application for all platforms that can be used to upload your own music and convert it from .mp3 format to ring tone format and send it to your phone in a text message
Kor-Vi parallel corpus collection
every things about my collected corpus
MySQL Image Hosting System
This (very light) script will host your image in MySQL. You can add an antileech script too.
Speedy Communication
Develop algorithms and software to speed communications, compress files, save disk space and band width and enable much faster file sharing. Use hashing and encryption to overcome problems and enable users to share multiple files simultaneously.
UnderLoader is a free based Python script to upload files to massive file servers like RapidShare or MegaUpload
ultimate data sharing
ultimate data sharing


text:
Heron Glass
Murrine Ball Ornament
Product Actions
A great addition to any collection, this intricately designed murrine glass ornament is hand made and features sea-themed images, including shells and starfish.
Style # 501953547
Need Help? Have Questions? Contact Us.
Please call 1.888.222.7639 to speak with a Customer Service Representative.
We're here to help you:
Monday - Friday, 9 AM - 9 PM (ET)
Saturday - Sunday, 10:30 AM - 7 PM (ET)
If you prefer email, we can be reached anytime at firstname.lastname@example.com.
Free Shipping & Returns on all U.S. Orders. See Details.


text:
Sometimes I get data feed like this:
-65° to 180°F. I unescaped this HTML, which will give me -65° to 180°F. whereas what I need is -65° to 180°F. Which brings me to conclusion that I need to unescape the HTML twice.
I've use this simple code to unescapeHTML twice.
String newtext = StringEscapeUtils.unescapeHtml(text);
String newtext2 = StringEscapeUtils.unescapeHtml(newtext);
But when I print the newtext2 contents, it's still shows -65° to 180°F. This still happened even if I unescaped it thrice. Why did the unescapeHTML can't unescape the HTML the second time? How can I work around this?


text:
As Hurricane Irene barrels toward the east coast and NYC Mayor Bloomberg considers...
As Hurricane Irene barrels toward the east coast and NYC Mayor Bloomberg considers evacuations, shares of some commercial and homeowner insurers look vulnerable to a temporary drop - and a possible buying opportunity - Sandler O'Neill analysts say. Today, insurance stocks (KIE -1.6%) are sinking: CB -4%, TRV -2.6%, AFL -2.3%, XL -1.3%, AIG -0.7%.
From other sites
Video at CNBC.com (Oct 3, 2014)
Video at CNBC.com (Aug 25, 2014)
Video at CNBC.com (Aug 15, 2014)
Video at CNBC.com (Jul 3, 2014)
Video at CNBC.com (May 16, 2014)
ETF Hub
ETF Screener: Search and filter by asset class, strategy, theme, performance, yield, and much more
ETF Performance: View ETF performance across key asset classes and investing themes
ETF Investing Guide: Learn how to build and manage a well-diversified, low cost ETF portfolio
ETF Selector: An explanation of how to select and use ETFs


text:
On Sunday, Malaysian authorities revealed a particularly eerie detail in the case of the missing jetliner: When someone at the controls calmly said the last words heard from the plane, one of the Boeing 777's communications systems had already been disabled, adding to suspicions that one or both of the pilots were involved in the disappearance of the flight.
Malaysian Defense Minister Hishammuddin Hussein said at a news conference that the final, reassuring words from the cockpit - "All right, good night" - were spoken to air traffic controllers after the ACARS system was shut down. Whoever spoke did not mention any trouble on board, seemingly misleading ground control.
Investigators examined a flight simulator confiscated from the home of one of the pilots and dug through the background of all 239 people on board, as well as the ground crew that serviced the plane.
The Malaysia Airlines jet took off from Kuala Lumpur in the wee hours of March 8, headed to Beijing. On Saturday, the Malaysian government announced findings that strongly suggested the plane was deliberately diverted and may have flown as far north as Central Asia or south into the vast reaches of the Indian Ocean.
Authorities have said someone on board the plane first disabled one of its communications systems - the Aircraft and Communications Addressing and Reporting System, or ACARS - about 40 minutes after takeoff. The ACARS equipment sends information about the jet's engines and other data to the airline.
Around 14 minutes later, the transponder that identifies the plane to commercial radar systems was also shut down. The fact that both systems went dark separately offered strong evidence that the plane's disappearance was deliberate.
Given the expanse of land and water that might need to be searched, finding the wreckage could take months or longer. Or it might never be located. Establishing what happened with any degree of certainty will probably require evidence from cockpit voice recordings and the plane's flight-data recorders.
The search area now includes 11 countries the plane might have flown over, Hishammuddin said, adding that the number of countries involved in the operation had increased from 14 to 25.
"The search was already a highly complex, multinational effort," he said. "It has now become even more difficult."
The search effort initially focused on the relatively shallow waters of the South China Sea and the Strait of Malacca, where the plane was first thought to be. Hishammuddin said he had asked governments to hand over sensitive radar and satellite data to try to get a better idea of the plane's final movements.
With more information, he said, the search zone could be narrowed "to an area that is more feasible."
Malaysia is leading the search for the plane and the investigation into its disappearance.
In the United States, Dan Pfeiffer, senior adviser to President Barack Obama, told NBC's "Meet the Press" that the FBI was supporting the criminal probe.
Rep. Peter King, chairman of the House Homeland Security subcommittee on counterterrorism and intelligence, said on ABC's "This Week" that so far "there's nothing out there indicating it's terrorists."
Investigators are trying to answer these questions: If the two pilots were involved in the disappearance, were they working together or alone, or with one or more of the passengers or crew? Did they fly the plane under duress or of their own will? Did one or more of the passengers manage to break into the cockpit or use the threat of violence to gain entry and then seize the plane? And what possible motive could there be for diverting the jet?
Malaysia's police chief, Khalid Abu Bakar, said he asked countries with citizens on board the plane to investigate their backgrounds, no doubt looking for anyone with terrorism ties, aviation skills or prior contact with the pilots. He said that the intelligence agencies of some countries had already done so and found nothing suspicious, but he was waiting for others to respond.
Police searched the homes of both pilots Saturday, the first time they had done so since the plane vanished, the government said. Asked why it took them so long, Khalid said authorities "didn't see the necessity in the early stages."
Police confiscated the elaborate flight simulator that one of the pilots, Zaharie Ahmad Shah, had built in his home and reassembled it in their offices to study it for clues, Khalid said.
Zaharie, 53, who has three grown children and one grandchild, had previously posted photos online of the simulator, which was made with three large computer monitors and other accessories. Earlier this week, the head of Malaysia Airlines said the simulator was not in itself cause for any suspicion.
Malaysian police were also investigating engineers and ground staff who may have had contact with the plane before it took off, Khalid said.
Even though the ACARS system was disabled on Flight 370, it continued to emit faint hourly pulses that were recorded by a satellite. The last "ping" was sent out at 8:11 a.m. - 7 hours and 31 minutes after the plane took off. That placed the jet somewhere in a huge arc as far north as Kazakhstan in Central Asia or far into the southern Indian Ocean.
While many people believe the plane has crashed, there is a small possibility it may have landed somewhere and be relatively intact. Affendi, the air force general, and Hishammuddin, the defense minister, said it was possible for the plane to "ping" when it was on the ground if its electrical systems were up and running.
Australia said it was sending one of its two AP-3C Orion aircraft involved in the search to remote islands in the Indian Ocean at Malaysia's request. The plane will search the north and west of the Cocos Islands, a remote Australian territory with an airstrip about 1,200 kilometers (745 miles) southwest of Indonesia, military chief Gen. David Hurley said.
Australian Prime Minister Tony Abbott said he will speak with Malaysian officials Monday to see if they wanted additional search help.
Asked whether any Australian agency had picked up any information suggesting the plane flew near Australia, Abbott said: "I don't have any information to that effect, but all of our agencies that could possibly help in this area are scouring their data to see if there's anything they can add to the understanding of this mystery."
Given that a northern route would have sent the plane over countries with busy airspace, most experts say the person in control of the aircraft would more likely have chosen to go south. The southern Indian Ocean is the world's third-deepest and one of the most remote stretches of water in the world, with little radar coverage.
Whoever disabled the plane's communication systems and then flew the jet must have had a high degree of technical knowledge and flying experience, putting one or both of the pilots high on the list of possible suspects, Malaysian officials and aviation experts said.
(MORE: Here's What Caused That Strange Oil Slick)
"The search was already a highly complex, multinational effort. It has now become even more difficult," Acting Transport Minister Hishammuddin Hussein said at a news conference Sunday. "It is our hope with the new information, parties that can come forward and narrow the search to an area that is more feasible."
As the search for the plane rages on, Malaysian authorities opened a formal criminal investigation into who in the plane was involved in the "deliberate" disappearance of the flight. Malaysian police searched the homes of both pilots of Flight 370 Saturday, confiscating the flight simulator plane in captain Zaharie Ahmad Shah's home.
Malaysian police chief Inspector General Khalid Abu Bakar told reporters that he had requested countries with citizens on board the plane to investigate their background. He said that the intelligence agencies of some countries had already done this and found nothing suspicious, but that he was waiting for others to respond.
Information from the Associated Press was used in this report
A member of Indonesian National Search and Rescue Agency uses a binocular to scan the horizon during a search operation for the missing Malaysia Airlines Boeing 777. (AP Photo/Heri Juanda)


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Contact Information
831 NJ-10 #3 Hanover, NJ 07981
831 New Jersey 10 #3USNew Jersey07981
(973) 428-5400meltingpot.com
Fondue Restaurant, BarToday 5–10PMMenu
Welcome to the Melting Pot of Whippany, located on Route 10 in the Pine Plaza Shopping Center. We offer a truly unique dining experience created by the art of fondue.
Whether you are celebrating a birthday, anniversary,romantic date night, or celebrating with a group, The Melting Pot restaurant is perfect for any occasion.
The Melting Pot has mouth-watering options for all tastes and budgets. Choose from our fresh salads served with signature dressings, or dip straight into our award-winning cheese fondue selections with vegetables, artisan bread, and delicious meat options like seafood and steak. Craving dessert? Enjoy our decadent chocolate fondue with a selection of dippers that satisfy any sweet tooth. We are also pleased to offer a gluten free menu.
Google+ URL


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Windows Phone 8: Using the Speech API
- Date: to
- Day 4
- B92 Magellan
- 3-050
- Speakers: F Avery Bishop
- 12,028 views
- 5 comments
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While we wait for the slides to become available if you could respond here with the URLs mentioned in the last slide that would be very helpful!
Online help for speech API in Windows Phone 8 is here.
November and December MSDN Magazine articles on Speech in Windows Phone.
The November issue is at
This blog entry by Rob Chambers has a lot of good links to resources on Windows Phone development, including speech.
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When Chris Connolly first came to Des Moines, he said he had little to expect from the city.
The general manager of the Iowa Events Center, Connolly said he accepted the Des Moines-based position from his bosses at Global Spectrum "sight unseen." He did it for the career move.
Fast-forward three and a half years, and Connolly said he loves living in Des Moines.
While primarily responsible for making sure the convention center stays in the black, he's also become involved in a major downtown project — an attached convention hotel — that he and others have said would bring the events center and the city to the next level.
Connolly sat down with the Register recently to discuss his move to Des Moines, his role as general manager and plans for the convention hotel.
Q: What was your thought process when coming to Iowa?
A: Honestly, I took this position primarily for the opportunity, the work opportunity. The social piece, living arrangements, everything else that comes along with Des Moines were sight unseen. ... I could not be happier, being in Des Moines. ... I've just been able to get involved in a lot of other things than just facility management. A lot of that pushes back to our business and improving our business with those connections. I love that piece. ... You don't get many communities like this.
Q: When you are bringing an act or an event to Des Moines, what do you have to do?
A:For us, quite simply why we've done so well: Our market's strong, the acts that come in sell out, they do very well, we have a great building and we treat them well.
We make it easy for them. From the time they load in at 8 o'clock in the morning and our stagehands are putting up the sound and lights to the time they leave at the end of the night, the goal for us is to, number one, sell tickets, do a great job marketing, make it easy on them in settlement and have them say when they are leaving Des Moines, "Hey, that was a great place to play."
Q: Has there ever been an act, a convention, a sports event that you haven't been able to bring in yet?
A: My comments there would be, far and away, men's NCAA basketball. ... We feel like we have what it takes to get it done.
Obviously, we've put bids in in the past and that hasn't worked out and that's really number one on the wish list. That's really where the attached convention center hotel comes in and that plays a big role and that would really help us.
Q: There's still a lot of work ahead for the hotel, but when does your role come into play?
A: Once a financial deal is reached and say the shovel gets put into the ground and we have a date of when it would officially open, we're going to go out right away and start pitching it. We'll start pitching it to some of our clients that we've either lost in the past or just haven't made it here because that piece was missing.
Q: When you say that you've lost clients, how do you know the convention hotel will help?
A: We know it's going to work because over the last five years of us tracking potential events and clients that we've lost, just getting that feedback. We have hard data on bigger clients saying, "Hey, we're not coming to Des Moines because of the (lack of an) attached convention hotel." ... The business that we have going on in there is great, but it's not the home-run hit. The home-run hit is getting a convention where there's 7,000 people coming to the city of Des Moines and they are staying four or five nights.
Chris Connolly
Age: 39.
FAMILY: 7-year-old son, Brayden.
EDUCATION: Bachelor's degree in business with a concentration on sports management, Widener University, 1997.
CAREER: Spent six years at the Wells Fargo Center in Philadelphia, starting as an intern and part-time worker. Worked as a marketing coordinator then event coordinator and finally a senior event manager for the center. Served as assistant general manager for four years at Budweiser Gardens in London, Ontario. Worked as general manager of the Roanoke Civic Center in Roanoke, Va. Came to Des Moines in March 2011 to work as the general manager of the Iowa Events Center.
Chris Connolly's favorite events
Chris Connolly's favorite live shows, he said, were the Zac Brown Band for their sound and Jimmy Buffett "because he's such a heavyweight and for him to come to Des Moines, that was a huge big deal."
As for sports events, he said working the NCAA Wrestling Championships in March 2013 was his favorite.
"We personally, we didn't know if we would be able to handle it. That was an incredible thing to work," he said.
Connolly also mentioned the 2012 Iowa caucuses and election, which brought political heavyweights and national media to Des Moines:
"For me, coming from the East Coast and not being familiar with politics out here in the Midwest, the caucuses in 2012, that was incredible. That was an incredible ordeal to be a part of. That was probably one of my biggest challenges, just trying to figure out how that all works."


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Dan Kulick has over 18 years of brewing experience. He started homebrewing while attending the University of Pittsburgh. He is still true to his homebrew roots by being vice president of the A.L.C.Y (Ales and Lagers Carbonated by Yeast) Homebrew club.
Dan then honed his craft as a professional Brewer at Rock Bottom Pittsburgh under the watchful eye of Brewmaster Matthew Carroll. He was the assistant Brewer at Rock Bottom for over four years. Now he brings his experience to Gettysburg to spread his wings!
Dan's favorite things to do outside of the Brewery is spending time trying products, hunting, watching NASCAR, and especially playing paintball as a member of the Whiskey Squad Paintball Team.
The brick farmhouse was completed around 1848 and the architecturally significant PA Dutch brick-end barn was completed the following year. Henry Monfort and his brother, Jacob, built the house and farmed the land. A family letter written on 8 July 1863, only 5 days after the battle of Gettysburg, documents events on the farm. As Johnson's Division began to be evacuated from Culps Hill, the farm was converted into a Confederate Field Hospital. Over 1,300 Confederates were brought here, making it one of the largest Confederate Hospitals, with soldiers occupying the house, barn and considerable space around the farm. When the Confederates retreated from Gettysburg, 446 soldiers were left at the farm. They remained for about 28 days before consolidation at Camp Letterman (Hospital Hill). Forty-seven died and were buried on the farm, but were disinterred and moved to Hollywood Cemetery in Richmond Virginia later. The families lost considerable livestock, crops, furniture, clothing, linens, etc. and were not compensated until the late 1880's. The farm remained in the Monfort family until around 1921.
Battlefield Brew Works' profits from its own Red Circle Ale goes directly to The Red Circle Foundation which supports the injured Special Operations Men and Women of our Armed forces. Read more about the Red Circle Foundation.
248 Hunterstown Road, Gettysburg, Pennsylvania 17325 (717)398-2907
email: email@example.com
Monday 4-9pm
Tuesday - CLOSED
Wednesday & Thursday 4 - 9pm
Friday 2 - 10pm
Saturday 12noon - 10pm
Sunday 2 - 8pm
248 Hunterstown Road Gettysburg, PA 17325
Singer/ Songwriter Canyon from Connecticut will be performing at the August Installment of the Fishbowl Sessions on Thursday the 4th! Music starts at 7pm!... read more
Hours for the Brewery/Distillery 248 Hunterstown Road Monday 4pm-9pm, CLOSED Tuesdays, Wednesday-Thursday 4pm-9pm, Friday 2pm-10pm, Saturday 12noon-10pm, Sunday 2pm-8pm Hours for the Tasting Room 45 Steinwehr Ave Monday- Wednesday 4pm-? Open while busy Thursday 4pm-9pm, Friday 2pm-10pm, Saturday 12noon-10pm, Sunday 12noon-5pm We be closed on July 4th Independence Day... read more
Please verify your age


text:
FORTY adorable kittens found homes of their own this past weekend through Seattle Humane Society's Snuggle Season $50 kitten promotion! Thank you to everyone who welcomed a loving, snuggly kitten into their lives and to everyone who helped spread the word.
Forty Kittens Adopted!
By joyce_zoldak on November 14, 2011 at 11:54 AM


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Bill banning minors from tanning beds sailing through legislature
Research shows melanoma rates for young women in Minnesota have increased about 5 percent every year for 15 years.
A bill that would prohibit minors from using tanning beds awaits floor votes in the House and Senate after sailing through committees in both chambers.
Current law requires parental consent for minors under 16 to use tanning beds, but the bill authored in the house by Rep. JoAnn Ward, D-Woodbury, would flat-out prohibit their use by anyone under 18.
See also:
Skin cancer rates for young women eight-times higher than in 1970, Mayo study finds
Ward says research showing tanning beds are especially harmful for young people motivated her to write the bill.
Rep. JoAnn Ward
"Research shows the ultraviolet radiation exposure in terms of carcinogenic production is equal to cigarettes and asbestos," Ward says. "The greatest instances of melanoma are men over 60 and young women in their 20s."
Ward says her bill enjoys "good strong bipartisan support," especially after the tanning industry recently came out in favor of it.
That was a significant development, as just a couple of years ago the Indoor Tanning Association was trying to blame Minnesotans' relatively pale skin, not tanning beds, for the state's rising skin cancer rates.
As for the argument that the state should allow parents to decide whether to let their kids tan, Ward counters that in cases where products or services are clearly harmful, regulation is warranted.
"As a parent you don't take your child and let them spend their money from mowing the grass on cigarettes or alcohol," Ward says.
-- Follow Aaron Rupar on Twitter at @atrupar. Got a tip? Drop him a line at [email protected]
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FDA Approves Lanreotide for Neuroendocrine Tumors »
"On December 16, 2014, the U. S. Food and Drug Administration approved lanreotide (Somatuline Depot Injection, Ipsen Pharma) for the treatment of patients with unresectable, well or moderately differentiated, locally advanced or metastatic gastroe"...
Read the FDA Approves Lanreotide for Neuroendocrine Tumors article »
(Generic versions may still be available.)
Generally, adverse effects following the use of Mithracin (plicamycin) , especially the hemorrhagic syndrome, are dose related. Therefore, following administration of an overdose, patients can be expected to experience an exaggeration of the usual adverse effects. Close monitoring of the hematologic picture, including factors involved in the clotting mechanism, hepatic and renal functions, and serum electrolytes, is necessary. No specific antidote for Mithracin (plicamycin) is known. Management of overdosage would include general supportive measures to sustain the patient through the period of toxicity.
Mithracin (plicamycin) is contraindicated in patients with thrombocytopenia, thrombocytopathy, coagulation disorder or an increased susceptibility to bleeding due to other causes. Mithracin (plicamycin) should not be administered to any patient with impairment of bone marrow function.
Mithracin (plicamycin) may cause fetal harm when administered to a pregnant woman. Mithracin (plicamycin) is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/8/2004
Mithracin FDA Prescribing Information
Additional Mithracin Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.


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Perry Farrell was just in the right place at the right time.
The 18-year-old University of Otago health sciences student
decided to find a more picturesque place to study on March 18
and ended up at St Clair Beach, where he saved a woman from
Fortunately, Mr Farrell is also a lifeguard for the Mt
Maunganui Surf Life Saving Club, and his actions have earned
him a special award from Surf Life Saving New Zealand.
A woman on a surfboard got caught in a rip near the rocks at
St Clair and was having trouble getting back to shore.
St Clair Surf Club was closed at the time, so Mr Farrell
grabbed a kneeboard and headed out beyond the breakers to
help the woman.
After bringing her back through the breakers to the safety of
the beach, he noticed she had very blue lips and looked
He sat her down and realised she needed treatment for
She was later taken to Dunedin Hospital by ambulance.
Each month, Surf Life Saving New Zealand selects a winning
rescue from each region.
Mr Farrell's rescue was named the top rescue of March for the
Southern Region.
Surf Life Saving New Zealand chairman Geoff Hamilton said the
''extraordinary'' effort shown by Mr Farrell was outstanding.
''Had Perry not been there that day, the woman had a fair
chance of drowning, as she was very tired and hypothermic,''
he said.
''Admiration of the skill and professionalism shown by those
involved in the incident is testament to qualities valued by
Surf Life Saving New Zealand and BP.''
Mr Farrell was unable to be contacted for comment.
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Focus: Linux Training
When I was in high school, many speakers came to talk to the students about our futures: jobs and options available after graduation. One thing every one of them stressed was the importance of going on to get further education and training. Without it, we were told we would face a life of work in the food industry or as sales clerks or low-level car mechanics. We were shown charts of how much more money we would make with the proper university degree or training certificate for the job we wanted. These things are still a top priority for most people entering the work force today. Developing skills that are fun as well as attractive to business consumes the minds of students approaching graduation and entering the real world.
Since our readers are Linux enthusiasts who would prefer to work with a Linux system rather than a Windows one, this month's focus is on Linux training. Training is needed so we can get out there and actually support ourselves using our favorite operating system. Many ways of getting that training are available, and we take a look at the ones most in use: traditional classrooms and web-based courses. All are geared toward getting Linux certification so that you can prove your worthiness to potential employers. We also have updates from the two existing certification programs: Linux Professional Institute and SAIR Linux.
We hope you have been enjoying our new "Cooking with Linux" column, which premiered last September and began in earnest with the January issue. Marcel Gagné is a talented author who has written for us in the past, and we are happy to have him join us as a regular contributor. He also writes a column called "SysAdmin's Corner" which appears on our web site (http://www.linuxjournal.com/). Marcel is a Linux geek with a nice sense of humor—what a guy!
Another web column you might like is "Currents" by Bryan Pfaffenberger, a university professor with a keen intellect, who probes the issues facing the computer and software industry today. He challenges us to think and form our own opinions about open source, copyrights, software patents and more.
—Marjorie Richardson, Editor in Chief
Trending Topics
Practical Task Scheduling Deployment
On Demand
One of the best things about the UNIX environment (aside from being stable and efficient) is the vast array of software tools available to help you do your job. Traditionally, a UNIX tool does only one thing, but does that one thing very well. For example, grep is very easy to use and can search vast amounts of data quickly. The find tool can find a particular file or files based on all kinds of criteria. It's pretty easy to string these tools together to build even more powerful tools, such as a tool that finds all of the .log files in the /home directory and searches each one for a particular entry. This erector-set mentality allows UNIX system administrators to seem to always have the right tool for the job.
Cron traditionally has been considered another such a tool for job scheduling, but is it enough? This webinar considers that very question. The first part builds on a previous Geek Guide, Beyond Cron, and briefly describes how to know when it might be time to consider upgrading your job scheduling infrastructure. The second part presents an actual planning and implementation framework.
Join Linux Journal's Mike Diehl and Pat Cameron of Help Systems.
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|The Firebird Project's Firebird Relational Database
|Jul 29, 2016
|Stunnel Security for Oracle
|Jul 28, 2016
|SUSE LLC's SUSE Manager
|Jul 21, 2016
|My +1 Sword of Productivity
|Jul 20, 2016
|Non-Linux FOSS: Caffeine!
|Jul 19, 2016
|Murat Yener and Onur Dundar's Expert Android Studio (Wrox)
|Jul 18, 2016
- Stunnel Security for Oracle
- The Firebird Project's Firebird Relational Database
- SUSE LLC's SUSE Manager
- Murat Yener and Onur Dundar's Expert Android Studio (Wrox)
- Managing Linux Using Puppet
- My +1 Sword of Productivity
- Non-Linux FOSS: Caffeine!
- Doing for User Space What We Did for Kernel Space
- Google's SwiftShader Released
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Geek Guides
With all the industry talk about the benefits of Linux on Power and all the performance advantages offered by its open architecture, you may be considering a move in that direction. If you are thinking about analytics, big data and cloud computing, you would be right to evaluate Power. The idea of using commodity x86 hardware and replacing it every three years is an outdated cost model. It doesn't consider the total cost of ownership, and it doesn't consider the advantage of real processing power, high-availability and multithreading like a demon.
This ebook takes a look at some of the practical applications of the Linux on Power platform and ways you might bring all the performance power of this open architecture to bear for your organization. There are no smoke and mirrors here—just hard, cold, empirical evidence provided by independent sources. I also consider some innovative ways Linux on Power will be used in the future.Get the Guide


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Loose-fitting garments modeled by a senior.
Or "友人" & "家族" in Japanese.
For the Rihanna Navy.
Coping with love, love lost and death with a new wave inspiration.
The French label and the fast-fashion brand connect on some bold pieces.
"Ecology is at the heart of this new work."
The Parisian streetwear brand returns with an all-new unisex capsule.
Taking inspiration from the minimalist Freizeit collections of the 1970′s.
Reinventing wardrobe essentials.
Are the pair collaborating on a hit track?


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PyCI is a web-based configuration interface written in Python for systems running OpenWRT.1 weekly downloads
This is only a port of the Widelands a realtime strategy game for the german tablet PC WeTab. The home site of widelands is http://widelands.org. Mor infos to widelands are there.1 weekly downloads


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WunderPhotos Upload
Ice Bells
Uploaded by: thomasanthony
Saturday December 5, 2009
Lawrence, KS (Current Weather Conditions)
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Boat Docks at Newland's Resort
Lakeview, Ohio 43331
Across the channel from Froggy's.
So close you could swim!
Call (937) 842-3021
Waterfront view from Newland's Resort
Cottage 1
Cottage 1
Take 33 W to Huntsville Exit - Route 117. Follow 117 seven miles. Turn left onto 235. Approximately 2 miles turn left at Sassafras Point (Newland's Resort).
From I-75
All cottages have Direct TV.
Cottage 1: Waterfront.Two bedrooms. One queen, and one full size bed. Includes air conditioning, a spacious living area, efficient kitchen, and a bathroom with shower. A futon is included on the enclosed porch to accomodate two.
Cottage 2: Waterfront.Two bedrooms, both with air conditioning, double beds, a futon, cozy living room, large kitchen, and a bathroom with shower. Also includes an enclosed porch.
Cottage 3: Sits on a hill overlooking Indian Lake. Walk down the hill to your boat dock. Two bedrooms, one queen, and one full size bed, a spacious living room, roomy kitchen , and a bathroom with a shower. Features a futon for two, picnic table with small grill, air conditioning, and a very large yard.
|Check In/Out Times
Cottage 1&2
Mon-Sat. Check In 2:00 - Check Out 10:00 Sunday.
Cottage 3
Check in 3:00 - Checkout 11:00
Air conditioning is available in all cottages
|Rates for May - September
Sunday-Thursday $100/night 2 adults $125/night 4 adults $150/night 6 adults
Friday and Saturday $150/night up to 4 adults $200/night 6 adults
Weekly rates $600 2 adults $700 4 adults $800 6 adults
These rates do not include holidays.
Sorry, No Pets Please.
Bring your own blankets and linens.
Call for availability and to reserve a cottage 937-842-3021 or Click here to email
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Boat Services
Contact: John Newland, JR. 937-935-4722
or email
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World Wide Web Enterprises, Inc.
Lakeview, Ohio 43331
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