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Economic benefits of subcutaneous rapid push versus intravenous immunoglobulin infusion therapy in adult patients with primary immune deficiency
Martin, A
Lavoie, L
Goetghebeur, M
Schellenberg, R
Transfusion Medicine (Oxford, England)
The objective of this study is to evaluate the economic benefits of immunoglobulin replacement therapy achieved subcutaneously (subcutaneous immunoglobulin, SCIG) by the rapid push method compared to intravenous infusion therapy (intravenous immunoglobulin, IVIG) in primary immune deficiency (PID) patients from the healthcare system perspective in the context of the adult SCIG home infusion program based at St Paul's Hospital, Vancouver, Canada.
Materials and methods
SCIG and IVIG options were compared in cost-minimisation and budget impact models (BIMs) over 3 years. Sensitivity analyses were performed for both models to evaluate the impact of varying modality of IVIG treatments and proportion of patients switching from IVIG to SCIG.
The cost-minimisation model estimated that SCIG treatment reduced cost to the healthcare system per patient of $5736 over 3 years, principally because of less use of hospital personnel. This figure varied between $5035 and $8739 depending on modality of IVIG therapy. Assuming 50% of patients receiving IVIG switched to SCIG, the BIM estimated cost savings for the first 3 years at $1·308 million or 37% of the personnel and supply budget. These figures varied between $1·148 million and $2·454 million (36 and 42%) with varying modalities of IVIG therapy. If 75% of patients switched to SCIG, the reduced costs reached $1·962 million or 56% of total budget.
This study demonstrated that from the health system perspective, rapid push home-based SCIG was less costly than hospital-based IVIG for immunoglobulin replacement therapy in adult PID patients in the Canadian context.
budget impact model; cost minimisation; IVIG; primary immune deficiencies; SCIG
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Subcutaneous Immunoglobulin-G Replacement Therapy with Preparations Currently Available in the United States for Intravenous or Intramuscular Use: Reasons and Regimens
Chouksey, Akhilesh
Duff, Kimberly
Wasserbauer, Nancy
Berger, Melvin
Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology
For patients who require replacement therapy for primary immunodeficiency, subcutaneous infusions of immunoglobulin G (IgG) may be preferable to intravenous infusions for several reasons. However, at present, there is no preparation marketed for use by this route in North America. In this article, we describe the reasons patients have selected this route of therapy and the range of treatment regimens used. Approximately 20% of our patients have chosen the subcutaneous route, mainly because of adverse effects from intravenous (IV) infusions or difficulties with venous access. Unit dose regimens using whole bottles of currently available 16% intramuscular preparations or sucrose-containing lyophilized preparations intended for IV use but reconstituted to 15% IgG for subcutaneous administration were individually tailored to each patient. In most cases, self-infusions or home infusions were administered once or twice a week, most commonly requiring two subcutaneous sites and 2 to 3 hours per infusion. On average, patients took 0.18 mL of IgG per kilogram of body weight per site per hour. There were no systemic adverse effects. In patients for whom comparative data were available, trough serum IgG levels were higher with subcutaneous therapy than with IV therapy.
Related Articles
Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease
Skoda-Smith, Suzanne
Torgerson, Troy R
Ochs, Hans D
Therapeutics and Clinical Risk Management
Antibody deficiency is the most frequently encountered primary immunodeficiency disease (PIDD) and patients who lack the ability to make functional immunoglobulin require life-long replacement therapy to prevent serious bacterial infections. Human serum immunoglobulin manufactured from pools of donated plasma can be administered intramuscularly, intravenously or subcutaneously. With the advent of well-tolerated preparations of intravenous immunoglobulin (IVIg) in the 1980s, the suboptimal painful intramuscular route of administration is no longer used. However, some patients continued to experience unacceptable adverse reactions to the intravenous preparations, and for others, vascular access remained problematic. Subcutaneously administered immunoglobulin (SCIg) provided an alternative delivery method to patients experiencing difficulties with IVIg. By 2006, immunoglobulin preparations designed exclusively for subcutaneous administration became available. They are therapeutically equivalent to intravenous preparations and offer patients the additional flexibility for the self-administration of their product at home. SCIg as replacement therapy for patients with primary antibody deficiencies is a safe and efficacious method to prevent serious bacterial infections, while maximizing patient satisfaction and improving quality of life.
subcutaneous immunoglobulin; primary immunodeficiency disease; antibody deficiency; X-linked agammaglobulinemia; common variable immune deficiency
Related Articles
Home-based subcutaneous immunoglobulin G replacement therapy under real-life conditions in children and adults with antibody deficiency
Hoffmann, F
Grimbacher, B
Thiel, J
Peter, HH
Belohradsky, BH
European Journal of Medical Research
Subcutaneous immunoglobulin (SCIG) therapy is an alternative to intravenous immunoglobulin (IVIG) therapy.
We evaluated the efficacy and safety of the SCIG Vivaglobin® (formerly known as Beriglobin® SC) under real-life conditions in a post-marketing observational study in 82 patients with primary or secondary antibody deficiencies. Health-related quality of life (HRQoL) was evaluated in a subset of 30 patients previously treated with IVIG (including 11 children < 14 years) using the Short Form 36 (SF-36) for patients ≥ 14 years of age (adults) and the Child Health Questionnaire - Parental Form 50 (CHQ-PF50) for children < 14 years of age. Treatment preferences were assessed in adults.
The mean serum immunoglobulin G (IgG) trough level during SCIG treatment (7.5 g/L) was higher than during previous IVIG treatment (6.6 g/L; p < 0.01). The investigators assessed the efficacy of SCIG therapy as "excellent" in 89% of patients. No systemic adverse drug reactions were observed. Improvements by ≥ 5 points were observed in 5 of 8 SF36 subscales and in 6 of 12 CHQ-PF50 subscales. Statistically significant improvements (p ≤ 0.05) were observed for the SF-36 subscales of bodily pain, general health perceptions, and vitality (adults), and for the CHQ-PF50 subscales of general health perceptions, parental impact - time, parental impact - emotional, and family activities (children). Patients preferred SCIG over IVIG therapy (92%) and home therapy over therapy at the clinic/physician (83%).
This study confirms that therapy with Vivaglobin® at home is effective, safe, well tolerated, and improves quality of life in patients with antibody deficiency.
antibody deficiency; subcutaneous immunoglobulin therapy; quality of life; children; adults
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Immune Globulin Subcutaneous (Human) 20%
McCormack, Paul L.
Immune globulin subcutaneous 20% is a new high-concentration (200 g/L) solution of highly purified human IgG (≥98%) indicated in the EU and the US for antibody replacement therapy in patients with primary immunodeficiency with antibody deficiency, and in the EU for replacement therapy in humoral immunodeficiency secondary to myeloma or chronic lymphocytic leukaemia.
Immune globulin subcutaneous 20% is formulated with L-proline, which imparts long-term stability at room temperature and a relatively low viscosity.
In two pivotal phase III trials in stably treated patients with primary immunodeficiency, immune globulin subcutaneous 20% at weekly subcutaneous dosages either equivalent to each patient's previous intravenous or subcutaneous replacement therapy, or providing equivalent systemic exposure to previous intravenous therapy, produced mean serum IgG trough levels equal to or greater than pre-study levels. In each trial, there were no serious bacterial infections during treatment throughout the 28-week or 12-month efficacy periods. The rates of infectious episodes, days missed from work/school, days hospitalized or days with antibiotics were low.
Immune globulin subcutaneous 20% was generally well tolerated. A high proportion of patients experienced local infusion-site reactions, but infusion-related systemic adverse events were relatively infrequent. Most adverse events were of mild or moderate intensity and did not interfere with therapy.
Related Articles
Immunoglobulin replacement treatment by rapid subcutaneous infusion
Gaspar, J
Gerritsen, B
Jones, A
Archives of Disease in Childhood
Long term intravenous immunoglobulin (IVIG) infusion is an effective treatment for children with immunodeficiencies, but can be complicated by poor venous access, systemic adverse reactions, and the need for frequent hospital admission. Rapid subcutaneous immunoglobulin (SCIG) infusion has been found to be effective in adults with primary immunodeficiency. Twenty six children were treated with SCIG for a median period of two years (range six months to 3.5 years). Fifteen children had previously been treated with IVIG. Retrospective analysis showed that trough IgG concentrations while receiving SCIG were comparable with those while receiving IVIG during maintenance treatment. In severe hypogammaglobulinaemia, however, initial loading with SCIG or IVIG is probably indicated. During the treatment period there was no systemic adverse reaction nor severe reaction requiring admission to hospital. The subjective impression of all families was a significant improvement in the quality of life. This preliminary experience with SCIG in children suggests that it is an effective, convenient, and well tolerated alternative to intravenous treatment. Larger prospective studies are required to determine the place of SCIG in the management of immunodeficiencies.
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Subcutaneous immunoglobulin therapy: a new option for patients with primary immunodeficiency diseases
Kobrynski, Lisa
Biologics : Targets & Therapy
Since the 1950s, replacement of immunoglobulin G using human immunoglobulin has been the standard treatment for primary immunodeficiency diseases with defects in antibody production. These patients suffer from recurrent and severe infections, which cause lung damage and shorten their life span. Immunoglobulins given intravenously (IVIG) every 3–4 weeks are effective in preventing serious bacterial infections and improving the quality of life for treated patients. Administration of immunoglobulin subcutaneously (SCIG) is equally effective in preventing infections and has a lower incidence of serious adverse effects compared to IVIG. The tolerability and acceptability of SCIG has been demonstrated in numerous studies showing improvements in quality of life and a preference for subcutaneous immunoglobulin therapy in patients with antibody deficiencies.
primary immunodeficiency diseases; subcutaneous immunoglobulin; immunoglobulin G
Related Articles
Intravenous immunoglobulins improve the function and ameliorate joint involvement in systemic sclerosis: a pilot study
Nacci, F
Righi, A
Conforti, M L
Miniati, I
Fiori, G
Martinovic, D
Melchiorre, D
Sapir, T
Blank, M
Shoenfeld, Y
Pignone, A Moggi
Cerinic, M Matucci
Annals of the Rheumatic Diseases
In systemic sclerosis (SSc), joint involvement may reduce the functional capacity of the hands. Intravenous immunoglobulins have previously been shown to benefit patients with SSc.
To verify the efficacy of intravenous immunoglobulins on joint involvement and function in SSc.
Patients and methods
7 women with SSc, 5 with limited and 2 with diffuse SSc, with a severe and refractory joint involvement were enrolled in the study. Methotrexate and cyclophosphamide pulse therapy did not ameliorate joint symptoms. Hence, intravenous immunoglobulins therapy was prescribed at a dosage of 2 g/kg body weight during 4 days/month for six consecutive courses. The presence of joint tenderness and swelling, and articular deformities (due to primary joint involvement and not due to skin and subcutaneous changes) were evaluated. Before and after 6 months of treatment, patients were subjected to (1) Ritchie Index (RI) evaluation of joint involvement; (2) Dreiser Algo‐Functional Index (IAFD) evaluation of hand joint function; (3) pain visual analogue scale (VAS) to measure joint pain; (4) Health Assessment Questionnaire (HAQ) to evaluate the limitations in everyday living and physical disability; and (5) modified Rodnan Skin Score for skin involvement.
After 6 months of intravenous immunoglobulins therapy, joint pain and tenderness, measured with the VAS, decreased significantly (p<0.03), and hand function (IAFD) improved significantly (p<0.02), together with the quality of life (HAQ; p<0.03). All patients significantly improved, except for one. The skin score after 6 months of intravenous immunoglobulins therapy was significantly reduced (p<0.003).
This pilot study suggests that intravenous immunoglobulins may reduce joint pain and tenderness, with a significant recovery of joint function in patients with SSc with severe and refractory joint involvement. The cost of intravenous immunoglobulins might limit their use only to patients who failed disease‐modifying antirheumatic drugs.
Related Articles
Efficacy and Safety of a New 20% Immunoglobulin Preparation for Subcutaneous Administration, IgPro20, in Patients With Primary Immunodeficiency
Hagan, John B.
Fasano, Mary B.
Spector, Sheldon
Wasserman, Richard L.
Melamed, Isaac
Rojavin, Mikhail A.
Zenker, Othmar
Orange, Jordan S.
Journal of Clinical Immunology
Subcutaneous human IgG (SCIG) therapy in primary immunodeficiency (PID) offers sustained IgG levels throughout the dosing cycle and fewer adverse events (AEs) compared to intravenous immunoglobulin (IVIG). A phase I study showed good local tolerability of IgPro20, a new 20% liquid SCIG stabilized with L-proline. A prospective, open-label, multicenter, single-arm, phase III study evaluated the efficacy and safety of IgPro20 in patients with PID over 15 months. Forty-nine patients (5–72 years) previously treated with IVIG received weekly subcutaneous infusions of IgPro20. The mean serum IgG level was 12.5 g/L. No serious bacterial infections were reported. There were 96 nonserious infections (rate 2.76/patient per year). The rate of days missed from work/school was 2.06/patient per year, and the rate of hospitalization was 0.2/patient per year. Ninety-nine percent of AEs were mild or moderate. No serious, IgPro20-related AEs were reported. IgPro20 effectively protected patients with PID against infections and maintained serum IgG levels without causing unexpected AEs.
Subcutaneous immunoglobulin (SCIG); primary immunodeficiency; local tolerability; serum IgG trough levels; L-proline; home infusion therapy
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Evaluation of correlation between dose and clinical outcomes in subcutaneous immunoglobulin replacement therapy
Orange, J S
Belohradsky, B H
Berger, M
Borte, M
Hagan, J
Jolles, S
Wasserman, R L
Baggish, J S
Saunders, R
Grimbacher, B
Clinical and Experimental Immunology
The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non-standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.
dose; IgG replacement therapy; immunoglobulin; primary immunodeficiency; subcutaneous
Related Articles
Evaluation of correlation between dose and clinical outcomes in subcutaneous immunoglobulin replacement therapy
Orange, J S
Belohradsky, B H
Berger, M
Borte, M
Hagan, J
Jolles, S
Wasserman, R L
Baggish, J S
Saunders, R
Grimbacher, B
Clinical and Experimental Immunology
The importance of serum immunoglobulin (Ig)G concentration in IgG replacement therapy for primary immunodeficiency diseases is established in certain settings. Generally, IgG is infused via the intravenous (IVIG) or subcutaneous (SCIG) route. For IVIG infusion, published data demonstrate that higher IgG doses and trough levels provide patients with improved protection from infection. The same conclusions are not yet accepted for SCIG; data from two recent Phase III studies and a recent post-hoc analysis, however, suggest the same correlation between higher SCIG dose and serum IgG concentration and decreased incidence of infection seen with IVIG. Other measures of clinical efficacy have not been considered similarly. Thus, combined analyses of these and other published SCIG studies were performed; a full comparison of the 13 studies was, however, limited by non-standardized definitions and reporting. Despite these limitations, our analyses indicate that certain clinical outcomes improve at higher SCIG doses and associated higher serum IgG concentrations, and suggest that there might be opportunity to improve patient outcomes via SCIG dose adjustment.
dose; IgG replacement therapy; immunoglobulin; primary immunodeficiency; subcutaneous
Related Articles
Common infusion-related reactions to subcutaneous immunoglobulin therapy: Managing patient expectations
Wasserman, Richard L.
Patient preference and adherence
The availability of weekly subcutaneous infusions of subcutaneous immunoglobulin (SCIg) provides an additional therapeutic option for patients with primary immunodeficiency disease. With proper patient education, individuals can safely transition to SCIg therapy and experience minimal side effects.
Research design
Case reports.
A plan for successful implementation of SCIg therapy is presented. Case reports illustrate the how to manage the transition from IVIg to home infusion of SCIg. In Case 1, despite training, home infusion was complicated by infusion-site reactions, the most common adverse event. Troubleshooting by the medical staff identified improper administration of SCIg, a correctable cause of reactions. In Case 2, patient education enabled this woman to successfully transition to SCIg without adverse effects, and without the headache and fatigue she experienced with IVIg.
Home infusion of SCIg can be successfully implemented with careful planning, patient/caregiver education, support, and follow-up.
immunodeficiency; primary; IgG deficiency; therapy; immunoglobulins; IV; subcutaneous; adverse effects
Related Articles
Direct Comparison of the Safety and Efficacy of Ferric Carboxymaltose versus Iron Dextran in Patients with Iron Deficiency Anemia
Hussain, Iftikhar
Bhoyroo, Jessica
Butcher, Angelia
Koch, Todd A.
He, Andy
Bregman, David B.
Several intravenous iron complexes are available for the treatment of iron deficiency anemia (IDA). Iron dextran (DEX) is associated with an elevated risk of potentially serious anaphylactic reactions, whereas others must be administered in several small infusions to avoid labile iron reactions. Ferric carboxymaltose (FCM) is a nondextran intravenous iron which can be administered in high single doses. A randomized, open label, and multicenter comparison of FCM to DEX in adults with IDA and baseline hemoglobin of ≤11.0 g/dL was conducted. A total of 160 patients were in the safety population (FCM n = 82; DEX n = 78). Adverse events, including immune system disorders (0% in FCM versus 10.3% in DEX, P = 0.003) and skin disorders (7.3% in FCM versus 24.4% in DEX, P = 0.004), were less frequently observed in the FCM group. A greater portion of patients in the FCM group experienced a transient, asymptomatic decrease in phosphate compared to patients in the DEX group (8.5% in FCM versus 0% in DEX, P = 0.014). In the FCM arm, the change in hemoglobin from baseline to the highest observed level was 2.8 g/dL, whereas the DEX arm displayed a change of 2.4 g/dL (P = 0.20). Treatment of IDA with FCM resulted in fewer hypersensitivity-related reactions than DEX.
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Managing diabetic ketoacidosis in non-intensive care unit setting: Role of insulin analogs
Karoli, R.
Fatima, J.
Salman, T.
Sandhu, S.
Shankar, R.
Indian Journal of Pharmacology
To compare the efficacy and safety of rapid acting insulin analog lispro given subcutaneously with that of standard low-dose intravenous regular insulin infusion protocolin patients with mild to moderate diabetic ketoacidosis.
Materials and Methods:
In this prospective, randomized and open trial, 50 consecutive patients of mild to moderate diabetic ketoacidosis were randomly assigned to two groups. The patients in group 1 were treated with intravenous regular insulin infusion and admitted in intensive care unit. The patients in group 2 were treated with subcutaneous insulin lispro 2 hourly and managed in the emergency medical ward. Response to therapy was assessed by duration of treatment and amount of insulin administered until resolution of hyperglycemia and ketoacidosis, total length of hospital stay, and number of hypoglycemic events in the two study groups.
The baseline clinical and biochemical parameters were similar between the two groups. There were no differences in the mean duration of treatment and amount of insulin required for correction of hyperglycemia and ketoacidosis. There was no mortality and no difference in the length of hospital stay between the two groups. The length of stay and amount of insulin required for correction of hyperglycemia was greater in patients who had infection as the precipitating cause than those with poor compliance. The hypoglycemic events were higher in the regular insulin group (2 vs1) than in the lispro group.
Patients with uncomplicated diabetic ketoacidosis can be managed in the medical wards with appropriate supervision and careful monitoring. Rapid acting insulin analog lispro is a safe and effective alternative to intravenous regular insulin for this subset of patients.
Diabetic ketoacidosis; hyperglycemic crises; insulin analog
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Thromboembolic complications of intravenous immunoglobulin (IVIG) in an immunocompromised patient with Chronic Lymphocytic Leukemia: a case report
Milani, Cannon
Dalia, Samir M
Colvin, Gerald A
Cases Journal
Infectious complications represent a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The etiology is postulated to be secondary to aberrations in cell-mediated immunity, as well as to therapy-related immunosuppression. Hypogammaglobulinemia, which occurs in virtually all patients with CLL, may be profound and correlates with disease duration and stage. Intravenous immunoglobulin (IVIG) therapy has been used successfully to prevent and treat infections in this cohort of patients. However IVIG administration and treatment is not benign and should be used with caution given the potential manifestations of thromboembolic complications. High concentration and rapid infusion rate of the IVIG, as well as increased dose and osmolarity of the solution are thought to predispose to thrombotic events. Serum viscosity is the implicated mechanism for compromised blood flow and predisposition of high-risk patients to cardiovascular or cerebrovascular infarction. We report a case of IVIG related thromboembolic manifestations in a CLL patient, to highlight the importance of risk stratifying patients prior to treatment administration.
Case presentation
We present a 55-year-old Caucasian man with CLL who presented to our clinic with neutropenic fevers following a cycle of chemotherapy. Laboratory parameters revealed hypogammaglobulinemia prompting IVIG administration. Shortly thereafter, he developed a massive cascade of thromboembolic phenomena precipitating his demise.
The current consensus surrounding IVIG is that of a relatively safe treatment, with minor adverse effects such as hypertension, fever and chills, nausea, myalgias, or headache. However our report highlights the importance of proceeding with caution in the application of this therapy, as it's proclivity for thrombotic complications has not been fully elucidated in patients with underlying malignancies. Pre-existing thrombogenic risk factors should be carefully evaluated in patients undergoing treatment with IVIG. Clinical evaluation, with careful attention to vascular history and underlying co-morbidities can potentially unmask the high-risk patient where IVIG could be lethal.
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Population Pharmacokinetics of Sifalimumab, an Investigational Anti-Interferon-α Monoclonal Antibody, in Systemic Lupus Erythematosus
Narwal, Rajesh
Roskos, Lorin K.
Robbie, Gabriel J.
Clinical Pharmacokinetics
Background and Objectives
Sifalimumab is a fully human immunoglobulin G1κ monoclonal antibody that binds to and neutralizes a majority of the subtypes of human interferon-α. Sifalimumab is being evaluated as a treatment for systemic lupus erythematosus (SLE). The primary objectives of this analysis were (a) to develop a population pharmacokinetic model for sifalimumab in SLE; (b) to identify and quantitate the impact of patient/disease characteristics on pharmacokinetic variability; and (c) to evaluate fixed versus body weight (WT)-based dosing regimens.
Sifalimumab serum concentration-time data were collected from a phase Ib study (MI-CP152) designed to evaluate the safety and tolerability of sifalimumab in adult patients with SLE. Sifalimumab was administered every 14 days as a 30- to 60-minute intravenous infusion with escalating doses of 0.3, 1.0, 3.0, and 10 mg/kg and serum concentrations were collected over 350 days. A total of 120 patients provided evaluable pharmacokinetic data with a total of 2,370 serum concentrations. Sifalimumab serum concentrations were determined using a validated colorimetric enzyme-linked immunosorbent assay (ELISA) with a lower limit of quantitation of 1.25 μg/mL. Population pharmacokinetic modeling of sifalimumab was performed using a non-linear mixed effects modeling approach with NONMEM VII software. Impact of patient demographics, clinical indices, and biomarkers on pharmacokinetic parameters were explored using a stepwise forward selection and backward elimination approach. The appropriateness of the final model was tested using visual predictive check (VPC). The impact of body WT-based and fixed dosing of sifalimumab was evaluated using a simulation approach. The final population model was utilized for phase IIb dosing projections.
Sifalimumab pharmacokinetics were best described using a two-compartment linear model with first order elimination. Following intravenous dosing, the typical clearance (CL) and central volume of distribution (V1) were estimated to be 176 mL/day and 2.9 L, respectively. The estimates (coefficient of variation) of between-subject variability for CL and V1 were 28 and 31 %, respectively. Patient baseline body WT, interferon gene signature from 21 genes, steroid use, and sifalimumab dose were identified as significant covariates for CL, whereas only baseline body WT was a significant covariate for V1 and peripheral volume of distribution (V2). Although the above-mentioned covariates were statistically significant, they did not explain variability in pharmacokinetic parameters to any relevant extent (<7 %). Thus, no dosing adjustments are necessary. VPC confirmed good predictability of the final population pharmacokinetic model. Simulation results demonstrate that both fixed and body WT-based dosing regimens yield similar median steady state concentrations and overall variability. Fixed sifalimumab doses of 200, 600, and 1,200 mg monthly (with a loading dose at Day 14) were selected for a phase IIb clinical trial.
A two-compartment population pharmacokinetic model adequately described sifalimumab pharmacokinetics. The estimated typical pharmacokinetic parameters were similar to other monoclonal antibodies without target mediated elimination. Although the population pharmacokinetic analysis identified some statistically significant covariates, they explained <7 % between-subject variability in pharmacokinetic parameters indicating that these covariates are not clinically relevant. The population pharmacokinetic analysis also demonstrated the feasibility of switching to fixed doses in phase IIb clinical trials of sifalimumab.
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Anti-D immunoglobulin treatment for thrombocytopenia associated with primary antibody deficiency
Longhurst, H J
O'Grady, C
Evans, G
De Lord, C
Hughes, A
Cavenagh, J
Helbert, M R
Journal of Clinical Pathology
Aims: To review our experience of anti-D immunoglobulin for immune thrombocytopenia (ITP) in patients with primary antibody deficiency.
Methods/patients: A retrospective case notes review of four Rhesus positive patients with ITP and primary antibody deficiency, treated with anti-D. Patients were refractory to steroids and high dose intravenous immunoglobulin (IVIG). Two patients were previously splenectomised.
Results: All patients responded to anti-D immunoglobulin. Improved platelet counts were sustained for at least three months. Side effects included a fall in haemoglobin in all cases; one patient required red blood cell transfusion. Two patients had transient neutropenia (< 1 × 109/litre).
Conclusion: Anti-D immunoglobulin may be an effective treatment for antibody deficiency associated thrombocytopenia, even after splenectomy. Anti-D immunoglobulin may have considerable clinical advantages in this group of patients, where treatments resulting in further immunosuppression are relatively contraindicated.
anti-D immunoglobulin; immune thrombocytopenia; primary antibody deficiency; splenectomy
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Meningococcal meningitis in two patients with primary antibody deficiency treated with replacement intravenous immunoglobulin
Lear, S
Eren, E
Findlow, J
Borrow, R
Webster, D
Jolles, S
Journal of Clinical Pathology
The current treatment of primary antibody deficiency (PAD) is the early recognition of the condition and replacement immunoglobulin combined with prompt treatment of infections and complications. The route of administration (intravenous or subcutaneous), dose and frequency of administration of immunoglobulin still vary between centres and countries. Most infections in patients with PAD are reduced but not entirely prevented by replacement immunoglobulin, with sinopulmonary infections accounting for the bulk of the remainder. Although there have been reports of meningitis in patients with PAD before replacement treatment, we describe the first two cases of bacterial meningitis (group B Neisseria meningitidis) on adequate immunoglobulin replacement and discuss the involvement of potential cofactors.
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The safety and efficacy of intravenous ferric carboxymaltose in anaemic patients undergoing haemodialysis: a multi-centre, open-label, clinical study
Covic, Adrian
Mircescu, Gabriel
Nephrology Dialysis Transplantation
Background. Patients with chronic kidney disease (CKD) often present with iron depletion and iron deficiency anaemia (IDA) because of frequent blood (and iron) loss. Therapy consists of repletion of iron stores and intravenous (i.v.) iron has become the standard care in this setting. However, older i.v. iron preparations have their limitations. This study primarily investigated the safety, and also the efficacy, of ferric carboxymaltose (FCM), a next-generation i.v. iron formulation, given as a bolus–push injection in patients with CKD undergoing maintenance haemodialysis (HD).
Methods. Patients (aged 18–65 years) with IDA undergoing HD received 100–200 mg of iron as FCM via an i.v. bolus–push injection into the HD venous line, two to three times weekly for ≤6 weeks. Safety assessments included incidence of adverse events (AEs). Treatment responders were patients attaining ≥1.0 g/dl increase in haemoglobin (Hb) from baseline at any time during the study. Enrolled patients (safety population) receiving ≥1 dose of study medication were included in the efficacy analyses [intent-to-treat (ITT) population].
Results. Of 163 patients enrolled, 150 (92%) completed the study. The mean ± SD total cumulative dose of iron as FCM administered was 2133.3 ± 57.7 mg. In total, 193 AEs were reported in 89 out of 163 (54.6%) patients. Almost three-quarters of patients (73.6%) received erythropoiesis-stimulating agents (ESAs), but the dose remained stable during the study. Serious AEs occurred in 12 out of 163 (7.4%) patients and two patients died; none of these was considered by the investigator to be related to the study medication. Only five out of 163 (3.1%) patients discontinued study medication due to an AE. Overall, 100 out of 162 (61.7%; ITT population) patients were treatment responders, and mean Hb levels increased from 9.1 ± 1.30 g/dl at baseline to 10.3 ± 1.63 g/dl at follow-up.
Conclusions. FCM is well-tolerated and effective in the correction of Hb levels and iron stores in patients with IDA undergoing HD. As changes in anaemia treatment other than i.v. FCM (e.g. increased ESA doses) were not permitted during the study, the clinically relevant increase in Hb in the majority of patients can be solely attributed to efficient iron utilization. The incidence of AEs was as expected for this population.
clinical trial; efficacy; ferric carboxymaltose; haemodialysis; iron deficiency anaemia; safety
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A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma.
Prados, Michael D.
Schold SC JR, S. Clifford
Fine, Howard A.
Jaeckle, Kurt
Hochberg, Fred
Mechtler, Laszlo
Fetell, Michael R.
Phuphanich, Surasak
Feun, Lynn
Janus, Todd J.
Ford, Kathleen
Graney, William
RMP-7, a bradykinin analog, temporarily increases the permeability of the blood-brain tumor barrier to chemotherapy drugs like carboplatin. We conducted a randomized, controlled trial of carboplatin and RMP-7 versus carboplatin and placebo in patients with recurrent malignant glioma. The primary outcome measure was time to tumor progression (TTP). Adults with recurrent glioblastoma multiforme or anaplastic glioma were randomized in a 1:1 ratio to receive carboplatin and either RMP-7 or placebo. Radiation therapy had failed in all patients, and they may have received prior chemotherapy. Carboplatin (dosed to achieve an area under the curve of 5 mg/ml x time for patients who had received prior chemotherapy, or 7 mg/ml x time for those who had not) was given intravenously every 4 weeks, followed by intravenous infusion of either RMP-7 or placebo (300 ng/kg). TTP, tumor response, neuropsychological assessments, functional independence, and quality of life assessments were analyzed every 4 weeks. There were 122 patients enrolled, 62 in the RMP-7 and carboplatin group and 60 in the placebo and carboplatin group. Median TTP was 9.7 weeks (95% CI, 8.3-12.6 weeks) for the RMP-7 and carboplatin group and 8.0 weeks (95% CI, 7.4-12.6 weeks) for the placebo and carboplatin group. Median survival times were 26.9 weeks (95% CI, 21.3-37.6 weeks) for the RMP-7 group and 19.9 weeks (95% CI, 15.0-31.3 weeks) for the placebo group. No differences were noted for time to worsening of neuropsychological assessments, functional independence, or quality of life assessments. The use of RMP-7 had no effect on the pharmacokinetics or toxicity of carboplatin. At the dose and schedule used in this trial, RMP-7 did not improve the efficacy of carboplatin. Recent preclinical pharmacokinetic modeling of RMP-7 suggests that higher doses of RMP-7 may be required to increase carboplatin delivery to tumor.
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Survey of infection in patients receiving antibody replacement treatment for immune deficiency
Pettit, S J
Bourne, H
Spickett, G P
Journal of Clinical Pathology
Background:0 Primary antibody deficiency disorders are a heterogeneous group of disorders, which are treated by regular infusions of immunoglobulin. Despite replacement treatment, patients remain susceptible to infection. Effective management of infections is necessary to prevent the complications of chronic infection.
Aims: This retrospective survey of clinical practice examined the management of infections in patients who receive immunoglobulin replacement for immune deficiency.
Methods: Patients who received immunoglobulin replacement treatment in Newcastle during the year 2000 were identified. Medical records were reviewed. Basic clinical information and details of immunoglobulin replacement treatment were recorded. Episodes of infection were defined by documented symptoms, signs, or investigation results, and by the prescription of an antibiotic course. Details of episodes of infection and antimicrobial treatment were recorded.
Results: Thirty seven patients received immunoglobulin replacement during 2000. There were 101 episodes of infection. There was no correlation between the frequency of infection and the IgG trough value. Respiratory tract infections were most common (71 of 101). Where documented, 80% of infections were associated with clinical signs, 21% with pyrexia, and 64% with a raised C reactive protein value. Microbiological culture was performed in 30% of infections. Antimicrobial treatment was instituted along "best guess" lines in 99 of 101 episodes of infection.
Conclusions: Management of respiratory tract infections represents the largest problem in antibody deficient patients. Greater use of microbiological culture might allow more effective prescription of antimicrobial treatment. The generation of treatment guidelines and improved communication with general practitioners could improve the management of all episodes of infection.
infection; antibody deficiency; hypogammaglobulinaemia
Related Articles
Management of primary antibody deficiency by consultant immunologists in the United Kingdom: a paradigm for other rare diseases.
Spickett, G P
Askew, T
Chapel, H M
Quality in Health Care
Variation in clinical practice and its effect on outcome is little known for rare diseases such as primary antibody deficiency. As part of a national audit a survey of all 30 consultant immunologists in the United Kingdom dealing with primary antibody deficiency syndromes in adults and children was carried out in 1993 to ascertain their practices in diagnosis and management. Consensus guidelines were published after the survey was completed. Comparison of the survey results of clinical practice at the time the guidelines were published with the standards identified highlighted that the practice of a minority of specialists was at variance with their peers and with the consensus document, particularly in the use of intramuscular immunoglobulin, the dose and frequency of intravenous immunoglobulin, and target trough immunoglobulin G concentration, which has implications for the quality of patient care. However, much closer agreement existed in the key areas of management, such as diagnosis and selection of intravenous immunoglobulin. The approach and the problems identified are relevant to the management of other rare diseases, in which diagnosis and management is complex and there are few specialists with the necessary knowledge to undertake such care. This survey, the first attempted audit of practice, shows that within a motivated group of specialists highly significant differences in practice may exist and the authors emphasise the importance of setting clear guidelines against which care can be assessed.
Related Articles
Transverse sinus thrombosis and IVIg treatment: a case report and discussion of risk–benefit assessment for immunoglobulin treatment
Evangelou, N
Littlewood, T
Anslow, P
Chapel, H
Journal of Clinical Pathology
A 54 year old woman presented with symptoms resulting from a thrombosis of the lateral transverse and sagittal sinuses the day after an infusion of intravenous immunoglobulin (IVIg) replacement treatment. She had previously suffered a milder episode after IVIg. Following recurrent bacterial chest infections and sinusitis for more than 40 years, a diagnosis of IgG1 deficiency had been made two years earlier, after exclusion of other causes. She made a good recovery from the thrombosis but high platelet counts were investigated and primary thrombocythaemia was diagnosed. Investigation of humoral immunity revealed protective amounts of IgG antibodies to pathogens, and because the previous IgG1 deficiency had resolved IVIg infusions were not restarted. She made a good response to treatment with hydroxyurea, with improvement of the headaches and lowering of the platelet counts. Prophylactic antibiotics reduced the number of bacterial chest infections and nasal corticosteroids improved the chronic sinusitis. This case is presented to highlight the need to look for other contributing factors for severe recurrent headaches after IVIg treatment, and to consider the risk of thrombosis even when replacement doses of IVIg are used. It is also important to emphasise the need to ensure that an isolated IgG subclass deficiency is not transient; that failure to produce specific IgG antibodies to immunisation and/or exposure antigens is confirmed, thus meeting the criteria for the diagnosis of primary antibody deficiency. A thorough risk–benefit assessment is essential before blood product treatment is started.
immunoglobulins; thrombosis
Related Articles
Intravenous iron monotherapy for the treatment of non-iron-deficiency anemia in cancer patients undergoing chemotherapy: a pilot study
Abdel-Razeq, Hikmat
Abbasi, Salah
Saadi, Iyad
Jaber, Rana
Abdelelah, Hazem
Drug Design, Development and Therapy
Anemia in patients with cancer who are undergoing active therapy is commonly encountered and may worsen quality of life in these patients. The effect of blood transfusion is often temporary and may be associated with serious adverse events. Erythropoiesis-stimulating agents are not effective in 30%–50% of patients and may have a negative effect on overall survival.
To assess the efficacy and feasibility of intravenous iron therapy in patients with cancer who have non-iron-deficiency anemia and who are undergoing treatment with chemotherapy without the use of erythropoiesis-stimulating agents.
Adult patients with solid cancers and non-iron-deficiency anemia were included. Ferric sucrose at a dose of 200 mg was given in short intravenous infusions weekly for a total of 12 weeks. Hemoglobin level was measured at baseline, every 3 weeks, and 2 weeks after the last iron infusion (week 14). Adverse events related to intravenous iron were prospectively reported.
Of 25 patients included, 19 (76.0%) completed at least three iron infusions and 14 (56.0%) finished the planned 12 weeks of therapy. The mean hemoglobin level of the 25 patients at baseline was 9.6 g/dL (median, 9.9 g/dL; range, 6.9 g/dL 10.9 g/dL). The mean change in hemoglobin level for the 15 patients who completed at least 9 treatments was 1.7 g/dL (median, 1.1 g/dL; range, −1.9 g/dL to 3.2 g/dL); it reached 2.1 g/dL (median, 1.3 g/dL; range, −0.2 g/dL to 4.6 g/dL; P = 0.0007) for the 14 patients who completed all 12 weekly treatments. Five (20.0%) patients were transfused and considered as treatment failures. No treatment-related adverse events were reported.
Intravenous iron treatment alone is safe and may reduce blood transfusion requirements and improve hemoglobin level in patients with cancer who are undergoing anticancer therapy. Further randomized studies are needed to confirm these findings.
anemia; cancer; chemotherapy; intravenous iron; transfusion
Related Articles
Iron status in hypogammaglobulinaemia.
Atrah, H I
Journal of the Royal Society of Medicine
Iron, transferrin and ferritin were measured in serum samples from 16 patients with primary hypogammaglobulinaemia. Transferrin saturation was low in 12 patients (75%) and serum ferritin was low in 9 patients (56.25%). Both parameters were low, confirming the state of iron deficiency, in 6 patients (37.5%). These figures are highly significant (P less than 0.01) when compared with the prevalence of iron deficiency in the general population. Eight patients were maintained on intravenous immunoglobulin infusions and the rest on intramuscular immunoglobulin injections, their mean serum IgG being 4.4 g/l and 2.6 g/l respectively. There was no difference in the prevalence of iron deficiency between the two groups.
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Home > News > Nanotechnology enhanced fabrics using Nanoprotex TC from Nanotec
March 6th, 2008
Nanotechnology enhanced fabrics using Nanoprotex TC from Nanotec
Abstract: Nanoprotex TC from Nanotec is a water-based, nanotechnology surface treatment for fabrics. Once applied, treated fabrics become water repellent, stain resistant and stay cleaner for longer.The Nanoprotex TC nanotechnology product creates an invisible coating bonded to the fabric fibres which provides the water repellent and stain resistant surface. The product has high resistance to washing out under normal washing machine conditions.
News and information
Thailand to tell it all at Seed and Need Seminar in Japan December 5th, 2013
6th Bangalore INDIA NANO Awards Presented December 5th, 2013
Stepping-up the Performance of Structural Ceramics: Innovnano produces nanostructured 3YSZ powder for demanding applications December 5th, 2013
3-D printing and custom manufacturing: from concept to classroom: Strategic investments from NSF help engineers revolutionize the manufacturing process December 5th, 2013
Study shows how water dissolves stone, molecule by molecule: International team uses computers, experiments to better predict chemical dissolution December 5th, 2013
Laser light at useful wavelengths from semiconductor nanowires: Nanowire lasers could work with silicon chips, optical fibers, even living cells December 5th, 2013
DNA helicity and elasticity explained on the nanoscale: Korean researchers propose simple model to explain DNA helicity and elasticity on a nanometer scale December 5th, 2013
Technology and Fashion industries need to come together for future of wearable tech: Beecham Research calls for convergence of aesthetics and technology in new video published today: Wearable Technology: Towards Function with Style December 4th, 2013
Nanotechnology Used in Production of Cotton-based Goods November 26th, 2013
Solar-powered battery woven into fabric overcomes hurdle for 'wearable electronics' November 20th, 2013

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War Thunder
PC / Simulation / Release: TBA / ESRB: U
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Assassin's Creed IV: Black Flag Freedom Cry launch trailer
Adewale, Captain Edward Kenway's first mate, heads fifteen years into the future after the conclusion of Assassin's Creed IV: Black Flag to take command of the Experto Crede.
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SteamOS beta (Alchemist) 1.0
Use at your own risk. SteamOS is a fork (derivative) of Debian GNU/Linux. The first version (SteamOS 1.0) is called 'alchemist' and it is based on the Debian 'wheezy' (stable 7.1) distribution.
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Thief Stories from the City Queen of Beggars trailer
The second entry into the Stories from the City trailer series for the reboot of the supernatural Thief, detailing the Queen of Beggars and the sure to be thrilling encounters you'll have with her.
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Ultra Street Fighter IV overview trailer
Capcom presents an overview trailer for the upcoming release of Ultra Street Fighter IV, a stand-alone game releasing in early 2014.
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Sniper Elite 3 Tobruk trailer
Get an overview of Tobruk in Sniper Elite III from Rebellion Oxford and Rebellion Developments for the PC and Playstation 4.
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Batman: Arkham Origins Copperhead behind the scenes trailer
Go behind Batman: Arkham Origins to see the motion capture process for the slick martial arts scenes.
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Ryse: Son of Rome update trailer
Crytek and Microsoft announce new, free content for Ryse: Son of Rome including new level events in Gladiator mode with brand new character skins.
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Shadow Warrior Survival Mode trailer
Welcome to the brand new Survival Mode coming to the recent Shadow Warrior, along with Rise of the Triad integration!
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Tekken Revolution Eliza character trailer
Eliza comes to Tekken Revolution in a brand new update for the free to play game on Playstation 3.
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Battle Worlds: Kronos demo 1.0
The classic turn-based strategy – exciting, involved gaming that calls for long-term planning, clever tactics, transparent rules and tough decisions – is making a comeback. Many gamers may have seen and enjoyed recent examples of great turn-based gaming, but might not be aware of classics like Battle Isle or Advance Wars. Have you ever wondered what games of that calibre would look like today? Play Battle Worlds: Kronos to find out.
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War Thunder Heroes cinematic trailer
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- Take to the skies as the heroes of dogfighting rule the blue beyond in War Thunder.
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War Thunder client downloader 184.108.40.206
War Thunder offers a highly detailed and personalized aviation experience, giving players access to hundreds models of planes with detailed cockpits, dozens of upgradeable weapons, and flying skills that can be honed and improved with each mission. Thanks to the game's painstaking attention to detail, you'll truly feel like a World War II fighter pilot as you plunge into battle.
Posted Mar 07, 2013 11:28am PST 26 Downloads Download Now
The genuine World War II experience isn't limited to the skies. The massive historical battles featured in War Thunder cannot be fought by aviation alone, so the game will also expose players to combat on land and at sea.
Read more about the game and sign up for an account here.


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- May 22, 2011
- 12:40 p.m.
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Tanguman writes:
When i read this story my heart immediattely filled with pride. I do not know either man nor their families but feel that this was the greatest show of respect or brotherhood that one man can do for another given Mr. Rokohl's current physical condition.
One can only imagine what was going through his head the entire time he was walking and the days before during his training. This would make a great ending for an otherwise tragic story.
To those speaking ill of American soldiers and the expense of the wars/conflicts that America has decided to take part in here is something to chew on: Since the late 1970's the entirety of the U.S. Military has been a VOLUNTEER Military. That means that these men and women who are serving CHOSE to do so, either as a means to make a better life due to college not being readily available to them or even out of a sense of duty and some even carrying on a family tradition.
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That's right! Look at everything that Obama has done so far to restrict gun rights ! ! ! Keep the Lies alive ! ! ! VOTE REPUBLICAN ! ! ! ! !
gun sales were not at an alltime high
Actually they were, at least the NICS system never processed so many transactions before.


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The DM-CAM-VDWM1-A is a quality wall mounting bracket from Dedicated Micros which has been designed to be used with the PTZ speed dome DM-CAM-SDAO-A outdoor housing, the DM-CAM-SDAI-A indoor housing, and the VSD10X, VDN4IR/A, DVDN5/A, and DVDN4/A dome sec.
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As temperatures drop and frost coats the ground, farmers markets in Washington County are drawing to a close. The Beaverton Farmers Market will cease to open from 9 a.m. to 1:30 p.m. on Saturdays after Nov. 23.
The market will lie dormant until February, when the winter market will open. But Market Master Ginger Rapport encouraged shoppers to stop by the fall market, which features about 100 vendors, by Nov. 23. The winter market is smaller, she said, with about 60 vendors.
Rapport said the next couple of weeks provide a great opportunity to stock up for the winter ahead.
"This is my favorite time of year because a lot of your warm-season crops (tomatoes, corn, peppers) are in, but so are your cold-weather crops (cabbage, kale, winter squash)," she said.
While the market will offer fewer fruits, apples and pears are abundant this time of year, Rapport said.
In addition to fresh fruits and vegetables, the Beaverton Farmers Market offers meat, dairy and a wide range of hand-crafted gifts for the holidays.
Rapport and Bette Sinclair, who coordinates public relations for the market, named a few of their favorite gifts available at the market. Click through the gallery above, and if you want to learn more about a product, click the corresponding link in the list below.
- Brittle from Malou's Gourmet Brittle & More
- Sausage from Olympic Provisions
- Eggnog from Lady-Lane Farm
- Garlic from Three D Ranch
- Rose hip wreaths from Sun Gold Farm
- Centerpieces, wreaths and bird feeders from Pumpkin Ridge Gardens
- Pasta from Esotico
- Pepper jelly from Rose City Pepperheads
- Belgian-inspired ale from Ambacht Brewery
- Pacific Rum from Bull Run Distilling Company
- Dungeness crab cakes from Quinn's Hand Made Crab Cakes


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The business sector pays tribute to Nelson Mandela.
It's now up to us to live Tata's dream, says a Fin24 user.
Share your memories of Nelson Mandela with Fin24 users.
Reserve Bank governor Gill Marcus. (AFP)
It has been the worst-performing emerging market currency this year' depreciating by more than 7% against the dollar.
"The Sarb thinks fair value is around R8.50-R8.75. Therefore, by definition where we are now is overdone," said Montalto.
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- January 23, 2010
- 4:26 p.m.
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papabob (Inactive) writes:
in response to stude54:
I guess this means here are no longer any children left in Knoxville needing to be adopted and we have to go to Haiti to find adoptable kids.
First stude, congratulations for being the first with something negative to say about this act of altruism.
These children had next to nothing to look foreward to unless someone with a big heart took them under their wing.
Then there is that bit from Jesus that goes like:"What so ever you do to these, the least of my brethern, that you do unto me."
To paraphrase another saying:"No good deed goes without criticsm."
To the folks from the church: (o:
To stude54: )o:
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If Hurricane Sandy had also triggered a chemical disaster it would have exponentially increased the already historic impact it has already wrought. It's time to get serious about these hazards.
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* PSEG Salem and Hope Creek reactors likely to shut * Reactors in Pennsylvania and Maryland could shut By Scott DiSavino Oct 29 (Reut...
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The Sarasota Opera's regular season may have ended, but the company was alive with the sounds of music last week when it presented a celebration of the 150th anniversary of the Unification of Italy in a "risorgimento" (revival or awakening) concert. And, in his travels through the complete works of Verdi, Victor DeRenzi gave us an aural insight into the alternate versions of well-known operas that, in the evening opened with the Overture to "I vespri siciliani," played by the wonderful musicians of the Sarasota Opera Orchestra, who were led by DeRenzi. Four excerpts from "I Lombardi," one of the Verdi operas in this season's repertoire, were followed by standout performances from tenors Rafael Davila, Steven Uliana and Bernard Holcomb, mezzo Sarah Larsen, bass-baritone Carlos Monzon and tenors Abla Lynn Hamza and Bethany Kiral.
The rarely heard "Mass for Rossini" came next and was positively startling in its fascinating early workings of the later and much more famous "Requiem." Maria D'Amato (whom we heard as Mimi earlier in the season) sublimely sang the soprano solos with an equally exalted chorus intoning the "Libera me" and "Dies Irae" with a drama rarely heard in concert.
Vocal excerpts from "Attila," "Il Trovatore," "I vespri siciliani" and "Macbeth," sung with power and energy by Davila, D'Amato and Kevin Short, were in the second half, along with the Overture (rather than the usual "Prelude") to "Aida," "Suona la tromba," (a vibrant chorus specially composed by Verdi to show his espousal of the Unification), a section from Montemezzi's "L'amore dei tre re," (the only work on the program not by Verdi) and, finally, "Va, pensiero," the chorus from "Nabucco" that makes us all proud to be Italian, if only by proxy.
Verdi wrote in a letter during his first trip to Florence, Italy, "How really beautiful this Italy of ours is." The Sarasota Opera concert would have made the maestro say, "How really beautiful this Sarasota of ours is," because the real stars of the evening were the musicians: instrumentalists (on stage and seen), the chorus (singing spectacularly) and DeRenzi, who masterminded this masterful evening.
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- Dec
11 Let it Snow
5:30 pm - 10:00 pm - Dec
13 "Jazz at Two" with the Rodney Rojas Quartet
2:00 pm - 4:00 pm - Dec
13 Cirque Des Voix "Joy and Wonder"
7:00 pm - 5:00 pm - Dec
15 A Celtic Christmas
7:00 pm - 9:00 pm - Dec
20 Hasselbarth
6:00 pm - 9:00 pm - Dec
20 The Sarasota Ballet presents Program 3 | John Ringling's Circus Nutcracker
8:00 pm - Dec
21 The Sarasota Ballet presents Program 3 | John Ringling's Circus Nutcracker
2:00 pm - Dec
21 The Sarasota Ballet presents Program 3 | John Ringling's Circus Nutcracker
8:00 pm
Resident keeps eye on the pie
Inspired by her mother's homemade banana cream pie, Bird Key resident Kim Manning had a sweet idea: key lime with a twist. -
Show us your spirit this season
This week, our reporters will make our final decisions on our favorite displays of holiday cheer for our "Spirit of the Season" contest. This year's competition isn't limited to lights. -
Paint the town red and green
This year, we won't just be on the lookout for the most festive holiday lights on the Key. We'll be on the prowl for anything that embodies the happiness of the holidays with our new "Spirit of the Season" contest.


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Honolulu and Oahu: Places to Explore
- Overview
- Places to Explore
- Sights
- Restaurants
- Hotels
- Entertainment
- Shopping
- Activities
- Travel Tips
- Features
- Fodor's Choice
- Deals
Central Oahu
View MapOahu's central plain is a patchwork of old towns and new residential developments, military bases, farms, ranches, and shopping malls, with a few visit-worthy attractions and historic sites scattered about. Central Oahu encompasses the Moanalua Valley, residential Pearl City and Mililani, and the old plantation town of Wahiawa, on the uplands halfway to the North Shore.
Central Oahu at a Glance
Elsewhere in Honolulu and Oahu
See Also
Fodor's Trip Planning Ideas
- Fodor's 100 Hotel Awards: Check out the winners of 2013
- Weekend Getaways: Fodor's Recommends the Best Weekend Escapes in the US
- Great American Vacation: Find Your Next U.S. Trip with Fodor's
- 80 Degrees: Fodor's Helps You Find Your Best Beach Vacation Spots
- Best of Europe: Fodor's Picks the Best Places to Visit in Europe


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Intuitive Biosciences provides high-throughput protein analysis tools for the life science industry. Our proprietary SilverQuant® detection system coupled with expertise in developing highly validated assays to deliver a continually expanding portfolio of the most reliable tools, protein microarray kits and services in the industry. Learn more.
Our Colony Surveillance Assays (CSA™) are built specially for serological monitoring of animal health
Custom AIM™ assays for a broad range of uses


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Rock Chapel Church of God,
Granite Falls
Driven Quartet, will be at the Rock Chapel Church of God in Granite Falls, NC, January 19th at 10 am. The church is located at 49 N Main St in Granite Falls...
Statesville 828-450-1482 events
Driven Quartet
Sunday, Jan 19
Thai Yoga Bodywork Certification Training in Charlotte, NC
Saturday, Mar 1
Elemental Healing,
This training prepares one in all the skills necessary to offer a complete and safe full body Thai massage...
30th Annual Dr. Martin Luther King, Jr. Commemoration
Tuesday, Jan 21
An Evening with Soledad O'Brien
Solded O'Brien will be speaking at Appalachian State University as part of the 30th MLK Commemoration...
Take a "First" Hike
Wednesday, Jan 1
Elk Knob State Park,
It has been said that whatever you do the first day of the year, you will do the rest of the year. Why not get outside and take a hike...


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Boss 101
A boy and his jetpack save the world against an army of randomly generated bosses.
4.01 / 5.00 38,857 ViewsSift Heads World - Act 3, Alonzo's Reinforcement
Storyline :
Throughout Act 3 we will revisit Chicago and its dark and sombre areas of the underground crime organization. After a hard-hitting blow from Alonzo our team is back on the hunt. But it won't be so easy this time, cause Alonzo has some very influencing friends in high places. Vinnie and his partners will need the help of the Mayor in Chicago... Play the game to find out the final outcome of this third episode.
Features :
- Vinnie, Shorty and Kiro are wanted by the Chicago Police
- Palermo has been refreshed with new locations
- Customizable weapons now available! (See guide for details)
- 13 main missions and 6 secondary missions ...
- A new closet to store your various outfits
- New treasures ...
- and more ...
Controls :
Left Click : Shoot / Action
SpaceBar : Draw your Weapon
(R) : Reload
(Q) : Switch Quality
We hope this Act will please all Sift Heads fans and maybe create some new ones!
Frontpaged ! Thx Newgrounds !!!
love it<3
love the game! love it so much, could play it all day!
Nice of ya' to add some new features, but...
Towards the end the game just takes a nose dive with the several nearly bulletproof dudes and having to pop in and out of cover like an over cafinated trapdoor-spider just to shift their kevlar asses, all of which adds up to a grinding experience similar to shoving a diamond-saw up your ass. It also doesn't help that you can't switch weapons or reload in cover either.
So the last ten minutes before you swiftly toss your monitor out the window feels like trying to eat a meat-loaf that's been streched out with sawdust from a rubber tree.


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The Guiraud 2007 has a typically unabashed, exuberant bouquet with tangerine, pear, white peach and honeysuckle. The palate is medium-bodied with a lovely viscous entry, very good weight of fruit, and a lot of botrytis; smooth and very harmonious towards the finish that would benefit from a little more clarity and dare I say, "personality". Still, a very fine Sauternes. Drink 2012-2035.
A blend of 80% Sauvignon and 20% Semillon that hit 14% natural alcohol, this is serious wine boasting notes of lemon and lime marmalade intermixed with honeysuckle, a whiff of freshly cut grass and a waxy, melony character. Aromatically complex, this relatively big Malartic Lagraviere should drink well for up to 20 or more years. A great wine!


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Robert Martin
Robert Martin is a curator of biological anthropology at the Field Museum of Natural History. He initially studied zoology at Oxford University. Postdoctoral research in France consolidated his interests in primates and led to his first academic appointment in anthropology at University College London. He was also a senior research fellow at the Zoological Society of London and visiting professor at Yale University and the Musée de l'Homme, Paris. He directed the Anthropological Institute in Zürich, Switzerland for 15 years prior to his appointment at Chicago's Field Museum.


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Elvis photographed by Alfred Wertheimer at the Warwick Hotel in NY, March 17, 1956.
gets me every time
Hahahaha. People have told me that this scene ruined the movie for them, because they love Lord of the Rings so much. I thought it was excellent, and I love the Lord of the Rings.
So I feel like I should source this because it's actually real and somehow not just a joke
Detroit represent!


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Where For Fiberglass Repair?
Altezza Club Of NZ/Australia
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Where For Fiberglass Repair?
- May 1, 2012 11:34 PM (GMT)
Anybody suggest/recommend a fiberglass repair place in Auckland?
I know of some places but wondering if anybody has had some work done somewhere or if ACNZ gets deals somewhere.
My bonnet needs a bit of attention, structurally looks fine but the paint work isn't and might be hiding something underneath.
Other option is ditch it and pick up a new one (carbon one on TM at the mo, $400)
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Doralice Handal's Life as a Cheesemonger
Have you ever found yourself at a cheese shop, wondering about life at the other end of the counter? Elizabeth Cosin at the Healdsburg Press Democrat gives you a glimpse into the cheesemongering life with a profile of local seller Doralice Handal.
"She is one of the best things we have in Healdsburg," says Chef Mateo Granados owner of Mateo's Cocina Latina, who adds he often taps Handal's cheese wisdom. "I will tell her what kind of salad I'm thinking about and she recommends cheese for me. She knows everything about a cheese. No, she knows everything about everything — and she loves what she does."
For the last seven years, since Handal bought the store from its original owner, she has been a favorite of locals, area chefs and wineries, and through her online store, has even shipped cheese to places as far away as Japan and Barbados. Her focus, she says, has been on local producers and her love: telling their stories.


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About Article
A Technical Blog, originally posted at http://www.adamtibi.net/07-2012/using-c-sharp-net-user-defined-functions-udf-in-excel
Exposing .NET functions to be consumed as Excel functions, otherwise known in Excel as "User Defined Functions" . Those .NET exposed functions can be easily used from Excel's cells. This article presents two ways to achieve this and the pros and cons of each.
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Man throws away trove of Bitcoin worth $7.5 million Get the Insider News free each morning.Related Articles


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- Heavy snow to arrive at mid-afternoon
- Historic status for Downtown district approved for nomination
- Recounts confirm Reynoldsburg school board and Truro trustee elections
- Gee to be interim president at West Virginia University
- Retired judge named acting Fairfield County court clerk
- Former DeSales choir director indicted on sex charges
- Memorial for homeless to remember 32, at least
- Petition seeks vote to end Columbus' payments on Nationwide Arena
- Photo: Schools honored
- Photo: Holidays on track at Main Library
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The E-Edition includes all of the news, comics, classifieds and advertisements of the newspaper. And it's available to subscribers before 6 a.m. every day.
Current home-delivery subscribers may add Digital D, 24/7 E-Edition and unlimited premium Dispatch.com access, for a nominal additional charge. Or, you can choose a digital-only subscription for unlimited access to the E-Edition via computer and iPad. Subscribe today!
The Dispatch strives to be fair and accurate. The newspaper corrects any significant errors of fact brought to the attention of the editors. If you think an error has been made, call 614-461-5271. Corrections will be printed below.
• Rent-to-own company Aaron's did not admit or deny allegations in settling charges by the Federal Trade Commission that its computers contained software that allowed it to collect unauthorized information from customers. Because of incorrect information from the Atlanta Journal-Constitution, a news brief on Page D2 of Thursday's Business section indicated otherwise.
• First Community Church has locations on the Northwest Side and in Marble Cliff. Because of a reporter's error, a story on Page B6 of Friday's Metro & State section indicated otherwise.
• Rick Tilton is an assistant director of the Columbus Department of Public Service. Because of a reporter's error, his title was wrong in a story on Page B1 of yesterday's Metro & State section.


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Thursday, December 12, 2013
Maine Blueberry Cake from "Lighten Up America" by Allison Fishman Task (Photo courtesy Oxmoor House)
Right off the bat, I will admit that this post is a little bit self-serving, but I'm so excited I hope I can be forgiven.
Yesterday, a terrific cookbook I had the great pleasure of working on, "Lighten Up America," was released by Oxmoor House under the Cooking Light brand. Written by my talented friend — chef, cooking instructor, Cooking Light contributing editor and TV spokesperson Allison Fishman Task — the book celebrates the best of American regional cooking, just a little less full of fat and calories.
Allison is also the mother of 8-month-old twin boys and although she has enviable energy, cookbook writing while pregnant and traveling around the country for her (now on hiatus) Yahoo! web series, "Blue Ribbon Hunter," was a tall order. In late summer 2012, I was thrilled when she asked me to help develop a number of the dessert recipes for the book and ended up developing some of the savory dishes as well (I'm especially proud of the "cat head" biscuits with sausage gravy). Each of the recipes had to meet Cooking Light's nutrition guidelines, be tasted and approved by Allison and tested in the Cooking Light test kitchen.
Maine is well represented in the book by a classic lobster roll, a stovetop lobster bake and a lightened-up version of Maine blueberry cake (inspired by a recipe given to me years ago by June Elderkin, a painter on Southport Island). A great recipe source and a fun read, "Lighten Up America" is available via Amazon/com.
Stovetop Maine Lobster Bake from "Lighten Up America" by Allison Fishman Task (Photo courtesy of Oxmoor House)
TweetMeredith Goad has harvested oysters on the Chesapeake Bay, eaten reindeer in Finland and sipped hot chai in the Himalayas. She writes the weekly Soup to Nuts column and enjoys a good cocktail.
Meredith can be contacted at 791-6332 or
On Twitter: @meredithgoad
Susan Axelrod's food writing career began in the kitchen; she owned a restaurant and catering business before turning to journalism more than a decade ago. To relax, she bakes, gardens and hikes with her husband and their two dogs. A newcomer to Portland, she is an online content producer for the Press Herald.
Susan can be contacted at 791-6310 or saxelrod [at] pressherald.com.
On Twitter: @susansaxelrod


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Next tie 8-9 February 2014 Sweden will compete in World Group II in 2014, hosting Poland in the first round. This will be the sixth meeting between the two nations and they have historically been close-fought contests. Poland lead the head-to-head 3-2, but Sweden won the last meeting in 2012. Last tie 20-21 April 2013 Sweden were charged with the tricky task of taking down a USA team that included both Williams sisters, Sloane Stephens and Varvara Lepchenko. Although the Swedes finished up losing 3-2, Sofia Arvidsson pulled off a good win against Stephens and Johanna Larsson made life difficult for her opponents. History Sweden are four-time Fed Cup quarterfinalists, reaching the last eight in 1970, 1977, 1980 and 1988.
Next Tie08 Feb 2014
World Group II - First Round
Swedenv Poland
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Anne from WobiSobi shares a tutorial over at Brassy Apple showing how to make this t-shirt skirt. It's a super simple refashion, requiring just one cut and just one seam. But if you want to give it some fancy, she also shows how to add sequin trim to the hem. Go to Brassy Apple to get the tutorial.
[photo from WobiSobi]
By Anne Weaver


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Kallio: 'We had an almost perfect bike'
Mika Kallio believes his crew chief Fabiano Sterlacchini helped him achieve an almost perfect setting for his Desmosedici GP9 at Jerez on Sunday afternoon.
Jumping from 13th place on the Sunday morning free practice timesheet with a best lap of 1'41.600 to a surprise sixth place in the afternoon BMW M Award session with a vastly improved 1'40.149 effort, Mika Kallio was in a confident mood at the end of the Official MotoGP test at Jerez.
The Finnish MotoGP rookie felt he could have gone even faster had it not been for some difficulties in the final section of the circuit, but he acknowledged the work of his Pramac Racing staff as he stated that they had been close to perfection in setting up his Desmosedici GP9.
The 250cc graduate commented on Sunday evening, "With the data we gathered on Saturday and on Sunday morning I assessed the situation with the track and the bike, alongside my Technical Director, Fabiano Sterlacchini. We put together all the positive things we found and we had an almost perfect bike. I was still losing too much time in the last sector, otherwise we could have finished in an even better position. We are doing a great job and I'm sure we can keep up that good work in the first race in Qatar."
Kallio was one of the nine MotoGP riders who re-emerged after the BMW M Award session, in the third and final free practice, putting in 17 laps of wet riding as he rounded off the preparations for his debut campaign in the premier class. He also concluded that session sixth on an abridged timesheet, again lapping faster than fellow debutants Niccolò Canepa and Yuki Takahashi.
Latest news
- Tuesday, 17 December 2013
- Further collarbone surgery for Lorenzo
- Monday, 16 December 2013
- GP Commission discusses Moto3™ cost-cutting
- Scott Redding to star at Thundersprint 2014
- Friday, 13 December 2013
- FIM updates 2014 MotoGP™ calendar
- Thursday, 12 December 2013
- #Rookie93MarcMarquez: 'Behind the Scenes' with the Champion
- Bridgestone's Yamada looks back on 2013
- Wednesday, 11 December 2013
- PBM announces Broc Parkes for 2014
- Wednesday, 4 December 2013
- A Post-season Catch-up: Livio Suppo
- Thursday, 5 December 2013
- A Post-season Catch-up: Tito Rabat
- Tuesday, 3 December 2013
- A Post-season Catch-up: Sandro Cortese
- Friday, 29 November 2013
- Terol: 'Ending season with win was extra bonus'
- Monday, 25 November 2013
- Rea seals full-time entry with AGT Rea Racing
- Wednesday, 20 November 2013
- Provisional 2014 Moto2™ entry list
- Tuesday, 19 November 2013
- Luthi quick and feeling confident before break
- Herrin and Zarco test Caterham at Almeria
- Monday, 18 November 2013
- Luthi sets pace in Monday Valencia test
- Friday, 15 November 2013
- Luthi fastest as Jerez test comes to an end
- Wednesday, 18 December 2013
- Kornfeil and Viñales to ride for Team Calvo in 2014
- Ana Carrasco to ride for RW Racing GP in 2014
- Wednesday, 27 November 2013
- Fabio Quartararo: A new star is born
- Beirer on Husqvarna's identity and KTM's future
- Friday, 22 November 2013
- Miller needs rest and recuperation after surgery
- Wednesday, 20 November 2013
- Provisional 2014 Moto3™ entry list
- Friday, 15 November 2013
- Miller once again on top in Jerez testing
- Thursday, 14 November 2013
- Miller quickest on first day of Moto3™ Jerez test
- Saturday, 9 November 2013
- Rins grabs pole for championship decider


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Karen Kay McKinney
Published: Wednesday, January 5, 2005 at 3:30 a.m.
Last Modified: Tuesday, January 4, 2005 at 11:00 p.m.
BRENT | Karen Kay McKinney, age 63, of Brent, died Jan. 3, 2005 at U.A.B. West. Services will be 11 a.m. Friday at Rockco Funeral Home Chapel in Centreville. Burial will follow in Enon Cemetery with Rockco Funeral Home of Centreville directing. Visitation will be Thursday night from 6 to 8 p.m. at the funeral home.
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Hello,,, your group sounds interesting.. Wendy
that I'm over 40, have two grandchildren, like to laugh and shop. and that's it~
No answer yet
No answer yet
Thanks for all you do, Sue
Sign in to post a Greeting.
Hello, wendy
I am a single baby boomer. I just reach out to you to share an official Young Senior dating site .... ♥http://dating50plus.jigsy.com ♥...... the largest dating site for baby boomers. the place to meet senior for fun, romance, relationships, love and more. Meet and chat instantly with seniors from all over the world with instant messenger system! Look forward to see you soon!
Love your honest answer on the wing-person question! Love the candor!
Hey Wendy, I haven't learned yet how to reply to messages people send me, but I'll keep trying to figure it out :-) Anyway, you asked how we are purchasing tix to the Stills concert. If you look in the description of the Meetup, I added a link for tickets.
Another Wendy D. :)
Thanks for joining - looking forward to meeting you soon. :)
Hi Wendy -- did you grow up in Haverhill and go to HHS? I graduated in 1963 and we're having our 50 yrs reunion in October at Diburro's. Wonder if we know each other or mutual people.
Hi Wendy,
I am going to Spain and wonder if you would like to be roommates again. Hope all is well.
Hi Wendy,
Do you have a roommate for Canada, we are roommate this weekend in Maine. Kelley
Hi - If we don't meet before Ogunquit I look forward to meeting you then - we can share our 'babysitting" stories. Hope PIP is working out for you
Hi Wendy, how are you. I would like to share a great dating site for over 50 mature singles. ___searchingsenior.com___ My friend just had a success there. Hope it can help more single people find their love, romance and friendship.
Hi Wendy! Thanks so much for joining, I look forward to meeting you!
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A collection of news and information related to Concerts published by this site and its partners.
Top Concerts Articles
Displaying items 45-55
Rockin' with Rick Vito: Former Fleetwood Mac guitarist returns to alma mater Kutztown University
Story | Oct 19, 2013 | 4:22 AMOn a December night in 1968, guitarist Rick Vito left Kutztown University and drove with musician friends to the old Electric Factory in Philadelphia to see Fleetwood Mac — then a burgeoning blues band fronted by extraordinary guitarist Peter Green.... -
REVIEW: Silvertide at Sands Bethlehem Event Center shows music doesn't have to be new or different, just good
Story | Sep 30, 2013 | 4:23 PMThe flurry of basic, blues-based rock revival bands that made a splash in the early 2000s and didn't seem to fare too well in the long run – perhaps because, in the long run, the music offered nothing new or...... -
Interviewing Tracy Morgan: Expect edgy stand-up, not '30 Rock,' at Musikfest Cafe tonight
Story | Sep 27, 2013 | 4:22 AMTracy Morgan says that when he comes to Musikfest Cafe in Bethlehem for two comedy shows tonight, Sept. 27, the audience shouldn't expect to see Tracy Jordan, his self-centered prima donna character from the hit NBC-TV show "30 Rock."... -
Bucks County man faces first battle to advance on NBC-TV's 'The Voice'
Story | Oct 16, 2013 | 4:22 PMA Bucks County preacher's son who last month won over celebrity judges in record time on the season premiere of the NBC-TV singing competition "The Voice" faced his first round of head-to-head competition Tuesday. And this time, judges... -
Silvertide reunited, ready to pick up where it left off with Sands show Sunday
Story | Sep 27, 2013 | 4:23 PMAlmost a decade ago, Philadelphia rock band Silvertide was well on its way to being the biggest band from the city of Brotherly Love in a long time. Silvertide Signed to a major label when its members were still in...... -
REVIEW: The Hooters rock (and get nostalgic) in epic return to Ardmore Music Hall
Story | Sep 22, 2013 | 4:23 PM"This really is a special night," Rob Hyman of The Hooters said near the end of the band's show Saturday at Ardmore Music Hall. "We have a real history here." The Hooters, in file photo And a special night it...... -
REVIEW: Tedeschi Trucks Band makes up mind to play great show at Allentown's Miller Symphony Hall
Story | Sep 20, 2013 | 4:23 PMTedeschi Trucks Band's 2011 debut album "Revelator" won the Grammy Award for Best Blues Album because it was the entire package: Derek Trucks' guitar playing as good as any on the scene today, Susan Tedeschi's voice equally... -
Global Citizens music festival in NYC to feature Bono, Stevie Wonder ... LV congressman
Story | Sep 20, 2013 | 4:23 PMA Lehigh Valley congressman will be with the United Nations secretary general as well as music icons such as U2 frontman Bono and Stevie Wonder next weekend at a massive music festival in New York's Central Park to focus on...... -
REVIEW: A Day to Remember is Nickelback of metal at Sands Bethlehem Event Center
Story | Oct 13, 2013 | 4:22 PMIt's tough to figure what has made Florida rock band A Day to Remember so popular. Its metalcore/screamo songs, despite four of them cracking the Top 40, are far from impressive – standard fare in which singer Jeremy McKinnon shouts...... -
Talking with The Hooters' Eric Bazilian: Return to reopened Philly venue revives memories
Story | Sep 20, 2013 | 4:22 AMEric Bazilian, singer and guitarist for Philadelphia-area favorite The Hooters, says he was hesitant to play the grand opening weekend at the new Ardmore Music Hall. The Hooters, with Bazilian second from right The Ardmore was once the legendary 23...... -
Singer Glenn Tilbrook of Squeeze remembers first U.S. concert in Bethlehem
Story | Oct 11, 2013 | 4:22 PMGlenn Tilbrook, the guitarist and vocalist for British new wave band Squeeze, got his first look at American audiences way back in 1978 when, on the first date of its first American tour, the band played the long-gone bar The......


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If the Obamacaid web site (plus back-end IT infrastructure) is 70% feature-complete, works for 80% of users, and has 90% uptime...
That works out to just about 50% baked, no?
So it seems the Obamacare website (the easy part, remember) still isn't up to the "works 80% of the time" standard.
Let's review reliability numbers, shall we?
99.999%, five nines: about the minimum you can get away with selling to a serious business that depends on your product or service (but where no lives are at stake).
99.9%, three nines: OK for many non-critical uses. Don't try to sell it for serious uses unless you have an effective monopoly.
99%, two nines: possibly acceptable for cheap consumer goods.
90%, one nine: broken.
80%, zero nines: not even broken.
Then, at the high end, we have the wonderful world of aerospace and medical equipment, where... well, how many failures are acceptable over the 30-year working life of an airliner or a deep-space probe, or during open-heart surgery? The teams that work on that stuff need to live reliability.
Of course, all these numbers really apply to hardware, even if there's also software involved. For software, if it ever fails, it's broken; we just put up with a certain amount of brokenness in the software that we use day to day (e.g., any known word processor or web browser). The question becomes, is it so broken that it's positively unusable, or is it merely inconvenient and infuriating on rare occasions?
Update: The Administration is positively boasting of one-nine availability.
With all the talk of how much better Single Payer would be than Obamacaid (because it'd all be run by the Feral Gummint, and therefore inherently much more efficient than a haphazard quasi-private health-care payment sytem)...
Y'know, we have an example of Single Payer in the U.S.
We have Single Payer Military Procurement.
Which, with its wondrous efficiency, has recently brought us LCS, F-35A/B/C, NLOS-C, ... er. Not such great examples?
And various targeted contracts, whereby, e.g., the Army contracts with a preferred bidder (i.e., the one whose owner checks the most boxes on the "oppressed minority" form), which has no ability to deliver on the contract, and just passes it through to some non-minority-owned company, all facilitated by a group of rich white Beltway Bandits.
And the infamous $600 hammer ($10 for the hammer, and $590 for the paperwork to prove that the Government isn't getting ripped off).
(No, the Air Force's expensive Mr. Coffee doesn't exactly belong here. That wasn't a Mr. Coffee. 'Twas a restaurant-grade coffeemaker, plus a requirement to operate on a moving aircraft without splling hot coffee all over everywhere. Mostly bona fide operational requirements, and not at all comparable to a household appliance.)
From here:
I continue to believe, and [I am] absolutely convinced, that at the end of the day, people are going to look back at the work we've done to make sure that in this country you don't go bankrupt when you get sick, that families have that security," Obama said. "That is going be a legacy I am extraordinarily proud of."
Uh, right. Except:
The happy-shiny is all image, so the ruling class can feel good about itself. The reality is that, once again, the working class gets the short end of the stick. And, if you get seriously sick and don't have a large cash reserve (and good luck building one while paying big bucks for your health-plan premiums), you'll end up bankrupt.
Not only do they not get any money from me because, as I said right at the beginning of the call, I don't have any money to spare at this point....
Their fundraiser went right ahead and pissed me off by reciting the stock litany of Democrat gripes about the silly little crap* the "extremists" are forever trying to pull in Republican states (plus the over-the-top Democrat panic over arguably legitimate measures such as voter ID laws)...
...while totally ignoring the massive attacks on civil liberties being perpetrated by the crooks in power in, e.g, D.C. and Sacramento.
OK, guys. If you want to be a narrowly partisan organization, go right ahead. But you'll go without me.
* Like, oh, trying to impose Swedish-style restrictions on abortion.
Patterico has also picked up the story about the Obamacare website's back end being only about half-baked (60% done, 60% not done yet... not that much difference).
Not even the payment system? Not coded yet?
Why am I not surprised?
After all, the front end - the part the end-users see - is the easy part. A reasonably competent web-development team - say, three good developers and a manager - could have done the job, and done it well, in a couple of months, given a coherent spec to start with. Heck, I could have done it in a single-digit number of months, and I'm not even a web developer!
And yet: after three years, the front end code was far from ready for prime time. It didn't work.
Lurking behind the easy front-end code is the far more complicated back end, which deals with all the various, incompatible, fiddly databases, looks up your premium, calculates your subsidy, runs your application past the Department of Homeland Security, takes your money, and sends everything off to the third-party payment company of your choice. Basically the stuff ehealthinsurance.com has been doing for a while, plus the incredible extra complexity of dealing with the government bureaucracy and the subsidy system.
And, unsurprisingly given the state of the front end, this part turns out to be about half written. Tested? Working? What do those mean?
The really big complexity, of course, is the actual operation of the third-party payment system, and its interaction with the vast chaotic system that is the American Public.
Those of use who've been paying attention have been expecting, all along, the third part of the system to fail... but I, for one, was expecting the death spiral to start around the middle of next year (moved up from my earlier prediction of 2016-ish, once I saw what the premiums were going to look like) and proceed gradually, with things falling apart over a period of a few years. Now, with even the easy stuff not working, the premiums turning out to be even more out of line with what ordinary people can afford, the coverage on offer being largely substandard, and the cancellation notices going out? Dead and rotted by New Year's.
And meanwhile we have even more laws and regulations getting in the way of real reform. Progress!
Addendum: and what's with "getting the system working for 80% of the users" or whatever the latest promise is? Where I come from, that's called "zero-nines reliability," or, more commonly, "Does. Not. Work."
Because if he isn't... well.
Behold a tale straight out of tin-foil-hat territory, with four dead bodies (known, so far), government snoopery, high-risk raids in response to accusations (subsequently found to have been false) of minor skulduggery, and... oh, go read the whole thing.
This is just so implausible, right? Our government, here, in the good old U. S. of A., would never do such things.
Or, rather: it's implausible unless you've been paying attention to the news the past few decades. If you have been paying attention? Alas, not that much of a stretch.
From the latest at TSM, taken in turn from a comment there:
Coming off my yearly engagement with the think tanks, I've heard, for the first time, a series of data points coming from hospital CEOs that add up to one thing: the admission that exercising a hospital's primary function is no longer a source of value and revenue, it is viewed as entirely cost, risk, and liability. Consequently, they are no longer building any capacity, and are in fact looking for ways to reduce their capacity and eliminate hospital beds.
This is what happens when a business is run by the bean counters... which happens when it's big, or when it's publicly traded.
I've seen it many times in the high-tech area: under current accounting rules, R&D is pure expense. You can't go investing in the company's future by developing the next innovative product, because that's classified as spending the shareholders' money to no good purpose.
Which is why established companies can only create ever-shinier cosmetic variations on the old product line, and replace R&D with M&A: to get a novel product, wait until some little startup company develops it, then buy the company.
Oh, and little things like manufacturing test are also classified as expenses. Quality: we've heard of it, but have no budget for it.
All of which calls for a lengthy rant, but it's Monday morning and I'm already running late.
According to this in the NYT:
But unlike Mr. Bush, who faced confrontational but occasionally cooperative Democrats, Mr. Obama is battling a Republican opposition that has refused to open the door to any legislative fixes to the health care law....
Hello? Until a couple of weeks ago, 'twere Obama who refused to consider legislative fixes that might involve Republicans. True, when the Republicans were trying to delay the individual mandate through legislation (y'know, legally), they were really bent on killing the whole thing... but now that Obama is proposing to delay it by executive fiat (i.e., illegally), suddenly Republican opposition to changing the law is the problem?
Seems the fabled "Internet Kill Switch" is officially known as "Standard Operating Procedure 303."
Is that anything like Rule 303?


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Status: Open
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I didn't like an item on my plate And the manager told me they would charge me to fix it but took off less than I would've paid. The manager didn't even come to the table to formally apologize. He/she just sent her employees to do his/her bidding. I wasn't trying to get free food, I just felt like I shouldn't have to waste money on something I didn't like. Which was what it seemed like they...
I've eaten there several times & once my eggs weren't cooked as I ordered them & they quickly made them correctly with appologies & had our waitress & manager come out to make sure everything was ok You get good service & the food is good
Trading Post Cafe is located at 750 W Bankhead Hwy Ste C, Villa Rica, GA. This business specializes in Cafes.
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Domestic car sales dip 4% but bikes up 18% in October
Domestic passenger car sales declined by 3.88 percent to 1,63,199 units in October this year compared to 1,69,788 in the same month of 2012. #Numbers #Two wheelers #car sales #SIAM
Forget the Verna and City, small cars back in favour as austerity sets in
Smaller the car, lesser is its cost of ownership is the logic at present. #car sales #BRIO #SIAM #Ford EcoSport #Renault Duster #WagonR
Second year of falling car sales for India, can launches save the day?
Car sales in India have fallen 4.7 percent in the first six months of the fiscal year, the sharpest decline in half-year sales since 2002-2003, according to figures released by the Society of Indian Automobile Manufacturers (SIAM). #car sales #SIAM #auto sales #EcoSport #Vikram Kirloskar
Car dispatches slowest in 11 years, a third of auto facilities lie idle
According to data released by the Society of Indian Automobile Manufacturers (SIAM) today, car dispatches to dealerships were lower between April and September this year than even the gloom period just after the collapse of Lehman Brothers in 2008-09. #Numbers #Society of Indian Automobile Manufacturers #Automobile #Car sales slump #Vikram Kirloskar #motorcycles sales
Sep car sales disappoint again, up just 0.7%; bikes jump 17%
According to the data released by the Society of Indian Automobile Manufacturers (SIAM), motorcycle sales in last month grew by 17.44 percent to 8,85,117 units from 7,53,693 units in the same month previous year. #Numbers #passenger car sales #Society of Indian Automobile Manufacturers #SIAM #Two wheeler sales #motorcycle sales #total sales of vehicles
High rates, rising prices push back hopes of auto sales recovery
A surprise increase in interest rates and rising car prices in September have tempered hopes for a turnaround in India's struggling autos sector, with some analysts pushing back forecasts for a sustained recovery to next financial year. #Maruti Suzuki #car sales #Mahindra and Mahindra #SIAM #auto sales #automobiles
The Daily Mail
Bargain carmaker Dacia sees sales soar as Britons snap up 300 a week
Britons are snapping up more than 300 cars a week from bargain motor manufacturer Dacia, which has seen sales surge by 21.1 per cent across Europe in 2013... #europe
New York Daily News
Queens used car dealer gets 7 years for money laundering
A rags-to-riches used car dealer from Queens was sentenced Wednesday to seven years in prison for a massive money laundering scheme that included falsely reporting his yacht named "B LOW ME" stolen to collect the insurance payout. The rise-and-fall o... #trump world tower #southampton, ny #long island, ny #queens, ny
TIME Magazine
Apple's Cylindrical Mac Pro Desktop Available Tomorrow
The long wait is finally over. After about three years without a major overhaul, Apple's latest Mac Pro desktop is about to go on sale. Starting tomorrow, you'll be able to order the 9.9-inch-tall cylindrical aluminum whatsit from Apple's site and re... #mitsubishi