text: Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts during HAART interruption: a randomized controlled trialPorter, Brian Oa; Anthony, Kara Ba; Shen, Jeanb; Hahn, Barbarab; Keh, Chris Ea; Maldarelli, Frankc; Blackwelder, William Ca; Lane, Henry Clifforda; Kovacs, Joseph Ad; Davey, Richard Ta; Sereti, IriniaAIDS: January 14th, 2009 - Volume 23 - Issue 2 - p 203–212 doi: 10.1097/QAD.0b013e32831cc114 Clinical Science Abstract Author Information Article Outline Objective: To evaluate whether interleukin (IL)-2 in patients with chronic HIV infection can maintain CD4 T cell counts during 6 months of HAART interruption. Design: Prospective, randomized, controlled, open-label phase II noninferiority trial comparing IL-2 with HAART interruption or continuous HAART. Methods: Forty-one IL-2-experienced (three or more prior cycles) HIV-1-infected adults with CD4 cell count at least 500 cells/μl were randomized in the ratio 2: 1 to interrupted (I = 27) or continuous (C = 14) HAART for 6 months following an initial IL-2 cycle. Subsequent IL-2 cycles were triggered by CD4 T cell counts less than 90% of baseline. Immune, metabolic, and quality of life indices were compared (Mann–Whitney and Fisher's exact tests), defining noninferiority as a percentage difference (C– I) in treatment success (CD4 T cells ≥90% of baseline at 6 months) with a 95% confidence interval (CI) lower limit greater than −20%. Results: Demographic and immune parameters were similar between the groups at baseline. Median CD4 T cell count, HIV viral load, and treatment success differed significantly at 6 months (I: 866 cells/μl, 39 389 copies/ml, 48.1%; C: 1246 cells/μl, <50 copies/ml, 92.3%; P ≤ 0.001). Group I was inferior to C (% difference = −44.2%; 95% CI: −64.2%, −11.2%; P = 0.013). Minor statistically significant differences in HgbA1c and energy level occurred at 6 months (I > C). Following HAART interruption, single cases of acute retroviral syndrome, secondary syphilis, non-Hodgkin's lymphoma, and Kaposi's sarcoma recurrence were observed. Conclusion: IL-2 alone was inferior to IL-2 with HAART in maintaining baseline CD4 T cell counts. HAART interruption had a small impact on metabolic parameters and quality of life. aNational Institute of Allergy & Infectious Diseases, USA bCritical Care Medicine Department, USA cNational Cancer Institute, USA dClinical Center, National Institutes of Health, Bethesda, Maryland, USA. Received 11 June, 2008 Revised 10 September, 2008 Accepted 29 September, 2008 Correspondence to Dr Irini Sereti, National Institutes of Health, Building 10-Magnuson Clinical Center, Room 11C103, 10 Center Drive, Bethesda, MD 20982, USA. Tel: +1 301 496 5533; fax: +1 301 402 4097; e-mail: email@example.com Abstract Introduction Methods Participants Study design Study medications Immunologic parameters Virologic parameters Metabolic function and quality of life measures Statistical considerations Safety assessments Results Study participants Interleukin-2 cycling and HAART resumption Primary outcome: treatment success at month 6 Secondary metabolic and quality of life analyses Secondary treatment success analyses Rates of change in HIV viral load and CD4 T cell count T cell phenotype and function Safety assessment Discussion Acknowledgements References Back to Top | Article Outline Introduction HAART has dramatically improved the outcome of HIV infection [1–3] but can be associated with high costs, medication fatigue, and adverse effects, including hepatotoxicity [4] and a metabolic lipodystrophy syndrome involving insulin resistance, hyperlipidemia, and fat redistribution [5,6]. HAART interruption strategies have been evaluated to minimize these adverse effects [7], but their safety was questioned by several large, randomized studies [8–12], which revealed increased rates of HIV disease progression and non-HIV-associated clinical events (e.g., the Strategies of Management of Anti-Retroviral Therapy (SMART) trial [11]). In attempts to abrogate CD4 T cell losses and reemergence of HIV viremia seen with HAART interruption, immunomodulatory approaches, including interleukin (IL)-2 cytokine therapy, have been evaluated. When used with antiretroviral agents (ARV), intermittent courses of intravenous or subcutaneous IL-2 can significantly expand the CD4 T cell pool in HIV-infected patients [13,14]. This results primarily from increased survival of naive [15,16] and central memory [17,18] CD4 T cells, including a cytokine-expanded naive CD4+CD25+ FoxP3-expressing subset, which resembles regulatory T cells [19,20]. Two international, multicenter, phase III clinical trials [Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT), Study of IL-2 in People with Low CD4+ T Cell Counts on Active Anti-HIV Therapy (SILCAAT)] are currently underway to determine the clinical relevance of these IL-2 effects with regard to HIV disease progression [21,22]. In addition to its adjuvant role in ARV therapy [13,23–25], IL-2 has also been studied with therapeutic immunization [26,27] and in the absence of ARV [14,28–30]. The potential role of IL-2 during HAART interruption was studied in AIDS Clinical Trials Group (ACTG) 5102 [28], which evaluated IL-2 recipients versus nonrecipients with chronic HIV infection following HAART interruption. Although higher CD4 T cell counts were observed with IL-2, no differences were noted in virologic rebound or in the time for CD4 T cell counts to fall below 350 cells/ml. The kinetics of CD4 T cell expansion with IL-2 was were also studied in a self-paired National Institutes of Health (NIH) cohort of HIV-infected patients – first, in the presence of continuous HAART and, second, followed immediately by HAART interruption. This revealed short-term CD4 T cell count increases in both settings, although to a lesser extent with HAART interruption [29]. The present study (ICARUS or Interrupted versus Continuous Antiretrovirals involving Randomization from the Umbrella Study) was a randomized, controlled trial in which HIV-infected, IL-2-experienced patients first underwent a baseline IL-2 cycle on HAART and were then randomized to either HAART interruption and intermittent IL-2 therapy or continuous ARV for a minimum of 6 months. The ability of IL-2 to maintain CD4 T cells off HAART was evaluated, as well as whether 6 months of HAART interruption could mitigate ARV-associated lipodystrophy syndrome, reduce hepatotoxicity, and improve quality of life. Back to Top | Article Outline Methods Participants Forty men and one woman with HIV-1 infection were recruited between September 2002 and June 2005, primarily from an NIH IL-2-recipient follow-up protocol [14]. Inclusion criteria were a minimum of three preenrollment IL-2 cycles, a CD4 T cell count at least 500 cells/μl, and willingness to interrupt or maintain HAART for 6 months, per randomization. Exclusion criteria included chronic hepatitis B, participation in other HAART interruption studies within the previous 6 months, malignancy requiring chemotherapy within the past 2 years, HIV complications necessitating ongoing HAART, and multidrug-resistant HIV requiring salvage ARV therapy. The study was approved by the National Institute of Allergy and Infectious Diseases (NIAID) Institutional Review Board (IRB), and all participants signed informed consent. Back to Top | Article Outline Study design The ICARUS study was a prospective, controlled, open-label phase II noninferiority trial. All participants received a baseline cycle of subcutaneous IL-2 upon enrollment [3–7.5 million international units (MIU) twice daily for 5 days] at the highest tolerated dose from their last IL-2 cycle. Participants were then randomized 2: 1 to interrupt or continue HAART, using a permuted block design with masked block size. For HAART interrupters, nonnucleoside reverse transcriptase inhibitors were stopped 2 days after the baseline IL-2 cycle, with all other ARV discontinued a week later. All participants had monthly clinical and laboratory evaluations. After the 6-month primary study period, HAART interrupters could continue this intervention over a 6-month extension phase, whereas participants randomized to continuous HAART could crossover to interrupt ARV (i.e., late HAART interrupters) for the next 6 months or end study participation. Over the entire 12-month study period, intermittent courses of IL-2 were given up to every 8 weeks to participants in either group, if consecutive CD4 T cell counts drawn at least 1 week apart declined to less than 90% of baseline, allowing for a maximum of three additional IL-2 cycles during the 6-month primary study phase. HAART could be restarted at any point according to patient's desirability, clinical indication, or if CD4 cell count fell to less than 350 cells/μl on two occasions within 8 weeks of receiving an IL-2 cycle. HAART interrupters received 10 days of non-abacavir protease inhibitor-based HAART with each 5-day IL-2 cycle, starting 3 days before and stopping 2 days after its completion, to abate possible IL-2-induced HIV replication [31,32]. The primary outcome measure was CD4 T cell count at month 6 (and at least 4 weeks after the last IL-2 cycle), with treatment success defined as maintaining randomization assignment and having a CD4 T cell count at least 90% of baseline. Secondary end-points included HIV viral load at month 6, treatment success at month 12, and rates of change in CD4 T cells and HIV viremia following HAART interruption. Back to Top | Article Outline Study medications Recombinant human IL-2 was provided by Novartis (Emeryville, California, USA). ARV usage was recorded and monitored throughout the study. Back to Top | Article Outline Immunologic parameters CD4 and CD8 T cell counts (total and percentage) were measured monthly in a Clinical Laboratory Improvement Amendments- approved laboratory. CD4+CD25+ T cells (previously shown to expand with IL-2 [33]) and peripheral blood mononuclear cell (PBMC) 3H-thymidine proliferation assays using HIV p24, tetanus toxoid, and phytohemagglutinin [34] were also followed. Back to Top | Article Outline Virologic parameters HIV viral load was measured by ultrasensitive branched DNA assay (bDNA version 3, Chiron Corporation, Emeryville, California, USA) with a lower detection limit of 50 copies/ml. HIV genotyping (TRUGENE, Visible Genetics Inc., Suwanee, Georgia, USA) was performed at baseline or a preenrollment time point with HIV RNA more than 1000 copies/ml, the initial time point with similar viral rebound following HAART interruption, and at end-of-study or prior to resuming ARV (whichever occurred first) to check for new resistance mutations, using TRUGENE Guidelines. Additional preenrollment genotypes were completed as needed to determine whether mutations were preexistent, though not detected at baseline. Participants who remained off HAART after end-of-study were followed up to 4 years to assess their capacity to suppress HIV viremia upon restarting ARV. Back to Top | Article Outline Metabolic function and quality of life measures Metabolic indices measured at baseline and month 6 included external body composition (weight; BMI; % body fat; multisite skinfold widths, including suprailiac, subscapular, biceps, triceps, calf, and abdomen; limb circumferences for forearm, mid-arm, calf, and thigh; body widths at the hips, waist, abdomen, and neck) and both subcutaneous and visceral adiposity determined via single-slice axial computed tomography at lumbar vertebral levels 2–3 and 4–5 [35]. Markers of endocrine and hepatic function included total cholesterol, high-density lipoprotein, low-density lipoprotein, fasting triglycerides, apolipoprotein A1 and B, glycosylated hemoglobin (HgbA1c), oral glucose tolerance testing (75 gm bolus), thyrotropin, free and total thyroxine, triiodothyronine, reverse triiodothyronine, uric acid, L-lactate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and total bilirubin. The MOS-HIV Health Survey, an established tool in HIV-related quality of life research [36–38], was also administered. Back to Top | Article Outline Statistical considerations Both intent to treat and per protocol analyses were performed. For the primary study end-point, the likelihood score method [39] was used to determine a two-sided 90% confidence interval (CI) to estimate the difference in proportions of participants with treatment success between interrupted and continuous HAART groups at month 6. The target sample size of 65 participants would have provided 79% power to obtain a lower confidence limit greater than −0.2 for P (interrupted) − P (continuous), assuming 90% treatment success and 10% attrition [equivalent to 79% power to reject H0: P (interrupted) − P (continuous) ≤−0.2 at a one-sided 5% significance level]. Due to slow recruitment, enrollment was closed at 41 participants, providing 80% power for two-sample t-tests of laboratory parameters with an effect size at least one SD at a two-sided 5% significance level. Mann–Whitney and Wilcoxon signed-rank tests were used for nonparametric median comparisons between and within groups, respectively, whereas Fisher's exact test was used for proportional comparisons. Back to Top | Article Outline Safety assessments Safety monitoring was completed via interview and laboratory assessment, following the Food and Drug Administration adverse event criteria and NIAID IRB guidelines. Adverse events were graded on a predetermined toxicity scale from 0–4. Back to Top | Article Outline Results Study participants Protocol flow of study participants is summarized in Fig. 1. Demographic and baseline characteristics are shown in Table 1. Fig. 1 Table 1 Back to Top | Article Outline Interleukin-2 cycling and HAART resumption Following the baseline IL-2 cycle, the need for additional on-study IL-2 cycling triggered by CD4 T cell counts less than 90% of baseline differed between the groups, with eight (29.6%) HAART interrupters receiving a single IL-2 cycle each during the primary phase (median of 52.5 MIU per participant) and 15 (51.9%) receiving a total of 17 cycles during the secondary phase (median of 45 MIU per participant). In contrast, no one in the continuous HAART group required IL-2 during the primary phase and only three (30%) late HAART interrupters received a single IL-2 cycle each during the secondary phase (median of 45 MIU per participant). No early HAART interrupters restarted ARV during the primary phase, although six (22.2%) restarted during the extension phase due to falling CD4 cell counts or rising HIV viremia, and one restarted after end-of-study due to a B cell lymphoma. By comparison, two (20%) late HAART interrupters restarted ARV while on-study (Fig. 1) due to an acute ARV syndrome and a case of secondary syphilis, with another restarting at end-of-study for recurrent Kaposi's sarcoma. Of the remaining participants, all but two early and two late HAART interrupters restarted ARV after end-of-study due to decreased CD4 cell counts or increasing viremia. Back to Top | Article Outline Primary outcome: treatment success at month 6 A larger proportion of participants (92.3%) in the continuous HAART group maintained CD4 T cell counts within 10% of baseline at month 6 (the primary study end-point), compared with HAART interrupters [48.1%, P = 0.013, Fisher's exact test] (Table 2). The 95% CI for the difference in these proportions (from −64.2 to −11.2%, interrupted–continuous) had a lower limit well below the predetermined noninferiority standard of −20%. Figure 2a depicts lower median CD4 T cell counts in interrupted in comparison with continuous HAART groups throughout the primary study phase and at month 6 (P < 0.001). Thus, IL-2 with HAART interruption was inferior in terms of treatment success at month 6, compared with IL-2 with continuous HAART. Table 2 Fig. 2 One participant in the continuous HAART arm withdrew from the study after 4 months in order to stop ARV. Inclusion of that participant as a treatment nonsuccess gives P value 0.041 for the difference in treatment success rates, and the noninferiority criterion is still not met. As month 6 data are unavailable for that participant, he was excluded from all other analyses. Back to Top | Article Outline Secondary metabolic and quality of life analyses No significant differences were observed in anthropometric indices between the interrupted and continuous HAART groups at baseline or month 6 (Mann–Whitney test; data not shown). For laboratory measures (Table 3), significantly lower values were seen at month 6 in the interrupted compared with continuous HAART group for total cholesterol (161 versus 190 mg/dl, P < 0.05) and apolipoprotein A1 (98.5 versus 111 mg/dl, P < 0.05). In contrast, HgbA1c was significantly higher in HAART interrupters at month 6 (5.4 versus 4.95%, P < 0.001). However, medians in both groups at baseline and month 6 were within normal range (<6%). Table 3 Physical and mental health scores on the MOS-HIV did not differ significantly between the groups at either time point (data not shown). However, the change in score from baseline to month 6 on the Energy/Fatigue subscale (a vitality measure from 0 to 100) was significantly greater in HAART interrupters compared with continuous HAART participants (interrupted: median change = 5, 95% CI: 0, 15; continuous: median change = −5, 95% CI: −25, 0; P < 0.001). Of note, completion rates for the MOS-HIV were lower at month 6 (interrupted = 74.1%, continuous = 84.6%) than at baseline (interrupted = 96.3%, continuous = 92.3%). Back to Top | Article Outline Secondary treatment success analyses Treatment success rates at month 6 versus month 12 within early HAART interrupters (48.1 versus 22.2%; P = 0.016; McNemar test) indicated declines in CD4 T cells observed in the primary study phase did not abate during the extension phase. Treatment success rates in early HAART interrupters at month 6 (n = 27) and late HAART interrupters at month 12 (n = 10) revealed no difference whether HAART interruption occurred immediately (48.1%) or 6 months (50%) after the baseline IL-2 cycle (Fisher's exact test; P = 1.0). Back to Top | Article Outline Rates of change in HIV viral load and CD4 T cell count Logistic regression analysis was used to calculate median rates of change in HIV viral load and CD4 T cell count over the first 6 months of HAART interruption, using all data points until first HAART reexposure (i.e., either IL-2 cycling or resumption of HAART). To evaluate the effects of timing of HAART interruption relative to the baseline IL-2 cycle, median rates of change were compared between early and late HAART interrupters. No significant difference in rate of HIV viral load increase was seen (early: 6356 copies/ml per month, late: 1162 copies/ml per month; P = 0.16; Mann–Whitney test). However, the rate of CD4 T cell decline was steeper in late (−96 cells/μl per month) than in early (−38 cells/μl per month) HAART interrupters (P < 0.001), indicating that 6 months of HAART following a baseline IL-2 cycle did not mitigate and, in fact, may have exacerbated this decline (Fig. 2b). Median rates of change were also compared in intragroup analyses within early or late HAART interrupters between subjects considered treatment successes versus nonsuccesses. Within early HAART interrupters, although the rates of HIV viral load increase did not differ significantly (nonsuccesses: 7631 copies/ml per month, successes: 3174 copies/ml per month; P = 0.20), treatment nonsuccesses had a steeper CD4 T cell decline compared with treatment successes (77 versus 3 cells/μl per month; P < 0.001; Fig. 2c). Similar comparisons among late HAART interrupters did not reveal any significant differences (data not shown). Back to Top | Article Outline T cell phenotype and function The percentage of CD4+CD25+ T cells did not differ between the groups at baseline (17% for both groups, P = 0.77) but was significantly lower in HAART interrupters at month 6 (18 versus 29%, P = 0.018). No significant differences in PBMC proliferative responses to HIV p24, tetanus toxoid, or phytohemagglutinin were observed between interrupted and continuous HAART groups or early and late HAART interrupters during the primary or secondary phases (data not shown). Proportional (Fisher's exact test) and median (Mann–Whitney test) comparisons were done to identify predictors of treatment success in either early or late interrupters, including baseline HIV viral load less than 50 copies/ml, peak on-study HIV viral load, nadir and baseline CD4 T cell counts, %CD4, and %CD4+CD25+ T cells. Only nadir CD4 count in early HAART interrupters significantly differed between treatment successes (422 cells/μl) and nonsuccesses (248.5 cells/μl; P = 0.023). Back to Top | Article Outline Safety assessment Grade 3 adverse events were constitutional symptoms previously reported with IL-2 therapy [40], including fatigue (n = 8), fever (n = 2), and abdominal pain (n = 2). The only Grade 4 event was an episode of transient hyperbilirubinemia due to underlying Gilbert's syndrome. Significant clinical events were detailed in the section on HAART resumption. HIV genotypic analysis indicated no novel resistance mutations emerged following HAART interruption, although two changes were noted. An early HAART interrupter with a reverse transcriptase T215Y change prior to enrollment developed a T215NTDA mutation, which reflects preexisting polymorphisms in ARV-naive individuals, as reversion from T215Y often occurs after HAART interruption. Another common polymorphism in ARV-naive individuals (protease I15V mutation; Stanford HIV Drug Resistance Database [41]) was observed in a late HAART interrupter. All participants who restarted HAART had virologic suppression to less than 50 copies/ml, except for two who continued treatment interruption beyond end-of-study: the first had documented medication nonadherence and the second had no prior HIV viral loads of less than 50 copies/ml, though after restarting HAART, his viral load decreased by more than 1 log from 9742 to 781 copies/ml. Back to Top | Article Outline Discussion The present prospective, randomized trial demonstrated IL-2 alone was inferior in maintaining CD4 T cell counts at least 90% of baseline in IL-2-experienced recipients after 6 months of HAART interruption, compared with IL-2 along with HAART. Despite a baseline IL-2 cycle administered in the setting of moderate to high CD4 T cell counts (range: 538–1390 cells/μl) and largely suppressed HIV viremia, this immune intervention could not sufficiently overcome the CD4 T cell declines associated with HAART interruption, as compared with patients who received IL-2 and remained on HAART. Several phase II studies [13,18,24,25,42] have documented IL-2 dose-dependent expansions of CD4 T cells, with increases in naive and memory subsets due to improved survival and decreased immune activation when administered with HAART. The immune restoration conferred by HAART alone is incomplete, however, despite reductions in CD4 T cell activation, turnover, and lymphopenia [43–46]. Thus, significant interest remains in IL-2 to augment the benefits of HAART by further reducing immune activation [47], as changes in plasma HIV RNA explain only 3–6% of the variability in CD4 T cell loss [48,49]. Regarding its use with HAART interruption, the results of Agence Nationale de Recerche sur le Sida (ANRS) 095 [50] and ACTG 5102 [28] suggested IL-2 conferred no benefit to HIV-infected persons, regardless of whether ARV were initiated during primary infection or later in the disease. Nonetheless, earlier data from the ICARUS cohort comparing preenrollment and baseline IL-2 cycling indicated CD4 T cell increases were achievable with IL-2 followed by HAART interruption [29]. The recently published TILT trial demonstrated IL-2 could reduce the probability of restarting ARV by 50% following 2 years of HAART interruption [51]. The different conclusions in ICARUS and TILT may be explained by the stricter criterion for treatment success used in the former. Whereas we sought to maintain CD4 T cells within 10% of baseline levels (947 cells/μl), in TILT, IL-2 cycles were triggered by CD4 T cell counts less than 350 cells/μl, and HAART was restarted for CD4 T cell counts less than 200 cells/μl [51]. In fact, CD4 T cell increases following IL-2 with HAART were similar in these studies, with half the HAART interrupters in ICARUS qualifying as treatment successes at month 6. This occurred despite the potential for self-referral bias within the ICARUS cohort of patients who tolerated IL-2 well and had high baseline CD4 T cell counts. As in past studies [28,52,53], higher CD4 T cell nadirs were associated with treatment success (i.e., higher CD4 cell counts) in the ICARUS cohort, although baseline CD4 cell count [52,54] and HIV viral suppression [52] were not. Whereas lack of CD4+CD25+ T cell expansion in early HAART interrupters suggested the importance of viral suppression in the IL-2-induced expansion of this subset [19,20,33], delaying HAART interruption for 6 months after a baseline IL-2 cycle was not more successful in maintaining CD4 T cells, despite greater CD4 cell count increases and prolonged viral suppression prior to interruption. This was reflected in similar treatment success rates in early and late HAART interrupters, with a steeper CD4 cell count decline in the latter (−96 cells/μl per month), similar to previous studies [28,55]. By comparison, CD4 declines in IL-2-naive patients following HAART interruption range widely in the literature from −10 to −200 cells/μl per month [28,55–57]. Six months of HAART interruption in our study also provided little benefit to HAART interrupters, with only small decreases in total cholesterol (similar to ACTG 5102 [58]) and apolipoprotein A1. Although HgbA1c was lower in the continuous HAART group at month 6, the clinical relevance of this is unclear, as values in both groups remained within normal range. This may reflect the expected increase in erythrocyte life span after stopping nucleoside reverse transcriptase inhibitors and reducing subclinical hemolysis [59]. A small (10% median group difference) though significant increase in energy level from baseline to month 6, as measured by the MOS-HIV Health Survey, was also observed in interrupted compared with continuous HAART participants, indicating IL-2 cycling (which was more frequent in HAART interrupters) did not adversely affect this quality of life measurement. The findings of the ICARUS trial showed that IL-2 alone was inferior in maintaining baseline CD4 T cell counts after 6 months of HAART interruption, compared with IL-2 along with HAART. In the post-SMART era [11], HAART interruptions are of limited scope and conducted under close supervision in clinical trials. However, adjunctive therapies to limit HAART exposure and abrogate the chronic inflammation of HIV infection (presumed to be a major cause of non-HIV-related complications [12,60]) merit exploration. Studies are underway to evaluate the capacity of IL-2 to delay HAART initiation in early HIV infection (STALWART) [61], and preliminary data from ANRS 119 suggest IL-2 can delay CD4 T cell decline and prolong time to an AIDS-defining event or HAART initiation in ARV-naive individuals [62]. Although unlikely to be of value as part of a HAART interruption strategy, the clinical impact of IL-2 in HIV disease will become clearer with the availability of data from the ESPRIT and SILCAAT trials. Back to Top | Article Outline Acknowledgements The authors would like to thank all study participants and the staff of outpatient clinic 8 at NIAID for their help in completing this trial, Christine Salaita for collecting anthropometric measurements, and Francine Thomas for reading the CT scans. B.P. contributed to data organization, analysis, and interpretation, and wrote the article. K.A., B.H., C.L., J.K., and R.D. contributed to the development and implementation of the protocol, and review of the article. J.S. contributed to the implementation of the protocol, data organization and analysis, and review of the article. C.K. and F.M. contributed to data organization, analysis, and interpretation, and review of the article. W.B. contributed to development of the protocol, data organization, analysis, and interpretation, and review of the article. I.S. contributed to the development and implementation of the protocol, data organization, analysis, and interpretation, and editing of the article. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy & Infectious Diseases, Clinical and Molecular Retrovirology Section (Bethesda, Maryland). The US Government has been granted a patent for the use of intermittent subcutaneous IL-2 as therapy in HIV infection, listing H.C. Lane and J.A. Kovacs as coinventors. This work was funded through the National Institute of Allergy & Infectious Diseases Clinical and Molecular Retrovirology Section of the National Institutes of Health (Bethesda, Maryland, USA). Human recombinant IL-2 was provided by Novartis (Emeryville, California, USA). These findings have not been published previously in their present form. 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Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N Engl J Med 1995; 332:567–575. Cited Here... 32. Davey RT Jr, Chaitt DG, Piscitelli SC, Wells M, Kovacs JA, Walker RE, et al. Subcutaneous administration of interleukin-2 in human immunodeficiency virus type 1-infected persons. J Infect Dis 1997; 175:781–789. Cited Here... 33. Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV, Fleisher TA, et al. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med 2005; 11:1238–1243. Cited Here... 34. Stevens R, Lempicki R, Natarajan V, Higgins J, Adelsberger J, Metcalfe J. General immunologic evaluation of patients with human immunodeficiency virus infection. In: Detrick B, Folds RHJ, editors. Manual of molecular and clinical laboratory immunology. 7th ed. Washington, DC: ASM Press; 2006. pp. 847–861. Cited Here... 35. Ellis KJ, Grund B, Visnegarwala F, Thackeray L, Miller CG, Chesson CE, et al. Visceral and subcutaneous adiposity measurements in adults: influence of measurement site. Obesity (Silver Spring) 2007; 15:1441–1447. Cited Here... 36. Volberding PA, Lagakos SW, Koch MA, Pettinelli C, Myers MW, Booth DK, et al. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med 1990; 322:941–949. Cited Here... 37. Wu AW, Revicki DA, Jacobson D, Malitz FE. Evidence for reliability, validity and usefulness of the Medical Outcomes Study HIV Health Survey (MOS-HIV). Qual Life Res 1997; 6:481–493. Cited Here... 38. Safrin S, Finkelstein DM, Feinberg J, Frame P, Simpson G, Wu A, et al. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group. Ann Intern Med 1996; 124:792–802. Cited Here... 39. Gart JJ, Nam JM. Approximate interval estimation of the difference in binomial parameters: correction for skewness and extension to multiple tables. Biometrics 1990; 46:637–643. Cited Here... 40. Davey RT Jr, Chaitt DG, Albert JM, Piscitelli SC, Kovacs JA, Walker RE, et al. A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient therapy for early human immunodeficiency virus type 1 infection. J Infect Dis 1999; 179:849–858. Cited Here... 41. http://hivdb.stanford.edu/. Stanford University HIV Drug Resistance Database. 2008. Cited Here... 42. Mitsuyasu R, Gelman R, Cherng DW, Landay A, Fahey J, Reichman R, et al. The virologic, immunologic, and clinical effects of interleukin 2 with potent antiretroviral therapy in patients with moderately advanced human immunodeficiency virus infection: a randomized controlled clinical trial – AIDS Clinical Trials Group 328. Arch Intern Med 2007; 167:597–605. Cited Here... 43. Di Mascio M, Sereti I, Matthews LT, Natarajan V, Adelsberger J, Lempicki R, et al. Naive T-cell dynamics in human immunodeficiency virus type 1 infection: effects of highly active antiretroviral therapy provide insights into the mechanisms of naive T-cell depletion. J Virol 2006; 80:2665–2674. Cited Here... 44. Anthony KB, Yoder C, Metcalf JA, DerSimonian R, Orenstein JM, Stevens RA, et al. Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover. J Acquir Immune Defic Syndr 2003; 33:125–133. Cited Here... 45. Hunt PW, Brenchley J, Sinclair E, McCune JM, Roland M, Page-Shafer K, et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis 2008; 197:126–133. Cited Here... 46. Kovacs JA, Lempicki RA, Sidorov IA, Adelsberger JW, Herpin B, Metcalf JA, et al. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. J Exp Med 2001; 194:1731–1741. Cited Here... 47. Sereti I, Lane HC. Immunopathogenesis of human immunodeficiency virus: implications for immune-based therapies. Clin Infect Dis 2001; 32:1738–1755. Cited Here... 48. Rodriguez B, Sethi AK, Cheruvu VK, Mackay W, Bosch RJ, Kitahata M, et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 2006; 296:1498–1506. Cited Here... 49. Mellors JW, Margolick JB, Phair JP, Rinaldo CR, Detels R, Jacobson LP, Munoz A. Prognostic value of HIV-1 RNA, CD4 cell count, and CD4 cell count slope for progression to AIDS and death in untreated HIV-1 infection. JAMA 2007; 297:2349–2350. Cited Here... 50. Goujard C, Marcellin F, Hendel-Chavez H, Burgard M, Meiffredy V, Venet A, et al. Interruption of antiretroviral therapy initiated during primary HIV-1 infection: impact of a therapeutic vaccination strategy combined with interleukin (IL)-2 compared with IL-2 alone in the ANRS 095 Randomized Study. AIDS Res Hum Retroviruses 2007; 23:1105–1113. Cited Here... 51. Angus B, Lampe F, Tambussi G, Duvivier C, Katlama C, Youle M, et al. TILT: a randomized controlled trial of interruption of antiretroviral therapy with or without interleukin-2 in HIV-1 infected individuals. AIDS 2008; 22:737–740. Cited Here... 52. Fox Z, Antunes F, Davey R, Gazzard B, Klimas N, Labriola A, et al. Predictors of CD4 count change over 8 months of follow up in HIV-1-infected patients with a CD4 count > or =300 cells/microL who were assigned to 7.5 MIU interleukin-2. HIV Med 2007; 8:112–123. Cited Here... 53. Markowitz N, Bebchuk JD, Abrams DI. Nadir CD4+ T cell count predicts response to subcutaneous recombinant interleukin-2. Clin Infect Dis 2003; 37:e115–e120. Cited Here... 54. Read SW, Lempicki RA, Mascio MD, Srinivasula S, Burke R, Sachau W, et al. CD4 T cell survival after intermittent interleukin-2 therapy is predictive of an increase in the CD4 T cell count of HIV-infected patients. J Infect Dis 2008; 198:843–850. Cited Here... 55. Davey RT Jr, Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A 1999; 96:15109–15114. Cited Here... 56. Ruiz L, Paredes R, Gomez G, Romeu J, Domingo P, Perez-Alvarez N, et al. Antiretroviral therapy interruption guided by CD4 cell counts and plasma HIV-1 RNA levels in chronically HIV-1-infected patients. AIDS 2007; 21:169–178. Cited Here... 57. Tarwater PM, Parish M, Gallant JE. Prolonged treatment interruption after immunologic response to highly active antiretroviral therapy. Clin Infect Dis 2003; 37:1541–1548. Cited Here... 58. Tebas P, Henry WK, Matining R, Weng-Cherng D, Schmitz J, Valdez H, et al. Metabolic and immune activation effects of treatment interruption in chronic HIV-1 infection: implications for cardiovascular risk. PLoS ONE 2008; 3:e2021. Cited Here... 59. Diop ME, Bastard JP, Meunier N, Thevenet S, Maachi M, Capeau J, et al. Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected patients. AIDS Res Hum Retroviruses 2006; 22:1242–1247. Cited Here... 60. Emery S, Neuhaus J, Phillips A, Babiker A, Cohen CJ, Gatell J, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis 2008; 197:000–10. Cited Here... 61. http://www3.niaid.nih.gov/healthscience/clinicalstudies/HIVandInfectious/HIVstudies/STALWART.htm. NIAID HIV and Emerging Infectious Diseases Program: STALWART Study; 2008. Cited Here... 62. Molina J LY, Fournier I, Boulet T, Bentata M, Beck-Wirth G, Sereni D, et al. Predictors of slow disease progression in antiretroviral (ART) naive HIV-1 infected patients treated with IL-2: three-year extended follow-up of the Interstart ANRS 119 trial. In: 15th Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; 2008. Cited Here... Keywords:CD4 lymphocyte count; HAART; HIV infections; interleukin-2; lipodystrophy; randomized controlled trial © 2009 Lippincott Williams & Wilkins, Inc. Article Outline Abstract Introduction Methods Participants Study design Study medications Immunologic parameters Virologic parameters Metabolic function and quality of life measures Statistical considerations Safety assessments Results Study participants Interleukin-2 cycling and HAART resumption Primary outcome: treatment success at month 6 Secondary metabolic and quality of life analyses Secondary treatment success analyses Rates of change in HIV viral load and CD4 T cell ... T cell phenotype and function Safety assessment Discussion Acknowledgements References Source Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts during HAART interruption: a randomized controlled trial AIDS23(2):203-212, January 14th, 2009. Full-Size Email + Favorites Export View in Gallery Email to a Colleague Colleague's E-mail is Invalid Your Name: (optional) Your Email: Colleague's Email: Separate multiple e-mails with a (;). 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tl;dr; if you want to code, you should, regardless of gender identity. To find out what a modern programmer does, talk to one.
This article is a response to the disgraceful clickbait published by someone who should know better. It was called "Why Women Shouldn't Code" and was published in Medium and I'll let you look it up, as I prefer not to enable more click-throughs for her. A certain amount of uproar has already occurred over the internet and the article was amply eviscerated by Jenn Schiffer and Kelly Ellis:
Jenn gives good advice. Before I start in on this, I thought it would be useful to contextualize my perspective. First, I'm 44. My mom was a former first-grade teacher who decided to stay at home after she started having children because, in her opinion, there were only three professions open to women in the 60s: airline stewardess (which is what they were called), teacher, or housewife. She did one, then switched to the other, and was happy, but she always told me that my opportunities would be vastly expanded growing up as I did during the second wave of feminism in the 80s and 90s. Even Girl Scouts got really career-focused in this era, and we were constantly told that we could do anything, be anything, we just had to shoot for the moon. It was a good message, and not anyone's fault that I was drawn to more traditionally feminine pursuits – I learned how to knit, crochet, tat, make lace, cook, draw, and sew clothes, but I wasn't particularly interested in my three brothers' legos or reverse engineering of that TRS-80 computer. After earning a Ph.D. in a highly specialized corner of French studies at Cal Berkeley, I was lucky enough to realize quickly that this career path was a dead end and I was able to retrain, starting back at ground zero with a remote internship, and gradually learning how to design, then code, then work with databases, then build mobile apps, then write about the whole experience. So you find me now a Developer Advocate at a great company with a bunch of Github commits, a portfolio of commercial apps, and something like 14 years' job experience in Engineering. It's been a great ride, sometimes bumpy, but almost never have I been discouraged from shooting for the moon…just like we were taught in the 80s.
So it was with real horror that I read an article that posits that women are not suited to the work of the programmer, but are rather more suited to the interactive status of the marketer, PR person, etc, based on their "innate biology":
"In general, women are more intuitive and more perceptive. There's mountains of research about that. They're also more nurturing. That's hard-coded into them for the preservation of the race."
As someone who went to grad school in the 1990s when Judith Butler wrote her groundbreaking book on gender as performance, this concept seems incredibly dated. It reminded me immediately of the concept in Saudi Arabia that women are not innately suited to drive cars because they are emotionally unable to drive. It's so ridiculous that it really doesn't merit a response, but since a woman wrote this article it has the same credibility of someone like Phyllis Schlafly whose baking skills were extremely effective in crushing the ERA (yes, I remember!). These people are dangerous, which is why I'm writing this article.
But rather than debating the opinion that women are better suited to one or another career, I wanted to answer a different part of this article which is demonstrably inaccurate and makes me wonder if she has any earthly idea of the work process of a modern programmer:
"It requires enormous concentration, and it is exacting. It's often done in a dark room with no interruptions. But the most important people in the company don't write the code, they tell the coders what to write. Coders don't make the big decisions."
Other authors have demonstrated that coders who become CEOs or CTOs actually do make quite big decisions. I want to call out the concept that programmers dwell, like mushrooms, in dark rooms, like the guy from "Office Space", which I fear has influenced this article. I want to tell you about my own work process.
For the past few years I have happily worked from home. I have experienced various other types of work environments, including small offices (as in a sort of closet with another person), a cubicle in a big company (horror!), a regular office in a smaller company, but I find that working from home works best from me as the mother of two kids. I have always accepted employment offers only if remote work is acceptable as I know that I am most productive in my own environment. Right now I am typing this at my kitchen table, close to my coffee maker and plate of biscotti. My regular office has a standing desk and several monitors but I can switch from room to room at will. When the kids come home at 2:30, I can meet them with a hot cocoa and a snack. In the morning I can go for a run or do a different workout. At lunch I can eat outside. During the day I am constantly chatting with my colleagues on Skype or Slack, and often have face-to-face meetings over Skype. I am not in a dark room unless I turn out the lights, I am not working in isolation, and I do not look much like a mushroom unless I don't bother with makeup that day.
My home office
What I am trying to say is that by caricaturing the work of programmers, the author (Francine Hardaway, who again, should know better) is doing those of us who are evolving the field a real disservice. Her vision of the profession seems deliberately calculated to try to scare people, especially people who identify as gendered feminine, away. Why that is I don't know, but I would like to invite women and girls who are considering the field to shadow current programmers to get an idea of what we actually do. You can contact me via this blog if you want to learn more. Alternately, if you can find a chapter of Girl Develop It or Girls Who Code in your area, talk to the pros who run it and see what they say about their daily work. If it sounds interesting or exciting, maybe it is for you! Because this is America, women and girls have real choices here, and it's 2015 and I shouldn't even have to write this article.

subset: commoncrawl


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As you think about new places to visit and ideas to road trip this year or anytime…try some of these places…
Carhenge is a must visit in Alliance, Nebraska! On the western edge of the Sandhills of Nebraska, it's a vintage car replica of England's mystical Stonehenge. Or if you're coming from far away to visit Nebraska during the annual sandhill crane migration in early spring, perhaps plan a visit to Carhenge as well.
National Parks…under Teddy Roosevelt, five National Parks were created, doubling the exisiting number. Roosevelt slept under the stars with another John Muir, another hero for saving our natural treasures. Check out the wonderful PBS documentary by Ken Burns as well.
The town of Buffalo, WY is interesting…you can stay at the Occidental Hotel, where Butch Cassidy and the gang stayed. In Jackson there was a neat chocolatier CocoLove, where one of only two "master chocolatiers" in the U.S. is working and making chocolate.
If you're in Estes Park, Colorado…there is the historic Stanley Hotel where Steven King stayed. The Stanley was the inspiration behind "The Shining." Didn't see or feel any ghosts, but felt lots of history and good vibes!


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Cape Town - University of Zimbabwe lecturer and Zanu-PF apologist Vimbai Gukwe Chivaura has declared President Robert Mugabe a "spirit medium" who would never die, News Day reported on Monday. According to the report, Chivaura said Mugabe was a spirit medium like the country's historical spirit mediums Mbuya Nehanda and Chaminuka."The President is a svikiro [spirit medium] which will never die. He might die physically, but his spirit will remain with us, just like Mbuya Nehanda and Chamunika. We will continue fighting the British and other imperialists using his spirit," said Chivaura.Chivaura urged Zimbabwe's traditional chiefs to "support this great man because he will always be in us. Many youngsters are now admiring him and they want to be like him".Mugabe has ruled Zimbabwe since independence in 1980 and his critics say the 88-year-old leader, who is in the twilight of his political career, plans to die in office.During the Zanu-PF December 2011 annual conference, the party endorsed him as its candidate in the next elections.
If only he was a spirit!
If only we were not looking after millions of his citizens.
Why would anyone aspire to be like Mugabe after the untold damage he's done to the once beautiful and prosperous Zimbabwe and its people?
British and other Imperialist? God knows an african man always craves an enemy to blame - when all he really needs is a mirror.
Because they invented guns germs and steel and used it to destroy the whole flippen continent.
Well, you are one African that obviously has a very fertile and diseased imagination.
Do you really believe that Europeans invented germs?
Then we have guns, well you have a point there, although guns woulld have been pretty pointless without gunpowder, and that was invented by the Vhinese in the 9th century. Even conceding a small point to you about guns, it is generally recognised that the Chinese also are responsible for the earliest models called fire lances.
As for steel, Europeans were as pri itive as Africans when that happened in the Middle East, followed by India's invention of crucible steel in the 1st century BCE.
Maybe you should do a sanity check to see if what you think you know is anything close to reality!
criticallyhones. ok now this is about who invented what, cool. westerners used gunpowder(from china) and steel( india) and germs (smallpox) to mashup the continent. you havent refuted my comment you have just denied and split ish up sort of spreading the guilt across. are you denying that the west mashed up our continent? comon man , i wont stoop to you level and judge your intellect and imagination,, you have already done that.
Michael - Africa has not contributed one single invention or tool of betterment - If it wasn,t for the other continents, you'd still be walking everywhere and spending your time in tribal warfare (as you still are today) Ignorance of the facts is how the cANCerous leaders like to keep you!
Ya, looking at how he stuffed up his country, his spirit will haunt the Zimbabwians for years to come. I agree. What an idiot
Lord have mercy!
Looks like their leader's syphilis has affected the minds of his followers as well.
So sad ...
"... imperialists using his spirit..." why don't you use his "living"spirit now and feed your people who are busy begging on the street corners in SA
I think the lecturer has been partaking of to many spirits .....
I like men who fight . Fight them British to the bitter end so that they must no this is our Africa .
The headline is misleading, I thought the devil had died.
Did you just call Bob Mugabe the Devil?
Yes! Penny... And I was going to call him a 'demon', but devil sounded less offensive.
@Carlton: I feel you, I figured something was skew, but you can always hope...
Hahaha! That's hilarious! By far the funniest thing I have read all day. We can only have a guess as to how Vimbai Gukwe Chivaura got appointed to the university of Zimbabwe (it probably wasn't his IQ). I wonder if they run a course on how best to lick bObs butt for the Zimbabwean people at the university? My only hope on the matter is that tyrant bOb sees justice by way of being kicked out and tried of crimes against humanity before that A$$hole eventually kicks the bucket.
Not his spirit, but his ideologies will one day unite and save Africa when all the coward and selfish leaders are weakned.
....and your spirit is floating around over the ashes of what remains of Africa. IDIOT!
Unfortunately more like 'unite and burn Africa'. I can't disagree about the leaders though.
Ignorant tw@
Great things he's doing foe the future of Zimbabwe - or maybe you think that's the way Africans should remain - dumb and pigsh*t ignorant?
LOL, what a load of feces
There is no doubt
A stupid person saying a stupid thing.... News? I think not.
LoL, oh but of course he is!
Obviously they are preparing their country for Mugabe's death, by convincing all his vulnarable followers that he is a spirit medium they will be able to hold on to power even after their death claiming that their party is "guided" by their soon dead president. That's what the spirits are telling me Mr. President.
" Die in office...." I would prefer it if he died in extreme agony.
Man this headline is missing leading for a second i thought the old bastard is dead how nice that would have been
Cornell U study by Prof. Dunning; Some people are too stupid to realise that they are stupid. Add to this DNA problems and Chivaura suffers adouble whammy.
It's because of your 'spirit mediums' that your country is in the state it is.
I can imagine parents scaring their children in years to come - if you don't hide your pocket money, rob mugabe will come and rob you.
I hope he burns in hell.
I have some news for you boet - he is going to die, as surely as the sun goes down in the evening. The only real question to be asked is whether Zim will still exist by that time as his people all seem to be living in SA, you have no currency, no value and are of no real use to anybody.
See what the spirits have to say about that.......
only that will remain is the theiving spirit of his leadership
Piss off idiot !!!
Maybe they can feature his spirit on "most Haunted" lol
President Mugabe is my hero too and should be to every self respecting African.
Aahh.. would you say that to the black Zimbabweans killed during the 1983 Matabeleland genocide? How conveniently you forget that he is responsible for the torture and killing of thousands of his own countrymen.
So Mugabe is now declared a spirit medium by some poor deluded fool? In that case, I declare David Cameron as a godlike being who can possess any white person at will, and he can vaporize anyone by simply thinking about them. I also declare that he shoots lasers from his eyes and can summon meteors to crush those who dare oppose him. Credible information, folks!
We all wish, I think. Just imagine.... that's Bob gone, and Malema...
Zimbabwe has more than its fair share of University Lecturers whose public utterances, particularly on political issues, has left many wondering whether their really deserve their intellectual status. Vimbai Chivaura is just one more mentally retarded University Lecturers; Professors Arthur Mutambara, Wellish Ncube, Jonathan Moyo and John Makumbe are but a few of the others!
Would be great if he could hurry up now, with the becoming "spirit part"
Mr Chivaura, it sounds like you are on spirits yourself. Could it be "Mainstay?".....or maybe just "Brainslay"
Great theory, the real question remains, HOW SOON CAN WE TEST YOUR THEORY?
Bob gaan gaan kole gooi! Besig om
die vroot vuur te stook !!!
I wouls like to point out to one of the guys on this forum.....when "advanced" countries left their shores, which were populated with towns , roads, streets etc, which had horses pulling carts and wagons, gas lighting etc... in ships they built...and came to the shores of the vast backward uncivilised black continent...they realised its potential...especially when they saw the unclothed wild bunch that "greeted" them. We have all been on this earth for the same length of time....AFRICA keeps telling us we are all stemmed from Africa...so what happened to you guys who were"left behind" while the rest of us forged on and discovered all the mod cons we have today???
Damn! The article title got my hopes up that this ultimate scumbag has gone to Hell....
Or any of the "Happy" places that the different religions have, for the Stalins and Hitlers that this planet has spawned
He clings to life like a leech.
He knows where he is going... That's why he clings to life.
WHEN ONE DIES,THEY ARE DEAD BURIED AND GONE.death kills you until you die.


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Just watched the show. and found
Sigh..How u guys find the show?
Just watched the show. and found
Sigh..How u guys find the show?
Agree with you, story meaningless.
the movie, is designed in such a way, that it is not for watching the story one.... its for "viewing" pleasure..
ok...i will be more "direct", dun u find the people in the movie very well endowed? ya.. thats wat u pay for to see in this movie.
To be frank, this kind of shows, especially by the zhang director, are very boring... For us in our kind of society, i dunno how to enjoy the show in the artistic sense at all.
I think, unless we are living in the period of the romance of the 3 kingdoms, maybe i will know how to appreciate the show.
Look like it is telling us the population they have in China.
The soldier in the movie can occupy the whole orchard road.
Should have put this "movie" in the fashion show segment instead...not much story line and climax...very disappointed...not putting to good use the talent of Chow Yuen Fatt...
Gong lai Gong kee, ko si Gong na liang Li.....
ZYM is a talented movie making man.
If you judge from his past movies. (not Hero!) Like Raise the Red Lantern.
CYF is a good actor and GL is a good actress.
The movie is probably way below the standard and abilities of all 3.
But they all act dumb in this movie. Why?
Because the Money Man calls the shots.
The Producer / Director / actors / actresses will all give the one who has the Money what he wants.
If the the Money Man wants a movie to be made in a lousy way and pays ZYM, CYF and GL $$$Millions, why should they argue with it?
I enjoy watching his movies mainly for the scenery and cinematography though, not so much for acting or deep storyline.
i havent watched it but i think i'll watch. not for the storyline or wat but for the artistic values (if any)... even my film teacher is a fan of his.. so i guess i'll just watch it for the sake of seeking his filmmaking techniques n style, etc...
He is pandering to the audience who will pay good money to watch it, the critics who will like it, the voters who will vote for it. Mostly European/Americans pundits who will succumb to the "beauty", something their own movies did not do(sell) very well. But this genre when done by Yimou and his team seems to be right on the MONEY.
Yimou is just doing what he likes, or what he thinks his style is, and the money couldn't hurt.


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Fashion Institute of Technology coaching staff
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Get info about Fashion Institute of Technology coaching staff, and registering for departmental seminars and elective lectures. Not all recruiting is done like NCAA Division I teams. It's practically impossible for college coaches to watch every player who has expressed interest in their program, so if you get the chance, make a memorable first impression by visiting the campus in person. Finally, check with your major department for assistance with prerequisites, tuition payment deadlines, and Fashion Institute of Technology Athletics information. Please use the form above to request admissions info for Fashion Institute of Technology.
Stay in great shape, even through the off-season. Being physically fit includes knowing about nutrition, staying healthy, and not overworking your body before big games. Practice the basics, over and over, especially targeting skills related to your position. Become a super-specialist, and you'll always find your place on an athletic team. Keep your eyes on the ball, and sacrifice your body if you must, but don't drop the ball.
Watch the ball all the way into your hands, and get a good initial grip. Your sixth sense needs to be developed to stay aware of other players at the same time. Follow the advice that college coaches give you, and it will make a big difference in how you play. That's because most college coaching staff were star players at some point in their careers. Students must meet specific eligibility requirements each year to participate in Pamlico Community College football starting lineup. Beyond consideration for Fashion Institute of Technology coaching staff, you may think about University of Manitoba special problems for complementary electives to your primary course of study.
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I am about to upgrade CanadianFoodies.com to WordPress 2.5.
So please ignore any short term randomness as I disable plugins, upgrade and (hopefully not) troubleshoot. We'll be back to our regularly scheduled program shortly!
Thanks for your patience.
* Update (15 minutes later) – Upgrade complete. If you notice any further randomness, it is completely my fault!


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The takeover of two banks by the government of Iceland has been determined to be credit events that trigger payouts under credit default swaps. Landsbanki, which the government has put into receivership, is said to be first such event since the financial crisis began in Europe to trigger ...
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delete plugins via FTP borks the site
In the not too distant past, when a plug in was acting up and I could no longer get access to the dashboard via /wp-admin or /wp-login all I had to do was to FTP in and remove (delete) the offending plugin… presto, /wp-admin worked again.
On two of my domains, each has a different plugin causing a problem, FTP in and delete now causes more problems, not less.
on one domain the plugin wp-geo is a likely culprit
is the one with WP Geo removed (via FTP delete.
now look what happens when you attempt
Please HELP!
I'm guessing a path problem?
a manual edit of /wp-config perhaps?
Or am I going to have to get my hands dirty with PHP Admin (I hope not)
on another wp3-total cache is the probable cause of a borked website.
FTP and delete did not fix either domain
- The topic 'delete plugins via FTP borks the site' is closed to new replies.


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Flush Toxins and Strengthen the Body's Defenses
What does it mean to flush toxins? Most people think of fasting, diets and cleanses. And while these can help you flush toxins from your body, they tend to be only a temporary fix and may even cause undesired effects like dehydration, anxiety or fatigue.
In this article, we'll teach you a few tips that will help you eliminate toxins and strengthen your immune system. We'll also show you which foods you should eat for their detoxifying properties.
The detox process
Detoxification is actually a natural process of the liver, the largest internal organ in the body. Unfortunately, it's often overworked as it gets bombarded by toxins in the air, ground, water, foods, the home, office and transportation.
All this quickly depletes the body's ability to detoxify itself. A weakened detox system allows chronic conditions (like heart disease, obesity, cancer and autoimmune diseases) to develop.
To prevent toxins from accumulating, it's important to eat healthy while reducing your exposure to toxins. How? By adopting a healthy diet and lifestyle.
How to flush toxins and increase your defenses
Eat raw fruits and vegetables
These foods will help your body produce more detoxifying enzymes. For example, broccoli contains sulforaphane, which is believed to increase detox enyzymes and help prevent cancer and premature aging. Other detoxifying foods that you should include in your diet are:
- Cranberries
- Raspberries
- Apples
- Papaya
- Artichokes
- Chard
- Beets
- Spinach
Season your food
Season your dishes with herbs and spices like rosemary, cilantro and garlic. It's a simply way to add extra flavor to your food while increasing your defenses and detoxifying the body. The allicin in garlic, apigenin in celery and the carnosol in rosemary are compounds that help detox enzymes do a better job.
Use natural cleaning products
Your cleaning products shouldn't contain bleach. Opt for non-toxic "green" products to clean your home like vinegar, baking soda or lemon. This way you'll avoid inhaling harmful chemicals.
Pay attention to air quality
Every home should have a carbon monoxide filter and fire alarm installed. You should also invest in a radon kit. Prolonged exposure to this gas, which seeps into your home from the ground, can cause lung cancer. Also be careful with older stoves and furnaces because they can release more carbon monoxide into the air.
If you have to pass by a fire, a factory that's spewing smoke out of its chimney, or are walking in the city center, try to wear a mask to keep from breathing in harmful compounds. If you don't like the idea of walking down the street with a mask on, try to avoid the busiest areas. Stay away from smokers.
Exercise at least 3 times a week
Physical activity gets your heart rate up and gets your blood flowing to carry nutrients to your organs and remove waste products. It's been shown that exercising produces healthy changes in your DNA.
Researchers at Karolinksa University in Stockholm (Sweden) studied healthy volunteers who were instructed to ride a bicycle using only one leg. Several analyses showed that the exercised legs developed new methylation patterns linked to genes that regulate energy, inflammation and insulin response.
Fight fire with fire
Capsacin is a chemical compound that is responsible for the heat found in peppers, jalapenos, and Cayenne pepper. By stimulating blood flow and the metabolism, these foods help the body flush toxins.
It may be a meal for the more daring, but you can also get the same warming effects (increased blood flow and metabolism) by eating foods like garlic, ginger and mustard.
Foods that help flush toxins and improve the immune system
While we've already named a few above, it's worth mentioning these foods that are also good for your immune system. Take a look at this list of foods that you should never be without:
Tomatoes contain vitamin C, which helps increase your body's defenses to keep you from getting sick. They're also loaded with licopene, a phytochemical that fights cancer in the body, especially in the stomach, lungs and prostate. Tomatoes also help protect the dermis from the sun's harmful UV rays.
Grapes help cleanse the blood and intestines, strengthen the heart, and reduce cholesterol. They're also diuretic and possess laxative properties.
Grapes contain antioxidants that stimulate cardiovascular function and fight cancer. Of all the varieties, red grapes are the most recommended as they prevent blood clots and contain high levels of fiber and potassium.
Celery allows you to remove residues that accumulate in the body. In addition, celery improves intestinal transit (thanks to the fiber content) and improves blood circulation. Celery also contains vitamin C and strengthens cell walls.
Asparagus contains folic acid, potassium, fiber, vitamin C and beta-carotene. It fortifies brain and nervous system function, prevents and fights cancer and ocular disorders. Asparagus is diuretic and will help you flush toxins out through the urine.
Lemons cleanse and purifies the body, they're loaded with vitamin C and other antioxidants to strengthen cells. They also stimulate the gallbladder and help the digestive system and liver to function better.
Watercress contains 15 different vitamins and minerals. It's diuretic, purifies the blood, prevents fluid retention, and improves liver function and skin health. Watercress contains more calcium than milk, as much vitamin C as an orange and more iron than spinach.


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Cultivation of Cannabis in Florida Cultivation of Marijuana
AT&T, Sprint & T-Mobile Users Can Dial **LAWYERS
We are Criminal Defense Lawyers who Represent Clients Charged with Cultivation of Cannabis in Florida
In Florida, the growing, cultivation, or manufacture of marijuana (cannabis) is unlawful. It is unlawful for any person to manufacture or possess with intent to manufacture a controlled substance, including cannabis.
Proof Required for Cultivation Charges
In order to prove the charge of cultivation or manufacture of marijuana in Florida, the prosecution must prove three elements beyond a reasonable doubt:
- The defendant engaged in manufacturing,
- The manufacturing was of a controlled substance (marijuana/cannabis), and
- The defendant had knowledge of the presence of the marijuana or cannabis.
Penalties for the Criminal Cultivation of Cannabis in Florida
Criminal Cultivation of Cannabis in Florida is a third degree felony punishable by up to five (5) years in prison and a $5,000 fine. Cultivating or manufacturing of marijuana may be classified as a second degree felony punishable by up to fifteen (15) years in prison when the accused is in actual or constructive possession of the grow house and is found in possession of more than twenty-five (25) cannabis plants. If minors are present or residing at the location where the plants are grown, the offense may be charged as a first degree felony.
Manufacture of Cannabis Charges in Florida
In Florida, manufacture of cannabis is the production, preparation, packaging, labeling or re-labeling, propagation, compounding, cultivating, growing, conversion or processing of a controlled substance, either directly or indirectly.
Defenses to Marijuana Cultivation
Many of the defenses available in ordinary drug possession cases are available with cultivation or manufacturing charges, including constitutional legal defenses that challenge unlawful searches or seizures by law enforcement. Some common Fourth Amendment defenses available in cultivation cases include: absence of a warrant, defective warrant, unlawful execution of a search warrant, absence of probable cause to obtain a warrant, stale information forming the basis of the warrant, exceeding the scope of the search authorized by the warrant, invalid consent to search, coercive "knock and talk", constructive entry during knock and talk, exceeding the scope of a consensual search, unlawful arrest or detention, absence of exigent circumstances, controlled substances not in plain view, warrant-less search within the curtilage of a residence, Miranda violations, 5th and 6th amendment right to counsel violations, overly broad search incident to arrest, overly broad protective sweep, use of unlawful police tactics constituting a "search."
Early Negotiation is Critical in a Sale of Marijuana Defense in Florida
Early contact in the criminal process communicates competence, resolve, and establishes a rapport that may be needed during future negotiations.
We will make early contact with the prosecutor to present factual defenses, legal issues, and mitigating circumstances that may have a dramatic impact on the State's decision to move forward against you.
We also happen to be Florida criminal law attorneys.
We can help you.
Our Florida criminal lawyers serve clients charged with the cultivation of marijuana cases in Palm Beach County, Broward County, Miami Dade County, and most other Florida cities and counties.
We handle criminal law cases and the cultivation of cannabis charges in Palm Beach, Broward, Miami Dade County and throughout Florida.
Call us.
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text:
Once upon a time actors did plays instead of casting director workshops. They had soulful black-and-white photos they chose after looking at paper contact sheets with a 'loupe.' And each morning agents on both coasts would stand by their fax machines and wait for The Breakdowns, the daily list of roles currently being sought by LA and NY casting directors sent to licensed representatives who subscribe to the service. Once this magical document appeared, Ms. Agent looked at her client list and made little notes above each role with the clients to submit. Ms. Agent procured appointments by sending pictures and resumes by messenger to the casting director. She waited for a phone call telling her the appointments she had received. She called the answering service (!!) of the client with an audition appointment, and the client would walk up hill both ways through snow to pick up her sides.
Things changed. Enterprising souls realized that instead of spending thousands to mount productions of The Cherry Orchard in dank NY basements in the hope that harried casting directors would venture downtown, they could offer them money to watch scenes in an office after hours and everyone would be home in time to walk the dog. The advent of digital photography ushered in a more spontaneous headshot aesthetic (and knocked photo reproduction costs way down – see progress isn't all bad!). And Ms. Agent's overworked/underpaid assistant discovered she could make a few bucks by surreptitiously forwarding the now-emailed Breakdowns directly to actors for a monthly fee.
Actors started calling their agents with things they "heard about." Actors started banging their heads against walls because now they knew exactly which roles they weren't being seen for. Actors sunk into existential malaise realizing their agents weren't lazy idiots and there simply weren't any parts for them right now.
Ah, wasn't ignorance bliss?! To believe the auditions would magically appear once we switched agencies! To not have to worry about what color shirts we brought to our headshot shoot! And just maybe the 1970s were the Golden Age of American Acting because actors spent their evenings in basements doing The Cherry Orchard instead of a page-and-a-half of October Road we've been given ten minutes to prepare…sorry, was just brushing the snow off my boots.
It's not 1975
It's The Information Age, and who wants to be the actor without the information? With fewer and fewer agencies with larger and larger lists, most actors want every edge, and more and more are making reading The Breakdowns a meaningful part of their budget and daily work-hunt routine. Here we'll look at why and how two Los Angeles actors use The Breakdowns to further their careers.
But, Wait, Isn't Getting The Breakdowns, Like, Illegal?
Yes. Putting cash in an envelope each month and mailing it to some girl/guy you've never met with an anonymous PO box in Van Nuys in exchange for a daily email copy of The Breakdowns = buying stolen property. As much as Minerva loves you, she will not facilitate your life of crime. Though, she suspects that if you are in a professional acting class or networking group in LA, getting the BD's is an inquiry or 2 away.
Gary Marsh, owner of Breakdown Services, has been contending with people taking his proprietary info since founding the company in 1971 (and that's quite a story – more on that next week). He busted his first thief (an agent!) in 1977. With the switch to an email format in 1997 things went crazy, and in 2002 he put a lawyer on retainer to sue the people he catches selling them. Mr. Marsh contends that the lawyer is busy and successful in his endeavor and more than pays for his retainer in proceeds he wins for Breakdown Services. At present, Mr. Marsh has chosen to focus his litigation on those selling the BD's, not the actors buying them. At present.
Working with Your Agent
Ellis Morton* (*all actors' names have been changed) is in his early 40s. He moved to LA last year after having spent nearly a decade in NY with a couple of exploratory stretches out west. Ellis has an Ivy League education and graduated from one of the nation's best MFA Programs nine years ago.
Soon after graduation, a classmate told him of a yahoo group where the Breakdowns were anonymously posted each day. Although he was represented, at the time he didn't think of bombarding his agent with submission suggestions from his ill-gotten source.
Instead, he says, "I was really just trying to learn the lay of the land. I was back in New York after graduate school and wanted to know what percentage of work casting was in town versus out of town, musical versus non-musical." Eventually the free BD's on yahoo disappeared and his classmate pointed him to a for-pay source.
Ellis considers one of his strengths to be his ability to nurture professional relationships. He struggled with how to use the BD's without annoying his agent. As his resume and contacts grew he saw more projects on the BD's to which he had a connection – he had worked with the director before, he had played a role before that was currently casting, etc., and he began emailing and/or calling his agent with roles he, yes, "heard about." But, he did so only if he could add value to his submission by giving his agent concrete information that would strengthen his pitch to the casting director ("I've always wanted to play Hamlet!" doesn't fall under that category).
When Ellis moved to LA last year, now with several co-stars, guest stars and roles in New York and regional theater under his belt, he cut to the chase with his new agent at the bicoastal boutique where he's represented. "I said, 'I get The Breakdowns. Is it okay if I call or email you when I have specific information that can help you position me?'"
His agent said, "Yes, I can use all the information I can get. But you have to trust me in how I decide to use it." He knows it's up to his agent to discern whether a particular casting director is going to be impressed that he did the director's thesis production of Pains of Youth or married his wife's college roommate.
Researching this article, I learned that some casting offices demand that Breakdown Services only send their projects to a select list of the agencies that subscribe to the service (more on that next week). So it's indeed possible that the girl/guy in Van Nuys with your cash envelope is not on the A-list.
"How do you know," I asked Ellis, "if your Breakdowns are from…"
"Endeavor…" he said, knowing where this was going.
"Or," I said, "'Bob's Talent Factory'?"
Recently, Ellis had a tough couple of weeks in Breakdowns Land. "I saw some things that I thought I was spot-on for at offices where I've been planting seeds and no appointments…oh, and definitely 'Bob's Talent Factory'. My agent got me an audition for a show I've been keeping my eyes out for. He emailed me the breakdown along with my sides and it totally wasn't on my copy for the day."
So much for the Information Age – it's kind of hard to ask that PO Box if it regularly sees listings for Heroes.
Getting to the Source
Mary Wen* is an actress in her mid-twenties who also graduated from a rigorous conservatory program. She too is represented by a well-respected boutique agency, but although the firm has a great name in the business, she doesn't feel like she's a priority for her agent amidst all the series regulars on his list.
The Breakdowns are just one resource Mary uses to market her work. She regularly attends casting director workshops, is a member of a networking group that meets monthly, and strategizes with a career coach. With her coach, she's assembled a list of fewer than ten television shows to focus her energies on. When she sees a breakdown for a show on her list she does a drop-off if the office accepts hard copy submissions. She recently got her first audition for one of her 'hit list' shows after her tenth drop off at the office!
Mary will call the casting office if she's previously met the casting director or associate and/or the role is very specific for her (eg, if her special skills or ethnicity are specified), and she practices her telephone pitch with her coach. She usually opens with a reminder of when she last met the cd ("…we met last month at Reel Pros" or "we met last May through a referral from…"), the role she's interested in, and why she's right for the part ("I play guitar and have great comic timing…"). "It's terrifying," she says, "but money's tight and I can't afford many casting workshops right now, so I'm trying to get over my fear of the phone."
She recently transcended that fear when she called an office and pitched herself for a guest star she'd spotted on the BD's. She was asked to email her photo/resume, but ultimately wasn't brought in for the role. The office did call her, however, to read for a co-star for which the office hadn't released a breakdown. She booked the job.
"Basically, I act like I don't have an agent," she says. But she admits there are critical times when having a well-respected agent comes in handy. She booked two co-stars this pilot season and her agent was able to negotiate a much better rate than had she accepted the initial offer at scale.
As much progress as she's making in her television goals, however, Mary has found another use for The Breakdowns that she finds very gratifying. "Most of us get into this business because we like working with other artists. Casting directors are the gatekeepers, and sometimes they inhibit that exchange between artists. I often use The Breakdowns to get around casting directors. A lot of directors and producers are on Facebook and LinkedIn, so if I see a film on The Breakdowns I'm interested in, I'll try to get in touch that way and send a link to my website and reel. The other day I saw a short film and I don't know the casting director. I googled the director and found her production company's website and sent her an email."
Means to an End
Many working actors I spoke to feel no need to monitor The Breakdowns, and those who do stress that it's only one component of their work search routine. They also warn that it's not the end-all of what's out there. As we've seen, many roles aren't released and certain offices don't release to certain agencies.
Mary said she plans to use The Breakdowns until she feels she's on enough casting radars or her agent relationship is strong enough that "I don't have to." However, when I spoke to her she seemed most excited about a contact she'd made the (kind of) old-fashioned way. "This year I really, really want to work at The Sundance Institute. So when the directors were announced on the (Sundance) website I googled them and found one who got his MFA at Yale. I found him on Facebook, and, thinking we had something in common both coming from conservatories, I reached out making that connection. We exchanged some really nice emails about what we're working on!"
As Mary demonstrates, once you focus on the projects you want to do, there are a multitude of ways to get (free! legal!) information about who's doing what and how you can be a part of it. Let us know your tried-and-true and/or out-of-the box methods for getting face time with producers, directors, and casting directors and booking the work you want.
Next week we'll hear the agent and casting director perspective on actors using The Breakdowns and sit down with Gary Marsh, owner of Breakdown Services, Actors Access, and CastingAbout.com and a true authority on the LA Actor Hustle. He'll tell us why getting the 'illegal' BD's is a waste of our time and money, and he'll give us tips on how to make our (legitimately procured) submissions pop.
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Light My Fire
The Jewish Museum
- December 9, 2014
( 38)
Celebrate Hanukkah wherever you are! Select a contemporary or traditional Hanukkah lamp from the world-renowned collection of New York's Jewish Museum. Choose a unique background or upload your own photo to place it on, light the lamp, and then share with your family and friends. You can also save the lamps to your very own collection.
The blessings are available in English, Hebrew, and transliterated Hebrew.
The Jewish Museum
5th Ave at 92nd St
New York, NY 10128
The blessings are available in English, Hebrew, and transliterated Hebrew.
The Jewish Museum
5th Ave at 92nd St
New York, NY 10128
Saving it I can save it on my tablet, but I can't save it on my Galaxy S5. When I click on the app I have to set it up each time. Does anyone know how to save it on their phone?
Great when you don't own a menorah! You even have a choice of menorah! You can place it where you like, even on the moon! And share it with friends and family
Does not save!! Hopeless
Nice! Nice app. Help me celebrate Chanukah anywhere. Thank you guys. Blessings from Costa Rica.
Great app and simple to use This app is pretty nifty. Very nice UI and cool visual effects.
Fantastic Very simple, I like that the info about each menorah is viewable. Having access to the blessings is also really smart.
What's New
Light My Fire 1.1 is updated to take advantage of the latest Android platform. Improved share function now includes Instagram.


text:
The technology industry becomes more competitive, widespread and important with every passing year. Businesses wishing to make it big and remain ahead of their competitors are faced with the task of staying current, educated and up-to-speed with the latest trends in technology. Software enables users to be creative and translate their ideas into impactful products and services. For the creators of these innovative and vital programs, failure to protect the software can result in major loss and exploitation. Copyrights have been created and implemented to help creators maintain ownership and claim the right to any successes associated with the release of their software. Here is a simple introduction to the world of technology and copyrights.
Why Are Copyrights Important?
Creating successful software that allows technology users to discover a new and efficient way of doing something is definitely a feat to be proud of. Once you decide to publish the technology you have invented, its benefits become available to the public. Along with the hundreds of users who are quickly learning to navigate and use your software, there are those deceptive infringers who want nothing more than to make a quick buck by reselling someone else's hard work as their own. Taking the simple steps necessary to register with the U.S. Copyright Office can make all the difference in your ability to effectively protect your innovation.
When Should I Register My Software?
The minute you publish your software and make the technology available to your users, you should immediately begin the registration process. Failure to do so can mean grievous consequences ahead. For example, investors are usually much less interested in funding technology if it doesn't have a copyright to ensure protection and return on capital. Secondly, without a copyright to your name, your chances of winning an infringement battle are much lower. Last but not least, if you are dealing with infringement of property, the U.S. Copyright Office will not allow you to file any lawsuit unless you can provide a copyright with your name. So, when you decide to publish your technology, make sure your next step is to attain a copyright.
The Registration Process
For many people, the word copyright immediately evokes feelings of anxiety or stress. While the word may seem overbearing and sound like an intimidating amount of work, the process is relatively easy. Plus, registration is now entirely online. The few self-explanatory steps on the federal website will quickly direct you through the process so you can be on the road to success with the confidence of software protection. Your application will require the following information:
- Title
- Name of author
- Date of creation
- Name of copyright owner
Once this information has been recorded, you will be prompted to include your application fee along with one or two copies of the software you have created. This completed application will then be sent to the U.S. Copyright Office for final approval.
As a general rule, always keep a duplicate of your application for your records. Having this document in an accessible place will be of value should you ever need to reference it later on during an infringement case. You may consider enlisting the help of a legal professional to aid you in writing, filling out, and submitting the registration form. At the very least, consult with your lawyer for tips and suggestions regarding intellectual property law. This is an excellent way to make sure you understand the process and complete everything in an orderly and legitimate way.
If you have created valuable software that is useful to your consumers, then it is certainly in your best interest to copyright your creation. By taking a brief moment to submit an application form, you can ensure your protection, creative rights and success.
Legal Disclaimer
The content on our website is only meant to provide general information and is not legal advice. We make our best efforts to make sure the information is accurate, but we cannot guarantee it. Do not rely on the content as legal advice. For assistance with legal problems or for a legal inquiry please contact you attorney.


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Panasonic Mobile Service Center in Ponta Sahib
Panasonic Mobile Service Center in Ponta Sahib, Himachal Pradesh – Address, Contact Number are listed below. If you have any problem with your Panasonic mobile, kindly contact the service center officials. There is 1 Panasonic authorized mobile service center in Ponta Sahib
List of Panasonic Authorized Mobile Service Centers in Ponta Sahib:
Panasonic mobile service center in Ponta Sahib
Name: Dhiman Mobile Service Centre
Address: Main Market Majra, The. Paonta Sahib, Dist. Sirmour
City: Ponta Sahib
State: Himachal Pradesh
Pincode: 173021
Contact Number 1: 9318978376
Email: email@example.com
Working Hours: 10:00 AM to 6:00 PM
Working Days: Monday to Saturday [Sunday Holiday]
* Call the PANASONIC Service Center before planning your visit, to ensure that the service center address is correct and is open for service.
** Please comment below if you find any of the above information incorrect, we will fix it immediately. Thanks in advance