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In the pivotal phase 3 efficacy trial (NCT02747927) of the TAK-003 dengue vaccine, 5 of 13,380 TAK-003 recipients and 13 of 6,687 placebo recipients experienced two episodes of symptomatic dengue between the first dose and the end of the study, ∼57 months later (patients received the second dose 3 months after the first dose). Two of these participants experienced repeat infection with the same serotype (i.e., homotypic reinfection). In comparison with placebo, the relative risk of a subsequent episode of symptomatic dengue was 0.19 (95% CI, 0.07–0.54) in TAK-003 recipients. Based on the small number of subsequent episodes, these data suggest a potential incremental effect of TAK-003 beyond prevention of the first episode of symptomatic dengue after vaccination.

This article has two main objectives. One, to advance methodological development in both discourse theory and media and communications research by proposing an eclectic, replicable methodology. Two, to demonstrate how to apply that methodology to furnish both ontic and ontological explanations for the contingent origins of a discourse using the editorials of the Pakistani newspaper The Nation on the Pakistan Steel Mills privatization case as a case study. An earlier study had identified the surprising conclusion that this traditionally conservative paper had from the outset fully endorsed the radical opposition to the government’s suspension of the Chief Justice of the Supreme Court of Pakistan which led to an uprising known as the Lawyers’ Movement. This article locates the origins of that shift in the newspaper’s reaction to the Pakistan Steel Mills privatization issue. The article has implications for the fields of discourse theory, media and communication studies, and political science.

A main tenet of discourse theory, as derived from the original scholarship of Laclau and Mouffe, is that any social order is the contingent outcome of a political project. Such project is itself a consequence of material discursive practice, the pervasiveness of which is measurable in part by the extent to which its verbal articulations get disseminated with the help of news media. Thus, investigating news media agents which initiate, further, counter and discontinue the discursive process can be effective in mapping the political constitution of the social. But the question is: how to operationalize discourse theory for in-depth analysis of news media artifacts? Glynos and Howarth’s (2007) logics approach is a major step forward, but their account is too generalized to pass as an instructive account of their method. Others who have attempted to operationalize this approach have also left data analysis underspecified, particularly regarding the method of identifying the self-interpretations of social actors, on which the uncovering of logics initially depends. This article offers a more comprehensive methodological account. Through a sample analysis of one news report, we demonstrate that discourse theory’s analytical resources can be bolstered by subjecting the textual data to an approach derived from the literature on frame analysis. In the course of this illustration, we additionally hope to contribute to framing theory’s analytical repertoire.

Background Takeda’s dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. Methods Children (20 099, 4–16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. Results Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%–77.3%), including 67.0% (95% CI, 53.6%–76.5%) in dengue-naive and 89.2% (95% CI, 82.4%–93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%–66.8%) with the largest decline in 4–5 year olds (24.5%; 95% CI, −34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%–72.4%) in 6–11 year and 71.2% (95% CI, 41.0%–85.9%) in 12–16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year. Conclusions TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further. Clinical Trials Registration. NCT02747927. Takeda’s tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4–16 year olds in dengue-endemic countries.

This article builds on previous research on the communicational practices of the United Nations human rights monitoring system (Wallace 2017). Treaties such as those responsible for women’s and children’s rights lack direct enforcement mechanisms, so interest falls on the means by which treaty monitoring committees can encourage state compliance. The proceedings are bookended by writing (state reports and committee concluding observations), the focus of my earlier research. However, there is also an oral component, invariably characterized by the committees (but less frequently by the states) as “constructive dialogue” where the objective is “to assist and not to judge.” I explicate the structure and practices of these proceedings and find much that is justifiable, given the communicational context, but also some potential for reconsideration.

A substantial unmet need remains for safe and effective vaccines against dengue virus disease, particularly for individuals who are dengue-naive and those younger than 9 years. We aimed to assess the efficacy, safety, and immunogenicity of a live attenuated tetravalent dengue vaccine (TAK-003) in healthy children aged 4-16 years.We present data up to 18 months post-vaccination from an ongoing phase 3, randomised, double-blind trial of TAK-003 in endemic regions of Asia and Latin America (26 medical and research centres across Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). Healthy children aged 4-16 years were randomly assigned 2:1 (stratified by age and region) to receive two doses of TAK-003 or two doses of placebo, 3 months apart. Investigators, participants and their parents or guardians, and sponsor representatives advising on trial conduct were masked to trial group assignments. Participants presenting with febrile illness were tested for virologically confirmed dengue (VCD) by serotype-specific RT-PCR. In timeframes beginning 30 days post-second dose, the primary endpoint (overall vaccine efficacy) was assessed in the first 11 months, and the secondary endpoints (efficacy by baseline serostatus, serotype, hospitalised dengue, and severe dengue) in the first 17 months. This study is registered with ClinicalTrials.gov, NCT02747927.20 099 participants were randomly assigned and vaccinated between Sept 7, 2016, and Aug 18, 2017; 19 021 (94·6%) were included in the per protocol analysis, and 20 071 (99·9%) in the safety set. The primary endpoint was achieved with an overall vaccine efficacy of 80·2% (95% CI 73·3 to 85·3; 61 cases of VCD in the TAK-003 group vs 149 cases of VCD in the placebo group). In the secondary endpoint assessment timeframe, an overall vaccine efficacy of 73·3% (95% CI 66·5 to 78·8) was observed. Analysis of secondary endpoints showed efficacies of 76·1% (95% CI 68·5 to 81·9) in individuals who were seropositive at baseline, 66·2% (49·1 to 77·5) in individuals who were seronegative at baseline, 90·4% (82·6 to 94·7) against hospitalised dengue, and 85·9% (31·9 to 97·1) against dengue haemorrhagic fever. Efficacy varied by individual serotypes (DENV 1, 69·8% [95% CI 54·8 to 79·9]; DENV 2, 95·1% [89·9 to 97·6]; DENV 3, 48·9% [27·2 to 64·1]; DENV 4, 51·0% [-69·4 to 85·8]). Cumulative rates of serious adverse events were similar in TAK-003 (4·0%) and placebo (4·8%) recipients, and were consistent with expected medical disorders in the study population. Infection was the most frequent reason leading to serious adverse events. 20 participants (0·1% of the safety set) were withdrawn from the trial due to 21 adverse events by the end of part two; 14 of these participants received TAK-003 and six received placebo.TAK-003 was well tolerated and efficacious against symptomatic dengue in children regardless of serostatus before immunisation. Vaccine efficacy varied by serotype, warranting continued follow-up to assess longer-term vaccine performance.Takeda Vaccines.

Takeda has developed a live-attenuated dengue tetravalent vaccine candidate (TAK-003) which has been shown to be immunogenic with acceptable reactogenicity in phase 1 trials. In agreement with World Health Organization prequalification requirements for dengue vaccines, Takeda has manufactured a lyophilized formulation of TAK-003 that allows stable storage at +2°C to +8°C. This randomized, double-blind, phase 2 study (NCT02193087) was performed in 1002 healthy dengue-naïve adults, 18–49 years of age, across seven centers in the USA to compare the safety and immunogenicity of one or two doses of a lyophilized TAK-003 formulation with the liquid TAK-003 formulation used in previous phase 1 studies. The primary objective was to show immunologic equivalence in terms of geometric mean titers (GMT) of neutralizing antibodies to the four dengue serotypes one month after one dose of the lyophilized and liquid formulations. Secondary assessments were of safety and seropositivity rates, including after a second dose. The primary endpoint was not met, because immunologic equivalence after one dose was only shown for the DENV-2 serotype. Nonetheless, GMTs and seropositivity rates to all four serotypes were achieved with all formulations after two doses and are in line with what was observed in previous studies. Additionally, in view of the acceptable reactogenicity, with no vaccine-related serious adverse events reported, these data support continuing further clinical development of the lyophilized TAK-003 formulation.

Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019.We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype.Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively).TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927.).

Background Takeda’s live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data. Methods Healthy 4–16 year olds (n = 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction. Results Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6–66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8–88.4) against hospitalized VCD. Efficacy was 54.3% (41.9–64.1) against VCD and 77.1% (58.6–87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9–70.1) against VCD and 86.0% (78.4–91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5–54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6–83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified. Conclusions TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.

Traditional forestry, ecology, and fuels monitoring methods can be costly and error-prone, and are often used beyond their original assumptions due to difficulty or unavailability of more appropriate methods. These traditional methods tend to be rigid and may not be useful for detecting new ecological changes or required data at modern levels of precision [1]. The integration of Terrestrial Laser Scanning (TLS) methods into forest monitoring strategies can cost effectively standardize data collection, improve efficiency, and reduce error, with datasets that can easily be analyzed to better inform management decisions. Affordable (sub-$20K) off-the-shelf TLS units—such as the Leica BLK360— have been used commercially in the built environment but have untapped potential in the natural world for monitoring. Here, we provide a methodology that successfully integrates LiDAR scanning with existing monitoring methods. This new method:•Allows for simplified and quick extraction of forestry, fuels and ecological vegetation variables from a single TLS point cloud and quick transect sampling.•Streamlines the data collection process, removes sampling bias, and produces data that can be easily processed to provide inputs for models and decision support frameworks.•Is adaptable to integrate additional or new environmental measurements., Graphical abstract Image, graphical abstract

Background: As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country. Methods: Peripheral blood mononuclear cells were collected from a subset of 67 participants > 10 years old included in a phase 2 clinical trial of TAK-003 (Clinicaltrials.gov: NCT02302066). Following stimulation with dengue peptides, the frequency, magnitude, and cross-reactivity of the CD8+ and CD4+ T cell IFN-c, TNF-a and IL-2 responses were assessed by flow cytometry. Results: Intracellular cytokine staining identified NS1, NS3, and NS5 as the most common non-structural (NS) targets of the CD4+ T-cell response (IFN-c+); NS3 and NS5 were the main NS targets of the CD8+ T cell response (IFN-c+). Both CD4+ and CD8+ T-cell responses were multi-functional (IFN-c + TNF-a + IL-2+) and cross-reactive against DENV-1, -3, and -4 serotypes. Similar responses were seen in all CMI assessments irrespective of participant baseline status for dengue neutralizing antibodies and T cells. Conclusions: TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background We report long-term safety and immunogenicity of Takeda’s tetravalent dengue vaccine candidate (TAK-003) in healthy children and adults living in dengue-endemic areas in Puerto Rico, Columbia, Singapore, and Thailand. Methods In part 1 of this phase 2, randomized, placebo-controlled trial we sequentially enrolled 1.5–45 year olds (n = 148) into 4 age-descending groups, randomized 2:1 to receive 2 doses of TAK-003 or placebo 90 days apart. In part 2, 1–11 year olds (n = 212) were enrolled and randomized 3:1 to TAK-003 or placebo groups. We assessed neutralizing antibody titers for the 4 dengue serotypes (DENV) up to month 36 in part 1, and symptomatic dengue and serious adverse events (SAEs) up to month 36 in both parts. Results At month 36, seropositivity rates were 97.3%, 98.7%, 88.0% and 56.0% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates varied significantly for DENV-4 according to serostatus at baseline (89.5% in seropositives versus 21.6% in seronegatives). No vaccine-related SAEs were reported. Conclusions The trial demonstrated persistence of neutralizing antibody titers against TAK-003 over 3 years in children and adults living in dengue-endemic countries, with limited contribution from natural infection. TAK-003 was well tolerated. Clinical Trials Registration NCT01511250

Summary Background An unmet clinical need remains for an effective tetravalent dengue vaccine suitable for all age groups, regardless of serostatus. We assessed the immunogenicity and safety of three different dose schedules of a tetravalent dengue vaccine (TAK-003) over a 48-month period in children living in dengue-endemic countries. Methods We did a large, phase 2, double-blind, placebo-controlled trial at three sites in the Dominican Republic, Panama, and the Philippines. Healthy participants aged 2–17 years were randomly assigned 1:2:5:1 using an interactive web response system with stratification by age to receive either a two-dose primary series (days 1 and 91), one primary dose (day 1), one primary dose plus booster (days 1 and 365), or placebo. Participants and relevant study personnel were masked to the random assignment until completion of the study at month 48. To maintain masking, TAK-003 recipients were administered placebo doses when appropriate. The primary objective was assessment of neutralising geometric mean titres for each serotype to month 48 assessed in the per-protocol immunogenicity subset. Secondary safety endpoints included proportions of participants with serious adverse events and symptomatic virologically confirmed dengue. This study is registered with ClinicalTrials.gov , NCT02302066 . Findings Between Dec 5, 2014, and Feb 13, 2015, 1800 children were randomly assigned to the following groups: two-dose primary series (n=201), one primary dose (n=398), one primary dose plus 1-year booster (n=1002), and placebo (n=199). Of them, 1479 (82%) participants completed the 48-month study. Immunogenicity endpoints were assessed in 562 participants enrolled in the immunogenicity subset, of whom 509 were included in the per-protocol subset. At month 48, antibody titres remained elevated in all TAK-003 groups compared with placebo, irrespective of baseline serostatus. At month 48, geometric mean titres were 378 (95% CI 226–632) in two-dose, 421 (285–622) in one-dose, 719 (538–960) in one-dose plus 1-year booster, and 100 (50–201) in placebo recipients against DENV 1; 1052 (732–1511), 1319 (970–1794), 1200 (927–1553), and 208 (99–437) against DENV 2; 183 (113–298), 201 (135–298), 288 (211–392), and 71 (37–139) against DENV 3; and 152 (97–239), 164 (114–236), 219 (165–290), and 46 (26–82) against DENV 4; and tetravalent seropositivity rate was 89% (79–96), 86% (80–92), 97% (93–99), and 60% (47–72), respectively. Virologically confirmed dengue was recorded in 37 (2%) TAK-003 and 13 (7%) placebo participants, with a relative risk of 0·35 (0·19–0·65). No vaccine-related serious adverse events or severe dengue virus disease were reported. Interpretation TAK-003 elicited antibody responses against all four serotypes, which persisted to 48 months post-vaccination, regardless of baseline serostatus. No important safety risks were identified. We observed a long-term reduction in risk of symptomatic dengue virus disease in vaccinees. Results from this study provide a long-term safety database and support assessment of the vaccine in the ongoing phase 3 efficacy study. Funding Takeda Vaccines.

Background As part of the ongoing search for an effective dengue vaccine, Takeda performed a phase 1b study to investigate the safety and immunogenicity of an early low-dose tetravalent dengue vaccine candidate formulation (LD-TDV), based on an attenuated serotype 2 backbone, when administered intradermally with an injector device (PharmaJet®), or needle-syringe. Methods The study was performed in two centers in the US, in healthy 18–45 year old subjects with no history of dengue vaccination or disease. One or two vaccine doses were given on Day 0, and another dose or placebo on Day 90. Neutralizing antibodies were measured up to Day 270; safety was assessed as laboratory measurements and solicited and unsolicited adverse events on diary cards. Results Changes in World Health Organization prequalification guidance for new vaccines concerning storage conditions favored the use of lyophilized preparations, and led to the early cessation of enrolment, but not before 67 subjects were enrolled in four treatment groups. Sixty-five subjects completed the planned schedule. There were no safety signals or serious adverse events. All vaccination regimens elicited neutralizing antibodies. Titers of neutralizing antibodies against serotypes 1 and 2 were higher than those against serotypes 3 and 4. There were no consistent increases in responses with two doses given either concomitantly or 90 days apart. Conclusions Simultaneous injection of two LD-TDV doses was shown to have the potential to improve seroconversion rates to serotypes 1 and 2, and to increase serotype 2 antibody titers. A primary dose of LD-TDV administered by PharmaJet was shown to induce more rapid seroconversion to serotypes 1, 2, and 3 compared with administration by needle-syringe ( ClinicalTrials.gov : NCT01765426).

Summary Background Development of vaccines that are effective against all four dengue virus serotypes (DENV-1–4) in all age groups is important. Here, we present 18-month interim data from an ongoing study undertaken to assess the immunogenicity and safety of Takeda's tetravalent dengue vaccine (TDV) candidate over 48 months in children living in dengue-endemic countries. Methods We undertook a phase 2, multicentre, randomised, double-blind, placebo-controlled study at three sites in the Dominican Republic, Panama, and the Philippines. We randomly assigned children aged 2–17 years to receive either two TDV doses 3 months apart (group 1), one TDV dose (group 2), one TDV dose and a booster dose 1 year later (group 3), or placebo (group 4). We did the randomisation (1:2:5:1) using an interactive web response system stratified by age. The primary endpoint of this 18-month interim analysis was DENV serotype-specific antibody geometric mean titres (GMTs) in the per-protocol immunogenicity subset on days 1, 28, 91, 180, 365, 393, and 540. Secondary safety endpoints were the proportions of participants with serious adverse events and with virologically confirmed dengue in the safety set, and solicited and unsolicited adverse events in the immunogenicity subset. This trial is registered with ClinicalTrials.gov, number NCT02302066. Findings Between Dec 5, 2014, and Feb 13, 2015, 1800 children were randomly assigned to group 1 (n=201), group 2 (n=398), group 3 (n=1002), and group 4 (n=199). 1794 participants received at least one dose of TDV or placebo (safety set), of whom 562 participated in the immunogenicity subset and 509 were included in the per-protocol set. Antibody titres remained elevated 18 months after vaccination in all TDV groups. At day 540, in groups 1, 2, 3, and 4, respectively, DENV-1 GMTs were 476 (95% CI 286–791), 461 (329–647), 1056 (804–1388), and 92 (49–173); DENV-2 GMTs were 1212 (842–1744), 1242 (947–1628), 1457 (1182–1796), and 177 (93–337); DENV-3 GMTs were 286 (171–478), 298 (205–433), 548 (411–730), and 78 (44–137); and DENV-4 GMTs were 98 (65–150), 102 (75–139), 172 (133–222), and 33 (21–52). Limited differences in GMTs were observed between groups 1 and 2 (in which participants received one and two doses of TDV, respectively). In baseline-seronegative participants, a 1-year booster clearly increased GMTs. Vaccine-related unsolicited adverse events occurred in 14 (2%) of 562 participants, but no vaccine-related serious adverse events arose. Symptomatic, virologically confirmed dengue was recorded in 21 (1·3%) of 1596 participants vaccinated with TDV compared with nine (4·5%) of 198 placebo recipients. Interpretation TDV was well tolerated and immunogenic against all four dengue serotypes, irrespective of baseline dengue serostatus. These data provide proof of concept for TDV and support the ongoing phase 3 efficacy assessment of two doses 3 months apart. Funding Takeda Vaccines.

How can conduct be enforced when governmental relations are entirely reliant on linguistic exchange? This is the question at stake in such jurisdictions as the United Nations when nations sign up to legally non-binding commitments. The few commentators in this area hold that non-enforceability gives states the upper hand in this relationship. The research reported here, however, challenges that conclusion. By looking at textual exchanges of reporting and assessment respectively between the New Zealand government and the Committee on the Rights of the Child over a twenty year period, this paper identifies the linguistic and rhetorical strategies by which each party attempts to orient the conduct of the other. The conclusion reached, which can still only be provisional, is that, through nothing other than unwavering reiteration of its mandate, the UN committee gradually exhausts the evasive and countering tactics of the state party to bring about a degree of compliance.

Summary Background Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1–4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4). Methods An ongoing phase 2, randomised, double-blind, placebo-controlled trial of a TDV is being done at three sites in dengue-endemic countries (Dominican Republic, Panama, and the Philippines) to determine its safety and immunogenicity over 48 months in healthy participants aged 2–17 years who were randomly assigned (1:2:5:1) using an interactive web response system (stratified by age) to subcutaneous TDV injection (one 0·5 mL dose containing 2·5 × 10 4 plaque-forming units [PFU] of TDV-1; 6·3 × 10 3 PFU of TDV-2; 3·2 × 10 4 PFU of TDV-3; and 4·0 × 10 5 PFU of TDV-4) in different dose schedules (two-dose regimen at 0 and 3 months, one dose at 0 months, or one dose at 0 months and a booster at 12 months) or placebo. The primary endpoint of this 6 month interim analysis was geometric mean titres (GMTs) of neutralising antibodies against DENV-1–4 in the per-protocol immunogenicity subset at 1 month, 3 months, and 6 months after the first injection. Safety was assessed as a secondary outcome as percentage of participants with serious adverse events in all participants who were injected (safety set), and solicited and unsolicited adverse events (immunogenicity subset). This trial is registered with ClinicalTrials.gov, number NCT02302066. Findings 1800 participants were enrolled between Dec 5, 2014, and Feb 13, 2015. 1794 participants were given study injection as follows: 200 participants were given two-dose regimen at 0 and 3 months (group 1), 398 were given one dose at 0 months (group 2), 998 were given one dose at 0 months and will be given (trial ongoing) a booster at 12 months (group 3), and 198 were given placebo (group 4). These 1794 participants were included in the safety set; 562 participants were randomly assigned to the immunogenicity subset, of which 503 were included in the per-protocol set. TDV elicited neutralising antibodies against all DENV serotypes, which peaked at 1 month and remained elevated above baseline at 6 months. At 6 months, GMTs of neutralising antibodies against DENV-1 were 489 (95% CI 321–746) for group 1, 434 (306–615) for group 2, 532 (384–738) for group 3, and 62 (32–120) for group 4; GMTs of neutralising antibodies against DENV-2 were 1565 (1145–2140) for group 1, 1639 (1286–2088) for group 2, 1288 (1031–1610) for group 3, and 86 (44–169) for group 4; GMTs of neutralising antibodies against DENV-3 were 160 (104–248) for group 1, 151 (106–214) for group 2, 173 (124–240) for group 3, and 40 (23–71) for group 4; and GMTs of neutralising antibodies against DENV-4 were 117 (79–175) for group 1, 110 (80–149) for group 2, 93 (69–125) for group 3, and 24 (15–38) for group 4. No vaccine-related serious adverse events occurred; 15 (3%) of 562 participants in the immunogenicity subset reported vaccine-related unsolicited adverse events. The reactogenicity profile of TDV was acceptable, and similar to previous findings with TDV. Interpretation TDV is safe and immunogenic in individuals aged 2–17 years, irrespective of previous dengue exposure. A second TDV dose induced enhanced immunogenicity against DENV-3 and DENV-4 in children who were seronegative before vaccination. These data supported the initiation of phase 3 evaluation of the efficacy and safety of TDV given in a two-dose schedule 3 months apart, with analyses that take into account baseline age and dengue serostatus. Funding Takeda Vaccines.

Background Early formulations of Takeda’s tetravalent dengue vaccine candidate (TAK-003) have demonstrated notably higher neutralizing antibody responses against serotype 2 than other serotypes. Here, we assessed the immunogenicity and tolerability in adults living in Singapore of two TAK-003 formulations: an early formulation, referred to as HD-TDV, and a new formulation with 10-fold lower serotype 2 potency, referred to as TDV (NCT02425098). Methods Subjects aged 21–45 years were stratified by baseline dengue serostatus and randomised 1:1 to receive a single dose of either HD-TDV or TDV. Immunogenicity was evaluated at Days 15, 30, 90, 180, and 365 post-vaccination as geometric mean titres (GMTs) of neutralising antibodies and seropositivity rates. Viremia was assessed per vaccine strain. Solicited and unsolicited adverse events (AEs) were assessed by severity and causality. Results Of 351 subjects randomised, 176 received HD-TDV and 175 received TDV. Peak GMTs against all serotypes were observed at Day 30, with highest GMTs against DENV-2 in both groups. In subjects seronegative at baseline, the response to DENV-2 was less dominant with TDV (Day 30 GMTs: 813 for TDV, 10,966 for HD-TDV). In these subjects, DENV-4 seropositivity rates and GMTs were higher with TDV (Day 30 GMTs: 58 for TDV, 21 for HD-TDV; seropositivity rates: 76% for TDV, 60% for HD-TDV). Viremia mainly occurred for TDV-2 in both vaccine groups, with a lower incidence in TDV recipients, and mostly resolved by Day 30. Both vaccine formulations showed an acceptable safety profile with similar overall rates of solicited and unsolicited AEs across vaccine groups. Conclusions These results suggest a more balanced immune response with the new formulation TDV compared with the early formulation HD-TDV, particularly in subjects who were seronegative prior to vaccination, and support the choice of the new formulation for the phase 3 efficacy assessment.

Muscle loss is a debilitating side effect to prostate cancer (PCa) experienced by nearly 60% of men. The purpose of this study was to test the hypothesis that Nexrutine®, a bark extract from the Phellodendrum amurense, can protect against prostate cancer induced muscle loss in a similar manner as exercise, using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Forty‐five, 8‐ to 10‐week old TRAMP mice were randomized to either control, Nexrutine® (600 mg/kg pelleted in chow) or exercise (voluntary wheel running). Mice were serially sacrificed at weeks 4, 8, 12, and 20, at which time either the left or right gastrocnemius muscle was harvested, weighted, and frozen. Proteolysis inducing factor (PIF), ubiquitin, and NF‐κB concentrations were quantified using ELISA kits. Nexrutine® and exercise were equally able to protect TRAMP mice against PCa‐induced muscle loss (P = 0.04). Both interventions decreased intramuscular PIF concentrations at 20 weeks compared to control (P

Dengue fever is caused by infection with one of four dengue virus (DENV) serotypes (DENV-1–4), necessitating tetravalent dengue vaccines that can induce protection against all four DENV. Takeda’s live attenuated tetravalent dengue vaccine candidate (TDV) comprises an attenuated DENV-2 strain plus chimeric viruses containing the prM and E genes of DENV-1, -3 and -4 cloned into the attenuated DENV-2 ‘backbone’. In Phase 1 and 2 studies, TDV was well tolerated by children and adults aged 1.5–45 years, irrespective of prior dengue exposure; mild injection-site symptoms were the most common adverse events. TDV induced neutralizing antibody responses and seroconversion to all four DENV as well as cross-reactive T cell-mediated responses that may be necessary for broad protection against dengue fever.

Dengue is a significant threat to public health worldwide. Currently, there are no licensed vaccines available for dengue. Takeda Vaccines Inc. is developing a live, attenuated tetravalent dengue vaccine candidate (TDV) that consists of an attenuated DENV-2 strain (TDV-2) and three chimeric viruses containing the prM and E protein genes of DENV-1, -3 and -4 expressed in the context of the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4, respectively). TDV has been shown to be immunogenic and efficacious in nonclinical animal models. In interferon-receptor deficient mice, the vaccine induces humoral neutralizing antibody responses and cellular immune responses that are sufficient to protect from lethal challenge with DENV-1, DENV-2 or DENV-4. In non-human primates, administration of TDV induces innate immune responses as well as long lasting antibody and cellular immunity. In Phase 1 clinical trials, the safety and immunogenicity of two different formulations were assessed after intradermal or subcutaneous administration to healthy, flavivirus-naive adults. TDV administration was generally well-tolerated independent of dose and route. The vaccine induced neutralizing antibody responses to all four DENV serotypes: after a single administration of the higher formulation, 24-67%% of the subjects seroconverted to all four DENV and >80% seroconverted to three or more viruses. In addition, TDV induced CD8(+) T cell responses to the non-structural NS1, NS3 and NS5 proteins of DENV. TDV has been also shown to be generally well tolerated and immunogenic in a Phase 2 clinical trial in dengue endemic countries in adults and children as young as 18 months. Additional clinical studies are ongoing in preparation for a Phase 3 safety and efficacy study.

BACKGROUND: As increasing numbers of dengue vaccines and therapeutics are in clinical development, standardized consensus clinical endpoint definitions are urgently needed to assess the efficacy of different interventions with respect to disease severity. We aimed to convene dengue experts representing various sectors and dengue endemic areas to review the literature and propose clinical endpoint definitions for moderate and severe disease based on the framework provided by the WHO 2009 classification. METHODS: The endpoints were first proposed and discussed in a structured expert consultation. After that, the Delphi method was carried out to assess the usefulness, validity and feasibility of the standardized clinical disease endpoints for interventional dengue research. RESULTS: Most respondents (> 80%) agreed there is a need for both standardized clinical endpoints and operationalization of severe endpoints. Most respondents (67%) felt there is utility for moderate severity endpoints, but cited challenges in their development. Hospitalization as a moderate endpoint of disease severity or measure of public health impact was deemed to be useful by only 47% of respondents, but 89% felt it could bring about supplemental information if carefully contextualized according to data collection setting. Over half of the respondents favored alignment of the standard endpoints with the WHO guidelines (58%), but cautioned that the endpoints could have ramifications for public health practice. In terms of data granularity of the endpoints, there was a slight preference for a categorical vs numeric system (e.g. 1-10) (47% vs 34%), and 74% of respondents suggested validating the endpoints using large prospective data sets. CONCLUSION: The structured consensus-building process was successful taking into account the history of the debate around potential endpoints for severe dengue. There is clear support for the development of standardized endpoints for interventional clinical research and the need for subsequent validation with prospective data sets. Challenges include the complexity of developing moderate disease research endpoints for dengue. ispartof: BMC MEDICAL RESEARCH METHODOLOGY vol:18 issue:1 ispartof: location:England status: published

Background The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue-naive population. Methods Healthy 18–60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination—equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively. Results 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). Conclusions Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated.

Dengue is a potentially fatal viral disease for which treatment is limited to supportive care, and prevention and control are based on mosquito vector control programs. It is the fastest growing arboviral infection and is currently endemic in more than 100 tropical and subtropical countries, placing over 40% of the world's population at risk. At least 50 million infections are thought to occur annually, resulting in approximately 500 000 hospitalizations, mainly in children. In the context of an expanding and potentially fatal infectious disease without effective prevention or specific treatment, the public health value of a protective vaccine is clear. This review considers some of the challenges to dengue vaccine development, and in particular the challenges of demonstrating dengue vaccine efficacy.

Summary Background Roughly half the world's population live in dengue-endemic countries, but no vaccine is licensed. We investigated the efficacy of a recombinant, live, attenuated tetravalent dengue vaccine. Methods In this observer-masked, randomised, controlled, monocentre, phase 2b, proof-of-concept trial, healthy Thai schoolchildren aged 4–11 years were randomly assigned (2:1) to receive three injections of dengue vaccine or control (rabies vaccine or placebo) at months 0, 6, and 12. Randomisation was by computer-generated permuted blocks of six and participants were assigned with an interactive response system. Participants were actively followed up until month 25. All acute febrile illnesses were investigated. Dengue viraemia was confirmed by serotype-specific RT-PCR and non-structural protein 1 ELISA. The primary objective was to assess protective efficacy against virologically confirmed, symptomatic dengue, irrespective of severity or serotype, occurring 1 month or longer after the third injection (per-protocol analysis). This trial is registered at ClinicalTrials.gov, NCT00842530. Findings 4002 participants were assigned to vaccine (n=2669) or control (n=1333). 3673 were included in the primary analysis (2452 vaccine, 1221 control). 134 cases of virologically confirmed dengue occurred during the study. Efficacy was 30·2% (95% CI −13·4 to 56·6), and differed by serotype. Dengue vaccine was well tolerated, with no safety signals after 2 years of follow-up after the first dose. Interpretation These data show for the first time that a safe vaccine against dengue is possible. Ongoing large-scale phase 3 studies in various epidemiological settings will provide pivotal data for the CYD dengue vaccine candidate. Funding Sanofi Pasteur.

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials., Author summary Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective, and early recognition of severe dengue and timely supportive care remain the only means to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding deployment of such vaccines or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers, vaccine developers, and public health specialists to develop endpoints. After two working group meetings and discussions at international meetings, the Delphi methodology was used to clarify and further develop endpoints such that 70% or greater agreement was reached on most endpoint definitions including moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. The process identified areas for further evaluation and standardization within the context of ongoing clinical studies. The endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.

Purpose – The aim of this paper is to review the use of scenario‐building at the central government level in New Zealand and to consider an alternative technique – national imaging – for stimulating public discussion of the future.Design/methodology/approach – The paper briefly surveys New Zealand's history of prospective government before examining scenario construction during the Foresight Project convened by the Ministry of Research, Science and Technology during the late 1990s. Both the official scenarios produced and the guidance given to sector participants to produce their own scenarios are discussed.Findings – Scenario‐building in a national government context has pitfalls and limitations, namely that the technique is too ambitious, too socially unitary, and too implicitly long‐term to be really useful as a primary focus. Consideration of the shortcomings gives rise to an alternative procedure which focuses on developing images of national identity or conduct rather than envisioning or predicting ...

BACKGROUND A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries. METHODS This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4. RESULTS Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups. CONCLUSIONS TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure.

Introduction A safe, effective dengue vaccine that can simultaneously induce immunity to all four dengue virus serotypes (DENV-1–4) is a public health priority. A chimeric tetravalent dengue vaccine (TDV) based on an attenuated DENV-2 serotype backbone was evaluated in healthy, flavivirus-seronegative adults. Methods In this randomized, multicenter, Phase 1b study conducted in the United States, the safety and immunogenicity of TDV were evaluated in 140 participants aged 18–45 years in six dosing regimen study groups. Participants were injected subcutaneously on Days 0 and 90; placebo (saline) was injected where appropriate to maintain double blinding. Three different TDV dosages (TDV, a vaccine in which TDV-4 had been increased three-fold, and a one-tenth TDV dose), and single or double dosing were evaluated in one and/or both arms. Primary endpoints were solicited and unsolicited adverse events (AEs) and seroconversion rates to DENV-1–4 at Day 120. Results The severity of all AEs was generally mild. The most common unsolicited AEs were headache (52%), fatigue (43%) and myalgia (29%). The incidence of injection site pain ranged from 29 to 64% and 5 to 52% among study groups after the first and second doses, respectively. At Day 120, the ranges of seroconversion rates among the groups were DEN-1: 84–100%; DEN-2: 96–100%; DEN-3: 83–100%; and DEN-4: 33–77%. More than 80% of participants in each group seroconverted to at least three dengue serotypes. Substantial GMT increases from baseline were observed for DEN-1–3 at all time points from Day 30 onward; DEN-4 GMT increases were lower. Increasing TDV-4 slightly increased DEN-4 GMT, did not impact DEN-2 and DEN-3 GMT, but reduced DEN-1 GMT. Neither multiple dosing in both arms, nor one-tenth TDV dosing meaningfully impacted GMT increases relative to TDV. Conclusions All TDV doses and dosing schedules were well tolerated and immunogenic in healthy flavivirus-naive adults (ClinicalTrials.gov NCT01511250 ).

Over the past 30 years New Zealand’s system of public management has seen a number of positive changes, both systematic and incremental. That process made New Zealand a world leader in public management. Despite this, it remains difficult to gain traction on some of the most complex problems in society. Further, citizens have begun to demand more from their public service than just outputs and efficiency. In order to continue the positive trend of the previous decades, the system must evolve to appreciate the importance of outcomes and effectiveness.

A strong focus in political and policy circles on ‘managing’ the future – most visible during the latter half of last century in tools and techniques of central and strategic planning – was itself the outcome of an explosion of interest, dating from the beginning of that century, in the idea of establishing a science of administration. This idea was in turn related to the burgeoning throughout the 19th century of the social sciences, and of ‘governmentality’ in general (Wallerstein, 1991; Dean, 1999). In the early 1900s, Charles Merriam, a political scientist who later headed the United States National Resources Planning Board, coined a term which is emblematic of this whole development. The proper object of politics, he wrote, was no longer ‘the art of the traditional’ but ‘the science of constructive social control’ (quoted in Marini, 2001, 29).

The recent threats to a presumed international order posed by acts of heightened terrorism have overshadowed the promise of an emergent order evoked by such concepts as ‘the third way’ and ‘the knowledge society’. Part of the problem with these notions is that they have resonance for only a fairly selective group of intellectuals. Additionally, the terms are somewhat amorphous, so they have not achieved secure purchase in the popular media. But their meanings are not necessarily cancelled by the disordering events of political extremism, worrying as those events are. In the domestic policies of governments, and in workplaces, these other calls to (a beneficent) order continue to be heard and acted upon. The questions are those one must ask of any putative order: what kind of order is it, and is it really beneficial? It is perhaps all the more important to ask these questions when we might be otherwise distracted by the more dramatic events. The End of History? Both the knowledge society and the third way are variations on the ‘end of history’ thesis proposed by the US political scientist, Francis Fukuyama, after the collapse of the Soviet Union. For Fukuyama, as is by now well known, this collapse (for him of Marxism or communism, not just of the Soviet Union) ushered in the triumph of liberalism and capitalism as practiced in the United States and other Western-style democracies. In the third way thesis, as propounded by Anthony Giddens and others, a similar conviction about the bankruptcy of Marxism is accompanied by a more tempered view of liberal capitalism. The third way is, in practice, a middle path between the two, one which recognizes the need for State intervention, not only to condition and discipline the market – which left to its own devices will inevitably have detrimental social effects – but also to facilitate optimum participation in society generally. Hence, the focus of governments on what they call ‘capacity building’, which strongly emphasizes education and training amongst their responsibilities. As a result, the antithesis between communism and capitalism can now appear to have been resolved in a higher synthesis, leaving no room for further dramatic shifts in social organization. The knowledge society – formerly and still sometimes referred to as ‘the knowledge economy’ – has a similar ‘end of history’ flavor because it promises to resolve or at least ameliorate class conflict. It is based on the idea that, increasingly, machines can perform repetitive work, and that basic necessities can be easily met in modern economies. This creates ample scope for product differentiation (niche marketing) and for the provision of cultural goods – entertainment and so on. Everybody will have the opportunity to learn and apply knowledge, and therefore find fulfilling work. Everybody will have the capacity to innovate, and therefore improve the company’s performance, by which each person gains satisfaction and a stake in the future of the business. Technology is also frequently evoked: the interactive new media are said to be particularly amenable to knowledge sharing and innovation. At least in theory, the knowledge society can itself be seen as a third way, or meeting point, between economics and culture, science and arts; and therefore all disciplines, all areas of education and training, are equally important to future social and economic wellbeing. Both these notions have their clear attractions, and can be logically argued to institute improvements on previous orders. But how fully can they achieve their promises, or more importantly, are their promised benefits not just logical entailments but reasonably certain consequences of their social realization? Or can this new order be exploited to the same ends as previous orders? In this short essay, I can do no more than signal a few warnings or reservations concerning the promises that have been made. Social Unity? First of all, both concepts appeal to a putative unity of society, typically grounded in such notions as ‘social capital’ or ‘civil society’. This is problematic, if it is suspected that such unity is a chimera, impossible to achieve, and indeed a dangerous ambition in that it licenses the powerful to find a scapegoat for its elusiveness. Glyn Daly sums the situation up as follows: In every attempt to command the social terrain – to create an antagonism-free new order – various culprits are identified and made responsible for the original loss, or theft, of the fantastical object: Society, Harmony, Salvation, etc. Indeed, the very construction(s) of the social might be understood as a never-ending attempt to solve the original ‘crime’: to identify who has possession of the lost/stolen objects that would enable the full realization/representation of ‘us’. (79) So today, in my own country, New Zealand, we are given a false picture of a nation that lacks enterprise, drives away its best young intellects, can’t convert ideas into business reality, and so on. That paradise of the past when we ‘punched above our weight’, produced Nobel Prize winners and dominated the world in sports, has been stolen away from us. But all around is evidence that is at least partially to the contrary (it is also a fact that it is a big world, and the rest of it is catching up to our once privileged position). Any edition of the Dominion Post’s technology supplement, Info Tech Weekly, is bursting with technological and new media success stories: new start-ups, joint ventures, profitable sellouts, investment from overseas, revolutionary software, value-added agricultural products. Some of these crash and burn: contrary to the myth about the over-gentle, risk-averse New Zealanders, this is sometimes the result of brashness, rashness, and arrogance. New Artisans? Secondly, similar promises about new and improved orders of capitalism have been made before, but the situation was turned to the advantage of capital. In his book on Walter Benjamin, Julian Roberts refers to the ‘cooperative patterns of control’ implied by technology in the new order emerging between the wars. The production management systems that came to be known as Taylorism and Fordism, for example, by instituting processes based on the division of labor, ensured – in theory – that all participants in production were mutually dependent and therefore in some sense equal. Roberts suggests that these new arrangements threatened the old dispensation centered on private ownership of the means of production, and corrective action was not long following. ‘In order to retain this ownership, capitalism . . . resorted to a number of stratagems of which the most important was the division of the world into thinkers and doers, directors and directed, controllers and controlled’ (170). Does contemporary technology, particularly the advent of computers and the Internet as a significant means of production, imply a change in the pattern of control? Conceivably, computer technology and virtual knowledge products (software, etc.) could facilitate a return to a widespread artisan-like mode of production, and we see this to some extent in the new start-ups based on one or a few individuals, engaged in small-scale production. But we have also already seen that where these new enterprises are successful, they tend to expand and subsume, or are bought out by larger concerns. Significantly, we are in a business climate that remains strongly pro-growth, a feature of which is the repeated exhortation of self-employed or small firms to expand, to gear up to an export level of production. In the dissemination of this entrepreneurial message, the business media, which have themselves multiplied in recent years, have played a prominent role. Diverse and Mutually Enriching Knowledges? The concept of knowledge society has come to privilege science and technology. In the news media, as influenced by powerful interests, knowledge society and science and technology are more or less conflated. They are as well in the minds of important people, including those in the all-important research-funding bodies. A pertinent example in New Zealand is the Foundation for Research, Science and Technology. While official foundation publicity is relatively embracing of different approaches to knowledge – ‘the concept of a knowledge society includes the creation, distribution and application of new knowledge to all aspects and across all parts of society’ (FRST, “Foundation’s Role” 4) – specific individual pronouncements betray the actual emphases. For example, in announcing the appointment of a new CEO, the foundation’s Chairman, Neil Richardson said: ‘We live in exciting times and one can sense that the country is finally embracing the value of science and innovation and with it, the concept of a knowledge economy’ (FRST, “Permanent CEO” 1). By such means, ‘knowledge society’ is being used to maintain a division between science and arts, science and culture, when the term’s initial appearance promised a new or renewed awareness of the entanglement of these categories. (This is an outcome which has been only partly mitigated by the burgeoning of the creative industries, since there has been a trend to coining other terms such as ‘the creative economy’ to characterize this phenomenon.) In consequence, a fully nuanced evaluation of the role of scientific and technological development in contemporary society, as well as of its creeping commercialization, is further postponed. Conclusion Immanuel Wallerstein suggests that what he calls the Capitalist World-System has entered a period of transition towards a new system that may or may not be better than the present one. It is possible to imagine that the ‘third way’ and the ‘knowledge society’ – despite the reservations I have outlined – represent a moderating of the capitalist order that will usher in or help condition the arrival of the new. Or failing that, the privileging of knowledge will foster a reflectivity that will enable society to find a better way. Interestingly, however, Wallerstein suspects that such moderation will only prolong the current order, and that something more drastic (if not revolutionary) will be required in the long run if any significant improvement is to be achieved. And as far as reflectivity is concerned, the opposite is arguably true: that ‘knowledge’ merely serves rhetorically to conceal an intensification of the drive for profit and the general expansion of the business mentality. Note I am grateful for the comments of the anonymous referees of this article, which have been helpful in bringing it to its final form. References Daly, Glyn. ‘Politics and the Impossible: Beyond Psychoanalysis and Deconstruction’. Theory, Culture & Society 16.4 (1999): 75-98. Fukuyama, Francis. The End of History and the Last Man. London: Hamish Hamilton, 1992. Foundation for Research, Science and Technology, ‘The Foundation’s Role in Creating Value from Knowledge’. http://www.frst.govt.nz/public/thesource/FRSTrole.htm, 2001. Foundation for Research, Science and Technology. ‘Permanent CEO for FRST’. Media statement, 22 August, 2001. Giddens, Anthony. The Third Way: The Renewal of Social Democracy. Cambridge: Polity Press, 1998. Roberts, Julian. Walter Benjamin. London: Macmillan, 1982. Wallerstein, Immanuel. Unthinking Social Science: The Limits of Nineteenth-century Paradigms. Cambridge: Polity Press, 1991. Citation reference for this article MLA Style Wallace, Derek. "Knowledge Society and Third Way: A New Beneficent Order?." M/C Journal 7.6 (2005). echo date('d M. Y'); ?> . APA Style Wallace, D. (Jan. 2005) "Knowledge Society and Third Way: A New Beneficent Order?," M/C Journal, 7(6). Retrieved echo date('d M. Y'); ?> from .