Journal articles on the topic 'Committee for Men Blinded in Battle'

Even more than the noise and the clouds of dust raised by men and horses, the flashing of bronze armour and weapons is characteristic of Homeric panoramas of battle. When the Greeks armed themselves with helmets, shields, corslets and spears, the brightness lit up the sky, and all around the earth beamed in the shine of bronze (19.359–63). It blinded eyes, the glare of bronze from shining helmets, newly-polished corslets and bright shields, as they advanced in their masses (14.340–3).

This article covers the relationship between the National Labour Confederation of Spain and the Comintern and its union adjunct the Profintern, from the Confederation's initial support for the October Revolution to its subsequent outright rejection of communist politics, with reference to the positions adopted by revolutionary syndicalist movements in other countries. During this period a small number of individuals attempted to tie the Confederation to the Communist International, but failed. The article covers an important period in Spanish labour history, and helps to explain the mistrust that would bedevil the Spanish revolutionary working-class movement until the Civil War. Previous research has presented the battle for control of the CNT as a straightforward battle between anarchists and communists. This was not the case. The pro-communists were a miniscule faction, led by men recently affiliated to the CNT and who had no understanding of the depth of rejection of politics by Confederal militants. They only managed to take control of the national committee by chance. Aware of their weakness they were forced to act in a secretive and often underhand manner. Using material not consulted in previous studies this article shows the extent of their subterfuge and of the opposition this created in the Confederation, as well as demonstrating that the CNT was not the only revolutionary organisation to reject the Bolshevik International.

AbstractObjectives:To compare the use of computed tomography – positron emission tomography and whole-body magnetic resonance imaging for the staging of head and neck cancer.Patients and methods:From January to July 2009, 15 consecutive head and neck cancer patients (11 men and four women; mean age 59 years; age range 19 to 81 years) underwent computed tomography – positron emission tomography and whole-body magnetic resonance imaging for pre-therapeutic evaluation. All scans were staged, as per the American Joint Committee on Cancer tumour–node–metastasis classification, by two blinded consultant radiologists, in two sittings. Diagnoses were confirmed by histopathological examination of endoscopic biopsies, and in some cases whole surgical specimens.Results:Tumour staging showed a 74 per cent concordance, node staging an 80 per cent concordance and metastasis staging a 100 per cent concordance, comparing the two imaging modalities.Conclusion:This study found radiological staging discordance between the two imaging modalities. Whole-body magnetic resonance imaging is an emerging staging modality with superior visualisation of metastatic disease, which does not require exposure to ionising radiation.

TPS262 Background: Robot-assisted radical prostatectomy (RARP) offers cure for localised prostate cancer but is associated with considerable toxicity. Potency and urinary continence are improved when the neurovascular bundles (NVBs) are preserved during a nerve-sparing (NS) RARP. The NeuroSAFE (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) seeks to promote optimal NS to maximise the opportunity for functional recovery without jeopardising oncological safety. The NeuroSAFE technique in RP has never been evaluated against a standard of care in an randomised controlled trial. Methods: This is a pragmatic, multicentre, single-blinded randomised controlled trial (RCT) in which men are allocated in a 1:1 ratio to NeuroSAFE RARP or standard RARP. Men in the NeuroSAFE RARP arm will undergo RARP with NS guided by the NeuroSAFE technique. Men in the standard RARP arm will undergo RARP with NS guided by standard current practice (prostate cancer clinical characteristics, multi-parametric magnetic resonance imaging (mpMRI) recommendations and digital rectal examination (DRE)). Eligible men will have operable localised prostate cancer, will be opting for RARP as primary treatment and will have good baseline erectile function (EF) (as defined by an Internatinoal Index of Erectile Function (IIEF)-5 score >21). The primary outcome is the proportion of men who achieve EF recovery at 12-months according to the IIEF. Oncological safety will be ensured by the independent DMC who will routinely review proportions of men with treatment failure (adjuvant therapy or biochemical recurrence (BCR)) in each arm. A sample size of 404 is estimated required. NeuroSAFE PROOF will continue to follow participant recovery for 5 years following treatment. Key secondary outcomes include patient-reported urinary continence recovery, sexual satisfaction, quality of life, and economic analyses. NeuroSAFE PROOF will be the first RCT of frozen section in radical prostatectomy (RP) in the world. Ethics and dissemination: Ethical approval was obtained from the National Research Ethics Committee North London (17/LO/1978). Results of this study will be disseminated through national and international papers, and to study participants. Clinical trial information: NCT03317990.

IntroductionActive surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether a patient truly has low risk PC based on biopsy alone. Multiparametric MRI scan together with biopsy, appears useful in separating patients who need curative therapy from those for whom AS may be safe. Two small clinical trials have shown short-term high-dose vitamin D supplementation may prevent PC progression. There is no substantial evidence for its long-term safety and efficacy, hence its use in the care of men with PC on AS needs assessment. This protocol describes the ProsD clinical trial which aims to determine if oral high-dose vitamin D supplementation taken monthly for 2 years can prevent PC progression in cases with low-to-intermediate risk of progression.Method and analysisThis is an Australian national multicentre, 2:1 double-blinded placebo-controlled phase II randomised controlled trial of monthly oral high-dose vitamin D supplementation (50 000 IU cholecalciferol), in men diagnosed with localised PC who have low-to-intermediate risk of disease progression and are being managed by AS. This trial will assess the feasibility, efficacy and safety of supplementing men with an initial oral loading dose of 500 000 IU cholecalciferol, followed by a monthly oral dose of 50 000 IU during the 24 months of AS. The primary trial outcome is the commencement of active therapy for clinical or non-clinical reason, within 2 years of AS.Ethics and disseminationThis trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals.Trial registration numberACTRN12616001707459.

Cheonan at the Late Period of Korean Empire was in an atmosphere of growing sense of crisis over colonization, including the Battle of Sesung Mountain, the Battle of Seonghwan, the development of Jiksan Gold Mine, and the construction of the Gyeongbu Rail. Meanwhile, foreign debt has snowballed, threatening the nation’s existence. The movement to protect national sovereignty by repaying foreign debts was felt everywhere. Articles emphasizing the responsibilities and duties of the people were frequently reported in newspapers. The decisive factor that changed the situation was the national debt redemption movement based on ‘sharing and responsibility’. The signal fire started in Daegu, but immediately spread to Korea and abroad. Like other regions, Cheonan actively participated in this trend. Residents of Cheonan approached themself as if they were the main character. Enlightenment officials issued a statement of intent and organized a national debt redemption movement committee to raise donations. This was the same as an important ‘stepping bridge’ that led to voluntary and competitive participation. Change came as a great stimulus to remind residents of their responsibilities as members of society. The various national movements here during the Korean Empire share this historical background. The status of the National Debt Redemption Movement was part of paying back the national debt, but it greatly changed the values of the people of the time. Changes in perception to pursue ‘social publicity’ have made progress in line with this. The scene that awakened the importance of living together could be done in The status of the National Debt Redemption Movement. Isn’t the historical fact that was not limited to men and women of all ages despite their status a true spiritual legacy that must coexist in the Multicultural Era. In the end, peace and freedom, which are universal values of mankind, are essential factors such as responsibility and sacrifice.

IntroductionProstate MRI is a well-established tool for the diagnostic work-up for men with suspected prostate cancer (PCa). Current recommendations advocate the use of multiparametric MRI (mpMRI), which is composed of three sequences: T2-weighted sequence (T2W), diffusion-weighted sequence (DWI) and dynamic contrast-enhanced sequence (DCE). Prior studies suggest that a biparametric MRI (bpMRI) approach, omitting the DCE sequences, may not compromise clinically significant cancer detection, though there are limitations to these studies, and it is not known how this may affect treatment eligibility. A bpMRI approach will reduce scanning time, may be more cost-effective and, at a population level, will allow more men to gain access to an MRI than an mpMRI approach.MethodsProstate Imaging Using MRI±Contrast Enhancement (PRIME) is a prospective, international, multicentre, within-patient diagnostic yield trial assessing whether bpMRI is non-inferior to mpMRI in the diagnosis of clinically significant PCa. Patients will undergo the full mpMRI scan. Radiologists will be blinded to the DCE and will initially report the MRI using only the bpMRI (T2W and DWI) sequences. They will then be unblinded to the DCE sequence and will then re-report the MRI using the mpMRI sequences (T2W, DWI and DCE). Men with suspicious lesions on either bpMRI or mpMRI will undergo prostate biopsy. The main inclusion criteria are men with suspected PCa, with a serum PSA of ≤20 ng/mL and without prior prostate biopsy. The primary outcome is the proportion of men with clinically significant PCa detected (Gleason score ≥3+4 or Gleason grade group ≥2). A sample size of at least 500 patients is required. Key secondary outcomes include the proportion of clinically insignificant PCa detected and treatment decision.Ethics and disseminationEthical approval was obtained from the National Research Ethics Committee West Midlands, Nottingham (21/WM/0091). Results of this trial will be disseminated through peer-reviewed publications. Participants and relevant patient support groups will be informed about the results of the trial.Trial registration numberNCT04571840.

IntroductionA potential link exists between prostate cancer (PCa) disease and treatment and increased inflammatory levels from gut dysbiosis. This study aims to examine if exercise favourably alters gut microbiota in men receiving androgen deprivation therapy (ADT) for PCa. Specifically, this study will explore whether: (1) exercise improves the composition of gut microbiota and increases the abundance of bacteria associated with health promotion and (2) whether gut health correlates with favourable inflammatory status, bowel function, continence and nausea among patients participating in the exercise intervention.Methods and analysisA single-blinded, two-armed, randomised controlled trial will explore the influence of a 3-month exercise programme (3 days/week) for men with high-risk localised PCa receiving ADT. Sixty patients will be randomly assigned to either exercise intervention or usual care. The primary endpoint (gut health and function assessed via feacal samples) and secondary endpoints (self-reported quality of life via standardised questionnaires, blood biomarkers, body composition and physical fitness) will be measured at baseline and following the intervention. A variety of statistical methods will be used to understand the covariance between microbial diversity and metabolomics profile across time and intervention. An intention-to-treat approach will be utilised for the analyses with multiple imputations followed by a secondary sensitivity analysis to ensure data robustness using a complete cases approach.Ethics and disseminationEthics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (ID: 19827 NEWTON). Findings will be reported in peer-reviewed publications and scientific conferences in addition to working with national support groups to translate findings for the broader community. If exercise is shown to result in favourable changes in gut microbial diversity, composition and metabolic profile, and reduce gastrointestinal complications in PCa patients receiving ADT, this study will form the basis of a future phase III trial.Trial registration numberANZCTR12618000280202.

Abstract BACKGROUND Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI. METHODS After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments. RESULTS New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17–3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028). CONCLUSIONS hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.

IntroductionCoronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process.Method and analysisIn this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses.Ethics and disseminationThere are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported.Trial registration numberNCT05500443.

Purpose Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. Patients and Methods Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. Results A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post–random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). Conclusion Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes.

IntroductionRobot-assisted laparoscopic prostatectomy (RALP) offers potential cure for localised prostate cancer but is associated with considerable toxicity. Potency and urinary continence are improved when the neurovascular bundles (NVBs) are spared during a nerve spare (NS) RALP. There is reluctance, however, to perform NS RALP when there are concerns that the cancer extends beyond the capsule of the prostate into the NVB, as NS RALP in this instance increases the risk of a positive surgical margin (PSM). The NeuroSAFE technique involves intraoperative fresh-frozen section analysis of the posterolateral aspect of the prostate margin to assess whether cancer extends beyond the capsule. There is evidence from large observational studies that functional outcomes can be improved and PSM rates reduced when the NeuroSAFE technique is used during RALP. To date, however, there has been no randomised controlled trial (RCT) to substantiate this finding. The NeuroSAFE PROOF feasibility study is designed to assess whether it is feasible to randomise men to NeuroSAFE RALP versus a control arm of ‘standard of practice’ RALP.MethodsNeuroSAFE PROOF feasibility study will be a multicentre, single-blinded RCT with patients randomised 1:1 to either NeuroSAFE RALP (intervention) or standard RALP (control). Treatment allocation will occur after trial entry and consent. The primary outcome will be assessed as the successful accrual of 50 men at three sites over 15 months. Secondary outcomes will be used to aid subsequent power calculations for the definitive full-scale RCT and will include rates of NS; PSM; biochemical recurrence; adjuvant treatments; and patient-reported functional outcomes on potency, continence and quality of life.Ethics and disseminationNeuroSAFE PROOF has ethical approval (Regional Ethics Committee reference 17/LO/1978). NeuroSAFE PROOF is supported by National Institute for Healthcare Research Research for Patient Benefit funding (NIHR reference PB-PG-1216-20013). Findings will be made available through peer-reviewed publications.Trial registration numberNCT03317990.

IntroductionA novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission.Methods and analysisWe hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine.Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4–7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested.The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data.Ethics and disseminationThe study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals.Trial registration numberNational Clinical Trial Registry (NCT04464408).

ImportanceIn the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial, there was a significant reduction in the adjudicated primary outcome among patients with stable atherosclerotic vascular disease randomized to dual pathway inhibition (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily) vs aspirin monotherapy, but not with rivaroxaban 5 mg twice daily vs aspirin monotherapy. Whether the results are similar without adjudication is unknown.ObjectiveTo examine the impact of dual pathway inhibition (with rivaroxaban plus aspirin) or rivaroxaban monotherapy compared with aspirin monotherapy on investigator-reported CV events and to understand the extent of concordance between investigator-reported and centrally adjudicated clinical events.Design, Setting, and ParticipantsThis is a secondary analysis of the COMPASS trial, an international, double-blind, double-dummy, randomized clinical trial with a 3-by-2 partial factorial design that evaluated participants with stable atherosclerotic vascular disease receiving rivaroxaban plus aspirin, rivaroxaban monotherapy, or aspirin monotherapy. End points were collected by blinded site investigators and adjudicated by a blinded clinical end point committee. Data were analyzed from March 2013 through February 2017.InterventionsParticipants received dual inhibition pathway (2.5 mg rivaroxaban twice daily plus 100 mg aspirin once daily), rivaroxaban monotherapy (5 mg twice daily), or aspirin monotherapy (100 mg once daily).Main Outcomes and MeasuresThe primary efficacy outcome was a composite of cardiovascular (CV) death, stroke, or myocardial infarction (MI). Adjudicated and investigator-reported end points were compared.ResultsA total of 27 395 patients (mean [SD] age, 68.2 [7.9] years; 78.0% men) were assessed, including 9152 patients randomized to dual pathway inhibition, 9117 patients randomized to rivaroxaban monotherapy, and 9126 patients randomized to aspirin monotherapy. Adjudication reduced the number of events by 10% to 15% for most end points. Among investigator-reported end points, dual pathway inhibition significantly reduced the rate of the primary efficacy outcome compared with aspirin alone (411 patients [4.5%] vs 542 patients [5.9%]; hazard ratio [HR], 0.75 [95% CI, 0.66-0.85]; P &amp;lt; .001), with similar reduction in adjudicated end points, (379 patients [4.1%] vs 496 patients [5.4%]; HR, 0.76 [95% CI, 0.66-0.86]; P &amp;lt; .001). Likewise, effects on ischemic end points were highly concordant (κ statistic = 0.94 [95% CI, 0.93-0.95] for the primary composite end point). Unlike with adjudicated outcomes, there was a significant reduction in the primary end point with rivaroxaban monotherapy vs aspirin monotherapy using investigator-reported events (477 patients [5.2%] vs 542 patients [5.9%]; HR, 0.88 [95% CI, 0.78-0.99]; P = .04) compared with adjudicated events (448 patients [4.9%] vs 496 patients [5.4%]; HR, 0.90 [95% CI, 0.79-1.03]; P = .12).Conclusions and RelevanceThis secondary analysis of the COMPASS trial found that whether assessed by blinded site investigators or adjudicators, dual pathway inhibition significantly reduced CV events among patients with stable atherosclerotic disease compared with aspirin plus placebo. These findings suggest that using investigator-reported events in blinded clinical trials may be a more efficient alternative to adjudication.Trial RegistrationClinicalTrials.gov Identifier: NCT01776424

IntroductionObese men with prostate cancer have an increased risk of biochemical recurrence, metastatic disease and mortality. For those undergoing androgen deprivation therapy (ADT), substantial increases in fat mass are observed in the first year of treatment. Recently, we showed that a targeted supervised clinic-based exercise and nutrition intervention can result in a substantial reduction in fat mass with muscle mass preserved in ADT-treated patients. However, the intervention needs to be accessible to all patients and not just those who can access a supervised clinic-based programme. The purpose of this study was to evaluate the efficacy of telehealth delivered compared with supervised clinic-based delivered exercise and nutrition intervention in overweight/obese patients with prostate cancer.Methods and analysisA single-blinded, two-arm parallel group, non-inferiority randomised trial will be undertaken with 104 overweight/obese men with prostate cancer (body fat percentage ≥25%) randomly allocated in a ratio of 1:1 to a telehealth-delivered, virtually supervised exercise and nutrition programme or a clinic-based, face-to-face supervised exercise and nutrition programme. Exercise will consist of supervised resistance and aerobic exercise performed three times a week plus additional self-directed aerobic exercise performed 4 days/week for the first 6 months. Thereafter, for months 7–12, the programmes will be self-managed. The primary endpoint will be fat mass. Secondary endpoints include lean mass and abdominal aortic calcification, anthropometric measures and blood pressure assessment, objective measures of physical function and physical activity levels, patient-reported outcomes and blood markers. Measurements will be undertaken at baseline, 6 months (post intervention), and at 12 months of follow-up. Data will be analysed using intention-to-treat and per protocol approaches.Ethics and disseminationEthics approval has been obtained from the Edith Cowan University Human Research Ethics Committee (ID: 2021–02157-GALVAO). Outcomes from the study will be published in academic journals and presented in scientific and consumer meetings.Trial registration numberACTRN12621001312831.

Background: Randomized double blind clinical trial is the most used and accepted method of clinical research involving human subjects. Clinical researches are performed under strict regulatory regulations including Helsinki Declaration and International Conference for Harmonization Good Clinical Practice (ICH – GCP) recommendations. As per ICH GCP principles safety and well being of clinical trials patients should prevail over research objectives and their health status should be monitored throughout the trial using objective and concise indicators such as but not limited to laboratory analysis. This study aims to identify factors that might unblind risperidone treatment arms for patients enrolled in randomized double blind schizophrenia clinical trials using risperidone versus comparator, as a result of reviewing safety laboratory analysis. Methods: This study included 134 controlled schizophrenia patients who received treatment with risperidone versus antipsychotic agents with lower dopamine antagonist potency. Prolactine values were determined using imunoenzimatic and colorimetric method (ELISA) for cantitative determination of prolactine from serum or plasma. Results: 84% percent of the patients treated with risperidone showed elevated levels for prolactine above laboratory reference ranges defined as: Men ( 1.8 – 17.0 ng/ml) ; Women ( fertile 1.2 – 19.5 ng/ml, menopause 1.5 – 18.5 ng/ml) Conclusions: High elevated values of prolactin were determined for risperidone treated patients which might disclose the patient treatment arm to blinded investigator and jeopardize the research. As lab results are an essential safety factor of clinical trial those cannot be overruled and establishing Independent Data Monitoring Committee to oversee patients’ data and warn the investigator is recommended.

IntroductionAortic stenosis is a common heart valve disease, and due to the growing elderly population, the prevalence is increasing. The disease is progressive with increasing calcification of the valve cusps. A few attempts with medical preventive treatment have failed; thus, presently, the only effective treatment of aortic stenosis is surgery. This study will examine the effect of menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). We hypothesise that MK-7 supplementation will slow down the calcification process.Methods and analysisIn this multicenter and double-blinded, placebo-controlled study, 400 men aged 65–74 years with substantial AVC are randomised (1:1) to treatment with MK-7 (720 µg/day) supplemented by the recommended daily dose of vitamin D (25 µg/day) or placebo treatment (no active treatment) for 2 years. Exclusion criteria are treatment with vitamin K antagonist or coagulation disorders. To evaluate AVC score, a non-contrast CT scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is difference in AVC score from baseline to follow-up at 2 years. Intention-to-treat principle is used for all analyses.Ethics and disseminationThere are no reported adverse effects associated with the use of MK-7. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20170059) and the Data Protection Agency (17/19010). It is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported.Trial registration numberNCT03243890.

IntroductionSarcopenia is a progressive loss in muscle mass, strength and function, the adverse consequences of which are severe, affecting quality of life and placing an increasing burden on social and healthcare systems. Vitamin D status is known to be associated with markers of sarcopenia, namely muscle mass, strength and function. Also, resistance exercise training (RET) is currently the only proven intervention to treat sarcopenia. However, very little data exist on the influence of combining the two interventions of vitamin D supplementation and resistance exercise training, although a recent systematic review provides tentative support for the current study’s hypothesis that the combined intervention may further improve musculoskeletal function above exercise training alone. The aim of the present study is to determine whether vitamin D3supplementation is any more effective in improving musculoskeletal function when combined with RET compared with exercise training alone in older adults.Methods and analysisThis double-blinded randomised placebo-controlled trial will recruit a target of 127 eligible men and women aged ≥65 years living independently or in sheltered housing within the Birmingham area to two groups: (1) 6 months RET and placebo or (2) 6 months RET and 800 IU/d vitamin D3. Measures of muscle power (Nottingham Power Rig), body composition (dual energy X-ray absorptiometry), muscle function (short physical performance battery, timed up and go), falls and fractures as events will be assessed. Assessments will take place at baseline and postintervention, with intermittent monitoring of bone turnover, calcium and vitamin D. The primary outcome will be lower limb extensor power output. Analyses of within-group changes and between-group differences in outcome measures are planned.Ethics and disseminationThe EXVITD study has ethical approval granted by the Black Country National Health Service Research Ethics Committee (14/WM/1220). Results of this trial will be submitted for publication in peer-reviewed journals and presented at conferences. The study is being conducted according to the principles of the Declaration of Helsinki.Trial registration numberNCT02467153; Post-results.

IntroductionPostoperative urinary retention (POUR) is a common complication after inguinal hernia repair with a reported incidence up to 34%. It can be described as the inability to initiate urination or insufficient bladder emptying following surgery. It usually requires the use of catheterisation to empty the bladder in order to prevent further injury to the bladder or kidneys and to relief from pain. Tamsulosin is a medication that is commonly used in men with urinary symptoms related to an enlarged prostate. There is some evidence to suggest that it may also potentially be beneficial for preventing POUR.Methods and analysisThis is a multicentre, blinded, prospective, phase IV randomised controlled trial with parallel allocation. Six hundred and thirty-four patients scheduled for elective endoscopic inguinal hernia repair surgery will be recruited. There will be effective (concealed) randomisation of the subjects to the intervention/control groups. Group assignment will be performed using a covariate-adaptive allocation procedure to provide a balance for selected covariates. The interventional group receives 0.4 mg tamsulosin hydrochloride and the control-group receives one placebo capsule matching the active study drug, both daily, starting from 5 days prior to the day of surgery, at the day of surgery and for 1 day following surgery. The primary outcome is any need for urinary catheterisation postoperatively as a binary outcome. Secondary outcome measures include postoperative pain, change in International Prostate Symptom Score from baseline prior to surgery to after surgery and hospital stay.Ethics and disseminationThe study has been approved by the Northwestern and Central Switzerland Ethics Committee (2020–00569) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.Trial registration numbersSNCTP000003904. NCT04491526.

AbstractProspective studies assessing the association between fibre intake or fibre-rich food consumption and the risk of CVD have often been limited by baseline assessment of diet. Thus far, no study has used yearly repeated measurements of dietary changes during follow-up. Moreover, previous studies included healthy and selected participants who did not represent subjects at high cardiovascular risk. We used yearly repeated measurements of diet to investigate the association between fibre intake and CVD in a Mediterranean cohort of elderly adults at high cardiovascular risk. We followed-up 7216 men (55–80 years) and women (60–80 years) initially free of CVD for up to 7 years in the PREvención con DIeta MEDiterránea study (registered as ISRCTN35739639). A 137-item validated FFQ was repeated yearly to assess diet. The primary end point, confirmed by a blinded ad hoc Event Adjudication Committee, was a composite of cardiovascular death, myocardial infarction and stroke. Time-dependent Cox’s regression models were used to estimate the risk of CVD according to baseline dietary exposures and to their yearly updated changes. We found a significant inverse association for fibre (Pfor trend=0·020) and fruits (Pfor trend=0·024) in age-sex adjusted models, but the statistical significance was lost in fully adjusted models. However, we found a significant inverse association with CVD incidence for the sum of fruit and vegetable consumption. Participants who consumed in total nine or more servings/d of fruits plus vegetables had a hazard ratio 0·60 (95 % CI 0·40, 0·96) of CVD in comparison with those consuming <5 servings/d.

IntroductionUrinary incontinence (UI) is one of the main complications of radical prostatectomy. Electrical pudendal nerve stimulation (EPNS) has been used to treat stress UI based on its mechanism of passive pelvic floor muscle contraction reported in the previous research. However, there are no studies comparing the effects of EPNS and active pelvic floor muscle training (PFMT) in the treatment of postradical prostatectomy UI (PPUI). Here, we describe the protocol for a randomised controlled trial to evaluate the efficacy of EPNS in treating PPUI compared with PFMT.Methods and analysisThis study is designed as an open-label randomised controlled trial with blinded assessment and analysis. A total of 90 eligible men will be randomly allocated to two groups. The treatment group (n=45) will receive EPNS while the control group will perform PFMT by doing the Kegel exercise. Forty EPNS treatment sessions will occur over a period of 8 weeks. The primary outcome measure will be improvement rate, and the secondary outcome measures, the number of pads used, 24-hour pad test, and International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form will be compared between baseline and the study endpoint. The International Consultation on Incontinence Questionnaire-Lower Urinary Tract Symptoms Quality of Life and care compared as the quality of life and satisfaction outcomes between groups.Ethics and disseminationThis protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (approval no. 2021 KL-040-02). Written informed consent will be obtained from each participant. The results of the study will be published in peer-reviewed journals.Trial registration numberChiCTR2200055461.

Abstract Introduction Working during the night interferes with the timing of normal daily activities and it is associated with an increased risk for several chronic diseases. Interventions focused on nutrition and sleep can mitigate the short-term adverse effects of shift work under controlled experimental conditions. However, it is unclear how these results translate to real life, and relate to long-term health. Therefore, the current study aims to implement a personalized sleep and nutritional intervention among night shift workers and to evaluate its effect on various health outcomes. Methods This non-blinded controlled intervention study evaluates various health outcomes at baseline, at the start and end of a 3-month intervention, and at a 1-year follow-up. Three study arms are included: nutritional intervention, sleep intervention, and control group (n=25 each). Participants are healthy 18-60-year-old men, working 12h shifts (18:00-6:00 or 6:00-18:00). The intervention is a personalized sleep or nutritional advise based on sleep information (using ActiWatch and sleep diaries), continuous glucose measurements, food diary, and questionnaires collected during the baseline period. This study was approved by the Medical Ethical Review Committee of Erasmus University Medical Center. Results In this ongoing study main outcomes are objective and subjective sleep measurements and continuous interstitial glucose levels. Furthermore, biomarkers and general (mental) health parameters are determined to further evaluate effects on indicators of long-term health. Discussion and conclusion This study aims to make a meaningful contribution to the translation of findings from controlled experimental conditions to a real-life setting, with the ultimate goal to improve long-term health in night shift workers.

IntroductionVitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification.Methods and analysisThe InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52–82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance.Ethics and disseminationOral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported.Trial registration numberNCT05259046.

Abstract Background: Anemia is one of the major public health problems that affected 2.36 billion individuals worldwide in 2015. Half of all causes of anemia are iron or other nutrient deficiency anemia (WHO, 2015). Currently available treatment options for anemia include iron or other nutrient supplementation, nutritional interventions in the form of food fortification, blood transfusion, and erythropoietic agent infusion. However, conventional treatments are not without adverse effects. In this context, medicinal plants with bioactive components have been receiving considerable attention from researchers as natural hematinic agents complemented with or alternatives to conventional treatment. Olive leaf (Olea europaea L. Oleaceae) extract (OLE) is rich in bioactive compounds and have been reported to have several health benefits (Gorzynik-Debicka et al., 2018). Previously we showed that apigetrin and apigenin, components of OLE, induced erythroid differentiation in K562 cells (Tsolmon et al., 2011 and Isoda et al., 2014). Also, OLE and its phenolic compounds induced erythroid differentiation in hHSCs (Kondo et al., 2021, Samet et al., 2015). Additionally, we have reported that long-term consumption of OLE tea increased RBC count, Hb%, and hematocrit (Ht) in female volunteers aged between 40 - 70 years old (Ferdousi et al., 2019). However, none of the participants were anemic at the baseline. Therefore, in the present study, we aimed to investigate the effects of oral intake of OLE on hematological parameters in healthy to mildly anemic young adults. Study Design and Methods A double-blinded, randomized, placebo-controlled study will be conducted in Bangladesh. Total 165 apparently healthy adults with Hb level at least 10g/dl for females (nonpregnant, non-breastfeeding) and 11g/dl for males, and aged between 18 to 59 years will be enrolled from the local community. Major exclusion criteria will include currently pregnant women or breastfeeding mothers, moderate to severe anemia (Hb concentration &lt; 10 g / dL for women and &lt; 11 g / dL for men), any medical condition, such as hematological diseases, malignant tumors, aplastic anemia, uncontrolled hypertension, chronic kidney disease, irritable bowel syndrome, and cardiovascular diseases, and currently taking medicine for diabetes or hypertension and taking regular iron or other supplements, etc. After providing informed written consent, study participants will be randomly assigned to placebo, 250 mg OLE and 500 mg OLE groups. Participants will take OLE or placebo capsules in two divided doses every day for 12 weeks. Hematological parameters, Hb concentration, RBC count, WBC count, Ht, MCV, MCH, MCHC, serum Fe and ferritin levels will be investigated at baseline and after 6 and 12 weeks of intervention. Liver and renal function tests will be conducted for safety assessment. Additionally, lipid profile will be investigated to understand how lipid parameters will be regulated if anemia condition is improved by OLE intervention (Araki et al., 2019). Given that fatigue is one of the most common symptoms of anemia, we will also evaluate the effect of OLE on the score of each item of the Fatigue Assessment Scale (FAS) questionnaire during the intervention. The analysis will be carried out on an intention-to-treat basis involving all the participants who will consume the test samples at least once. We will replace the missing data from dropouts using the baseline observation carried forward method. ANOVA with Bonferroni's post hoc test will be used for normally distributed data; otherwise, the Mann-Whitney U test or Kruskal-Wallis H(K) test will be used. Categorical variables will be compared by the Chi-square or Fisher's exact test. A one-way repeated-measures ANOVA with Bonferroni's post hoc test (Within-group) and ANOVA followed by Bonferroni's post hoc test (between-group) will be performed. Significance is at p &lt; 0.05. This protocol is registered with UMIN-CTR Clinical Trial (UMIN000039023), and has been approved by University of Tsukuba Hospital Clinical Research Ethics Review Committee (R01-292) and the Ethical Review Committee of icddr,b (PR-21017). This study is funded by the Japan Society for the Promotion of Science (19K20106) and partly by the Japan Science and Technology Agency-SATREPS (JPMJSA1506). Disclosures Suidasari: Nutrition Act Co. Ltd.: Current Employment. Yokozawa: Nutrition Act Co. Ltd.: Current Employment. Yamauchi: Nutrition Act Co. Ltd.: Current Employment.

IntroductionProstate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy.Methods and analysisThe PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. Sample size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management.Ethics and disseminationThis study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute.Trial registration numberACTRN12620000261910.

5008 Background: Multiparametric MRI (mpMRI) of the prostate followed by targeted biopsy is recommended in men at risk of prostate cancer. Dissemination of this pathway may be limited by cost, variable scan and reporting quality, and contraindicated in the presence of metallic implants and claustrophobia. Multi-parametric ultrasound (mpUSS) is a point of care test with low cost that combines b-mode, colour Doppler, elastography and contrast enhancement. CADMUS compared the diagnostic performance of mpUSS to mpMRI. Methods: CADMUS recruited 370 patients from seven sites to a prospective, multicentre, paired-cohort trial (ISRCTN 38541912). Ethics committee approval was obtained. Patients underwent both mpUSS and mpMRI independently, each with a positive test defined as a Likert score of >3. Those with either a positive mpUSS or mpMRI, or both, were advised to undergo targeted biopsies. Reporting of each scan was carried out blind to the other and prior to biopsy; patients advised for biopsy were blinded to which test was positive. The order of mpUSS and mpMRI targeting was randomised. Primary outcomes were proportion of positive tests and detection of clinically significant cancer (csPCa) defined as Gleason >4+3 of any length and/or maximum cancer core length of >6mm of any grade [PROMIS definition1]. Results: 306 completed both mpUSS and mpMRI. Agreement in lesion detection between mpUSS and mpMRI was 73.2% (kappa 0.06, p = 0.14). 257 with positive results on mpUSS, mpMRI or both had targeted biopsies. Agreement on detection of csPCa was 91.1% (expected 59.8%, kappa 0.78, p < 0.01). Overall, mpUSS detected 4.3% fewer csPCa than mpMRI (95% CI = [-8.3%, -1.5%]; p = 0.042 [Bonferroni correction]). mpUSS detected 7.2% (6/83) csPCa missed by mpMRI; mpMRI detected 20.5% (17/83) csPCa that mpUSS missed. At a less stringent definition of significant cancer, Gleason grade >3+4 of any length (definition 3), agreement was 89.1% (expected 55.6%, kappa 0.75, p < 0.01) mpUSS detected 5.4% fewer definition 3 cancers than mpMRI overall. mpUSS detected 7% (7/99) definition 3 cancers that mpMRI missed; mpMRI detected 21% (21/99) definition 3 cancers that mpUSS missed. Conclusions: The CADMUS trial shows mpUSS has a diagnostic performance approaching that of mpMRI and significant cancer detection is improved by the use of both scans over mpMRI alone. Clinical trial information: 38541912. [Table: see text]

OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0–79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0–7.9 mm), y = 9.6 ± 0.9 mm (range 8.0–11.6 mm), z = −7.5 ± 1.2 mm (range −5.4 to −10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2–4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 (clinicaltrials.gov)

TPS1104 Background: Estrogen receptor-positive (ER+) BC comprises ~70% of all BC and advanced/metastatic ER+ disease (mBC) remains a major clinical challenge. The addition of CDK4/6i to ET has improved progression-free survival (PFS); however, novel treatments are needed after progression. Putative mechanisms of endocrine resistance, such as ESR1 mutations (mESR1), also indicate the need for additional therapies. Elacestrant, an oral selective estrogen receptor degrader (SERD), demonstrated anti-tumor activity in preclinical models of ER+ BC, including models resistant to CDK4/6i and models with mESR1. An interim evaluation of a phase 1 trial ( NCT02338349 ) of elacestrant in heavily pretreated patients (pts) with mBC, demonstrated an overall response rate (ORR) of 27% with a PFS of 5.4 mo (Bardia, SABCS, 2017). Responses were seen in pts with prior CDK4/6i and with wild-type (WT) or mESR1. Methods: This is a multicenter, international, randomized, open-label, active-controlled phase 3 trial for post-menopausal women or men with mBC. Pts must have received 1-2 prior lines of ET, ≤1 line of chemotherapy for mBC, and have documented progression on a CDK4/6i. Pts with measurable disease (RECIST v1.1) or bone-only disease are eligible. Pts are randomized 1:1 to elacestrant (400 mg orally daily) or IC of fulvestrant or an aromatase inhibitor. Stratification factors include ESR1 mutation status (detected by ctDNA), prior fulvestrant treatment and presence of visceral disease. The primary endpoints are PFS by blinded independent review committee (IRC) in pts with mESR1 and in all pts (WT or mESR1). Secondary endpoints include: overall survival; PFS by IRC in WT, PFS by investigator review; ORR, duration of response, and clinical benefit rate; safety; pharmacokinetics; and quality of life. Approximately 466 pts will be enrolled to detect 340 PFS events in all pts (power ≥90%, hazard ratio (HR) = 0.667) and 160 PFS events in the mESR1 subset (power ≥80%, HR = 0.610), overall α level at 2-sided 5% using the Hochberg procedure. The EMERALD study is open for enrollment. Clinical trial information: NCT03778931.

TPS1109 Background: Endocrine therapy (ET) + CDK4/6i is standard of care for HR+, HER2− ABC; however, CDK4/6i resistance, in which the phosphatidylinositol-3-kinase (PI3K) pathway has a key role, remains challenging. Progression-free survival (PFS) for ≥ 2nd-line ET monotherapy post CDK4/6i is poor; prognosis may be worse in patients with a PI3KCA mutation. ALP (PI3K-α selective inhibitor and degrader) + FUL is approved by the European Medicines Agency (EMA) for HR+, HER2–, PIK3CA-mutated ABC after ET monotherapy. Outside the EMA, ALP + FUL approval includes post-CDK4/6i use. ALP + FUL has shown clinical activity and consistent safety in a small subpopulation in SOLAR-1 with prior CDK4/6i treatment (n = 9) and in BYLieve Cohort A (CDK4/6i + AI as immediate prior treatment; n = 121). The EPIK-B5 study aims to confirm the efficacy and safety of ALP + FUL in a larger population with HR+, HER2–, PIK3CA-mutated ABC with prior CDK4/6i + AI treatment. Methods: EPIK-B5 is a Phase III, randomized (1:1), double-blind, placebo-controlled study assessing the efficacy and safety of ALP (300 mg/d orally starting Cycle 1 Day 1 [C1D1]) + FUL (500 mg intramuscularly on C1D1 and C1D15, and D1 of subsequent cycles) in patients (N ≈ 234) with HR+, HER2–, PIK3CA-mutated ABC progressing on/after CDK4/6i + AI. Patients randomized to placebo + FUL can cross over to ALP + FUL after progression. Randomization is stratified by presence of lung and/or liver metastasis and prior CDK4/6i setting. Adult men or postmenopausal women with confirmed HR+, HER2–, PIK3CA-mutated ABC and ≥ 1 measurable lesion are eligible. The primary endpoint is PFS per blinded independent review committee assessment. Secondary endpoints include overall survival, overall response and clinical benefit rates, duration of and time to response, PFS by PIK3CA-mutation status in circulating tumor DNA, PFS on next-line treatment, time to definitive deterioration of ECOG status, quality of life (QoL), and safety and tolerability. Exploratory endpoints include biomarker analyses, additional QoL endpoints, and time to subsequent chemotherapy. Recruitment is ongoing, with enrollment planned over 2 years in 18 countries; completion of primary data collection is anticipated in 2026. Clinical trial information: NCT05038735; EUDRACT2021-001966-39.

TPS1109 Background: Endocrine therapy (ET) + CDK4/6i is standard of care for HR+, HER2− ABC; however, CDK4/6i resistance, in which the phosphatidylinositol-3-kinase (PI3K) pathway has a key role, remains challenging. Progression-free survival (PFS) for ≥ 2nd-line ET monotherapy post CDK4/6i is poor; prognosis may be worse in patients with a PI3KCA mutation. ALP (PI3K-α selective inhibitor and degrader) + FUL is approved by the European Medicines Agency (EMA) for HR+, HER2–, PIK3CA-mutated ABC after ET monotherapy. Outside the EMA, ALP + FUL approval includes post-CDK4/6i use. ALP + FUL has shown clinical activity and consistent safety in a small subpopulation in SOLAR-1 with prior CDK4/6i treatment (n = 9) and in BYLieve Cohort A (CDK4/6i + AI as immediate prior treatment; n = 121). The EPIK-B5 study aims to confirm the efficacy and safety of ALP + FUL in a larger population with HR+, HER2–, PIK3CA-mutated ABC with prior CDK4/6i + AI treatment. Methods: EPIK-B5 is a Phase III, randomized (1:1), double-blind, placebo-controlled study assessing the efficacy and safety of ALP (300 mg/d orally starting Cycle 1 Day 1 [C1D1]) + FUL (500 mg intramuscularly on C1D1 and C1D15, and D1 of subsequent cycles) in patients (N ≈ 234) with HR+, HER2–, PIK3CA-mutated ABC progressing on/after CDK4/6i + AI. Patients randomized to placebo + FUL can cross over to ALP + FUL after progression. Randomization is stratified by presence of lung and/or liver metastasis and prior CDK4/6i setting. Adult men or postmenopausal women with confirmed HR+, HER2–, PIK3CA-mutated ABC and ≥ 1 measurable lesion are eligible. The primary endpoint is PFS per blinded independent review committee assessment. Secondary endpoints include overall survival, overall response and clinical benefit rates, duration of and time to response, PFS by PIK3CA-mutation status in circulating tumor DNA, PFS on next-line treatment, time to definitive deterioration of ECOG status, quality of life (QoL), and safety and tolerability. Exploratory endpoints include biomarker analyses, additional QoL endpoints, and time to subsequent chemotherapy. Recruitment is ongoing, with enrollment planned over 2 years in 18 countries; completion of primary data collection is anticipated in 2026. Clinical trial information: NCT05038735; EUDRACT2021-001966-39.

Abstract Background: The relative benefit-to-risk ratio of various LMWH in the setting of colorectal cancer surgery has never been directly compared. Objective: We performed a multicenter, randomized, double-blind study to compare the efficacy and safety of enoxaparin 40 mg (4000 anti-Xa IU) and nadroparin 0.3 mL (2850 anti-Xa IU) in the prevention of venous thromboembolism (VTE) after colorectal cancer surgery. Methods: Patients undergoing elective colorectal adenocarcinoma resection under general anesthesia were recruited. They were randomized to receive once daily either nadroparin 0.3 mL or enoxaparin 40 mg subcutaneously for 9±2 days, starting 2 to 4 hours preoperatively. The primary efficacy outcome was the composite of deep-vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism (PE) up to Day 12. The main safety outcomes were major bleeding and all-cause death. A blinded independent committee adjudicated all outcomes. Results: A total of 1288 patients (median age: 69, range: 26–97 years; men: 61.4%) were randomized either to nadroparin (n=653) or to enoxaparin (n=635). Efficacy was evaluable in 950 (73.8%) patients who underwent contrast venography or had a symptomatic thromboembolic event. The rate of VTE at Day 12 was 15.9% for nadroparin and 12.6% for enoxaparin (relative risk reduction 21.3% [95% CI: −7.75; 42.5]). This difference was not statistically significant (p=0.13, Chi-squared test). In contrast, there were more symptomatic VTE, including symptomatic PE, in the enoxaparin group than in the nadroparin group (Table). Furthermore, the rate of major bleeding was significantly lower in nadroparin-treated patients than in enoxaparin-treated patients (Table). By Day 12, there were three (0.5%) deaths related to VTE or major bleeding in enoxaparin patients compared with none in nadroparin patients. By Day 60, 23 (3.5%) patients receiving nadroparin and 23 (3.5%) patients receiving enoxaparin had died. Conclusion: Enoxaparin 40 mg was not more effective than nadroparin 0.3 mL in the prevention of total VTE in patients undergoing colorectal cancer surgery. The non-significant difference between the two groups was mainly due to a lower rate of asymptomatic distal DVT in the enoxaparin group than in the nadroparin group. However, nadroparin was more effective than enoxaparin for reducing symptomatic VTE, including PE, and was associated with significantly less major bleeding. Efficacy and safety results at Day 12 Nadroparin 0.3 mL, n/N (%) Enoxaparin 40 mg, n/N (%) p *Chi-squared test Total VTE 74/464 (15.9) 61/486 (12.7) 0.13* Asymptomatic proximal DVT 15/503 (3.0) 14/515 (2.7) 0.81 Asymptomatic distal DVT 58/503 (11.5) 42/515 (8.2) 0.07 Symptomatic VTE 1/643 (0.2) 9/628 (1.4) 0.01 Symptomatic proximal DVT 1/643 (0.2) 4/628 (0.6) 0.22 Symptomatic PE 0/643 (0.0) 5/628 (0.8) 0.03 Major bleeding 47/643 (7.3) 72/628 (11.5) 0.01 All-cause death 2/643 (0.3) 8/628 (1.3) 0.06

BackgroundIn recent years, the high economic impact of biologic therapies (BT) on health care systems has promoted great interest in optimizing BT in Rheumatoid Arthritis (RA) patients in sustained clinical remission (CR). A relevant percentage of those optimized patients present clinical relapses. RA patients in CR have been shown to have active synovitis detectable by ultrasound (U). U can identify synovitis in patients about to present clinical relapse. U can be a useful tool in the optimization decision.ObjectivesThe main objective was to demonstrate that the optimization strategy using U is more useful than the strategy using clinical index. U used as an outcome measure, can further refine the choice of patients who are candidates for a reduction in treatment and therefore achieve lower relapse rates. To do this, we calculated the relapse rates in each of the groups and the time from the beginning in which it appears, and we compared them to assess whether they differ significantly and support our hypothesis. Secondary objective was evaluating the ultrasound remission in this group of patients.MethodsWe conducted a multicenter, randomize, prospective study in 5 tertiary centers in RA patients in sustained CR (>9 months). All signed the informed consent. Approval by the ethical committee was obtained (VDH-INF-2017-01). Two blinded and randomize arms, clinical (A) and U (B) were created to decide tapering (1/2, 1/3 or no reduction treatment) and compare flare rates (>1.2 DAS28 or >16 SDAI/CDAI increase) in 52 weeks (basal, 1, 6, 9 & 12 months). Demographic at baseline, US & clinic variables, and ESR & CRP at each visit, were registered. By using U with grayscale (GS) and power Doppler (PD) in a semiquantitative articular (A) and tendon (T) scale we studied: wrist, 1-5 MCP, 1-5 PIP, ankle, subtalar joint, 2nd, and 5th MTP, extensor tendons (Text) and flexors (Tflex) of the carpus, flexor tendons of the fingers, posterior tibial and peroneal tendons. DAS28 <2.6 was used as the clinical remission criteria, and the absence of synovitis was defined as U remission (EG and PD = 0). U activity was defined as GS≥1 and PD ≥1.Results78 patients were included, 48 completed 12 moths follow up and 28 were retired (5 screening failure, 16 flare, 5 lost follow up & 4 patient decision). 33 men and 45 women, 11.92 years of disease. Group A presented a significative more flare rates than group B (10 vs 6). Using SDAI or CDAI only 7 presented a clinical flare, and for SDAI (7 vs 0) & CDAI (7 vs 0) differences were significative (p<0.005), but not for DAS28 (10 vs 6) (Table 1). In U at baseline, the main involved joint was the wrist (28.6%), and of the tendons the Text (11.2%). In 53% a pathological U (A and T) was observed, 46.9% had pathological A and in 30% pathological T was observed. Considering as remission an ultrasound score of EG + PD = 0, only 46.9% were in remission.ConclusionUltrasound can improve tapering strategy when we used SDAI or CDAI score in patients in sustained clinical remission. Clinical and ultrasound remission are not equivalent. More than half of the patients do not fulfill UR and in one fifth of them a strict control should be carried out to avoid a relapse of the disease if it is decided to optimize.Table 1.baseline clinical characteristics of the subjects included in the sample, comparing according to the treatment group and outbreaks according to clinical indicesVariableGroupTotalpABTotal1_41(100%)37(100%)NsESR (mm/hr)24115.39(10.07)3711.27(8.92)7813.449.71NsCRP (mg/dl)2400.58(1.32)361.18(2.59)760.872.03NsRF(UI/ml)24096.60(126.31)36164.85(330.84)76128.93246.08NsACPA (UA)239264.29(409.93)36230.48(601.26)75248.06507.51NsSJC2410.00(0.00)370.03(0.16)780.010.11NsTJC2410.17(0.83)370.24(0.60)780.210.73NsPtGA2413.10(8.28)373.43(9.24)783.268.69NsPGA2410.82(3.12)371.71(5.31)781.244.29NsDAS282411.85(0.70)361.80(0.62)771.820.66NsSDAI2411.67(2.23)372.32(2.59)781.982.41NsCDAI2411.59(2.21)372.15(2.56)781.862.38NsHAQ2380.30(0.46)330.32(0.38)710.310.42NsDAS28 flare10616NsSDAI flare707<0.005CDAI flare707<0.005REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

This paper shows how political cultures in uence the use of scienti c data in the construction of critique among climate change activists. Based on an ethnographic study of the Danish NGO, „ e Climate Move- ment in Denmark’s“, steering committee, it is shown how the members carefully choose speci c scienti c references in their work. ey are chosen based on two criteria. First, the committee’s perceived ideas about the references’ ability to convince the Danish population about the severe consequences of climate change. And second, the references’ ability to unite all citizens across political and social barriers in the battle. In its way of using science, the committee assumes that the entire nation would be united in solidarity, if they were not blinded by what we (with thanks to Marx and Engels) have chosen to call ‘false con ictuality’; the idea that con icting scienti c statements divide and confuse ordinary people which prevent them from protesting. Following this, it becomes the NGO’s task to enlighten and thereby unite. e focus on creat- ing consensus among citizens with di erent backgrounds and con icting interest is interpreted as a typical instance of traditional Danish ‘Consensus Culture’ where agreement is seen as a precondition for change. But the paper nally argues that it might prove di cult to create solidarity solely based on carefully chosen scienti c statements without any reference to cultural visions for a better common future.

Abstract Background Infertility is a common problem globally and impaired semen quality is responsible for up to 40% of all cases. Almost all infertile couples are treated with either insemination or assisted reproductive techniques (ARTs) independent of the etiology of infertility because no medical treatment exists. Denosumab is an antibody that blocks RANKL signaling and inhibition of testicular RANKL signaling has been suggested to improve semen quality in a pilot study. This RCT aims to assess whether treatment with denosumab can improve spermatogenesis in infertile men selected by serum AMH as a positive predictive biomarker. This paper describes the design of the study. Methods/design FITMI is a sponsor-investigator-initiated, double-blinded, placebo-controlled 1:1, single-center, randomized clinical trial. Subjects will be randomized to receive either a single-dose denosumab 60 mg subcutaneous injection or placebo. The study will be carried out at the Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen. The primary outcome of the study is defined as the difference in sperm concentration (millions pr. mL) one spermatogenesis (80 days) after inclusion. Discussion We describe a protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve the semen quality in infertile men selected by using serum AMH as a positive predictive biomarker. The results will provide evidence crucial for future treatment in a patient group where there is a huge unmet need. Trial registration Clinical Trials.gov NCT05212337. Registered on 14 January 2022. EudraCT 2021–003,451-42. Registered on 23 June 2021. Ethical committee H-21040145. Registered on 23 December 2021.

Introduction: The randomized, double-blind SOCRATES study (NCT01994720) was the first trial with the reversibly binding P2Y12 receptor blocker ticagrelor in patients with acute ischemic stroke (AIS) or TIA. The main safety objective was assessment of PLATO defined major bleedings, with special focus on intracranial hemorrhage (ICH). Methods: An independent adjudication committee blinded to study treatment (ticagrelor or ASA) classified bleedings according to PLATO, TIMI and GUSTO definitions. The definition of major bleeding was adapted to the acute stroke population by excluding asymptomatic hemorrhagic transformations of ischemic cerebral infarctions and micro-bleeds <10 mm evident only on gradient-echo MRI from being considered ICH and major bleedings. The on-treatment (OT) period was defined as OT + 7 days after stop of study drug. Results: In total, 13130 (of 13199 randomized) patients received at least one dose of study drug (safety analysis set). PLATO major bleedings occurred in 31 (0.5%) patients on ticagrelor and 38 (0.6%) on ASA (HR 0.83, 95% CI 0.52 to 1.34). TIMI major bleedings were identified in 21 patients on ticagrelor vs 27 on ASA; and for GUSTO severe 18 vs 21. Patients with PLATO major bleedings had a mean age of 70.2 ±11.2 years, 60.9% were men, and 78.3% were randomized as AIS and 21.7% as TIA, as compared with the overall SOCRATES safety population with mean age 65.9 ± 11.3 years, 58.5% men, AIS in 73.3% and high-risk TIA in 26.7%. The most common locations of major bleedings were intracranial and gastrointestinal. ICH was reported in 12 (0.2%) patients on ticagrelor and 18 (0.3%) on ASA. There were 6 spontaneous, 3 traumatic and 3 procedural ICHs on ticagrelor. For ASA the corresponding numbers were 13, 3 and 2. Thirteen (4 on ticagrelor vs 9 on ASA) were hemorrhagic strokes and 4 (2 vs 2) were symptomatic hemorrhagic transformations. The ICH was fatal in 6/12 patients on ticagrelor and 4/18 on ASA. In total, 9 fatal bleedings occurred on ticagrelor and 4 on ASA. The composite of ICH or fatal bleeding included 15 patients on ticagrelor versus 18 on ASA. Conclusions: Antiplatelet therapy with ticagrelor in patients with AIS or TIA showed a similar bleeding profile as ASA for major bleedings. There were few ICHs.

Introduction: Lifestyle modification like increasing fruits/vegetables consumption is one of the key approaches in treating arterial hypertension: a major risk factor for mortality worldwide. Beta vulgaris (beetroot) and other vegetables consume frequently could be a rich source of inorganic nitrates, which will be converted to nitric oxide. Objective: To evaluate the effect of the roots of Beta vulgaris (Chenopodiaceae) juice on adults’ subjects with grade 1 hypertension under dietary regime. Methodology: Beetroot was obtained at the local market and decontaminated. Beetroot juice (BJ) was extracted and freeze till utilization. Recruitment was hospital-based, were included all adult subjects of both sexes, with grade 1 hypertensive according to the Joint National Committee 7, not subject to pharmacological treatment, non-gravid women. A single-blinded, randomized, placebo-controlled trial was performed during 4 weeks. Volunteers were randomized to receive either 250 mL of BJ or water (placebo) during 02 weeks and blood pressure (BP) registered in triplicates at baseline, 3 h, at 24 h. BP was recorded daily at home during trial, a week before, and after receiving BJ using an automatic BP machine. Blood and urine nitrates were assessed at baseline and 3 h after drinking juice. Results: A total of 14 subjects participated in the trial including 9 women and 5 men. An overall non-significant decrease in BP of 4.5/0.41 mmHg (decrease of 5.62/2.25 mmHg at H3 [p-value = 0.2427/0.3385], and decrease of 1.4 mmHg in systolic blood pressure at the 24th hour [p-value = 0.4150]) in the intervention group compared to the control group respectively for systolic and diastolic blood pressure of the intervention was observed [p-value = 0.1255/0.1612]. No change in blood and urine nitrite was registered. Conclusion: Beetroot juice decrease non-significantly blood pressure.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pocket hematoma is one of the most frequent complications (10%) of the cardiac devices implant. To reduce the risk of bleeding, once the wound is sutured and isolated with a sterile dressing, the nurse performs a compression bandage over the area of the generator pocket. The choice of the type of bandage on the wound of the generator pocket is the responsibility of the nurse and there are several methods that vary according to the center. The vasocontrictive property of ice is known but its applicability is not demonstrated in these types of wounds. Objective Evaluate the efficacy of the hypothermic compression bandage versus conventional compression bandage, for the prevention of surgical wound post cardiac device implant hematoma in chronic oral anticoagulant and / or platelet antiaggregant treatment. Methodology This is a randomized prospective study. The protocol was accepted by ethical committee. The team of nurses from the arrhythmia laboratory recruited 310 patients (sample size with statistical calculation) who were going to undergo an implant or replacement of a pacemaker or internal defibrillator. Those patients who were under treatment with oral anticoagulant and/or platelet antiaggregants were selected. Through a list of random numbers two therapeutic branches were created: the intervention group was applied a compressive bandage with ice and the usual group lacked the conventional compressive bandage. Both bandages placed just at the end of wound closure and for 6 hours post-implant. Skin status was stratified between healthy, ecchymosis, mild hematoma and severe hematoma. The assessment of the state of the skin was performed by a blinded nurse, in the control of the wound at 7 days post intervention. The primary endpoint was the appearance of hematoma. The secundary endpoint was the appearance of severe hematoma, defined as bleeding with vital commitment that required drainage or rehospitalization. Results 310 patients participated in the study. 156 patients were randomized to the intervention group and 153 to usual care. The mean age of the sample was 73.77 ± 10.68 years and 74.8% were men. There were no significant differences between the intervention and usual care groups on any baseline demographic or clinical characteristics. A total of 13 patients presented hematoma and 36 patients presented ecchymosis. In the intervention group, 5.88% (n = 18) of ecchymosis and 1.3% (n = 4) of mild hematoma were observed. In the usual care group, 5.88% (n = 18) of ecchymosis and 2.9% (n = 9) of mild hematoma were observed. No patient in neither groups had severe hematoma. No significant differences were observed between the two types of bandage in any of the 3 levels of hematomas. There were also no significant differences between hematoma and the type of platelet antiaggregants or oral anticoagulant. Conclusion After this study it is observed that there is no difference between applying a compression bandage with or without cold.

IntroductionIn 2011, Four Corners — the flagship current affairs program of the Australian national broadcaster, ABC (Australian Broadcasting Corporation) — aired an investigative report on the conditions in Indonesian slaughterhouses. Central to the report was a focus on how Australian cows were being killed for human consumption. Moral outrage ensued. The Federal Government responded with a temporary ban on the live export of cattle to Indonesia. In 2010 the Australian Government initiated legal action in the International Court of Justice (ICJ) opposing Japanese whaling in the Southern Ocean, following a sustained period of public opposition. This article pays close attention to expressions of public opposition to the killing of what have come to be referred to as our cows and our whales, and the response of the Federal Government.Australia’s recent history with the live export of farmed animals and its transformation into an anti-whaling nation provides us with a foundation to analyse these contemporary disputes. In contrast to a focus on “Australian cow making” (Fozdar and Spittles 76) during the live export controversy, this article investigates the processes through which the bodies of cows and whales became sites for the mapping of Australian identity and nationhood – in other words, a relational construction of Australianness that we can identify as a form of animal nationalism (Dalziell and Wadiwel). What is at stake are claims about desired national self-image. In what we might consider as part of a history of cows and whales is in many ways a ‘history of people with animals in it” (Davis 551). In other words, these disputes are not really about cows and whales.The Live Export IndustryAustralia is the largest exporter of live farmed animals, primarily sheep and cows, to the Middle East and Southeast Asia respectively (Phillips and Santurtun 309). The live export industry is promoted and supported by the Federal Government, with an explicit emphasis on the conditions experienced by these farmed animals. According to the Government, “Australia leads the world in animal welfare practices … [and] does not tolerate cruelty towards animals and will not compromise on animal welfare standards” (Department of Agriculture and Water Resources). These are strong and specific claims about Australia’s moral compass. What is being asserted is the level of care and concern about how Australia’s farmed animals are raised, transported and killed.There is an implicit relationality here. To be a ‘world leader’ or to claim world’s best practice, there must be some form of moral or ethical measure to judge these practices against. We can locate these more clearly and directly in the follow-up sentence on the above claim: “Our ongoing involvement in the livestock export trade provides an opportunity to influence animal welfare conditions in importing countries” (Department of Agriculture and Water Resources). The enthusiasm expressed in this statement manifests in explicitly seeking to position Australia as an exporter of moral progress (see Caulfield 76). These are cultural claims about us.In its current form the Australian live export industry dates back to the early 1960s, with concerns about the material conditions of farmed animals in destination countries raised from the outset (Caulfield 72; Villanueva Pain 100). In the early 1980s animal activists formed the Australian Federation of Animal Societies to put forward a national unified voice. Protests and political lobbying lead to the formation of a Senate Select Committee on Animal Welfare, reflecting what Gonzalo Villanueva has referred to as a social and political landscape that “appeared increasingly favourable to discussing animal welfare” (Transnational 89-91).The Select Committee’s first report focussed on live export and explicitly mentioned the treatment of Australian farmed animals in the abattoirs of destination countries. The conditions in these facilities were described as being of a lower “standard of animal welfare” to those in Australia (Senate Select Committee on Animal Welfare xiii). These findings directly mirror the expressions of concern in the wake of the 2011 controversy.“A Bloody Business”On 30 May 2011, Four Corners aired a report entitled ‘A Bloody Business’ on the conditions in Indonesian slaughterhouses. The investigation followed-up on footage provided by Animals Australia and Royal Society for the Prevention of Cruelty to Animals (RSPCA Australia). Members from these groups had travelled to Indonesia in order to document conditions in slaughterhouses and prepare briefing notes which were later shared with the ABC. Their aim was to increase public awareness of the conditions Australian farmed cattle faced in Indonesia, provide a broader indictment of the live export industry, and call for an end the practice. The nationwide broadcast which included graphic footage of our cows being killed, enabled broader Australia to participate from the comfort of their own homes (see Della Porta and Diani 177-8).The program generated significant media coverage and public moral outrage (Dalziell and Wadiwel 72). Dr Bidda Jones, Chief Scientist of RSPCA Australia, referred to “28,000 radio stories, 13,000 TV mentions and 3,000 press stories” making it one of the top five national issues in the media for five weeks. An online petition created by the activist organisation GetUp! collected more than 260,000 signatures over a period of three days and $300,000 was raised for campaign advertising (Jones 102). Together, these media reports and protest actions influenced the Federal Government to suspend live exports to Indonesia. A front-page story in The Age described the Federal Government as having “caved in to public and internal party pressure” (Willingham and Allard). In her first public statement about the controversy, Prime Minister Julia Gillard outlined the Government’s intent: “We will be working closely with Indonesia, and with the industry, to make sure we can bring about major change to the way cattle are handled in these slaughter houses” (Willingham and Allard).The Prime Minister’s statement directly echoed the claims made on the Department of Agriculture and Water Resources website introduced above. Implicit is these statements is a perceived ability to bring about “major change” and an assumption that we kill better. Both directly align with claims of leading the world in animal welfare practices and the findings of the 1985 Select Committee report. Further, the controversy itself was positioned as providing an “opportunity to influence animal welfare conditions in importing countries” (Department of Agriculture and Water Resources).Four Corners provided a nationwide platform to influence decision-makers (see Della Porta and Diani 168-9). White, Director of Strategy for Animals Australia, expressed this concisely:We should be killing the animals here under Australian conditions, under our control, and then they should only be shipped as meat products, not live animals. (Ferguson, Doyle, and Worthington)Jones provided more context, describing the suffering experienced by “Australian cattle” in Indonesia as “too much,” especially when “a clear, demonstrated and successful alternative to the live export of animals” was already available (“Broader”; Jones 188). Implicit in these calls for farmed cows to be killed in Australia was an inference to technical and moral progress, evoking Australia’s “national self-image” as “a modern, principled culture” (Dalziell and Wadiwel 84). The clean, efficient and modern processes undertaken in Australia were relationally positioned against the bloody practices conducted in the Indonesian facilities. In other words, we kill cows in a nicer, more humane and better way.Australia and WhalingAustralia has a long and dynamic history with whaling (Salter). A “fervently” pro-whaling nation, the “rapidly growing” local industry went through a modernisation process in the 1950s (Day 19; Kato 484). Operations became "clean and smooth,” and death became "instant, swift and painless”. As with the live export controversy, an inference of a nicer, more humane and better way of killing was central the Australian whaling industry (Kato 484-85). Enthusiastic support for an Australian whaling industry was superseded within three decades by what Charlotte Epstein describes as “a dramatic historical turnabout” (Power 150). In June 1977, the International Whaling Commission (IWC) came to Canberra, and protests were organised across Australia to coincide with the meeting.The IWJ meeting was seen as a political opportunity. An IWC meeting being held in the last English-as-first-language nation with a commercial whaling operation provided an ideal target for the growing anti-whaling movement (Epstein, Power 149). In parallel, the opportunity to make whaling an electoral issue was seen as a priority for locally based activists and organisations (Pash 31). The collective actions of those campaigning against the backdrop of the IWC meeting comprised an array of performances (Tarrow 29). Alongside lobbying delegates, protests were held outside the venue, including the first use of a full-sized replica inflatable sperm whale by anti-whaling activists. See Image 1. The symbol of the whale became a signifier synonymous for the environment movement for decades to follow (see Epstein, Power 110-11). The number of environmental organisations attending exceeded those of any prior IWC meeting, setting in place a practice that would continue for decades to follow (M’Gonigle 150; Pash 27-8).Image 1: Protest at Australia’s last whaling station August 28, 1977. Photo credit: Jonny Lewis Collection.Following the IWC meeting in Canberra, activists packed up their equipment and prepared for the long drive to Albany in Western Australia. Disruption was added to their repertoire (Tarrow 99). The target was the last commercial whaling operation in Australia. Two months later, on August 28, demonstrations were held at the gates of the Cheynes Beach Whaling Company. Two inflatable Zodiac boats were launched, with the aim of positioning themselves between the whales being hunted and the company’s harpoon vessels. Greenpeace was painted on the side — the first protest action in Australia under the organisation’s banner (Pash 93-94).In 1978, Prime Minister Fraser formally announced an Inquiry into the future of whaling in Australia, seeking to position Australia as being on the right side of history, “taking a decisive step forward in the human consciousness” (Epstein, World 313). Underpinning announcement was a (re)purposing of whales bodies as a site for the mapping of relational constructions of Australian identity and nationhood:Many thousands of Australians — and men, women and children throughout the world — have long felt deep concern about the activities of whalers… I abhor any such activity — particularly when it is directed against a species as special and intelligent as the whale.(Qtd. in Frost vii)The actions of those protesting against whaling and the language used by Fraser in announcing the Inquiry signalled Australia’s becoming as the first nation in which “ethical arguments about the intrinsic value of the whale” displaced “scientific considerations of levels of endangerment” (Epstein, Power 150). The idea of taking action for whales had become about more than just saving their lives, it was an ethical imperative for us.Standing Up for (Our) WhalesThe Inquiry into “whales and whaling” provided specific recommendations, which were adopted in full by Prime Minister Fraser:The Inquiry’s central conclusion is that Australian whaling should end, and that, internationally, Australia should pursue a policy of opposition whaling. (Frost 206)The inquiry found that the majority of Australians viewed whaling as “morally wrong” and as a nation we should stand up for whales internationally (Frost 183). There is a direct reference here to the moral values of a civilised community, what Arne Kalland describes as a claim to “social maturity” (130). By identifying itself as a nation on the right side of the issue, Australia was pursuing a position of moral leadership on the world stage. The Whale Protection Act (1980) replaced the Whaling Act (1960). Australia’s policy of opposition to whaling was “pursued both domestically and internationally though the IWC and other organizations” (Day 19).Public opposition to whaling increased with the commencement of Japan’s scientific research whaling program in the Southern Ocean, and the dramatic actions of Greenpeace and Sea Shepherd Conservation Society. The Daily Telegraph which ran a series of articles under the banner of “our whales” in June 2005 (see, for example, Hossack; Rehn). The conservative Federal Government embraced the idea, with the Department of the Environment and Heritage website including a “Save Our Whales” page. Six months out from the 2007 federal election, opposition leader Kevin Rudd stated “It's time that Australia got serious when it comes to the slaughter of our whales” (Walters). As a “naturally more compassionate, more properly developed” people, we [Australians] had a duty to protect them (Dalziell and Wadiwel 84).Alongside oft-repeated claims of Australia’s status as a “world leader” and the priority placed on the protection of whales nationally and internationally, saveourwhales.gov.au wristbands were available for order from the government website — at no charge. By wearing one of these wristbands, all Australians could “show [their] support for the protection of whales and dolphins” (Department of the Environment and Heritage). In other words, the wearer could join together with other Australians in making a clear moral and ethical statement about both how much whales mean to us and that we all should stand up for them. The wristbands provided a means to individually and collectively express this is what we do in unobtrusive everyday way.Dramatic actions in the Southern Ocean during the 2008/09 whaling season received a broader audience with the airing of the first season of the reality TV series Whale Wars, which became Animal Planets most viewed program (Robé 94). As with A Bloody Business, Whale Wars provided an opportunity for a manifestly larger number of people to eyewitness the plight of whales (see Epstein, Power 142). Alongside the dramatised representation of the risky and personally sacrificial actions taken by the crew, the attitudes expressed reflected those of Prime Minister Fraser in 1977: protecting special and intelligent whales was the right and civilised thing to do.These sentiments were framed by the footage of activists in the series. For example, in episode four of season two, Lockhart McClean, Captain of the MV Gojira referred to Japanese whalers and their vessels as “evil” and “barbaric”, and their practices outdated. The drama of the series revolved around Sea Shepherd patrolling the Southern Ocean, their attempts to intervene against the Japanese fleet and protect our whales. The clear undercurrent here is a claim of moral progress, situated alongside an enthusiasm to export it. Such sentiments were clearly echoed by Bob Brown, a respected former member of federal parliament and spokesperson for Sea Shepherd: “It’s just a gruesome, bloody, medieval, scene which has no place in this modern world” (Japanese Whaling).On 31 May 2010 the Federal Government initiated proceedings against Japan in the ICJ. Four years later, the Court found in their favour (Nagtzaam, Young and Sullivan).Conclusion, Claims of Moral LeadershipHow the 2011 live export controversy and opposition to Japanese whaling in the Southern Ocean have unfolded provide us with an opportunity to explore a number of common themes. As Dalziell and Wadiwell noted with regard to the 2011 live export controversy, our “national self-image” was central (84). Both disputes encompass claims about us about how we want to be perceived. Whereas our cows and whales appear as key players, both disputes are effectively a ‘history of people with animals in it” (Davis 551). In other words, these disputes were not really about the lives of our farmed cows or whales.The Federal Government sought to reposition the 2011 live export controversy as providing (another) opportunity "to influence animal welfare conditions in importing countries,” drawing from our own claimed worlds-best practices (Department of Agriculture and Water Resources). The “solution” put forward by White and Jones solution was for Australian farmed cows to be killed here. Underpinning both was an implicit claim that we kill cows in a nicer, more humane and better way: "Australians are naturally more compassionate, more properly developed; more human” (Dalziell and Wadiwel 84).Similarly, the Federal Government’s pursuit of a position of world-leadership in opposing whaling was rooted in claims of our moral progress as a nation. Having formally recognised the specialness of whales in the 1970s, it was our duty to pursue their protection internationally. We could individually and collectively express national identity on our wrists, through wearing a government-provided saveourwhales.gov.au wristband. Collectively, we would not stand by and let the "gruesome, bloody, medieval” practice of Japanese whaling continue in our waters (“Japanese”). Legal action undertaken in the ICJ was the penultimate pronouncement.In short, expressions of concerns for our cows whales positioned their bodies as sites for the mapping of relational constructions of our identity and nationhood.Author’s NoteFor valuable comments on earlier drafts, I thank Talei Vulatha, Ben Hightower, Scott East and two anonymous referees.References“Broader Ban the Next Step: Animal Group.” Sydney Morning Herald, 8 June 2011. 11 July 2018 <https://www.smh.com.au/environment/conservation/broader-ban-the-next-step-animal-group-20110608-1frsr.html>.Caulfield, Malcolm. Handbook of Australian Animal Cruelty Law. North Melbourne: Animals Australia, 2009.Dalziell, Jacqueline, and Dinesh Joseph Wadiwel. “Live Exports, Animal Advocacy, Race and ‘Animal Nationalism’.” Meat Culture. Ed. Annie Potts. Brill Academic Pub., 2016. 73-89.Day, David. The Whale War. Random House, Inc., 1987.Della Porta, Donatella, and Mario Diani. Social Movements: An Introduction. Malden, MA: Blackwell, 2006.Department of Agriculture and Water Resources. “Live Animal Export Trade.” Canberra: Australian Government, 2015. 15 May 2018 <http://www.agriculture.gov.au/animal/welfare/export-trade/>.Department of the Environment and Heritage. “Save Our Whales.” Canberra, Australian Government, 2007. 31 May 2017 <https://web.archive.org/web/20070205015403/http://www.environment.gov.au/coasts/species/cetaceans/intro.html>.Epstein, Charlotte. The Power of Words in International Relations: Birth of an Anti-Whaling Discourse. Cambridge, MA: MIT P, 2008.———. “WorldWideWhale. Globalisation/Dialogue of Cultures.” Cambridge Review of International Affairs 16.2 (2003): 309-22.Ferguson, Sarah, Michael Doyle, and Anne Worthington. “A Bloody Business Transcript.” Four Corners, 2011. 30 May 2018 <http://www.abc.net.au/4corners/4c-full-program-bloody-business/8961434>.Fozdar, Farida, and Brian Spittles. “Of Cows and Men: Nationalism and Australian Cow Making.” Australian Journal of Anthropology 25 (2014): 73-90.Frost, Sydney. Whales and Whaling. Vol. 1 Canberra: Australian Government Publishing Service, 1978.Hossack, James. “Japan Vow to Go It Alone on Culling — Save Our Whales.” Daily Telegraph, 2005: 4.“Japanese Whaling Fleet Kills Minke Whales in Southern Ocean Whale Sanctuary, Sea Shepherd Says.” ABC News, 6 Jan. 2014. 16 May 2018 <http://www.abc.net.au/news/2014-01-06/sea-shephard-says-japan-whaling-fleet-inside-sanctuary/5185942>.Jones, Bidda. Backlash: Australia’s Conflict of Values over Live Exports. Braidwood, NSW: Finlay Lloyd Publishers, 2016.Kalland, Arne. “Management by Totemization: Whale Symbolism and the Anti-Whaling Campaign.” Arctic 46.2 (1993): 124-33.Kato, Kumi. “Australia’s Whaling Discourse: Global Norm, Green Consciousness and Identity.” Journal of Australian Studies 39.4 (2015): 477-93.M’Gonigle, R. Michael. “The Economizing of Ecology: Why Big, Rare Whales Still Die.” Ecology Law Quarterly 9.1 (1980): 119-237.Nagtzaam, Gerry. “Righting the Ship?: Australia, New Zealand and Japan at the ICJ and the Barbed Issue of ‘Scientific Whaling’.” Australian Journal of Environmental Law 1.1 (2014): 71-92.Pash, Chris. The Last Whale. Fremantle P, 2008.Phillips, C.J., and E. Santurtun. “The Welfare of Livestock Transported by Ship.” Veterinary Journal 196.3 (2013): 309-14.Rehn, Alison. “Winning a Battle But Not the War — Save Our Whales.” Daily Telegraph, 2005: 4.———. “Children Help Sink Japanese — Save Our Whales.” Daily Telegraph, 2005: 4.———. “Japan’s Vow: You Won’t Stop Us Killing Your Whales — Save Our Whales.” Daily Telegraph, 2005: 1.———. “Another Blow for Japanese — IWC Rejects Coastal Hunts — Save Our Whales.” Daily Telegraph, 2005: 10.Robé, Christopher. “The Convergence of Eco-Activism, Neoliberalism, and Reality TV in Whale Wars.” Journal of Film and Video 67.3-4 (2015): 94-111.Salter, Colin. “Opposition to Japanese Whaling in the Southern Ocean.” Animal Activism: Perspectives from Australia and New Zealand. Ed. Gonzalo Villanueva. Sydney: Sydney UP, forthcoming.Senate Select Committee on Animal Welfare. Export of Live Sheep From Australia: Report By the Senate Select Committee on Animal Welfare. Canberra: Australian Government Publishing Service, 1985.Tarrow, Sidney G. Power in Movement: Social Movements and Contentious Politics. New York: Cambridge UP, 2011.Villanueva, Gonzalo. “‘Pain for Animals. Profit for People’: The Campaign against Live Sheep Exports.” Animals Count: How Population Size Matters in Animal-Human Relations. Eds. Nancy Cushing and Jodi Frawley. Routledge, 2018. 99-109.———. "A Transnational History of the Australian Animal Movement 1970-2015." Palgrave Studies in the History of Social Movements. Eds. S. Berger and M. Boldorf. London: Palgrave Macmillan, 2018.Walters, Patrick. “Labor Plan to Board Whalers.” The Australian, 2007.Willingham, Richard, and Tom Allard. “Ban on Live Cattle Trade to Indonesia.” The Age, 2011: 1.Young, Margaret A., and Sebatisan Rioseco Sullivan. “Evolution through the Duty to Cooperate: Implications of the Whaling Case at the International Court of Justice”. Melbourne Journal of International Law 16.2 (2015): 1-33.

Introduction In October 2007, the federal Coalition government legislated that all eligible migrants and refugees who want to become Australian citizens must sit and pass the newly designed Australian citizenship test. Prime Minister John Howard stated that by studying the essential knowledge on Australian culture, history and values that his government had defined in official citizenship test resources, migrants seeking the conferral of Australian citizenship would become "integrated" into the broader, "mainstream" community and attain a sense of belonging as new Australian citizens (qtd. in "Howard Defends Citizenship Test"). In this paper, I conduct a genealogical analysis of Becoming an Australian Citizen, the resource booklet that contains all of the information needed to prepare for the test. Focusing specifically on the section in the booklet entitled A Story of Australia which details Australian history and framing my research through a Foucauldian perspective on governmentality that focuses on the interrelationship with truth, power and knowledge in the production of subjectivities, I suggest that the inclusion of the subject of history in the test was constituted as a new order of knowledge that aimed to shape new citizens' understanding of what constituted the "correct" version of Australian identity. History was hence promoted as a form of knowledge that relied on objectivity in order to excavate the truths of Australia's past. These truths, it was claimed, had shaped the very values that the Australian people lived by and that now prospective citizens were expected to embrace. My objective is to problematise this claim that the discipline of history consists of objective truths and to move beyond recent debates in politics and historiography known as the history wars. I suggest that history instead should be viewed as a "curative science" (Foucault 90), that is, a transformative form of knowledge that focuses on the discontinuities as well as the continuities in Australia's past and which has the potential to "delimit truths" (Weeks) and thus heal the fatal impact of an official history dominated by notions of progress and achievements. This kind of cultural research not only has the capacity to influence policy-making in the field of civic education for migrant citizens, but it also has the potential to broaden understanding of Australia's past by drawing on alternative stories of Australia including the ruptures and counter stories that come together to form the multiplicity that is Australian identity. Values Eclipsing History The test was introduced at a time when the impact of globalisation was shifting conceptions of the conferral of citizenship in many Western nations from a notion of new citizens gaining legal and political rights to a concept through which becoming a naturalized citizen meant adopting a nation's particular way of life and embracing a set of core national values (Allison; Grattan; Johnson). In Australia, these values were defined as a set of principles based around liberal-democratic notions of freedom, equality, the rule of law and tolerance and promoted as "central to Australia remaining a stable, prosperous and peaceful community" (DIC 5). The Howard government believed that social cohesion was threatened by the differences emanating from recent arrivals, particularly non-Christian and non-white arrivals who did not share Australian values. These threats were contextualized through such incidents as asylum seekers allegedly throwing children overboard, the Cronulla Beach riots in 2005 and terrorist attacks close to home in Bali. Adopting Australian values was promoted as the solution to this crisis of difference. In this way, the Australian values promoted through the Australian citizenship test were allotted "a reforming role" whilst migrants and their differences were targeted as "objects of reform" (Bennett 105). Reform would be achieved by prospective citizens engaging freely in the ethical conduct of self-study of the history and values contained in the citizenship resource booklet. With some notable exceptions (see e.g. Lake and Tavan), inclusion of historical content in the test received less public scrutiny than Australian values. This is despite the fact that 37 per cent of the booklet's content was dedicated to Australian history compared to only 7 per cent dedicated to Australian values. This is also remarkable since previously, media and scholarly attention over the preceding two decades had agonised over how British colonisation and indigenous dispossession were to be represented in Australian public institutions. Popularly known as the history wars, these debates now seemed irrelevant for regulating the conduct of new citizens. The Year of the Apology: The End of the History Wars? There was also a burgeoning feeling among the broader community that a truce was in sight in the history wars (cf. Riley; Throsby). This view was supported by the outcome of the November 2007 federal election when the Howard government was defeated after eleven years in office. John Howard had been a key player in the history wars, intervening in decisions as wide ranging as the management of national museums and the preparation of high school history curricula. In his final year as prime minister, Howard became involved with overseeing what historical content was to be included in Becoming an Australian Citizen (cf. Andrews; Hirst). This had a lasting impact as even after Howard's electoral defeat, the Australian citizenship test and its accompanying resource booklet still remained in use for another two years as the essential guide that was to inform test candidates on how to be model Australian citizens. Whilst Howard's test was retained Kevin Rudd made the official Apology to the Stolen Generation as one of his first acts as prime minister in February 2008. His electoral victory was heralded as the coming of "a new intellectual culture" with "deep thinking and balanced analysis" (Nile). The Apology was also celebrated in both media and academic circles as the beginning of the process of reconciliation for both relations with indigenous and non-indigenous Australians as well as "reconciling" the controversies in history that had plagued Howard's prime ministership. In popular culture, too, the end of the history wars seemed imminent. In film, the Apology was celebrated with the release of Australia in November of that same year. Luhrmann's film became a box office hit that was later taken up by Tourism Australia to promote the nation as a desirable destination for international tourists. Langton praised it as an "eccentrically postmodern account of a recent frontier" that "has leaped over the ruins of the 'history wars' and given Australians a new past" and concluded that the film presented "an alternative history from the one John Howard and his followers constructed" (12). Similar appraisals had been made of the Australian citizenship test as the author of the historical content in the resource booklet, John Hirst, revealed that the final version of A Story of Australia "was not John Howard's and was organised contrary to his declared preference for narrative" (35). Hirst is a conservative historian who was employed by the Howard government to write "the official history of Australia" (28) for migrants and who had previously worked on other projects initiated by the Howard government, including the high school history curriculum review known as the History Summit in 2006. In an article entitled Australia: The Official History and published in The Monthly of that very same year as the Apology, Hirst divulged how in writing A Story of Australia for the citizenship resource booklet, his aim was to be "fair-minded and balanced" (31). He claimed to do this by detailing what he understood as the "two sides" in Australia's historical and political controversies relating to "Aboriginal affairs" (31), known more commonly as the history wars. Hirst's resolve was to "report the position of the two sides" (31), choosing to briefly focus on the views of historian Henry Reynolds and the political scientist Robert Manne on the one side, as well as presenting the conservative views of journalists Keith Windshuttle and Andrew Bolt on the other side (31-32). Hirst was undoubtedly referring to the two sides in the history wars that are characterised by on the one hand, commentators who believe that the brutal impact of British colonisation on indigenous peoples should be acknowledged whilst those on the other who believe that Australians should focus on celebrating their nation's relatively "peaceful past". Popularly characterised as the black armband view against the white blindfold view of Australian history, this definition does not capture the complexities, ruptures and messiness of Australia's contested past or of the debates that surround it. Hirst's categorisation, is rather problematic; while Windshuttle and Bolt's association is somewhat understandable considering their shared support in denying the existence of the Stolen Generation and massacres of indigenous communities, the association of Reynolds with Manne is certainly contestable and can be viewed as a simplistic grouping together of the "bleeding hearts" in discourses surrounding Australian history. As with the film Australia, Hirst wanted to be "the recorder of myth and memory and not simply the critical historian" (32). Unlike the film Australia, Hirst remained committed to a particular view of the discipline of history that was committed to notions of objectivity and authenticity, stating that he "was not writing this history to embody (his) own views" (31) but rather, his purpose was to introduce to new citizens what he thought captured "what Australians of today knew and valued and celebrated in their history" (32). The textual analysis that follows will illustrate that despite the declaration of a "balanced" view of Australian history being produced for migrant consumption and the call for a truce in the history wars, A Story of Australia still reflected the values and principles of a celebratory white narrative that was not concerned with recognising any side of history that dealt with the fatal impact of colonialism in stories of Australia. Disrupting the Two Sides of History The success of Australia was built on lands taken from Aboriginal people after European settlement in 1788 (DIC 32). [...]The Aboriginal people were not without friends […]. Governor Macquarie (1810-1821) took a special interest in them, running a school for their children and offering them land for farming. But very few Aboriginal people were willing to move into European society; they were not very interested in what the Europeans had to offer. (DIC 32) Despite its author's protestations against a narrative format, A Story of Australia is written as a thematic narrative that is mainly concerned with describing a nation's trajectory towards progress. It includes the usual primary school project heroes of European explorers and settlers, all of them men: Captain James Cook, Arthur Phillip and Lachlan Macquarie (17-18). It privileges a British heritage and ignores the multicultural make-up of the Australian population. In this Australian story, the convict settlers are an important factor in nation building as they found "new opportunities in this strange colony" (18) and "the ordinary soldier, the digger is a national hero" (21). Indigenous peoples, on the other hand, are described in the past tense as part of pre-history having "hunter-gatherer traditions" (32), whose culture exists today only in spectacle and who have only themselves to blame for their marginalisation by refusing the help of the white settlers. Most notable in this particular version of history are the absent stories and absent characters; there is little mention of the achievements of women and nation-building is presented as an exclusively masculine enterprise. There is also scarce mention of the contribution of migrants. Also absent is any mention of the colonisation of the Australian continent that dispossessed its Indigenous peoples. For instance, the implementation of the assimilation policy that required the forcible removal of Aboriginal children from their families is not even named as the Stolen Generation in the resource booklet, and the fight for native land rights encapsulated in the historic Mabo decision of 1992 is referred to as merely a "separatist policy" (33). In this way, it cannot be claimed that this is a balanced portrayal of Australia's past even by Hirst's own standards for it is difficult to locate the side represented by Reynolds and Manne. Once again, comparisons with the film Australia are useful. Although praised for raising "many thorny issues" relating to "national legitimacy and Aboriginal sovereignty" (Konishi and Nugent), Ashenden concludes that the film is "a mix of muttering, avoidance of touchy topics, and sporadic outbursts". Hogan also argues that the film Australia is "an exercise in national wish fulfillment, staged as a high budget, unabashedly commercial and sporadically ironic spectacle" that "offers symbolic absolution for the violence of colonialism" (63). Additionally, Hirst's description of a "successful" nation being built on the "uncultivated" indigenous lands suggests that colonisation was necessary and unavoidable if Australia was to progress into a civilised nation. Both Hirst's A Story of Australia and his Australia: The Official History share more than just the audacious appropriation of a proper noun with the film Australia as these cultural texts grant prominence to the values and principles of a celebratory white narrative of Australian history while playing down the unpalatable episodes, making any prospective citizen who does not accept these "balanced" versions of historical truths as deviant and unworthy of becoming an Australian citizen. Our Australian Story: Reconciling the Fatal Impact The Australian citizenship test and its accompanying booklet, Becoming an Australian Citizen were replaced in October 2009 with a revised test and a new booklet entitled, Australian Citizenship: Our Common Bond. The Australian Citizenship Test Review Committee deemed the 2007 original test to be "flawed, intimidating to some and discriminatory" (Australian Citizenship Test Review Committee 3). It replaced mandatory knowledge of Australian values with that of the Citizenship Pledge and determined that the subject of Australian history, although "nice-to-know" was not essential for assessing the suitability of the conferral of Australian citizenship. History content is now included in the new booklet in the non-testable section under the more inclusive title of Our Australian Story. This particular version of history now names the Stolen Generation, includes references to Australia's multicultural make up and even recognises some of the fatal effects of British colonisation. The Apology features prominently over three long paragraphs (71) and Indigenous dispossession is now described under the title of Fatal Impact as follows: The early governors were told not to harm the Aboriginal people, but the British settlers moved onto Aboriginal land and many Aboriginal people were killed. Settlers were usually not punished for committing these crimes. (58) So does this change in tone in the official history in the resource booklet for prospective citizens "prove" that the history wars are over? This more conciliatory version of Australia's past is still not the "real proof" that the history wars are over for despite broadening its categories of what constitutes as historical truth, these truths still privilege an exclusive white perspective. For example, in the new resource booklet, detail on the Stolen Generation is included as a relevant historical event in relation to what the office of Prime Minister, the Bringing Them Home Report and the Official Apology have achieved for Indigenous Australians and for the national identity, stating that "the Sorry speech was an important step forward for all Australians" (71). Perhaps then, we need to discard this way of thinking that frames the past as an ethical struggle between right and wrong and a moral battle between victors and losers. If we cease thinking of our nation's history as a battleground between celebrators and mourners and stop framing our national identity in terms of achievers and those who were not interested in building the nation, then we recognise that these "war" discourses are only the products of "games of truth" invented by governments, expert historians and their institutions. In this way, official texts can produce the possibility for a range of players from new directions to participate in what content can be included as historical truths in Australian stories and what is possible in productions of official Australian identities. The Australian Citizenship Review Committee understood this potential impact as it has recommended "the government commit to reviewing the content of the book at regular intervals given the evolving nature of Australian society" (Australian Citizenship Test Review Committee 25). In disrupting the self-evident notion of a balanced history of facts with its evocation of an equal society and by exposing how governmental institutions have used these texts as instruments of social governance (cf. Bennett), we can come to understand that there are other ways of being Australian and alternative perspectives on Australian history. The production of official histories can work towards producing a "curative science" that heals the fatal impact of the past. The impact of this kind of cultural research should be directed towards the discourse of history wars. In this way, history becomes not a battlefield but "a differential knowledge of energies and failings, heights and degenerations, poisons and antidotes" (Foucault 90) which has the capacity to transform Australian society into a society inclusive of all indigenous, non-indigenous and migrant citizens and which can work towards reconciliation of the nation's history, and perhaps, even of its people. References Allison, Lyn. "Citizenship Test Is the New Aussie Cringe." The Drum. ABC News. 4 Dec. 2011 ‹http://www.abc.net.au/news/2007-09-28/citizenship-test-is-the-new-aussie-cringe/683634›. Andrews, Kevin. "Citizenship Test Resource Released." MediaNet Press Release Wire 26 Aug. 2007: 1. Ashenden, Dean. "Luhrmann, Us, and Them." Inside Story 18 Dec. 2008. 4 Dec. 2011 ‹http://inside.org.au/luhrmann-us-and-them/›. Australian Citizenship Test Review Committee. Moving Forward... Improving Pathways to Citizenship. Canberra: Commonwealth of Australia, 2008. Australian Government. Australian Citizenship: Our Common Bond. Belconnen: National Communications Branch of the Department of Immigration and Citizenship, 2009.Bennett, Tony. Culture: A Reformer's Science. St Leonards: Allen and Unwin, 1998. DIC (Department of Immigration and Citizenship). Becoming an Australian Citizen: Citizenship. Your Commitment to Australia. Canberra, 2007.Foucault, Michel. "Nietzsche, Genealogy, History." The Foucault Reader. New York: Pantheon Books, 1984. 76-100. Grattan, Michelle. "Accept Australian Values or Get Out." The Age 25 Aug. 2005: 1. Hirst, John. "Australia: The Official History." The Monthly 6 Feb. 2008: 28-35. "Howard Defends Citizenship Test." The Age 11 Dec. 2006. Howard, John. "A Sense of Balance: The Australian Achievement in 2006 - Address to the National Press Club, 25 January." PM's News Room: Speeches. Canberra: Department of Prime Minister and Cabinet. Johnson, Carol. "John Howard's 'Values' and Australian Identity." Australian Journal of Political Science 42.2 (2007): 195-209. Konishi, Shino, and Maria Nugent. "Reviewing Indigenous History in Baz Luhrmann's Australia." Inside Story 4 Dec. 2009. 4 Dec. 2011 ‹http://inside.org.au/reviewing-indigenous-history-in-baz-luhrmanns-australia/›. Lake, Marilyn. "Wasn't This a Government Obsessed with Historical 'Truth'?" The Age 29 Oct. 2007: 13. Langton, Marcia. "Faraway Downs Fantasy Resonates Close to Home." Sunday Age 23 November 2008: 12. Nile, Richard. "End of the Culture Wars." Richard Nile Blog. The Australian 28 Nov. 2007. Riley, Mark. "Sorry, But the PM Says the Culture Wars Are Over." Sydney Morning Herald 10 Sep. 2003: 1. Tavan, Gwenda. "Testing Times: The Problem of 'History' in the Howard Government's Australian Citizenship Test." Does History Matter? Making and Debating Citizenship, Immigration and Refugee Policy in Australia and New Zealand. Eds. Neumann, Klaus and Gwenda Tavan. Canberra: ANU E P, 2009. Throsby, David. "A Truce in the Culture Wars." Sydney Morning Herald 26 Apr. 2008: 32. Weeks, Jeffrey. "Foucault for Historians." History Workshop 14 (Autumn 1982): 106-19.

In the heady expansion of capital’s productive capacity during the post-war period, E.P. Thompson wondered optimistically at potentials accruing to humanity by accelerating automation. He asked, “If we are to have enlarged leisure, in an automated future, the problem is not ‘how are men going to be able to consume all these additional time-units of leisure?’ but ‘what will be the capacity for experience of the men who have this undirected time to live?’” (Thompson 36). Indeed, linear and economistic variants of Marxian materialism have long emphasised that the socialisation of production by the use of machinery will eventually free us from work. At the very least, the underemployment produced by the automation of pivotal labour roles is supposed to create a political subject capable of agitating successfully against bourgeois and capitalist hegemony. But contrary to these prognostications, the worker of 2019 is caught up in a process of generalising work far beyond what is considered necessary by tradition, or at least the convention of what David Harvey calls “embedded liberalism” (11). As Anne Helen Peterson wrote in a recent Buzzfeed article,even the trends millennials have popularized — like athleisure — speak to our self-optimization. Yoga pants might look sloppy to your mom, but they’re efficient: you can transition seamlessly from an exercise class to a Skype meeting to child pickup. We use Fresh Direct and Amazon because the time they save allows us to do more work. (Peterson)For the work-martyr, activity in its broadest Aristotelian sense is evaluated by and subordinated to the question of efficiency and productivity. Occupations of time that were once considered external to “work” as matters of “life” (to use Kathi Weeks’s vocabulary) are reconceived as waste when not deployed in the service of value-generation (Weeks 15).The point here, then, is to provide some answers for why the decrease in socially-necessary labour time in an age of automation has not coincided with the Thompsonian expansion of free time. The current dilemma of the neoliberal “work-martyr” is traceable to the political responses generated by crises in production during the depression and the stagflationary disaccumulation of the 1960s-70s, and the major victory in the “battle for ideas” was the transformation of the political subject into human capital. This “intensely constructed and governed” suite of possible values is tasked, according to Wendy Brown, “with improving and leveraging its competitive positioning and with enhancing its (monetary and nonmonetary) portfolio value across all of its endeavours and ventures” (Brown 10). Connecting the creation of this subject in relation to personal or free time is important partly because of time’s longstanding importance to philosophies of subjectivity. But more to the point, the focus on time is important because it serves to demonstrate the economic foundations of the incursion of capitalist governance into the most private domains of existence. Against the criticism of Marx’s ‘abstract’ theory of value, one can see that the laws of capitalist accumulation make their mark in all parts of contemporary human being, including temporality. By tracing the emergence of afterwork as the unpaid continuation of the accumulation of value, one can show how each subject increasingly ‘lives’ capital. This marks a turning point in political economy. When work spills over a temporal limit, its relationship to reproduction is finally blurred to the point of indistinction. What this means for value-creation in 2019 is something in urgent need of critique.State ReproductionAccording to the Marxian theory, labour’s minimum cost is abstractly determined by the price of the labourer’s necessities. Once they have produced enough objects of value to cover these costs, the rest of their work is surplus value in the hands of the capitalist. The capitalist’s aim, then, is to extend the overall working-day for as long beyond the minimum as possible. Theoretically, the full 24 hours of the day may be used. The rise of machine production in the 19th century allowed the owners to make this theory a reality. The only thing that governed the extension of work-time was the physical minimum of labour-power’s reproduction (Marx 161). But this was on the provision that all the labourer’s “free” time was to be spent regrouping their energies. Anything in excess of this was a privilege: time wasted that could have been spent in the factory. “If the labourer consumes his disposable time for himself”, says Marx, “he robs the capitalist” (162).This began to change with the socialisation of the work process and the increase in technical proficiency that labour demanded in early 20th-century industry. With the changes in the sophistication of the manufacture process, the labourer came to be factored in the production process less as an “appendage of the machine” and more as a collection of decisive skills. Fordism based itself around the recognition that capital itself was “dependent on a family-based reproduction” (Weeks 27). In Ford’s America, the sense that work’s intensity might supplant losses in the working day propelled owners of production to recognise the economic need of ensuring a robust culture of social reproduction. In capital’s original New Deal, Ford provided an increase in wages (the Five Dollar Day) in exchange for a rise in productivity (Dalla Costa v). To preserve the increased rhythm of industrial production required more than a robust wage, however. It required “the formation of a physically efficient and psychologically disciplined working class” (Dalla Costa 2). Companies began to hire sociologists to investigate how workers spent their spare time (Dalla Costa 8). They led the charge in a what we might call the first “anthropological revolution” of the American 20th century, whereby the improved wage of the worker was underpinned by the economisation of their reproduction. This was enabled by the cheapening of social necessities (and thus a reduction in socially-necessary labour time) in profound connection to the development of household economy on the backs of unpaid female labour (Weeks 25).This arrangement between capital and labour persisted until 1929. When the inevitable crisis came, however, wages faltered, and many workers joined the ranks of the unemployed. Unable to afford even the basics of their own reproduction, the working-class looked to the state. They created political and social pressure through marches, demonstrations, attacks on shops and the looting of supply trucks (Dalla Costa 40). The state held out against them, but the crisis in production eventually reached such a point of intensity that the government was forced to intervene. Hoover instituted the Emergency Relief Act and Financial Reconstruction Corporation in 1932. This was expanded the following year by FDR’s New Deal, transforming Emergency Relief into a federal institution and creating the Civil Works Association to stimulate the job market (Dalla Costa 63). The security of the working class was decisively linked to the state through the wage guarantees, welfare measures and even the legal guarantee of collective bargaining.For the most part, the state’s intervention in social reproduction took the pressure off industry by ensuring that the workforce would remain able to handle its burdens and that the unemployed would remain employable. It guaranteed a minimum wage for the employed to ensure that demand didn’t collapse, and provided care outside the workforce to women, children and the elderly.Once the state took responsibility for reproduction, however, it immediately became interested in how free time could be made efficient and cost effective. Abroad, they noted the example of European statist and corporativist approaches. Roosevelt sent a delegation to Europe to study the various measures taken by fascist and United Front governments to curb the effects of economic crisis (Dogliani 247). Among these was Mussolini’s OND (Opera Nazionale Dopolavoro) which sought to accumulate the free time of workers to the ends of production. Part of this required the responsibilisation of the broader community not only for regeneration of labour-power but the formation of a truly fascist political subject.FDR’s social reform program was able to reproduce this at home by following the example of workers’ community organisation during the depression years. Throughout the early ‘30s, self-help cooperatives, complete with “their own systems of payment in goods or currency” emerged among the unemployed (Dalla Costa 61). Black markets in consumer goods and informal labour structures developed in all major cities (Dalla Costa 34). Subsistence goods were self-produced in a cottage industry of unpaid domestic labour by both men and women (Dalla Costa 71). The paragon of self-reproducing communities was urbanised black Americans, whose internal solidarity had saved lives throughout the depression. The state took notice of these informal economies of production and reproduction, and started to incorporate the possibility of community engineering into their national plan. Roosevelt convened the Civilian Conservation Corps to absorb underemployed elements of the American workforce and recover consumer demand through direct state sponsorship (wages) (Dogliani, 247). The Committee of Industrial Organisation was transformed into a “congress” linking workers directly to the state (Dalla Costa 74). Minium wages were secured in the supreme court in 1937, then hiked in 1938 (78). In all, the state emerged at this time as a truly corporativist entity- the guarantor of employment and of class stability. From Social Reproduction to Human Capital InvestmentSo how do we get from New Deal social engineering to yoga pants? The answer is deceptively simple. The state transformed social reproduction into a necessary part of the production process. But this also meant that it was instrumentalised. The state only had to fund its workforce’s reproduction so long as this guaranteed productivity. After the war, this was maintained by a form of “embedded liberalism” which sought to provide full employment, economic growth and welfare for its citizens while anchoring the international economy in the Dollar’s gold-value. However, by providing stable increases in “relative value” (wages), this form of state investment incentivised capital flight and its spectacular consequent: deindustrialisation. The “embedded liberalism” of the state-capital-labour compromise began to breakdown with a new crisis of accumulation (Harvey 11-12). The relocation of production to non-union states and decolonised globally-southern sites of hyper-exploitation led to an ‘urban crisis’ in the job market. But as capitalist expansion carried on abroad, inflation kept dangerous pace with the rate of unemployment. This “stagflation” put irresistible pressure on the post-war order. The Bretton-Woods policy of maintaining fixed interest rates while pinning the dollar to gold was abandoned in 1971 and exchange rates were floated all over the world (Harvey 12). The spectre of a new crisis loomed, but one which couldn’t be resolved by the simple state sponsorship of production and reproduction.While many solutions were offered in place of this, one political vision singled out the state’s intervention into reproduction as the cause of the crisis. The ‘neoliberal’ political revolution began at the level of individual groups of capitalist agitants seeking governmental influence in a crusade against communism. It was given its first run on the historical pitch in Chile as part of the CIA-sponsored Pinochet revanchism, and then imported to NYC to deal with the worsening urban crisis of the 1970s. Instead of focusing on production (which required state intervention to proceed without crisis), neoliberal theory promulgated a turn to monetisation and financialisation. The rule of the New York banks after they forced the City into near-bankruptcy in 1975 prescribed total austerity in order to make good on its debts. The government was forced by capital itself to withdraw from investment in the reproduction of its citizens and workers. This was generalised to a federal policy as Reagan sought to address the decades-long deficit during the early years of his presidential term. Facilitating the global flow of finance and the hegemony of supranational institutions like the IMF, the domestic labour force now became beholden to an international minimum of socially-necessary labour time. At the level of domestic labour, the reduction of labour’s possible cost to this minimum had dramatic consequences. International competition allowed the physical limitations of labour to, once again, vanish from sight. Removed from the discourse of reproduction rights, the capitalist edifice was able to focus on changing the ratio of socially necessary labour to surplus. The mechanism that enabled them to do so was competition among the workforce. With the opening of the world market, capital no longer had to worry about the maintenance of domestic demand.But competition was not sufficient to pull off so grand a feat. What was required was a broader “battle of ideas”; the second anthropological revolution of the American century. The protections that workers had relied upon since the Fordist compromise and the corporativist solution eroded as the new “class-power” of the bourgeoisie levelled neoliberal assaults against associated labour (Harvey 23). While unions were gradually disempowered to fight the inevitable tide of deindustrialisation and capital flight, individual workers were coddled by a stream of neoliberal propaganda promising “Freedom” to those who would leave the stifling atmosphere of collective association. The success of this double enervation crippled union power, and the capitalist could rely increasingly on internal workplace wage stratification to regulate labour at an enterprise level (Dalla Costa 25). Incentive structures transformed labour rights into privileges; imagining old entitlements as concessions from above. In the last thirty years, the foundation of worker protections at large has, according to Brown, become illegible (Brown 38).Time and ValueThe reduction of time needed to produce has not coincided with an expansion of free time. The neoliberal anthropological revolution has wormed its way into the depth of the individual subject’s temporalising through a dual assault on labour conditions and propaganda. The privatisation of reproduction means that its necessary minimum is once again the subject of class struggle. Time spent unproductively outside the workplace now not only robs the capitalist, but the worker. If an activity isn’t a means to increase one’s “experience” (the vector of employability), it is time poorly spent. The likelihood of being hired for a job, in professional industries especially, is dependent on your ability to outperform others not only in your talents and skills, but in your own exploitability. Brown points out that the groups traditionally defined by the “middle strata … works more hours for less pay, fewer benefits, less security, and less promise of retirement or upward mobility than at any time in the past century” (Brown 28-29).This is what is meant by the transformation of workers into ‘human capital’. As far as the worker is concerned, the capitalist no longer purchases their labour-power: they purchase the sum of their experiences and behaviours. A competitive market has emerged for these personality markers. As a piece of human capital, one must expend one’s time not only in reproduction, but the production of their own surplus value. Going to a play adds culture points to your brand; speaking a second language gives you a competitive edge; a robust Instagram following is the difference between getting or missing out on a job. For Jess Whyte, this means that the market is now able to govern in place of the state. It exercises a command over people’s lives in and out of the workplace “which many an old tyrannical state would have envied” (Whyte 20).There is a question here of change and continuity. A survey of the 20th century shows that the reduction of ‘socially necessary labour time’ does not necessarily mean a reduction in time spent at work. In fact, the minimum around which capitalist production circulates is not worktime but wages. It is only at the political level that the working class prevented capital from pursuing this minimum. With the political victory of neoliberalism as a “restoration of class power” to the bourgeoisie, however, this minimum becomes a factor at the heart of all negotiations between capital and labour. The individual labourer lying at the heart of the productive process is reduced to his most naked form: human capital. This capital must spend all its time productively for its own benefit. Mundane tasks are avoidable, as stipulated by the piece of human capital sometimes known as Anne Helen Peterson, if they “wouldn’t make my job easier or my work better”. People are never really after-work under neoliberalism; their spare time is structurally adjusted into auxiliary labour. Competition has achieved what the state could never have dreamed of: a total governance of spare hours. This governance unites journalists tweeting from bed with Amazon workers living where they work, not to mention early-career academics working over a weekend to publish an article in an online journal that is not even paying them. These are all ways in which the privatisation of social reproduction transforms afterwork into unpaid overtime.ReferencesBrown, Wendy. Undoing the Demos: Neoliberalism’s Stealth Revolution. New York: Zone Books, 2015.Dalla Costa, Maria. Family, Welfare, and the State: Between Progressivism and the New Deal. Brooklyn: Common Notions, 2015.Harvey, David. A Brief History of Neoliberalism. Oxford: Oxford UP, 2005.Engels, Friedrich, and Karl Marx. The Marx-Engels Reader. Ed. R.C. Tucker. New York: Norton, 1978.Marx, Karl. Capital: A Critical Analysis of Capitalist Production. Vol. 1 and 2. Trans. E. Aveling and E. Untermann. Hertfordshire: Wordsworth Classics of World Literature, 2013.Peterson, Anne Helen. “How Millennials Became the Burnout Generation.” Buzzfeed. 10 Oct. 2019 <https://www.buzzfeednews.com/article/annehelenpetersen/millennials-burnout-generation-debt-work>.Postone, Moishe. Time, Labour and Social Domination. Cambridge: Cambridge UP, 1993.Thompson, E.P. “Time, Work-Discipline, and Industrial Capitalism.” In Stanley Aronowitz and Michael J. Roberts, eds., Class: The Anthology. Hoboken: Wiley, 2018.Wang, Jackie. Carceral Capitalism. Los Angeles: Semiotext(e), 2018.Weeks, Kathi. The Problem with Work: Feminism, Marxism, Antiwork Politics, and Postwork Imaginaries. Durham: Duke UP, 2011.Whyte, Jessica. “The Invisible Hand of Friedrich Hayek: Submission and Spontaneous Order.” Political Theory (2017): 1-29.