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Objectives To report on the methods, peri-operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF feasibility study (NCT03317990). Patients and methods Between May 2018 and March 2019, 49 patients at two UK centres underwent robot-assisted radical prostatectomy (RARP). Twenty-five patient were randomized to NeuroSAFE RARP (intervention arm) and 24 to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 patients in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. Results Fifty neurovascular bundles (NVBs) from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n = 250, average five per side), we noted a sensitivity of 100%, a specificity of 99.2%, and an area under the curve (AUC) of 0.994 (95% confidence interval [CI] 0.985 to 1; P ≤0.001). On an NVB basis (n = 50), sensitivity was 100%, specificity was 92.7%, and the AUC was 0.963 (95% CI 0.914 to 1; P ≤0.001). NeuroSAFE RARP lasted a mean of 3 h 16 min (knife to skin to off table, 95% CI 3 h 2 min-3 h 30 min) compared to 2 h 4 min (95% CI 2 h 2 min-2 h 25 min; P ≤0.001) for standard RARP. There was no morbidity associated with the additional length of operating time on in the NeuroSAFE arm. Conclusion This feasibility study demonstrates the safety, reproducibility and excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Although the technique increases the duration of RARP, this does not cause short-term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF randomized controlled trial, which is currently under way at four sites in the UK.

Background Although the use of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer is of increasing interest, existing data are derived from small cohorts. Objective We describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring. Design, setting, and participants Data on 672 men enrolled in AS between August 2004 and November 2017 (inclusion criteria: Gleason 3 + 3 or 3 + 4 localised prostate cancer, presenting prostate-specific antigen, Take Home Message We report excellent clinical outcomes from one of the largest imaging-based active surveillance cohorts to date. Magnetic resonance imaging (MRI)-visible cancer at baseline, along with 3 + 4 Gleason grade, predicts a greater likelihood of treatment at five years. MRI-visible lesions appear to have a distinct clinical trajectory from less conspicuous ones.

Context Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility., Take Home Message The genomic evidence surrounding multiparametric magnetic resonance imaging (mpMRI) visibility is varied and often discordant; however, the literature suggests that tumour mpMRI visibility correlates with aggressive genomic features.

The deliberate disclosures of vast tranches of classified information to the media is a relatively recent phenomenon, with some scholars predicting that “the mass leaker may replace or supplement t...

Multiparametric magnetic resonance imaging (mpMRI) has enhanced the risk stratification for men with suspected prostate cancer 1\ud and inevitable implementation challenges around pathway modification, capacity and quality control are well rehearsed. 2\ud Use of pre-biopsy prostate mpMRI is now well-established following publication of multiple Level 1 evidence trials, 1\ud however, views of men undergoing this pathway have not yet been explored, in-depth.

Counterfeiting in its various iterations presents a potentially significant threat to our international reputation as a premium exporter of primary products. Taking existing international scholarly research in the area of food fraud, this article presents a typology of counterfeit activity as it pertains to the New Zealand primary industry sector. Through selected case studies, we explain how counterfeiting is a far more nuanced and complex problem than generally considered, and conclude that there should be a much stronger appetite for an integrated public-private identification framework that understands these variations in order to effectively pre-empt and mitigate the impact of primary product counterfeiting in this country.

This paper sets out to consider Brendon Tarrant in the context of New Zealand terrorism. While Tarrant’s attack on 15 March 2019 was unprecedented in terms of its scale, he was in many ways a somew...

IntroductionThere is an increasing body of evidence to suggest that visibility of prostate cancer on magnetic resonance (MRI) may be related to likelihood of adverse pathological outcomes. Biochemical recurrence (BCR) after radical prostatectomy remains a significant clinical challenge and a means of predicting likelihood of this prior to surgery could inform treatment choice. It appears that MRI could be a potential candidate strategy for BCR prediction, and as such, there is a need to review extant literature on the prognostic capability of MRI. Here, we describe a protocol for a systematic review and meta-analysis of the utility of biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) in predicting BCR following radical prostatectomy for prostate cancer treatment.Methods and analysisPubMed, MEDLINE, Embase and Cochrane databases will be searched and screening will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In order to meet the inclusion criteria, papers must be English-language articles involving patients who have had bpMRI or mpMRI for suspected prostate cancer and have undergone radical prostatectomy as definitive therapy. Patients must have had prostate-specific antigen monitoring before and after surgery. All relevant papers published from July 1977 to October 2020 will be eligible for inclusion. The Newcastle-Ottawa score will be used to determine the quality and bias of the studies. This protocol is written in-line with the PRISMA protocol 2015 checklist.Ethics and disseminationThere are no relevant ethical concerns. Dissemination of this protocol will be via peer-reviewed journals as well as national and international conferences.PROSPERO registration numberCRD42020206074.

Cribriform, from the Latin for 'sieve-like,' describes an aggressive prostate cancer pattern associated with poor prognosis, including biochemical recurrence after prostatectomy [1]. Following progressive integration of multiparametric magnetic resonance imaging (mpMRI) into risk stratification for suspected prostate cancer, there has been understandable concern that particular morphologies (including, intraductal, mucinous and cribriform) may have reduced visibility on mpMRI [2]. If undetected, mpMRI-invisible pathology may avoid biopsy interrogation, resulting in delayed presentation, management, and adverse clinical outcome. However, evidence surrounding mpMRI conspicuity of cribriform disease is contradictory, and given the clinical importance of this phenomenon, warrants discussion.

The COVID-19 crisis brought about increased surveillance, restrictions on movement, loss of freedoms, and the shutdown of ‘normal’ everyday life in Aotearoa New Zealand. Complex interplays of power, choice, and coercion in relation to people ceding their privacy and freedom to the state in return for the potential of health and economic security were brought to the fore. This chapter explores these dialectical tensions around risks and [in]securities in civil society using the multi-faceted lens offered by Assemblage Theory, and concepts of the Social Contract. The ‘Psycurity Accord’ offers an explanatory tool for understanding trade-offs between various risks and (in)securities, and issues of privacy and freedom. With references to different news updates regarding the evolving crisis, we consider how trade-offs around risks and [in]securities are never fixed and are re-assembled as new events occur, and the situation evolves. New orders of authority emerge from (re)alignments of different interest groups and (re)inscriptions around risk, security, freedom, and privacy.

International audience; Senescent cells accumulate with age in all tissues. Although senescent cells undergo cell-cycle arrest, these cells remain metabolically active and their secretomeknown as senescence-associated secretory phenotype (SASP)-is responsible for a systemic pro-inflammatory state, which contributes to an inflammatory microenvironment. Senescent cells can be found in the ageing prostate and the SASP and can be linked to benign prostatic hyperplasia and prostate cancer. Indeed, a number of signalling pathways provide biological plausibility for the role of senescence in both BPH and prostate cancer, although proving causality is difficult. The theory of senescence as a mechanism for prostate disease has a number of clinical implications, and could offer opportunities for targetting in the future.

In mid-February 2020 New Zealand released its long overdue ‘Countering terrorism and violent extremism national strategy.’ This article draws on the experience of three academic commentators who cast a critical eye over the document and whose respective thoughts are brought together here. The approach taken is to discuss the purpose and fundamentals of what strategy is to provide a framework with which to review New Zealand’s first publicly released counter-terrorism strategy. Unfortunately, this important and long overdue strategy, in the view of the authors, comes up well short of what it should be. The authors offer a challenge to New Zealand’s policy makers concerned with national security to seek more depth in the consideration of their approach, to present a strategy with less graphic design, more substantial discussion of the fundamental questions relating to the management of modern terrorism and violent extremism, and an appreciation of the nuanced New Zealand experience with political violence from late twentieth century to the present day.

Download PDFPDF\udUrology\udProtocol\udGenetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis\ud\ud Joseph M Norris1, Benjamin S Simpson1, Marina A Parry2, Clare Allen3, Rhys Ball4, Alex Freeman4, Daniel Kelly5, Alex Kirkham3, Veeru Kasivisvanathan1, Hayley C Whitaker1, Mark Emberton1\ud\udAuthor affiliations\udAbstract\ud\udIntroduction The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%–20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic review and novel bioinformatic analysis of the genomic basis of prostate cancer conspicuity on mpMRI.\ud\udMethods and analysis A systematic search of MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included papers will be full text articles, written between January 1980 and December 2019, comparing molecular characteristics of mpMRI-visible lesions and mpMRI-invisible lesions at the DNA, DNA-methylation, RNA or protein level. Study bias and quality will be assessed using a modified Newcastle-Ottawa score. Additionally, we will conduct a novel bioinformatic analysis of supplementary material and publicly available data, to combine transcriptomic data and reveal common pathways highlighted across studies. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist.\ud\udEthics and dissemination Ethical approval will not be required, as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.

We commend Alanee et al for their detailed description of prostate cancers not detected by multiparametric magnetic resonance imaging (mpMRI). 1 They analyzed radical prostatectomy findings for 33 men lacking mpMRI-conspicuous prostate cancer (defined as Prostate Imaging Reporting and Data System [PI-RADS] scores 1-2) on preoperative mpMRI. They found 27% (9/33) of men with negative mpMRI had Gleason Grade Group (GGG) 3-5 cancer at prostatectomy, including 9 with extraprostatic extension, and 1 with Gleason grade 5 + 5 disease. Ostensibly, these findings are at odds with contemporary evidence in which mpMRI-invisible disease harbors reassuring molecular and histopathological features (ie, overall GGG ≤2). 2 , 3 We believe that this discrepancy is attributable to certain methodological concerns, including quality of mpMRI acquisiton. 4

Multiparametric magnetic resonance imaging (mpMRI) has enhanced risk stratification for men at risk of prostate cancer, through accurate pre‐biopsy detection of high‐risk disease [1]. However, it has become apparent that not all clinically significant prostate cancer is detected by mpMRI. Approximately 10‐20% of significant disease is invisible to mpMRI, depending on the threshold set for significance, and on the quality of mpMRI acquisition and interpretation. The threshold for significance has recently been challenged by the 29‐year follow‐up of the SPCG‐4 study, in which men with overall Gleason score 3 + 4 did not suffer prostate‐cancer‐related death [2], whilst those with overall Gleason score 4 + 3 did suffer prostate‐cancer related death (adjusted relative risk 5.73; 95% CI 1.59–20.67) potentially suggesting a new threshold for clinically significant disease. This finding is important, given that in PROMIS, no men with overall Gleason score 4 + 3 had negative pre‐biopsy mpMRI [1], indicating that actually mpMRI may identify all truly significant cancer (if SPCG‐4 is used to guide our threshold). Nonetheless, over the past two years, there has been increasing drive to better understand the nature of mpMRI‐inconspicuous disease, particularly at the molecular level.

IntroductionMultiparametric MRI (mpMRI) has improved risk stratification for men with suspected prostate cancer. Indeed, mpMRI-visible tumours tend to be larger and of higher pathological grade than mpMRI-invisible tumours; however, concern remains around significant cancer that is undetected by mpMRI. There has been considerable recent interest to investigate whether tumour conspicuity on mpMRI is associated with additional histopathological features (including cellular density, microvessel density and unusual prostate cancer subtypes), which may have important clinical implications in both diagnosis and prognosis. Furthermore, analysis of these features may help reveal the radiobiology that underpins the actual mechanisms of mpMRI visibility (and invisibility) of prostate tumours. Here, we describe a protocol for a systematic review of the histopathological basis of prostate cancer conspicuity on mpMRI.Methods and analysisA systematic search of the MEDLINE, PubMed, Embase and Cochrane databases will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be used to guide screening, thematic reporting and conclusions drawn from all eligible studies. Included papers will be full-text, English-language articles, comparing the histopathological characteristics of mpMRI-visible lesions and mpMRI-invisible tumours. All studies published between January 1950 and January 2020 will be eligible for inclusion. Studies using confirmatory immunohistochemistry for the identification of immune subsets or structural components will be included. Study bias and quality will be assessed using a modified Newcastle-Ottawa scale. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist. If appropriate, a meta-analysis will be conducted comparing histopathological feature frequency between mpMRI-visible and mpMRI-invisible disease.Ethics and disseminationNo ethical approval will be required as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals and presentations at national and international conferences.PROSPERO registration numberCRD42020176049

In 1955, the New Zealand government authorised the creation of a Special Forces unit to operate with British forces in Malaya to counter a communist-inspired guerrilla insurgency. Drawing upon the operational experiences of the New Zealand SAS largely taken from the Cold War period, and underpinned by Colin Gray's Special Forces essentials of ‘economy of force’ and ‘expansion of choice’, this article will show how New Zealand's SAS is now accepted not only as a respected and relevant part of the nation's military capability, but also empowers its political decision-makers with the confidence to take on significant, and at times difficult, strategic foreign-policy choices.

The authors have attempted to ascertain the priorities for training in both adult and child psychiatry through questionnaires based on widely accepted residency training objectives. The results obtained are based on the first 76 returns. Significant differences between countries and specialities are reviewed. The authors found that there are few differences when priorities are compared for training in the United States, Canada and Australia. Similarly the priorities for training in child psychiatry are virtually the same as those for adult psychiatry although additional objectives had to be added for the subspecialty area.