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Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell–like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas. Significance: Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1–BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma.

Supplementary Figure from BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma

Supplementary Table from BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma

Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell–like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas.Significance:Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1–BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma.See related commentary by Beytagh and Weiss, p. 2730.See related article by Mo et al., p. 2906.This article is highlighted in the In This Issue feature, p. 2711

To evaluate the epidemiology of primary and metastatic pediatric brain tumors in the United States according to the WHO CNS 4th and 5th editions classifications.Pediatric patients (age ≤ 14) presenting between 2004 and 2017 with a brain tumor were identified in the National Cancer Database and categorized by NICHD age stages. Patients' age, sex, race/ethnicity, overall survival, and tumor characteristics were evaluated according to WHO CNS 4th and 5th editions.23,978 pediatric brain tumor patients were identified. Overall, other (i.e. circumscribed) astrocytic gliomas (21%), diffuse astrocytic/oligodendroglial gliomas (21%; 64% of which were midline), and embryonal tumors (16%) predominated. A minority of brain tumors were of ependymal (6%), glioneuronalneuronal (6%), germ cell tumor (GCT; 4%), mesenchymal non-meningothelial (2%), cranial nerve (2%), choroid plexus (2%), meningioma (2%), pineal (1%), and hematolymphoid (0.4%) types. GCTs were more likely in patients of Asian/Pacific Islander race/ethnicity. Brain metastases were exceedingly rare, accounting for 1.4% overall, with the most common primary tumor being neuroblastoma (61%) and non-CNS sarcoma (16%). Brain metastatic, choroid plexus, and embryonal tumors peaked during infancy and toddlerhood; whereas diffuse gliomas peaked in middle-late childhood. GCTs and glioneuronalneuronal tumors uniquely displayed bimodal distributions, with elevated prevalence in both infancy and middle-to-late childhood.We systematically described the epidemiology of pediatric brain tumors in the context of contemporary classification schema, thereby validating our current understanding and providing key insights.

In the era of #metoo, conversations regarding rape and sexual violence have received increased attention in mainstream media, giving voice to some of the many victims impacted by sexual assault. Despite the significant social upheaval this movement has given credence to, male victims of female-perpetrated sexual assault remain largely absent from Australian media. Adherence to strict representations of masculinity and femininity, often reinforced on social media, has resulted in cultural omission and problematic characterisations of both offenders and victims. International research has examined socially-constructed, gendered perceptions; however, Australian literature remains limited. This study examined what factors influence perceptions of male victims of female-perpetrated sexual violence, evaluated through Christie’s (1986) Ideal Victim/Offender framework. This mixed-method study analysed social media users’ comments on incidents of female-perpetrated sexual assault on men, presented in 28 Facebook posts, across 13 popular Australian newspapers. The findings identified a tendency of users to question victims’ masculinity, downplay harms experienced by male victims, or deny victimisation entirely. Furthermore, women were typecast as ‘fragile nurturers’ who did not have the capacity to offend, rejecting the possibility of male victims. Conclusions highlight the need for further Australian-based research and practical support, as male victims are more than simply an online myth.

PDGFRA has been shown to be commonly altered in high-grade gliomas (HGGs), including histone 3 lysine 27-mutated diffuse midline gliomas (H3K27M DMG), a disease with almost no long-term survivors. Here, we performed comprehensive genomic and transcriptomic analysis of 260 high-grade glioma cases, which revealed PDGFRA genomic alterations (mutations and/or amplifications) in 13% of patients. H3K27M DMGs had significantly higher PDGFRA expression compared to H3 wild-type tumors, and PDGFRA gene amplification resulted in even higher expression levels in H3K27M DMGs as well as H3 wild-type HGGs. We tested a panel of patient- derived pHGG/H3K27M DMG models against a range of PDGFRA inhibitors, including avapritinib, a potent small molecule inhibitor with relatively selective activity against both wild-type and mutant PDGFRA. Avapritinib showed supra-micromolar blood-brain barrier penetration in our pre-clinical models and demonstrated significant survival impact in an aggressive patient-derived H3K27M DMG mouse xenograft model. Finally, building on this preclinical activity, we report here the first clinical experience using avapritinib in eight pediatric and young adult patients with high-grade glioma (H3K27M DMG and/or PDGFRA altered). Avapritinib has thus far been well tolerated with no significant acute toxicities. Most importantly, our preliminary data reveal radiographic response evaluated by RAPNO criteria in 50% of patients, a striking outcome rarely seen in this patient population. In summary, we report that avapritinib is a selective, CNS-penetrant small molecule inhibitor of PDGFRA that shows potent activity in preclinical models and produces promising clinical responses with good tolerability in patients with high-grade glioma. This suggests a promising role for avapritinib therapy in this population with previously dismal outcomes. Citation Format: Lisa Mayr, Maria Trissal, Kallen Schwark, Jenna Labelle, Andrew Groves, Julia Furtner-Srajer, Jeffrey Supko, Liesa Weiler-Wichtl, Olivia Hack, Jacob Rozowsky, Joana G. Marques, Eshini Pandatharatna, Ulrike Leiss, Verena Rosenmayr, Frank Dubois, Noah F. Greenwald, Sibylle Madlener, Armin S. Guntner, Hana Pálová, Natalia Stepien, Daniela Lötsch-Gojo, Christian Dorfer, Karin Dieckmann, Andreas Peyrl, Amedeo A. Azizi, Alicia Baumgartner, Ondřej Slabý, Petra Pokorná, Pratiti Bandopadhayay, Rameen Beroukhim, Keith Ligon, Christof Kramm, Annika Bronsema, Simon Bailey, Ana Guerreiro Stücklin, Sabine Mueller, David T. Jones, Natalie Jäger, Jaroslav Štěrba, Leonhard Müllauer, Christine Haberler, Chandan Kumar-Sinha, Arul Chinnaiyan, Rajen Mody, Mary Skrypek, Nina Martinez, Daniel C. Bowers, Carl Koschmann, Johannes Gojo, Mariella Filbin. Clinical response to the PDGFRα inhibitor avapritinib in high-grade glioma patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5719.

Contract cheating remains a significant problem for universities and higher education (HE) generally, both within Australia and internationally. In 2020, the Australian Federal Government passed legislation establishing a new criminal offence, criminalising the provision or advertisement of academic cheating services by individuals and businesses. This legislation represents the Australian Government’s formal commitment to a criminal justice response to address the problem of contract cheating behaviour, which seeks to prevent and minimise the use and/or promotion of such cheating services within the higher education sector. This paper provides a political discourse analysis (PDA) and interpretive policy analysis (IPA) of Australian Parliamentary Hansard documents regarding debate of the Tertiary Education Quality and Standards Agency Amendment (Prohibiting Academic Cheating Services) Bill 2019. Our findings suggest a discord between the putative purpose of this legislation and the way the contract cheating problem has been represented in Australian Parliament. We argue that debates regarding the solution to, or at least how to address contract cheating first need to understand and agree on the problem if they are to meaningfully prevent crime. Our analysis exposes the politicisation of the higher education sector and associated discourse, where concern about contract cheating, in this case, was used as a vehicle to further rationalise ongoing Government paternalism and interference in tertiary institutions, underscoring the need for critical evaluation of criminological interventions.

Hub and spoke (or ‘A to B to C’) infringements arise where anti-competitive behaviour between two competitors or ‘spokes’ (A and C) is co-ordinated or facilitated by a third party ‘hub’ (B) which typically acts at a different level of the supply chain. This article considers the legal tests that are applicable in establishing an infringement of the Chapter I prohibition of the Competition Act 1998 and the evidence that may be relied on by the Competition and Markets Authority in doing so.

This article interrogates the positioning of socks as a culturally transgressive garment by football casuals through a case study of the British Sock Fetish Council (BSFC). While most studies contextualize casuals within a discourse of hooliganism and violence, their use of dress as a means of negotiating shared masculine identities remains under-researched. Founded in 2011, the BSFC quickly grew to over 1000 card-carrying members, holding meets at Newcastle, Manchester, Birmingham and London, as well as at football matches throughout the United Kingdom. Within the BSFC, the term ‘fetish’ is not used to denote a sexual predilection by an almost entirely heterosexual community. Instead, it acknowledges the members’ obsession with clothing and highlights the sub-textual tensions inherent in their individual and collective practices. The author was an active participant within the BSFC, witnessing first-hand the community’s development through the online dissemination of highly constructed, self-generated imagery, featuring colourful, patterned socks juxtaposed with rare trainers. This article explores the self-reflexive use of social media to construct group practices and provides insights into how socks were instrumental in establishing consensus on inclusive and hybrid masculine identities within this community.

Pediatric high-grade glioma (pHGG) is an incurable disease with a median survival of less than 6 months post-progression and no effective targeted therapy. PDGFRA is commonly altered in pHGG, but targeting PDGFRA in this disease has been unsuccessful, likely due to poor central nervous system (CNS) penetrance. Avapritinib is a novel and CNS-penetrant PDGFRA/KIT inhibitor that is FDA-approved for adults with unresectable or metastatic PDGFRA exon 18-mutant gastrointestinal stromal tumor (GIST) and is being studied in CNS tumors. We performed a pre-clinical and clinical assessment to determine the potential suitability of avapritinib therapy in PDGFRA-driven glioma. A multi-institutional cohort genetic analysis revealed PDGFRA amplification and mutation in 10.2% and 6.1% of pHGG, respectively. Additionally, PDGFRA expression in the absence of genetic events was significantly increased in H3K27-altered diffuse midline glioma (DMG) compared to H3-wildtype pHGG. Avapritinib performed well in: (i) mutant PDGFRA enzyme inhibition and wildtype inhibition at high dose, (ii) minimal off-target kinase inhibition, (iii) brain penetration (peak 10 µM), and (iv) proliferation/pPDGFRA reduction in PDGFRA-amplified and mutant pHGG cell lines. Avapritinib treatment in an aggressive PDX model of pHGG resulted in significant survival benefit. We pursued treatment of eight pediatric and young adult HGG patients with avapritinib across seven institutions. Patients were a mixture of local (N = 4) and metastatic disease (N = 4); all patients were post-initial radiation, with 7/8 having progressed on prior treatment. 7/8 patients had PDGFRA amplifications or mutations, and 7/8 had H3K27M mutations. Therapy was generally well-tolerated. 4/8 patients showed radiographic response to avapritinib, with one patient demonstrating complete response of target lesion and remains on therapy. Avapritinib levels in patients’ CSF and brain tumor tissue reached micromolar levels. These results demonstrate that avapritinib is a potent, selective, and CNS-penetrant PDGFRA/KIT inhibitor that is promising for further study in pHGG with relevant alterations.

One of the biggest obstacles in developing effective therapies for CNS tumors is drug delivery due to the enigmatic challenge of penetrating the blood-brain barrier. 5-azacytidine is a DNA methyltransferase inhibitor which was the first epigenetic targeting chemotherapeutic approved by the FDA. Altered DNA methylation is a hallmark of many cancers, including diffuse intrinsic pontine glioma (DIPG). 5-azacytidine has been shown to be active in DIPG cell lines, with only modest in-vivo activity. We have previously shown in a non-human primate model that intravenous (IV) administration of 5-azacitidine does not result in measurable CSF penetration, while intrathecal (IT) administration does and is well tolerated. To follow up these studies in a tumor-bearing mouse model (HSJD DIPG007), we performed pharmacokinetic (PK) and pharmacodynamic (PD) analysis following IV vs. IT administration. Forty mice were randomized to receive four weekly doses of IV 5-azacytidine (25 mg/kg), IT 5-azacytidine (40 μg), or corresponding vehicle controls. Four mice from each arm were sacrificed 30 minutes after the last dose and brain tissue was collected for PK/PD analysis. Drug concentration was quantified using ultra-high-performance liquid chromatography with tandem mass spectrometric detection, while pharmacodynamic methylation profiling was performed using the Infinium MethylationEPIC BeadChip (850K). Brain tissue concentrations were comparable between IV (7.6-58.0 pg/mg) and IT (6.9-63.9 pg/mg) dosing. Methylation profiling unexpectedly showed a significantly more pronounced pharmacodynamic effect with IV dosing vs. IT, with a mean decrease of 13.6% vs. 2.6% in global DNA methylation score (GDMS = percentage of highly methylated (beta ≥ 0.7) genomic loci) compared to vehicle controls. For the remaining mice, there was no significant difference in survival. Our results are encouraging that phenotypically relevant demethylating effects can be achieved in the CNS with IV 5-azacytidine administration; however, further research is needed to develop promising combination strategies in DIPG.

Diffuse intrinsic pontine glioma (DIPG) remains one of the most lethal brain tumors in all of childhood with no effective treatments besides radiation, which only extends survival a few months. Against this backdrop, our lab recently executed a focused CRISPR negative selection screen in DIPG cell lines after treatment with the histone deacetylase (HDAC) inhibitor panobinostat and discovered a strong co-dependence with the histone demethylase LSD1. To further explore the therapeutic potential of this synergistic interaction, we tested a drug library of HDAC- and LSD1- targeting drugs with the goal of identifying a combination with optimal synergy and blood brain barrier (BBB) penetration suitable for clinical translation. We were surprised to find that traditional catalytic LSD1 inhibitors had minimal effect in isolation and did not seem to synergize with HDAC inhibitors, while a recently described CoREST/LSD1 degrader named UM171 phenocopied the effects seen in our CRISPR screen. Degraders are a class of compounds that recruit an E3 ubiquitin ligase to a protein-of-interest and cause target ubiquitination and proteasomal degradation. Given our unexpected finding, we hypothesized that UM171 induces synergy with HDAC inhibitors through elimination of a scaffolding function of LSD1. To prove this, we knocked out LSD1 using CRISPR/Cas9 and subsequently treated with a panel of HDAC inhibitors, which showed a signification sensitization of DIPG cells to HDAC inhibitors compared to standard controls. We also confirmed that UM171 interacts with the CoREST complex (members include LSD1, RCOR1, HDAC1/2) by performing streptavidin bead pull down with a newly synthesized biotin-conjugated UM171 probe. In summary, our results show that targeting LSD1 for degradation in combination with HDAC inhibition is a synergistic strategy in DIPG worthy of further translational study.

Background Desmoplastic small round cell tumor (DSRCT) is a rare aggressive sarcoma that affects children and young adults, and portends poor outcomes despite intensive multimodal treatment approaches. We report toxicity, response, and outcomes of patients with DSRCT treated with the addition of vincristine, irinotecan, and temozolomide (VIT) to interval-compressed chemotherapy as per Children's Oncology Group ARST08P1. Methods All newly diagnosed pediatric patients with DSRCT treated at Dana-Farber Cancer Institute and Boston Children's Hospital between 2014 and 2019 as per ARST08P1, Arm P2 with replacement of VAC cycles with VIT, were identified. Medical records were reviewed for clinical and disease characteristics, and treatment response and outcomes. Results Six patients were treated as per the above regimen. Median age at diagnosis was 15.1 years (range 3.2-16.4) and five patients were male. Five patients had abdominal primary tumors, of which one had exclusively intraabdominal and four had extraabdominal metastases. Two initial cycles of VIT were well tolerated with nausea, vomiting, diarrhea, and constipation as the most common adverse events. Overall response rate defined as partial or complete response after two initial cycles of VIT was 50%. For local control, all patients had surgical resection followed by radiotherapy, and two patients received hyperthermic intraperitoneal chemotherapy at the time of surgery. Of the four patients who have completed therapy to date, three remain disease-free with median follow-up time of 46.7 months. Conclusions The addition of VIT to interval-compressed chemotherapy is tolerable and active in DSRCT, with activity warranting additional investigation.

The rapid increase of low-cost consumer-grade to enterprise-level unmanned aerial systems (UASs) has resulted in the exponential use of these systems in many applications. Structure from motion with multiview stereo (SfM-MVS) photogrammetry is now the baseline for the development of orthoimages and 3D surfaces (e.g., digital elevation models). The horizontal and vertical positional accuracies (x, y and z) of these products in general, rely heavily on the use of ground control points (GCPs). However, for many applications, the use of GCPs is not possible. Here we tested 14 UASs to assess the positional and within-model accuracy of SfM-MVS reconstructions of low-relief landscapes without GCPs ranging from consumer to enterprise-grade vertical takeoff and landing (VTOL) platforms. We found that high positional accuracy is not necessarily related to the platform cost or grade, rather the most important aspect is the use of post-processing kinetic (PPK) or real-time kinetic (RTK) solutions for geotagging the photographs. SfM-MVS products generated from UAS with onboard geotagging, regardless of grade, results in greater positional accuracies and lower within-model errors. We conclude that where repeatability and adherence to a high level of accuracy are needed, only RTK and PPK systems should be used without GCPs.

Collaborative research projects with service providers and their clients are becoming increasingly important for capturing a more comprehensive understanding of criminological matters. This article...

While considerable literature has explored the complex nature of victimisation, few empirical studies have examined the role of alcohol and other drugs (AODs) in victims’ experiences, specifically victims’ self-medication using AODs and its impact on ongoing health and welfare needs. Addressing the dearth of empirical research on the nature and extent of victims’ self-medication, and drawing upon quantitative data from a survey ( n = 102) of victims from Adelaide, South Australia this article explores individuals’ experiences of victimisation and AOD use against type of victimisation, type of peer support network and type of consumption. The findings indicate support for the self-medication for trauma hypothesis, namely that victimisation is positively associated with considerable increase in AOD consumption. On the other hand, there is a lack of support for the supplementary hypothesis that network support is associated with victimisation/re-victimisation. The authors demonstrate that further empirical work is needed to deepen understanding of victims’ AOD use and expedite the development of evidence-based policy and support frameworks.

The 'war on drugs' has engendered significant recent debate, encompassing a variety of opinions, evidence and knowledge (though often polarised), from a wide range of sources. In Australia, much of this debate has focused on the harms and risks associated with illicit drugs. Often of concern has been young people's use of illicit drugs in nightclubs, which recent media and government reports suggest has increased and requires critical review given young people's relative lack of knowledge and their desire for risk-taking behaviour. While there have been many attempts to address this subject, the persistence of this practice questions the effectiveness of current 'expert' strategies and highlights the need for a more nuanced, bottom-up approach. This article draws from mixed-method research that examined young people's risk perceptions, leisure practices and, for some, use of methamphetamines in five key nightclubs in Adelaide, South Australia. The article provides a snapshot of the prevalence of methamphetamine use, evaluates current policy responses, and details key empirical findings, concluding that there is need for a more open and diverse policy dialogue.

We began this book with an anecdote about COs, in particular how many, it was claimed, found their work not only challenging, but threatening, or even dangerous. Officers were commonly afraid to go to work, it was said. The ramifications of such a statement being true are profoundly disturbing. It has integrity-threatening implications as well as broader consequences for prisoner and officer conditions. Most importantly for present purposes, such a story underlines the inextricable links among correctional structures, cultures and environments, as well as matters such as integrity. In this book, we have deliberately resisted the temptation to call simply for better management, more training or more situational measures as ways of mitigating the incidence of or harms from correctional corruption. Although each of such measures has a place in any coordinated effort, each such measure must also reference the correctional environment—in particular, the ways in which policies, resources, political and public expectations define the terrain within which correctional institutions and their officers operate.

Information records play a highly significant role in correctional settings. One scholar has referred to the “supremacy that information has within the prison system” (McIlwain 2004: 254). This system dependence has grown greater as bureaucracy has intensified and psychological risk-management principles have come to play a greater part in institutional life (Crewe 2011b). The significance of written reports and other information collected by officers lies largely in their constitutive character—how information that enters the official record comes to represent, correctly or incorrectly, the identity/character of the prisoner (or probationer or parolee) for a variety of system decisions, including classification for accommodation purposes, as well as access to programs and to health-related treatment. How this information is shaped, in short, has material, and potentially prejudicial, consequences in the lives of correctional clients, and thus creates conditions for integrity breaches (see Ruppert 2013).

While researching this book, two of the authors undertook a number of visits to correctional centres across several Australian jurisdictions, the USA and the UK, in order to personally review the settings in which the types of corruption discussed in this book occur. During these visits, we were frequently drawn into conversation with prison staff. One of the most memorable comments we heard came from a prison manager during a visit to a large metropolitan prison, who said, in effect, “Eighty percent of staff of this prison should not be working here.” This comment could not pass without our asking why this was the case. The manager replied, “Because they’re scared to come to work.” Later in the book, we will return to this point, as it aptly characterises the nature of correctional settings as both places of work and places to become drawn into workplace-related corruption.

It has been said that, “Few activities create greater temptations or offer more opportunities for corruption than public sector procurement” (Transparency International 2006: 13). Procurement of goods and services constitutes a common area for corruption in private and public sector settings (see Graycar and Prenzler 2013; CCC 2008; Ware et al. 2011). Transparency International (2006) has estimated that, worldwide, approximately US $400 billion per year is lost as a direct consequence of bribery, maladministration and corruption in public procurement. Procurement corruption in corrections means that money intended for expenditure on goods and services related to the purposes of correctional services is being spent either inefficiently or being diverted away into private hands. In an era of “mass incarceration,” the size of the correctional sector means that considerable amounts of money, often in the millions and tens of millions of dollars, can be involved in contracts entered into by correctional authorities with outside suppliers for building and leasing of prisons, jails and detention centres, and for supplying provisions and other goods and services essential for running these facilities. In sheer opportunity terms, the temptations for illicit profiteering (bribes, kickbacks, etc.) by officers and managers from exogenous relationships with outside providers are substantial, as we will see below.

In this chapter, we examine the primary factors that affect the uncovering (discovery) and reporting of correctional corruption, in particular by officers and contractors. It will be argued that, more broadly, there is a considerable organisational, cultural and political resistance to admitting to, or searching for, instances of correctional corruption. In addition, for the same reasons, it is typically very difficult for individual officers to report suspicions or evidence of corruption within correctional settings. Establishing organisational structures, cultures and climates conducive to reporting corrupt practices requires an acknowledgement of the difficult balancing act between integrity and current understandings of prison security and safety, and the need for a more open and honest discussion about priorities. If, as we argue, Sykes was correct about the inevitable corruption of authority associated with the smooth running of a prison system, then what is prioritised as unacceptable corruption needs to be clearly established, and the costs of uncovering and reporting it fully calculated and provided for in the structures, training and resourcing needed for pursuing those priorities.

Violence, it has been suggested, is “omnipresent in prison” (Kupers 1996: 189). The ability of a correctional facility “to protect prisoners and staff from physical harm is a fundamental measure of the success or failure of that institution,” Gibbons and Katzenbach (2006: 21) argue. Physical harm can occur within prisons at the hands of other prisoners or COs. Given the book’s focus on correctional integrity, this chapter is concerned primarily with the latter phenomenon. We shall argue that its prevalence and importance reflects the often tenuous nature of staff control over the establishments in which they work, as well as the strongly masculinist nature of many correctional settings. As the histories of penal establishments show, too often “cultures can develop…where staff [become] careless and occasionally brutal with the power they hold” (Liebling et al. 2011: 115). Violence, whether by officers or by clients, has been said to be a part of the “prison economy” (Copes et al. 2011). This latter description implies that violence rarely occurs in a vacuum and, more commonly, it is an expression or outcome of other factors affecting correctional settings. Consistent with our approach in this book, those factors may be situational, structural or environmental in nature. Yet despite there being considerable evidence that fear of being physically victimised in prison shapes many prisoners’ as well as officers’ perceptions of their environment (Toch 1992), staff-driven violence against prisoners has received little attention to date in comparison with the much larger prisoner-on-prisoner violence literature (see Wooldredge 1991, 1998; Copes et al. 2011; Hochstetler and DeLisi 2005; Liebling and Arnold 2012).

Human cancers are composed of cells with heterogeneous genetic and epigenetic states, resulting in substantial phenotypic diversity. Medulloblastoma (MB), a clinically challenging, malignant childhood brain tumor, is no exception. A better understanding of its cellular heterogeneity is urgently needed in order to develop more efficacious therapeutic strategies that eliminate all tumor subclones underlying MB initiation, maintenance, progression, and relapse. We used single-cell RNA sequencing to assess intratumoral heterogeneity in 20 MB samples representing all four molecular subgroups. Fresh surgical biopsies were dissociated and flow sorted into single cells prior to full-length transcriptome sequencing using the Smart-seq2 protocol. Computational analyses conducted on >6,000 single cells identified cellular hierarchies ranging from proliferative, undifferentiated cell types to more differentiated neural- and astrocyte-like progeny. Transcriptional differences in undifferentiated cell populations between MB subgroups suggested distinct cellular origins, and informed oncogenic pathways believed to promote MB pathogenesis. Identification of transcriptional programs active in single cells aided the deconvolution of published bulk RNA-seq profiles, providing a deeper understanding of the heterogeneity characteristic of Group 3/4 subtypes. Lastly, inference of copy-number variations and probable driver-gene mutations from the single-cell data provided evidence for genetic subclones in a subset of patients. Overlaying transcriptional profiles on MB genetic subclones unveiled how oncogenic programs adapted during tumor evolution. These interim results provide unparalleled insights into the cellular heterogeneity of MB subgroups. Analyses aimed at further resolving molecular substructure in Group 3/4, verifying the developmental origins of MB subgroups, and implicating defined cell populations driving tumorigenesis are ongoing.

Since its emergence in the mid-1990s the increased use, illegal importation and home production of methamphetamine in Australia have sparked significant concern among the community, law enforcement agencies and policy-makers alike. In particular, the normalisation of methamphetamine consumption within some sub-groups, notably young people through the dance-party scene, has elicited a strong media concern and reactive law enforcement response. The classification and sale of pseudoephedrine through pharmacies, the implementation of Project STOP, and the intensification of punitive regulations are just some examples of the tough-on-crime reaction of the Federal and State governments. However, the response to the emerging methamphetamine so-called 'epidemic' in Australia should also encompass a critical analysis of the demand-side of the illicit drug industry. Given the need to focus on the safety and welfare of individuals within the community, Australia's response to this synthetic drug has recently begun moving towards more comprehensive demand-reduction initiatives and treatments.

Recent gerontological literature has focused on the special needs of elderly persons regarding the location and types of housing available in the community. Using Guttman's facet design, aspects of the physical and social environment were rated in relation to suburb preference and type of dwelling. The multidimensional scaling of results indicated four distinct regions with responses corresponding to the four sets of structuples generated by the facets of housing type and suburb type. These results indicated an initial preference for remaining in one's own home in one's current suburb, a second preference for a hostel in the current suburb, followed by a home in another suburb or a hostel in another suburb. Within groupings, the distinction between the physical and social aspects was maintained.

The correspondence between theory and observation is often evaluated by a comparison between a hypothesized constraint matrix and the spatial representation of a pxp similarity matrix. This comparison of constraint and proximity matrices assumes the accurate translation of similarities to proximities. If the translation is not exact (i.e., a stress or alienation coefficient greater than zero), the hypothesized structure is evaluated using a false representation of the observed data. The proposed model eliminates the need for spatial representation by making a direct comparison between the hypothesized constraint matrix and the multivariate structure of the bivariate similarities. Goodness of fit indices are used for three model comparisons; (1) single data set, one hypothesized structure; (2) single data set, two hypothesized structures; and (3) two data sets, one hypothesized structure.