Towards a social harm approach in drug policy.

In this paper, we explore how the social harm approach can be adapted within drug policy scholarship. Since the mid-2000s, a group of critical criminologists have moved beyond the concept of crime and criminology, towards the study of social harm. This turn proceeds decades of research that highlights the inequities within the criminal legal system, the formation of laws that protect the privileged and punish the disadvantaged, and the systemic challenge of the effectiveness of retribution and punishment at addressing harm in the community. The purpose of this paper is to first identify parallels between the social harm approach and critical drug scholarship, and second to advocate for the adoption of a social harm lens in drug policy scholarship. In the paper, we draw out the similarities between social harm and drug policy literatures, as well as outline what the study of social harm can bring to an analysis of drug policy. This includes a discussion on the ontology of drug crime, the myth of drug crime and the ineffective use of the crime control system in response to drug use. The paper then discusses how these conversations in critical criminology and critical drugs scholarship can be brought together to inform future drug policy research. This reflection details the link between social harm and the impingement of human flourishing, explores the role of decolonizing drug policy, advocates for the centralization of lived experience within the research process and outlines how this might align with harm reduction approaches. We conclude by arguing that the social harm approach challenges the idea that neutrality is the goal in drug policy and explicitly seeks to expand new avenues in activist research and social justice approaches to policymaking.

The Coloniality of drug prohibition.

There have been several recent commentaries which have highlighted the relevance of the postcolonial perspective to drug prohibition and called for the decolonisation of drug policy (Daniels et al., 2021; Hillier, Winkler & Lavallée, 2020; Lasco, 2022; Mills, 2019). While these are significant interventions in the field, sparse drugs scholarship has engaged more directly with well-developed literature and concepts from Critical Indigenous Studies (Moreton-Robinson, 2016) and Indigenous Standpoint Theory (Moreton-Robinson, 2013; Nakata, 2007) and reflected on its applicability to the drug and alcohol field. In contrast to the postcolonial perspective, which understands colonisation as a historical event with contemporary impacts, Indigenous scholarship conceptualises colonisation as an active and ongoing part of how the settler-state continues to impose itself. From this vantage point I explore coloniality as a system of power and reflect on the way prohibition acts as a key arm of the settler-colonial state. The paper explores the way concepts like vulnerability, marginality, overrepresentation, disproportionality and addiction involve colonial violence, knowledge practices and narratives which are central to the way coloniality is maintained and continues to assert itself in contemporary settler societies.

Convolutional Neural Networks for Raw Signal Classification in CNC Turning Process Monitoring.

This study addresses the need for advanced machine learning-based process monitoring in smart manufacturing. A methodology is developed for near-real-time part quality prediction based on process-related data obtained from a CNC turning center. Instead of the manual feature extraction methods typically employed in signal processing, a novel one-dimensional convolutional architecture allows the trained model to autonomously extract pertinent features directly from the raw signals. Several signal channels are utilized, including vibrations, motor speeds, and motor torques. Three quality indicators-average roughness, peak-to-valley roughness, and diameter deviation-are monitored using a single model, resulting in a compact and efficient classifier. Training data are obtained via a small number of experiments designed to induce variability in the quality metrics by varying feed, cutting speed, and depth of cut. A sliding window technique augments the dataset and allows the model to seamlessly operate over the entire process. This is further facilitated by the model's ability to distinguish between cutting and non-cutting phases. The base model is evaluated via k-fold cross validation and achieves average F1 scores above 0.97 for all outputs. Consistent performance is exhibited by additional instances trained under various combinations of design parameters, validating the robustness of the proposed methodology.

Association between lifetime smoking and cutaneous squamous cell carcinoma: A 2-sample Mendelian randomization study.

Background/Purpose: Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies worldwide. While several environmental risk factors for cSCC are well established, there is conflicting evidence on cigarette smoking (and its potential causal effect) and cSCC risk. Furthermore, it is unclear if these potential associations represent causal, modifiable risk factors for cSCC development. This study aims to assess the nature of the associations between cigarette smoking traits (smoking initiation, amount smoked, and lifetime smoking exposure) and cSCC risk using two-sample Mendelian randomization analyses. Methods: Genetic instruments, based on common genetic variants associated with cigarette smoking traits (P < 5 × 10-8), were derived from published genome-wide association studies (GWASs). For cSCC, we used GWAS summary statistics from the Kaiser Permanente GERA cohort (7701 cSCC cases and 60,167 controls; all non-Hispanic Whites). Results: We found modest evidence that genetically determined lifetime smoking was associated with cSCC (inverse-variance weighted method: OR[95% CI] = 1.47[1.09-1.98]; P = .012), suggesting it may be a causal risk factor for cSCC. We did not detect any evidence of association between genetically determined smoking initiation or amount smoked and cSCC risk. Conclusion: Study findings highlight the importance of smoking prevention and may support risk-stratified cSCC screening strategies based on carcinogen exposure and other genetic and clinical information.

PROMISE Registry: A prostate cancer registry of outcomes and germline mutations for improved survival and treatment effectiveness.

BACKGROUND: Recently approved treatments and updates to genetic testing recommendations for prostate cancer have created a need for correlated analyses of patient outcomes data via germline genetic mutation status. Genetic registries address these gaps by identifying candidates for recently approved targeted treatments, expanding clinical trial data examining specific gene mutations, and understanding effects of targeted treatments in the real-world setting. METHODS: The PROMISE Registry is a 20-year (5-year recruitment, 15-year follow-up), US-wide, prospective genetic registry for prostate cancer patients. Five thousand patients will be screened through an online at-home germline testing to identify and enroll 500 patients with germline mutations, including: pathogenic or likely pathogenic variants and variants of uncertain significance in genes of interest. Patients will be followed for 15 years and clinical data with real time patient reported outcomes will be collected. Eligible patients will enter long-term follow-up (6-month PRO surveys and medical record retrieval). As a virtual study with patient self-enrollment, the PROMISE Registry may fill gaps in genetics services in underserved areas and for patients within sufficient insurance coverage. RESULTS: The PROMISE Registry opened in May 2021. 2114 patients have enrolled to date across 48 US states and 23 recruiting sites. 202 patients have met criteria for long-term follow-up. PROMISE is on target with the study's goal of 5000 patients screened and 500 patients eligible for long-term follow-up by 2026. CONCLUSIONS: The PROMISE Registry is a novel, prospective, germline registry that will collect long-term patient outcomes data to address current gaps in understanding resulting from recently FDA-approved treatments and updates to genetic testing recommendations for prostate cancer. Through inclusion of a broad nationwide sample, including underserved patients and those unaffiliated with major academic centers, the PROMISE Registry aims to provide access to germline genetic testing and to collect data to understand disease characteristics and treatment responses across the disease spectrum for prostate cancer with rare germline genetic variants.

Global epidemiology of actinic keratosis in the general population: a systematic review and meta-analysis.

BACKGROUND: Actinic keratosis (AK) is a common dermatological condition, and among the most common dermatological diagnoses in older populations. Although the prevalence of AK depends on demographic and environmental factors, little is known about the global context of AK. OBJECTIVES: To provide a comprehensive and updated analysis of the global prevalence rate and incidence of AK in the general population through a systematic review and meta-analysis, and - through subgroup analyses - to identify high-risk phenotypes, demographic and lifestyle risk factors and regional variations in disease prevalence. METHODS: A systematic search of Embase, MEDLINE, Web of Science and Google Scholar was performed on 20 May 2022. Two reviewers independently screened and assessed the quality of each study using a validated critical appraisal checklist. Epidemiological measurements (e.g. prevalence) from individual studies performed in the general population were then pooled in a random-effects meta-analysis. Subgroup analyses (i.e. population age, geographical region, occupation, sex and study quality) were conducted. RESULTS: Of the 65 articles that made it through the full-text screening, 60 reported a point prevalence. A meta-analysis of these articles yielded an overall point prevalence of 14% [95% confidence interval (CI) 14-15]. In further analyses, the calculated prevalence rate varied depending on subgroup. The pooled incidence rate from the seven eligible studies analysed was 1928 per 100 000 person-years (PY; 95% CI -439 to 4294). CONCLUSIONS: This comprehensive meta-analysis provides an updated global prevalence rate of AK of 14%, indicating a significant worldwide disease burden. The incidence rate of AK was found to be 1928 per 100 000 PY, emphasizing a growing public health concern. However, high heterogeneity among studies suggests that various factors influence the AK prevalence rate, necessitating further research to understand the observed differences.

The Potential Utility of Salivary and Tear Proteomics to Discriminate Sjögren's Disease from Non-Sjögren's Sicca.

Sjögren's Disease (SjD) is an autoimmune disorder associated with decreased saliva and/or tear secretions, resulting in patients reporting dryness in the mouth and eyes. Serum autoantibodies directed against the Ro60/SS-A and La/SS-B autoantigens are a distinctive feature of the disease. Analysis of the saliva and tear proteomes represents one promising alternative method of both classifying and monitoring the condition, and research into salivary and tear proteomics in patients with SjD, with and without sicca, has shown its efficacy and practicality in both clinical and research settings. Studies analyzing the saliva proteomics of SjD patients have generally shown an overexpression of proteins involved in T-cell activation, the immune response, ß-2 microglobulin, and the recruitment of pro-inflammatory agents. These studies also show a decrease in or downregulation of proteins involved in salivary secretion. Studies analyzing the tear proteomics of patients with SjD have generally indicated an upregulation of proteins involved with TNF-α signaling, B-cell survival, and the recruitment of pro-inflammatory agents. Studies also note the differential expression of tear protein folding as a hallmark of ocular involvement in this condition. These findings help to elucidate the biochemical relationship between the proteomes of saliva/tear fluids and the general pathophysiology of the gland involved with the pathogenesis of this condition, giving further credence to the potential role of salivary and tear proteomics in the future of diagnosis and treatment for patients with SjD.

The gendered violence of injecting-related stigma among relatively affluent, suburban women who inject drugs.

INTRODUCTION: In honouring the legacy of Jude Byrne's life-long advocacy for women and mothers who use drugs, this paper presents a case study of a group of women about whom we know little about and hear even less from: women who inject drugs in relatively affluent suburbs. METHODS: Based on a 2020 qualitative study of people who inject drugs in an affluent area of Sydney known as 'The Beaches', we use in-depth interview data to thematically explore the lived experiences of gendered stigma among women who inject drugs. RESULTS: Even when women occupy the 'ideal' social position in terms of class (middle-class) and race (White) they remain subject to harmful forms of gendered stigma related to injecting drug use. Participants had internalised negative attitudes around injection drug use as a form of failed femininity and, despite being part of 'good' families and neighbourhoods, participants experienced forced child removal. DISCUSSION AND CONCLUSIONS: Taking the lead from feminist intersectionality scholarship, our data illustrate how stigma and discrimination act as a form of structural violence against women who inject drugs in affluent communities. While the social relations of gender provide some degree of protection by 'performing proximity to Whiteness', gendered stigma and violence persist.

Enhancement and Implementation of a Health Information Technology Module to Improve the Discrete Capture of Cancer Staging in a Diverse Regional Health System.

PURPOSE: Cancer staging is the foundation for all cancer management decisions. For real-time use, stage must be embedded in the electronic health record as a discrete data element. The objectives of this quality improvement (QI) initiative were to (1) identify barriers to utilization of an existing discrete cancer staging module, (2) identify health information technology (HIT) solutions to support discrete capture of cancer staging data, and (3) increase capture across the oncology enterprise in our diverse health system. METHODS: Six sigma QI methodologies were used to define barriers and solutions to improve discrete cancer staging. Design thinking principles informed solution development to test prototypes. Two multidisciplinary teams of disease-specific clinicians within GI and genitourinary conducted phased testing pilots to determine health system solutions. Solutions were expanded to all oncology specialties across our health system. RESULTS: Baseline average discrete staging capture across our health system was 31%. Poor workflow efficiency, limited accountability, and technical design gaps were key barriers to timely, complete staging. Implementation of more than 25 design enhancements to a HIT solution and passive user alerts led to a postimplementation capture rate of 58% across 55 outpatient clinics involving more than 400 clinicians. CONCLUSION: We identified key barriers to discrete data capture and designed solutions through iterative use of QI methodologies and disease-specific pilots. After implementation, discrete capture of cancer staging nearly doubled across our diverse health system. This approach is scalable and transferable to other initiatives to develop and implement clinically relevant HIT solutions across a diverse health system.

Is non-medical use normal? Normalisation, medicalisation and pharmaceutical consumption.

The theory of the normalisation of youth drug use in advanced capitalist societies has had an enduring legacy in contemporary drug scholarship. While the literature on the normalisation of 'illicit' drugs is well developed, less has been written about application of the theory to emerging discourse of pharmaceutical 'abuse', and how this might necessitate different thinking around what can be considered normal consumption. Pharmaceuticals are not directly associated with criminality, and their use does not traditionally attract stigma. In fact, social science scholarship has illustrated how many substances deemed illicit are normalised in the context of an ever-growing set of medical treatments. This paper explores the assumptions about legality, sociality and pleasure which sit behind the drug normalisation thesis, by reflecting on the relevance of drug normalisation in relation to pharmaceuticals, as well as examining scholarship on the medicalisation of society and qualitative research on non-medical use to illustrate the parallel processes of normalisation that apply to pharmaceuticals. The paper argues that questions of normalisation in relation to pharmaceutical use require a deeper engagement with the normative expectations we attach to pleasure, consumption and medicine, and the way this is structured by proximity to medical authority, whiteness and middle-classness.

Improving the Accuracy, Robustness, and Dynamic Range of Digital Bead Assays.

We report methods that improve the quantification of digital bead assays (DBA)─such as the digital enzyme-linked immunosorbent assay (ELISA)─that have found widespread use for high sensitivity measurement of proteins in clinical research and diagnostics. In digital ELISA, proteins are captured on beads, labeled with enzymes, individual beads are interrogated for activity from one or more enzymes, and the average number of enzymes per bead (AEB) is determined based on Poisson statistics. The widespread use of digital ELISA has revealed limitations to the original approaches to quantification that can lead to inaccurate AEB. Here, we have addressed the inaccuracy in AEB due to deviations from Poisson distribution in a digital ELISA for Aß-40 by changing the AEB calculation from a fixed threshold between digital counting and average normalized intensity to a smooth, continuous combination of digital counting and intensity. We addressed issues with determining the average product fluorescence intensity from single enzymes on beads by allowing outlier, high intensity arrays to be removed from average intensities, and by permitting the use of a wider range of arrays. These approaches improved the accuracy of a digital ELISA for tau protein that was affected by aggregated detection antibodies. We increased the dynamic range of a digital ELISA for IL-17A from AEB ∼25 to ∼130 by combining long and short exposure images at the product emission wavelength to create virtual images. The methods reported will significantly improve the accuracy and robustness of DBA based on imaging─such as single molecule arrays (Simoa)─and flow detection.

Longitudinal Assessment of the Prevalence of Actinic Keratosis and Extensive Risk Factor Evaluation: An Update from the Rotterdam Study.

Population-based studies available to analyze the prevalence, risk factors, and longitudinal outlook of actinic keratoses (AKs) are limited. These features mentioned earlier were assessed using Rotterdam study participants aged ≥40 years who underwent a full-body skin examination by a dermatology-trained physician. ORs with 95% confidence intervals were calculated for the associations between risk factors and the presence of AK. Among 8,239 eligible participants, the prevalence of one or more AKs was 21.1% (95% confidence interval = 20.2-22.0) and was higher in men. Male sex, age, lighter hair and eye color, baldness, genetic risk score, and digital photoaging measures (digitally assessed pigmented spots, telangiectasias, and global facial wrinkling) had a positive association with AK. Cigarette smokers had reduced odds of having AK, with current smokers having the lowest risk. Among patients with two AK assessments, there was no difference in the presence of AK during follow-up between treated and untreated participants. In conclusion, genetic risk score and digital photoaging measures showed associations with increased lesion count. At the individual level, patients were most likely to decrease in AK severity group over time, possibly regardless of whether or not participants were treated.

Non-thermal disruption of ß-adrenergic receptor-activated Ca2+ signalling and apoptosis in human ES-derived cardiomyocytes by microwave electric fields at 2.4 GHz.

The ubiquity of wireless electronic-device connectivity has seen microwaves emerge as one of the fastest growing forms of electromagnetic exposure. A growing evidence-base refutes the claim that wireless technologies pose no risk to human health at current safety levels designed to limit thermal (heating) effects. The potential impact of non-thermal effects of microwave exposure, especially in electrically-excitable tissues (e.g., heart), remains controversial. We exposed human embryonic stem-cell derived cardiomyocytes (CM), under baseline and beta-adrenergic receptor (ß-AR)-stimulated conditions, to microwaves at 2.4 GHz, a frequency used extensively in wireless communication (e.g., 4G, Bluetooth™ and WiFi). To control for any effect of sample heating, experiments were done in CM subjected to matched rates of direct heating or CM maintained at 37 °C. Detailed profiling of the temporal and amplitude features of Ca2+ signalling in CM under these experimental conditions was reconciled with the extent and spatial clustering of apoptosis. The data show that exposure of CM to 2.4 GHz EMF eliminated the normal Ca2+ signalling response to ß-AR stimulation and provoked spatially-clustered apoptosis. This is first evidence that non-thermal effects of 2.4 GHz microwaves might have profound effects on human CM function, responsiveness to activation, and survival.

Guidance for the use and reporting of anaesthetic agents in BJP manuscripts involving work with animals.

Scientists who plan to publish in the British Journal of Pharmacology (BJP) should read this article before undertaking studies utilising anaesthetics in mammalian animals. This editorial identifies certain gaps in the reporting of details on the use of anaesthetics in animal research studies published in the BJP. The editorial also provides guidance, based upon current best practices, for performing in vivo experiments that require anaesthesia. In addition, mechanisms of action and physiological impact of specific anaesthetic agents are discussed. Our goal is to identify best practices and to provide guidance on the information required for manuscripts submitted to the BJP that involve the use of anaesthetic agents in studies with experimental animals.

Injection drug use in an affluent beachside community in Sydney: An exploratory qualitative study.

INTRODUCTION: Social research on injection drug use has focussed on marginalised groups and communities, leaving a large gap in the field's understanding of how it is experienced in other settings, including in relatively affluent communities. METHODS: This research is based on fieldwork and 18 in-depth qualitative interviews conducted in suburban beach-side communities in Sydney collectively known as the Northern Beaches. RESULTS: Participants did not experience stigmatisation by local health services as the norm or as a deterrent to access. Drug acquisition on the Northern Beaches occurred among closed networks of friends and acquaintances, and injecting use rarely occurred in public settings. Police contact was minimal, resulting in lower levels of criminalisation. DISCUSSION AND CONCLUSIONS: Unlike many of the participants featured in the literature, our study participants grew up in middle and upper middle-class households, typically experiencing comfortable childhoods with little to no exposure to injection drug use. In this setting injection drug use operates covertly within the normal rhythms of middle-class life, hidden in amongst the bustle of cafés and shopping centres, and through the friendliness of neighbourhood driveway and doorstep interactions. Drug use is described as common in the area, with injecting behaviours stigmatised in ways that set it against the 'good' families and neighbourhoods of this beach-side enclave. In contrast to much of the Australian qualitative literature which frames injection drug use as a means of psychological relief or a subcultural norm, our participants described injecting as motivated by the desire to enhance pleasure and social connection.

Remote-Microphone Benefit in Noise and Reverberation for Children Who are Hard of Hearing.

BACKGROUND: Remote-microphone (RM) systems are designed to reduce the impact of poor acoustics on speech understanding. However, there is limited research examining the effects of adding reverberation to noise on speech understanding when using hearing aids (HAs) and RM systems. Given the significant challenges posed by environments with poor acoustics for children who are hard of hearing, we evaluated the ability of a novel RM system to address the effects of noise and reverberation. PURPOSE: We assessed the effect of a recently developed RM system on aided speech perception of children who were hard of hearing in noise and reverberation and how their performance compared to peers with "normal" hearing. The effect of aided speech audibility on sentence recognition when using an RM system also was assessed. STUDY SAMPLE: Twenty-two children with mild to severe hearing loss and 17 children with normal "hearing" (7-18 years) participated. DATA COLLECTION AND ANALYSIS: An adaptive procedure was used to determine the signal-to-noise ratio for 50 and 95% correct sentence recognition in noise and noise plus reverberation (RT 300 ms). Linear mixed models were used to examine the effect of listening conditions on speech recognition with RMs for children who were hard of hearing compared to children with "normal" hearing and the effects of aided audibility on performance across all listening conditions for children who were hard of hearing. RESULTS: Children who were hard of hearing had poorer speech recognition for HAs alone than for HAs plus RM. Regardless of hearing status, children had poorer speech recognition in noise plus reverberation than in noise alone. Children who were hard of hearing had poorer speech recognition than peers with "normal" hearing when using HAs alone but comparable or better speech recognition with HAs plus RM. Children with better-aided audibility with the HAs showed better speech recognition with the HAs alone and with HAs plus RM. CONCLUSIONS: Providing HAs that maximize speech audibility and coupling them with RM systems has the potential to improve communication access and outcomes for children who are hard of hearing in environments with noise and reverberation.

Novel Methods of Targeting IL-1 Signalling for the Treatment of Breast Cancer Bone Metastasis.

Breast cancer bone metastasis is currently incurable. Evidence suggests that inhibiting IL-1 signalling with the IL1R antagonist, Anakinra, or the IL1ß antibody, Canakinumab, prevents metastasis and almost eliminates breast cancer growth in the bone. However, these drugs increase primary tumour growth. We, therefore, investigated whether targeting other members of the IL-1 pathway (Caspase-1, IL1ß or IRAK1) could reduce bone metastases without increasing tumour growth outside of the bone. Inhibition of IL-1 via MLX01 (IL1ß secretion inhibitor), VRT043198/VX765 (Caspase-1 inhibitor), Pacritinib (IRAK1 inhibitor) or Anakinra (IL1R antagonist) on tumour cell viability, migration and invasion were assessed in mouse mammary E0771 and Py8119 cells in vitro and on primary tumour growth, spontaneous metastasis and metastatic outgrowth in vivo. In vitro, Inhibition of IL-1 signalling by MLX01, VRT043198 and Anakinra reduced migration of E0771 and Py8119 cells and reversed tumour-derived IL1ß induced-increased invasion and migration towards bone cells. In vivo, VX765 and Anakinra significantly reduced spontaneous metastasis and metastatic outgrowth in the bone, whereas MLX01 reduced primary tumour growth and bone metastasis. Pacritinib had no effect on metastasis in vitro or in vivo. Targeting IL-1 signalling with small molecule inhibitors may provide a new therapeutic strategy for breast cancer bone metastasis.