Wearable Sensor-Based Assessments for Remotely Screening Early-Stage Parkinson's Disease.

Prevalence estimates of Parkinson's disease (PD)-the fastest-growing neurodegenerative disease-are generally underestimated due to issues surrounding diagnostic accuracy, symptomatic undiagnosed cases, suboptimal prodromal monitoring, and limited screening access. Remotely monitored wearable devices and sensors provide precise, objective, and frequent measures of motor and non-motor symptoms. Here, we used consumer-grade wearable device and sensor data from the WATCH-PD study to develop a PD screening tool aimed at eliminating the gap between patient symptoms and diagnosis. Early-stage PD patients (n = 82) and age-matched comparison participants (n = 50) completed a multidomain assessment battery during a one-year longitudinal multicenter study. Using disease- and behavior-relevant feature engineering and multivariate machine learning modeling of early-stage PD status, we developed a highly accurate (92.3%), sensitive (90.0%), and specific (100%) random forest classification model (AUC = 0.92) that performed well across environmental and platform contexts. These findings provide robust support for further exploration of consumer-grade wearable devices and sensors for global population-wide PD screening and surveillance.

25 year trends in cancer incidence and mortality among adults aged 35-69 years in the UK, 1993-2018: retrospective secondary analysis.

OBJECTIVE: To examine and interpret trends in UK cancer incidence and mortality for all cancers combined and for the most common cancer sites in adults aged 35-69 years. DESIGN: Retrospective secondary data analysis. DATA SOURCES: Cancer registration data, cancer mortality and national population data from the Office for National Statistics, Public Health Wales, Public Health Scotland, Northern Ireland Cancer Registry, NHS England, and the General Register Office for Northern Ireland. SETTING: 23 cancer sites were included in the analysis in the UK. PARTICIPANTS: Men and women aged 35-69 years diagnosed with or who died from cancer between 1993 to 2018. MAIN OUTCOME MEASURES: Change in cancer incidence and mortality age standardised rates over time. RESULTS: The number of cancer cases in this age range rose by 57% for men (from 55 014 cases registered in 1993 to 86 297 in 2018) and by 48% for women (60 187 to 88 970) with age standardised rates showing average annual increases of 0.8% in both sexes. The increase in incidence was predominantly driven by increases in prostate (male) and breast (female) cancers. Without these two sites, all cancer trends in age standardised incidence rates were relatively stable. Trends for a small number of less common cancers showed concerning increases in incidence rates, for example, in melanoma skin, liver, oral, and kidney cancers. The number of cancer deaths decreased over the 25 year period, by 20% in men (from 32 878 to 26 322) and 17% in women (28 516 to 23 719); age standardised mortality rates reduced for all cancers combined by 37% in men (-2.0% per year) and 33% in women (-1.6% per year). The largest decreases in mortality were noted for stomach, mesothelioma, and bladder cancers in men and stomach and cervical cancers and non-Hodgkin lymphoma in women. Most incidence and mortality changes were statistically significant even when the size of change was relatively small. CONCLUSIONS: Cancer mortality had a substantial reduction during the past 25 years in both men and women aged 35-69 years. This decline is likely a reflection of the successes in cancer prevention (eg, smoking prevention policies and cessation programmes), earlier detection (eg, screening programmes) and improved diagnostic tests, and more effective treatment. By contrast, increased prevalence of non-smoking risk factors are the likely cause of the observed increased incidence for a small number of specific cancers. This analysis also provides a benchmark for the following decade, which will include the impact of covid-19 on cancer incidence and outcomes.

Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Triad influence on the detection of crime in Hong Kong.

We use bootstrap data envelopment analysis, adjusting for endogeneity, to examine police efficiency in detecting crime in Hong Kong. We address the following: (i) is there a correlation between the detection of crime and triad influence? (ii) does the level of triad influence affect the efficiency in translating inputs (police strength) into outputs (crime detection)? and (iii) how can the allocation of policing resources be adjusted to improve crime detection? We find that nighty-eight percent of Hong Kong police districts in our sample were found to be inefficient in the detection of crime. Variation was found across districts regarding the detection of violent, property and other crimes. Most inefficiencies and potential improvements in the detection of crime were found in the categories violent and other crimes. We demonstrate how less efficient police districts can modify police resourcing decisions to better detect certain crime types while maintaining current levels of resourcing. Finally, we highlight how the method we outline improves efficiency estimation by adjusting for endogeneity and measuring the conditional efficiency of each district (i.e. the efficiency of crime detection taking the instrumental variables (e.g. influence of triads) into consideration). The use of frontier models to assist in evaluating policing performance can lead to improved efficiency, transparency, and accountability in law enforcement, ultimately resulting in better public safety outcomes and publicly funded resource allocation.

Understanding and preventing the advertisement and sale of illicit drugs to young people through social media: A multidisciplinary scoping review.

ISSUES: The sale of illicit drugs online has expanded to mainstream social media apps. These platforms provide access to a wide audience, especially children and adolescents. Research is in its infancy and scattered due to the multidisciplinary aspects of the phenomena. APPROACH: We present a multidisciplinary systematic scoping review on the advertisement and sale of illicit drugs to young people. Peer-reviewed studies written in English, Spanish and French were searched for the period 2015 to 2022. We extracted data on users, drugs studied, rate of posts, terminology used and study methodology. KEY FINDINGS: A total of 56 peer-reviewed papers were included. The analysis of these highlights the variety of drugs advertised and platforms used to do so. Various methodological designs were considered. Approaches to detecting illicit content were the focus of many studies as algorithms move from detecting drug-related keywords to drug selling behaviour. We found that on average, for the studies reviewed, 13 in 100 social media posts advertise illicit drugs. However, popular platforms used by adolescents are rarely studied. IMPLICATIONS: Promotional content is increasing in sophistication to appeal to young people, shifting towards healthy, glamourous and seemingly legal depictions of drugs. Greater inter-disciplinary collaboration between computational and qualitative approaches are needed to comprehensively study the sale and advertisement of illegal drugs on social media across different platforms. This requires coordinated action from researchers, policy makers and service providers.

The Effect of COVID-19 Restrictions on Routine Activities and Online Crime.

Objectives: Routine activity theory suggests that levels of crime are affected by peoples' activity patterns. Here, we examine if, through their impact on people's on- and off-line activities, COVID-19 restriction affected fraud committed on- and off-line during the pandemic. Our expectation was that levels of online offending would closely follow changes to mobility and online activity-with crime increasing as restrictions were imposed (and online activity increased) and declining as they were relaxed. For doorstep fraud, which has a different opportunity structure, our expectation was that the reverse would be true. Method: COVID-19 restrictions systematically disrupted people's activity patterns, creating quasi-experimental conditions well-suited to testing the effects of "interventions" on crime. We exploit those conditions using ARIMA time series models and UK data for online shopping fraud, hacking, doorstep fraud, online sales, and mobility to test hypotheses. Doorstep fraud is modelled as a non-equivalent dependent variable, allowing us to test whether findings were selective and in line with theoretical expectations. Results: After controlling for other factors, levels of crime committed online were positively associated with monthly variation in online activities and negatively associated with monthly variation in mobility. In contrast, and as expected, monthly variation in doorstep fraud was positively associated with changes in mobility. Conclusions: We find evidence consistent with routine activity theory, suggesting that disruptions to people's daily activity patterns affect levels of crime committed both on- and off-line. The theoretical implications of the findings, and the need to develop a better evidence base about what works to reduce online crime, are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s10940-022-09564-7.

Confounds and overestimations in fake review detection: Experimentally controlling for product-ownership and data-origin.

The popularity of online shopping is steadily increasing. At the same time, fake product reviews are published widely and have the potential to affect consumer purchasing behavior. In response, previous work has developed automated methods utilizing natural language processing approaches to detect fake product reviews. However, studies vary considerably in how well they succeed in detecting deceptive reviews, and the reasons for such differences are unclear. A contributing factor may be the multitude of strategies used to collect data, introducing potential confounds which affect detection performance. Two possible confounds are data-origin (i.e., the dataset is composed of more than one source) and product ownership (i.e., reviews written by individuals who own or do not own the reviewed product). In the present study, we investigate the effect of both confounds for fake review detection. Using an experimental design, we manipulate data-origin, product ownership, review polarity, and veracity. Supervised learning analysis suggests that review veracity (60.26-69.87%) is somewhat detectable but reviews additionally confounded with product-ownership (66.19-74.17%), or with data-origin (84.44-86.94%) are easier to classify. Review veracity is most easily classified if confounded with product-ownership and data-origin combined (87.78-88.12%). These findings are moderated by review polarity. Overall, our findings suggest that detection accuracy may have been overestimated in previous studies, provide possible explanations as to why, and indicate how future studies might be designed to provide less biased estimates of detection accuracy.

Cochlear implant imaging in the mouse and guinea pig using light-sheet microscopy.

Postmortem examination of the cochlea with a cochlear implant in the scala tympani presents several challenges. It is technologically difficult to section a cochlea with an implant due to the presence of its wires and metal components that are adjacent to the membranous and bony tissues of the cochlea. These metal components damage traditional steel blades of a microtome in celloidin, paraffin or frozen embedded tissues. However, plastic embedded implanted cochleas have been successfully sectioned using specialized methods (Irving et al., 2013). An alternative non-destructive method is to optically section a chemically cleared cochlea using light-sheet microscopy, which we will describe in this publication. However, since this method uses a light-sheet to section the cochlea the opaque and reflective metal components of the implant results in some artifacts in the 2D optical sections. The best image quality using light-sheet fluorescent microscopy is when the implant is removed prior to imaging.

Household occupancy and burglary: A case study using COVID-19 restrictions.

Introduction: In response to COVID-19, governments imposed various restrictions on movement and activities. According to the routine activity perspective, these should alter where crime occurs. For burglary, greater household occupancy should increase guardianship against residential burglaries, particularly during the day considering factors such as working from home. Conversely, there should be less eyes on the street to protect against non-residential burglaries. Methods: In this paper, we test these expectations using a spatio-temporal model with crime and Google Community Mobility data. Results: As expected, burglary declined during the pandemic and restrictions. Different types of burglary were, however, affected differently but largely consistent with theoretical expectation. Residential and attempted residential burglaries both decreased significantly. This was particularly the case during the day for completed residential burglaries. Moreover, while changes were coincident with the timing and relaxation of restrictions, they were better explained by fluctuations in household occupancy. However, while there were significant decreases in non-residential and attempted non-residential burglary, these did not appear to be related to changes to activity patterns, but rather the lockdown phase. Conclusions: From a theoretical perspective, the results generally provide further support for routine activity perspective. From a practical perspective, they suggest considerations for anticipating future burglary trends.

Activity in a prefrontal-periaqueductal gray circuit overcomes behavioral and endocrine features of the passive coping stress response.

The question of how the brain links behavioral and biological features of defensive responses has remained elusive. The importance of this problem is underscored by the observation that behavioral passivity in stress coping is associated with elevations in glucocorticoid hormones, and each may carry risks for susceptibility to a host of stress-related diseases. Past work implicates the medial prefrontal cortex (mPFC) in the top-down regulation of stress-related behaviors; however, it is unknown whether such changes have the capacity to buffer against the longer-lasting biological consequences associated with aversive experiences. Using the shock probe defensive burying test in rats to naturalistically measure behavioral and endocrine features of coping, we observed that the active behavioral component of stress coping is associated with increases in activity along a circuit involving the caudal mPFC and midbrain dorsolateral periaqueductal gray (PAG). Optogenetic manipulations of the caudal mPFC-to-dorsolateral PAG pathway bidirectionally modulated active (escape and defensive burying) behaviors, distinct from a rostral mPFC-ventrolateral PAG circuit that instead limited passive (immobility) behavior. Strikingly, under conditions that biased rats toward a passive coping response set, including exaggerated stress hormonal output and increased immobility, excitation of the caudal mPFC-dorsolateral PAG projection significantly attenuated each of these features. These results lend insight into how the brain coordinates response features to overcome passive coping and may be of importance for understanding how activated neural systems promote stress resilience.

Imaging the Aging Cochlea with Light-Sheet Fluorescence Microscopy.

Deafness is the most common sensory impairment, affecting approximately 5% or 430 million people worldwide as per the World Health Organization1. Aging or presbycusis is a primary cause of sensorineural hearing loss and is characterized by damage to hair cells, spiral ganglion neurons (SGNs), and the stria vascularis. These structures reside within the cochlea, which has a complex, spiral-shaped anatomy of membranous tissues suspended in fluid and surrounded by bone. These properties make it technically difficult to investigate and quantify histopathological changes. To address this need, we developed a light-sheet microscope (TSLIM) that can image and digitize the whole cochlea to facilitate the study of structure-function relationships in the inner ear. Well-aligned serial sections of the whole cochlea result in a stack of images for three-dimensional (3D) volume rendering and segmentation of individual structures for 3D visualization and quantitative analysis (i.e., length, width, surface, volume, and number). Cochleae require minimal processing steps (fixation, decalcification, dehydration, staining, and optical clearing), all of which are compatible with subsequent high-resolution imaging by scanning and transmission electron microscopy. Since all the tissues are present in the stacks, each structure can be assessed individually or relative to other structures. In addition, since imaging uses fluorescent probes, immunohistochemistry and ligand binding can be used to identify specific structures and their 3D volume or distribution within the cochlea. Here we used TSLIM to examine cochleae from aged mice to quantify the loss of hair cells and spiral ganglion neurons. In addition, advanced analyses (e.g., cluster analysis) were used to visualize local reductions of spiral ganglion neurons in Rosenthal's canal along its 3D volume. These approaches demonstrate TSLIM microscopy's ability to quantify structure-function relationships within and between cochleae.

Synaptic Mechanisms Regulating Mood State Transitions in Depression.

Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects of stress and depression on synapse function, enhancing neurotransmission, increasing plasticity, and generating new synapses in stress-sensitive brain regions. These properties are shared to varying degrees by all known antidepressants, suggesting that synaptic remodeling could play a key role in depression pathophysiology and antidepressant function. Still, it is unclear whether and precisely how synaptogenesis contributes to mood state transitions. Here, we review evidence supporting an emerging model in which depression is defined by a distinct brain state distributed across multiple stress-sensitive circuits, with neurons assuming altered functional properties, synapse configurations, and, importantly, a reduced capacity for plasticity and adaptation. Antidepressants act initially by facilitating plasticity and enabling a functional reconfiguration of this brain state. Subsequently, synaptogenesis plays a specific role in sustaining these changes over time.

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Cryptocurrencies and future financial crime.

BACKGROUND: Cryptocurrency fraud has become a growing global concern, with various governments reporting an increase in the frequency of and losses from cryptocurrency scams. Despite increasing fraudulent activity involving cryptocurrencies, research on the potential of cryptocurrencies for fraud has not been examined in a systematic study. This review examines the current state of knowledge about what kinds of cryptocurrency fraud currently exist, or are expected to exist in the future, and provides comprehensive definitions of the frauds identified. METHODS: The study involved a scoping review of academic research and grey literature on cryptocurrency fraud and a 1.5-day expert consensus exercise. The review followed the PRISMA-ScR protocol, with eligibility criteria based on language, publication type, relevance to cryptocurrency fraud, and evidence provided. Researchers screened 391 academic records, 106 of which went on to the eligibility phase, and 63 of which were ultimately analysed. We screened 394 grey literature sources, 128 of which passed on to the eligibility phase, and 53 of which were included in our review. The expert consensus exercise was attended by high-profile participants from the private sector, government, and academia. It involved problem planning and analysis activities and discussion about the future of cryptocurrency crime. RESULTS: The academic literature identified 29 different types of cryptocurrency fraud; the grey literature discussed 32 types, 14 of which were not identified in the academic literature (i.e., 47 unique types in total). Ponzi schemes and (synonymous) high yield investment programmes were most discussed across all literature. Participants in the expert consensus exercise ranked pump-and-dump schemes and ransomware as the most profitable and feasible threats, though pump-and-dumps were, notably, perceived as the least harmful type of fraud. CONCLUSIONS: The findings of this scoping review suggest cryptocurrency fraud research is rapidly developing in volume and breadth, though we remain at an early stage of thinking about future problems and scenarios involving cryptocurrencies. The findings of this work emphasise the need for better collaboration across sectors and consensus on definitions surrounding cryptocurrency fraud to address the problems identified.

A Reconfigurable and Adjustable Compliance System for the Measurement of Interface Orthotic Properties.

Custom foot orthoses (CFOs) have shown treatment effectiveness by providing improved pressure/load redistribution, skeletal support and comfort level. However, the current design methodologies of CFOs have some problems: (1) the plantar surface is captured without considering the soft tissue impedance, (2) the stiffness of the CFOs is limited to rigid, semi-rigid and soft, which ignores the potential effect of local variation of stiffness on the interface pressure/load distribution and subjective evaluations, and (3) the lack of a human-in-the-loop may lead to multiple design-to-deliver iterations. A new prescription methodology of CFOs is required to satisfy the pressure/load distribution, improve comfort level and decrease iterations. METHOD: A measurement system which provides INterface with Tunable Ergonomic properties using a Reconfigurable Framework with Adjustable Compliant Elements (INTERFACE system) is developed to implement the Rapid Evaluate and Adjust Device (READ) methodology. The geometry and stiffness of the Medial Longitudinal Arch (MLA) support provided by the INTERFACE system can be adjusted via linear actuators and tunable stiffness mechanisms, based on objective interface pressure/load distribution and subjective feedback evaluations. Validation tests were conducted on 13 subjects to measure the plantar pressure/load distribution and record the subjective feedback in different combinations of geometry and stiffness. RESULTS: The interface pressure/load distribution and subjective feedback of the support level indicate the efficacy of the adjustable geometry and stiffness. As the stiffness and geometrical height increased, the plantar loadings increased in the MLA region and decreased in the rear foot. Geometrical fitting can be achieved with the reconfigurable MLA support. The integration of locally adjustable stiffness makes it possible to fine tune the plantar pressure/load and provides the subjects with options of orthotic stiffness. CONCLUSION: The proposed INTERFACE system can be applied to conduct the measurement of the desired orthotic properties which satisfy the interface pressure/load requirement and the subject's comfort.

Tablet-Based Cognitive Impairment Screening for Adults With HIV Seeking Clinical Care: Observational Study.

BACKGROUND: Neurological complications including cognitive impairment persist among people with HIV on antiretrovirals; however, cognitive screening is not routinely conducted in HIV clinics. OBJECTIVE: Our objective for this study was 3-fold: (1) to determine the feasibility of implementing an iPad-based cognitive impairment screener among adults seeking HIV care, (2) to examine the psychometric properties of the tool, and (3) to examine predictors of cognitive impairment using the tool. METHODS: A convenience sample of participants completed Brain Baseline Assessment of Cognition and Everyday Functioning (BRACE), which included (1) Trail Making Test Part A, measuring psychomotor speed; (2) Trail Making Test Part B, measuring set-shifting; (3) Stroop Color, measuring processing speed; and (4) the Visual-Spatial Learning Test. Global neuropsychological function was estimated as mean T score performance on the 4 outcomes. Impairment on each test or for the global mean was defined as a T score ≤40. Subgroups of participants repeated the tests 4 weeks or >6 months after completing the first test to evaluate intraperson test-retest reliability and practice effects (improvements in performance due to repeated test exposure). An additional subgroup completed a lengthier cognitive battery concurrently to assess validity. Relevant factors were abstracted from electronic medical records to examine predictors of global neuropsychological function. RESULTS: The study population consisted of 404 people with HIV (age: mean 53.6 years; race: 332/404, 82% Black; 34/404, 8% White, 10/404, 2% American Indian/Alaskan Native; 28/404, 7% other and 230/404, 58% male; 174/404, 42% female) of whom 99% (402/404) were on antiretroviral therapy. Participants completed BRACE in a mean of 12 minutes (SD 3.2), and impairment was demonstrated by 34% (136/404) on Trail Making Test A, 44% (177/404) on Trail Making Test B, 40% (161/404) on Stroop Color, and 17% (67/404) on Visual-Spatial Learning Test. Global impairment was demonstrated by 103 out of 404 (25%). Test-retest reliability for the subset of participants (n=26) repeating the measure at 4 weeks was 0.81 and for the subset of participants (n=67) repeating the measure almost 1 year later (days: median 294, IQR 50) was 0.63. There were no significant practice effects at either time point (P=.20 and P=.68, respectively). With respect for validity, the correlation between global impairment on the lengthier cognitive battery and BRACE was 0.63 (n=61; P<.001), with 84% sensitivity and 94% specificity to impairment on the lengthier cognitive battery. CONCLUSIONS: We were able to successfully implement BRACE and estimate cognitive impairment burden in the context of routine clinic care. BRACE was also shown to have good psychometric properties. This easy-to-use tool in clinical settings may facilitate the care needs of people with HIV as cognitive impairment continues to remain a concern in people with HIV.

"Show this thread": policing, disruption and mobilisation through Twitter. An analysis of UK law enforcement tweeting practices during the Covid-19 pandemic.

Crisis and disruption are often unpredictable and can create opportunities for crime. During such times, policing may also need to meet additional challenges to handle the disruption. The use of social media by officials can be essential for crisis mitigation and crime reduction. In this paper, we study the use of Twitter for crime mitigation and reduction by UK police (and associated) agencies in the early stages of the Covid-19 pandemic. Our findings suggest that whilst most of the tweets from our sample concerned issues that were not specifically about crime, especially during the first stages of the pandemic, there was a significant increase in tweets about fraud, cybercrime and domestic abuse. There was also an increase in retweeting activity as opposed to the creation of original messages. Moreover, in terms of the impact of tweets, as measured by the rate at which they are retweeted, followers were more likely to 'spread the word' when the tweet was content-rich (discussed a crime specific matter and contained media), and account holders were themselves more active on Twitter. Considering the changing world we live in, criminal opportunity is likely to evolve. To help mitigate this, policy makers and researchers should consider more systematic approaches to developing social media communication strategies for the purpose of crime mitigation and reduction during disruption and change more generally. We suggest a framework for so doing.