Preloading with drugs before entry to the nighttime entertainment district: presentation, intoxication rates, and effects of police presence during assessment.

BACKGROUND: Past research has either focused on alcohol or drug preloading before a night out, but not on the interaction between them. With increased risks of harm through interaction effects, we wished to build upon previous research in this area. We sought to determine who drug preloads, why do people engage in this practice, what drug/s are people using, and how inebriated they are as they enter the NED. Additionally, we examined what impact varying levels of police presence has on the collections of sensitive data in this context. METHODS: We captured estimates of drug and alcohol preloading from 4723 people entering nighttime entertainment districts (NEDs) in Queensland, Australia. Data collection occurred under three varying conditions of police presence (i.e., no police present, police present but not engaging with participants, and police engaging with participants). RESULTS: People who admitted to preloading drugs were found to be younger in age than non-drug admitters, more likely to be male than female, use one type of drug (mostly stimulants) rather than multiple (if we exclude alcohol), significantly more intoxicated upon arrival, and more subjectively affected from their use of alcohol and drugs as Breath Approximated Alcohol Concertation levels increased. People were more likely to admit having used drugs in the absence of police, but this had only a small effect. CONCLUSIONS: People who drug preload are a vulnerable subset of the youth population that is susceptible to experiencing harms in this context. As they drink more alcohol, they experience higher affects than those who do not report to also take drugs. Police engagement through service rather than force may mitigate some risks. Further enquiry is needed to better understand those who engage in this practice and to have quick, cheap, objective tests of what drugs these people are using.

Pre-Loading with Drugs before Entering the Nighttime Entertainment District: A Scoping Review.

Background: Nighttime entertainment districts attract many people who pre-load with alcohol and other substances before entering licensed venues. Despite the harms and dangers associated with both alcohol pre-loading and drug use respectively, there is a paucity of research on drug and polysubstance pre-loading. Objectives: The primary objectives of this scoping review are to systematically map out the body of existing literature on drug and polysubstance pre-loading, discuss methodological potentials and pitfalls in field-based research, identify gaps in knowledge, and derive practical implications and opportunities for future research. Methods: Using the PRISMA (ScR) guidelines, we conducted a search of Medline, PsycINFO, Embase, Scopus, CINAHL, Social Services Abstracts, Sociological Abstracts, and Web of Science databases. We followed this up by conducting an author and citation analysis of relevant articles. Results: Of the 632 data sources identified, 338 articles were reviewed after removing duplicates. Overall, only nine articles were included and thematically analyzed. In our review and analysis of the literature, we find people who drug pre-load to be a particularly vulnerable subset of the population. We also posit that the point-of-entry design has greater sensitivity than the commonly used portal-in design. From this, we also draw attention to various time points where field-based researchers can provide intervention. Conclusions: Given the high prevalence of young adults engaging in the behavior, clinicians should consider pre-loading behaviors when assessing for risk and vulnerability. Field-based research would elucidate the full breadth and scope of the growing pre-loading phenomenon and the dangers associated with this practice.

This is the rhythm of the night: Examining the phases of a night-out on preloading motivations and intentions to backload.

BACKGROUND: Field research into the preloading phenomena has rarely examined how patrons move and transition into target events. We conceptualised three phases of the night (PotN) - entering, within and leaving - which a patron can be intercepted by a research group. Our research tested the differences between the PotN on preloading, preloading motivations and alcohol consuming behaviours in a popular night-time entertainment district (NED). METHODS: The sample comprised 1,585 young-adult patrons (934 Men, 651 Women; ages 18-27 years) collected in a cross-sectional design over three PotN. We measured the patron's preloading motivations, current alcohol intoxication and backloading intentions between three different phases of a night-out on Thursday, Friday and Saturday nights, from 9:00p.m. - 4:00 a.m. in Brisbane NEDs (Queensland, Australia). RESULTS: The phases contributed to a difference in preloading rates - one that decreased over the night (p <.001). Between the phases, the motivation of 'saving money' (≈45%) decreased as a reason for preloading and to 'socialise' (≈20%) increased. Enhancement-based preloading motivations (i.e., 'enjoy the feeling' and 'get drunk') were related to increased alcohol intoxication and backloading intentions at different PotN. However, 'saving money' motivations were also associated with a decrease in alcohol intoxication and backloading intentions (i.e., planning to return home to continue alcohol consumption). CONCLUSIONS: Preloading is valued highly by patrons when proximal to the actual preloading. There is a difference between the PotN on preloading rates, preloading motivations, intentions to backload and drinking outcomes as patrons shift from preloading, to entering the NED, to eventually leaving.

Accuracy of mandibular proximal segment position using virtual surgical planning and custom osteosynthesis plates.

The purpose of this study was to determine whether the use of custom osteosynthesis plates increased the accuracy of proximal segment position following bilateral sagittal split osteotomy in a cohort of 30 patients when compared to a control group of 25 patients who had surgery with conventional plates. Surgery was performed by a single surgeon between October 2015 and December 2017. Post-surgical cone beam computed tomography scans were segmented using Mimics Innovation Suite (Materialise NV), and surface-based superimposition was achieved using ProPlan CMF (Materialise NV). However, there was a tendency for the rotational error to be smaller in the custom group than in the control group. The root mean square error in both groups and for all variables fell within clinical parameters of 2 mm and 4°. In conclusion, the results of this study indicate that customized mandibular fixation plates do not necessarily improve the accuracy of the proximal segments post-surgically; however they may be of benefit in individual patients.

Apparatus for skidding sensitivity testing of energetic materials.

A remote-operated apparatus for testing the detonation sensitivity of energetic materials is detailed. Using an air ram and rotating disk, the normal force and transverse velocity of the impact plane are controlled independently, enabling the exploration of varying impact conditions over a wide parameter space. A microcontroller local to the apparatus is used to automate apparatus operation and ensure temporal alignment of the impacting ram head with the rotating disk. Calculation of the firing parameters and issuing of operational commands are handled by a remote computer and relayed to the local microcontroller for execution at the hardware level. Impact forces are taken from fast strain measurements obtained from gauges incorporated into the ram head. Infrared imaging of explosive samples provides insight into the peak thermal temperatures experienced at the sample surface during the impact event.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

A Proposal for a Taxonomy of Pre-Loading.

Background: Pre-loading of alcohol and other drugs has become a prevalent start to nights out in many countries. Studies into pre-loading have been using different operational definitions and descriptions, leading to confusion and debate in the research literature. Purpose/Objective: We wish to propose a full taxonomy so that research into preloading, of any substances, can be specific and standardized. Methods: We address this problem by analyzing (1) terminology used throughout the literature, (2) the evolving nature of this phenomenon, and (3) the operational components comprising this substance use practice. Additionally, we provide a context and rationale for how we view pre-loading in relation to the broader event-level session. Results: Our results propose a full operational definition and taxonomy of pre-loading to be used, and built upon, by researchers. We also provide a visual representation of pre-loading within an event-level session and provide a method to facilitate consistency across cultures. Conclusions: We propose that this system will lead to greater specificity and higher reliability in the interpretation of research results.

Pelvic vein embolization: an assessment of the readability and quality of online information for patients.

INTRODUCTION: Pelvic congestion syndrome is a controversial topic. Pelvic vein embolization is a minimally invasive treatment for pelvic congestion syndrome. We aimed to assess the quality of information available on the Internet and determine how accessible information provided by the main IR societies was to patients. MATERIALS AND METHODS: The most commonly used term relating to pelvic vein embolization was searched across the five most-used English language search engines, with the first 25 web pages returned by each engine included for analysis. Duplicate web pages, nontext content and web pages behind paywalls were excluded. Web pages were analyzed for quality and readability using validated tools: DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. RESULTS: The most common applicable term was "Pelvic Vein Embolization". Mean DISCERN quality of information provided by websites is "fair". Flesh-Kincaid readability tests and Gunning-Fog Index demonstrated an average "college level" of reading ease. HON code certification was demonstrated in less than one third of web pages. Professional societies and scientific journals demonstrated the highest average JAMA and DISCERN scores, while for-profit organizations and healthcare providers demonstrated the lowest. Only information from 1 of 3 interventional societies was included in the first 25 search engine pages. CONCLUSION: The quality of information available online to patients is "fair" and outside of scientific journals the majority of web pages do not meet the JAMA benchmark criteria. These findings call for the production of high-quality and comprehensible content regarding interventional radiology, where physicians can reliably direct their patients for information.

The evolution and understanding of skeletal complication endpoints in clinical trials of tumors with metastasis to the bone.

Bone metastases are a frequent complication of solid tumors, leading to significant skeletal sequelae that negatively impact quality of life and survival. Prevention and management of skeletal-related complications are critical treatment goals in oncology. Endpoints used in clinical trials to evaluate skeletal-related complications have evolved. In contrast to single measures of bone health, contemporary clinical trial endpoints reflect composite measures of skeletal-related complications, and increasingly also survival. In addition, key symptomatic components, which are more reflective of quality of life and the patient experience, are being incorporated. Given the evolution and resulting diversity of the endpoints being used in pivotal trials, it is becoming increasingly relevant to clarify the utility and the potential clinical impact of these measures not only within the context of trials but also in the real-world setting. Here, we describe the development and evolution of skeletal endpoints used in trials, and discuss their clinical relevance.

Chromatic adaptation from achromatic stimuli with implied color.

Previous research has shown that the typical or memory color of an object is perceived in images of that object, even when the image is achromatic. We performed an experiment to investigate whether the implied color in greyscale images could influence the perceived color of subsequent, simple stimuli. We used a standard top-up adaptation technique along with a roving-pedestal, two-alternative spatial forced-choice method for measuring perceptual bias without contamination from any response or decision biases. Adaptors were achromatic images of natural objects that are normally seen with diagnostic color. We found that, in some circumstances, greyscale adapting images had a biasing effect, shifting the achromatic point toward the implied color, in comparison with phase-scrambled images. We interpret this effect as evidence of adaptation in chromatic signaling mechanisms that receive top-down input from knowledge of object color. This implied color adaptation effect was particularly strong from images of bananas, which are popular stimuli in memory color experiments. We also consider the effect in a color constancy context, in which the implied color is used by the visual system to estimate an illuminant, but find our results inconsistent with this explanation.

Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA.

BACKGROUND: The advent of effective adjuvant therapies for patients with resected melanoma has highlighted the need to stratify patients based on risk of relapse given the cost and toxicities associated with treatment. Here we assessed circulating tumor DNA (ctDNA) to predict and monitor relapse in resected stage III melanoma. PATIENTS AND METHODS: Somatic mutations were identified in 99/133 (74%) patients through tumor tissue sequencing. Personalized droplet digital PCR (ddPCR) assays were used to detect known mutations in 315 prospectively collected plasma samples from mutation-positive patients. External validation was performed in a prospective independent cohort (n = 29). RESULTS: ctDNA was detected in 37 of 99 (37%) individuals. In 81 patients who did not receive adjuvant therapy, 90% of patients with ctDNA detected at baseline and 100% of patients with ctDNA detected at the postoperative timepoint relapsed at a median follow up of 20 months. ctDNA detection predicted patients at high risk of relapse at baseline [relapse-free survival (RFS) hazard ratio (HR) 2.9; 95% confidence interval (CI) 1.5-5.6; P = 0.002] and postoperatively (HR 10; 95% CI 4.3-24; P < 0.001). ctDNA detection at baseline [HR 2.9; 95% CI 1.3-5.7; P = 0.003 and postoperatively (HR 11; 95% CI 4.3-27; P < 0.001] was also associated with inferior distant metastasis-free survival (DMFS). These findings were validated in the independent cohort. ctDNA detection remained an independent predictor of RFS and DMFS in multivariate analyses after adjustment for disease stage and BRAF mutation status. CONCLUSION: Baseline and postoperative ctDNA detection in two independent prospective cohorts identified stage III melanoma patients at highest risk of relapse and has potential to inform adjuvant therapy decisions.

Spatial and temporal variation of three biomarkers in Mytilus edulis.

Environmental conditions and xenobiotic exposure can be sources of stress to living organisms. Biological markers are measurable indicator of changes which may happen at any biological level and which can be considered an early warning signal of some biological or environmental state or condition. A structured field study was undertaken to investigate the relationship between three biomarker assays and the spatial and temporal variation of each biomarker in samples of Mytilus edulis. The three biomarkers were the neutral red retention assay, micronucleus assay and comet assay, which indicate damage at different cellular/molecular levels. Three sites in Poole Harbour, an area on the South coast of the UK were sampled on six separate occasions at least three weeks apart. The results for the comet assay showed a significant difference between sites and between sampling dates whereas the results for the other two assays did not show a significant difference for either factor. There was no significant correlation between the results of any pair of the three biomarkers. The results of the micronucleus assay showed a significant correlation with water temperature. This temperature effect, as well as induced repair, may contribute to explain the lack of a strict correspondence between pollution gradients and biomarkers responses.

Fuel-cell breathalyser use for field research on alcohol intoxication: an independent psychometric evaluation.

BACKGROUND: Several field studies have used fuel-cell breathalysers (FCB) to investigate the prevalence of alcohol intoxication. However, there is a lack of evidence evaluating the psychometric properties of these breathalysers outside of the forensic disciplines. METHODS: The current research describes four studies designed that assess the reliability and validity of portable platinum FCBs for research on alcohol intoxication. Utilising the Alcolizer LE5 breathalyser and, to a lesser degree, the Lifeloc FC-20 and the Lion Intoxilyzer 8000, each study sampled patrons frequenting popular night-time entertainment districts with varying levels of alcohol intoxication. RESULTS: Study one and two found excellent test-retest reliability and inter-instrument reliability for FCBs. Study three and four provided evidence to support the convergent validity of the two FCBs (the LE5 with the FC20), and with an evidential breathalyser (i.e., the Lion Intoxilyzer 8000; EB). DISCUSSION: A 93-97% agreement rate between breathalyser readings was found across the four studies. Portable FCB are recommended as a reliable and valid instrument for research designs requiring quick alcohol intoxication estimations in large populations. Strategies to enhance reliable and valid readings are provided for field researchers.

Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma.

Background: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma. Patients and methods: We carried out droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial. Results: Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval [DFI; hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.79-5.47; P < 0.0001] and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80-5.79; P < 0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status and disease stage (DFI: HR 3.26, 95% CI 1.83-5.83, P < 0.0001; DMFI: HR 3.45, 95% CI 1.88-6.34, P < 0.0001). Five-year overall survival rate for patients with detectable ctDNA was 33% (95% CI 14%-55%) versus 65% (95% CI 56%-72%) for those with undetectable ctDNA. Overall survival was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40-4.96); P = 0.003) and remained significant after adjustment for performance status (HR 2.50, 95% CI 1.32-4.74, P = 0.005). Conclusion: ctDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy. Clinical trial number: ISRCTN 81261306.

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients.

INTRODUCTION: Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. MATERIALS AND METHODS: A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients. RESULTS: Baseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/µl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/µl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(µl*cm3), P = 0.024). CONCLUSIONS: We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.

Atrial natriuretic peptide and brain natriuretic peptide changes after epicardial percutaneous left atrial appendage suture ligation using LARIAT device.

Percutaneous left atrial appendage closure is an alternative treatment for stroke and systemic thromboembolism risk reduction in non-valvular atrial fibrillation (AF). However, the neurohormonal impact of epicardial exclusion of the left atrial appendage (LAA) with the LARIAT procedure is unknown. Evaluation of changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels in AF patients underwent percutaneous LAA suture ligation. Sixty six patients underwent successfully percutaneous LAA suture ligation using LARIAT device. The level of ANP and BNP was measured before and 3 months after procedure. Mean ANP level before procedure was 249 ± 77 pg/mL (range from 95 pg/mL to 503 pg/mL) and mean BNP level was 481 ± 517 pg/mL (range from 34 pg/mL to 2508 pg/mL). Three months after procedure mean ANP level was 249 ± 79 pg/mL (range from 98 pg/mL to 492 pg/mL) and mean BNP level was 495 ± 526 pg/mL (range from 52 pg/mL to 2420 pg/mL). At 3 months follow up after percutaneous LAA suture ligation there were no significant differences in ANP and BNP levels.

Endovascular Therapy Research in Lower Limb Peripheral Arterial Disease Published Over a 5-Year Period: Who is Publishing and Where?

INTRODUCTION: Peripheral arterial disease (PAD) is being increasingly managed by endovascular therapies. In this study, we identified the clinical services publishing research as well as the journals of publication over a 5-year period. METHODS: Twenty keywords and phrases related to endovascular intervention were identified, and a literature search was performed through the PubMed database from January 2009 to January 2014. Inclusion criteria were English language, study population more than five patients, and matching the keyword search. Eligible studies were collated into a database and classified by journal of publication, PubMed number, article title, publishing clinical service, type of publication, country of origin, and authors. RESULTS: 825 studies from 114 different journals were identified. 297 papers were excluded. Of the 528 included papers, 204 (39%) were published by Vascular Surgery (VS), 157 (30%) by Interventional Radiology (IR), 101 (19%) by Cardiology, 43 (8%) by Angiology, 6 (1%) by Vascular Medicine, and 17 (3%) from miscellaneous services. 283 (54%) studies originated from Europe, 157 (30%) from North America, 76 (14%) from Asia, 6 from Australia, 3 each from South America and Africa. IR published the most papers on PAD endovascular intervention in Europe with VS second while this trend was reversed in the USA. The 528 papers were published in 98 different journals with retrospective case series (72%), the majority. CONCLUSION: IR continues to play a significant research role in endovascular intervention in PAD, particularly in Europe, and specifically in below the knee intervention, pedal intervention, and drug-eluting technologies.