Spot size measurement of a deuterium-tritium dense plasma focus using neutron radiography.

Neutron radiography is a technique uniquely suited to applications in nuclear diagnostics, non-destructive testing, and subcritical experiments. The spatial resolution of neutron radiographs is degraded by optical blur in the imaging system and the neutron source size, where the ideal source is point-like to optimize the point-spread function. A potential neutron source for radiography is the dense plasma focus (DPF), a coaxial Z-pinch that produces thermonuclear and beam-target neutrons. To assess if the source size is suitable for radiography, a neutron imaging system was used to measure the source size of the 4 MA Sodium DPF at the Nevada National Security Site operating with deuterium-tritium gas-fill. The source size was measured using the edge-spread function of tungsten objects, each having a rolled (convex) edge. The spot size was found to be 7-12 mm full-width at half-max (FWHM) assuming a Gaussian source, though comparison is presented for Lorentzian and Bennett distributions. The average FWHM was found to be 8.6 ± 1.2 mm vertically and 10.8 ± 1.2 mm horizontally with respect to the image plane, averaging over varied edges and alignments. The results were sensitive to source alignment and edge metrology, which introduced notable uncertainties. These results are consistent with separate experimental measurements as well as magnetohydrodynamics simulations of this DPF, which suggest that neutron production can originate from pinches ∼5-7 mm off-axis. These results suggest that the DPF should be used for radiography at low magnification (M < 1) where spot size does not dominate spatial blur.

Applying Social Practice Theory to Explore Australian Preschool Children's Oral Health.

INTRODUCTION: Despite substantial research and provision of dental care, significant morbidity remains for children's oral health. Guided by social practice theory (SPT), this research moves away from the often-ineffective focus on changing individual behavior to rethinking the centrality of the social world in promoting or undermining oral health outcomes. We define social practice as a routinized relational activity linking and integrating certain elements (competence, materials, and meanings) into the performance of a practice that is reproduced across time and space. OBJECTIVE: To investigate oral health in preschool children in Perth, Western Australia, using social practice theory. METHODS: With no definitive methodology for investigating SPT, we chose focused ethnography as a problem-focused, context-specific approach using mainly interviews to investigate participants' experience caring for their children's oral health. The focus of analysis was the practice of oral health care, not individual behavior, where themes identified from participants' transcripts were organized into categories of elements and performance. RESULTS: Eleven parents, all of whom were married or partnered, were interviewed in 2021. Findings identified social practices relevant to oral health within parenting and family relations linked to routine daily activities, including shopping, consumption of food and beverages, and toothbrushing. Oral health literacy was reflected in integrating competence, materials, and meanings into performing oral health care, notably preferences for children to drink water over sugary beverages and information often being sourced from social media and mothers' groups rather than health providers. CONCLUSION: Focusing on social practices as the unit of analysis offers a more layered understanding of elements in young children's oral health care that can indicate where the problem may lie. Findings provide an opportunity to consider future research and policy directions in children's oral health. KNOWLEDGE TRANSFER STATEMENT: Examining social practices related to young children's oral health care identifies parents/carers' knowledge about, for example, toothbrushing, the resources required, and why toothbrushing is important. Analyzing these separate elements can reveal both enablers and barriers to oral health care. This provides researchers, clinicians and policymakers an opportunity to focus on not changing individual behavior but understanding how social context impacts parents/carers' capacity to make optimum decisions around young children's oral health.

Traveling the road toward academic promotion for faculty with a DNP degree.

There is a widely recognized need for nursing faculty in the United States. To prepare a practice-ready workforce, schools of nursing are hiring faculty with Doctor of Nursing Practice (DNP) preparation to ensure clinical expertise is embedded into curriculum by practice experts. However, nurses transitioning from clinical nursing to faculty positions require tailored support and guidance in navigating the academic environment. Preparation for academic promotion is essential to integration into an academic setting. Support in navigating the new environment is essential for building confidence, to lay a foundation for a successful transition, and ultimately retaining these qualified educators. This article provides strategies to support nursing faculty planning to embark on an academic career track and provides guidance on how to prepare these DNP-prepared faculty for career progression and future promotion along academic ranks. These strategies include school and institutional orientation, faculty development plans, mentorship, leadership development, and performance review processes.

Standardization of a silver stain to reveal mesoscale myelin in histological preparations of the mammalian brain.

BACKGROUND: The brain is built of neurons supported by myelin, a fatty substance that improves cellular communication. Noninvasive magnetic resonance imaging (MRI) is now able to measure brain structure like myelin and requires histological validation. NEW METHOD: Here we present work in small and large biomedical model mammals to standardize a silver impregnation method as a high-throughput histological myelin visualization procedure. Specifically, we built a new staining well plate to increase batch size, and then systematically varied the staining and clearing cycles to describe the staining response curve across taxa and conditions. We compared tissues fixed by immersion or perfusion, mounted versus free-floating, and cut as thicker or thinner slices, with two-weeks of post-fixation. RESULTS: The staining response curves show optimal staining with a single exposure across taxa when incubation and clearing epochs are held to within 3-9 min. We show that clearing was slower in mounted vs free-floating tissue, and that staining was faster and caused fracturing earlier in thinner sliced and smaller volumes of tissue. COMPARISON WITH EXISTING METHODS: We developed a batch processing approach to increase throughput while ensuring reproducibility and demonstrate the optimal conditions for fine myelinated fiber morphology visualization with short cycles (<9 minutes). CONCLUSIONS: We present our optimized protocol to reveal mesoscale neuroanatomical myelin content in histology across mammals. This standard staining procedure will facilitate multiscale analyses of myelin content across development as well as in the presence of injury or disease.

Intentional benzodiazepine poisoning in older adults reported to United States Poison Centers.

INTRODUCTION: Despite known contraindications, benzodiazepines are frequently prescribed for older adults. This study utilizes poison control center data on benzodiazepine-involved cases aged 50 and above to compare the characteristics of suspected suicide attempt with other intentional misuse cases. We also examined associations of major medical outcomes (major effect/death) with demographic characteristics and other co-used substances in each group. METHODS: The study employed data from the America's Poison Center National Poison Data System from 2015-2022. Descriptive statistics and binary logistic regression models were used. RESULTS: Of the benzodiazepine-poisoning cases of intentional misuse (n = 93,245), 85 percent were suicide attempts and 15 percent were other intentional misuses. Reports to poisons centers showed a decline from 2019-2022 when compared to 2015-2016. However, the likelihood of a reported suicide attempt, compared to other intentional misuse, was greater in 2019-2022 compared to 2015-2016 and among those who co-used antidepressants, anxiolytics, atypical antipsychotics, other benzodiazepines, other analgesics, anticonvulsants, and alcohol. The odds of major effect/death in both groups were also greater in 2019-2022, with suicide attempt cases in advanced ages showing higher odds. The co-use of antidepressants, prescription opioids, atypical antipsychotics, anticonvulsants, and other analgesics were associated with a higher likelihood of major effect/death in both exposure groups. For instance, adjusted odds ratios for co-used prescription opioids were 2.20 (95 percent confidence intervals: 2.09-2.31) among suicide attempt cases and 3.51 (95 percent confidence intervals: 3.10-3.97) among other intentional misuse cases. DISCUSSION: Healthcare providers need to screen for suicidal ideation among benzodiazepine users, with special attention to an increased risk of suicide attempt among those who co-use antidepressants and opioids and to decreasing adverse outcomes in all misuse cases. Assessments of underlying mental health and substance use problems and medication regimens to minimize polypharmacy and drug interactions are needed to reduce adverse outcomes. CONCLUSIONS: Though the numbers of benzodiazepine-involved suicide attempt and other intentional misuse cases reported to United States poison centers decreased in recent years, the likelihood of major medical effect/death among these cases have increased.

Effectiveness of an Online Preceptor Development Program Across Health Professions.

Introduction: An online Preceptor Development Program (PDP) was developed to meet the needs of geographically dispersed preceptors across health professions. We aimed to measure the audience, their engagement, and effectiveness of an online PDP developed and implemented amid the COVID-19 pandemic. Methods: The mixed methods study included survey and attendance data for live and asynchronous formats. T-tests compared overall session perception to self-reported session impact. Objective alignment and self-reported measures of impact were analyzed around Kirkpatrick's levels of reaction, learning, and behavior. Results: Participants engaged in live and/or asynchronous PDP sessions from various professions, specialties, and geographical locations. Quantitative findings indicated significant associations between overall session perception and knowledge (session 2), competence (sessions 1, 2), and performance (session 1). Objectives were met, and key learning takeaways were reported. While most participants indicated no barriers to implementation, two barriers identified were a lack of time and uninterested students. Conclusion: Participants were afforded flexibility and choice and likely benefitted in the areas of knowledge, competence, and behavior. This online PDP effectively addressed preceptor needs in common areas, including feedback. Future program development may include advisory group input and interactive learning opportunities.

The oral health of adults with learning disabilities: A secondary analysis of the Adult Dental Health Survey 2009.

OBJECTIVES: Adults who have learning disabilities are a vulnerable group, little is known about their oral health and how this affects their quality of life. The aims of this secondary analysis of data from the 2009 Adult Dental Health Survey (ADHS) were to describe the oral health status of adults with learning disabilities, determine if severity of learning disability is associated with oral health and identify some of the methodological complexities of working with this population. The survey yields the most recent representative data on the oral health of adults with learning disabilities in England and importantly, contains information about oral health related quality of life (OHRQoL). BASIC RESEARCH DESIGN: Secondary analysis of data from a supplemental survey of adults with learning disabilities collected alongside the 2009 ADHS. PARTICIPANTS: 607 participants with a diagnosed learning disability aged 18 years and over. RESULTS: Adults with learning disabilities had similar levels of active dental caries, fewer natural teeth, and fewer fillings than comparable participants from the general population. Self-reported oral and general health were worse for adults with learning disabilities than the general population. Possible associations between the severity of learning disability and the numbers of decayed, missing or filled teeth were identified. However, large amounts of missing data limited the analysis. CONCLUSIONS: There are important questions relating to the accessibility of existing self-reported oral health questionnaires and the reliability of proxy-reported questions about OHRQoL that should be addressed to give a fuller picture of the oral health of adults with learning disabilities.

Predictors of Quality of Life Decline in Patients with Oligometastases treated with Stereotactic Ablative Radiotherapy: Analysis of the Population-Based SABR-5 Phase II Trial.

AIMS: Most patients experience stable quality of life (QoL) after stereotactic ablative radiotherapy (SABR) treatment for oligometastases. However, a subset of patients experience clinically relevant declines in QoL on post-treatment follow-up. This study aimed to identify risk factors for QoL decline. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases. Prospective QoL was measured using treatment site-specific tools at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. The time to persistent QoL decline was calculated as the time from SABR to the first decline in QoL score meeting minimum clinically important difference with no improvement to baseline score on subsequent assessments. Univariable and multivariable logistic regression analyses were carried out to determine factors associated with QoL decline. RESULTS: One hundred and thirty-three patients were included with a median follow-up of 32 months (interquartile range 25-43). Thirty-five patients (26%) experienced a persistent decline in QoL. The median time until persistent QoL decline was not reached. The cumulative incidence of QoL decline at 2 and 3 years were 22% (95% confidence interval 14.0-29.6) and 40% (95% confidence interval 28.0-51.2), respectively. In multivariable analysis, disease progression (odds ratio 5.23, 95% confidence interval 1.59-17.47, P = 0.007) and adrenal metastases (odds ratio 9.70, 95% confidence interval 1.41-66.93, P = 0.021) were associated with a higher risk of QoL decline. Grade 3 or higher (odds ratio 3.88, 95% confidence interval 0.92-16.31, P = 0.064) and grade 2 or higher SABR-associated toxicity (odds ratio 2.24, 95% confidence interval 0.85-5.91, P = 0.10) were associated with an increased risk of QoL decline but did not reach statistical significance. CONCLUSIONS: Disease progression and adrenal lesion site were associated with persistent QoL decline following SABR. The development of grade 3 or higher toxicities was also associated with an increased risk, albeit not statistically significant. Further studies are needed, focusing on the QoL impact of metastasis-directed therapies.

Exploring experiences of living with removable dentures-A scoping review of qualitative literature.

OBJECTIVE: Examine the literature on the experiences of living with removable dentures (complete or partial) to identify any gaps and provide a map for future research. BACKGROUND: Increasing proportions of society are living partially dentate with some form of restoration, including removable dentures. Previous studies have reported on the location, materials and usage of these prostheses, along with effects on oral-health-related quality of life (OHRQoL). However, less is known about experiences with removable dentures from a patient-centred perspective. METHODS: A scoping review of the qualitative literature was undertaken using the framework of Arksey and O'Malley, updated by Levac et al. Literature searches were carried out using Medline and Web of Science. Papers were screened by title and abstract using inclusion and exclusion criteria. Remaining papers were read in full and excluded if they did not meet the required criteria. Nine papers were included in the final review. FINDINGS: Key themes from these papers were: impact of tooth loss and living without teeth, and its impacts in relation to social position, appearance, confidence and function (chewing and speaking); social norms and tooth loss, including attitudes to tooth retention and treatment costs, and changes in intergenerational norms towards dentures; expectations of treatment, including patients being more involved in decision making, viewing the denture as a "gift" and dentures helping to achieve "an ideal"; living with a removable denture (complete or partial), including patient preparedness for a denture, adaptation and impacts on activities and participation; and the dentist-patient relationship, including issues with information and communication, and differing priorities between patients and dentists. CONCLUSION: Little qualitative research exists on experiences of living with a removable denture. Existing literature demonstrates the importance of dispersed activities in differing social, spatial and temporal contexts when wearing removable dentures. Focusing on processes of positive adaptation to dentures and OHRQoL, rather than deficits, is also required to fully understand patients' experiences. Additionally, more complex technological advances may not always be in the best interest of every patient.

Prospective Longitudinal Assessment of Quality of Life After Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-based SABR-5 Phase II Trial.

AIMS: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). RESULTS: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. CONCLUSIONS: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL.

Development and psychometric validation of the gum health experience questionnaire.

AIM: To develop and validate a new health-related quality of life measure to capture a wide range of gum-related impacts. MATERIALS AND METHODS: The measure was developed using a multi-stage approach and a theoretical model. Development involved semi-structured interviews, pilot testing, cross-sectional analysis among a general population (n = 152) to assess psychometric properties and test-retest reliability among a subsample (n = 27). RESULTS: Psychometric analysis supports the validity and reliability of the measure's impact scale. The measure has excellent internal reliability (nearly all item-total correlations above .4; Cronbach's alpha between .84 and .91 for subscales), with test-retest reliability also performing well (Intra-class correlation coefficient [ICC] of .91-.97 for subscales). Good content validity (indicated by large standard deviations for item and total scores) and construct validity (correlations of .54-.73 with global gum health rating for subscales, all p < .05) were also observed. Qualitative and quantitative data indicate that people with gum health-related symptoms experience different degrees of discomfort and impacts caused by their condition. CONCLUSIONS: The gum health experience questionnaire holds substantial promise as a measure of gum-related quality of life in people across the gum health-disease continuum. Further face validity, refining and reducing the number of items and longitudinal studies to test evaluative properties are required before the measure can be used with confidence.

Awareness, Knowledge, and Attitude Towards Urinary Tract Infections: An Appraisal From Saudi Arabia.

Introduction Urinary tract infections (UTIs) are a common global health issue, yet awareness and knowledge about UTIs among the general population can vary widely. This study aimed to assess the awareness, knowledge, and attitudes regarding UTIs among Saudi Arabian citizens residing in Al-Ahsa, Saudi Arabia. Methods A descriptive cross-sectional study was conducted among Saudi Arabian citizens aged 18 and above residing in Alhassa. A structured questionnaire was used to collect data on participants' awareness, knowledge, attitudes, and experiences related to UTIs. Data were analyzed using IBM® SPSS® Statistics. Results The study included 445 participants, predominantly males, with 279 (62.7%) and a range of educational backgrounds. Approximately 302 (70.1%) of the participants were aware of UTIs. However, misconceptions about the definition of UTI and its risk factors were common. Most participants recognized bacteria as the primary cause of UTIs, with 261 (58.7%) identifying this factor. Symptoms such as painful urination were recognized by 390 participants, which is a significant proportion. When experiencing UTI symptoms, 285 (66.1%) indicated they would go to the hospital. Significant associations were found between awareness, knowledge, and socio-demographic factors. Conclusion This study highlights the need for increased awareness and knowledge about UTIs among Saudi Arabian citizens in Alhassa. Tailored educational interventions are essential to correct misconceptions, promote accurate risk factor awareness, and encourage appropriate management strategies. Public health campaigns can contribute to reducing the burden of UTIs in the community.

New hominin dental remains from the ∼2.04-1.95 Ma Drimolen Main Quarry, South Africa.

BACKGROUND: The Drimolen Palaeocave site is situated within the UNESCO Fossil Hominid Sites of South Africa World Heritage Area and has yielded numerous hominin fossils since its discovery in 1992. Most of these fossils are represented by isolated dental elements, which have been attributed to either of two distinct hominin genera, Paranthropus and Homo. AIM: This paper provides morphological descriptions for a further 19 specimens that have been recovered from the ∼2.04-1.95 Ma Drimolen Main Quarry (DMQ) deposits since 2008. This paper also discusses the two primary hypotheses used to explain Paranthropus robustus variation: sexual dimorphism, and micro-evolution within a lineage. SUBJECTS AND METHODS: These 19 fossils are represented by 47 dental elements and expand the sample of DMQ early Homo from 13 to 15, and the sample of Paranthropus robustus from 69 to 84. RESULTS: The evidence presented in this paper was found to be inconsistent with the sexual dimorphism hypothesis. CONCLUSION: Some support was found for the micro-evolution hypothesis.

Inflammatory biomarker signatures in post-surgical drain fluid may detect anastomotic leaks within 48 hours of colorectal resection.

BACKGROUND: The optimal treatment of colorectal cancer is surgical resection and primary anastomosis. Anastomotic leak can affect up to 20% of patients and creates significant morbidity and mortality. Current diagnosis of a leak is based on clinical suspicion and subsequent radiology. Peritoneal biomarkers have shown diagnostic utility in other conditions and could be useful in providing earlier diagnosis. This pilot study was designed to assess the practical utility of peritoneal biomarkers after abdominal surgery utilising an automated immunoassay system in routine use for quantifying cytokines. METHODS: Patients undergoing an anterior resection for a rectal cancer diagnosis were recruited at University Hospital of Wales, Cardiff between June 2019 and June 2021. A peritoneal drain was placed in the proximity of the anastomosis during surgery, and peritoneal fluid was collected at days 1 to 3 post-operatively, and analysed using the Siemens IMMULITE platform for interleukin (IL)-1ß, IL-6, IL-10, CXCL8, tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). RESULTS: A total of 42 patients were recruited (22M:20F, median age 65). Anastomotic leak was detected in four patients and a further five patients had other intra-abdominal complications. The IMMULITE platform was able to provide robust and reliable results from the analysis of the peritoneal fluid. A metric based on the combination of peritoneal IL-6 and CRP levels was able to accurately diagnose three anastomotic leaks, whilst correctly classifying all negative control patients including those with other complications. CONCLUSIONS: This pilot study demonstrates that a simple immune signature in surgical drain fluid could accurately diagnose an anastomotic leak at 48 h postoperatively using instrumentation that is already widely available in hospital clinical laboratories.

Correlation between Multiparametric MR Imaging and Molecular Genetics in Pontine Pediatric High-Grade Glioma.

BACKGROUND AND PURPOSE: Molecular profiling is a crucial feature in the "integrated diagnosis" of CNS tumors. We aimed to determine whether radiomics could distinguish molecular types of pontine pediatric high-grade gliomas that have similar/overlapping phenotypes on conventional anatomic MR images. MATERIALS AND METHODS: Baseline MR images from children with pontine pediatric high-grade gliomas were analyzed. Retrospective imaging studies included standard precontrast and postcontrast sequences and DTI. Imaging analyses included median, mean, mode, skewness, and kurtosis of the ADC histogram of the tumor volume based on T2 FLAIR and enhancement at baseline. Histone H3 mutations were identified through immunohistochemistry and/or Sanger or next-generation DNA sequencing. The log-rank test identified imaging factors prognostic of survival from the time of diagnosis. Wilcoxon rank-sum and Fisher exact tests compared imaging predictors among groups. RESULTS: Eighty-three patients had pretreatment MR imaging and evaluable tissue sampling. The median age was 6 years (range, 0.7-17 years); 50 tumors had a K27M mutation in H3-3A, and 11, in H3C2/3. Seven tumors had histone H3 K27 alteration, but the specific gene was unknown. Fifteen were H3 wild-type. Overall survival was significantly higher in H3C2/3- compared with H3-3A-mutant tumors (P = .003) and in wild-type tumors compared with any histone mutation (P = .001). Lower overall survival was observed in patients with enhancing tumors (P = .02) compared with those without enhancement. H3C2/3-mutant tumors showed higher mean, median, and mode ADC_total values (P < .001) and ADC_enhancement (P < .004), with lower ADC_total skewness and kurtosis (P < .003) relative to H3-3A-mutant tumors. CONCLUSIONS: ADC histogram parameters are correlated with histone H3 mutation status in pontine pediatric high-grade glioma.

Substance use and medical outcomes in those age 50 and older involving cocaine and metamfetamine reported to United States poison centers.

CONTEXT: Cocaine and metamfetamine use and overdose deaths among United States adults have been increasing in recent years. We examined associations of medical outcomes with co-used opioids and other substances among cocaine, and metamfetamine exposures in people age ≥50 years (N = 9300) reported to the National Poison Data System, 2015-2021. METHODS: We first described increases in these exposures over time. We fitted generalized linear models for a Poisson distribution with a log link, one for cocaine exposures and the other for metamfetamine exposures, to examine associations of medical outcomes (major effects/death versus all others) with co-used other substances, controlling for exposure year and demographics. RESULTS: The number of exposures increased steadily during the seven years, but metamfetamine exposures increased more rapidly starting in 2018. One-fifth of cocaine and one-sixth of metamfetamine exposures suffered major effects/death. Co-use of prescription opioids (incident risk ratio = 2.00, 95% CI = 1.76-2.28 for cocaine; incident risk ratio = 1.62, 95% CI = 1.27-2.07 for metamfetamine), illicit fentanyl (incident risk ratio =1.88, 95% CI = 1.08-3.27 for cocaine; incident risk ratio = 2.05, 95% CI = 1.04-4.06 for metamfetamine), heroin (incident risk ratio =1.62, 95% CI = 1.37-1.90 for cocaine), or amfetamine (incident risk ratio =1.73, 95% CI = 1.28-2.33 for cocaine) was associated with a higher likelihood of major effects/death. DISCUSSION: Increases in the number of cocaine and metamfetamine exposures among older adults reported to poison centers are of concern, and so is the increased risk of major effects/death from polysubstance use, especially prescription and illicit opioids, among these illicit psychostimulant users. CONCLUSIONS: Healthcare provider screening of individuals at risk of cocaine and/or metamfetamine use and psychoeducation about the dangers of these substance use are needed.

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates.

Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.

Gum health and quality of life-subjective experiences from across the gum health-disease continuum in adults.

BACKGROUND: There has been a lack of qualitative work investigating the effects of the wide range of gum-related symptoms, and the perceived everyday impacts associated with these including on quality of life. While periodontal disease has been shown to have significant effects on quality of life, fewer studies have researched the perceived impacts of gingivitis and symptoms from across the entire gum health-disease continuum, despite evidence that these can also negatively affect quality of life. The aim of this study was to investigate perceived everyday impacts and explore the subjective experiences of adults with a variety of symptoms from across the self-reported gum health-disease continuum, and how these may affect quality of life. METHODS: Participants were recruited at a large UK University using purposive sampling, for self-reported symptoms ranging from mild gingivitis to severe periodontal disease. Semi-structured interviews gathered details on symptom history, changes occurring over time and associated beliefs, as well as perceived impacts on everyday life, and links between these experiences and identity. Interviews were analysed using framework analysis based on the Wilson and Cleary health-related quality of life model. RESULTS: Twenty-seven participants were recruited - 15 with symptoms of gingivitis, 12 with more severe periodontal symptoms. Prominent themes included description of symptoms, changes in daily life, social impacts, psychological impacts, identity, and overall impacts and quality of life. Differences were noted in severity, extent and frequency of symptoms and participant experiences, with greater perceived impacts often felt by those with periodontal disease. However, participants from across the gum health-disease continuum often expressed similar experiences and concerns. CONCLUSION: Findings demonstrate the range of experiences from participants with a variety of gum-related symptoms; notably, gingivitis was reported to have a range of perceived impacts on quality of life alongside those reported by periodontal disease sufferers. Future work should look to include symptoms from across the entire gum health-disease continuum when considering quality of life, as well as considering a more patient-centred approach which could be valuable in both clinical and research settings.

Validation of the Prognostic Utility of ESTRO/EORTC Oligometastatic Disease Classification: A Secondary Analysis From the Population-Based Phase II SABR-5 Trial.

PURPOSE: The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme. METHODS AND MATERIALS: The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling. RESULTS: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P < .001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS. CONCLUSIONS: In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required.

Polypharmacy and Healthcare Service Use Among Prescription Opioid Poisoning Cases Age 50.

Objectives: To examine relationships between polypharmacy and level of healthcare service use among prescription opioid poisoning cases age 50 and older. Methods: Data came from the American Association of Poison Control Center's National Poison Data System, 2015-2020. We used multinomial logistic regression to examine the study questions. Results: Of the 77 946 cases with prescription opioid exposures, 64.5% were managed at a healthcare facility (HCF). Of HCF-managed cases, 41.2% were treated/evaluated and released and 21.3% and 37.5% were admitted for noncritical care and critical care, respectively. Medications for cardiovascular disease, benzodiazepines, other types of sedatives/hypnotics, antipsychotics, muscle relaxants, acetaminophen, and gabapentin were associated with increased risk of admission to both noncritical and critical care compared to treatment/evaluation and release. Acetaminophen use had the highest relative risk ratios (RRRs) for noncritical care (1.70, 95% CI = 1.51-1.91) and critical care (1.56, 95% CI = 1.39-1.76). Each additional medication/substance used was associated with 1.14 (95% CI = 1.11-1.17) and 1.19 (95% CI = 1.16-1.22) greater risk of noncritical and critical care admissions, respectively. Conclusions: Among older-adult poison control center cases for prescription opioid exposures, co-use of several commonly prescribed/used medicines was associated with increased risk of admissions to both noncritical and critical care units. Careful monitoring of medication use among older adults who use prescription opioids may reduce the risk of unintentional and intentional opioid poisoning.