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INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p

BACKGROUND: Spinal cord stimulation (SCS) is an established chronic pain treatment, but the effectiveness of traditional, open-loop paradigms has been plagued by variable sustainability in a real-world setting. A new approach, utilizing evoked compound action potential (ECAP) controlled closed-loop (CL) SCS, continuously monitors spinal cord activation and automatically adjusts the stimulation amplitude of every pulse, maintaining stimulation at the prescribed ECAP level through this continual feedback mechanism. Recent studies demonstrated the long-term safety and efficacy of ECAP-controlled CL-SCS. Here, we report the design of a prospective, multicenter, single-arm feasibility study to characterize clinical outcomes in a real-world chronic pain population utilizing ECAP-controlled CL-SCS. Objective neurophysiological measurements such as device performance and patient therapy compliance, will be analyzed against baseline biopsychosocial assessments, to explore the clinical utility of these objective physiologic biomarkers in patient phenotyping. METHODS: This study will enroll up to 300 subjects with chronic, intractable trunk and/or limb pain in up to 25 United States investigation sites. Subjects meeting eligibility criteria will undergo a trial procedure and a permanent implant following a successful trial. Neurophysiological measurements (measured in-clinic and continuously during home use) and clinical outcomes including pain, quality-of-life, psychological, emotional, and functional assessments will be collected at baseline, trial end, and up to 24-months post-implantation. DISCUSSION: Associations between objective neurophysiological data, clinical evaluation and patient-reported outcomes may have important clinical and scientific implications. They may provide novel insights about the chronic pain pathophysiology, its modulation during CL-SCS, and identification of pain phenotypes and/or mechanisms associated with treatment response during SCS trials and long-term therapy. Data from the ECAP study could lead to improvements in diagnosis, assessment, patient identification and management of chronic pain. It could also provide the foundation for development of a new SCS treatment approach customized by the patients pain phenotype, unique neurophysiology, and disease severity.

INTRODUCTION: Chronic pain is a major public health concern, as is the associated use of opioid medications, highlighting the importance of alternative treatments, such as spinal cord stimulation (SCS). Here, we present the final 24-month results of the Avalon study, which investigated the use of the first closed-loop SCS system in patients with chronic pain. The system measures the evoked compound action potentials (ECAPs) elicited by each stimulus pulse and drives a feedback loop to maintain the ECAP amplitude near constant. METHODS: Fifty patients were implanted with the Evoke system (Saluda Medical) and followed over 24-months. Pain, quality of life (QOL), function, sleep, and medication use were collected at baseline and each scheduled visit. ECAP amplitudes and programming adjustments were also monitored. RESULTS: At 24 months, responder rates (≥ 50% pain reduction) and high responder rates (≥ 80% pain reduction) for overall pain were 89.5% and 68.4%, respectively, the latter up from 42.2% at 3 months. Significant improvements from baseline were observed in QOL, function, and sleep over the 24 months, including ≥ 80% experiencing a minimally important difference in QOL and > 50% experiencing a clinically significant improvement in sleep. At 24 months, 82.8% of patients with baseline opioid use eliminated or reduced their opioid intake. Over the course of the study, reprogramming need fell to an average of less than once a year. CONCLUSION: Over a 24-month period, the Evoke closed-loop SCS maintained its therapeutic efficacy despite a marked reduction in opioid use and steady decrease in the need for reprogramming.

This article examines the implications of the transition to online or blended learning for first generation scholars (FGS) brought about by COVID-19. We present the findings of a mixed methods project that draws data from both in-depth qualitative interviews and a large quantitative survey of students at Durham University. We offer a comparative analysis of how FGS contrast to the general student body in relation to a range of key challenges that COVID-19 and the consequent 'online pivot' posed to university life including technological, social and resource based issues. Our findings demonstrate that FGS were particularly affected by this shift to online or blended learning. The final substantive section discusses a range of potential mitigation strategies adopted by the School of Government and International Affairs, Durham University, with the assumption that some, at least, of these, and our data, will be of wider relevance in the sector.

BACKGROUND: Spinal cord stimulation (SCS) activates the dorsal column fibers using electrical stimuli. Current SCS systems function in fixed-output mode, delivering the same stimulus regardless of spinal cord (SC) activation. OBJECTIVE: To present long-term outcomes of a novel closed-loop SCS system that aims to maintain the SC activation near a set target level and within a therapeutic window for each patient. SC activation is measured through the evoked compound action potential (ECAP) generated by each stimulus pulse. METHODS: Fifty patients with lower back and/or leg pain who were successfully trialed received a permanent system (Evoke; Saluda Medical, Sydney, Australia). Ratings of pain (visual analog scale), quality of life, function, sleep, and medication use were collected at baseline and at each visit. SC activation levels were reported in summary statistics. The therapeutic window for each individual patient was defined as the range of ECAP amplitudes between sensation threshold and uncomfortably strong stimulation. RESULTS: At 12 mo, the proportion of patients with ≥50% relief was 76.9% (back), 79.3% (leg), and 81.4% (overall), and the proportion with ≥80% pain relief was 56.4% (back), 58.6% (leg), and 53.5% (overall). Patients spent a median of 84.9% of their time with stimulation in their therapeutic window, and 68.8% (22/32) eliminated or reduced their opioid intake. Statistically significant improvements in secondary outcomes were observed. CONCLUSION: The majority of patients experienced more than 80% pain relief with stable SC activation, as measured by ECAP amplitude at 12 mo, providing evidence for the long-term effectiveness of the Evoke closed-loop SCS system.

The Moscow Mule cocktail, which contains ginger beer, lime juice, and vodka, is commonly served in a copper mug. There has been increasing concern that copper can leach into the cocktail, given the acidic nature of the drink. Under the experimental conditions studied, copper does leach from the copper mug into the beverage. We observed copper leaching into the cocktail solution at a rate of 0.048 [+ or -] 7 * [10.sup.-4] ppm copper/min at room temperature. The leaching rate was found to be dependent on the acidity of the solution (increasing at lower pH) and molecular oxygen content. We quantified the copper concentration using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The rate of copper leaching into the Moscow Mule cocktail was found to be significant and accumulated copper concentration exceeds the U.S. Environmental Protection Agency standards for drinking water within 27 minutes (World Health Organization, 2004). Any risk posed by the accumulation of copper, however, can be mitigated by serving the Moscow Mule cocktail in a copper mug lined with stainless steel to avoid direct contact of the acidic liquid with the copper surface directly, as stipulated by the Food and Drug Administration model Food Code., Introduction Identifying the conditions under which potentially hazardous chemical agents, such as metal ions, are released from surfaces in contact with foodstuffs and beverages is an important first step in [...]

The National Institute of Justice reported that current methods for processing sexual assault samples have a high failure rate, with 60 to 80 percent of tested kits unable to produce usable DNA profiles. Even when samples test positive for male DNA, 34 percent of sexual assault kits (SAKs) do not yield recovered male DNA after differential extraction. Less than 30% recovery of available sperm DNA contributes to this low success rate. The SpermX™ method (SX) has been shown to recover 80 percent or more of sperm DNA from sexual assault samples. An interlaboratory evaluation compared SX to standard differential extraction (DE) protocols. Mock samples with known ratios of female epithelial cells and sperm cells were processed using both methods. Results revealed that SX consistently provided CODIS up-loadable DNA profiles, even with as few as 25 sperm cells, whereas DE failed to produce usable results. On average, SX yielded a seven-fold increase in the recovery of unshared male alleles compared to DE. In conclusion, SX outperformed DE in recovering higher quantities of male DNA with minimal female carryover in sexual assault-type samples. This improved success rate in obtaining usable DNA profiles can significantly aid in solving sexual assault cases. [ABSTRACT FROM AUTHOR]

Since Y‐STR typing only amplifies male Y chromosomal DNA, it can simplify the interpretation of some DNA mixtures that contain female DNA. However, if there are multiple male contributors, mixed Y‐STR DNA profiles will often be obtained. Y‐STR mixture analysis cases are particularly challenging though as, currently, there are no validated probabilistic genotyping (PG) software solutions commercially available to aid in their interpretation. One approach to fully deconvoluting these challenging mixtures into their individual donors is to conduct single‐cell genotyping by isolating individual cells from a mixture prior to conducting DNA typing. In this work, a physical micromanipulation technique involving a tungsten needle and direct PCR with decreased reaction volume and increased cycle number was applied to equimolar 2‐ and 3‐person buccal cell male DNA mixtures and a mock touch DNA case scenario involving the consecutive firing of a handgun by two males. A consensus DNA profiling approach was then utilized to obtain YFiler™ Plus Y‐STR haplotypes. Buccal cells were used to optimize and test the direct single‐cell subsampling approach, and 2–3 person male buccal cell mixtures were fully deconvoluted into their individual donor Y‐STR haplotypes. Single‐cell (or agglomerated cell clump) subsampling from the gun's trigger recovered single‐source Y‐STR profiles from both individuals who fired the gun, the owner, and the other unrelated male. Only the non‐owner's DNA was found in the cells recovered from the handle. In summary, direct single‐cell subsampling as described represents a potential simple way to analyze and interpret Y‐STR mixtures. [ABSTRACT FROM AUTHOR]