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CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2-19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3-10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI -2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.

We present the results of a search for 10-1000 GeV neutrinos from 2268 gamma-ray bursts (GRBs) over 8 yr of IceCube-DeepCore data. This work probes burst physics below the photosphere where electromagnetic radiation cannot escape. Neutrinos of tens of giga electronvolts are predicted in sub-photospheric collision of free-streaming neutrons with bulk-jet protons. In a first analysis, we searched for the most significant neutrino-GRB coincidence using six overlapping time windows centered on the prompt phase of each GRB. In a second analysis, we conducted a search for a group of GRBs, each individually too weak to be detectable, but potentially significant when combined. No evidence of neutrino emission is found for either analysis. The most significant neutrino coincidence is for Fermi-GBM GRB bn 140807500, with a p-value of 0.097 corrected for all trials. The binomial test used to search for a group of GRBs had a p-value of 0.65 after all trial corrections. The binomial test found a group consisting only of GRB bn 140807500 and no additional GRBs. The neutrino limits of this work complement those obtained by IceCube at tera electronvolt to peta electronvolt energies. We compare our findings for the large set of GRBs as well as GRB 221009A to the sub-photospheric neutron-proton collision model and find that GRB 221009A provides the most constraining limit on baryon loading. For a jet Lorentz factor of 300 (800), the baryon loading on GRB 221009A is lower than 3.85 (2.13) at a 90% confidence level.

IceCube alert events are neutrinos with a moderate-to-high probability of having astrophysical origin. In this study, we analyze 11 yr of IceCube data and investigate 122 alert events and a selection of high-energy tracks detected between 2009 and the end of 2021. This high-energy event selection (alert events + high-energy tracks) has an average probability of ≥0.5 of being of astrophysical origin. We search for additional continuous and transient neutrino emission within the high-energy events’ error regions. We find no evidence for significant continuous neutrino emission from any of the alert event directions. The only locally significant neutrino emission is the transient emission associated with the blazar TXS 0506+056, with a local significance of 3σ, which confirms previous IceCube studies. When correcting for 122 test positions, the global p-value is 0.156 and compatible with the background hypothesis. We constrain the total continuous flux emitted from all 122 test positions at 100 TeV to be below 1.2 × 10−15 (TeV cm2 s)−1 at 90% confidence assuming an E −2 spectrum. This corresponds to 4.5% of IceCube’s astrophysical diffuse flux. Overall, we find no indication that alert events in general are linked to lower-energetic continuous or transient neutrino emission.

The Hydra nervous system is the paradigm of a simple nerve net. Nerve cells in Hydra, as in many cnidarian polyps, are organized in a nerve net extending throughout the body column. This nerve net is required for control of spontaneous behavior: elimination of nerve cells leads to polyps that do not move and are incapable of capturing and ingesting prey (Campbell, 1976). We have re-examined the structure of the Hydra nerve net by immunostaining fixed polyps with a novel antibody that stains all nerve cells in Hydra. Confocal imaging shows that there are two distinct nerve nets, one in the ectoderm and one in the endoderm, with the unexpected absence of nerve cells in the endoderm of the tentacles. The nerve nets in the ectoderm and endoderm do not contact each other. High-resolution TEM (transmission electron microscopy) and serial block face SEM (scanning electron microscopy) show that the nerve nets consist of bundles of parallel overlapping neurites. Results from transgenic lines show that neurite bundles include different neural circuits and hence that neurites in bundles require circuit-specific recognition. Nerve cell-specific innexins indicate that gap junctions can provide this specificity. The occurrence of bundles of neurites supports a model for continuous growth and differentiation of the nerve net by lateral addition of new nerve cells to the existing net. This model was confirmed by tracking newly differentiated nerve cells.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

Invention activities and worked solutions are considered to be effective learning tasks. To date, limited research has been conducted regarding these tasks in teacher education and the process of solving these tasks. This study focuses on the solution quality of student teachers' task solutions. 149 students were randomly assigned to one of two experimental conditions: invention activity and worked solution. The latter group were given a set of categories; the former group had to invent their own categories to compare two constructed contrasting auditive cases with a focus on the subject classroom management. To determine whether it is more effective to compare cases with given categories (worked solution) or with self-generated categories (invention activity), we coded the 149 solutions regarding the content-related solution quality using qualitative content analysis. Students in the worked solution condition demonstrated a significantly higher content-related solution quality than those in the invention activity condition. Thus, it may be assumed that students of the worked solution gained a better conceptual understanding of classroom management through working on this task. Implications for the use of this task format in teacher education are discussed.

The IceCube Neutrino Observatory instruments about 1ĝ€¯km3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.

BACKGROUND: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. METHODS: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. RESULTS: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2-161.5], p = 0.0028). Similarly, oxygenation index decreased by - 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus - 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI - 8.6 to - 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5-47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. CONCLUSIONS: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Ample research has demonstrated that electrocoagulation is a versatile technology capable of facilitating the removal of a wide range of physical, biological, organic, and inorganic constituents such as suspended solids, turbidity, bacteria, viruses, oil and grease, organic carbon (including chemical and biological oxygen demand), silica, fluoride, and so on. Despite its purported advantages and extensive lab-scale evaluations, it has not yet been widely adopted for water and wastewater treatment and reuse at commercial scale. This is symptomatic of a chasm between its technological capabilities on one hand and field performance and reputation on the other. Herein, we opine as to why this might be the case using our collective experiences with the oil and gas industry as an exemplar. We highlight scientific, technological, engineering, and business issues that need to be addressed to realize the full potential of this promising technology.

The LIGO/Virgo collaboration published the catalogs GWTC-1, GWTC-2.1, and GWTC-3 containing candidate gravitational-wave (GW) events detected during its runs O1, O2, and O3. These GW events can be possible sites of neutrino emission. In this paper, we present a search for neutrino counterparts of 90 GW candidates using IceCube DeepCore, the low-energy infill array of the IceCube Neutrino Observatory. The search is conducted using an unbinned maximum likelihood method, within a time window of 1000 s, and uses the spatial and timing information from the GW events. The neutrinos used for the search have energies ranging from a few GeV to several tens of TeV. We do not find any significant emission of neutrinos, and place upper limits on the flux and the isotropic-equivalent energy emitted in low-energy neutrinos. We also conduct a binomial test to search for source populations potentially contributing to neutrino emission. We report a nondetection of a significant neutrino-source population with this test.

The energy transition towards a more sustainable and renewable future is a pivotal global endeavor. Central to this shift for the United States is the critical role of domestically sourced lithium, a key mineral in the production of high-performance batteries essential for electric vehicles and renewable energy storage systems. This has driven the United States to invest heavily in a domestic supply chain for battery-grade lithium to enhance energy security, reduce supply chain vulnerabilities, and foster economic growth by tapping into local resources. A notable example is the Biden Administration’s “American Battery Materials Initiative,” which was included in the $2.8-billion Bipartisan Infrastructure Law (The White House, 2022). The “Salton Sea Known Geothermal Resource Area” in Imperial County, California has been identified as a potential domestic U.S. resource of lithium due to the brine-hosted lithium in the deep subsurface geothermal reservoir. An analysis funded by the U.S. Department of Energy provides an overview of opportunities and challenges associated with developing the lithium resource in the Salton Sea geothermal reservoir, as well as potential environmental and societal impacts to the county and surrounding region. The geologic history of the region suggests that lithium in the subsurface brines could have come from multiple sources, including water and sediments from the Colorado River, which have been periodically deposited over the past several million years; rocks from the mountain ranges surrounding the Imperial Valley; and lithium-bearing volcanic rocks and igneous intrusions from past geologic events. Further, several processes may have concentrated lithium in the brine over time, including evaporative concentration of lithium-bearing water that flowed into the basin and leaching of lithium from the sediments and rocks by the circulating geothermal brines. Geothermal brine production at the Salton Sea Geothermal Field, the area with existing geothermal power plants, has averaged just over 120 million metric tons per year since 2004. Using an approximate lithium brine concentration of 198 parts per million (ppm), the amount of dissolved lithium contained in these produced brines is estimated to be 127,000 metric tons of lithium carbonate equivalent (LCE) per year. The total dissolved lithium content in the well-characterized portion of the Salton Sea Geothermal Reservoir is estimated at 4.1 million metric tons of LCE, and the estimated total resource increases to 18 million metric tons of LCE if assumptions for porosity and total reservoir size are increased to reflect the probable resource extent. Analysts measured lithium concentrations in the reservoir rocks, which were shown to vary with depth and mineralogy. These data were used to help refine conceptual and computer models of the reservoir; specifically, two complementary computer models of the reservoir were developed. Analysts used the first model to simulate the approximate 30-year history of geothermal power production in the area using historical production and reinjection data, then used that model to simulate a 30-year forecasting period. This forecast assumed continued production and reinjection rates at current levels but removes 95% of the lithium from the produced geothermal brine starting January 1, 2024. The model found that lithium recovery declines by more than half, from 0.8 to 0.3 kilograms per second (kg/s). Forecast scenarios that are optimized to both recover lithium and harness geothermal energy are expected to sustain lithium production rates much more effectively.The second model included more detailed simulations of the movement of brine and chemical reactivity of lithium within the reservoir. It showed that the reactions of relatively stable lithium-bearing minerals are slow, and that the primary replenishment mechanism for lithium in the brines is the upward flux of convecting lithium-rich brine from below the producing reservoir. However, these replenishment rates are not fast enough to produce significant increases in lithium, which could limit the long-term sustainability of the lithium resource. It is important to note that these models are preliminary and are based on current understanding of fluid replenishment rates, the minerals present in the geothermal system, and their chemical properties and reactivity. Further work should be undertaken to improve them and the associated predictions. The report also considered potential impacts on regional water resources, air quality, chemical use, and solid waste disposal needs, as well as the seismic risk associated with geothermal power production and lithium extraction activity. These investigations highlighted the need to proceed with good monitoring and verification systems and with appropriate mitigation technologies. However, the analysis illustrates that if these things are done properly, lithium development is not likely to create significant negative environmental impacts.Specifically, expanding geothermal energy production and lithium extraction will have a modest impact on water availability in the region. Initial estimates suggested that ~3% of historically available water supply for the region would be needed for currently proposed geothermal energy and lithium recovery operations; the majority of current water usage is for agriculture. It is not anticipated that expanding geothermal capacity or lithium production would impact the availability or quality of water used for human consumption and will not directly affect the water quality of the Salton Sea. However, the long-term drought conditions in the western United States may restrict future availability of water to the region, which is sourced from the Colorado River.In terms of regional air emissions of all pollutants identified in the analysis (particulate matter, hydrogen sulfide, ammonia, and benzene, expanding geothermal energy and adding lithium extraction overall have a small impact. Chemical use involved in geothermal power production and lithium extraction is consistent with chemical use in industrial settings, and the analysis did not identify any persistent organic pollutants or acutely toxic chemicals among those currently being used. Moving fluids within the subsurface can impact subsurface pressures and stresses, potentially triggering seismic activity. Early in geothermal energy production, increasing seismicity rates in the Salton Sea Geothermal Field correlated strongly with energy production activity; however, that correlation weakened after 1996. Even following the onset of geothermal energy production, seismic hazard in the Salton Sea Geothermal Field has not increased beyond that of the surrounding region.In addition to technical outcomes from the analysis, the report describes an initial effort to incorporate community engagement into lithium research by understanding the local context and priorities and identifying how to effectively communicate to share information and gather feedback. The report includes information about the social and historical context of the region to enable a more holistic understanding of the resource and its potential impact, and identifies key community questions by observing public meetings, visiting the region, and consulting with local organizations. The report provides recommendations about how future research efforts can address community concerns and implement more community-engaged practices. These include developing formal partnerships with local organizations and establishing a community advisory board to facilitate ongoing dialogue and opportunities for feedback. The future work will build on and further refine the models and scenarios presented in the report and strive to deepen engagement with local communities.

Dark matter particles in the Galactic Center and halo can annihilate or decay into a pair of neutrinos producing a monochromatic flux of neutrinos. The spectral feature of this signal is unique and it is not expected from any astrophysical production mechanism. Its observation would constitute a dark matter smoking gun signal. We performed the first dedicated search with a neutrino telescope for such signal, by looking at both the angular and energy information of the neutrino events. To this end, a total of five years of IceCube's DeepCore data has been used to test dark matter masses ranging from 10 GeV to 40 TeV. No significant neutrino excess was found and upper limits on the annihilation cross section, as well as lower limits on the dark matter lifetime, were set. The limits reached are of the order of 10-24 cm3/s for an annihilation and up to 1027 s for decaying dark matter. Using the same data sample we also derive limits for dark matter annihilation or decay into a pair of Standard Model charged particles.

We present a catalog of likely astrophysical neutrino track-like events from the IceCube Neutrino Observatory. IceCube began reporting likely astrophysical neutrinos in 2016, and this system was updated in 2019. The catalog presented here includes events that were reported in real time since 2019, as well as events identified in archival data samples starting from 2011. We report 275 neutrino events from two selection channels as the first entries in the catalog, the IceCube Event Catalog of Alert Tracks, which will see ongoing extensions with additional alerts. The Gold and Bronze alert channels respectively provide neutrino candidates with a 50% and 30% probability of being astrophysical, on average assuming an astrophysical neutrino power-law energy spectral index of 2.19. For each neutrino alert, we provide the reconstructed energy, direction, false-alarm rate, probability of being astrophysical in origin, and likelihood contours describing the spatial uncertainty in the alert's reconstructed location. We also investigate a directional correlation of these neutrino events with gamma-ray and X-ray catalogs, including 4FGL, 3HWC, TeVCat, and Swift-BAT.

Residual fragments can remain after kidney stone extraction which may necessitate another intervention. A new approach needs to be developedis needed to lower the risk of disease severe side effects caused by these fragments. Magnetic nanoparticles can be applied due to their properties of being able to bind to residual fragments and to be extracted by an external magnetic field. Fractals and magnetic nanoparticles have been synthesized and characterized thoroughly. The small nanoparticles bind covalently to the kidney stones and a magnetic extraction of calcium oxalate fractals with magnetic nanoparticles is possible. The aggregation of nanoscale iron oxide nanoparticles can be induced with the addition of salt which improves the extraction process. The separation is validated by simulation and experimentally in a porcine kidney as well as in artificial kidney models. This proof-of-concept study successfullyis the fundament for a new waydemonstrated of extracting kidney stones extraction and including their fractals and might pave the way for new procedures in urology.

While it has been demonstrated that invasive alien plants pose a threat to co-occurring wild-growing native plants by attracting their pollinators, we know almost nothing about their impact on crop pollination. Alien plants with attractive flowers sometimes occur close to crops and may influence yields when they share the same pollinators and have overlapping flowering periods. We present the results of an experiment on the impact of alien balsam (Impatiens glandulifera) on the pollination of cherry tomato (Solanum lycopersicum var. cerasiforme). We verified whether balsam decreases the number of insect visits to the tomato flowers or, conversely, whether balsam may have a positive influence on the pollination rate of the crop. We also assessed crop production with and without the insect visitors. The study was conducted in southern Poland under garden and greenhouse experimental conditions simulating small-scale cultivation of the crop with a neighbouring patch of the alien plant. The studied plants were exposed to insects visiting flowers of the following variants: only one of the two species was exposed or both species were exposed together. Moreover, two factors that may influence insect visits in flowers were assessed: the chemical composition of the floral scent that attracts insects and floral pathogens infesting pollinators that may deter them. The number of insect visits (mainly Bombus pascuorum) on the tomato flowers decreased significantly when the plants were exposed to the alien balsam. Moreover, alien balsam secreted more flower attractants (mainly fatty acids and their esters) than tomatoes, which could explain more frequent insect visits in balsam flowers. However, the floral pathogens probably had a negligible impact on the number of insect visits to the flowers of the two plants. The level of infestation on both studied species was relatively low (I. glandulifera: 5.1% of all pathogen colonies grown in a laboratory, S. lycopersicum var. cerasiforme: 4.2% and 2.6% of all colonies in the garden and greenhouse, respectively) and we found no pathogens known to infect pollinators. It should be noted, however, that some of these pathogens (e.g. Botrytis cinerea, Fusarium oxysporum and Sclerotinia sclerotiorum) are known to cause severe diseases in many crops. Our results revealed that the presence of attractive invasive alien species near small-scale cultivations may negatively affect crop pollination, resulting in smaller fruit size and irregular shape. The impact of such alien species on crop production and the agricultural economy on a large scale requires further study.

Abstract Chronic heart failure (CHF) is one of the most common diseases with a prevalence of 1–2% in adults, disproportionately affecting the elderly. Despite consistent drug therapy, physical activity (PA) is an integral part of current guidelines. Yet adherence to regular PA and exercise interventions is poor and potential predictors and barriers to PA remain elusive. We examined the effects of a telemonitoring-based exercise intervention in 699 CHF patients in a prospective, randomized-controlled (1:1), multicenter trial. The study was registered in the German Clinical Trials Register under DRKS00019022 on 28.05.2020. For both, the exercise and control group, self-reported PA (MET*h/week) increased and sedentary behavior declined during the 12-month intervention period. In the exercise group, daily step count as analyzed via activity trackers remained stable (pre: 6459 [4016] steps/day, post: 6532 [3858] steps/day; p = 0.621). The average number of completed exercise instruction videos provided via an online application was 1.50 [1.44] videos/week at the beginning and gradually decreased to 1.00 [1.50] videos/week; p

Abstract Background In recent studies, receipt of chiropractic care has been associated with lower odds of receiving prescription opioids and, among those already prescribed, reduced doses of opioids among patients with non-cancer spine pain. These findings suggest that access to chiropractic services may reduce reliance on opioids for musculoskeletal pain. Objective To assess the impact of chiropractic care on initiation, or continued use, of prescription opioids among patients with non-cancer spine pain. Methods We will search for eligible randomized controlled trials (RCTs) and observational studies indexed in MEDLINE, Embase, AMED, CINAHL, Web of Science, and the Index to Chiropractic Literature from database inception to June 2024. Article screening, data extraction, and risk-of-bias assessment will be conducted independently by pairs of reviewers. We will conduct separate analyses for RCTs and observational studies and pool binary outcomes (e.g. prescribed opioid receipt, long-term opioid use, and higher versus lower opioid dose) as odds ratios (ORs) with associated 95% confidence intervals (CIs). When studies provide hazard ratios (HRs) or relative risks (RRs) for time-to-event data (e.g. time-to-first opioid prescription) or incidence rates (number of opioid prescriptions over time), we will first convert them to an OR before pooling. Continuous outcomes such as pain intensity, sleep quality, or morphine equivalent dose will be pooled as weighted mean differences with associated 95% CIs. We will conduct meta-analyses using random-effects models and explore sources of heterogeneity using subgroup analyses and meta-regression. We will evaluate the certainty of evidence of all outcomes using the GRADE approach and the credibility of all subgroup effects with ICEMAN criteria. Our systematic review will follow the PRISMA statement and MOOSE guidelines. Discussion Our review will establish the current evidence informing the impact of chiropractic care on new or continued prescription opioid use for non-cancer spine pain. We will disseminate our results through peer-reviewed publication and conference presentations. The findings of our review will be of interest to patients, health care providers, and policy-makers. Trial registration Systematic review registration: PROSPERO CRD42023432277.

Abstract Controlling many-body interactions in two-dimensional systems remains a formidable task from the perspective of both fundamental physics and application. Here, we explore remarkable electronic structure alterations of MoS2 monolayer islands on graphene on Ir(111) induced by non-invasive self-intercalation. This introduces significant differences in morphology and strain of MoS2 as a result of the modified interaction with the substrate. Consequently, considerable changes of the band gap and non-rigid electronic shifts of valleys are detected, which are a combined effect of the screening of the many-body interactions and strain in MoS2. Furthermore, theory shows that each substrate leaves a unique stamp on the electronic structure of two-dimensional material in terms of those two parameters, restricted by their correlation.

Training helps to maintain and improve sufficient muscle function, body control, and body coordination. These are important to reduce the risk of fracture incidents caused by falls, especially for the elderly or people recovering from injury. Virtual reality training can offer a cost-effective and individualized training experience. We present an application for the HoloLens 2 to enable musculoskeletal training for elderly and impaired persons to allow for autonomous training and automatic progress evaluation. We designed a virtual downhill skiing scenario that is controlled by body movement to stimulate balance and body control. By adapting the parameters of the ski slope, we can tailor the intensity of the training to individual users. In this work, we evaluate whether the movement data of the HoloLens 2 alone is sufficient to control and predict body movement and joint angles during musculoskeletal training.We record the movements of 10 healthy volunteers with external tracking cameras and track a set of body and joint angles of the participant during training. We estimate correlation coefficients and systematically analyze whether whole body movement can be derived from the movement data of the HoloLens 2. No participant reports movement sickness effects and all were able to quickly interact and control their movement during skiing. Our results show a high correlation between HoloLens 2 movement data and the external tracking of the upper body movement and joint angles of the lower limbs.

Abstract Background Four out of five people living with osteoarthritis (OA) also suffer with at least one other long-term health condition. The complex interaction between OA and multiple long-term conditions (MLTCs) can result in difficulties with self-care, restricted mobility, pain, anxiety, depression and reduced quality of life. The aim of the MulTI-domain Self-management in Older People wiTh OstEoarthritis and Multi-Morbidities (TIPTOE) trial is to evaluate the clinical and cost-effectiveness of the Living Well self-management support intervention, co-designed with people living with OA, integrated into usual care, in comparison to usual care alone. Methods TIPTOE is a multi-centre, two-arm, individually randomised controlled trial where 824 individuals over 65 years old with knee and/or hip joint pain from their OA affected joint and at least one other long-term health condition will be randomised to receive either the Living Well Self-Management support intervention or usual care. Eligible participants can self-refer onto the trial via a website or be referred via NHS services across Wales and England. Those randomised to receive the Living Well support intervention will be offered up to six one-to-one coaching sessions with a TIPTOE-trained healthcare practitioner and a co-designed book. Participants will be encouraged to nominate a support person to assist them throughout the study. All participants will complete a series of self-reported outcome measures at baseline and 6- and 12-month follow-up. The primary outcome is symptoms and quality of life as assessed by the Musculoskeletal Health Questionnaire (MSK-HQ). Routine data will be used to evaluate health resource use. A mixed methods process evaluation will be conducted alongside the trial to inform future implementation should the TIPTOE intervention be found both clinically and cost-effective. An embedded ‘Study Within A Project’ (SWAP) will explore and address barriers to the inclusion of under-served patient groups (e.g. oldest old, low socioeconomic groups, ethnic groups). Discussion TIPTOE will evaluate the clinical and cost-effectiveness of a co-designed, living well personalised self-management support intervention for older individuals with knee and/or hip OA and MLTCs. The trial has been designed to maximise inclusivity and access. Trial registration ISRCTN 16024745 . Registered on October 16, 2023.

Abstract Background Despite comparatively low rates of COVID-19 admissions and recorded deaths in sub-Saharan Africa (SSA), the pandemic still had significant impact on health service utilization (HSU). The aim of this scoping review is to synthesize the available evidence of HSU in SSA during the pandemic, focusing on types of studies, changes in HSU compared with the pre-pandemic period, and changes among specific patient groups. Methods The scoping review was guided by the methodological framework for conducting scoping reviews developed by Arksey and O’Malley. We identified relevant studies through a search of PubMed (MEDLINE), Embase, Scopus, and Web of Science. We then provided a general descriptive overview of the extracted data focusing on the types of studies, patient groups, and change in HSU. Results We identified 262 studies reporting on HSU in 39 SSA countries. Studies were mainly quantitative (192; 73.3%), involving multiple centers (163; 62.2%), conducted in hospitals (205; 78.2%), and in urban settings (121; 46.2%). The median number of participants was 836.5 (IQR: 101.5–5897) involving 62.5% females. Most studies (92; 35.1%) focused on communicable diseases and mainly among outpatients (90; 34.2%). Maternal and child health studies formed the largest patient group (58; 22.1%) followed by people living with HIV (32; 12.2%). Change in HSU was reported in 249 (95.0%) studies with 221 (84.4%) studies reporting a decrease in HSU. The median decrease in HSU was 35.6% (IQR: 19.0–55.8) and median increase was 16.2% (IQR: 9.1–31.9). The patient group with the largest percentage decrease was cardiovascular diseases (68.0%; IQR: 16.7–71.1) and the lowest percentage decrease was in patients with infections (27.0%; IQR: 16.6–45.6). Conclusions A large body of literature is available on the effects of the pandemic on HSU in SSA. Most studies report decreases in HSU during the pandemic. However, patterns differ widely across disease categories, patient groups, and during different time periods of the pandemic.

Introduction: The World Health Organization (WHO) has proposed to monitor intrinsic capacity (IC) in the older population as a public health strategy through the Integrated Care for Older People (ICOPE) program. Although the program has been developed based on solid concepts, scientific evidence on its practical applicability is still scarce. Objectives: To evaluate IC in Brazilian older adults, its progress over time, and its association with sociodemographic and health factors and outcomes. To evaluate the psychometric properties of the WHO/ICOPE screening tool. Methods: This is a prospective multicenter cohort study with a 36-month follow-up. We will recruit 3838 people aged ≥ 60 years, registered in the health care units included in the study by the participating centers. We will collect sociodemographic and health data and will administer tools to assess IC domains, both those provided for in the ICOPE screening tool and the sequence of confirmatory assessments provided for in the program. Participants will be reassessed every 6 months for 36 months. Expected results: To establish the profile of IC in the study population and to understand its progress and the variables associated with the clinical outcomes of interest. To reveal the diagnostic and psychometric properties of the WHO/ICOPE screening tool. The project is funded by the Brazilian National Council for Scientific and Technological Development (CNPq). Relevance: Understanding the potential use of the ICOPE public health strategy proposed by the WHO within the scope of the Brazilian Unified Health System (SUS) by integrating several research centers in the field of Geriatrics and Gerontology throughout Brazil.

Although calls for responding to migration-related diversity in education are not novel, few studies have examined linguistic and affective outcomes of diversity-sensitive approaches for vocabulary teaching. This article reports on an intervention study in which beginner English-foreign-language learners (N = 51, M[subscript age] = 8.67 years) worked on one textbook unit (five 45-min lessons). Teachers supplemented the unit with translingual scaffolds and encouraged students to draw on and use their linguistic resources (plurilingual group), or stimulated appreciation of plurilingualism and positive language attitudes (motivation group). We assessed language gains through pre-, post-, and follow-up tests, and measured affect after each lesson. Both intervention groups outperformed the control group, which worked only with the textbooks, regarding productive vocabulary learning. Translingual scaffolding was beneficial for sustaining vocabulary gains. The data further indicate that motivational activities stimulate positive affect, but only the plurilingual group showed lower negative affect than the control group. Overall, the data suggest that intervention activities can augment productive vocabulary and support student well-being. We argue that future studies should pay more attention to affective outcomes when exploring ways of addressing migration-related diversity in the classroom.