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ObjectiveOne aim of the Back Pain Consortium (BACPAC) Research Program is to develop an integrated model of chronic low back pain that is informed by combined data from translational research and clinical trials. We describe efforts to maximize data harmonization and accessibility to facilitate Consortium-wide analyses.MethodsConsortium-wide working groups established harmonized data elements to be collected in all studies and developed standards for tabular and nontabular data (eg, imaging and omics). The BACPAC Data Portal was developed to facilitate research collaboration across the Consortium.ResultsClinical experts developed the BACPAC Minimum Dataset with required domains and outcome measures to be collected by use of questionnaires across projects. Other nonrequired domain-specific measures are collected by multiple studies. To optimize cross-study analyses, a modified data standard was developed on the basis of the Clinical Data Interchange Standards Consortium Study Data Tabulation Model to harmonize data structures and facilitate integration of baseline characteristics, participant-reported outcomes, chronic low back pain treatments, clinical exam, functional performance, psychosocial characteristics, quantitative sensory testing, imaging, and biomechanical data. Standards to accommodate the unique features of chronic low back pain data were adopted. Research units submit standardized study data to the BACPAC Data Portal, developed as a secure cloud-based central data repository and computing infrastructure for researchers to access and conduct analyses on data collected by or acquired for BACPAC.ConclusionsBACPAC harmonization efforts and data standards serve as an innovative model for data integration that could be used as a framework for other consortia with multiple, decentralized research programs.

ObjectiveBiomechanics represents the common final output through which all biopsychosocial constructs of back pain must pass, making it a rich target for phenotyping. To exploit this feature, several sites within the NIH Back Pain Consortium (BACPAC) have developed biomechanics measurement and phenotyping tools. The overall aims of this article were to: 1) provide a narrative review of biomechanics as a phenotyping tool; 2) describe the diverse array of tools and outcome measures that exist within BACPAC; and 3) highlight how leveraging these technologies with the other data collected within BACPAC could elucidate the relationship between biomechanics and other metrics used to characterize low back pain (LBP).MethodsThe narrative review highlights how biomechanical outcomes can discriminate between those with and without LBP, as well as among levels of severity of LBP. It also addresses how biomechanical outcomes track with functional improvements in LBP. Additionally, we present the clinical use case for biomechanical outcome measures that can be met via emerging technologies.ResultsTo answer the need for measuring biomechanical performance, our "Results" section describes the spectrum of technologies that have been developed and are being used within BACPAC.Conclusion and future directionsThe outcome measures collected by these technologies will be an integral part of longitudinal and cross-sectional studies conducted in BACPAC. Linking these measures with other biopsychosocial data collected within BACPAC increases our potential to use biomechanics as a tool for understanding the mechanisms of LBP, phenotyping unique LBP subgroups, and matching these individuals with an appropriate treatment paradigm.

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program's goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.

Social network research has evidenced the role of peer effects in the adoption of behaviours. Little is known, however, about whether policies affect how behaviours are shared in a network. To contribute to this literature, we apply the concept of diffusion centrality to school tobacco policies and adolescent smoking. Diffusion centrality is a measure of centrality which refers to a person's ability to diffuse a given property--in our case, smoking-related behaviours. We hypothesized that stronger school tobacco policies are associated with less diffusion centrality of smoking on school premises and of smoking in general. A whole network study was carried out in 2013 and 2016 among adolescents (n = 18,805) in 38 schools located in six European cities. Overall, diffusion centrality of smoking in general and of smoking on school premises significantly decreased over time. Diffusion centrality of smoking significantly decreased both in schools where the policy strengthened or softened over time, but for diffusion of smoking on school premises, this decrease was only significant in schools where it strengthened. Finally, stronger school tobacco policies were associated with lower diffusion centrality of smoking on school premises and of smoking in general, though to a lesser extent. With such policies, smoking may, therefore, become less prevalent, less popular, and less clustered, thereby lowering the risk of it spreading within networks in, and even outside the school.

Abstract Background During the COVID-19 pandemic, provision of non-COVID healthcare was recurrently severely disrupted. The objective was to determine whether disruption of non-COVID hospital use, either due to cancelled, postponed, or forgone care, during the first pandemic year of COVID-19 impacted socioeconomic groups differently compared with pre-pandemic use. Methods National population registry data, individually linked with data of non-COVID hospital use in the Netherlands (2017–2020). in non-institutionalised population of 25–79 years, in standardised household income deciles (1 = low, 10 = high) as proxy for socioeconomic status. Generic outcome measures included patients who received hospital care (dichotomous): outpatient contact, day treatment, inpatient clinic, and surgery. Specific procedures were included as examples of frequently performed elective and acute procedures, e.g.: elective knee/hip replacement and cataract surgery, and acute percutaneous coronary interventions (PCI). Relative risks (RR) for hospital use were reported as outcomes from generalised linear regression models (binomial) with log-link. An interaction term was included to assess whether income differences in hospital use during the pandemic deviated from pre-pandemic use. Results Hospital use rates declined in 2020 across all income groups. With baseline (2019) higher hospital use rates among lower than higher income groups, relatively stronger declines were found for lower income groups. The lowest income groups experienced a 10% larger decline in surgery received than the highest income group (RR 0.90, 95% CI 0.87 – 0.93). Patterns were similar for inpatient clinic, elective knee/hip replacement and cataract surgery. We found small or no significant income differences for outpatient clinic, day treatment, and acute PCI. Conclusions Disruption of non-COVID hospital use in 2020 was substantial across all income groups during the acute phases of the pandemic, but relatively stronger for lower income groups than could be expected compared with pre-pandemic hospital use. Although the pandemic’s impact on the health system was unprecedented, healthcare service shortages are here to stay. It is therefore pivotal to realise that lower income groups may be at risk for underuse in times of scarcity.

Abstract As thermal stress and disease outbreaks decimate coral reefs throughout the tropics, there is growing evidence that higher latitude marine environments may provide crucial refuges for many at-risk, temperature-sensitive coral species. However, our understanding of how coral populations expand into new areas and sustain themselves over time is constrained by the limited scope of modern observations. Here, we provide geological insights into coral range expansions by reconstructing the composition of a Late Holocene-aged subfossil coral death assemblage on the southeast Florida reef tract and comparing it to modern reefs throughout the region. Our findings show that the Late Holocene coral assemblages were dominated by now critically endangered Acropora species between ~3500 and 1800 years before present, mirroring classic zonation patterns characteristic of healthy pre-1970s Caribbean reefs. In contrast, the modern reefs off southeast Florida are becoming increasingly dominated by stress-tolerant species like Porites astreoides and Siderastrea siderea despite modest expansions of Acropora cervicornis over the past several decades. Our results suggest that ongoing anthropogenic stressors, not present during the Late Holocene, are likely limiting the ability of modern higher latitude reefs in Florida to function as long-term climate refugia.

Objective: Despite a nationwide ban on tobacco sales to people under 18 years of age, adolescents can still buy tobacco products in Amsterdam. This study aimed to understand the influence of the retail environment in adolescents' activity spaces on their tobacco-purchasing behaviour. Method: Interviews were conducted with 13 adolescents (aged 14-19 years) who went to school in Amsterdam and had ever bought tobacco products. Questions were based on the capability, opportunity, motivation, behaviour (COM-B) model. City maps showing all tobacco outlets were used to visualise respondents' activity spaces and purchasing areas. Transcripts were analysed thematically. Results: Adolescents preferred purchasing tobacco at shops where they had successfully purchased it before, instead of going to just any shop close by. They purchased tobacco products mostly in small shops. Supermarkets were avoided, as employees complied with age-verification procedures. The city centre provided easy access because the density of small shops was high. In adolescents' residential area, acquaintances behind the counter might facilitate tobacco purchase, while it was a barrier for minors who secretly smoked. At school, adolescents developed a collective knowledge of shops that sold tobacco products to minors either near school or further away. Tobacco was also bought on the black market because it was cheaper or because it was possible to buy specific products (e.g. snus). Conclusion: Tobacco purchasing by minors is less about the proximity and more about which stores in their activity spaces sell tobacco products to minors. Policies should therefore be aimed at the enforcement of age limits and reducing the number of small shops selling tobacco.

The disaccharide (β-D-glucopyranosyluronic acid)-(1→4)-β-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 3. A conjugate of the disaccharide with BSA (di-BSA conjugate) adjuvanted with aluminum hydroxide induced — in contrast to the non-adjuvanted conjugate — IgG1 antibody production and protected mice against S. pneumoniae serotype 3 infection after intraperitoneal prime-boost immunization. Adjuvanted and non-adjuvanted conjugates induced production of Th1 (IFNγ, TNFα); Th2 (IL-5, IL-13); Th17 (IL-17A), Th1/Th17 (IL-22), and Th2/Th17 cytokines (IL-21) after immunization. The concentration of cytokines in mice sera was higher in response to the adjuvanted conjugate, with the highest level of IL-17A production after the prime and boost immunizations. In contrast, the non-adjuvanted conjugate elicited only weak production of IL-17A, which gradually decreased after the second immunization. After boost immunization of mice with the adjuvanted di-BSA conjugate, there was a significant increase in the number of CD45+/CD19+ B cells, TCR+ γδ T cell, CD5+ В1 cells, and activated cells with MHC II+ expression in the spleens of the mice. IL-17A, TCR+ γδ T cells, and CD5+ В1 cells play a crucial role in preventing pneumococcal infection, but can also contribute to autoimmune diseases. Immunization with the adjuvanted and non-adjuvanted di-BSA conjugate did not elicit autoantibodies against double-stranded DNA targeting cell nuclei in mice. Thus, the molecular and cellular markers associated with antibody production and protective activity in response to immunization with the di-BSA conjugate adjuvanted with aluminum hydroxide are IL-17A, TCR+ γδ T cells, and CD5+ В1 cells against the background of increasing MHC II+ expression.

Abstract Staphylococcus aureus forms biofilms that cause considerable morbidity and mortality in patients who receive implanted devices such as prosthetics or fixator pins. An ideal surface for such medical devices would inhibit biofilm growth. Recently, it was reported that surface modification of stainless steel materials with carbon-infiltrated carbon nanotubes (CICNT) inhibits the growth of S. aureus biofilms. The purpose of this study was to investigate this antimicrobial effect on titanium materials with CICNT coated surfaces in a variety of surface morphologies and across a broader spectrum of S. aureus isolates. Study samples of CICNT-coated titanium, and control samples of bare titanium, a common implant material, were exposed to S. aureus. Viable bacteria were removed from adhered biofilms and quantified as colony forming units. Scanning electron microscopy was used to qualitatively analyze biofilms both before and after removal of cells. The CICNT surface was found to have significantly fewer adherent bacteria than bare titanium control surfaces, both via colony forming unit and microscopic analyses. This effect was most pronounced on CICNT surfaces with an average nanotube diameter of 150 nm, showing a 2.5-fold reduction in adherent bacteria. Since S. aureus forms different biofilm structures by isolate and by growth conditions, we tested 7 total isolates and found a significant reduction in the biofilm load in six out of seven S. aureus isolates tested. To examine whether the anti-biofilm effect was due to the structure of the nanotubes, we generated an unstructured carbon surface. Significantly more bacteria adhered to a nonstructured carbon surface than to the 150 nm CICNT surface, suggesting that the topography of the nanotube structure itself has anti-biofilm properties. The CICNT surface possesses anti-biofilm properties that result in fewer adherent S. aureus bacteria. These anti-biofilm properties are consistent across multiple isolates of S. aureus and are affected by nanotube diameter. The experiments performed in this study suggest that this effect is due to the nanostructure of the CICNT surface.

ABSTRACT: Introduction. Current publications and technologies for digital modeling of construction projects often entail considerable expenses and lengthy project timelines. In order to effectively monitor and control a large number of objects, there is a need to develop laser scanning technologies specifically for unmanned aerial vehicles, eliminating the need for ground-based imaging. Materials and methods. The study employed a hexacopter-type unmanned aerial vehicle equipped with a laser scanner, as well as specialized software for processing aerial imagery and laser scanning data, which included tools developed by the authors. The octant method was utilized when developing an algorithm for point cloud comparison. Results and discussion. In the course of the study, a technology for automating the monitoring and control of construction work was developed, in accordance with which aerial photography is performed once and an orthophotomap of the object is built (to accommodate laser scanning data). Then, with a certain frequency, laser surveys are carried out from an unmanned aerial vehicle, dense clouds of points are formed for different dates. To compare them, a linear computational algorithm has been developed, which, using data on two dense point clouds, allows obtaining the resulting cloud, which reflects the progress in the construction work. A feature of the algorithm is that the search for points is not carried out over the entire cloud, but within the boundaries of octants. This speeds up data processing and reduces the load on computing power. The technology received software implementation in the web application “Management system for monitoring construction work at facilities that have passed the state examination.” It allows the user to quickly get a visual representation of the change in the construction object for the selected period, to carry out all the necessary measurements (coordinates, geometric parameters, material consumption, etc.). Conclusions. The developed technology for automating the monitoring of construction work can be used by developers, customers, state and municipal authorities to quickly obtain information in order to control and support managerial decision-making

Abstract Background Previous studies found that tobacco outlets were unevenly distributed by area socioeconomic status (SES). However, evidence from continental Europe is limited. This study aims to assess differences in tobacco outlet presence, density and proximity by area SES in the Netherlands. Methods All tobacco outlets in four Dutch cities (Amsterdam, and medium-sized cities Eindhoven, Haarlem, and Zwolle) were mapped between September 2019 and June 2020. We estimated associations between average property value of neighbourhoods (as an indicator of SES, grouped into quintiles) and (1) tobacco outlet presence in the neighbourhood (yes/no), (2) density (per km2), and (3) proximity to the closest outlet (in meters), using logistic and linear regression models. Results 46% of neighbourhoods contained at least one tobacco outlet. Tobacco outlets were mostly situated in city centres, but the distribution of tobacco outlets varied per city due to differences in urban structures and functions. In the medium-sized cities, each quintile higher neighbourhood-SES was associated with lower tobacco outlet presence (OR:0.71, 95%CI:0.59;0.85), lower density (B:-1.20 outlets/km2, 95%CI:-2.20;-0.20) and less proximity (B:40.2 m, 95%CI 36.58;43.83). Associations were the other way around for Amsterdam (OR:1.22, 95%CI:1.05;1.40, B:3.50, 95%CI:0.81;6.20, and B:-18.45, 95%CI:-20.41;-16.49, respectively). Results were similar for most types of tobacco outlets. Conclusion In medium-sized cities in the Netherlands, tobacco outlets were more often located in low-SES neighbourhoods than high-SES. Amsterdam presented a reverse pattern, possibly due to its unique urban structure. We discuss how licensing might contribute to reducing tobacco outlets in low-SES neighbourhoods.

Abstract Background While it is known that educational inequalities in smoking start during early and middle adolescence, it is unknown how they further develop until adulthood. The aim of this article is to map, in the Portuguese context, how educational inequalities in smoking emerge from pre-adolescence until young adulthood. Methods This study used longitudinal data from the EPITeen Cohort, which recruited adolescents enrolled in schools in Porto, Portugal. We included the 1,038 participants followed at ages 13 (2003/2004), 17, 21, and 24 years. We computed the odds ratio (OR) for the prevalence of smoking states (never smoking, experimenter, less-than-daily, daily and former smoker) and the incidence of transitions between these states, as function of age and education, stratified by sex. We also added interaction terms between age and education. Results Educational inequalities in daily smoking prevalence, with higher prevalence among those with lower educational level, emerged at 17 years old and persisted until higher ages. They were formed in a cumulative way by the increased risk of experimenting between 13 and 17 years, and increased risk of becoming daily smoker between 17 and 21 years. The incidence of smoking cessation was higher among the higher educated. Inequalities were formed similarly for women and men, but with lower level and showed no significance among women. Conclusions These results highlight that actions to prevent smoking should also take in account the potential impact in smoking inequalities, and should focus not only on middle adolescence but also on late adolescence and early adulthood.

Abstract Reconfigurable transistors are an emerging device technology adding new functionalities while lowering the circuit architecture complexity. However, most investigations focus on digital applications. Here, we demonstrate a single vertical nanowire ferroelectric tunnel field-effect transistor (ferro-TFET) that can modulate an input signal with diverse modes including signal transmission, phase shift, frequency doubling, and mixing with significant suppression of undesired harmonics for reconfigurable analogue applications. We realize this by a heterostructure design in which a gate/source overlapped channel enables nearly perfect parabolic transfer characteristics with robust negative transconductance. By using a ferroelectric gate oxide, our ferro-TFET is non-volatilely reconfigurable, enabling various modes of signal modulation. The ferro-TFET shows merits of reconfigurability, reduced footprint, and low supply voltage for signal modulation. This work provides the possibility for monolithic integration of both steep-slope TFETs and reconfigurable ferro-TFETs towards high-density, energy-efficient, and multifunctional digital/analogue hybrid circuits.

The effect of prepressing of birch and alder wood on the pyrolysis process, structure and properties of biocarbon scaffolds were investigated. It is shown that after pressing process, internal stresses in the wood are preserved, which leads to a change in shrinkage during pyrolysis, especially in the pressing direction. The limitation of the samples expansion in the pressing direction made it possible to increase the density of biocarbon scaffolds (up to ∼ 1 g/cm3) and to obtain a linear dependence of their density on the density of compressed wood. Deformation of wood did not lead to a noticeable change in the atomic structure of biocarbon, but defects in the cell walls that affect the electrical resistivity of the biocarbon scaffolds were formed. The bending strength of biocarbon samples based on compressed wood was primarily determined by their density and weakly depended on the particular species. The obtained strength values were not inferior to the published data, which indicates that the defects formed during deformation were not stress concentrators.

Intracellular lipolysis—the enzymatic breakdown of lipid droplet-associated triacylglycerol (TAG)—depends on the cooperative action of several hydrolytic enzymes and regulatory proteins, together designated as lipolysome. Adipose triglyceride lipase (ATGL) acts as a major cellular TAG hydrolase and core effector of the lipolysome in many peripheral tissues. Neurons initiate lipolysis independently of ATGL via DDHD domain-containing 2 (DDHD2), a multifunctional lipid hydrolase whose dysfunction causes neuronal TAG deposition and hereditary spastic paraplegia. Whether and how DDHD2 cooperates with other lipolytic enzymes is currently unknown. In this study, we further investigated the enzymatic properties and functions of DDHD2 in neuroblastoma cells and primary neurons. We found that DDHD2 hydrolyzes multiple acylglycerols in vitro and substantially contributes to neutral lipid hydrolase activities of neuroblastoma cells and brain tissue. Substrate promiscuity of DDHD2 allowed its engagement at different steps of the lipolytic cascade: In neuroblastoma cells, DDHD2 functioned exclusively downstream of ATGL in the hydrolysis of sn-1,3-diacylglycerol (DAG) isomers but was dispensable for TAG hydrolysis and lipid droplet homeostasis. In primary cortical neurons, DDHD2 exhibited lipolytic control over both, DAG and TAG, and complemented ATGL-dependent TAG hydrolysis. We conclude that neuronal cells use noncanonical configurations of the lipolysome and engage DDHD2 as dual TAG/DAG hydrolase in cooperation with ATGL.

BackgroundIntervertebral body fusion devices (IBFDs) are a widely used type of spinal implant placed between two vertebral bodies to stabilize the spine for fusion in the treatment of spinal pathologies. Assessing mechanical performance of these devices is critical during the design, verification, and regulatory evaluation phases of development. While traditionally evaluated with physical bench testing, empirical assessments are at times supplemented with computational models and simulations such as finite element analysis (FEA). However, unlike many mechanical bench tests, FEA lacks standardized practices and consistency of implementation.ObjectivesThe objectives of this study were twofold. First, to identify IBFD 510(k) submissions containing FEA and conduct a comprehensive review of the elements provided in the FEA reports. Second, to engage with spinal device manufacturers through an anonymous survey and assess their practices for implementing FEA.MethodsFirst, a retrospective analysis of 510(k) submissions for IBFDs cleared by the FDA between 2013 and 2017 was performed. The contents of FEA test reports were quantified according to FDA guidance. Second, a survey inquiring about the use of FEA was distributed to industry and academic stakeholders. The survey asked up to 20 questions relating to modeler experience and modeling practices.ResultsSignificant gaps were present in model test reports that deemed the data unreliable and, therefore, unusable for regulatory decision-making in a high percentage of submissions. Nonetheless, the industry survey revealed most stakeholders employ FEA during device evaluation and are interested in more prescriptive guidelines for executing IBFD models.ConclusionsThis study showed that while inconsistencies and gaps in FEA execution do exist within the spinal device community, the stakeholders are eager to work together in developing standardized approaches for executing computational models to support mechanical performance assessment of spinal devices in regulatory submissions.

Background: Image guidance to assist left ventricular (LV) lead placement may improve outcome after cardiac resynchronization therapy (CRT), but previous approaches and results varied greatly, and multicenter feasibility is lacking altogether. Objective: We sought to investigate the multicenter feasibility of image guidance for periprocedural assistance of LV lead placement for CRT. Methods: In 30 patients from 3 hospitals, cardiac magnetic resonance imaging was performed within 3 months prior to CRT to identify myocardial scar and late mechanical activation (LMA). LMA was determined using radial strain, plotted over time. Segments without scar but clear LMA were classified as optimal for LV lead placement, according to an accurate 36-segment model of the whole heart. LV leads were navigated using image overlay with periprocedural fluoroscopy. After 6 months, volumetric response and super-response were defined as ≥15% or ≥30% reduction in LV end-systolic volume, respectively. Results: Periprocedural image guidance was successfully performed in all CRT patients (age 66 ± 10 years; 59% men, 62% with nonischemic cardiomyopathy, 69% with left bundle branch block). LV leads were placed as follows: within (14%), adjacent (62%), or remote (24%) from the predefined target. According to the conventional 18-segment model, a remote position occurred only once (3%). On average, 86% of patients demonstrated a volumetric response (mean LV end-systolic volume reduction 36 ± 29%), and 66% of all patients were super-responders. Conclusion: On-screen image guidance for LV lead placement in CRT was feasible in a multicenter setting. Efficacy will be further investigated in the randomized controlled ADVISE (Advanced Image Supported Lead Placement in Cardiac Resynchronization Therapy) trial (NCT05053568).