The ability to detect changes in patient-perceived pain after total joint arthroplasty (TJA) is critical to manage postoperative pain. The minimal clinically important difference (MCID) for visual ...analog scale for pain (VAS-P) has not been investigated in this population. This study investigated the MCID for VAS-P in the TJA population.
Postoperative pain scores were collected on 139 total hip arthroplasty (THA) and 165 total knee arthroplasty (TKA) patients. VAS-P was measured and Likert scores for changes in pain recorded together throughout the hospitalization per patient. Using a linear mixed model, the mean difference between preceding and current VAS-P was calculated and correlated with Likert score, when the patient reported at least slight improvement or worsening in pain, defining the MCID. Minimal detectable change was calculated using the VAS-P standard error of the means for patients reporting “no change.”
For THA, the overall mean and average highest VAS-P were 35.0 mm and 50.4 mm, respectively. For TKA, the overall mean and average highest VAS-P were 42.6 mm and 61.1 mm, respectively. The minimal detectable change in VAS-P was 14.9 mm for THA and 16.1 mm for TKA. The MCID for THA and TKA pain improvement was −18.6 mm and −22.6 mm, respectively, and for worsening was 23.6 mm and 29.1 mm, respectively.
In the postoperative TJA population, VAS-P MCID changes depend on the type of surgical intervention, and whether pain is improving or worsening. Statistically significant VAS-P, improving −18.6 mm and −22.6 mm for THA and TKA patients, respectively, sets a reasonable threshold to identify clinically meaningful pain intervention with high specificity.
Historical Simulations With HadGEM3‐GC3.1 for CMIP6 Andrews, Martin B.; Ridley, Jeff K.; Wood, Richard A. ...
Journal of advances in modeling earth systems,
June 2020, 2020-06-00, 20200601, 2020-06-01, Letnik:
12, Številka:
6
Journal Article
Recenzirano
Odprti dostop
We describe and evaluate historical simulations which use the third Hadley Centre Global Environment Model in the Global Coupled configuration 3.1 (HadGEM3‐GC3.1) model and which form part of the ...UK's contribution to the sixth Coupled Model Intercomparison Project, CMIP6. These simulations, run at two resolutions, respond to historically evolving forcings such as greenhouse gases, aerosols, solar irradiance, volcanic aerosols, land use, and ozone concentrations. We assess the response of the simulations to these historical forcings and compare against the observational record. This includes the evolution of global mean surface temperature, ocean heat content, sea ice extent, ice sheet mass balance, permafrost extent, snow cover, North Atlantic sea surface temperature and circulation, and decadal precipitation. We find that the simulated time evolution of global mean surface temperature broadly follows the observed record but with important quantitative differences which we find are most likely attributable to strong effective radiative forcing from anthropogenic aerosols and a weak pattern of sea surface temperature response in the low to middle latitudes to volcanic eruptions. We also find evidence that anthropogenic aerosol forcings play a role in driving the Atlantic Multidecadal Variability and the Atlantic Meridional Overturning Circulation, which are key features of the North Atlantic ocean. Overall, the model historical simulations show many features in common with the observed record over the period 1850–2014 and so provide a basis for future in‐depth study of recent climate change.
Plain Language Summary
Historical simulations, which successfully reproduce features of the observed climate from the end of the preindustrial period to the near‐present day, contribute to our understanding of the underlying mechanisms that drive or influence climate variability and climate change. The historical simulations described in this paper use the third Hadley Centre Global Environment Model in the Global Coupled configuration 3.1 model. These simulations form part of the UK's contribution to the sixth Coupled Model Intercomparison Project. We assess various aspects of the historical climate system in our simulations against observations. This includes the evolution of global mean surface temperature, ocean heat content, sea ice extent, ice sheet mass balance, permafrost extent, snow cover, North Atlantic sea surface temperature and circulation, and decadal precipitation. The key findings include (a) that the model global mean surface temperature broadly follows the observed record, with a few quantitative differences, and (b) that the ocean circulation and sea surface temperatures of the North Atlantic are likely influenced by historical forcings. In general, the simulations respond to historically evolving influences in a similar manner to the observed world. Therefore, these simulations contribute, as part of the wider CMIP6 multimodel effort, to the understanding of the causes of observed climate change since 1850.
Key Points
We describe and evaluate the UK's CMIP6 historical simulations
We identify drivers of the modeled global temperature evolution and compare with the observed record
We find that anthropogenic aerosol forcings influence the simulation of North Atlantic ocean variability
Full restoration of arm function using a prosthesis remains a grand challenge; however, advances in robotic hardware, surgical interventions, and machine learning are bringing seamless human-machine ...interfacing closer to reality.
Through extensive data logging over 1 year, we monitored at-home use of the dexterous Modular Prosthetic Limb controlled through pattern recognition of electromyography (EMG) by an individual with a transhumeral amputation, targeted muscle reinnervation, and osseointegration (OI).
Throughout the study, continuous prosthesis usage increased (1% per week,
< 0.001) and functional metrics improved up to 26% on control assessments and 76% on perceived workload evaluations. We observed increases in torque loading on the OI implant (up to 12.5% every month,
< 0.001) and prosthesis control performance (0.5% every month,
< 0.005), indicating enhanced user integration, acceptance, and proficiency. More importantly, the EMG signal magnitude necessary for prosthesis control decreased, up to 34.7% (
< 0.001), over time without degrading performance, demonstrating improved control efficiency with a machine learning-based myoelectric pattern recognition algorithm. The participant controlled the prosthesis up to one month without updating the pattern recognition algorithm. The participant customized prosthesis movements to perform specific tasks, such as individual finger control for piano playing and hand gestures for communication, which likely contributed to continued usage.
This work demonstrates, in a single participant, the functional benefit of unconstrained use of a highly anthropomorphic prosthetic limb over an extended period. While hurdles remain for widespread use, including device reliability, results replication, and technical maturity beyond a prototype, this study offers insight as an example of the impact of advanced prosthesis technology for rehabilitation outside the laboratory.
Due to the fact that morphology and perinatal growth of the piglet brain is similar to humans, use of the piglet as a translational animal model for neurodevelopmental studies is increasing. Magnetic ...resonance imaging (MRI) can be a powerful tool to study neurodevelopment in piglets, but many of the MRI resources have been produced for adult humans. Here, we present an average in vivo MRI-based atlas specific for the 4-week-old piglet. In addition, we have developed probabilistic tissue classification maps. These tools can be used with brain mapping software packages (e.g. SPM and FSL) to aid in voxel-based morphometry and image analysis techniques. The atlas enables efficient study of neurodevelopment in a highly tractable translational animal with brain growth and development similar to humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mesopelagic fishes are important consumers of zooplankton and are the prey of oceanic predators. Some mesopelagic fishes (e.g., Myctophidae) undertake a diel vertical migration where they ascend to ...the near-surface waters during the night to feed and descend into the depths during the day to avoid predators. Other mesopelagic fishes (e.g.,
Sternoptyx
) remain at depth throughout the day. Although fishes of different depths eat different prey items, vertical migration likely leads to overlap in species distributions and diet, potentially linking trophically transmitted surface and deep-pelagic parasite communities. The study of gut contents and parasites can yield insights into the trophic dynamics occurring within these assemblages. We examined the diet and parasite assemblages of 18 mesopelagic fish species in the Gulf of Mexico. We identified six different feeding guilds within this assemblage based on gut contents: copepods, copepods/mesozooplankton, copepods/ostracods, gelatinous zooplankton, generalist mesozooplankton, and upper-trophic level items such as fish. Although parasite abundances were generally low, mesopelagic fishes hosted a diverse assemblage of parasites, including larval and adult digeneans, larval cestodes, larval nematodes, and larval acanthocephalans. The parasite assemblages differed significantly among host feeding guilds. Large, vertically migrating fishes that predate upon fish and squid communities had a greater likelihood of having one or more parasites compared to the other fishes examined. Results from this study suggest that upper-trophic level mesopelagic fishes are more regularly involved in the life cycle of parasites in the Gulf of Mexico than zooplanktivorous fishes.
Understanding the immunological control of pathogens requires a detailed evaluation of the mechanistic contributions of individual cell types within the immune system. While knockout mouse models ...that lack certain cell types have been used to help define the role of those cells, the biological and physiological characteristics of mice do not necessarily recapitulate that of a human. To overcome some of these differences, studies often look towards nonhuman primates (NHPs) due to their close phylogenetic relationship to humans. To evaluate the immunological role of select cell types, the NHP model provides distinct advantages since NHP more closely mirror the disease manifestations and immunological characteristics of humans. However, many of the experimental manipulations routinely used in mice (e.g., gene knock-out) cannot be used with the NHP model. As an alternative, the
infusion of monoclonal antibodies that target surface proteins on specific cells to either functionally inhibit or deplete cells can be a useful tool. Such depleting antibodies have been used in NHP studies to address immunological mechanisms of action. In these studies, the extent of depletion has generally been reported for blood, but not thoroughly assessed in tissues. Here, we evaluated four depleting regimens that primarily target T cells in NHP: anti-CD4, anti-CD8α, anti-CD8β, and immunotoxin-conjugated anti-CD3. We evaluated these treatments in healthy unvaccinated and IV BCG-vaccinated NHP to measure the extent that vaccine-elicited T cells - which may be activated, increased in number, or resident in specific tissues - are depleted compared to resting populations in unvaccinated NHPs. We report quantitative measurements of
depletion at multiple tissue sites providing insight into the range of cell types depleted by a given mAb. While we found substantial depletion of target cell types in blood and tissue of many animals, residual cells remained, often residing within tissue. Notably, we find that animal-to-animal variation is substantial and consequently studies that use these reagents should be powered accordingly.
The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing ...insights for vaccination strategies. In addition, the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of 12 V1V2-directed neutralizing antibodies, CAP256-VRC26, isolated from an HIV-1 clade C-infected donor at years 1, 2, and 4 of infection (N. A. Doria-Rose et al., Nature 509:55-62, 2014, http://dx.doi.org/10.1038/nature13036). Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. Thirteen antibodies were isolated from B cell culture, and eight were isolated using trimeric envelope probes for differential single B cell sorting. One of the new antibodies displayed a 10-fold greater neutralization potency than previously published lineage members. This antibody, CAP256-VRC26.25, neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency. Among the viruses neutralized, the median 50% inhibitory concentration was 0.001 μg/ml. All 33 lineage members targeted a quaternary epitope focused on V2. While all known bNAbs targeting the V1V2 region interact with the N160 glycan, the CAP256-VRC26 antibodies showed an inverse correlation of neutralization potency with dependence on this glycan. Overall, our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent.
Studies of HIV-1 broadly neutralizing antibodies (bNAbs) provide valuable information for vaccine design, and the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of V1V2-directed neutralizing antibodies from an HIV-1 clade C-infected donor. Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. One of the new antibodies, CAP256-VRC26.25, displayed a 10-fold greater neutralization potency than previously described lineage members. It neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency: the median 50% inhibitory concentration was 0.001 μg/ml. Our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent.
The piglet was investigated as a potential model for studying brain and cognitive deficits associated with being born small for gestational age (SGA). Naturally farrowed SGA (0.7-1.0 kg BW) and ...average for gestational age (AGA, 1.3-1.6 kg BW) piglets were obtained on postnatal day (PD) 2, placed in individual cages, and provided a nutritionally adequate milk replacer diet (285 ml/kg/d). Beginning at PD14, performance in a spatial T-maze task was assessed. At PD28, piglets were anesthetized for magnetic resonance (MR) imaging to assess brain structure (voxel-based morphometry), connectivity (diffusion-tensor imaging) and metabolites in the hippocampus and corpus callosum (proton MR spectroscopy). Piglets born SGA showed compensatory growth such that BW of SGA and AGA piglets was similar (P>0.05), by PD15. Birth weight affected maze performance, with SGA piglets taking longer to reach criterion than AGA piglets (p<0.01). Total brain volume of SGA and AGA piglets was similar (P<0.05), but overall, SGA piglets had less gray matter than AGA piglets (p<0.01) and tended to have a smaller internal capsule (p = 0.07). Group comparisons between SGA and AGA piglets defined 9 areas (≥ 20 clusters) where SGA piglets had less white matter (p<0.01); 2 areas where SGA piglets had more white matter (p<0.01); and 3 areas where SGA piglets had more gray matter (p<0.01). The impact of being born SGA on white matter was supported by a lower (p<0.04) fractional anisotropy value for SGA piglets, suggesting reduced white matter development and connectivity. None of the metabolites measured were different between groups. Collectively, the results show that SGA piglets have spatial learning deficits and abnormal development of white matter. As learning deficits and abnormalities in white matter are common in SGA human infants, the piglet is a tractable translational model that can be used to investigate SGA-associated cognitive deficits and potential interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Centers for Medicare and Medicaid Services (CMS) links patient-reported outcome measures (PROMs) with hospital reimbursement in some value-based models for total joint arthroplasty (TJA). This ...study evaluates PROM reporting compliance and resource utilization using protocol-driven electronic collection of outcomes for commercial and CMS alternative payment models (APMs).
We analyzed a consecutive series of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) from 2016 and 2019. Compliance rates were obtained for reporting hip disability and osteoarthritis outcome score for joint replacement (HOOS-JR.), knee disability and osteoarthritis outcome score for joint replacement (KOOS-JR.), and 12-item short form survey (SF-12) surveys preoperatively and postoperatively at 6-months, 1 year, and 2- years. Of 43,252 THA and TKA patients, 25,315 (58%) were Medicare-only. Direct supply and staff labor costs for PROM collection were obtained. Chi-square testing compared compliance rates between Medicare-only and all-arthroplasty groups. Time-driven activity-based costing (TDABC) estimated resource utilization for PROM collection.
In the Medicare-only cohort, preoperative HOOS-JR./KOOS-JR. compliance was 66.6%. Postoperative HOOS-JR./KOOS-JR. compliance was 29.9%, 46.1%, and 27.8% at 6 months, 1 year, and 2 years, respectively. Preoperative SF-12 compliance was 70%. Postoperative SF-12 compliance was 35.9%, 49.6%, and 33.4% at 6 months, 1 year, and 2 years, respectively. Medicare patients had lower PROM compliance than the overall cohort (P < .05) at all time points except preoperative KOOS-JR., HOOS-JR., and SF-12 in TKA patients. The estimated annual cost for PROM collection was $273,682 and the total cost for the entire study period was $986,369.
Despite extensive experience with APMs and a total expenditure near $1,000,000, our center demonstrated low preoperative and postoperative PROM compliance rates. In order for practices to achieve satisfactory compliance, Comprehensive Care for Joint Replacement (CJR) compensation should be adjusted to reflect the costs associated with collecting these PROMs and CJR target compliance rates should be adjusted to reflect more attainable levels consistent with currently published literature.
Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present ...next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities. At the individual donor level, the next-generation NFP algorithms particularly improved the ability to detect multiple epitope specificities in a sample, as confirmed both for computationally simulated polyclonal sera and for samples from HIV-infected donors. Specifically, the next-generation NFP algorithms detected multiple specificities in twice as many samples of simulated sera. Further, unlike the first-generation NFP, the new algorithms were able to detect both of the previously confirmed antibody specificities, VRC01-like and PG9-like, in donor CHAVI 0219. At the cohort level, analysis of ~150 broadly neutralizing HIV-infected donor samples suggested a potential connection between clade of infection and types of elicited epitope specificities. Most notably, while 10E8-like antibodies were observed in infections from different clades, an enrichment of such antibodies was predicted for clade B samples. Ultimately, such large-scale analyses of antibody responses to HIV-1 infection can help guide the design of epitope-specific vaccines that are tailored to take into account the prevalence of infecting clades within a specific geographic region. Overall, the next-generation NFP technology will be an important tool for the analysis of broadly neutralizing polyclonal antibody responses against HIV-1.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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