Use of spinal cord stimulation in managing neuropathic foot pain: an observational pilot case series study

Objective: In cases of complex regional pain syndrome where conservative treatment is unsuccessful in controlling neuropathic foot pain spinal cord stimulation may be considered. To our knowledge there have been no such cases reported in the foot & ankle literature. The aim of the study was to establish useful information that may supplement our understanding of this complex multifactorial problem and help toinform future management of similar cases. Methods: A pilot observational case series study was undertaken to investigate the use of spinal cord stimulation in the management of neuropathic foot pain using five cases with complex regional pain syndrome (type I). Results: Reduced pain following spinal cord stimulation was reported. The interval between diagnosis and commencement of spinal cord stimulation was variable between cases and maybe responsible for differing levels and timing of pain relief experienced. Conclusion: Careful preoperative diagnosis, robust patient selection and close postoperative monitoring are vital for a successful outcome. The small sample size and potential for bias, limit the generalizability to a larger population. A larger study is therefore indicated to expand upon preliminary findings

Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria

Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity

State Regulatory Heterogeneity and Clean Water Act Compliance

This research evaluates the impact of state regulations regarding Clean Water Act (CWA) compliance on wastewater and drinking water violations in the continental United States from 2007 to 2017. Using data collected from the Environmental Protection Agency (EPA), community characteristics and state regulations are analyzed for their effects on CWA compliance. We use count data analysis techniques and annual county-level data on CWA and Safe Drinking Water Act (SDWA) violations from wastewater and drinking water facilities in the United States. The results show that total violations are higher when an additional state CWA regulation is implemented. One year after a new regulation is implemented, however, we observe a decrease in total violations relative to the number of violations prior to the introduction of additional policy or regulation. Total violations may decrease after the introduction of new regulations and policies as the facilities update their procedures, enforcement, or technology to be in compliance with new standards. Research findings confirm previous literature that higher non-white populations experience greater numbers of water violations, but also show that increased average per capita income mitigates the number of violations when the non-white population percentage is also taken into consideration

Validation and Improvement of Forest Health Risk Maps: A Case Study with Maple Decline/Dieback

Forest health data collected in a two-phased survey of maple dieback was used to build on previous work, extending analysis into mapping implications. Using the National Insect and Disease Risk Maps (NIDRM) published by the US Forest Service as a baseline, we compared our collected data from 2009-2012 and 2021-2022 with the published 240m resolution sugar maple decline risk map, finding the NIDRM map to be a poor predictor of sugar maple dieback measured at the plots. Measured sugar maple crown dieback was also compared to measured soil characteristics and nutrient levels, and augmented with soil survey maps and long-term climatic trends. We developed a linear regression framework utilizing multiple individual variables and composite variables generated through Principal Component Analysis. Only models created with covariates measured at each plot resulted in significant predictive models, but lacked temporal repeatability between study phases. The scale discrepancy between plot size and the 240m map pixel size limited the effectiveness of the NIDRM map and other spatially derived variables as predictors of maple canopy health in our study area, but these findings also highlight opportunities for improvement. As data sets improve with higher resolution and machine learning algorithms, it will be increasingly important to validate large-scale derivative models. Enhancing our understanding of forest health at a national level can inform regional decision-making and enable forest managers to tailor their management strategies to the specific threats facing their forest stands

A Theoretical Investigation of Composite Overwrapped Pressure Vessel (COPV) Mechanics Applied to NASA Full Scale Tests

A theoretical investigation of the factors controlling the stress rupture life of the National Aeronautics and Space Administration's (NASA) composite overwrapped pressure vessels (COPVs) continues. Kevlar (DuPont) fiber overwrapped tanks are of particular concern due to their long usage and the poorly understood stress rupture process in Kevlar filaments. Existing long term data show that the rupture process is a function of stress, temperature and time. However due to the presence of a load sharing liner, the manufacturing induced residual stresses and the complex mechanical response, the state of actual fiber stress in flight hardware and test articles is not clearly known. This paper is a companion to a previously reported experimental investigation and develops a theoretical framework necessary to design full-scale pathfinder experiments and accurately interpret the experimentally observed deformation and failure mechanisms leading up to static burst in COPVs. The fundamental mechanical response of COPVs is described using linear elasticity and thin shell theory and discussed in comparison to existing experimental observations. These comparisons reveal discrepancies between physical data and the current analytical results and suggest that the vessel s residual stress state and the spatial stress distribution as a function of pressure may be completely different from predictions based upon existing linear elastic analyses. The 3D elasticity of transversely isotropic spherical shells demonstrates that an overly compliant transverse stiffness relative to membrane stiffness can account for some of this by shifting a thin shell problem well into the realm of thick shell response. The use of calibration procedures are demonstrated as calibrated thin shell model results and finite element results are shown to be in good agreement with the experimental results. The successes reported here have lead to continuing work with full scale testing of larger NASA COPV hardware