Bridging the gap: Bringing together intentional and unintentional injury prevention efforts to improve health and well being

Abstract Problem: Intentional and unintentional injury prevention efforts have traditionally been independent and non-integrated. Fostering collaboration between the sub-fields would enhance work within both sub-fields and advance injury prevention work as a whole. Method: A systematic assessment of similarities and differences between the sub-fields was performed, including an examination of relevant definitions and norms, research methods and findings, key risk and resiliency factors, and prevention strategies that would promote collaboration and better advance current prevention efforts. Results/Summary: Several areas exist in which injury prevention efforts could be coordinated or ideas and practices could be cross-applied, including training of practitioners, data collection and analysis, application of tools and methodologies, examination of risk and resiliency factors, and identification of funding sources and partners. Impact on Industry: This paper delineates how intentional and unintentional injury prevention practitioners can more effectively collaborate to promote safer environments and further reduce incidence of injury. An integrated injury prevention approach could significantly impact the underlying contributors to both types of injury, allowing practitioners within both sub-fields to achieve greater outcomes through increased credibility, reduced duplication of efforts, more efficient use of resources, and unified injury prevention messages

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus

Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test a CRISPR-based homing gene drive for Culex quinquefasciatus, and show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes

Neptune Odyssey: A Flagship Concept for the Exploration of the Neptune–Triton System

The Neptune Odyssey mission concept is a Flagship-class orbiter and atmospheric probe to the Neptune-Triton system. This bold mission of exploration would orbit an ice-giant planet to study the planet, its rings, small satellites, space environment, and the planet-sized moon Triton. Triton is a captured dwarf planet from the Kuiper Belt, twin of Pluto, and likely ocean world. Odyssey addresses Neptune system-level science, with equal priorities placed on Neptune, its rings, moons, space environment, and Triton. Between Uranus and Neptune, the latter is unique in providing simultaneous access to both an ice giant and a Kuiper Belt dwarf planet. The spacecraft - in a class equivalent to the NASA/ESA/ASI Cassini spacecraft - would launch by 2031 on a Space Launch System or equivalent launch vehicle and utilize a Jupiter gravity assist for a 12 yr cruise to Neptune and a 4 yr prime orbital mission; alternatively a launch after 2031 would have a 16 yr direct-to-Neptune cruise phase. Our solution provides annual launch opportunities and allows for an easy upgrade to the shorter (12 yr) cruise. Odyssey would orbit Neptune retrograde (prograde with respect to Triton), using the moon's gravity to shape the orbital tour and allow coverage of Triton, Neptune, and the space environment. The atmospheric entry probe would descend in ~37 minutes to the 10 bar pressure level in Neptune's atmosphere just before Odyssey's orbit-insertion engine burn. Odyssey's mission would end by conducting a Cassini-like "Grand Finale,"passing inside the rings and ultimately taking a final great plunge into Neptune's atmosphere

Bridging the gap: Bringing together intentional and unintentional injury prevention efforts to improve health and well being

Abstract Problem: Intentional and unintentional injury prevention efforts have traditionally been independent and non-integrated. Fostering collaboration between the sub-fields would enhance work within both sub-fields and advance injury prevention work as a whole. Method: A systematic assessment of similarities and differences between the sub-fields was performed, including an examination of relevant definitions and norms, research methods and findings, key risk and resiliency factors, and prevention strategies that would promote collaboration and better advance current prevention efforts. Results/Summary: Several areas exist in which injury prevention efforts could be coordinated or ideas and practices could be cross-applied, including training of practitioners, data collection and analysis, application of tools and methodologies, examination of risk and resiliency factors, and identification of funding sources and partners. Impact on Industry: This paper delineates how intentional and unintentional injury prevention practitioners can more effectively collaborate to promote safer environments and further reduce incidence of injury. An integrated injury prevention approach could significantly impact the underlying contributors to both types of injury, allowing practitioners within both sub-fields to achieve greater outcomes through increased credibility, reduced duplication of efforts, more efficient use of resources, and unified injury prevention messages

Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles.

Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the drive-induced DNA break is repaired by error-prone pathways, which creates mutations that disrupt the gRNA recognition sequence and prevent further gene-drive propagation. Here, we attempt to counteract this by encoding additional gRNAs that target the most commonly generated resistance alleles into the gene drive, allowing a second opportunity at gene-drive conversion. Our presented "double-tap" strategy improved drive efficiency by recycling resistance alleles. The double-tap drive also efficiently spreads in caged populations, outperforming the control drive. Overall, this double-tap strategy can be readily implemented in any CRISPR-based gene drive to improve performance, and similar approaches could benefit other systems suffering from low HDR frequencies, such as mammalian cells or mouse germline transformations

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus

Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test the first CRISPR-based homing gene drive for Culex quinquefasciatus, demonstrating the possibility of using this technology to control Culex mosquitoes. Our results show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes

Characteristics associated with subjective and objective measures of treatment success in women undergoing percutaneous tibial nerve stimulation vs sham for accidental bowel leakage.

INTRODUCTION AND HYPOTHESIS: In randomized trials both percutaneous tibial nerve stimulation (PTNS) and sham result in clinically significant improvements in accidental bowel leakage (ABL). We aimed to identify subgroups who may preferentially benefit from PTNS in women enrolled in a multicenter randomized trial. METHODS: This planned secondary analysis explored factors associated with success for PTNS vs sham using various definitions: treatment responder using three cutoff points for St. Marks score (≥3-, ≥4-, and ≥5-point reduction); Patient Global Impression of Improvement (PGI-I) of ≥ much better; and ≥50% reduction in fecal incontinence episodes (FIEs). Backward logistic regression models were generated using elements with significance of p<0.2 for each definition and interaction terms assessed differential effects of PTNS vs sham. RESULTS: Of 166 women randomized, 160 provided data for at least one success definition. Overall, success rates were 65% (102 out of 158), 57% (90 out of 158), and 46% (73 out of 158) for ≥3-, ≥4-, and ≥5-point St Marks reduction respectively; 43% (68 out of 157) for PGI-I; and 48% (70 out of 145) for ≥50% FIEs. Of those providing data for all definitions of success, 77% (109 out of 142) met one success criterion, 43% (61 out of 142) two, and 29% (41 out of 142) all three success criteria. No reliable or consistent factors were associated with improved outcomes with PTNS over sham regardless of definition. CONCLUSIONS: Despite exploring diverse success outcomes, no subgroups of women with ABL differentially responded to PTNS over sham. Success results varied widely across subjective and objective definitions. Further investigation of ABL treatment success definitions that consistently and accurately capture patient symptom burden and improvement are needed

Quality of Life and Sexual Function 2 Years After Vaginal Surgery for Prolapse.

ObjectiveTo longitudinally assess the effect of native tissue vaginal apical prolapse repair with anti-incontinence surgery on quality of life, sexual function, and body image between uterosacral and sacrospinous suspensions.MethodsA planned secondary analysis was performed on 374 women enrolled in a randomized trial of the two types of native tissue repair for apical prolapse. Condition-specific and generic quality of life, sexual function, overall and de novo dyspareunia, and body image were assessed using validated instruments at baseline; 6, 12, and 24 months postoperatively; and changes from baseline were assessed and compared between surgical groups. General linear mixed models were used for comparisons and clinically significant differences were assessed using minimum important differences.ResultsOf the women randomized, 82% had outcomes available at 2 years. Overall, clinically and statistically significant improvements in generic and condition-specific quality of life and sexual function were observed after surgery. Dyspareunia rates decreased from 25% to 16% by 24 months with only 3% of all women undergoing treatment. De novo dyspareunia occurred in 5% and 10% by 12 and 24 months, respectively. Body image scores also significantly improved from baseline. There were no clinically meaningful or statistically significant differences between groups for any of these outcomes (all P>.05).ConclusionNative tissue vaginal prolapse surgery results in statistically and clinically significant improvements in quality of life, sexual function, and body image at 24 months with no significant differences between uterosacral and sacrospinous suspensions. One in 10 women experience de novo dyspareunia but few requested treatment.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT00597935