Cavitation in shock wave lithotripsy: the critical role of bubble activity in stone breakage and kidney trauma

Objective: Shock Wave Lithotripsy (SWL) is the use of shock waves to fragment kidney stones. We have undertaken a study of the physical mechanisms responsible for stone comminution and tissue injury in SWL. SWL was originally developed on the premise that stone fragmentation could be induced by a short duration, high amplitude positive pressure pulse. Even though the SWL waveform carries a prominent tensile component, it has long been thought that SW damage to stones could be explained entirely on the basis of mechanisms such as spallation, pressure gradients, and compressive fracture. We contend that not only is cavitation also involved in SWL, bubble activity plays a critical role in stone breakage and is a key mechanism in tissue damage. Methods: Our evidence is based upon a series of experiments in which we have suppressed or minimized cavitation, and discovered that both stone comminution and tissue injury is similarly suppressed or minimized. Some examples of these experiments are (1) application of overpressure, (2) time reversal of acoustic waveform, (3) acoustically-transparent, cavitation-absorbing films, and (4) dual pulses. In addition, using passive and active ultrasound, we have observed the existence of cavitation, in vivo, and at the site of tissue injury. Results: Numerical and experimental results showed mitigation of bubble collapse intensity by time-reversing the lithotripsy pulse and in vivo treatment showed a corresponding drop from 6.1% ± 1.7% to 0.0% in the hemorrhagic lesion. The time-reversed wave did not break stones. Stone comminution and hemolysis were reduced to levels very near sham levels with the application of hydrostatic pressure greater than the near 10-MPa amplitude of the negative pressure of the lithotripter shock wave. A Mylar sheet 3-mm from the stone surface did not inhibit erosion and internal cracking, but a sheet in contact with the stone did. In water, mass lost from stones in a dual pulse lithotripter is 8 times greater than with a single lithotripter, but in glycerol, which reduces the pressures generated in bubble implosion, the enhancement is lost. Conclusion: This cavitation-inclusive mechanistic understanding of SWL is gaining acceptance and has had clinical impact. Treatment at slower SW rate gives cavitation bubble clusters time to dissolve between pulses and increases comminution. Some SWL centers now treat patients at slower SW rate to take advantage of this effect. An elegant cavitation-aware strategy to reduce renal trauma in SWL is being tested in experimental animals. Starting treatment at low amplitude causes vessels to constrict and this interferes with cavitation-mediated vascular injury. Acceptance of the role of cavitation in SWL is beginning to be embraced by the lithotripter industry, as new dual-pulse lithotripters—based on the concept of cavitation control— have now been introduced

Soil resources, microbial activity, and primary production across an agricultural ecosystem

Includes bibliographical references (pages 169-170).The degree to which soil resource availability is linked to patterns of microbial activity and plant productivity within ecosystems has important consequences for our understanding of how ecosystems are structured and for the management of systems for agricultural production. We studied this linkage in a 48-ha site in southwest Michigan, USA, that had been cultivated and planted to row crops for decades. Prior to seeding the site to genetically identical soybean plants (Glycine max) in early spring, we removed soil samples from ≈600 locations; plant biomass was harvested from these same locations later in the season. Soil samples were analyzed for physical properties (texture, bulk density), chemical properties (moisture, pH, total C, total N, inorganic N), and biological attributes (microbial biomass, microbial population size, respiration potential, and nitrification and N-mineralization potentials). Plant analyses included biomass and C and N contents. Soil resource variability across this long-cultivated site was remarkably high, as was variability in microbial activity and primary productivity. In almost all cases variability exhibited a strong spatially explicit structure: for most properties and processes > 50% of sample variance was spatially dependent at a scale of 5–60 m. Exceptions included microtopography, soil pH, and inorganic P, which were spatially dependent across the entire 1–1200 m range of separation distances examined in this study, and the culturable-bacteria population, which was not spatially autocorrelated at any scale examined. Both topographic relief and soil pH exhibited strongly nested structures, with autocorrelation occurring within two (topography) or more (pH) distinct ranges. Multiple regression analysis showed surprisingly little correlation between biological processes (soybean productivity, soil N turnover, soil respiration), and static soil properties. The best predictor of soybean biomass at late reproductive stages (r2 = 0.42) was a combination of nitrate N, bulk density, inorganic P, N-mineralization rates, and pH. Overall, results suggest a remarkable degree of spatial variability for a pedogenically homogeneous site that has been plowed and cropped mostly as a single field for > 100 yr. Such variability is likely to be generic to most ecosystems and should be carefully evaluated when making inferences about ecological relationships in these systems and when considering alternative sampling and management strategies

Understanding variation in ambulance service non-conveyance rates: a mixed methods study

Background In England in 2015/16, ambulance services responded to nearly 11 million calls. Ambulance Quality Indicators show that half of the patients receiving a response by telephone or face to face were not conveyed to an emergency department. A total of 11% of patients received telephone advice only. A total of 38% of patients were sent an ambulance but were not conveyed to an emergency department. For the 10 large ambulance services in England, rates of calls ending in telephone advice varied between 5% and 17%. Rates of patients who were sent an ambulance but not conveyed to an emergency department varied between 23% and 51%. Overall non-conveyance rates varied between 40% and 68%. Objective To explain variation in non-conveyance rates between ambulance services. Design A sequential mixed methods study with five work packages. Setting Ten of the 11 ambulance services serving > 99% of the population of England. Methods (1) A qualitative interview study of managers and paramedics from each ambulance service, as well as ambulance commissioners (totalling 49 interviews undertaken in 2015). (2) An analysis of 1 month of routine data from each ambulance service (November 2014). (3) A qualitative study in three ambulance services with different published rates of calls ending in telephone advice (120 hours of observation and 20 interviews undertaken in 2016). (4) An analysis of routine data from one ambulance service linked to emergency department attendance, hospital admission and mortality data (6 months of 2013). (5) A substudy of non-conveyance for people calling 999 with breathing problems. Results Interviewees in the qualitative study identified factors that they perceived to affect non-conveyance rates. Where possible, these perceptions were tested using routine data. Some variation in non-conveyance rates between ambulance services was likely to be due to differences in the way rates were calculated by individual services, particularly in relation to telephone advice. Rates for the number of patients sent an ambulance but not conveyed to an emergency department were associated with patient-level factors: age, sex, deprivation, time of call, reason for call, urgency level and skill level of attending crew. However, variation between ambulance services remained after adjustment for patient-level factors. Variation was explained by ambulance service-level factors after adjustment for patient-level factors: the percentage of calls attended by advanced paramedics [odds ratio 1.05, 95% confidence interval (CI) 1.04 to 1.07], the perception of ambulance service staff and commissioners that advanced paramedics were established and valued within the workforce of an ambulance service (odds ratio 1.84, 95% CI 1.45 to 2.33), and the perception of ambulance service staff and commissioners that senior management was risk averse regarding non-conveyance within an ambulance service (odds ratio 0.78, 95% CI 0.63 to 0.98). Limitations Routine data from ambulance services are complex and not consistently collected or analysed by ambulance services, thus limiting the utility of comparative analyses. Conclusions Variation in non-conveyance rates between ambulance services in England could be reduced by addressing variation in the types of paramedics attending calls, variation in how advanced paramedics are used and variation in perceptions of the risk associated with non-conveyance within ambulance service management. Linking routine ambulance data with emergency department attendance, hospital admission and mortality data for all ambulance services in the UK would allow comparison of the safety and appropriateness of their different non-conveyance rates. Funding The National Institute for Health Research Health Services and Delivery Research programme

Cavitation in shock wave lithotripsy: the critical role of bubble activity in stone breakage and kidney trauma

Objective: Shock Wave Lithotripsy (SWL) is the use of shock waves to fragment kidney stones. We have undertaken a study of the physical mechanisms responsible for stone comminution and tissue injury in SWL. SWL was originally developed on the premise that stone fragmentation could be induced by a short duration, high amplitude positive pressure pulse. Even though the SWL waveform carries a prominent tensile component, it has long been thought that SW damage to stones could be explained entirely on the basis of mechanisms such as spallation, pressure gradients, and compressive fracture. We contend that not only is cavitation also involved in SWL, bubble activity plays a critical role in stone breakage and is a key mechanism in tissue damage. Methods: Our evidence is based upon a series of experiments in which we have suppressed or minimized cavitation, and discovered that both stone comminution and tissue injury is similarly suppressed or minimized. Some examples of these experiments are (1) application of overpressure, (2) time reversal of acoustic waveform, (3) acoustically-transparent, cavitation-absorbing films, and (4) dual pulses. In addition, using passive and active ultrasound, we have observed the existence of cavitation, in vivo, and at the site of tissue injury. Results: Numerical and experimental results showed mitigation of bubble collapse intensity by time-reversing the lithotripsy pulse and in vivo treatment showed a corresponding drop from 6.1% ± 1.7% to 0.0% in the hemorrhagic lesion. The time-reversed wave did not break stones. Stone comminution and hemolysis were reduced to levels very near sham levels with the application of hydrostatic pressure greater than the near 10-MPa amplitude of the negative pressure of the lithotripter shock wave. A Mylar sheet 3-mm from the stone surface did not inhibit erosion and internal cracking, but a sheet in contact with the stone did. In water, mass lost from stones in a dual pulse lithotripter is 8 times greater than with a single lithotripter, but in glycerol, which reduces the pressures generated in bubble implosion, the enhancement is lost. Conclusion: This cavitation-inclusive mechanistic understanding of SWL is gaining acceptance and has had clinical impact. Treatment at slower SW rate gives cavitation bubble clusters time to dissolve between pulses and increases comminution. Some SWL centers now treat patients at slower SW rate to take advantage of this effect. An elegant cavitation-aware strategy to reduce renal trauma in SWL is being tested in experimental animals. Starting treatment at low amplitude causes vessels to constrict and this interferes with cavitation-mediated vascular injury. Acceptance of the role of cavitation in SWL is beginning to be embraced by the lithotripter industry, as new dual-pulse lithotripters—based on the concept of cavitation control— have now been introduced

Individual associations of adolescent alcohol use disorder versus cannabis use disorder symptoms in neural prediction error signaling and the response to novelty

Two of the most commonly used illegal substances by adolescents are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with poorer decision-making in adolescents. In adolescents, level of AUD symptomatology has been negatively associated with striatal reward responsivity. However, little work has explored the relationship with striatal reward prediction error (RPE) representation and the extent to which any augmentation of RPE by novel stimuli is impacted. One-hundred fifty-one adolescents participated in the Novelty Task while undergoing functional magnetic resonance imaging (fMRI). In this task, participants learn to choose novel or non-novel stimuli to gain monetary reward. Level of AUD symptomatology was negatively associated with both optimal decision-making and BOLD response modulation by RPE within striatum and regions of prefrontal cortex. The neural alterations in RPE representation were particularly pronounced when participants were exploring novel stimuli. Level of CUD symptomatology moderated the relationship between novelty propensity and RPE representation within inferior parietal lobule and dorsomedial prefrontal cortex. These data expand on an emerging literature investigating individual associations of AUD symptomatology levels versus CUD symptomatology levels and RPE representation during reinforcement processing and provide insight on the role of neuro-computational processes underlying reinforcement learning/decision-making in adolescents

A synthesis of evidence for policy from behavioural science during COVID-19

Scientific evidence regularly guides policy decisions1, with behavioural science increasingly part of this process2. In April 2020, an influential paper3 proposed 19 policy recommendations (‘claims’) detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to behavioural interventions also had strong empirical support, as did appealing to social consensus or bipartisan agreement. Targeted language in messaging yielded mixed effects and there were no effects for highlighting individual benefits or protecting others. No available evidence existed to assess any distinct differences in effects between using the terms ‘physical distancing’ and ‘social distancing’. Analysis of 463 papers containing data showed generally large samples; 418 involved human participants with a mean of 16,848 (median of 1,699). That statistical power underscored improved suitability of behavioural science research for informing policy decisions. Furthermore, by implementing a standardized approach to evidence selection and synthesis, we amplify broader implications for advancing scientific evidence in policy formulation and prioritization

Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada

In three case-control studies and a household transmission cohort, Danuta Skowronski and colleagues find an association between prior seasonal flu vaccination and increased risk of 2009 pandemic H1N1 flu

A synthesis of evidence for policy from behavioural science during COVID-19

Scientific evidence regularly guides policy decisions 1, with behavioural science increasingly part of this process 2. In April 2020, an influential paper 3 proposed 19 policy recommendations (‘claims’) detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to behavioural interventions also had strong empirical support, as did appealing to social consensus or bipartisan agreement. Targeted language in messaging yielded mixed effects and there were no effects for highlighting individual benefits or protecting others. No available evidence existed to assess any distinct differences in effects between using the terms ‘physical distancing’ and ‘social distancing’. Analysis of 463 papers containing data showed generally large samples; 418 involved human participants with a mean of 16,848 (median of 1,699). That statistical power underscored improved suitability of behavioural science research for informing policy decisions. Furthermore, by implementing a standardized approach to evidence selection and synthesis, we amplify broader implications for advancing scientific evidence in policy formulation and prioritization