The HAVEN study-hydroxychloroquine in ANCA vasculitis evaluation-a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan.

BACKGROUND: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus. METHODS: Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine's efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission. DISCUSSION: This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS. TRIAL REGISTRATION: ISRCTN: ISRCTN79334891. Registered 07 June 2021. EudraCT: 2018-001268-40. Registered 13 September 2019. CLINICALTRIALS: gov: NCT04316494. Registered 20 March 2020.

Assessing classroom and laboratory spread of COVID-19 in a university after elimination of physical distancing.

The objective of this study was to assess COVID-19 classroom transmission in the university setting when physical distancing was eliminated. Data was collected in fall 2021 at a private university. Universal masking, robust contact tracing, vaccination requirement, and enforced testing were in place. Exposures were classified as classroom versus non-classroom. ANOVA and chi-squared tests were used to identify significant relationships between predictors and COVID-19 test result. Logistic regression was conducted to investigate the relationship between exposure type and test result. A total of 162 student cases were identified with 1,658 associated close contacts. One-third of contacts (31.1%, n = 516) only had a non-classroom exposure, 63.8% (n = 1,057) only had a classroom exposure, and 5.1% (n = 85) had both. Close contacts were significantly more likely to test positive if they had a non-classroom exposure (60 of 601; 10.0%) compared to a classroom exposure (1 of 1057; 0.1%) (OR 58.8, CI 18.5-333.3, p < 0.001). Removing physical distancing in classrooms that had universal masking did not result in high rates of COVID-19 transmission. This has policy implications because eliminating physical distancing does not greatly increase transmission risk when universal masking is in place.

Efficacy of Postpartum Pharmacologic Thromboprophylaxis: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of pharmacologic venous thromboembolism (VTE) prophylaxis in postpartum patients. DATA SOURCES: On February 21, 2022, a literature search was conducted on Embase.com , Ovid-Medline All, Cochrane Library, Scopus, and ClinicalTrials.gov using terms postpartum period AND thromboprophylaxis AND antithrombin medications including heparin and low molecular weight heparin. METHODS OF STUDY SELECTION: Studies that evaluated the outcome of VTE among postpartum patients exposed to pharmacologic VTE prophylaxis with or without a comparator group were eligible for inclusion. Studies of patients who received antepartum VTE prophylaxis, studies in which this prophylaxis could not be definitively ruled out, and studies of patients who received therapeutic dosing of anticoagulation for specific medical problems or treatment of VTE were excluded. Titles and abstracts were independently screened by two authors. Relevant full-text articles were retrieved and independently reviewed for inclusion or exclusion by two authors. TABULATION, INTEGRATION, AND RESULTS: A total of 944 studies were screened by title and abstract, and 54 full-text studies were retrieved for further evaluation after 890 studies were excluded. Fourteen studies including 11,944 patients were analyzed: eight randomized controlled trials (8,001 patients) and six observational studies (3,943 patients). Among the eight studies with a comparator group, there was no difference in the risk of VTE between patients who were exposed to postpartum pharmacologic VTE prophylaxis and those who were unexposed (pooled relative risk 1.02, 95% CI 0.29-3.51); however, six of eight studies had no events in either the exposed or unexposed group. Among the six studies without a comparator group, the pooled proportion of postpartum VTE events was 0.00, likely due to five of six studies having no events. CONCLUSION: The current literature provided an insufficient sample size to conclude whether postpartum VTE rates differ between those exposed to postpartum pharmacologic prophylaxis and those unexposed, given the rarity of VTE events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022323841.

Attitudes and opportunities: comparing climate change adaptation intentions and decisions of agricultural producers in Shaanxi, China, and British Columbia, Canada.

Climate change poses a major challenge for agricultural producers. There are a variety of adaptation strategies producers can use to enhance their resilience to the changing climate. The theory of planned behavior is applied as a framework to compare the adaptation intentions and choices of producers in Cariboo and Okanagan regions of the province of British Columbia (BC), Canada, and Baoji and Xi'an city prefectures of Shaanxi (SX) province, China. In BC, producers are more likely to explore the use of new crop varieties, and BC producers also seem to have a stronger intention to invest in irrigation efficiency. In contrast, producers in SX are far more likely to use online marketing methods to connect directly with consumers. Based on transcripts from a set of focus groups, community meetings, and interviews, differences in attitudes, social norms, and perceived behavioral control between SX and BC producers are identified that may contribute to their different adaptation choices. Multiple barriers to adaptation existed in both areas. Limited technical knowledge and doubts about adaptation effectiveness were more serious in BC, while limited support from local government and normative expectations were notable in SX. Education, targeted research, and public investments in irrigation and marketing may contribute to addressing some of these differences, improving the resilience of agricultural climate adaptation in both provinces.

Ambient air pollution associated with incidence and progression trajectory of cardiometabolic diseases: A multi-state analysis of a prospective cohort.

BACKGROUND: Previous studies on the association between ambient air pollution and cardiometabolic diseases (CMDs) focused on a single disease, without considering cardiometabolic multimorbidity (CMM) and the progression trajectory of CMDs. METHODS: Based on the UK Biobank cohort, we included 372,530 participants aged 37-73 years at baseline (2006-2010) with follow-up until September 2021. Incident CMDs cases were identified based on self-reported information and multiple health-related records in the UK Biobank. CMM was defined as the occurrence of at least two CMDs, including ischemic heart disease (IHD), stroke and type 2 diabetes (T2D). Exposure to ambient air pollutants, including particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2.5), ≤10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated at participants' geocoded residential addresses based on the high-resolution (1 × 1 km) pollution data from 2001 to 2021 provided by UK Department for Environment, Food and Rural Affairs. Multi-state models with adjustment for potential confounders were used to examine the impact of long-term exposure to ambient air pollution on transitions from healthy to first CMD (FCMD), subsequently to CMM, and further to death. RESULTS: During a median follow-up of 12.6 years, 40,112 participants developed at least one CMD, 3896 developed CMM, and 21,739 died. Among the four pollutants, PM2.5 showed the strongest associations with all transitions from healthy to FCMD, to CMM, and then to death [hazard ratios (95 % confidence intervals) per interquartile range (IQR) increment: 1.62 (1.60, 1.64) and 1.68 (1.61, 1.76) for transitions from healthy to FCMD and from FCMD to CMM, and 1.62 (1.59, 1.66), 1.67 (1.61, 1.73), and 1.52 (1.38, 1.67) for death risk from healthy, FCMD, and CMM, respectively]. After dividing FCMDs into three specific CMDs, we found that ambient air pollution had differential impacts on disease-specific transitions within the same transition phase. CONCLUSIONS: Our findings indicate that there is potential for air pollution mitigation in contributing to the prevention of the development and progression of CMDs.

Association between Pet Ownership and Threatened Abortion in Pregnant Women: The China Birth Cohort Study.

Background: The aim of this study was to assess the association between pet ownership and threatened abortion (TA) in pregnant Chinese women. Materials and Methods: We enrolled pregnant women from 18 provinces and autonomous regions across China between November 2017 and December 2020. Participants were grouped based on the presence or absence of pet ownership. Pet owners were further sub-grouped based on the presence or absence of close contact with their pets. Pet species included cats, dogs, and both. Generalised linear mixed models, with province as a random effect, were used to estimate the associations between pet ownership and TA. Results: Pet ownership, whether or not one had close contact with pets, was associated with greater odds of TA (OR: 1.30, 95% CI: 1.21, 1.40). Keeping pet cats (OR: 1.24, 95% CI: 1.11, 1.40), dogs (OR: 1.29, 95% CI: 1.18, 1.41), or both cats and dogs (OR: 1.36, 95% CI: 1.04, 1.68) during pregnancy were all risk factors for TA. We observed significant group differences (p for difference < 0.05) in pre-pregnancy body mass index, education levels, and annual household income. Conclusions: Cat or dog ownership during pregnancy was associated with an increased risk of TA, especially among overweight, less educated, or lower-income participants.

Barriers to human papillomavirus (HPV) vaccination among young adults, aged 18-35.

In the United States (US), an estimated 35,900 human papillomavirus (HPV)-related cancers are diagnosed annually. HPV vaccines are projected to eliminate âˆ¼90% of these cancers. Routine vaccination is recommended at age 11-12 with "catch-up" vaccination through age 26 and shared clinical decision making for ages 27-45. However, vaccine uptake has been slow with many young adults remaining unvaccinated. This study examined barriers to HPV vaccination among individuals aged 18-35 years and assessed likelihood of future HPV vaccination. Age-eligible participants (n = 499) recruited through Facebook advertisements, Facebook posts, and clinics (6/2019-3/2020) completed an online survey. Descriptive statistics and bivariate analysis examined HPV vaccine barriers and intent. Logistic regression models examined predictors of HPV vaccine intent. Most (57.1%) reported they were not at all likely to get vaccinated for HPV in the future. Lower intent was associated with belief that the vaccine is not necessary (aOR: 0.134, 95% CI: 0.073, 0.246) and not safe (aOR: 0.312, 95% CI: 0.126, 0.773). Intent was positively associated with the belief that health insurance would not cover vaccination (aOR: 2.226, 95% CI: 1.070, 4.631). Provider recommendation was not significantly associated with vaccine intention. This study highlights challenges to HPV vaccine uptake for young adults. Though several successful interventions exist, most target adolescents and their parents or providers. Future steps should use this evidence to inform development of targeted interventions to increase HPV vaccine intention and uptake in adults, ultimately reducing the burden of HPV-related cancers.

Ambient air pollution, lifestyle, and genetic predisposition associated with type 2 diabetes: findings from a national prospective cohort study.

BACKGROUND: The combined effects of ambient air pollution, lifestyle, and genetic predisposition on incident Type 2 Diabetes (T2D) have not been well documented. METHODS: A total of 263,733 participants without T2D at baseline were identified from the UK Biobank. Annual concentrations of five air pollutants were estimated using Land Use Regression, while a healthy lifestyle score (HLS) was constructed using 7 major lifestyle factors, and polygenic risk score (PRS) was generated using 73 genetic variants. Cox regression was used to determine the association between air pollution and incident T2D for different HLS/PRS categories. Potential HLS/PRS interactions and population attributable fraction (PAF) were also examined. RESULTS: During a median follow-up of 11.94 years, 7827 (2.97 %) incident T2D cases were identified. Association between air pollution and incident T2D was stronger among those with higher HLS/PRS in a dose-response fashion. In addition, synergistic interactions between lifestyles and air pollution were observed. Lifestyle was the leading risk factor of T2D with a weighted PAF of 25.54 % (95 % CI: 19.22 %, 27.77 %) for intermediate HLS and 24.24 % (18.24 %, 26.36 %) due to unhealthy HLS. Overall, we estimated that about 25 % of T2D cases could be attributable to air pollution and associated interactions. CONCLUSIONS: Associations between air pollution and T2D were stronger among individuals with unhealthier lifestyle on an additive interaction scale. Public health interventions that address both reduction of exposure to high levels of air pollution in addition to lifestyle changes may have more benefit on reducing T2D risk than focusing on lifestyle changes alone.

Evaluation of community-based CT abdomen for acute abdominal pain during COVID-19.

AIM: The purpose of this study was to determine the utility of community-based imaging to reduce use of inpatient surgical resources and enforce social distancing at the outset of the COVID-19 pandemic. METHOD: A prospective evaluation of community-based CT for patients presenting to Christchurch general practitioners with acute abdominal pain from April to November 2020. Eligible patients were discussed with the on-call general surgical team, and then referred for CT abdomen rather than hospital assessment. The positivity rate of CT scans, the 30-day all-cause hospital admission rate, and the proportion of patients where community scanning altered management setting and the number of incidental findings, were all assessed. RESULTS: Of 131 included patients, 67 (51%) patients had a positive CT scan. Thirty-nine (30%) patients were admitted to hospital within 30 days, 34 (87%) of whom had a positive CT scan and were admitted under a surgical specialty. Ninety-two (70%) patients did not require hospital admission for their acute abdominal pain, thirty-three (35%) of whom had a positive CT scan. There were three deaths within 30 days of the community CT, and the setting of the community CT did not contribute to the death of any of the cases. Forty patients (30%) had incidental findings on CT, 10 (25%) of which were significant and were referred for further investigation. CONCLUSION: Community based abdominal CT scanning is a feasible option in the management of acute abdominal pain. While trialed in response to the initial nationwide COVID-19 lockdown in New Zealand, there may be utility for acute community-based CT scanning in regular practice.

OECD Case Studies of Integrated Regional and Strategic Impact Assessment: What Does 'Integration' Look Like in Practice?

Increasingly, protocols for assessing the impacts of land-uses and major resource development projects focus not only on environmental impacts, but also social and human health impacts. Regional and Strategic Environmental Assessment (RSEAs) are one innovation that hold promise at better integrating these diverse land-use values into planning, assessment, and decision-making. In this contribution, a realist review methodology is utilized to identify case studies of "integrated RSEA"-those which are strategic, have a regional assessment approach, and seek to integrate environmental, community and health impacts into a singular assessment architecture. The results of a systematic literature review are described and six RSEA-like case studies are identified: Kimberly Browse LNG SEA; HS2 Appraisal of Sustainability; Lisbon International Airport SEA; Beaufort Regional Environmental Assessment; Nordstream 2 Transboundary EIA; and the Portland Harbour Sustainability Project. The case studies are examined according to their unique contexts, mechanisms and outcomes of their assessment protocols to determine the degree to which they consider more than environmental valued components, and the means by which they were included. Findings suggest that RSEA has a contentious relationship with the integration of more than environmental values, but that there are significant lessons to be learned to support project planning, especially for assessment contexts characterized by large, transboundary projects.

Assessing the Cumulative Social Effects of Projects: Lessons from Canadian Hydroelectric Development.

Cumulative effects assessments are often expected to include an analysis of cumulative social effects to people, their communities, and livelihoods caused by resource development projects and land use activities. Understanding cumulative social effects is important for decisions about prospective resource development projects, but there has been limited attention devoted to how to complete such an assessment. This paper critically examines how cumulative effects frameworks are applied to social impacts during environmental assessments. We do this by analyzing semi-structured interviews exploring practitioner experience in environmental assessments for hydroelectric development in British Columbia and Manitoba, Canada. The results provide a conceptual framework for cumulative social effects and illustrate how identified challenges for cumulative effects assessment are exacerbated by social impacts that introduce additional complexities in impact identification, assessment, and decision-making. The paper concludes with a discussion of how these challenges can be addressed and recommendations for improving environmental assessment practice.

Interactive effects of cold spell and air pollution on outpatient visits for anxiety in three subtropical Chinese cities.

BACKGROUND: Although low temperature and air pollution exposures have been associated with the risk of anxiety, their combined effects remain unclear. OBJECTIVE: To investigate the independent and interactive effects of low temperature and air pollution exposures on anxiety. METHOD: Using a case-crossover study design, the authors collected data from 101,636 outpatient visits due to anxiety in three subtropical Chinese cities during the cold season (November to April in 2013 through 2018), and then built conditional logistic regression models based on individual exposure assessments [temperature, relative humidity, particulate matter (PM2.5, PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2)] and twelve cold spell definitions. Additive-scale interactions were assessed using the relative excess risk due to interaction (RERI). RESULTS: Both cold spell and air pollution were significantly associated with outpatients for anxiety. The effects of cold spell increased with its intensity, ranging from 8.98% (95% CI: 2.02%, 16.41%) to 15.24% (95% CI: 6.75%, 24.39%) in Huizhou. Additionally, each 10 µg/m3 increase of PM2.5, PM10, NO2 and SO2 was associated with a 1.51% (95% CI: 0.61%, 2.43%), 1.58% (95% CI: 0.89%, 2.28%), 13.95% (9.98%, 18.05%) and 11.84% (95% CI: 8.25%, 15.55%) increase in outpatient visits for anxiety. Synergistic interactions (RERI >0) of cold spell with all four air pollutants on anxiety were observed, especially for more intense cold spells. For particulate matters, these interactions were found even under mild cold spell definitions [RERI: 0.11 (95% CI: 0.02, 0.21) for PM2.5, and 0.24 (95% CI: 0.14, 0.33) for PM10]. Stratified analyses yielded a pronounced results in people aged 18-65 years. CONCLUSIONS: These findings indicate that both cold spell and air pollution are important drivers of the occurrence of anxiety, and simultaneous exposure to these two factors might have synergistic effects on anxiety. These findings highlight the importance of controlling air pollution and improving cold-warning systems.

Noninvasive Low-Intensity Focused Ultrasound Mediates Tissue Protection following Ischemic Stroke.

Objective and Impact Statement. This study examined the efficacy and safety of pulsed, low-intensity focused ultrasound (LIFU) and determined its ability to provide neuroprotection in a murine permanent middle cerebral artery occlusion (pMCAO) model. Introduction. Focused ultrasound (FUS) has emerged as a new therapeutic strategy for the treatment of ischemic stroke; however, its nonthrombolytic properties remain ill-defined. Therefore, we examined how LIFU influenced neuroprotection and vascular changes following stroke. Due to the critical role of leptomeningeal anastomoses or pial collateral vessels, in cerebral blood flow restoration and tissue protection following ischemic stroke, we also investigated their growth and remodeling. Methods. Mice were exposed to transcranial LIFU (fundamental frequency: 1.1 MHz, sonication duration: 300 ms, interstimulus interval: 3 s, pulse repetition frequency: 1 kHz, duty cycle per pulse: 50%, and peak negative pressure: -2.0 MPa) for 30 minutes following induction of pMCAO and then evaluated for infarct volume, blood-brain barrier (BBB) disruption, and pial collateral remodeling at 24 hrs post-pMCAO. Results. We found significant neuroprotection in mice exposed to LIFU compared to mock treatment. These findings correlated with a reduced area of IgG deposition in the cerebral cortex, suggesting attenuation of BBB breakdown under LIFU conditions. We also observed increased diameter of CD31-postive microvessels in the ischemic cortex. We observed no significant difference in pial collateral vessel size between FUS and mock treatment at 24 hrs post-pMCAO. Conclusion. Our data suggests that therapeutic use of LIFU may induce protection through microvascular remodeling that is not related to its thrombolytic activity.

Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review.

New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely noninvasive, nonthermal, and nonionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even near critical structures. Additional benefits include real-time image guidance, high precision, and the ability to treat tumors of any predetermined size and shape. Unfortunately, the lack of clinically and physiologically relevant preclinical cancer models is often a significant limitation with all focal tumor ablation strategies. The majority of studies testing histotripsy for cancer treatment have focused on small animal models, which have been critical in moving this field forward and will continue to be essential for providing mechanistic insight. While these small animal models have notable translational value, there are significant limitations in terms of scale and anatomical relevance. To address these limitations, a diverse range of large animal models and spontaneous tumor studies in veterinary patients have emerged to complement existing rodent models. These models and veterinary patients are excellent at providing realistic avenues for developing and testing histotripsy devices and techniques designed for future use in human patients. Here, we provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports across a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients.

Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders.

Disrupted brain gamma-aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co-occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well-tolerated medication, FDA-approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double-blind, placebo-controlled, crossover (1-week/condition), multimodal-MRI (proton-MR spectroscopy, functional MRI) pilot study of gabapentin (1200 mg/day) in BD + CUD (n = 22). Primary analyses revealed that (1) gabapentin was well tolerated and adherence and retention were high, (2) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels and (3) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that in participants taking gabapentin versus placebo, (1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and (2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels and identification of statistical moderators that differed by randomization order (i.e. cigarette-smoking status on rBG glutamate levels and pMCC cue activation). Nonetheless, they provide the necessary foundation for a more robustly designed (urn-randomized, parallel-group) future study of adjuvant gabapentin for BD + CUD.

SARS-CoV-2 Transmission to Masked and Unmasked Close Contacts of University Students with COVID-19 - St. Louis, Missouri, January-May 2021.

Universities open for in-person instruction during the 2020-21 academic year implemented a range of prevention strategies to limit the transmission of SARS-CoV-2, the virus that causes COVID-19, including physical distancing, mask use, vaccination, contact tracing, case investigation, and quarantine protocols (1). However, in some academic programs, such as health-related programs, aviation, and kindergarten through grade 12 (K-12) education, maintaining physical distance while still providing instruction is difficult; for universities with such programs, a single confirmed case of COVID-19 could result in a large number of students, staff members, and instructors being designated close contacts and requiring quarantine if they are not fully vaccinated, even if masks were worn when contact occurred. In January 2021, the St. Louis City Health Department allowed Saint Louis University (SLU) to implement a modified quarantine protocol that considered mask use when determining which close contacts required quarantine.* To assess the impact of the protocol, SLU assessed positive SARS-CoV-2 test result rates by masking status of the persons with COVID-19 and their close contacts. During January-May 2021, 265 students received a positive SARS-CoV-2 test result; these students named 378 close contacts. Compared with close contacts whose exposure only occurred when both persons were masked (7.7%), close contacts with any unmasked exposure (32.4%) had higher adjusted odds ratios (aORs) of receiving a positive SARS-CoV-2 test result (aOR = 4.9; 95% confidence interval [CI] = 1.4-31.1). Any additional exposures were associated with a 40.0% increase in odds of a positive test result (aOR = 1.4; 95% CI = 1.2-1.6). These findings reinforce that universal masking and having fewer encounters in close contact with persons with COVID-19 prevents the spread of SARS-CoV-2 in a university setting. Universities opening for in-person instruction could consider taking mask use into account when determining which unvaccinated close contacts require quarantine if enforced testing protocols are in place. However, this study was conducted before the B.1.617.2 (Delta) variant became the dominant strain of SARS-CoV-2 in the United States, which could have affected these findings given that the Delta variant has been found to be associated with increased transmissibility compared to previous variants.

Histotripsy Ablation of Bone Tumors: Feasibility Study in Excised Canine Osteosarcoma Tumors.

Osteosarcoma (OS) is a primary bone tumor affecting both dogs and humans. Histotripsy is a non-thermal, non-invasive focused ultrasound method using controlled acoustic cavitation to mechanically disintegrate tissue. In this study, we investigated the feasibility of treating primary OS tumors with histotripsy using a 500-kHz transducer on excised canine OS samples harvested after surgery at the Veterinary Teaching Hospital at Virginia Tech. Samples were embedded in gelatin tissue phantoms and treated with the 500-kHz histotripsy system using one- or two-cycle pulses at a pulse repetition frequency of 250 Hz and a dosage of 4000 pulses/point. Separate experiments also assessed histotripsy effects on normal canine bone and nerve using the same pulsing parameters. After treatment, histopathological evaluation of the samples was completed. To determine the feasibility of treating OS through intact skin/soft tissue, additional histotripsy experiments assessed OS with overlying tissues. Generation of bubble clouds was achieved at the focus in all tumor samples at peak negative pressures of 26.2 ± 4.5 MPa. Histopathology revealed effective cell ablation in treated areas for OS tumors, with no evidence of cell death or tissue damage in normal tissues. Treatment through tissue/skin resulted in generation of well-confined bubble clouds and ablation zones inside OS tumors. Results illustrate the feasibility of treating OS tumors with histotripsy.

Ambient air pollution and low temperature associated with case fatality of COVID-19: A nationwide retrospective cohort study in China.

The evidence for the effects of environmental factors on COVID-19 case fatality remains controversial, and it is crucial to understand the role of preventable environmental factors in driving COVID-19 fatality. We thus conducted a nationwide cohort study to estimate the effects of environmental factors (temperature, particulate matter [PM2.5, PM10], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]) on COVID-19 case fatality. A total of 71,808 confirmed COVID-19 cases were identified and followed up for their vital status through April 25, 2020. Exposures to ambient air pollution and temperature were estimated by linking the city- and county-level monitoring data to the residential community of each participant. For each participant, two windows were defined: the period from symptom onset to diagnosis (exposure window I) and the period from diagnosis date to date of death/recovery or end of the study period (exposure window II). Cox proportional hazards models were used to estimate the associations between these environmental factors and COVID-19 case fatality. COVID-19 case fatality increased in association with environmental factors for the two exposure windows. For example, each 10 µg/m3 increase in PM2.5, PM10, O3, and NO2 in window I was associated with a hazard ratio of 1.11 (95% CI 1.09, 1.13), 1.10 (95% CI 1.08, 1.13), 1.09 (95 CI 1.03, 1.14), and 1.27 (95% CI 1.19, 1.35) for COVID-19 fatality, respectively. A significant effect was also observed for low temperature, with a hazard ratio of 1.03 (95% CI 1.01, 1.04) for COVID-19 case fatality per 1°C decrease. Subgroup analysis indicated that these effects were stronger in the elderly, as well as in those with mild symptoms and living in Wuhan or Hubei. Overall, the sensitivity analyses also yielded consistent estimates. Short-term exposure to ambient air pollution and low temperature during the illness would play a nonnegligible part in causing case fatality due to COVID-19. Reduced exposures to high concentrations of PM2.5, PM10, O3, SO2, and NO2 and low temperature would help improve the prognosis and reduce public health burden.

Focused ultrasound tumour ablation in small animal oncology.

The cancer incidence rates for humans and animals remain high, and efforts to improve cancer treatment are crucial. Cancer treatment for solid tumours includes both treatment of the primary tumour and of metastasis. Surgery is commonly employed to resect primary and metastatic tumours, but is invasive, and is not always the optimal treatment modality. Prevention and treatment of metastatic disease often utilizes a multimodal approach, but metastasis remains a major cause of death for both human and veterinary cancer patients. Focused ultrasound (FUS) tumour ablation techniques represent a novel non-invasive approach to treating cancer. FUS ablation is precise, thus sparing adjacent critical structures while ablating the tumour. FUS ablation can occur in a thermal or non-thermal fashion. Thermal FUS ablation, also known as high intensity focused ultrasound (HIFU) ablation, destroys tumour cells via heat, whereas non-thermal FUS, known as histotripsy, ablates tumour cells via mechanical disintegration of tissue. Not only can HIFU and histotripsy ablate tumours, they also demonstrate potential to upregulate the host immune system towards an anti-tumour response. The aim of this report is provide a description of HIFU and histotripsy tumour ablation, with a focus on the basic principles of their ablation mechanisms and their clinical applicability in the field of veterinary oncology.