Community trial evaluating the integration of Indigenous healing practices and a harm reduction approach with principles of seeking safety in an Indigenous residential treatment program in northern Ontario.

OBJECTIVE: Our primary objective was to evaluate how the Indigenous Healing and Seeking Safety (IHSS) model impacted residential addiction treatment program completion rates. Our secondary objective was to evaluate health service use 6 months before and 6 months after residential treatment for clients who attended the program before and after implementing IHSS. METHODS: We observed clients of the Benbowopka Residential Treatment before IHSS implementation (from April 2013 to March 31, 2016) and after IHSS implementation (from January 1, 2018 - March 31, 2020). The program data were linked to health administration data, including the Ontario Health Insurance Plan (OHIP) physician billing, the Registered Persons Database (RPDB), the National Ambulatory Care Reporting System (NACRS), and the Discharge Abstract Database (DAD). Chi-square tests were used to compare patient characteristics in the no-IHSS and IHSS groups. We used logistic regression to estimate the association between IHSS and treatment completion. We used generalized estimating equation (GEE) regression model to evaluate health service use (including primary care visits, ED visits overall and for substance use, hospitalizations and mental health visits), Results: There were 266 patients in the no-IHSS group and 136 in the IHSS group. After adjusting for individual characteristics, we observed that IHSS was associated with increased program completion rates (odds ratio = 1.95, 95% CI 1.02-3.70). There was no significant association between IHSS patients' health service use at time one or time two. Primary care visits time 1: aOR 0.55, 95%CI 0.72-1.13, time 2: aOR 1.13, 95%CI 0.79-1.23; ED visits overall time 1: aOR 0.91, 95%CI 0.67-1.23, time 2: aOR 1.06, 95%CI 0.75-1.50; ED visits for substance use time 1: aOR 0.81, 95%CI 0.47-1.39, time 2: aOR 0.79, 95%CI 0.37-1.54; Hospitalizations time 1: aOR 0.78, 95%CI 0.41-1.47, time 2: aOR 0.76, 95%CI 0.32-1.80; Mental health visits time 1: aOR 0.66, 95%CI 0.46-0.96, time 2: aOR 0.92 95%CI 0.7-1.40. CONCLUSIONS: Our results indicate that IHSS positively influenced program completion but had no significant effect on health service use. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov (identifier number NCT04604574). First registration 10/27/2020.

Trends in Blunt Splenic Injury Management: The Rise of Splenic Artery Embolization.

INTRODUCTION: Splenic injury is common in blunt trauma. We sought to evaluate the injury characteristics and outcomes of BSI admitted over a 10-y period to an academic trauma center. METHODS: A retrospective review of adult blunt splenic injury patients admitted between January 2009 and September 2018. RESULTS: The 423 patients meeting inclusion criteria were divided by management: Observational (OBS, n = 261), splenic surgery (n = 114 including 4 splenorrhaphy patients), SAE (n = 43), and multiple treatment modalities (3 had SAE followed by surgery and 2 OBS patients underwent splenic surgery at readmission). The most common mechanism of injury was motor vehicle collision (47.8%). The median ISS (OBS 17, SAE 22, Surgery 34) and spleen AIS (OBS 2, SAE 3, Surgery 4) were significantly different.  Complication rates (OBS 21.8%, SAE 9.3%, Surgery 45.6%) rates were significantly different, but mortality (OBS 7.3%, SAE 2.3%, Surgery 13.2%), discharge to home and readmission rates were not. Additional abdominal injuries were identified in 26.3% of the surgery group and 2.7% of OBS group. SAE rate increased from 3.0% to 28%; median spleen AIS remained 2-3. Thirty-five patients expired; 28 had severe head, chest, and/or extremity injuries (AIS ≥4). CONCLUSION: SAE rates increased over time. Splenorrhaphy rates were low. SAE was associated with relatively low rates of mortality and complications in appropriately selected patients.

A study protocol for a quasi-experimental community trial evaluating the integration of indigenous healing practices and a harm reduction approach with principles of seeking safety in an indigenous residential treatment program in Northern Ontario.

BACKGROUND: Indigenous communities in Canada face significant challenges with intergenerational trauma, which manifests in substance use disorders. There is consensus that connecting treatment approaches to culture, land, community, and spiritual practices is a pathway to healing trauma and substance use disorders for Indigenous peoples. Indigenous residential addiction treatment programs have been established as the primary intervention to provide healing for Indigenous peoples with substance use disorders and intergenerational trauma. However, there is limited evidence demonstrating the effectiveness of these programs. In collaboration with the Benbowopka Treatment Centre, this paper describes a study protocol which aims to evaluate the effectiveness of blending Indigenous Healing Practices and Seeking Safety for the treatment of Indigenous patients with intergenerational trauma and substance use disorders. METHODS: We will conduct a pre/post Quasi Experimental Community trial, to compare historical treatment outcomes for patients following the implementation of Indigenous Healing and Seeking Safety. We will conduct quantitative and qualitative analyses to understand the differences before and after the intervention is implemented. The pre- Indigenous Healing and Seeking Safety intervention study window will span from 2013 to 2016; n = 343, and the post-Indigenous Healing and Seeking Safety intervention study window from 2018 to 2020; n > 300. All participants will be enrolled in the Benbowopka residential treatment for the first time during the study periods. All data will be anonymized at the time of data entry. Propensity matching will be undertaken for patient characteristics, including sex/gender, age, and substance use type. RESULTS AND CONCLUSIONS: The study findings could be used to inform intergenerational trauma and substance use disorders residential treatment programming for Indigenous communities across Canada. Our work will contribute to the field of community-based intergenerational trauma and substance use disorders programming by addressing objectives that consider: (a) the patient perspective, (b) the program perspective, and (c) the community perspective. The study findings may validate an innovative approach for evaluating the effectiveness of residential addiction treatment and particularly the effective and appropriate care for Indigenous patients with intergenerational trauma and substance use disorders.

Secular decline in limb bone strength among South African Africans during the 19th and 20th centuries.

OBJECTIVES: South African Africans have been reported to have experienced negative or null secular trends in stature and other measures of skeletal structure across the 19th and 20th centuries, presumably due to poor living conditions during a time of intensifying racial discrimination. Here, we investigate whether any secular trend is apparent in limb bone strength during the same period. MATERIALS AND METHODS: Cadaver-derived skeletons (n = 221) were analyzed from female and male South African Africans who were born between 1839 and 1970, lived in and around Johannesburg, and died between 1925 and 1991 when they were 17-90 years of age. For each skeleton, a humerus and femur were scanned using computed tomography, and mid-diaphyseal cross-sectional geometric properties were calculated and scaled according to body size. RESULTS: In general linear mixed models accounting for sex, age at death, and skeletal element, year of birth was a significant (p < .05) negative predictor of size-standardized mid-diaphyseal cortical area (a proxy for resistance to axial loading) and polar moment of area (a proxy for resistance to bending and torsion), indicating a temporal trend toward diminishing limb bone strength. No significant interactions were detected between year of birth and age at death, suggesting that the decline in limb bone strength was mainly due to changes in skeletal maturation rather than severity of age-related bone loss. DISCUSSION: Limb bone strength is thus potentially another feature of the skeletal biology of South African Africans that was compromised by poor living conditions during the 19th and 20th centuries.

EULAR/EFORT recommendations for management of patients older than 50†years with a fragility fracture and prevention of subsequent fractures.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

A critical hybrid realist-outcomes systematic review of relationships between medical education programmes and communities: BEME Guide No. 35.

BACKGROUND: The relationships between medical schools and communities have long inspired and troubled medical education programmes. Successive models of community-oriented, community-based and community-engaged medical education have promised much and delivered to varying degrees. A two-armed realist systematic review was undertaken to explore and synthesize the evidence on medical school-community relationships. METHOD: One arm used standard outcomes criteria (Kirkpatrick levels), the other a realist approach seeking out the underlying contexts, mechanisms and outcomes. 38 reviewers completed 489 realist reviews and 271 outcomes reviews; 334 articles were reviewed in the realist arm and 181 in the outcomes arm. Analyses were based on: descriptive statistics on both articles and reviews; the outcomes involved; the quality of the evidence presented; realist contexts, mechanisms, and outcomes; and an analysis of underlying discursive themes. FINDINGS: The literature on medical school-community relationships is heterogeneous and largely idiographic, with no common standards for what a community is, who represents communities, what a relationship is based on, or whose needs are or should be being addressed or considered. CONCLUSIONS: Community relationships can benefit medical education, even if it is not always clear why or how. There is much opportunity to improve the quality and precision of scholarship in this area.

FRAX-based assessment and intervention thresholds--an exploration of thresholds in women aged 50 years and older in the UK.

UNLABELLED: Under current guidelines, based on prior fracture probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold (a fixed threshold from the age of 70 years) reduces this disparity, increases treatment access and decreases the need for bone densitometry. INTRODUCTION: Several international guidelines set age-specific intervention thresholds at the 10-year probability of fracture equivalent to a woman of average BMI with a prior fracture. At older ages (≥70 years), women with prior fracture selected for treatment are at lower average absolute risk than those selected for treatment in the absence of prior fracture, prompting consideration of alternative thresholds in this age group. METHODS: Using a simulated population of 50,633 women aged 50-90 years in the UK, with a distribution of risk factors similar to that in the European FRAX derivation cohorts and a UK-matched age distribution, the current NOGG intervention and assessment thresholds were compared to one where the thresholds remained constant from 70 years upwards. RESULTS: Under current thresholds, 45.1% of women aged ≥70 years would be eligible for therapy, comprising 37.5% with prior fracture, 2.2% with high risk but no prior fracture and 5.4% selected for treatment after bone mineral density (BMD) measurement. Mean hip fracture probability was 11.3, 23.3 and 17.6%, respectively, in these groups. Under the alternative thresholds, the overall proportion of women treated increased from 45.1 to 52.9%, with 8.4% at high risk but no prior fracture and 7.0% selected for treatment after BMD measurement. In the latter group, the mean probability of hip fracture was identical to that observed in women with prior fracture (11.3%). The alternative threshold also reduced the need for BMD measurement, particularly at older ages (>80 years). CONCLUSIONS: The alternative thresholds equilibrate fracture risk, particularly hip fracture risk, in those with or without prior fracture selected for treatment and reduce BMD usage at older ages.

Diurnal variation of the potassium layer in the upper atmosphere.

Measurements of the diurnal cycle of potassium (K) atoms between 80 and 110 km have been made during October (for the years 2004-2011) using a Doppler lidar at Kühlungsborn, Germany (54.1°N, 11.7°E). A pronounced diurnal variation is observed in the K number density, which is explored by using a detailed description of the neutral and ionized chemistry of K in a three-dimensional chemistry climate model. The model captures both the amplitude and phase of the diurnal and semidiurnal variability of the layer, although the peak diurnal amplitude around 90 km is overestimated. The model shows that the total potassium density (≈ K + K+ + KHCO3) exhibits little diurnal variation at each altitude, and the diurnal variations are largely driven by photochemical conversion between these reservoir species. In contrast, tidally driven vertical transport has a small effect at this midlatitude location, and diurnal fluctuations in temperature are of little significance because they are small and the chemistry of K is relatively temperature independent.

Combining data and meta-analysis to build Bayesian networks for clinical decision support.

Complex clinical decisions require the decision maker to evaluate multiple factors that may interact with each other. Many clinical studies, however, report 'univariate' relations between a single factor and outcome. Such univariate statistics are often insufficient to provide useful support for complex clinical decisions even when they are pooled using meta-analysis. More useful decision support could be provided by evidence-based models that take the interaction between factors into account. In this paper, we propose a method of integrating the univariate results of a meta-analysis with a clinical dataset and expert knowledge to construct multivariate Bayesian network (BN) models. The technique reduces the size of the dataset needed to learn the parameters of a model of a given complexity. Supplementing the data with the meta-analysis results avoids the need to either simplify the model - ignoring some complexities of the problem - or to gather more data. The method is illustrated by a clinical case study into the prediction of the viability of severely injured lower extremities. The case study illustrates the advantages of integrating combined evidence into BN development: the BN developed using our method outperformed four different data-driven structure learning methods, and a well-known scoring model (MESS) in this domain.

On the fluid dynamics of a laboratory scale single-use stirred bioreactor.

The commercial success of mammalian cell-derived recombinant proteins has fostered an increase in demand for novel single-use bioreactor (SUB) systems that facilitate greater productivity, increased flexibility and reduced costs (Zhang et al., 2010). These systems exhibit fluid flow regimes unlike those encountered in traditional glass/stainless steel bioreactors because of the way in which they are designed. With such disparate hydrodynamic environments between SUBs currently on the market, traditional scale-up approaches applied to stirred tanks should be revised. One such SUB is the Mobius® 3 L CellReady, which consists of an upward-pumping marine scoping impeller. This work represents the first experimental study of the flow within the CellReady using a Particle Image Velocimetry (PIV) approach, combined with a biological study into the impact of these fluid dynamic characteristics on cell culture performance. The PIV study was conducted within the actual vessel, rather than using a purpose-built mimic. PIV measurements conveyed a degree of fluid compartmentalisation resulting from the up-pumping impeller. Both impeller tip speed and fluid working volume had an impact upon the fluid velocities and spatial distribution of turbulence within the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza) producing an IgG4 antibody. Disparity in cellular growth and viability throughout the range of operating conditions used (80-350 rpm and 1-2.4 L working volume) was not substantial, although a significant reduction in recombinant protein productivity was found at 350 rpm and 1 L working volume (corresponding to the highest Reynolds number tested in this work). The study shows promise in the use of PIV to improve understanding of the hydrodynamic environment within individual SUBs and allows identification of the critical hydrodynamic parameters under the different flow regimes for compatibility and scalability across the range of bioreactor platforms.

Tissue biomarkers of breast cancer and their association with conventional pathologic features.

BACKGROUND: Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features. METHODS: To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed. RESULTS: From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer. CONCLUSION: This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients.

Balloon kyphoplasty compared to vertebroplasty and nonsurgical management in patients hospitalised with acute osteoporotic vertebral compression fracture: a UK cost-effectiveness analysis.

UNLABELLED: The purpose of the study was to estimate the cost-effectiveness of balloon kyphoplasty compared to nonsurgical management and vertebroplasty for the treatment of hospitalised osteoporotic vertebral compression fractures in the UK. A cost-effectiveness model was constructed and used for analysis. Balloon kyphoplasty may be cost-effective compared to relevant alternatives. INTRODUCTION: The objective of this study was to estimate the cost-effectiveness of balloon kyphoplasty (BKP) for the treatment of patients hospitalised with acute osteoporotic vertebral compression fracture (OVCF) compared to percutaneous vertebroplasty (PVP) and nonsurgical management (NSM) in the UK. METHODS: A Markov simulation model was developed to evaluate treatment with BKP, NSM and PVP in patients with symptomatic OVCF. Data on health-related quality of life (HRQoL) with acute OVCF were derived from the FREE and VERTOS II randomised clinical trials (RCTs) and normalised to the NSM arm in the FREE trial. Estimated differences in mortality among the treatments and costs for NSM were obtained from the literature whereas procedure costs for BKP and PVP were obtained from three National Health Service hospitals. It was assumed that BKP and PVP reduced hospital length of stay by 6 days compared to NSM. RESULTS: The incremental cost-effectiveness ratio was estimated at Great Britain Pound Sterling (GBP) 2,706 per quality-adjusted life year (QALY) and GBP 15,982 per QALY compared to NSM and PVP, respectively. Sensitivity analysis showed that the cost-effectiveness of BKP vs. NSM was robust when mortality and HRQoL benefits with BKP were varied. The cost-effectiveness of BKP compared to PVP was particularly sensitive to changes in the mortality benefit. CONCLUSION: BKP may be a cost-effective strategy for the treatment of patients hospitalised with acute OVCF in the UK compared to NSM and PVP. Additional RCT data on the benefits of BKP and PVP compared to simulated sham surgery and further data on the mortality benefits with BKP compared to NSM and PVP would reduce uncertainty.

Capture the Fracture: a Best Practice Framework and global campaign to break the fragility fracture cycle.

UNLABELLED: The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world. INTRODUCTION: FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk. METHODS: Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery. RESULTS: The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award 'Capture the Fracture Best Practice Recognition' to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities. CONCLUSION: Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.

Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides.

Mutations reducing the functional activity of leptin, the leptin receptor, alpha-melanocyte stimulating hormones (alpha-MSH) and the melanocortin-4 receptor (Mc4r) all lead to obesity in mammals. Moreover, mutant mice that ectopically express either agouti (Ay/a mice) or agouti-related protein (Agrp), antagonists of melanocortin signalling, become obese. These data suggest that alpha-MSH signalling transduced by Mc4r tonically inhibits feeding; however, it is not known to what extent this pathway mediates leptin signalling. We show here that Mc4r-deficient (Mc4r-/-) mice do not respond to the anorectic actions of MTII, an MSH-like agonist, suggesting that alpha-MSH inhibits feeding primarily by activating Mc4r. Obese Mc4r-/-mice do not respond significantly to the inhibitory effects of leptin on feeding, whereas non-obese Mc4r-/- mice do. These data demonstrate that melanocortin signalling transduced by Mc4r is not an exclusive target of leptin action and that factors resulting from obesity contribute to leptin resistance. Leptin resistance of obese Mc4r-/- mice does not prevent their response to the anorectic actions of ciliary neurotrophic factor (CNTF), corticotropin releasing factor (CRF), or urocortin; or the orexigenic actions of neuropeptide Y (NPY) or peptide YY (PYY), indicating that these neuromodulators act independently or downstream of Mc4r signalling.

Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.

Cowden disease (CD) is an autosomal dominant cancer predisposition syndrome associated with an elevated risk for tumours of the breast, thyroid and skin. Lhermitte-Duclos disease (LDD) cosegregates with a subset of CD families and is associated with macrocephaly, ataxia and dysplastic cerebellar gangliocytomatosis. The common feature of these diseases is a predisposition to hamartomas, benign tumours containing differentiated but disorganized cells indigenous to the tissue of origin. Linkage analysis has determined that a single locus within chromosome 10q23 is likely to be responsible for both of these diseases. A candidate tumour suppressor gene (PTEN) within this region is mutated in sporadic brain, breast and prostate cancer. Another group has independently isolated the same gene, termed MMAC1, and also found somatic mutations throughout the gene in advanced sporadic cancers. Mutational analysis of PTEN in CD kindreds has identified germline mutations in four of five families. We found nonsense and missense mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene. Thus, PTEN appears to behave as a tumour suppressor gene in the germline. Our data also imply that PTEN may play a role in organizing the relationship of different cell types within an organ during development.

Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass.

Genetic and pharmacological studies have defined a role for the melanocortin-4 receptor (Mc4r) in the regulation of energy homeostasis. The physiological function of Mc3r, a melanocortin receptor expressed at high levels in the hypothalamus, has remained unknown. We evaluated the potential role of Mc3r in energy homeostasis by studying Mc3r-deficient (Mc3r(-/-)) mice and compared the functions of Mc3r and Mc4r in mice deficient for both genes. The 4-6-month Mc3r-/- mice have increased fat mass, reduced lean mass and higher feed efficiency than wild-type littermates, despite being hypophagic and maintaining normal metabolic rates. (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia. Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels. Mice lacking both Mc3r and Mc4r become significantly heavier than Mc4r(-/-) mice. We conclude that Mc3r and Mc4r serve non-redundant roles in the regulation of energy homeostasis.

Comparison between ozone column depths and methane lifetimes computed by one- and three-dimensional models at different atmospheric O2 levels.

Recently, Cooke et al. (Cooke et al. 2022 R. Soc. Open Sci. 9, 211165. (doi:10.1098/rsos.211165)) used a three-dimensional coupled chemistry-climate model (WACCM6) to calculate ozone column depths at varied atmospheric O2 levels. They argued that previous one-dimensional (1-D) photochemical model studies, e.g. Segura et al. (Segura et al. 2003 Astrobiology 3, 689-708. (doi:10.1089/153110703322736024)), may have overestimated the ozone column depth at low pO2, and hence also overestimated the lifetime of methane. We have compared new simulations from an updated version of the Segura et al. model with those from WACCM6, together with some results from a second three-dimensional model. The discrepancy in ozone column depths is probably due to multiple interacting parameters, including H2O in the upper troposphere, lower boundary conditions, vertical and meridional transport rates, and different chemical mechanisms, especially the treatment of O2 photolysis in the Schumann-Runge (SR) bands (175-205 nm). The discrepancy in tropospheric OH concentrations and methane lifetime between WACCM6 and the 1-D model at low pO2 is reduced when absorption from CO2 and H2O in this wavelength region is included in WACCM6. Including scattering in the SR bands may further reduce this difference. Resolving these issues can be accomplished by developing an accurate parametrization for O2 photolysis in the SR bands and then repeating these calculations in the various models.

Dynamics of nephron-vascular network.

The paper presents a modeling study of the spatial dynamics of a nephro-vascular network consisting of individual nephrons connected via a tree-like vascular branching structure. We focus on the effects of nonlinear mechanisms that are responsible for the formation of synchronous patterns in order to learn about processes not directly amenable to experimentation. We demonstrate that: (i) the nearest nephrons are synchronized in-phase due to a vascular propagated electrical coupling, (ii) the next few branching levels display a formation of phase-shifted patterns due to hemodynamic coupling and mode elimination, and (iii) distantly located areas show asynchronous behavior or, if all nephrons and branches are perfectly identical, an infinitely long transient behavior. These results contribute to the understanding of mechanisms responsible for the highly dynamic and limited synchronization observed among groups of nephrons despite of the fairly strong interaction between the individual units.

A revised lower estimate of ozone columns during Earth's oxygenated history.

The history of molecular oxygen (O2) in Earth's atmosphere is still debated; however, geological evidence supports at least two major episodes where O2 increased by an order of magnitude or more: the Great Oxidation Event (GOE) and the Neoproterozoic Oxidation Event. O2 concentrations have likely fluctuated (between 10-3 and 1.5 times the present atmospheric level) since the GOE ∼2.4 Gyr ago, resulting in a time-varying ozone (O3) layer. Using a three-dimensional chemistry-climate model, we simulate changes in O3 in Earth's atmosphere since the GOE and consider the implications for surface habitability, and glaciation during the Mesoproterozoic. We find lower O3 columns (reduced by up to 4.68 times for a given O2 level) compared to previous work; hence, higher fluxes of biologically harmful UV radiation would have reached the surface. Reduced O3 leads to enhanced tropospheric production of the hydroxyl radical (OH) which then substantially reduces the lifetime of methane (CH4). We show that a CH4 supported greenhouse effect during the Mesoproterozoic is highly unlikely. The reduced O3 columns we simulate have important implications for astrobiological and terrestrial habitability, demonstrating the relevance of three-dimensional chemistry-climate simulations when assessing paleoclimates and the habitability of faraway worlds.

Implementation and evaluation of a two-eyed seeing approach using traditional healing and seeking safety in an indigenous residential treatment program in Northern Ontario.

Indigenous clients in need of residential care for substance use disorders (SUD) often present with the diagnosis of substance use disorder (SUD) combined with intergenerational trauma (IGT) or both. SUD is exceedingly prevalent amongst Indigenous peoples due to the health impacts of colonisation, residential school trauma, and IGT on this population's health. We evaluated the effectiveness of a Two-Eyed Seeing approach in a four-week harm reduction residential treatment programme for clients with a history of SUD and IGT. This treatment approach blended Indigenous Healing practices with Seeking Safety based on Dr. Teresa Marsh's research work known as Indigenous Healing and Seeking Safety (IHSS). The data presented in this study was drawn from a larger trial. This qualitative study was undertaken in collaboration with the Benbowopka Treatment Centre in Blind River, Northern Ontario, Canada. Patient characteristic data were collected from records for 157 patients who had enrolled in the study from April 2018 to February 2020. Data was collected from the Client Quality Assurance Survey tool. We used the qualitative thematic analysis method to analyse participants' descriptive feedback about the study. Four themes were identified: (1) Motivation to attend treatment; (2) Understanding Benbowopka's treatment programme and needs to be met; (3) Satisfaction with all interventions; and (4) Moving forward. We utilised a conceptualised descriptive framework for the four core themes depicted in the medicine wheel. This qualitative study affirmed that cultural elements and the SS Western model were highly valued by all participants. The impact of the harm reduction approach, coupled with traditional healing methods, further enhanced the outcome. This study was registered with clinicaltrials.gov (identifier number NCT0464574).