Impact of COVID-19 on electroconvulsive therapy practice across Canadian provinces during the first wave of the pandemic.

BACKGROUND: Electroconvulsive therapy (ECT) is a procedural treatment that is potentially life-saving for some patients with severe psychiatric illness. At the start of the global coronavirus disease 2019 (COVID-19) pandemic, ECT practice was remarkably disrupted, putting vulnerable individuals at increased risk of symptom exacerbation and death by suicide. This study aimed to capture the self-reported experiences of psychiatrists based at healthcare facilities across Canadian provinces who were delivering ECT treatments during the first phase of the COVID-19 pandemic (i.e., from mid-March 2020 to mid-May 2020). METHODS: A multidisciplinary team of experts developed a survey focusing on five domains: ECT unit operations, decision-making, hospital resources, ECT procedure, and mitigating patient impact. Responses were collected from psychiatrists providing ECT at 67 ECT centres in Canada, grouped by four geographical regions (Ontario, Quebec, Atlantic Canada, and Western Canada). RESULTS: Clinical operations of ECT programs were disrupted across all four regions - however, centres in Atlantic Canada were able to best preserve outpatient and maintenance care, while centres in Western Canada were able to best preserve inpatient and acute care. Similarly, Atlantic and Western Canada demonstrated the best decision-making practices of involving the ECT team and clinical ethicists in the development of pandemic-related guidelines. Across all four regions, ECT practice was affected by the redeployment of professionals, the shortage of personal protective equipment, and the need to enforce social distancing. Attempts to introduce modifications to the ECT delivery room and minimize bag-valve-mask ventilation were consistently reported. All four regions developed a new patient prioritization framework, and Western Canada, notably, aimed to provide ECT to only the most severe cases. CONCLUSIONS: The results suggest that ECT provision was disproportionately affected across different parts of Canada. Possible factors that could explain these interregional differences include population, distribution of urban vs. rural areas, pre-pandemic barriers in access to ECT, number of cases, ability to control the spread of infection, and the general reduction in physicians' activities across different areas of health care. Studying these factors in the future will inform how medical centres should respond to public health emergencies and pandemic-related circumstances in the context of procedural treatments.

Examining ACCURE's Nurse Navigation Through an Antiracist Lens: Transparency and Accountability in Cancer Care.

There are persistent disparities in the delivery of cancer treatment, with Black patients receiving fewer of the recommended cancer treatment cycles than their White counterparts on average. To enhance racial equity in cancer care, innovative methods that apply antiracist principles to health promotion interventions are needed. The parent study for the current analysis, the Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) intervention, was a system-change intervention that successfully eliminated the Black-White disparity in cancer treatment completion among patients with early-stage breast and lung cancer. The intervention included specially trained nurse navigators who leveraged real-time data to follow-up with patients during their treatment journeys. Community and academic research partners conducted thematic analysis on all clinical notes (n = 3,251) written by ACCURE navigators after each contact with patients in the specialized navigation arm (n = 162). Analysis was informed by transparency and accountability, principles adapted from the antiracist resource Undoing Racism and determined as barriers to treatment completion through prior research that informed ACCURE. We identified six themes in the navigator notes that demonstrated enhanced accountability of the care system to patient needs. Underlying these themes was a process of enhanced data transparency that allowed navigators to provide tailored patient support. Themes include (1) patient-centered advocacy, (2) addressing system barriers to care, (3) connection to resources, (4) re-engaging patients after lapsed treatment, (5) addressing symptoms and side effects, and (6) emotional support. Future interventions should incorporate transparency and accountability mechanisms and examine the impact on racial equity in cancer care.

Herbivory changes soil microbial communities and greenhouse gas fluxes in a high-latitude wetland.

Herbivory can have strong impacts on greenhouse gas fluxes in high-latitude ecosystems. For example, in the Yukon-Kuskokwim (Y-K) Delta in western Alaska, migratory goose grazing affects the magnitude of soil carbon dioxide (CO2) and methane (CH4) fluxes. However, the underlying drivers of this relationship are unclear, as few studies systematically tease apart the processes by which herbivores influences soil biogeochemistry. To examine these mechanisms in detail, we conducted a laboratory incubation experiment to quantify changes in greenhouse gas fluxes in response to three parameters altered by herbivores in situ: temperature, soil moisture content, and nutrient inputs. These treatments were applied to soils collected in grazing lawns and nearby ungrazed habitat, allowing us to assess how variation in microbial community structure influenced observed responses. We found pronounced differences in both fungal and prokaryotic community composition between grazed and ungrazed areas. In the laboratory incubation experiment, CO2 and CH4 fluxes increased with temperature, soil moisture, and goose fecal addition, suggesting that grazing-related changes in the soil abiotic environment may enhance soil C losses. Yet, these abiotic drivers were insufficient to explain variation in fluxes between soils with and without prior grazing. Differences in trace gas fluxes between grazed and ungrazed areas may result both from herbivore-induced shifts in abiotic parameters and grazing-related alterations in microbial community structure. Our findings suggest that relationships among herbivores and soil microbial communities could mediate carbon-climate feedbacks in rapidly changing high-latitude ecosystems.

Electroconvulsive Therapy in Canada During the First Wave of COVID-19: Results of the "What Happened" National Survey.

OBJECTIVES: The COVID-19 pandemic has disrupted the provision of essential and potentially life-saving procedural treatments such as electroconvulsive therapy (ECT). We surveyed ECT providers across Canada to understand how the first wave of the pandemic affected ECT delivery between mid-March 2020 and mid-May 2020. METHODS: The survey was administered to ECT team members and decision makers at 107 Canadian health care centers with a focus on 5 domains: operations, decision-making, hospital resources, ECT procedure, and patient impact. Responses were obtained from 72 institutions, and collected answers were used to derive representative responses reflecting the situation at each ECT center. For specific domains, responses were split into 2 databases representing the perspective of psychiatrists (n = 67 centers) and anesthesiologists (n = 24 centers). RESULTS: Provision of ECT decreased in 64% centers and was completely suspended in 27% of centers after the onset of the pandemic. Outpatient and maintenance ECT were more affected than inpatient and acute ECT. Programs reported a high level of collaboration between psychiatry and hospital leadership (59%) but a limited input from clinical ethicists (18%). Decisions were mostly made ad hoc leading to variability across institutions in adopted resource allocation, physical location of ECT delivery, and triaging frameworks. The majority of centers considered ECT to be aerosol-generating and incorporated changes to airway management. CONCLUSIONS: Electroconvulsive therapy services in Canada were markedly disrupted by the COVID-19 pandemic. The variability in decision-making across centers warrants the development of a rational approach toward offering ECT in pandemic contexts.

'It's like you don't have a roadmap really': using an antiracism framework to analyze patients' encounters in the cancer system.

Background: Cancer patients can experience healthcare system-related challenges during the course of their treatment. Yet, little is known about how these challenges might affect the quality and completion of cancer treatment for all patients, and particularly for patients of color. Accountability for Cancer Care through Undoing Racism and Equity is a multi-component, community-based participatory research intervention to reduce Black-White cancer care disparities. This formative work aimed to understand patients' cancer center experiences, explore racial differences in experiences, and inform systems-level interventions.Methods: Twenty-seven breast and lung cancer patients at two cancer centers participated in focus groups, grouped by race and cancer type. Participants were asked about what they found empowering and disempowering regarding their cancer care experiences. The community-guided analysis used a racial equity approach to identify racial differences in care experiences.Results: For Black and White patients, fear, uncertainty, and incomplete knowledge were disempowering; trust in providers and a sense of control were empowering. Although participants denied differential treatment due to race, analysis revealed implicit Black-White differences in care.Conclusions: Most of the challenges participants faced were related to lack of transparency, such that improvements in communication, particularly two-way communication could greatly improve patients' interaction with the system. Pathways for accountability can also be built into a system that allows patients to find solutions for their problems with the system itself. Participants' insights suggest the need for patient-centered, systems-level interventions to improve care experiences and reduce disparities.

Network portal: a database for storage, analysis and visualization of biological networks.

The ease of generating high-throughput data has enabled investigations into organismal complexity at the systems level through the inference of networks of interactions among the various cellular components (genes, RNAs, proteins and metabolites). The wider scientific community, however, currently has limited access to tools for network inference, visualization and analysis because these tasks often require advanced computational knowledge and expensive computing resources. We have designed the network portal (http://networks.systemsbiology.net) to serve as a modular database for the integration of user uploaded and public data, with inference algorithms and tools for the storage, visualization and analysis of biological networks. The portal is fully integrated into the Gaggle framework to seamlessly exchange data with desktop and web applications and to allow the user to create, save and modify workspaces, and it includes social networking capabilities for collaborative projects. While the current release of the database contains networks for 13 prokaryotic organisms from diverse phylogenetic clades (4678 co-regulated gene modules, 3466 regulators and 9291 cis-regulatory motifs), it will be rapidly populated with prokaryotic and eukaryotic organisms as relevant data become available in public repositories and through user input. The modular architecture, simple data formats and open API support community development of the portal.

Choice of anesthesia technique is associated with earlier hospital discharge and reduced costs after transcatheter transfemoral aortic valve implantation.

Background: Transcatheter aortic valve implantation (TAVI) has become a viable alternative to palliation in patients with severe aortic stenosis. We compared general anesthesia to conscious sedation for TAVI procedures with respect to post operative morbidity, hospital length of stay, and financial burden. Methods: We conducted a retrospective review of prospectively collected data in patients undergoing transfemoral TAVI procedures from 2012 to 2017. Patients were matched based on age and sex and classed into either general anesthesia or conscious sedation groups respectively. Conscious sedation was provided with a dexmedetomidine infusion, and patients in general anesthesia group received a standard induction, tracheal intubation, and maintenance with sevoflurane. The hospital case costs were compared between the two groups before and after adjustment for inflation. Results: We matched 124 pairs for a total of 248 patients. Both groups were similar with respect to demographic data, past medical history, medications, and intraoperative characteristics. There was no difference in postoperative morbidity and mortality between the two groups. The median hospital length of stay was 5 [interquartile range (IQR): 3, 10] and 7 (IQR: 4, 12) days, P=0.01, and after adjustment for inflation, the total hospital case costs were $48,984 (IQR: $44,802, $61,438) Canadian (CAD) vs. $55,333 (IQR: $46,832, $68,702) CAD, P=0.01, in the conscious sedation and general anesthesia groups, respectively. Conclusions: Advancements in TAVI technologies, conscious sedation and a collaborative, multidisciplinary team approach reduces overall length of hospital stay and procedure costs.

Electrogenic capacity and community composition of anodic biofilms in soil-based bioelectrochemical systems.

Although a number of bacteria are known to be capable of generating an electrical current, the diversity of electrogenic bacteria in soils and the commonality across soil types is relatively unknown. Simple bioelectrochemical cells were constructed to measure the electrogenic capacity and community composition of bacteria originating on cell anodes from three biogeochemically distinct soil types. All three soils supported electrogenic activity, amounting to a maximum sustained current of 1.5-2.1 mA over 55 days. Analysis of fatty acids identified differences in microbial community composition between anode biofilms and far-field soil materials. Anode communities showed greater percentages of fatty acids indicative of Gram-negative bacteria and Actinomycetes. By analysis of anode biofilm genomic DNA via terminal-restriction fragment-length polymorphisms, commonalities in community composition across the three soil types were identified, specifically, the putative presence of bacterial species belonging to the α- and ß-Proteobacteria and the Firmicutes. Subsequent culture and isolation of bacteria from the anodes confirmed the presence of similar classes of bacteria. Results showed that, under saturated conditions, different soils can support electrogenic activity and that the bacterial communities that develop on the anodes share certain common inherent community traits.

The 2019 neuro-rehabilitation implementation framework in Ireland: Challenges for implementation and the implications for people with brain injuries.

In 2019, eight years after the publication of Ireland's first neuro-rehabilitation strategy, an implementation framework was published. This paper describes and assesses the Irish health policy journey to the publication of the 2019 Implementation Framework with a particular focus on tracking the rehabilitation needs of people with acquired brain injury (ABI). Internationally, rehabilitation services are a low priority for governments, with policy makers having limited knowledge and understanding of rehabilitation. This low political priority and policy understanding contributes to under-developed and poorly co-ordinated services for people who need neuro-rehabilitation services, including people with Acquired Brain Injury (ABI). Despite the publication of the 2019 neuro-rehabilitation implementation framework, key challenges remain for people with ABI in Ireland, including the absence of services across the 'pathway', the under-resourcing of specialist rehabilitation services, the impact on the lives of people with brain injury of poor or no access to services, and the lack of good data on this population. The paper concludes with recommendations on how increased political priority of the rehabilitation needs of people with ABI could enhance implementation of the neuro-rehabilitation implementation framework.

The role of changing temperature in microbial metabolic processes during permafrost thaw.

Approximately one fourth of the Earth's Northern Hemisphere is underlain by permafrost, earth materials (soil, organic matter, or bedrock), that has been continuously frozen for at least two consecutive years. Numerous studies point to evidence of accelerated climate warming in the Arctic and sub-Arctic where permafrost is located. Changes to permafrost biochemical processes may critically impact ecosystem processes at the landscape scale. Here, we sought to understand how the permafrost metabolome responds to thaw and how this response differs based on location (i.e. chronosequence of permafrost formation constituting diverse permafrost types). We analyzed metabolites from microbial cells originating from Alaskan permafrost. Overall, permafrost thaw induced a shift in microbial metabolic processes. Of note were the dissimilarities in biochemical structure between frozen and thawed samples. The thawed permafrost metabolomes from different locations were highly similar. In the intact permafrost, several metabolites with antagonist properties were identified, illustrating the competitive survival strategy required to survive a frozen state. Interestingly, the intensity of these antagonistic metabolites decreased with warmer temperature, indicating a shift in ecological strategies in thawed permafrost. These findings illustrate the impact of change in temperature and spatial variability as permafrost undergoes thaw, knowledge that will become crucial for predicting permafrost biogeochemical dynamics as the Arctic and Antarctic landscapes continue to warm.

Establishing New Community-Based Participatory Research Partnerships using the Community-Based Participatory Research Charrette Model: Lessons from the Cancer Health Accountability for Managing Pain and Symptoms Study.

BACKGROUND: Community-based participatory research (CBPR) is a collaborative and equitable approach to research inquiry; however, the process of establishing and maintaining CBPR partnerships can be challenging. There is an ongoing need for innovative strategies that foster partnership development and long-term sustainability. In 2010, the University of North Carolina at Chapel Hill developed a CBPR charrette model to facilitate stakeholder engagement in translational research. OBJECTIVE: To describe how the Cancer Health Accountability for Managing Pain and Symptoms (CHAMPS) Study leveraged the CBPR charrette process to develop and strengthen its CBPR partnership and successfully implement research objectives. METHODS: Fourteen CHAMPS community, academic, and medical partners participated in the CBPR charrette. Two co-facilitators guided the charrette application process and in-person discussion of partnership strengths, needs, and challenges. Community experts (CEs) and academic experts (AEs) with extensive experience in CBPR and health disparities provided technical assistance and recommendations during the in-person charrette. CONCLUSIONS: Overall, the CHAMPS partnership benefited significantly from the charrette process. Specifically, the charrette process engendered greater transparency, accountability, and trust among CHAMPS partners by encouraging collective negotiation of project goals and implementation, roles and responsibilities, and compensation and communication structures. The process also allowed for the exploration of newly identified challenges and potential solutions with support from CEs and AEs. Furthermore, the charrette also functioned as a catalyst for capacity building among CHAMPS community, academic, and medical partners. Future studies should compare the impact of the CBPR charrette, relative to other approaches, on partnership development and process evaluation outcomes.

Removal of Exogenous Materials from the Outer Portion of Frozen Cores to Investigate the Ancient Biological Communities Harbored Inside.

The cryosphere offers access to preserved organisms that persisted under past environmental conditions. In fact, these frozen materials could reflect conditions over vast time periods and investigation of biological materials harbored inside could provide insight of ancient environments. To appropriately analyze these ecosystems and extract meaningful biological information from frozen soils and ice, proper collection and processing of the frozen samples is necessary. This is especially critical for microbial and DNA analyses since the communities present may be so uniquely different from modern ones. Here, a protocol is presented to successfully collect and decontaminate frozen cores. Both the absence of the colonies used to dope the outer surface and exogenous DNA suggest that we successfully decontaminated the frozen cores and that the microorganisms detected were from the material, rather than contamination from drilling or processing the cores.

High rate of invasive fungal infections following nonmyeloablative allogeneic transplantation.

Nonmyeloablative allogeneic transplantation is an emerging therapy for hematologic and solid malignancies and potentially offers patients reduced transplant-related toxicity. Data regarding infectious complications of these protocols are limited, but early studies have demonstrated little infectious morbidity, particularly low rates of invasive fungal infections (IFIs). In the present study, 31 consecutive cases of nonmyeloablative transplantation were reviewed over a 2.5-year period, with a specific focus on infectious complications. Twenty-six patients (84%) had at least 1 significant infection during the year after transplantation, and infection-related mortality was 37%. Cytomegalovirus end-organ disease was diagnosed in 3 patients (10%). Ten patients (32%) were given the diagnosis of IFI; 7 (23%) met criteria for proven IFI. Fungal-related mortality was 80% within the group of patients with IFI and accounted for a significant portion of the overall mortality in the study. Severe graft-versus-host disease, high-dose corticosteroid use, recurrent neutropenia, and relapsed or refractory disease were factors associated with development of IFI.

Human metabolism of [(14)C]indisulam following i.v. infusion in cancer patients.

Indisulam is a new anticancer drug with a unique mechanism of action, arresting the cell cycle at the G1/S transition. The major excretory pathway of indisulam is via the urine, accounting for 63% of the radioactive dose ([(14)C]indisulam) administered in a human mass balance study. Radiochromatographic profiling of urine samples resulted in the detection of several radioactive peaks. The purpose of the present investigation was to elucidate the chemical structures of these observed indisulam metabolites. We collected fractions after chromatographic separation of the urine samples. These fractions were analysed using tandem mass spectrometry. We propose the chemical structure of 15 indisulam metabolites in urine. The metabolism of indisulam is very complex, consisting of oxidative dechlorination, hydroxylation, hydrolysis, acetylation, sulphation and glucuronidation. The clinical relevance of the observed indisulam metabolites needs further investigation.

Quantitative determination of the novel anticancer drug E7070 (indisulam) and its metabolite (1,4-benzenedisulphonamide) in human plasma, urine and faeces by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

E7070 (indisulam) is a novel anticancer drug currently undergoing clinical investigation. We present a sensitive and specific method for the quantitative determination of E7070 and its metabolite M1 (1,4-benzenedisulphonamide) in human plasma, urine and faeces. The analytes and their tetra-deuterated analogues, which were used as internal standards, were isolated from the biological matrix by solid-phase extraction with OASIS cartridges (0.5 mL plasma or 1 mL urine) and by liquid-liquid extraction with ethyl acetate at pH 5 (1 mL faecal homogenate). The analytes were separated on a C8 reversed-phase chromatographic column and analyzed using electrospray ionization and tandem mass spectrometric detection in the negative ion mode. The validated concentration ranges in plasma were 0.1-20 microg/mL for E7070 and 0.01-2 microg/mL for M1. In urine and faecal homogenate, a concentration range from 0.05-10 microg/mL or microg/g, respectively, was validated for both analytes. Validation of the plasma assay was performed according to the most recent FDA guidelines. The assay fulfilled all generally accepted requirements for linearity (r > 0.99, residuals between -8 and 10%), accuracy (-13.5 to 1.4%) and precision (all less than 11%) in the tested matrices. We investigated recovery, stability (working solutions at -20 degrees C and at room temperature, biological matrices at -20 degrees C, room temperature and after 3 freeze/thaw cycles; final extracts at room temperature) and robustness. All these parameters were found acceptable. This method is suited for mass balance studies or therapeutic drug monitoring, as demonstrated by a case example showing plasma concentrations and cumulative excretion of E7070 and M1 in urine and faeces. Furthermore, we show the presence of E7070 metabolites in patient urine.

Pathogen discovery from human tissue by sequence-based computational subtraction.

We have recently reported a new pathogen discovery approach, "computational subtraction". With this approach, non-human transcripts are detected by sequencing cDNA libraries from infected tissue and eliminating those transcripts that match the human genome. We show now that this method is experimentally feasible. We generated a cDNA library from a tissue sample of post-transplant lymphoproliferative disorder (PTLD). 27,840 independent cDNA sequences were filtered by computational subtraction against the known human sequence to identify 32 nonmatching transcripts. Of these, 22 (0.1%) were found to be amplifiable from both infected and noninfected samples and were inferred to be human DNA not yet contained in the available human genome sequence. The remaining 10 sequences could be amplified only from Epstein-Barr virus (EBV)-infected tissues. All 10 corresponded to the known EBV sequence. This proof-of-principle experiment demonstrates that computational subtraction can detect pathogenic microbes in primary human-diseased tissue.

The genome sequence of the filamentous fungus Neurospora crassa.

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes--more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca2+ signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.