Antarctica is one of Earth's most untouched, inhospitable, and poorly known regions. Although knowledge of its biodiversity has increased over recent decades, a diverse, wide-ranging, and spatially explicit compilation of the biodiversity that inhabits Antarctica's permanently ice-free areas is unavailable. This absence hinders both Antarctic biodiversity research and the integration of Antarctica in global biodiversity-related studies.
View Article and Find Full Text PDFIntroduction: Computational fluid dynamics (CFD) is gaining momentum as a useful mechanism for analyzing obstructive disorders and surgeries in humans and warrants further development for application in equine surgery. While advancements in procedures continue, much remains unknown about the specific impact that different surgeries have on obstructive airway disorders. The objective of this study was to apply CFD analysis to an equine head inhalation model replicating recurrent laryngeal neuropathy (RLN) and four surgical procedures.
View Article and Find Full Text PDFBackground: Young patients ≤ 50 years old with multiple myeloma (MM) account for about 10% of cases and are underrepresented in the literature.
Methods: We explored disease characteristics, treatments, and outcomes following modern therapies of young MM patients using the Canadian Myeloma Research Group (CMRG) database. We included 493 patients ≤ 50 years old diagnosed with MM or plasma cell leukemia without concurrent amyloidosis or POEMS syndrome from January 1, 2010, to July 1, 2022.
One sixth of human cancers harbor pathogenic germline variants, but few studies have established their functional contribution to cancer outcomes. Here, we developed a humanized mouse model harboring a common East Asian polymorphism, the BIM deletion polymorphism (BDP), which confers resistance to oncogenic kinase inhibitors through generation of non-apoptotic splice isoforms. However, despite its clear role in mediating bulk resistance in patients, the BDP's role in cancer stem and progenitor cells, which initiate disease and possess altered BCL-2 rheostats compared to differentiated tumor cells, remains unknown.
View Article and Find Full Text PDFUnruptured intracranial aneurysms are common in the general population, and many uncertainties remain when predicting rupture risks and treatment outcomes. One of the cutting-edge tools used to investigate this condition is computational fluid dynamics (CFD). However, CFD is not yet mature enough to guide the clinical management of this disease.
View Article and Find Full Text PDFIn patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial.
View Article and Find Full Text PDFMultiple myeloma remains an incurable cancer mostly affecting older adults and is characterized by a series of remission inductions and relapses. This study aims to evaluate the outcomes in newly diagnosed transplant-ineligible patients using bortezomib/lenalidomide-based regimens in the Canadian real world as well as their outcomes in the second line. The Canadian Myeloma Research Group Database (CMRG-DB) is a national database with input from multiple Canadian Centres with now up to 8000 patients entered.
View Article and Find Full Text PDFBackground: Infusion failure may have severe consequences for patients receiving critical, short-half-life infusions. Continued interruptions to infusions can lead to subtherapeutic therapy.
Objective: This study aims to identify and rank determinants of the longevity of continuous infusions administered through syringe drivers, using nonlinear predictive models.
Fibroblast growth factor receptor (FGFR) kinase inhibitors have been shown to be effective in the treatment of intrahepatic cholangiocarcinoma and other advanced solid tumors harboring alterations, but the toxicity of these drugs frequently leads to dose reduction or interruption of treatment such that maximum efficacy cannot be achieved. The most common adverse effects are hyperphosphatemia caused by FGFR1 inhibition and diarrhea due to FGFR4 inhibition, as current therapies are not selective among the FGFRs. Designing selective inhibitors has proved difficult with conventional approaches because the orthosteric sites of FGFR family members are observed to be highly similar in X-ray structures.
View Article and Find Full Text PDFThe small ice-free areas of Antarctica are essential locations for both biodiversity and scientific research but are subject to considerable and expanding human impacts, resulting primarily from station-based research and support activities, and local tourism. Awareness by operators of the need to conserve natural values in and around station and visitor site footprints exists, but the cumulative nature of impacts often results in reactive rather than proactive management. With human activity spread across many isolated pockets of ice-free ground, the pathway to the greatest reduction of human impacts within this natural reserve is through better management of these areas, which are impacted the most.
View Article and Find Full Text PDFMultiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort.
View Article and Find Full Text PDFAutologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.
View Article and Find Full Text PDFIntroduction: Although daratumumab-containing regimens improve multiple myeloma (MM) outcomes, recurrence is inevitable.
Methods And Objective: We performed a retrospective study using the Canadian Myeloma Research Group Database to benchmark the efficacy of carfilzomib- or pomalidomide-based therapies immediately following progression on daratumumab treatment.
Results: We identified 178 such patients; median number of prior lines of therapy was 3, 97% triple-class exposed, and 60% triple-class refractory.
While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of patients not receiving subsequent therapy is useful for MM stakeholders. We performed an analysis of attrition rates in a large disease-specific database of patients with newly diagnosed MM who received at least one line of therapy between Jan 1/10-Dec 31/20.
View Article and Find Full Text PDFThe external ear develops from an organized convergence of ventrally migrating neural crest cells into the first and second branchial arches. Defects in external ear position are often symptomatic of complex syndromes such as Apert, Treacher-Collins, and Crouzon Syndrome. The low set ears (Lse) spontaneous mouse mutant is characterized by the dominant inheritance of a ventrally shifted external ear position and an abnormal external auditory meatus (EAM).
View Article and Find Full Text PDFIntroduction: Computational fluid dynamics (CFD) has proven useful in the planning of upper airway surgery in humans, where it is used to anticipate the influence of the surgical procedures on post-operative airflow. This technology has only been reported twice in an equine model, with a limited scope of airflow mechanics situations examined. The reported study sought to widen this application to the variety of procedures used to treat equine recurrent laryngeal neuropathy (RLN).
View Article and Find Full Text PDFAlthough the availability of effective novel treatments has positively impacted the quality of life and survival of newly diagnosed multiple myeloma (MM) patients, benefits in the transplant ineligible MM population may be limited by functional/frailty status. The Canadian Myeloma Research Group Consensus Guideline Consortium proposes consensus recommendations for the first-line treatment of transplant ineligible MM. To address the needs of physicians and people diagnosed with MM, this document further focuses on eligibility for transplant, frailty assessment, management of adverse events, assessment of treatment response, and monitoring for disease relapse.
View Article and Find Full Text PDFAntarctic terrestrial biodiversity faces multiple threats, from invasive species to climate change. Yet no large-scale assessments of threat management strategies exist. Applying a structured participatory approach, we demonstrate that existing conservation efforts are insufficient in a changing world, estimating that 65% (at best 37%, at worst 97%) of native terrestrial taxa and land-associated seabirds are likely to decline by 2100 under current trajectories.
View Article and Find Full Text PDFAntarctic biodiversity faces an unknown future with a changing climate. Most terrestrial biota is restricted to limited patches of ice-free land in a sea of ice, where they are adapted to the continent's extreme cold and wind and exploit microhabitats of suitable conditions. As temperatures rise, ice-free areas are predicted to expand, more rapidly in some areas than others.
View Article and Find Full Text PDFIntroduction: The main objective was to present characteristics and outcome of patients without sustained field return of spontaneous circulation (ROSC) transported to hospital with ongoing cardiopulmonary resuscitation (CPR). Our secondary objectives were to investigate hospital-based interventions and the performance of the universal Termination of Resuscitation-rule (uTOR).
Methods: In this retrospective observational cohort study, out-of-hospital cardiac arrest (OHCA) patients arriving to the emergency department of a university hospital in Sweden during a six-year period (2010-2015) were identified using a prospectively recorded hospital-based registry.
Antarctica's isolation has been breached by various non-native species, including microbes, a grass, and some invertebrates. As yet, no marine species have reportedly established populations. With increasing effects of climate change and human activity, continued concerted action is needed to keep Antarctica protected from the impacts of non-native species establishment.
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