Prognosis-Based Definitions for Potentially Inappropriate Treatment: Still Flawed, If Not Futile.

AbstractThis analysis of professional organizational policies regarding potentially inappropriate life-sustaining medical treatment (LSMT) focuses on the specific threshold criteria that policies apply for limiting LSMT, as well as when (if ever) override of patient/surrogate preferences may be reasonable. Our article offers a critical analysis of one influential approach, proffered by the Society of Critical Care Medicine, that applies a prognosis-based definition of nonbeneficial/inappropriate treatment to determine that ethical threshold. We observe that this prognosis-based threshold resembles rationing in important ways, though it pertains to settings where resources may not be limited.

IMPACT CKD: Holistic Disease Model Projecting 10-Year Population Burdens.

Introduction: The significant burden of chronic kidney disease (CKD) is not recognized as a global public health priority, although policies aimed at delaying progression to later stages are required. Therefore, there is need for a holistic disease model to inform decision making that accounts for the multidimensional impact of CKD, and the interrelated factors that modulate progression.

Methods: IMPACT CKD is a microsimulation model that simulates CKD progression and incorporates the effect of clinical events and comorbidities.

BUB1 Inhibition Overcomes Radio- and Chemoradiation Resistance in Lung Cancer.

: Despite advances in targeted therapies and immunotherapies, traditional treatments like microtubule stabilizers (paclitaxel, docetaxel), DNA-intercalating platinum drugs (cisplatin), and radiation therapy remain essential for managing locally advanced and metastatic lung cancer. Identifying novel molecular targets could enhance the efficacy of these treatments. : We hypothesize that BUB1 (Ser/Thr kinase) is overexpressed in lung cancers and its inhibition will sensitize lung cancers to chemoradiation.

The use of E. coli phylogrouping and microbial source tracking (non-species specific, human-specific, bovine-specific bacteroidales markers) to elucidate hydro(geo)logical contamination mechanisms in southeastern Ontario, Canada.

In Ontario, monitoring, maintenance, and treatment of private drinking systems (e.g. wells) are the responsibility of the well owner.

Onasemnogene-abeparvovec administration to premature infants with spinal muscular atrophy.

Twin girls born at 30 weeks' gestation with spinal muscular atrophy (SMA) received onsasemnogene-abeparvovec (OA) at 3.5 weeks of life. They had no treatment-related adverse events, normal acquisition of motor milestones, and normal neurological examination at 19 months.

Nearby and non-nested genes in the human genome have more similar genotype tissue expression.

Neighboring genes within a shared promoter arrangement (i.e. opposite direction with the neighboring ends as the transcriptional start sites) are expected to have a high similarity in genotype tissue expression due to the potential overlap in the promoter region.

The effect of visual cues at different heights on sit-to-stand movements in people with and without low back pain.

Background: Investigating movement strategies that can be utilized to avoid pain-provocation could enhance the management of low back pain episodes.

Objective: To assess the effect of visual cues at different heights on the kinematics of sit-to-stand movements, as well as perceived difficulty and pain levels.

Design: Cross-over design comparing individuals with low back pain to healthy controls.

Muscle short-range stiffness behaves like a maxwell element, not a spring: Implications for joint stability.

Introduction: Muscles play a critical role in supporting joints during activities of daily living, owing, in part, to the phenomenon of short-range stiffness. Briefly, when an active muscle is lengthened, bound cross-bridges are stretched, yielding forces greater than what is predicted from the force length relationship. For this reason, short-range stiffness has been proposed as an attractive mechanism for providing joint stability.

Heterogeneous Mechanical Stress and Interstitial Fluid Flow Predictions Derived from DCE-MRI for Rat U251N Orthotopic Gliomas.

Mechanical stress and fluid flow influence glioma cell phenotype in vitro, but measuring these quantities in vivo continues to be challenging. The purpose of this study was to predict these quantities in vivo, thus providing insight into glioma physiology and potential mechanical biomarkers that may improve glioma detection, diagnosis, and treatment. Image-based finite element models of human U251N orthotopic glioma in athymic rats were developed to predict structural stress and interstitial flow in and around each animal's tumor.

Development of a "big data" groundwater microbial contamination index and spatial comparisons with enteric infection rates in southern Ontario.

Big data have become increasingly important for policymakers and scientists but have yet to be employed for the development of spatially specific groundwater contamination indices or protecting human and environmental health. The current study sought to develop a series of indices via analyses of three variables: Non-E. coli coliform (NEC) concentration, E.

Probabilistic Nested Model Selection in Pharmacokinetic Analysis of DCE-MRI Data in Animal Model of Cerebral Tumor.

Purpose: Best current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel's CA time-trace.

Art Therapy for Paediatric Pain: A Scoping Review.

Pain is common in paediatric populations and is best treated with a multi-disciplinary approach. Art therapy interventions are gaining popularity in paediatrics; however, there is limited evidence on its impact on pain outcomes in children and adolescents. The objective of this scoping review is to map current research on art therapy's impact as an intervention in paediatric populations experiencing any type of pain (i.

BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy.

BUB1 is overexpressed in most human solid cancers, including breast cancer. Higher BUB1 levels are associated with a poor prognosis, especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay of treatment for TNBC.

Photoinitiated Single-Crystal to Single-Crystal Redox Transformations of Titanium-Oxo Clusters.

Titanium-oxo clusters can undergo photochemical reactions under UV light, resulting in the reduction of the titanium-oxo core and oxidation of surface ligands. This is an important step in photocatalytic processes in light-absorbing Ti/O-based clusters, metal-organic frameworks, and (nano)material surfaces; however, studying the direct outcome of this photochemical process is challenging due to the fragility of the immediate photoproducts. In this report, titanium-oxo clusters [TiO(OPr)(L)] ( = 4, L = OPPh, or = 6, L = OCCHBu) undergo a two-electron photoredox reaction in the single-crystal state via an irreversible single-crystal to single-crystal (SC-SC) transformation initiated by a UV laser.

BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.

A circumpolar study unveils a positive non-linear effect of temperature on arctic arthropod availability that may reduce the risk of warming-induced trophic mismatch for breeding shorebirds.

Seasonally abundant arthropods are a crucial food source for many migratory birds that breed in the Arctic. In cold environments, the growth and emergence of arthropods are particularly tied to temperature. Thus, the phenology of arthropods is anticipated to undergo a rapid change in response to a warming climate, potentially leading to a trophic mismatch between migratory insectivorous birds and their prey.

Novel Small Molecule, UTS-1401, as a Radioprotector for Total-Body Irradiation.

We report on a new radioprotector, UTS-1401, a small molecule that was synthesized (by one of us, JS) and evaluated here for its radioprotective effect against total-body irradiation (TBI). Female and male NIH Swiss mice were subjected to TBI at doses of 6.5, 7.

Attentional Distractions Do Not Influence Lumbar Spine Local Dynamic Stability during Repetitive Flexion-Extension Movements.

The association between low back pain and lumbar spine local dynamic stability (LDS) appears to be modulated by if and how someone catastrophizes about pain, suggesting that the cognitive perceptions of pain may influence an individual's ability to control lumbar spine motion. Previous work also demonstrates that directing cognitive resources and attentional focus can influence movement performance. Therefore, we aimed to examine whether distracting attentional focus would influence lumbar spine LDS during repetitive flexion-extension movements.

Why do avian responses to change in Arctic green-up vary?

Global climate change has altered the timing of seasonal events (i.e., phenology) for a diverse range of biota.

BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.

BUB1 inhibition sensitizes lung cancer cell lines to radiotherapy and chemoradiotherapy.

Background: Lung cancer is a major public health concern, with high incidence and mortality. Despite advances in targeted therapy and immunotherapy, microtubule stabilizers (paclitaxel, docetaxel), DNA intercalating platinum drugs (cisplatin) and radiation therapy continue to play a critical role in the management of locally advanced and metastatic lung cancer. Novel molecular targets would provide opportunities for improving the efficacies of radiotherapy and chemotherapy.