A Systematic Review of Prognostic Factors in Patients with Cancer Receiving Palliative Radiotherapy: Evidence-Based Recommendations.

(1) Background: Prognostication in patients with cancer receiving palliative radiotherapy remains a challenge. To improve the process, we aim to identify prognostic factors in this population from the literature and offer evidence-based recommendations on prognostication in patients undergoing palliative radiotherapy for non-curable or advanced cancers. (2) Methods: A systematic review was performed on the medical literature from 2005 to 2023 to extract papers on the prognosis of palliative radiotherapy patients with advanced cancer. The initial selection was performed by at least two authors to determine study relevance to the target area. Studies were then classified based on type and evidence quality to determine final recommendations. (3) Results: The literature search returned 57 papers to be evaluated. Clinical and biological prognostic factors were identified from these papers to improve clinical decision making or construct prognostic models. Twenty prognostic models were identified for clinical use. There is moderate evidence supporting (i) evidence-based factors (patient, clinical, disease, and lab) in guiding decision making around palliative radiation; (ii) that certain biological factors are of importance; (iii) prognostication models in patients with advanced cancer; and that (iv) SBRT or re-irradiation use can be guided by predictions of survival by prognostic scores or clinicians. Patients with more favorable prognoses are generally better suited to SBRT or re-irradiation, and the use of prognostic models can aid in this decision making. (4) Conclusions: This evaluation has identified several factors or tools to aid in prognosis and clinical decision making. Future studies should aim to further validate these tools and factors in a clinical setting, including the leveraging of electronic medical records for data availability. To increase our understanding of how causal factors interact with palliative radiotherapy, future studies should also examine and include prediction of response to radiation as an outcome.

Does Retirement and Work Stoppage Impact Body Weight and Waist Circumference Changes in Middle- and Older-Aged Women and Men? Results From the Canadian Longitudinal Study on Aging.

This study aimed to examine the impact of employment transitions (ETs) on anthropometric changes among middle-aged and older workers (ages 45y+). Using two waves of data from the Canadian Longitudinal Study on Aging, we analyzed the impact of ETs (stayed working, entered retirement, and stopped working) on change in body weight and waist circumference (WC) on continuous scales as well as categories (≥5% cut-off). Analyses were sex/gender-stratified. Women did not show significant weight or WC change that differed across ETs, but estimated directions suggested those who stopped working were more likely to have ≥5% change in weight. Estimated directions of continuous outcomes for women who stopped working relative to continued workers showed less weight gain and more WC gain. Men who retired gained less weight and had smaller WC gain compared to reference. The findings imply that the short-run impact of exiting the labor force may not exacerbate weight gain.

An Analysis of Clinical and Systemic Factors Associated with Palliative Radiotherapy Delivery and Completion at the End of Life in Alberta, Canada.

Radiotherapy (RT) is often utilized for symptom control at the end of life. Palliative RT (pRT) may not be taken to completion by patients, thus decreasing clinical benefits and adversely impacting resource allocation. We determined rates of incomplete pRT and examined predictors of non-completion using an electronic questionnaire. Methods: A questionnaire was embedded within the RT electronic prescribing system for all five cancer centers of Alberta, Canada, between 2017 and 2020. Prescribing radiation oncologists (ROs) were tasked with completing the questionnaire. Treatment variables were collected for 2040 patients prescribed pRT. Details on pRT courses delivered and completed were used to determine rates of incomplete RT. Electronic medical records of a subset of 367 patients randomly selected from the 2040 patients were then analyzed to examine for association of non-completion of RT with patient, disease, and therapy-related factors. Results: Overall, 10% of patients did not complete pRT. The rate of single fractions prescribed as a proportion of all RT fractions increased from 18% (pre-2017: pre-study era) to 29% (2017-2020: study era) (p < 0.0001). After conducting multivariate analysis on the overall group, multiple lifetime malignancies (OR:0.64) or increasing the number of pRT fractions (OR:0.08-0.17) were associated with non-completion. Being selected for stereotactic RT (OR:3.75) or survival > 30 days post-RT prescription (OR:2.20-5.02) were associated with greater rates of RT completion. The ROs' estimates of life expectancy at the time of RT prescription were not predictive of RT completion. In the multivariate analysis of the 367-patient subset, the presence of hepatic metastases (OR 2.59), survival 30-59 days (OR 6.61) and survival 90+ days (OR 8.18) post-RT prescription were associated with pRT completion. Only increasing pRT fractionation (OR:0.05-0.2) was associated with non-completion. Conclusion: One in ten patients prescribed pRT did not complete their treatment course. Decreasing pRT fractionation and improving prognostication in patients near the end of life may decrease rates of incomplete RT courses.

Economic evaluation of prostate cancer risk assessment methods: A cost-effectiveness analysis using population data.

BACKGROUND: The current prostate cancer (PCa) screening standard of care (SOC) leads to unnecessary biopsies and overtreatment because decisions are guided by prostate-specific antigen (PSA) levels, which have low specificity in the gray zone (3-10 ng/mL). New risk assessment tools (RATs) aim to improve biopsy decision-making. We constructed a modeling framework to assess new RATs in men with gray zone PSA from the British Columbia healthcare system's perspective. METHODS: We evaluated the cost-effectiveness of a new RAT used in biopsy-naïve men aged 50+ with a PSA of 3-10 ng/mL using a time-dependent state-transition model. The model was informed by engaging patient partners and using linked administrative health data, supplemented with published literature. The incremental cost-effectiveness ratio and the probability of the RAT being cost-effective were calculated. Probabilistic analysis was used to assess parameter uncertainty. RESULTS: In the base case, a RAT based on an existing biomarker's characteristics was a dominant strategy associated with a cost savings of $44 and a quality-adjusted life years (QALY) gain of 0.00253 over 18 years of follow-up. At a cost-effectiveness threshold of $50,000/QALY, the probability that using a RAT is cost-effective relative to the SOC was 73%. Outcomes were sensitive to RAT costs and accuracy, especially the detection rate of high-grade PCa. Results were also impacted by PCa prevalence and assumptions about undetected PCa survival. CONCLUSIONS: Our findings showed that a more accurate RAT to guide biopsy can be cost-effective. Our proposed general model can be used to analyze the cost-effectiveness of any novel RAT.

Health Care Costs Attributable to Prostate Cancer in British Columbia, Canada: A Population-Based Cohort Study.

We aimed to estimate the total health care costs attributable to prostate cancer (PCa) during care phases by age, cancer stage, tumor grade, and primary treatment in the first year in British Columbia (BC), Canada. Using linked administrative health data, we followed a cohort of men aged ≥ 50 years at diagnosis with PCa between 2010 and 2017 (Cohort 1) from the diagnosis date until the date of death, the last date of observation, or 31 December 2019. Patients who died from PCa after 1 January 2010, were selected for Cohort 2. PCa attributable costs were estimated by comparing costs in patients to matched controls. Cohort 1 (n = 22,672) had a mean age of 69.9 years (SD = 8.9) and a median follow-up time of 5.2 years. Cohort 2 included 6942 patients. Mean PCa attributable costs were the highest during the first year after diagnosis ($14,307.9 [95% CI: $13,970.0, $14,645.8]) and the year before death ($9959.7 [$8738.8, $11,181.0]). Primary treatment with radiation therapy had significantly higher costs each year after diagnosis than a radical prostatectomy or other surgeries in advanced-stage PCa. Androgen deprivation therapy (and/or chemotherapy) had the highest cost for high-grade and early-stage cancer during the three years after diagnosis. No treatment group had the lowest cost. Updated cost estimates could inform economic evaluations and decision-making.

A systematic review of evidence on employment transitions and weight change by gender in ageing populations.

BACKGROUND: Becoming unemployed is associated with poorer health, including weight gain. Middle- and older-age adults are a growing segment of workforces globally, but they are also more vulnerable to changes to employment status, especially during economic shocks. Expected workforce exits over the next decade may exacerbate both the obesity epidemic and the economic burden of obesity. This review extends current knowledge on economic correlates of health to assess whether employment transitions impact body weight by sex/gender among middle-aged and older adults. METHODS: Eight bibliometric databases were searched between June and July 2021, supplemented by hand-searches, with no restriction on publication date or country. Longitudinal studies, or reviews, were eligible when examining body weight as a function of employment status change in adults ≥50 years. Data extraction and quality appraisal used predefined criteria; reported findings were analysed by narrative synthesis. RESULTS: We screened 6,001 unique abstracts and identified 12 articles that met inclusion criteria. All studies examined retirement; of which two also examined job-loss. Overall, studies showed that retirement led to weight gain or no difference in weight change compared to non-retirees; however, reported effects were not consistent for either women or men across studies or for both women and men within a study. Reported effects also differed by occupation: weight gain was more commonly observed among retirees from physical occupations but not among retirees from sedentary occupations. Few studies assessed the role of health behaviours; sleep was the least studied. Most studies were medium quality. CONCLUSIONS: Existing studies do not provide a clear enough picture of how employment transitions affect body weight. Firm conclusions on the impact of employment transitions on weight cannot be made without further high-quality evidence that considers the role of gender, job-type, other health behaviours, and other transitions, like job-loss.

F-actin bending facilitates net actomyosin contraction By inhibiting expansion with plus-end-located myosin motors.

Contraction of actomyosin networks underpins important cellular processes including motility and division. The mechanical origin of actomyosin contraction is not fully-understood. We investigate whether contraction arises on the scale of individual filaments, without needing to invoke network-scale interactions. We derive discrete force-balance and continuum partial differential equations for two symmetric, semi-flexible actin filaments with an attached myosin motor. Assuming the system exists within a homogeneous background material, our method enables computation of the stress tensor, providing a measure of contractility. After deriving the model, we use a combination of asymptotic analysis and numerical solutions to show how F-actin bending facilitates contraction on the scale of two filaments. Rigid filaments exhibit polarity-reversal symmetry as the motor travels from the minus to plus-ends, such that contractile and expansive components cancel. Filament bending induces a geometric asymmetry that brings the filaments closer to parallel as a myosin motor approaches their plus-ends, decreasing the effective spring force opposing motor motion. The reduced spring force enables the motor to move faster close to filament plus-ends, which reduces expansive stress and gives rise to net contraction. Bending-induced geometric asymmetry provides both new understanding of actomyosin contraction mechanics, and a hypothesis that can be tested in experiments.

Thin-film lubrication model for biofilm expansion under strong adhesion.

Understanding microbial biofilm growth is important to public health because biofilms are a leading cause of persistent clinical infections. In this paper, we develop a thin-film model for microbial biofilm growth on a solid substratum to which it adheres strongly. We model biofilms as two-phase viscous fluid mixtures of living cells and extracellular fluid. The model explicitly tracks the movement, depletion, and uptake of nutrients and incorporates cell proliferation via a nutrient-dependent source term. Notably, our thin-film reduction is two dimensional and includes the vertical dependence of cell volume fraction. Numerical solutions show that this vertical dependence is weak for biologically feasible parameters, reinforcing results from previous models in which this dependence was neglected. We exploit this weak dependence by writing and solving a simplified one-dimensional model that is computationally more efficient than the full model. We use both the one- and two-dimensional models to predict how model parameters affect expansion speed and biofilm thickness. This analysis reveals that expansion speed depends on cell proliferation, nutrient availability, cell-cell adhesion on the upper surface, and slip on the biofilm-substratum interface. Our numerical solutions provide a means to qualitatively distinguish between the extensional flow and lubrication regimes, and quantitative predictions that can be tested in future experiments.

Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1.

Vascular endothelial cell growth factor (VEGF) is a key regulator of vascular permeability. Herein we aim to understand how acute and chronic exposures of VEGF induce different levels of vascular permeability. We demonstrate that chronic VEGF exposure leads to decreased phosphorylation of VEGFR2 and c-Src as well as steady increases of nitric oxide (NO) as compared to that of acute exposure. Utilizing heat-inducible VEGF transgenic zebrafish (Danio rerio) and establishing an algorithm incorporating segmentation techniques for quantification, we monitored acute and chronic VEGF-induced vascular hyperpermeability in real time. Importantly, dimethylarginine dimethylaminohydrolase-1 (DDAH1), an enzyme essential for NO generation, was shown to play essential roles in both acute and chronic vascular permeability in cultured human cells, zebrafish model, and Miles assay. Taken together, our data reveal acute and chronic VEGF exposures induce divergent signaling pathways and identify DDAH1 as a critical player and potentially a therapeutic target of vascular hyperpermeability-mediated pathogenesis.

Protein friction and filament bending facilitate contraction of disordered actomyosin networks.

We use mathematical modeling and computation to investigate how protein friction facilitates contraction of disordered actomyosin networks. We simulate two-dimensional networks using an agent-based model, consisting of a system of force-balance equations for myosin motor proteins and semiflexible actin filaments. A major advantage of our approach is that it enables direct calculation of the network stress tensor, which provides a quantitative measure of contractility. Exploiting this, we use repeated simulations of disordered networks to confirm that both protein friction and actin filament bending are required for contraction. We then use simulations of elementary two-filament systems to show that filament bending flexibility can facilitate contraction on the microscopic scale. Finally, we show that actin filament turnover is necessary to sustain contraction and prevent filament aggregation. Simulations with and without turnover also exhibit contractile pulses. However, these pulses are aperiodic, suggesting that periodic pulsation can only arise because of additional regulatory mechanisms or more complex mechanical behavior.

A thin-film extensional flow model for biofilm expansion by sliding motility.

In the presence of glycoproteins, bacterial and yeast biofilms are hypothesized to expand by sliding motility. This involves a sheet of cells spreading as a unit, facilitated by cell proliferation and weak adhesion to the substratum. In this paper, we derive an extensional flow model for biofilm expansion by sliding motility to test this hypothesis. We model the biofilm as a two-phase (living cells and an extracellular matrix) viscous fluid mixture, and model nutrient depletion and uptake from the substratum. Applying the thin-film approximation simplifies the model, and reduces it to one-dimensional axisymmetric form. Comparison with Saccharomyces cerevisiae mat formation experiments reveals good agreement between experimental expansion speed and numerical solutions to the model with O ( 1 ) parameters estimated from experiments. This confirms that sliding motility is a possible mechanism for yeast biofilm expansion. Having established the biological relevance of the model, we then demonstrate how the model parameters affect expansion speed, enabling us to predict biofilm expansion for different experimental conditions. Finally, we show that our model can explain the ridge formation observed in some biofilms. This is especially true if surface tension is low, as hypothesized for sliding motility.

Evaluation of a short, interactive diabetes self-management program by pharmacists for type 2 diabetes.

OBJECTIVE: Numerous barriers prevent patients with type 2 diabetes (T2D) from completing a diabetes self-management program. We investigated whether patients with T2D exhibited improved clinical outcomes after attending a relatively short, interactive diabetes self-management program conducted by pharmacist diabetes educators, compared to a physician's usual care. RESULTS: We retrospectively analyzed the data of adults with T2D who attended a diabetes self-management program (≥ 1 group meeting or individual appointment followed by a telephone interview from a pharmacist diabetes educator between May 2010 and Dec. 2012; n = 513) and compared their outcomes with those of T2D patients who received only their physician's usual care (n = 857). Each patient's A1C was assessed at baseline, 3 months, and 6 months post-intervention. The mean [SD] reduction in A1C percentage points in the T2D patients was significantly greater in the diabetes self-management program group compared to the physician's usual care group at both 3 months (- 0.8% [1.5] vs. - 0.2% [0.9], p < 0.001) and 6 months post-intervention (- 0.6% [1.3] vs. - 0.2% [1.1], p < 0.001). T2D patients significantly improved their glycemic control within 3-6 months of attending the diabetes self-management program compared to patients who only received their physician's usual care.

Gender, stressful life events and interactions with sleep: a systematic review of determinants of adiposity in young people.

OBJECTIVES: Overweight and obesity among young people are high and rising. Social stressors and sleep are independently associated with obesity, but are rarely studied together or examined for gender-specific effects. The literature regarding adolescent populations is especially lacking. This review assesses whether experiencing stressful life events results in greater adiposity in young women and young men compared with those who do not experience stressful life events, and whether the relationship is modified by sleep problems. DESIGN: We systematically searched six bibliometric databases (Web of Science, Embase Ovid, PsycINFO, CINHAL, PubMed, ProQuest Dissertations) supplemented by hand searches. Longitudinal prospective studies or reviews were eligible for inclusion when they examined gender-specific changes in adiposity in young adults (age 13-18 years) as a function of stressful life event alone or in combination with sleep problems. RESULTS: We found one study eligible for inclusion reporting mixed impact of stressful life events on body mass index (BMI) between genders. The study assessed specific life events and showed significantly lower BMI at follow-up among young men who experienced a residence change, but significantly higher BMI among young women who experienced setting up a family and who reported internal locus of control. CONCLUSIONS: Despite ample research on social stressors or sleep problems and weight, we still know little about the role of stressful life events, or combined effects with sleep, on obesity risk in adolescents from a gender perspective. Existing evidence suggests specific life events affect weight differently between the genders. Robust, high-quality longitudinal studies to decipher this dual burden on obesity during adolescence should be prioritised, as firm conclusions remain elusive.

Diffusion-Limited Growth of Microbial Colonies.

The emergence of diffusion-limited growth (DLG) within a microbial colony on a solid substrate is studied using a combination of mathematical modelling and experiments. Using an agent-based model of the interaction between microbial cells and a diffusing nutrient, it is shown that growth directed towards a nutrient source may be used as an indicator that DLG is influencing the colony morphology. A continuous reaction-diffusion model for microbial growth is employed to identify the parameter regime in which DLG is expected to arise. Comparisons between the model and experimental data are used to argue that the bacterium Bacillus subtilis can undergo DLG, while the yeast Saccharomyces cerevisiae cannot, and thus the non-uniform growth exhibited by this yeast must be caused by the pseudohyphal growth mode rather than limited nutrient availability. Experiments testing directly for DLG features in yeast colonies are used to confirm this hypothesis.

Nutrient-limited growth with non-linear cell diffusion as a mechanism for floral pattern formation in yeast biofilms.

Previous experiments have shown that mature yeast mat biofilms develop a floral morphology, characterised by the formation of petal-like structures. In this work, we investigate the hypothesis that nutrient-limited growth is the mechanism by which these floral patterns form. To do this, we use a combination of experiments and mathematical analysis. In mat formation experiments of the yeast species Saccharomyces cerevisiae, we observe that mats expand radially at a roughly constant speed, and eventually undergo a transition from circular to floral morphology. To determine the extent to which nutrient-limited growth can explain these features, we adopt a previously proposed mathematical model for yeast growth. The model consists of a coupled system of reaction-diffusion equations for the yeast cell density and nutrient concentration, with a non-linear, degenerate diffusion term for cell spread. Using geometric singular perturbation theory and numerics, we show that the model admits travelling wave solutions in one dimension, which enables us to infer the diffusion ratio from experimental data. We then use a linear stability analysis to show that two-dimensional planar travelling wave solutions for feasible experimental parameters are linearly unstable to non-planar perturbations. This provides a potential mechanism by which petals can form, and allows us to predict the characteristic petal width. There is good agreement between these predictions, numerical solutions to the model, and experimental data. We therefore conclude that the non-linear cell diffusion mechanism provides a possible explanation for pattern formation in yeast mat biofilms, without the need to invoke other mechanisms such as flow of extracellular fluid, cell adhesion, or changes to cellular shape or behaviour.