"You have to be sure that the patient has the full picture": Adaptation of the Best Case/Worst Case communication tool for geriatric oncology.

BACKGROUND: Shared decision making (SDM) is especially important for older adults with cancer given the risks of over- and undertreatment, uncertainty regarding benefits/harms worsened by research underrepresentation, and individual preferences. We aimed to adapt the Best Case/Worst Case (BC/WC) communication tool, which improves SDM in geriatric surgery, to geriatric oncology. METHODS: We conducted focus groups with 40 stakeholders (fourteen older adults with lung cancer, twelve caregivers, fourteen medical oncologists) to elicit perspectives on using the BC/WC tool for geriatric oncology and to identify components needing refinement. During each focus group, participants viewed a BC/WC demonstration video and answered questions modified from the Decision Aid Acceptability Scale. We analyzed transcripts using deductive and inductive thematic analyses. DISCUSSION: Participants believed that the BC/WC tool could help patients understand their cancer care choices, explore tradeoffs and picture potential outcomes, and deliberate about decisions based on their goals, preferences, and values. Oncologists also reported the tool could guide conversations to address points that may frequently be skipped (e.g., alternative options, treatment goals). Participant preferences varied widely regarding discussion of the worst-case scenario and desire for statistical information. CONCLUSION: The BC/WC tool is a promising strategy that may improve SDM in geriatric oncology and patient understanding of alternative options and treatment goals. Based on participant input, adaptations will include framing cancer care as a series of decisions, eliciting patient preferences and asking permission before offering the worst-case scenario, and selection of the two most relevant options to present if multiple exist.

Changes in older adults' life space during lung cancer treatment: A mixed methods cohort study.

BACKGROUND: Maintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown. METHODS: This mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA <60 is considered restricted. We used mixed-effects models to examine pretreatment LSA, change from 0 to 1 month, and change from 1 to 6 months. A subgroup participated in semistructured interviews pretreatment and at 2 and 6 months to understand the patient experience of life-space change. For each interview participant, we created joint displays of longitudinal LSA scores juxtaposed with illustrative quotes. RESULTS: Among 93 patients, median age was 73 (range 65-94). Mean pretreatment LSA score was 67.1. On average, LSA declined 10.1 points from pretreatment to 1 month and remained stable at 6 months. Pretreatment LSA score was associated with several demographic, clinical, geriatric assessment, and symptom characteristics. LSA decline at 1 month was greater among patients with high anxiety (slope = -12.6 vs. -2.3, p = 0.048). Pretreatment body mass index <21 kg/m2 was associated with LSA improvement from 1 to 6 months (slope = 4.1 vs. -0.04, p = 0.003). Joint displays illustrated the impact of different life-space trajectories on patients' lives in their words. CONCLUSION: Older adults with NSCLC have low pretreatment life space with many developing restricted life space during treatment. Incorporating life-space assessments into clinical cancer care may help older adults concretely visualize how treatment might impact their daily function to allow for informed decision making and identify early changes in mobility to implement supportive interventions.

High-throughput genotyping of hop (Humulus lupulus L.) utilising diversity arrays technology (DArT).

Implementation of molecular methods in hop (Humulus lupulus L.) breeding is dependent on the availability of sizeable numbers of polymorphic markers and a comprehensive understanding of genetic variation. However, use of molecular marker technology is limited due to expense, time inefficiency, laborious methodology and dependence on DNA sequence information. Diversity arrays technology (DArT) is a high-throughput cost-effective method for the discovery of large numbers of quality polymorphic markers without reliance on DNA sequence information. This study is the first to utilise DArT for hop genotyping, identifying 730 polymorphic markers from 92 hop accessions. The marker quality was high and similar to the quality of DArT markers previously generated for other species; although percentage polymorphism and polymorphism information content (PIC) were lower than in previous studies deploying other marker systems in hop. Genetic relationships in hop illustrated by DArT in this study coincide with knowledge generated using alternate methods. Several statistical analyses separated the hop accessions into genetically differentiated North American and European groupings, with hybrids between the two groups clearly distinguishable. Levels of genetic diversity were similar in the North American and European groups, but higher in the hybrid group. The markers produced from this time and cost-efficient genotyping tool will be a valuable resource for numerous applications in hop breeding and genetics studies, such as mapping, marker-assisted selection, genetic identity testing, guidance in the maintenance of genetic diversity and the directed breeding of superior cultivars.

Ethiopia's transforming wheat landscape: tracking variety use through DNA fingerprinting.

Ethiopia is the largest wheat producer in sub-Saharan Africa yet remains a net importer. Increasing domestic wheat production is a national priority. Improved varieties provide an important pathway to enhancing productivity and stability of production. Reliably tracking varietal use and dynamics is a challenge, and the value of conventional recall surveys is increasingly questioned. We report the first nationally representative, large-scale wheat DNA fingerprinting study undertaken in Ethiopia. Plot level comparison of DNA fingerprinting with farmer recall from nearly 4000 plots in the 2016/17 season indicates that only 28% of farmers correctly named wheat varieties grown. The DNA study reveals that new, rust resistant bread wheat varieties are now widely adopted. Germplasm originating from CGIAR centres has made a significant contribution. Corresponding productivity gains and economic benefits have been substantial, indicating high returns to investments in wheat improvement. The study provides an accurate assessment of wheat varietal status and sets a benchmark for national policy-makers and donors. In recent decades, the Ethiopian wheat landscape has transformed from local tetraploid varieties to widespread adoption of high yielding, rust resistant bread wheat. We demonstrate that DNA fingerprinting can be applied at scale and is likely to transform future crop varietal adoption studies.

Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans. Part A: use of FDA post-market reports to create a database of hepatobiliary and urinary tract toxicities.

The Informatics and Computational Safety Analysis Staff at the US FDA's Center for Drug Evaluation and Research has created a database of pharmaceutical adverse effects (AEs) linked to pharmaceutical chemical structures and estimated population exposures. The database is being used to develop quantitative structure-activity relationship (QSAR) models for the prediction of drug-induced liver and renal injury, as well as to identify relationships among AEs. The post-market observations contained in the database were obtained from FDA's Spontaneous Reporting System (SRS) and the Adverse Event Reporting System (AERS) accessed through Elsevier PharmaPendium software. The database contains approximately 3100 unique pharmaceutical compounds and 9685 AE endpoints. To account for variations in AE reports due to different patient populations and exposures for each drug, a proportional reporting ratio (PRR) was used. The PRR was applied to all AEs to identify chemicals that could be scored as positive in the training datasets of QSAR models. Additionally, toxicologically similar AEs were grouped into clusters based upon both biological effects and statistical correlation. This clustering created a weight of evidence paradigm for the identification of compounds most likely to cause human harm based upon findings in multiple related AE endpoints.

Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans: Part B. Use of (Q)SAR systems for early detection of drug-induced hepatobiliary and urinary tract toxicities.

This report describes the development of quantitative structure-activity relationship (QSAR) models for predicting rare drug-induced liver and urinary tract injury in humans based upon a database of post-marketing adverse effects (AEs) linked to approximately 1600 chemical structures. The models are based upon estimated population exposure using AE proportional reporting ratios. Models were constructed for 5 types of liver injury (liver enzyme disorders, cytotoxic injury, cholestasis and jaundice, bile duct disorders, gall bladder disorders) and 6 types of urinary tract injury (acute renal disorders, nephropathies, bladder disorders, kidney function tests, blood in urine, urolithiases). Identical training data sets were configured for 4 QSAR programs (MC4PC, MDL-QSAR, BioEpisteme, and Predictive Data Miner). Model performance was optimized and was shown to be affected by the AE scoring method and the ratio of the number of active to inactive drugs. The best QSAR models exhibited an overall average 92.4% coverage, 86.5% specificity and 39.3% sensitivity. The 4 QSAR programs were demonstrated to be complementary and enhanced performance was obtained by combining predictions from 2 programs (average 78.4% specificity, 56.2% sensitivity). Consensus predictions resulted in better performance as judged by both internal and external validation experiments.

Adherence to adjuvant endocrine therapy for breast cancer: importance in women with low income.

There are wide disparities in breast cancer-specific survival by patient sociodemographic characteristics. Women of lower income, for instance, have higher relapse and death rates from breast cancer. One possible contributing factor for this disparity is low use of adjuvant endocrine therapy-an extremely efficacious therapy in women with early stage, hormone receptor positive breast cancer, the most common subtype of breast cancer. Alone, adjuvant endocrine therapy decreases breast cancer recurrence by 50% and death by 30%. Data suggest that low use of adjuvant endocrine therapy is a potentially important and modifiable risk factor for poor outcome in low-income breast cancer patients.

Muscle fructose-2,6-bisphosphate and glucose-1,6-bisphosphate during insulin-induced hypoglycemia.

Glucose production during insulin-induced hypoglycemia in the fasted state is heavily dependent on the process of hepatic gluconeogenesis. Skeletal muscle glycogen is one possible source of lactate for hepatic gluconeogenesis. Fructose 2,6-bisphosphate (F-2,6-P2) and glucose 1,6-bisphosphate (G-1,6-P2) are two allosteric activators of muscle glycolysis. To investigate their putative role in the control of muscle lactate production during hypoglycemia, fasted rats were infused via jugular catheters with insulin in 0.9% NaCl or with 0.9% NaCl alone for 60 or 120 min. Muscles were removed and clamp frozen in liquid nitrogen. The insulin infusion produced plasma insulin values of 97 +/- 13 microU/ml after 1 h and 100 +/- 9 microU/ml after 2 h. Blood glucose in the saline-infused rats was 4.6 +/- 0.2 mM after 1 h and 5.1 +/- 0.1 mM after 2 h compared with 1.5 +/- 0.01 and 1.0 +/- 0.1 mM after 1 and 2 h, respectively, in the insulin-infused rats. The hypoglycemic rats had significantly elevated plasma epinephrine and blood lactate levels compared with the saline-infused rats. F-2,6-P2 and G-1,6-P2 were increased two- to five-fold in white quadriceps of hypoglycemic rats compared with that of saline-infused rats. The results are consistent with F-2,6-P2 and G-1,6-P2 playing a role in stimulating muscle lactate production as a source of gluconeogenic substrate during insulin-induced hypoglycemia.

Self-propelled anguilliform swimming: simultaneous solution of the two-dimensional navier-stokes equations and Newton's laws of motion

Anguilliform swimming has been investigated by using a computational model combining the dynamics of both the creature's movement and the two-dimensional fluid flow of the surrounding water. The model creature is self-propelled; it follows a path determined by the forces acting upon it, as generated by its prescribed changing shape. The numerical solution has been obtained by applying coordinate transformations and then using finite difference methods. Results are presented showing the flow around the creature as it accelerates from rest in an enclosed tank. The kinematics and dynamics associated with the creature's centre of mass are also shown. For a particular set of body shape parameters, the final mean swimming speed is found to be 0.77 times the speed of the backward-travelling wave. The corresponding movement amplitude envelope is shown. The magnitude of oscillation in the net forward force has been shown to be approximately twice that in the lateral force. The importance of allowing for acceleration and deceleration of the creature's body (rather than imposing a constant swimming speed) has been demonstrated. The calculations of rotational movement of the body and the associated moment of forces about the centre of mass have also been included in the model. The important role of viscous forces along and around the creature's body and in the growth and dissolution of the vortex structures has been illustrated.

Palliative Services in Long-Term Care: Meeting the special needs of veterans.

War veterans in long-term care are usually elderly; consequently, a significant proportion of them are admitted with a terminal illness or will develop one within a short time. To meet the need for a palliative service in long-term care, a project was organized using a Special Projects Nurse to introduce the service. The service uses an interdisciplinary approach to address the physical, psychosocial, and spiritual needs of the veterans and their families. Staff support and education are an integral part of the program.

Interactions between muscle activation, body curvature and the water in the swimming lamprey.

The travelling wave of curvature which propels a fish forward arises from the interaction of the patterns of motoneurone activity generated by the spinal cord with the mechanical properties of (1) the muscle, (2) the skin, bone and connective tissues of the body, and (3) the water in which it is swimming. Furthermore, in the lamprey, a powerful feedback system has been demonstrated which allows local body curvature to influence the timing of the activity pattern generated by the spinal cord. The relative timing between activation and curvature are illustrated for both closed- and open-loop conditions, using data from intact swimming lampreys and from an in vitro preparation of lamprey spinal cord and notochord. The mechanical behaviour of a lamprey has been simulated with a mathematical model based on springs, dashpots, light rods, point masses and power units incorporating properties of lamprey muscle. Results are presented which illustrate the behaviour of a lamprey out of water. To anticipate the inclusion of the lamprey body model in the computation of the fluid dynamics, a hydrodynamical model has been developed in which the body motion and the forward swimming have been prescribed by mathematical functions. Results are presented to illustrate the hydrodynamic vortex structure as predicted by a two-dimensional, time-dependent numerical solution of the Navier-Stokes equations, including both viscous and inertial terms.