Usability Testing of a Sensor-Controlled Digital Game to Engage Older Adults with Heart Failure in Physical Activity and Weight Monitoring

Background  Poor self-management of heart failure (HF) has contributed to poor health outcomes. Sensor-controlled digital games (SCDGs) integrates data from behavior-tracking sensors to trigger progress, rewards, content, and positive feedback in a digital game to motivate real-time behaviors. Objectives  To assess the usability of an SCDG prototype over a week of game-playing among 10 older adults with HF in their homes. Methods  During initial play, participants'' SCDG experiences were observed in their homes using a checklist based on the seven-item Serious Game User Evaluator (SeGUE) instrument. After a week of game-playing, participants completed a survey guided by the Intrinsic Motivation Inventory, to provide their perceptions of the SCDG''s usability. Qualitative analysis via semistructured interview-derived themes on experiences playing the SCDG, perceptions regarding engaging with the SCDG, and any usability issues encountered. Results  Ten HF participants (50% women and 50% White) played the SCDG for an average of 6 out of 7 days. Nine found the SCDG to be interesting, satisfying, and easy to play. The average step count over a week was 4,117 steps (range: 967–9,892). Average adherence with weight monitoring was 5.9 days in a week. Qualitative analysis yielded outcomes regarding attitudes toward SCDG, and barriers and facilitators that influenced participants'' engagement with the SCDG. Conclusion  To the best of the authors'' knowledge, this usability and feasibility study is the first to report an SCDG designed to improve HF self-management behaviors of older adults in their homes. Future research should consider several issues, such as user profiles, prior game-playing experiences, and network conditions most suitable for connected health interventions for older adults living in the community.     

Homologous Recombination Deficiency: Concepts,Definitions, and Assays

BackgroundHomologous recombination deficiency (HRD) is a phenotype that is characterized by the inability of a cell to effectively repair DNA double-strand breaks using the homologous recombination repair (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. However, to identify patients with these tumors, it is vital to understand how to best measure homologous repair (HR) status and to characterize the level of alignment in these measurements across different diagnostic platforms. A key current challenge is that there is no standardized method to define, measure, and report HR status using diagnostics in the clinical setting.MethodsFriends of Cancer Research convened a consortium of project partners from key healthcare sectors to address concerns about the lack of consistency in the way HRD is defined and methods for measuring HR status.ResultsThis publication provides findings from the group’s discussions that identified opportunities to align the definition of HRD and the parameters that contribute to the determination of HR status. The consortium proposed recommendations and best practices to benefit the broader cancer community.ConclusionOverall, this publication provides additional perspectives for scientist, physician, laboratory, and patient communities to contextualize the definition of HRD and various platforms that are used to measure HRD in tumors.     

The AWS from a parent's point of view:

The parents of 36 people with mental handicaps were interviewed concerning their views on more integrated services for their relatives. Most were in favour of such developments, but considerable opposition was expressed in a number of areas, especially in relation to day care and education. Parents of those with more severe handicaps tended to be least in favour of integration. Some implications for consumer involvement in the AWS are discussed.     

The importance of hydrology in routing terrestrial carbon to the atmosphere via global streams and rivers

The magnitude of stream and river carbon dioxide (CO₂) emission is affected by seasonal changes in watershed biogeochemistry and hydrology. Global estimates of this flux are, however, uncertain, relying on calculated values for CO₂ and lacking spatial accuracy or seasonal variations critical for understanding macroecosystem controls of the flux. Here, we compiled 5,910 direct measurements of fluvial CO₂ partial pressure and modeled them against watershed properties to resolve reach-scale monthly variations of the flux. The direct measurements were then combined with seasonally resolved gas transfer velocity and river surface area estimates from a recent global hydrography dataset to constrain the flux at the monthly scale. Globally, fluvial CO₂ emission varies between 112 and 209 Tg of carbon per month. The monthly flux varies much more in Arctic and northern temperate rivers than in tropical and southern temperate rivers (coefficient of variation: 46 to 95 vs. 6 to 12%). Annual fluvial CO₂ emission to terrestrial gross primary production (GPP) ratio is highly variable across regions, ranging from negligible (<0.2%) to 18%. Nonlinear regressions suggest a saturating increase in GPP and a nonsaturating, steeper increase in fluvial CO₂ emission with discharge across regions, which leads to higher percentages of GPP being shunted into rivers for evasion in wetter regions. This highlights the importance of hydrology, in particular water throughput, in routing terrestrial carbon to the atmosphere via the global drainage networks. Our results suggest the need to account for the differential hydrological responses of terrestrial–atmospheric vs. fluvial–atmospheric carbon exchanges in plumbing the terrestrial carbon budget.

The Earth’s water, carbon, and energy fluxes follow seasonal variations in the Earth’s solar radiation and climate variability (1, 2). As an integral part of terrestrial landscapes, streams and rivers receive significant water and carbon inputs from terrestrial and wetland ecosystems, which are further processed along the river to ocean continuum (3). As the largest carbon flux mediated by fluvial systems, carbon dioxide (CO₂) emission from stream and river surfaces (4–7) is double the lateral carbon transport to oceans (8), yet its spatial and temporal variations are not fully resolved. Stream and river CO₂ evasion changes considerably across space and time due to biogeochemical responses to climatic factors (3), the physics governing the transfer of gas across the water–air interface (9), and seasonal variations in the spatial extent of drainage networks (10, 11). However, seasonal variability of the flux has not been determined at the global scale, limiting our ability to understand controls at the macrosystem level.The rate at which streams and rivers exchange CO₂ with the atmosphere is determined by three factors: dissolved CO₂ concentration (often expressed as an equivalent atmospheric partial pressure [pCO₂]), water surface gas transfer velocity (k), and water surface area. To estimate flux at the monthly scale, all three factors need to be resolved at the same or finer temporal scale(s). To date, existing spatially explicit estimates of riverine CO₂ emission at the global scale (4, 12) relied exclusively on pCO₂ calculated from carbonate equilibria and historical archives of pH and alkalinity measurements. While these data have reasonable spatial coverage, the carbonate equilibria method is subject to inflated pCO₂ estimates due to biased pH measurements (13) and alkalinity contribution from organic acids (14), particularly in low–ionic strength waters. These errors, although reducible within individual datasets (15), are difficult to correct for when scaling globally. This problem has significantly undermined calculations and understanding of the flux at the global scale. More importantly, although global estimates of the stream and river surface area and gas transfer velocity at mean annual discharge have been achieved (4, 16), their seasonal extent, a major driver of within-year variability of riverine CO₂ flux, has not. This is largely because a temporally resolved reach-scale representation of global river hydrology has not been available until recently (17), and new understandings of aquatic surface area extent and water–air gas transfer rates are necessary to incorporate temporal variability into the riverine CO₂ flux estimate.We compiled a dataset of present-day direct pCO₂ measurements in global streams and rivers from the literature. The dataset has 5,910 individual measurements of different months that cover all major freshwater ecoregions of the world (18), despite a small percentage (∼0.5%) of measurements from southern temperate rivers (SI Appendix, Fig. S1). The dataset further has pCO₂ measurements in all months from each freshwater ecoregion (open water months for the polar freshwater ecoregion) except oceanic islands and large river deltas that make up only 0.4% of the global land area (SI Appendix, Fig. S1). These observations allowed for robust validation of the study’s results. Riverine pCO₂ was statistically modeled against a set of watershed properties (SI Appendix, Table S1) in order to understand biogeochemical and geophysical controls on pCO₂. Predictions of pCO₂, k, and surface area were based on a new representation of the global river networks (the Global Reach-Level A Priori Discharge Estimates for Surface Water and Ocean Topography [GRADES] river networks) (17), which contains daily discharge estimates at ∼3 million individual river reaches over a 35-y period. Monthly CO₂ flux estimates were achieved by coupling monthly pCO₂ estimates driven by monthly watershed properties to monthly k and surface area estimates driven by the GRADES discharge. Spatial and temporal variability of the flux was finally investigated to demonstrate a strong modulation of the terrestrial (and wetland) carbon routing to the atmosphere via streams and rivers by hydrology.     

Hallmarks of Metabolic Reprogramming and Their Role in Viral Pathogenesis

Metabolic reprogramming is a hallmark of cancer and has proven to be critical in viral infections. Metabolic reprogramming provides the cell with energy and biomass for large-scale biosynthesis. Based on studies of the cellular changes that contribute to metabolic reprogramming, seven main hallmarks can be identified: (1) increased glycolysis and lactic acid, (2) increased glutaminolysis, (3) increased pentose phosphate pathway, (4) mitochondrial changes, (5) increased lipid metabolism, (6) changes in amino acid metabolism, and (7) changes in other biosynthetic and bioenergetic pathways. Viruses depend on metabolic reprogramming to increase biomass to fuel viral genome replication and production of new virions. Viruses take advantage of the non-metabolic effects of metabolic reprogramming, creating an anti-apoptotic environment and evading the immune system. Other non-metabolic effects can negatively affect cellular function. Understanding the role metabolic reprogramming plays in viral pathogenesis may provide better therapeutic targets for antivirals.     

Reliability and Differences Between Sexes in Landing Mechanics when Performing the Lateral Bound Test

Background and PurposeAnterior cruciate ligament injuries are prevalent among the athletic population, imposing a heavy economic burden, and the risk of re-injury. Most current biomechanical screening tasks are performed in the sagittal plane, and there is a need for more screening tools that assess sports specific movements in the frontal plane. The purpose of this study was to determine the reliability of and examine differences between sexes in the performance of the Lateral Bound Test (LBT).Materials/MethodsEach subject performed three trials of a LBT which included jumping laterally from one leg over a hurdle and landing on the opposite leg. Two cameras were placed six feet from the landing marker. Maximum dynamic knee valgus using the frontal plane projection angle and knee flexion angle at initial contact and maximal knee flexion were measured upon landing leg using 2D video analysis software. Additionally, video of 10 individuals’ trials were analyzed twice with one week between the analyses to obtain intra-rater reliability while 12 participants were retested one week later to determine test-retest reliability.ResultsThirty healthy subjects, 16 males, 14 females participated. Intra-rater reliability was determined to be excellent for all variables (ICC>0.96). In contrast, the test-retest reliability had greater disparity. Test-retest reliability ranged from poor (ICC = 0.47) to excellent (ICC > 0.90). Significant differences existed between the sexes, including males being significantly taller, weighing more, and demonstrating greater bilateral dynamic knee valgus (p < 0.05). No significant differences existed between sexes for knee flexion angles.ConclusionThe new LBT had excellent intra-rater reliability for assessing dynamic knee valgus and initial and maximum knee flexion angle when performing a functional movement in the frontal plane. Furthermore, males landed with more dynamic knee valgus than females which is contradictory to what has been observed with functional screening tools performed in the sagittal plane.Level of Evidence3b (reliability study)     

Leukapheresis in rheumatoid arthritis association of clinical improvement with reversal of anergy

In order to study the clinical and immunologic effects of a brief course of leukapheresis, 14 patients with clinically similar rheumatoid arthritis were segregated into 2 subgroups. Group A (7 patients) had subnormal lymphocyte tritiated thymidine incorporation to soluble antigens. After a brief course of leukapheresis, 6 of these 7 patients demonstrated substantial clinical improvement associated with significantly enhanced lymphocyte tritiated thymidine incorporation to soluble antigens. In contrast, none of the 7 patients in group B (normal immune functions) demonstrated similar changes in articular indices or lymphocyte proliferation. Thus, clinical improvement induced in a subset of rheumatoid arthritis patients appears to reflect modulation of function, and not simply immuno-suppression.     

An emergency physician's guide to prosthetic heart valves: valve-related complications

Serious valve-related complications that occur in patients with prosthetic valves have been discussed. The emergency physician's role primarily is to recognize the high probability that one of these serious complications exists and hospitalize the patient so that rapid definitive diagnoses and therapeutic decisions are not delayed.     

Control of intracellular ionized calcium concentration by sarcolemmal and intracellular mechanisms

The regulation of the resting intracellular ionized calcium concentration [( Ca2+]i) has been studied in ferret papillary muscle using the photoprotein aequorin to measure [Ca2+]i. Elevating [Ca2+]o produced an initial rapid increase of [Ca2+]i and tension which then decayed to a steady level. This secondary fall of [Ca2+]i is attributed to a secondary decrease of Ca entry on Na-Ca exchange produced by the known fall of [Na+]i. Replacing external Na by K produced a large transient increase of both [Ca2+]i and tension which then decayed spontaneously to near the resting level. If Na was removed after metabolic inhibition with cyanide and deoxyglucose then neither tension nor [Ca2+]i recovered. The addition of the mitochondrial uncoupler FCCP to a muscle in Na-free solution produced a gradual rise of tension but only elevated [Ca2+]i after a delay of many minutes. Similarly caffeine did not elevate [Ca2+]i. These experiments do not support the hypothesis that the regulation of resting [Ca2+]i in Na-free solutions depends solely on intracellular sequestration of [Ca2+]i. The first twitch elicited in Na-containing solutions after exposure to Na-free solution was much larger than control and was associated with a large Ca transient attributed to increased loading of the sarcoplasmic reticulum with Ca in the Na-free solution. The elevation of [Ca2+]i in Na-free solutions was accompanied by spontaneous fluctuations of both [Ca2+]i and tension with a frequency of about 3 Hz. These fluctuations were abolished by drugs such as caffeine or ryanodine which interfere with sarcoplasmic reticulum function. These results provide direct evidence for the spontaneous release of Ca from the sarcoplasmic reticulum inferred from previous, less direct, work.