Expanding Rural Elder Care Options: Models That Work

Rural communities and elders need better access to elder care options that enable them to continue to live in the community. Despite a larger proportion of the population over age 65 than urban and suburban America, rural communities lack the services and care coordination systems older adults need to continue living independently in their own communities as they age. In November 2008, the Rural Long Term Care Workgroup convened a national Rural Long Term Care: Access and Options Workshop to identify lessons and strategies for building and sustaining rural community-based elder care services. Finding and building on successful models is an important step towards addressing the challenges faced by rural elders seeking care options in their communities. These options include home, community, and facility-based care supported by care coordination systems that enhance autonomy and quality of life of rural elders. These proceedings of the Workshop are organized around the following topics: The challenges and opportunities for expanding rural elder care options; Five rural elder care models that work; A Rural Elder Care Options Model, a web-based, interactive tool that rural communities can use to customize the options to their specific community; The organizational attributes and strong partnerships needed to build rural community options for elder care; Strategies for increasing access and options for elder care in rural communities; and Steps to move forward in building rural communities that support elder care

Forecasting Player Behavioral Data and Simulating in-Game Events

Understanding player behavior is fundamental in game data science. Video games evolve as players interact with the game, so being able to foresee player experience would help to ensure a successful game development. In particular, game developers need to evaluate beforehand the impact of in-game events. Simulation optimization of these events is crucial to increase player engagement and maximize monetization. We present an experimental analysis of several methods to forecast game-related variables, with two main aims: to obtain accurate predictions of in-app purchases and playtime in an operational production environment, and to perform simulations of in-game events in order to maximize sales and playtime. Our ultimate purpose is to take a step towards the data-driven development of games. The results suggest that, even though the performance of traditional approaches such as ARIMA is still better, the outcomes of state-of-the-art techniques like deep learning are promising. Deep learning comes up as a well-suited general model that could be used to forecast a variety of time series with different dynamic behaviors

Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

Protocol for the "Michigan Awareness Control Study": A prospective, randomized, controlled trial comparing electronic alerts based on bispectral index monitoring or minimum alveolar concentration for the prevention of intraoperative awareness

<p>Abstract</p> <p>Background</p> <p>The incidence of intraoperative awareness with explicit recall is 1-2/1000 cases in the United States. The Bispectral Index monitor is an electroencephalographic method of assessing anesthetic depth that has been shown in one prospective study to reduce the incidence of awareness in the high-risk population. In the B-Aware trial, the number needed to treat in order to prevent one case of awareness in the high-risk population was 138. Since the number needed to treat and the associated cost of treatment would be much higher in the general population, the efficacy of the Bispectral Index monitor in preventing awareness in all anesthetized patients needs to be clearly established. This is especially true given the findings of the B-Unaware trial, which demonstrated no significant difference between protocols based on the Bispectral Index monitor or minimum alveolar concentration for the reduction of awareness in high risk patients.</p> <p>Methods/Design</p> <p>To evaluate efficacy in the general population, we are conducting a prospective, randomized, controlled trial comparing the Bispectral Index monitor to a non-electroencephalographic gauge of anesthetic depth. The total recruitment for the study is targeted for 30,000 patients at both low and high risk for awareness. We have developed a novel algorithm that is capable of real-time analysis of our electronic perioperative information system. In one arm of the study, anesthesia providers will receive an electronic page if the Bispectral Index value is >60. In the other arm of the study, anesthesia providers will receive a page if the age-adjusted minimum alveolar concentration is <0.5. Our minimum alveolar concentration algorithm is sensitive to both inhalational anesthetics and intravenous sedative-hypnotic agents.</p> <p>Discussion</p> <p>Awareness during general anesthesia is a persistent problem and the role of the Bispectral Index monitor in its prevention is still unclear. The Michigan Awareness Control Study is the largest prospective trial of awareness prevention ever conducted.</p> <p>Trial Registration</p> <p>Clinical Trial NCT00689091</p

Programmable Ligand Detection System in Plants through a Synthetic Signal Transduction Pathway

There is an unmet need to monitor human and natural environments for substances that are intentionally or unintentionally introduced. A long-sought goal is to adapt plants to sense and respond to specific substances for use as environmental monitors. Computationally re-designed periplasmic binding proteins (PBPs) provide a means to design highly sensitive and specific ligand sensing capabilities in receptors. Input from these proteins can be linked to gene expression through histidine kinase (HK) mediated signaling. Components of HK signaling systems are evolutionarily conserved between bacteria and plants. We previously reported that in response to cytokinin-mediated HK activation in plants, the bacterial response regulator PhoB translocates to the nucleus and activates transcription. Also, we previously described a plant visual response system, the de-greening circuit, a threshold sensitive reporter system that produces a visual response which is remotely detectable and quantifiable.We describe assembly and function of a complete synthetic signal transduction pathway in plants that links input from computationally re-designed PBPs to a visual response. To sense extracellular ligands, we targeted the computational re-designed PBPs to the apoplast. PBPs bind the ligand and develop affinity for the extracellular domain of a chemotactic protein, Trg. We experimentally developed Trg fusions proteins, which bind the ligand-PBP complex, and activate intracellular PhoR, the HK cognate of PhoB. We then adapted Trg-PhoR fusions for function in plants showing that in the presence of an external ligand PhoB translocates to the nucleus and activates transcription. We linked this input to the de-greening circuit creating a detector plant.Our system is modular and PBPs can theoretically be designed to bind most small molecules. Hence our system, with improvements, may allow plants to serve as a simple and inexpensive means to monitor human surroundings for substances such as pollutants, explosives, or chemical agents

The YARHG Domain: An Extracellular Domain in Search of a Function

We have identified a new bacterial protein domain that we hypothesise binds to peptidoglycan. This domain is called the YARHG domain after the most highly conserved sequence-segment. The domain is found in the extracellular space and is likely to be composed of four alpha-helices. The domain is found associated with protein kinase domains, suggesting it is associated with signalling in some bacteria. The domain is also found associated with three different families of peptidases. The large number of different domains that are found associated with YARHG suggests that it is a useful functional module that nature has recombined multiple times

Heterogeneous Host Susceptibility Enhances Prevalence of Mixed-Genotype Micro-Parasite Infections

Dose response in micro-parasite infections is usually shallower than predicted by the independent action model, which assumes that each infectious unit has a probability of infection that is independent of the presence of other infectious units. Moreover, the prevalence of mixed-genotype infections was greater than predicted by this model. No probabilistic infection model has been proposed to account for the higher prevalence of mixed-genotype infections. We use model selection within a set of four alternative models to explain high prevalence of mixed-genotype infections in combination with a shallow dose response. These models contrast dependent versus independent action of micro-parasite infectious units, and homogeneous versus heterogeneous host susceptibility. We specifically consider a situation in which genome differences between genotypes are minimal, and highly unlikely to result in genotype-genotype interactions. Data on dose response and mixed-genotype infection prevalence were collected by challenging fifth instar Spodoptera exigua larvae with two genotypes of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), differing only in a 100 bp PCR marker sequence. We show that an independent action model that includes heterogeneity in host susceptibility can explain both the shallow dose response and the high prevalence of mixed-genotype infections. Theoretical results indicate that variation in host susceptibility is inextricably linked to increased prevalence of mixed-genotype infections. We have shown, to our knowledge for the first time, how heterogeneity in host susceptibility affects mixed-genotype infection prevalence. No evidence was found that virions operate dependently. While it has been recognized that heterogeneity in host susceptibility must be included in models of micro-parasite transmission and epidemiology to account for dose response, here we show that heterogeneity in susceptibility is also a fundamental principle explaining patterns of pathogen genetic diversity among hosts in a population. This principle has potentially wide implications for the monitoring, modeling and management of infectious diseases

Combination antibiotic therapy for community-acquired pneumonia

Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Combination antibiotic therapy achieves a better outcome compared with monotherapy and it should be given in the following subset of patients with CAP: outpatients with comorbidities and previous antibiotic therapy, nursing home patients with CAP, hospitalized patients with severe CAP, bacteremic pneumococcal CAP, presence of shock, and necessity of mechanical ventilation. Better outcome is associated with combination therapy that includes a macrolide for wide coverage of atypical pneumonia, polymicrobial pneumonia, or resistant Streptococcus pneumoniae. Macrolides have shown different properties other than antimicrobial activity, such as anti-inflammatory properties. Although this evidence comes from observational, most of them retrospective and nonblinded studies, the findings are consistent. Ideally, a prospective, multicenter, randomized trial should be performed to confirm these findings

A Quick Guide for Developing Effective Bioinformatics Programming Skills

Bioinformatics programming skills are becoming a necessity across many facets of biology and medicine, owed in part to the continuing explosion of biological dat