Establishing the values for patient engagement (PE) in health-related quality of life (HRQoL) research: an international, multiple-stakeholder perspective

PurposeActive patient engagement is increasingly viewed as essential to ensuring that patient-driven perspectives are considered throughout the research process. However, guidance for patient engagement (PE) in HRQoL research does not exist, the evidence-base for practice is limited, and we know relatively little about underpinning values that can impact on PE practice. This is the first study to explore the values that should underpin PE in contemporary HRQoL research to help inform future good practice guidance. MethodsA modified ‘World Café’ was hosted as a collaborative activity between patient partners, clinicians and researchers: self-nominated conference delegates participated in group discussions to explore values associated with the conduct and consequences of PE. Values were captured via post-it notes and by nominated note-takers. Data were thematically analysed: emergent themes were coded and agreement checked. Association between emergent themes, values and the Public Involvement Impact Assessment Framework were explored. ResultsEighty participants, including 12 patient partners, participated in the 90-min event. Three core values were defined: (1) building relationships; (2) improving research quality and impact; and (3) developing best practice. Participants valued the importance of building genuine, collaborative and deliberative relationships—underpinned by honesty, respect, co-learning and equity—and the impact of effective PE on research quality and relevance. Conclusions An explicit statement of values seeks to align all stakeholders on the purpose, practice and credibility of PE activities. An innovative, flexible and transparent research environment was valued as essential to developing a trustworthy evidence-base with which to underpin future guidance for good PE practice.Peer reviewe

Optimal Conservation of Migratory Species

Background. Migratory animals comprise a significant portion of biodiversity worldwide with annual investment for their conservation exceeding several billion dollars. Designing effective conservation plans presents enormous challenges. Migratory species are influenced by multiple events across land and sea-regions that are often separated by thousands of kilometres and span international borders. To date, conservation strategies for migratory species fail to take into account how migratory animals are spatially connected between different periods of the annual cycle (i.e. migratory connectivity) bringing into question the utility and efficiency of current conservation efforts. Methodology/Principal Findings. Here, we report the first framework for determining an optimal conservation strategy for a migratory species. Employing a decision theoretic approach using dynamic optimization, we address the problem of how to allocate resources for habitat conservation for a Neotropical-Nearctic migratory bird, the American redstart Setophaga ruticilla, whose winter habitat is under threat. Our first conservation strategy used the acquisition of winter habitat based on land cost, relative bird density, and the rate of habitat loss to maximize the abundance of birds on the wintering grounds. Our second strategy maximized bird abundance across the entire range of the species by adding the constraint of maintaining a minimum percentage of birds within each breeding region in North America using information on migratory connectivity as estimated from stable-hydrogen isotopes in feathers. We show that failure to take into account migratory connectivity may doom some regional populations to extinction, whereas including information on migratory connectivity results in the protection of the species across its entire range. Conclusions/Significance. We demonstrate that conservation strategies for migratory animals depend critically upon two factors: knowledge of migratory connectivity and the correct statement of the conservation problem. Our framework can be used to identify efficient conservation strategies for migratory taxa worldwide, including insects, birds, mammals, and marine organisms

Ankle Push-off Based Mathematical Model for Freezing of Gait in Parkinson’s Disease

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.Freezing is an involuntary stopping of gait observed in late-stage Parkinson's disease (PD) patients. This is a highly debilitating symptom lacking a clear understanding of its causes. Walking in these patients is also associated with high variability, making both prediction of freezing and its understanding difficult. A neuromechanical model describes the motion of the mechanical (motor) aspects of the body under the action of neuromuscular forcing. In this work, a simplified neuromechanical model of gait is used to infer the causes for both the observed variability and freezing in PD. The mathematical model consists of the stance leg (during walking) modeled as a simple inverted pendulum acted upon by the ankle-push off forces from the trailing leg and pathological forces by the plantar-flexors of the stance leg. We model the effect on walking of the swing leg in the biped model and provide a rationale for using an inverted pendulum model. Freezing and irregular walking is demonstrated in the biped model as well as the inverted pendulum model. The inverted pendulum model is further studied semi-analytically to show the presence of horseshoe and chaos. While the plantar flexors of the swing leg push the center of mass (CoM) forward, the plantar flexors of the stance leg generate an opposing torque. Our study reveals that these opposing forces generated by the plantar flexors can induce freezing. Other gait abnormalities nearer to freezing such as a reduction in step length, and irregular walking patterns can also be explained by the model.Engineering and Physical Sciences Research Council (EPSRC

High survivability of micrometeorites on Mars: Sites with enhanced availability of limiting nutrients

NASA's strategy in exploring Mars has been to follow the water, because water is essential for life, and it has been found that there are many locations where there was once liquid water on the surface. Now perhaps, to narrow down the search for life on a barren basalt‐dominated surface, there needs to be a refocusing to a strategy of “follow the nutrients.” Here we model the entry of metallic micrometeoroids through the Martian atmosphere, and investigate variations in micrometeorite abundance at an analogue site on the Nullarbor Plain in Australia, to determine where the common limiting nutrients available in these (e.g., P, S, Fe) become concentrated on the surface of Mars. We find that dense micrometeorites are abundant in a range of desert environments, becoming concentrated by aeolian processes into specific sites that would be easily investigated by a robotic rover. Our modeling suggests that micrometeorites are currently far more abundant on the surface of Mars than on Earth, and given the far greater abundance of water and warmer conditions on Earth and thus much more active weather system, this was likely true throughout the history of Mars. Because micrometeorites contain a variety of redox sensitive minerals including FeNi alloys, sulfide and phosphide minerals, and organic compounds, the sites where these become concentrated are far more nutrient rich, and thus more compatible with chemolithotrophic life than most of the Martian surface. Plain Language Summary NASA's exploration program has allowed the scientific community to demonstrate clearly that Mars had a watery past, so the search for life needs to move on to identifying the places where water and nutrients coincided. We have investigated the relative abundance of micrometeorites on Mars compared to the Earth because these contain key nutrients that the earliest life forms on Earth used, and because their contained minerals can be used to investigate past atmospheric chemistry. We suggest that micrometeorites should be far more abundant on the Martian surface than on Earth's, and that wind‐driven modification of sediments is expected to concentrate micrometeorites, and their contained nutrients, in gravel beds and cracks in exposed bedrock

Data-Driven Prediction of Freezing of Gait Events from Stepping Data

This is the final version. Available on open access from Frontiers Media via the DOI in this recordFreezing of gait (FoG) is typically a symptom of advanced Parkinson’s disease (PD) that negatively influences quality of life and is often resistant to pharmacological interventions. Novel treatment options that make use of auditory or sensory cues might be optimized by prediction of freezing events. These predictions might help to trigger external sensory cues – shown to improve walking performance – when behaviour is changed in a manner indicative of an impending freeze (i.e. when the user needs it the most), rather than delivering cue information continuously. A data-driven approach is proposed for predicting freezing events using Random Forrest (RF), Neural Network (NN) and Naive Bayes (NB) classifiers. Vertical forces, sampled at 100Hz from a force platform were collected from 9 PD subjects as they stepped in place until they at least had one freezing episode or for 90s. The F1 scores of RF/NN/NB algorithms were computed for different IL (input to the machine learning algorithm), and GL (how early the freezing event is predicted). A significant negative correlation between the F1 scores and GL, highlighting the difficulty of early detection is found. The IL that maximized the F1 score is approximately equal to 1.13 s. This indicates that the physiological (and therefore neurological) changes leading to freezing takes effect at-least one step before the freezing incident. Our algorithm has the potential to support the development of devices to detect and then potentially prevent freezing events in people with Parkinson’s which might occur if left uncorrected.Engineering and Physical Sciences Research Council (EPSRC

Multiple Neural Oscillators and Muscle Feedback Are Required for the Intestinal Fed State Motor Program

After a meal, the gastrointestinal tract exhibits a set of behaviours known as the fed state. A major feature of the fed state is a little understood motor pattern known as segmentation, which is essential for digestion and nutrient absorption. Segmentation manifests as rhythmic local constrictions that do not propagate along the intestine. In guinea-pig jejunum in vitro segmentation constrictions occur in short bursts together with other motor patterns in episodes of activity lasting 40–60 s and separated by quiescent episodes lasting 40–200 s. This activity is induced by luminal nutrients and abolished by blocking activity in the enteric nervous system (ENS). We investigated the enteric circuits that regulate segmentation focusing on a central feature of the ENS: a recurrent excitatory network of intrinsic sensory neurons (ISNs) which are characterized by prolonged after-hyperpolarizing potentials (AHPs) following their action potentials. We first examined the effects of depressing AHPs with blockers of the underlying channels (TRAM-34 and clotrimazole) on motor patterns induced in guinea-pig jejunum, in vitro, by luminal decanoic acid. Contractile episode durations increased markedly, but the frequency and number of constrictions within segmenting bursts and quiescent period durations were unaffected. We used these observations to develop a computational model of activity in ISNs, excitatory and inhibitory motor neurons and the muscle. The model predicted that: i) feedback to ISNs from contractions in the circular muscle is required to produce alternating activity and quiescence with the right durations; ii) transmission from ISNs to excitatory motor neurons is via fast excitatory synaptic potentials (EPSPs) and to inhibitory motor neurons via slow EPSPs. We conclude that two rhythm generators regulate segmentation: one drives contractions within segmentation bursts, the other the occurrence of bursts. The latter depends on AHPs in ISNs and feedback to these neurons from contraction of the circular muscle

A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches.

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell