Retinal imaging technologies in cerebral malaria: a systematic review.

BACKGROUND: Cerebral malaria (CM) continues to present a major health challenge, particularly in sub-Saharan Africa. CM is associated with a characteristic malarial retinopathy (MR) with diagnostic and prognostic significance. Advances in retinal imaging have allowed researchers to better characterize the changes seen in MR and to make inferences about the pathophysiology of the disease. The study aimed to explore the role of retinal imaging in diagnosis and prognostication in CM; establish insights into pathophysiology of CM from retinal imaging; establish future research directions. METHODS: The literature was systematically reviewed using the African Index Medicus, MEDLINE, Scopus and Web of Science databases. A total of 35 full texts were included in the final analysis. The descriptive nature of the included studies and heterogeneity precluded meta-analysis. RESULTS: Available research clearly shows retinal imaging is useful both as a clinical tool for the assessment of CM and as a scientific instrument to aid the understanding of the condition. Modalities which can be performed at the bedside, such as fundus photography and optical coherence tomography, are best positioned to take advantage of artificial intelligence-assisted image analysis, unlocking the clinical potential of retinal imaging for real-time diagnosis in low-resource environments where extensively trained clinicians may be few in number, and for guiding adjunctive therapies as they develop. CONCLUSIONS: Further research into retinal imaging technologies in CM is justified. In particular, co-ordinated interdisciplinary work shows promise in unpicking the pathophysiology of a complex disease.

The role of spatial structure in at-risk metapopulation recoveries.

Metapopulations are often managed as a single contiguous population despite the spatial structure underlying their local and regional dynamics. Disturbances from human activities can also be spatially structured with mortality impacts concentrated to just a few local populations among the aggregate. Scale transitions between local and regional processes can generate emergent properties whereby the whole system can fail to recover as quickly as expected for an equivalent single population. Here, we draw on theory and empirical case studies to ask: what is the consequence of spatially structured ecological and disturbance processes on metapopulation recoveries? We suggest that exploring this question could help address knowledge gaps for managing metapopulations including: Why do some metapopulations recover quickly while others remain collapsed? And, what risks are unaccounted for when metapopulations are managed at aggregate scales? First, we used model simulations to examine how scale transitions among ecological and disturbance conditions interact to generate emergent metapopulation recovery outcomes. In general, we found that the spatial structure of disturbance was a strong determinant of recovery outcomes. Specifically, disturbances that unevenly impacted local populations consistently generated the slowest recoveries and highest conservation risks. Ecological conditions that dampened metapopulation recoveries included low dispersal, variable local demography, sparsely connected habitat networks, and spatially and temporally correlated stochastic processes. Second, we illustrate the unexpected challenges of managing metapopulations by examining the recoveries of three USA federally listed endangered species: Florida Everglade snail kites, California and Alaska sea otters, and Snake River Chinook salmon. Overall, our results show the pivotal role of spatial structure in metapopulation recoveries whereby the interplay between local and regional processes shapes the resilience of the whole system. With this understanding, we provide guidelines for resource managers tasked with conserving and managing metapopulations and identify opportunities for research to support the application of metapopulation theory to real-world challenges.

European NCAP Driver State Monitoring Protocols: Prevalence of Distraction in Naturalistic Driving.

OBJECTIVE: examine the prevalence of driver distraction in naturalistic driving when implementing European New Car Assessment Program (Euro NCAP)-defined distraction behaviours. BACKGROUND: The 2023 introduction of Occupant Status monitoring (OSM) into Euro NCAP will accelerate uptake of Driver State Monitoring (DSM). Euro NCAP outlines distraction behaviours that DSM must detect to earn maximum safety points. Distraction behaviour prevalence and driver alerting and intervention frequency have yet to be examined in naturalistic driving. METHOD: Twenty healthcare workers were provided with an instrumented vehicle for approximately two weeks. Data were continuously monitored with automotive grade DSM during daily work commutes, resulting in 168.8 hours of driver head, eye and gaze tracking. RESULTS: Single long distraction events were the most prevalent, with .89 events/hour. Implementing different thresholds for driving-related and driving-unrelated glance regions impacts alerting rates. Lizard glances (primarily gaze movement) occurred more frequently than owl glances (primarily head movement). Visual time-sharing events occurred at a rate of .21 events/hour. CONCLUSION: Euro NCAP-described driver distraction occurs naturalistically. Lizard glances, requiring gaze tracking, occurred in high frequency relative to owl glances, which only require head tracking, indicating that less sophisticated DSM will miss a substantial amount of distraction events. APPLICATION: This work informs OEMs, DSM manufacturers and regulators of the expected alerting rate of Euro NCAP defined distraction behaviours. Alerting rates will vary with protocol implementation, technology capability, and HMI strategies adopted by the OEMs, in turn impacting safety outcomes, user experience and acceptance of DSM technology.

Marine and freshwater regime changes impact a community of migratory Pacific salmonids in decline.

Marine and freshwater ecosystems are increasingly at risk of large and cascading changes from multiple human activities (termed "regime shifts"), which can impact population productivity, resilience, and ecosystem structure. Pacific salmon exhibit persistent and large fluctuations in their population dynamics driven by combinations of intrinsic (e.g., density dependence) and extrinsic factors (e.g., ecosystem changes, species interactions). In recent years, many Pacific salmon have declined due to regime shifts but clear understanding of the processes driving these changes remains elusive. Here, we unpacked the role of density dependence, ecosystem trends, and stochasticity on productivity regimes for a community of five anadromous Pacific salmonids (Steelhead, Coho Salmon, Pink Salmon, Dolly Varden, and Coastal Cutthroat Trout) across a rich 40-year time-series. We used a Bayesian multivariate state-space model to examine whether productivity shifts had similarly occurred across the community and explored marine or freshwater changes associated with those shifts. Overall, we identified three productivity regimes: an early regime (1976-1990), a compensatory regime (1991-2009), and a declining regime (since 2010) where large declines were observed for Steelhead, Dolly Varden, and Cutthroat Trout, intermediate declines in Coho and no change in Pink Salmon. These regime changes were associated with multiple cumulative effects across the salmon life cycle. For example, increased seal densities and ocean competition were associated with lower adult marine survival in Steelhead. Watershed logging also intensified over the past 40 years and was associated with (all else equal) ≥97% declines in freshwater productivity for Steelhead, Cutthroat, and Coho. For Steelhead, marine and freshwater dynamics played approximately equal roles in explaining trends in total productivity. Collectively, these changing environments limited juvenile production and lowered future adult returns. These results reveal how changes in freshwater and marine environments can jointly shape population dynamics among ecological communities, like Pacific salmon, with cascading consequences to their resilience.

Assessing conservation status with extensive but low-resolution data: Application of frequentist and Bayesian models to endangered Athabasca River rainbow trout.

Use of extensive but low-resolution abundance data is common in the assessment of species at-risk status based on quantitative decline criteria under International Union for Conservation of Nature (IUCN) and national endangered species legislation. Such data can be problematic for 3 reasons. First, statistical power to reject the null hypothesis of no change is often low because of small sample size and high sampling uncertainty leading to a high frequency of type II errors. Second, range-wide assessments composed of multiple site-specific observations do not effectively weight site-specific trends into global trends. Third, uncertainty in site-specific temporal trends and relative abundance are not propagated at the appropriate spatial scale. A common result is the propensity to underestimate the magnitude of declines and therefore fail to identify the appropriate at-risk status for a species. We used 3 statistical approaches, from simple to more complex, to estimate temporal decline rates for a designatable unit (DU) of rainbow trout in the Athabasca River watershed in western Canada. This DU is considered a native species for purposes of listing because of its genetic composition characterized as >0.95 indigenous origin in the face of continuing introgressive hybridization with introduced populations in the watershed. Analysis of abundance trends from 57 time series with a fixed-effects model identified 33 sites with negative trends, but only 2 were statistically significant. By contrast, a hierarchical linear mixed model weighted by site-specific abundance provided a DU-wide decline estimate of 16.4% per year and a 3-generation decline of 93.2%. A hierarchical Bayesian mixed model yielded a similar 3-generation decline trend of 91.3% and the posterior distribution showed that the estimate had a >99% probability of exceeding thresholds for an endangered listing. We conclude that the Bayesian approach was the most useful because it provided a probabilistic statement of threshold exceedance in support of an at-risk status recommendation.

El uso de datos extensivos, pero de baja resolución, de la abundancia es una práctica común en la evaluación del estado de riesgo de una especie con base en los criterios cuantitativos de declinación establecidos por la Unión Internacional para la Conservación de la Naturaleza (UICN) y la legislación nacional sobre especies en peligro extinción. Dicha información puede ser problemática por tres razones: primero, el poder estadístico para rechazar la hipótesis nula de ningún cambio es frecuentemente bajo debido a un tamaño pequeño de la muestra y a la elevada incertidumbre del muestreo, lo que resulta en una frecuencia elevada de errores de tipo II; segundo, las evaluaciones de amplia variedad compuestas de varias observaciones específicas de sitio no sopesan efectivamente las tendencias específicas de sitio dentro de las tendencias globales; y tercero, la incertidumbre en las tendencias temporales específicas de sitio y en la abundancia relativa no se propagan a la escala espacial apropiada. Un resultado común del uso de esta información es la propensión a subestimar la magnitud de las declinaciones, y por lo tanto equivocarse en la identificación del estado de riesgo apropiado para la especie. Usamos tres estrategias estadísticas, de simples a más complejas, para estimar las tasas de declinación temporal para una unidad designable (UD) de trucha arcoíris en la cuenca del río Athabasca al oeste de Canadá. Esta UD es considerada una especie nativa por razones de listado debido a su composición genética, caracterizada como >0-95 de origen nativo de frente a la continua hibridación introgresiva con poblaciones introducidas a la cuenca. El análisis de las tendencias de abundancia de 57 series de tiempo con un modelo de efectos fijos identificó 33 sitios con tendencias negativas, pero sólo dos fueron estadísticamente significativas. En contraste, un modelo lineal mixto de jerarquías sopesado por abundancia específica de sitio proporcionó una estimación de declinación en toda la UD de 16.4% año−1 y una declinación a tres generaciones de 93.2%. Un modelo bayesiano de jerarquías produjo una tendencia de declinación a tres generaciones de 91.3% y la distribución posterior mostró que el estimado tuvo una probabilidad >99% de exceder los umbrales para la categorización como especie en peligro. Concluimos que la estrategia bayesiana fue la más útil porque proporcionó una afirmación probabilística de la superación del umbral a favor de una recomendación de categorizar el estado como en riesgo.

Capnocytophaga canimorsus meningitis in a 38-year-old immunocompetent woman from household pet exposure.

A 38-year-old otherwise healthy woman with no history of immunocompromise, recent travel, or concerning exposures presented to the ED with several days of nonspecific cold-like symptoms with associated generalized headache. After the patient was symptomatically treated and discharged, she returned several hours later with worsening of symptoms and new vomiting, confusion, and sensorineural hearing loss. Blood and cerebrospinal fluid cultures eventually returned positive for a Capnocytophaga canimorsus infection, a bacterial pathogen found in the saliva of dogs and cats. Only after that, the patient recalled being scratched and licked by her pets, two dogs and a cat. She was treated with a course of systemic steroids, antibiotics and discharged home.

Evaluating Driver Features for Cognitive Distraction Detection and Validation in Manual and Level 2 Automated Driving.

OBJECTIVE: This study aimed to investigate the impacts of feature selection on driver cognitive distraction (CD) detection and validation in real-world nonautomated and Level 2 automated driving scenarios. BACKGROUND: Real-time driver state monitoring is critical to promote road user safety. METHOD: Twenty-four participants were recruited to drive a Tesla Model S in manual and Autopilot modes on the highway while engaging in the N-back task. In each driving mode, CD was classified by the random forest algorithm built on three "hand-crafted" glance features (i.e., percent road center [PRC], the standard deviation of gaze pitch, and yaw angles), or through a large number of features that were transformed from the output of a driver monitoring system (DMS) and other sensing systems. RESULTS: In manual driving, the small set of glance features was as effective as the large set of machine-generated features in terms of classification accuracy. Whereas in Level 2 automated driving, both glance and vehicle features were less sensitive to CD. The glance features also revealed that the misclassified driver state was the result of the dynamic fluctuations and individual differences of cognitive loads under CD. CONCLUSION: Glance metrics are critical for the detection and validation of CD in on-road driving. APPLICATIONS: The paper suggests the practical value of human factors domain knowledge in feature selection and ground truth validation for the development of driver monitoring technologies.

Patient Characteristics Independently Associated With Knee Osteoarthritis Symptom Severity at Initial Orthopedic Consultation.

BACKGROUND/OBJECTIVE: The objective of this study was to identify patient and disease characteristics associated with the symptomatic severity of knee osteoarthritis (OA) at the time of initial knee OA diagnosis by an orthopedist. METHODS: This medical records review included patients initially diagnosed with knee OA during 2016 to 2017 by a single orthopedic surgeon in a university-based tertiary care setting. All variables were assessed at first OA diagnosis. Main outcomes were subscales of the Knee Injury and Osteoarthritis Outcome Score-Pain, other Symptoms, knee-related quality of life, and function in daily living. Multivariable regression analyses examined the following predictors of main outcomes: sex, race, age, insurance type, body mass index, Charlson comorbidity index, and radiographic OA severity (Kellgren-Lawrence grade). RESULTS: Of the 559 patients included in the study, most were African American (52.1%), female (71.7%), and had severe radiographic OA (Kellgren-Lawrence grade, 4; 68.7%). Female sex, African American racial/ethnic group, Medicaid insurance, younger age, and severe radiographic OA were independently statistically significantly associated with worse symptoms, pain, and function (p < 0.05 for all). Body mass index and Charlson comorbidity index were not statistically significant predictors of any outcome. CONCLUSIONS: This study identified disparities in the perception of knee OA problems at initial orthopedist diagnosis based on sex, age, race, insurance, and radiographic OA severity. Because most of these variables are also associated with more rapid progression of OA, identifying their biopsychosocial underpinnings may help determine which interventions are most likely to redress these disparities and delay progression to end-stage knee OA.

Protection by and maintenance of CD4 effector memory and effector T cell subsets in persistent malaria infection.

Protection at the peak of Plasmodium chabaudi blood-stage malaria infection is provided by CD4 T cells. We have shown that an increase in Th1 cells also correlates with protection during the persistent phase of malaria; however, it is unclear how these T cells are maintained. Persistent malaria infection promotes protection and generates both effector T cells (Teff), and effector memory T cells (Tem). We have previously defined new CD4 Teff (IL-7Rα-) subsets from Early (TeffEarly, CD62LhiCD27+) to Late (TeffLate, CD62LloCD27-) activation states. Here, we tested these effector and memory T cell subsets for their ability to survive and protect in vivo. We found that both polyclonal and P. chabaudi Merozoite Surface Protein-1 (MSP-1)-specific B5 TCR transgenic Tem survive better than Teff. Surprisingly, as Tem are associated with antigen persistence, Tem survive well even after clearance of infection. As previously shown during T cell contraction, TeffEarly, which can generate Tem, also survive better than other Teff subsets in uninfected recipients. Two other Tem survival mechanisms identified here are that low-level chronic infection promotes Tem both by driving their proliferation, and by programming production of Tem from Tcm. Protective CD4 T cell phenotypes have not been precisely determined in malaria, or other persistent infections. Therefore, we tested purified memory (Tmem) and Teff subsets in protection from peak pathology and parasitemia in immunocompromised recipient mice. Strikingly, among Tmem (IL-7Rαhi) subsets, only TemLate (CD62LloCD27-) reduced peak parasitemia (19%), though the dominant memory subset is TemEarly, which is not protective. In contrast, all Teff subsets reduced peak parasitemia by more than half, and mature Teff can generate Tem, though less. In summary, we have elucidated four mechanisms of Tem maintenance, and identified two long-lived T cell subsets (TemLate, TeffEarly) that may represent correlates of protection or a target for longer-lived vaccine-induced protection against malaria blood-stages.

PD-L1-Independent Mechanisms Control the Resistance of Melanoma to CD4+ T Cell Adoptive Immunotherapy.

Immunotherapy is becoming the standard of care for melanoma. However, resistance to therapy is a major problem. Previously, we showed that tumor-specific, cytotoxic CD4+ T cells from tyrosinase-related protein 1 transgenic mice could overcome secondary resistance to recurring melanoma when anti-programmed cell death 1 ligand (PD-L1) checkpoint blockade was combined with either anti-lymphocyte-activated gene 3 (LAG-3) Abs or depletion of tumor-specific regulatory T (Treg) cells. In this study, we show that PD-L1 expressed by the host, not B16 melanoma, plays a major role in the early stages of exhaustion or primary resistance. We observed durable regression of melanoma in tumor-bearing PD-L1-/-RAG-/- mice with transfer of naive tumor-specific CD4+ T cells. However, exhausted tumor-specific CD4+ T cells, which included tumor-specific Treg cells, failed to maintain durable regression of tumors in PD-L1-/-RAG-/- mice unless tumor-specific Treg cells were eliminated, showing nonredundant pathways of resistance to immunotherapy were present. Translating these findings to a clinically relevant model of cancer immunotherapy, we unexpectedly showed that anti-PD-L1 checkpoint blockade mildly improved immunotherapy with tumor-specific CD4+ T cells and irradiation in wild-type mice. Instead, anti-LAG-3 checkpoint blockade, in combination with tumor-specific CD4+ T cells and irradiation, overcame primary resistance and treated established tumors resulting in fewer recurrences. Because LAG-3 negatively regulates effector T cell function and activates Treg cells, LAG-3 blockade may be more beneficial in overcoming primary resistance in combination immunotherapies using adoptive cellular therapy and irradiation than blockade of PD-L1.

Response Complexity Reduces Errors on a Response Inhibition Task.

OBJECTIVE: The purpose of this investigation was to elucidate the role of button-response complexity to targets in a response inhibition task. BACKGROUND: Response inhibition is the ability to correctly inhibit an overt response to a target. The U.S. military is actively pursuing development of armed, combat robots as a force multiplier, which may present challenges to operators of combat robots in the form of response inhibition errors. METHOD: A total of 15 participants completed two 51-min versions of a modified sustained attention to response task (SART). Participants were outfitted with an electrocardiogram to index heart-rate variability and completed the NASA-Task Load Index (NASA-TLX) to index workload. RESULTS: The results demonstrated that the complex SART reduced errors of commission (4%) and slowed response times (874 ms) to correct Go targets relative to the simple SART (14%, 739 ms). The NASA-TLX did not show differences between the modified SARTs; however, heart-rate variability did demonstrate that Soldiers had an increased autonomic stress response to the complex SART. CONCLUSION: Increasing the behavioral response requirement during a response inhibition task can decrease errors of commission; however, it comes at the cost of slower response times to target stimuli. Heart-rate variability may provide better insight into objective workload relative to subjective measures. APPLICATION: The use of complex behavioral responses may provide a viable option to reduce potential "friendly fire" or collateral damage by Soldiers remotely engaging a target-rich environment.

Show Me, Tell Me, Encourage Me: The Effect of Different Forms of Feedback on Resistance Training Performance.

Weakley, J, Wilson, K, Till, K, Banyard, H, Dyson, J, Phibbs, P, Read, D, and Jones, B. Show me, tell me, encourage me: The effect of different forms of feedback on resistance training performance. J Strength Cond Res 34(11): 3157-3163, 2020-When performing resistance training, verbal kinematic feedback and visual kinematic feedback are known to enhance performance. In addition, providing verbal encouragement can assist in the attenuation of fatigue. However, the effects of these forms of feedback have never been compared. Consequently, this study aimed to quantify the effects of verbal kinematic feedback and visual kinematic feedback, and verbal encouragement on barbell velocity during the back squat. Furthermore, changes in performance were related to individual-reported conscientiousness. Twelve semiprofessional rugby union players volunteered to participate in the study that consisted of the subjects completing a set of the barbell back squat across 4 conditions (i.e., no-feedback [control], verbal feedback of kinematic information [verbal], visual feedback of kinematic information [visual], and verbal encouragement [encouragement]). In addition, participants completed a questionnaire before the study to assess conscientiousness. Magnitude-based inferences were used to assess differences between conditions, whereas Spearman's rank correlation coefficient was used to assess relationships between conscientiousness and changes in barbell velocity. All 3 forms of feedback showed almost certain improvements in barbell velocity, while differences between interventions were likely to very likely trivial. Changes in barbell velocity showed small to large inverse relationships with conscientiousness. These findings suggest that practitioners should supply kinematic feedback (verbally or visually) or, when technology is not available, provide athletes with encouraging statements while resistance training. Verbal encouragement may be of greatest benefit for individuals who demonstrate low levels of conscientiousness. Given these findings, practitioners are advised to use either technology or verbal encouragement to manipulate acute training outcomes.

Current state of urethral tissue engineering.

PURPOSE OF REVIEW: Urethrotomy remains the first-line therapy in the treatment of a urethral stricture despite data showing no real chance of a cure after repeated urethroplasties. An anastomotic or an augmentation urethroplasty with oral mucosa should be offered to patients with a failed urethrotomy. The availability of grafts can be a concern for both patients and surgeons. The potential for a tissue-engineered solution has been explored in recent years and is explored in this article. RECENT FINDINGS: More than 80 preclinical studies have investigated a tissue-engineered approach for urethral reconstruction mostly using decellularized natural scaffolds with or without cell seeding. The animal models used in preclinical testing are not representative of disease processes seen with strictures in man. The available clinical studies were of small sample size and lacked control groups. The choice of biomaterial were mostly acellular matrices derived from natural extracellular matrix. The reported success rates in the pilot clinical studies were highly variable. SUMMARY: The research with tissue engineering of the urethra has not yet been translated into a clinically available material. This is an area where much more research is needed and we would conclude that it is an area of unmet clinical need where users of tissue-engineered urethra in the future need to carry out a rigorous basic science programme and need to be cautious in drawing conclusions based on initial experience and report on long-term clinical results.

Life-history variation along environmental and harvest clines of a northern freshwater fish: Plasticity and adaptation.

Plasticity, local adaptation and evolutionary trade-offs drive clinal variation in traits associated with lifetime growth. Disentangling the processes and determinants that cause these traits to vary helps to understand species' responses to changing environments. This is particularly urgent for exploited populations, where size-selective harvest can induce life-history evolution. Lake trout (Salvelinus namaycush) are an exploited fish with a life history adapted to low-productivity freshwaters of northern North America, which makes them highly vulnerable to ecosystem changes and overfishing. We characterized life-history variation across a broad and diverse landscape for this iconic northern freshwater fish and evaluated whether clinal variation was consistent with hypotheses for local adaptation or growth plasticity. We estimated growth-associated traits for 90 populations exposed to a diversity of environments using a Bayesian multivariate hierarchical model. We tested for clinal variation in their somatic growth, size at maturity and reproductive allocation along environmental gradients of lake productivity, climate, prey and exploitation clines under competing hypotheses of plasticity and local adaptation. Clinal life-history variation was consistent with growth plasticity and local adaptations but not harvest-induced evolution. Variation in somatic growth was explained by exploitation, climate and prey fish occurrence. Increased exploitation, from pristine to fully exploited conditions, led to increased somatic growth (from 32 to 45 mm/year) and adult life spans, and reduced age at maturity (from 11 to 8 years). Variation in size at maturity was explained by climate and, less certainly, prey fish occurrence, while reproductive allocation was explained by evolutionary trade-offs with mortality and other traits, but not environment. Lake trout life-history variation within this range was as wide as that observed across dozens of other freshwater species. Lake trout life histories resulted from evolutionary trade-offs, growth plasticity and local adaptations along several environmental clines. Presuming a plastic response, we documented ~1.4-fold growth compensation to exploitation-lower growth compensation than observed in many freshwater fishes. These results suggest that harvested species exposed to spatially structured and diverse environments may have substantial clinal variation on different traits, but due to different processes, and this has implications for their resilience and successful management.

Dissemination of non-typhoidal Salmonella during Plasmodium chabaudi infection affects anti-malarial immunity.

Malaria-associated bacteremia accounts for up to one-third of deaths from severe malaria, and non-typhoidal Salmonella (NTS) has been reported as a major complication of severe malarial infection. Patients who develop NTS bacteremia during Plasmodium infection show higher mortality rates than individuals with malaria alone. Systemic bacteremia can be caused by a wound or translocation from epithelial or endothelial sites. NTS is an intestinal pathogen, however the contribution of bacterial translocation from the intestinal tract during Plasmodium infection is not well studied. Here, we investigated the integrity of the intestinal barrier function of P. chabaudi-infected mice using large molecules and Salmonella infection. Intestinal histology and the adaptive immune response to malaria were also studied using light microscopy and flow cytometry. P. chabaudi infection compromised intestinal barrier function, which led to increased intestinal cellular infiltration. In addition, we observed increased serum lipopolysaccharide binding protein and leakage of soluble molecules from the intestine into the blood in infected mice. Plasmodium infection also increased intestinal translocation and dissemination of NTS to the liver. The adaptive immune response to P. chabaudi infection was also significantly impacted by NTS translocation. Reduced B and T cell activation were observed in co-infected animals, suggesting interference in the malaria-specific immune responses by bacteremia. These studies demonstrate that P. chabaudi infection induces failure of the barrier function of the intestinal wall and enhanced intestinal bacterial translocation, affecting anti-malarial immunity.

Visual Feedback Attenuates Mean Concentric Barbell Velocity Loss and Improves Motivation, Competitiveness, and Perceived Workload in Male Adolescent Athletes.

Weakley, JJS, Wilson, KM, Till, K, Read, DB, Darrall-Jones, J, Roe, GAB, Phibbs, PJ, and Jones, B. Visual feedback attenuates mean concentric barbell velocity loss and improves motivation, competitiveness, and perceived workload in male adolescent athletes. J Strength Cond Res 33(9): 2420-2425, 2019-It is unknown whether instantaneous visual feedback of resistance training outcomes can enhance barbell velocity in younger athletes. Therefore, the purpose of this study was to quantify the effects of visual feedback on mean concentric barbell velocity in the back squat and to identify changes in motivation, competitiveness, and perceived workload. In a randomized-crossover design (Feedback vs. Control), feedback of mean concentric barbell velocity was or was not provided throughout a set of 10 repetitions in the barbell back squat. Magnitude-based inferences were used to assess changes between conditions, with almost certainly greater differences in mean concentric velocity between the Feedback (0.70 ± 0.04 m·s) and Control (0.65 ± 0.05 m·s) observed. In addition, individual repetition mean concentric velocity ranged from possibly (repetition number 2: 0.79 ± 0.04 vs. 0.78 ± 0.04 m·s) to almost certainly (repetition number 10: 0.58 ± 0.05 vs. 0.49 ± 0.05 m·s) greater when provided feedback, whereas almost certain differences were observed in motivation, competitiveness, and perceived workload, respectively. Providing adolescent male athletes with visual kinematic information while completing resistance training is beneficial for the maintenance of barbell velocity during a training set, potentially enhancing physical performance. Moreover, these improvements were observed alongside increases in motivation, competitiveness, and perceived workload providing insight into the underlying mechanisms responsible for the performance gains observed. Given the observed maintenance of barbell velocity during a training set, practitioners can use this technique to manipulate training outcomes during resistance training.

Elimination of intravascular thrombi prevents early mortality and reduces gliosis in hyper-inflammatory experimental cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is the most lethal outcome of Plasmodium infection. There are clear correlations between expression of inflammatory cytokines, severe coagulopathies, and mortality in human CM. However, the mechanisms intertwining the coagulation and inflammation pathways, and their roles in CM, are only beginning to be understood. In mice with T cells deficient in the regulatory cytokine IL-10 (IL-10 KO), infection with Plasmodium chabaudi leads to a hyper-inflammatory response and lethal outcome that can be prevented by anti-TNF treatment. However, inflammatory T cells are adherent within the vasculature and not present in the brain parenchyma, suggesting a novel form of cerebral inflammation. We have previously documented behavioral dysfunction and microglial activation in infected IL-10 KO animals suggestive of neurological involvement driven by inflammation. In order to understand the relationship of intravascular inflammation to parenchymal dysfunction, we studied the congestion of vessels with leukocytes and fibrin(ogen) and the relationship of glial cell activation to congested vessels in the brains of P. chabaudi-infected IL-10 KO mice. METHODS: Using immunofluorescence microscopy, we describe severe thrombotic congestion in these animals. We stained for immune cell surface markers (CD45, CD11b, CD4), fibrin(ogen), microglia (Iba-1), and astrocytes (GFAP) in the brain at the peak of behavioral symptoms. Finally, we investigated the roles of inflammatory cytokine tumor necrosis factor (TNF) and coagulation on the pathology observed using neutralizing antibodies and low-molecular weight heparin to inhibit both inflammation and coagulation, respectively. RESULTS: Many blood vessels in the brain were congested with thrombi containing adherent leukocytes, including CD4 T cells and monocytes. Despite containment of the pathogen and leukocytes within the vasculature, activated microglia and astrocytes were prevalent in the parenchyma, particularly clustered near vessels with thrombi. Neutralization of TNF, or the coagulation cascade, significantly reduced both thrombus formation and gliosis in P. chabaudi-infected IL-10 KO mice. CONCLUSIONS: These findings support the contribution of cytokines, coagulation, and leukocytes within the brain vasculature to neuropathology in malaria infection. Strikingly, localization of inflammatory leukocytes within intravascular clots suggests a mechanism for interaction between the two cascades by which cytokines drive local inflammation without considerable cellular infiltration into the brain parenchyma.

Behavioural and neurological symptoms accompanied by cellular neuroinflammation in IL-10-deficient mice infected with Plasmodium chabaudi.

BACKGROUND: Cerebral malaria is one of the most severe complications of Plasmodium falciparum infection and occurs mostly in young African children. This syndrome results from a combination of high levels of parasitaemia and inflammation. Although parasite sequestration in the brain is a feature of the human syndrome, sequestering strains do not uniformly cause severe malaria, suggesting interplay with other factors. Host genetic factors such as mutations in the promoters of the cytokines IL-10 and TNF are also clearly linked to severe disease. Plasmodium chabaudi, a rodent malaria parasite, leads to mild illness in wildtype animals. However, IL-10(-/-) mice respond to parasite with increased levels of pro-inflammatory cytokines IFN-γ and TNF, leading to lethal disease in the absence of sequestration in the brain. These mice also exhibit cerebral symptoms including gross cerebral oedema and haemorrhage, allowing study of these critical features of disease without the influence of sequestration. METHODS: The neurological consequences of P. chabaudi infection were investigated by performing a general behavioural screen (SHIRPA). The immune cell populations found in the brain during infection were also analysed using flow cytometry and confocal microscopy. RESULTS: IL-10(-/-) mice suffer significant declines in behavioural and physical capacities during infection compared to wildtype. In addition, grip strength and pain sensitivity were affected, suggestive of neurological involvement. Several immune cell populations were identified in the perfused brain on day 7 post-infection, suggesting that they are tightly adherent to the vascular endothelium, or potentially located within the brain parenchyma. There was an increase in both inflammatory monocyte and resident macrophage (CD11b(hi), CD45(+), MHCII(+), Ly6C(+/-)) numbers in IL-10(-/-) compared to wildtype animals. In addition, the activation state of all monocytes and microglia (CD11b(int), CD45(-), MHC-II(+)) were increased. T cells making IFN-γ were also identified in the brain, but were localized within the vasculature, and not the parenchyma. CONCLUSIONS: These studies demonstrate exacerbated neuroinflammation concurrent with development of behavioural symptoms in P. chabaudi infection of IL-10(-/-) animals.

Interaction of ecological and angler processes: experimental stocking in an open access, spatially structured fishery.

Effective management of socioecological systems requires an understanding of the complex interactions between people and the environment. In recreational fisheries, which are prime examples of socioecological systems, anglers are analogous to mobile predators in natural predator-prey systems, and individual fisheries in lakes across a region are analogous to a spatially structured landscape of prey patches. Hence, effective management of recreational fisheries across large spatial scales requires an understanding of the dynamic interactions among ecological density dependent processes, landscape-level characteristics, and angler behaviors. We focused on the stocked component of the open access rainbow trout (Oncorhynchus mykiss) fishery in British Columbia (BC), and we used an experimental approach wherein we manipulated stocking densities in a subset of 34 lakes in which we monitored angler effort, fish abundance, and fish size for up to seven consecutive years. We used an empirically derived relationship between fish abundance and fish size across rainbow trout populations in BC to provide a measure of catch-based fishing quality that accounts for the size-abundance trade off in this system. We replicated our experimental manipulation in two regions known to have different angler populations and broad-scale access costs. We hypothesized that angler effort would respond to variation in stocking density, resulting in spatial heterogeneity in angler effort but homogeneity in catch-based fishing quality within regions. We found that there is an intermediate stocking density for a given lake or region at which angler effort is maximized (i.e., an optimal stocking density), and that this stocking density depends on latent effort and lake accessibility. Furthermore, we found no clear effect of stocking density on our measure of catch-based fishing quality, suggesting that angler effort homogenizes catch-related attributes leading to an eroded relationship between stocking density and catch-based fishing quality at the timescale of annual surveys. We conclude that declines in fishing quality resulting from understocking (due to declines in catch rate with low fish abundance) and overstocking (due to suppressed growth and limited recruitment at high density) give an optimal stocking rate that depends on accessibility and latent effort.

Supply-demand equilibria and the size-number trade-off in spatially structured recreational fisheries.

Recreational fishing effort varies across complex inland landscapes (e.g., lake-districts) and appears influenced by both angler preferences and qualities of the fishery resource, like fish size and abundance. However, fish size and abundance have an ecological trade-off within a population, thereby structuring equal-quality isopleths expressing this trade-off across the fishing landscape. Since expressed preferences of recreational anglers (i.e., site-selection of high-quality fishing opportunities among many lakes) can be analogous to optimal foraging strategies of natural predators, adopting such concepts can aid in understanding scale-dependence in fish-angler interactions and impacts of fishing across broad landscapes. Here, we assumed a fish supply-angler demand equilibria and adapted a novel bivariate measure of fishing quality based on fish size and catch rates to assess how recreational anglers influence fishing quality among a complex inland landscape. We then applied this metric to evaluate (1) angler preferences for caught and released fish compared to harvested fish, (2) the nonlinear size-numbers trade-off with uncertainty in both traits, and (3) the spatial-scale of the equilibria across 62 lakes and four independent management regions in British Columbia's (BC) rainbow trout Oncorhynchus mykiss fishery. We found anglers had low preference for caught and released fish (~10% of the value compared to harvested fish), which modified anglers' perception of fishing quality. Hence, fishing quality and angler effort was not influenced simply by total fish caught, but largely by harvested fish catch rates. Fishing quality varied from BC's northern regions (larger fish and more abundant) compared to southern regions (smaller fish and less abundant) directly associated with a 2.5 times increase in annual fishing effort in southern regions, suggesting that latent fishing pressure can structure the size-numbers trade-off in rainbow trout populations. The presence of two different equal-quality isopleths suggests at least two effective landscapes support co-occurring ideal free distributions of recreational fishing effort in BC's rainbow fishery. Anglers' expressed preferences among lakes interacted with density dependent growth and survival within lakes to structure a size-numbers trade-off influencing how anglers perceive fishing quality and, ultimately, distribute across complex inland landscapes.