Making sense of bodily sensations: Do shared cancer narratives influence symptom appraisal?

Though new or altered bodily sensations are a common occurrence they rarely transition to biomedically defined symptoms. When they do, sensations are subject to an appraisal process that can culminate in help-seeking. The transition has particular relevance for cancer diagnoses. Studies of 'symptom appraisal' in cancer patients typically conclude that failure to regard sensations as serious or 'symptom misattribution' results in lengthier help-seeking intervals. Though multiple influences on appraisal processes are acknowledged, including the socio-cultural context, detailed description and analyses of how socio-cultural factors shape appraisal is lacking. In this paper we explore one substantial component of the sociocultural context, namely, publicly recognised shared cancer narratives, and their impact on appraisal. We undertook a secondary analysis of 24 interviews with Scottish colorectal cancer patients originally completed in 2006–2007. Our analysis showed that fear, death and severity dominated cancer narratives and were frequently restated throughout interviews. Yet, early bodily changes were often mild and vague, were commonly experienced in the context of 'feeling well' and failed to match preconceived ideas of what cancer 'feels like'. Moreover, few perceived themselves to be 'at risk' of cancer and diagnoses were characterised as 'shocking' events. Participants engaged in self-monitoring strategies and severe or painful changes prompted help-seeking. Far from misattributing symptoms, responses to bodily changes were sensible and measured; responses are particularly apt in relation to current policy rhetoric, which urges measured use of services. Our findings have resonance across healthcare settings as patients are required to negotiate a narrow and challenging space when making decisions to seek help. There is a pressing need for a more realistic approach to symptom appraisal in order to reduce help-seeking intervals. Future awareness campaigns should emphasise the importance of vague/minor bodily changes although this will necessitate discussions with health professionals on referral thresholds to achieve earlier detection

“Everything You Always Wanted to Know about Sex (but Were Afraid to Ask)” in Leishmania after Two Decades of Laboratory and Field Analyses

Leishmaniases remain a major public health problem today (350 million people at risk, 12 million infected, and 2 million new infections per year). Despite the considerable progress in cellular and molecular biology and in evolutionary genetics since 1990, the debate on the population structure and reproductive mode of Leishmania is far from being settled and therefore deserves further investigation. Two major hypotheses coexist: clonality versus sexuality. However, because of the lack of clear evidence (experimental or biological confirmation) of sexuality in Leishmania parasites, until today it has been suggested and even accepted that Leishmania species were mainly clonal with infrequent genetic recombination (see [1] for review). Two recent publications, one on Leishmania major (an in vitro experimental study) and one on Leishmania braziliensis (a population genetics analysis), once again have challenged the hypothesis of clonal reproduction. Indeed, the first study experimentally evidenced genetic recombination and proposed that Leishmania parasites are capable of having a sexual cycle consistent with meiotic processes inside the insect vector. The second investigation, based on population genetics studies, showed strong homozygosities, an observation that is incompatible with a predominantly clonal mode of reproduction at an ecological time scale (∼20–500 generations). These studies highlight the need to advance the knowledge of Leishmania biology. In this paper, we first review the reasons stimulating the continued debate and then detail the next essential steps to be taken to clarify the Leishmania reproduction model. Finally, we widen the discussion to other Trypanosomatidae and show that the progress in Leishmania biology can improve our knowledge of the evolutionary genetics of American and African trypanosomes

Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

Acknowledgements We wish to thank Jorge Galán, Gregory Pazour, Derek Toomre, Giuliano Callaini, Joel Rosenbaum, Alessandra Boletta and Francesco Blasi for generously providing reagents and for productive discussions, and Sonia Grassini for technical assistance. The work was carried out with the financial support of Telethon (GGP11021) and AIRC.Peer reviewedPostprin

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study

$\textbf{BACKGROUND}$: Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people. $\textbf{METHODS AND FINDINGS}$: We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011-2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors-cognitive and social activity, physical activity, diet, alcohol consumption, and smoking-and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%-23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%-27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve. $\textbf{CONCLUSIONS}$: Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health may be supported by a healthy and active lifestyle, in later life.The CFAS-Wales study was supported by Economic and Social Research Council grant RES-060-25-0060 to BW (principal investigator), CB, LC, and colleagues K. Bennett, V. Burholt, C. McCracken, J. Phillips, and G. Windle. FM is supported by Medical Research Council grant U105292687

Why are we not flooded by involuntary thoughts about the past and future? Testing the cognitive inhibition dependency hypothesis

© The Author(s) 2018In everyday life, involuntary thoughts about future plans and events occur as often as involuntary thoughts about the past. However, compared to involuntary autobiographical memories (IAMs), such episodic involuntary future thoughts (IFTs) have become a focus of study only recently. The aim of the present investigation was to examine why we are not constantly flooded by IFTs and IAMs given that they are often triggered by incidental cues while performing undemanding activities. One possibility is that activated thoughts are suppressed by the inhibitory control mechanism, and therefore depleting inhibitory control should enhance the frequency of both IFTs and IAMs. We report an experiment with a between-subjects design, in which participants in the depleted inhibition condition performed a 60-min high-conflict Stroop task before completing a laboratory vigilance task measuring the frequency of IFTs and IAMs. Participants in the intact inhibition condition performed a version of the Stroop task that did not deplete inhibitory control. To control for physical and mental fatigue resulting from performing the 60-min Stroop tasks in experimental conditions, participants in the control condition completed only the vigilance task. Contrary to predictions, the number of IFTs and IAMs reported during the vigilance task, using the probe-caught method, did not differ across conditions. However, manipulation checks showed that participants’ inhibitory resources were reduced in the depleted inhibition condition, and participants were more tired in the experimental than in the control conditions. These initial findings suggest that neither inhibitory control nor physical and mental fatigue affect the frequency of IFTs and IAMs.Peer reviewedFinal Published versio

Evidence of the Trade-Off between Starvation and Predation Risks in Ducks

The theory of trade-off between starvation and predation risks predicts a decrease in body mass in order to improve flight performance when facing high predation risk. To date, this trade-off has mainly been validated in passerines, birds that store limited body reserves for short-term use. In the largest avian species in which the trade-off has been investigated (the mallard, Anas platyrhynchos), the slope of the relationship between mass and flight performance was steeper in proportion to lean body mass than in passerines. In order to verify whether the same case can be applied to other birds with large body reserves, we analyzed the response to this trade-off in two other duck species, the common teal (Anas crecca) and the tufted duck (Aythya fuligula). Predation risk was simulated by disturbing birds. Ducks within disturbed groups were compared to non-disturbed control birds. In disturbed groups, both species showed a much greater decrease in food intake and body mass during the period of simulated high risk than those observed in the control group. This loss of body mass allows reaching a more favourable wing loading and increases power for flight, hence enhancing flight performances and reducing predation risk. Moreover, body mass loss and power margin gain in both species were higher than in passerines, as observed in mallards. Our results suggest that the starvation-predation risk trade-off is one of the major life history traits underlying body mass adjustments, and these findings can be generalized to all birds facing predation. Additionally, the response magnitude seems to be influenced by the strategy of body reserve management

Development of a mathematical model for predicting electrically elicited quadriceps femoris muscle forces during isovelocity knee joint motion

<p>Abstract</p> <p>Background</p> <p>Direct electrical activation of skeletal muscles of patients with upper motor neuron lesions can restore functional movements, such as standing or walking. Because responses to electrical stimulation are highly nonlinear and time varying, accurate control of muscles to produce functional movements is very difficult. Accurate and predictive mathematical models can facilitate the design of stimulation patterns and control strategies that will produce the desired force and motion. In the present study, we build upon our previous isometric model to capture the effects of constant angular velocity on the forces produced during electrically elicited concentric contractions of healthy human quadriceps femoris muscle. Modelling the isovelocity condition is important because it will enable us to understand how our model behaves under the relatively simple condition of constant velocity and will enable us to better understand the interactions of muscle length, limb velocity, and stimulation pattern on the force produced by the muscle.</p> <p>Methods</p> <p>An additional term was introduced into our previous isometric model to predict the force responses during constant velocity limb motion. Ten healthy subjects were recruited for the study. Using a KinCom dynamometer, isometric and isovelocity force data were collected from the human quadriceps femoris muscle in response to a wide range of stimulation frequencies and patterns. % error, linear regression trend lines, and paired t-tests were used to test how well the model predicted the experimental forces. In addition, sensitivity analysis was performed using Fourier Amplitude Sensitivity Test to obtain a measure of the sensitivity of our model's output to changes in model parameters.</p> <p>Results</p> <p>Percentage RMS errors between modelled and experimental forces determined for each subject at each stimulation pattern and velocity showed that the errors were in general less than 20%. The coefficients of determination between the measured and predicted forces show that the model accounted for ~86% and ~85% of the variances in the measured force-time integrals and peak forces, respectively.</p> <p>Conclusion</p> <p>The range of predictive abilities of the isovelocity model in response to changes in muscle length, velocity, and stimulation frequency for each individual make it ideal for dynamic applications like FES cycling.</p

A technical skill training framework and skill load measurements for the Rugby Union tackle

Drawing from skill acquisition and development literature, we present a novel tackle skill training framework. The framework outlines the training purpose (technique proficiency, technique capacity, skill proficiency and skill capacity), skill workload measurements (available information, task difficulty, rating of perceived challenge, skill load), as well as the training conditions and coaching style for the tackle in rugby union. Using this framework and skill load measurements, we propose a pre-season tackle training plan. This tackle skill framework and skill load measurements serve as potential preventive measures for tackle injury risk while improving players’ tackle performance