The barriers and enablers to education among scheduled caste and scheduled tribe adolescent girls in northern Karnataka, South India: A qualitative study

This qualitative study explored the barriers and enablers to scheduled caste/scheduled tribe (SC/ST) adolescent girls entering into, and completing secondary education in northern Karnataka, South India. In-depth interviews were conducted with 22 adolescent girls, their respective parent/guardian (n = 22) and 11 teachers, recruited purposively from 11 villages within two districts in northern Karnataka. Multiple barriers were identified to disadvantaged caste adolescent girls’ entry into and retention in education in this setting, and these operated at the individual, family, community and school levels. In addition, some enablers to education were also described. The study highlights the importance of involving multiple stakeholders to overcome the barriers to education for SC/ST girls, and of working to change beliefs and expectations around gender norms as well as improving the quality of education in this setting

Deception has no acute or residual effect on cycling time trial performance but negatively effects perceptual responses.

Feedback deception is used to explore the importance of expectations on pacing strategy and performance in self-paced exercise. The deception of feedback from a previous performance explores the importance of experience knowledge on exercise behaviour. This study aimed to explore the acute and residual effects of the deception of previous performance speed on perceptual responses and performance in cycling time trials.A parallel-group design.Twenty cyclists were assigned to a control or deception group and performed 16.1km time trials. Following a ride-alone baseline time trial (FBL), participants performed against a virtual avatar representing their FBL performance (PACER), then completed a subsequent ride-alone time trial (SUB). The avatar in the deception group, however, was unknowingly set 2% faster than their FBL.Both groups performed faster in PACER than FBL and SUB (p<0.05), but SUB was not significantly different to FBL. Affect was more negative and Ratings of Perceived Exertion (RPE) were higher in PACER than FBL in the deception group (p<0.05).The presence of a visual pacer acutely facilitated time trial performance, but deceptive feedback had no additional effect on performance. The deception group, however, experienced more negative affect and higher RPE in PACER, whereas these responses were absent in the control group. The performance improvement was not sustained in SUB, suggesting no residual performance effects occurred

Distance-dependent association of affect with pacing strategy in cycling time trials.

The psychological construct of affect is proposed to significantly contribute to pacing decisions during exercise. Borg’s RPE scale, another important regulator of work rate, is criticized as an inadequate measure of the multiple perceptual responses experienced. This study aimed to examine power output distribution and associated changes in affect, self-efficacy, perceptual cues, HR, and respiratory gases during both 16.1- and 40-km self-paced cycling time trials (TT). Secondly, the differentiation between physical perceptions of exertion and sense of effort in self-paced exercise was investigated. Method: Fifteen trained male cyclists completed 16.1- and 40-km TT using a CompuTrainer cycle ergometer. Time, power output distribution, affect, self-efficacy, physical RPE (P-RPE), task effort and awareness (TEA), HR, and respiratory gases were measured throughout each TT. Linear mixed models explored associations of these variables with power output distribution and the relationship between P-RPE and TEA. Results: Similar pacing strategies were adopted in the 16.1- and 40-km TT (P = 0.31), and the main effects were found for affect (P = 0.001) and RER (P G 0.001). Interactions between affect (P = 0.037) and RER (P = 0.004), with condition, indicated closer associations with power output distribution in 16.1 km than that in 40 km TT. P-RPE was not significantly different from TEA (P = 0.053). Conclusion: A significant association between affect and power output distribution suggests that affective responses are task dependent even in self-paced exercise, and a greater association is demonstrated in higher intensity, 16.1 km TT. Furthermore, physical perceptions of exertion are not clearly differentiated from the sense of effort in self-paced exercise

Deception studies manipulating centrally acting performance modifiers: a review.

Athletes anticipatorily set and continuously adjust pacing strategies before and during events to produce optimal performance. Selfregulation ensures maximal effort is exerted in correspondence with the end point of exercise, while preventing physiological changes that are detrimental and disruptive to homeostatic control. The integration of feedforward and feedback information, together with the proposed brain_s performance modifiers is said to be fundamental to this anticipatory and continuous regulation of exercise. The manipulation of central, regulatory internal and external stimuli has been a key focus within deception research, attempting to influence the self-regulation of exercise and induce improvements in performance. Methods of manipulating performance modifiers such as unknown task end point, deceived duration or intensity feedback, self-belief, or previous experience create a challenge within research, as although they contextualize theoretical propositions, there are few ecological and practical approaches which integrate theory with practice. In addition, the different methods and measures demonstrated in manipulation studies have produced inconsistent results. This review examines and critically evaluates the current methods of how specific centrally controlled performance modifiers have been manipulated, within previous deception studies. From the 31 studies reviewed, 10 reported positive effects on performance, encouraging future investigations to explore the mechanisms responsible for influencing pacing and consequently how deceptive approaches can further facilitate performance. The review acts to discuss the use of expectation manipulation not only to examine which methods of deception are successful in facilitating performance but also to understand further the key components used in the regulation of exercise and performance

Physiological and Psychological Effects of Deception on Pacing Strategy and Performance: A Review

The aim of an optimal pacing strategy during exercise is to enhance performance whilst ensuring physiological limits are not surpassed, which has been shown to result in a metabolic reserve at the end of the exercise. There has been debate surrounding the theoretical models that have been proposed to explain how pace is regulated, with more recent research investigating a central control of exercise regulation. Deception has recently emerged as a common, practical approach to manipulate key variables during exercise. There are a number of ways in which deception interventions have been designed, each intending to gain particular insights into pacing behaviour and performance. Deception methodologies can be conceptualised according to a number of dimensions such as deception timing (prior to or during exercise), presentation frequency (blind, discontinuous or continuous) and type of deception (performance, biofeedback or environmental feedback). However, research evidence on the effects of deception has been perplexing and the use of complex designs and varied methodologies makes it difficult to draw any definitive conclusions about how pacing strategy and performance are affected by deception. This review examines existing research in the area of deception and pacing strategies, and provides a critical appraisal of the different methodological approaches used to date. It is hoped that this analysis will inform the direction and methodology of future investigations in this area by addressing the mechanisms through which deception impacts upon performance and by elucidating the potential application of deception techniques in training and competitive settings

The establishment, maintenance, and adaptation of high- and low-impact chronic pain: a framework for biopsychosocial pain research

We present a framework for the study of states of chronic pain and transitions between those states. We capture in the framework the dynamic nature of pain: people live with pain that changes over time. First, we offer definitions of both acute and chronic pain and explore the contextual considerations related to the common use of this temporal dichotomy. Second, we promote the importance of incorporating the impact pain has on a person's life. Finally, we discuss the challenges and opportunities inherent in implementing this common approach. Our goal is to produce a framework for the study of the development, maintenance, and resolution of chronic pain. Whether a single brief event or a constant feature of life, pain interrupts to prioritise protection, interferes with activity, reduces quality of life, and can alter identity.44 Protection is achieved by escape from harm, avoidance of perceived danger, withdrawal for respite and repair, and communication of incapacity and environmental risk; longer-term protection is achieved by learning the cues for pain and injury.53 From this perspective, pain is most usefully considered a need state, fundamentally a motivational drive to protect.49 This approach centres our attention on the consequences of pain for the person in their context, on its duration and its impact

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies