Interleukin-3 promotes susceptibility in a mouse model of Cutaneous leishmaniasis

Cutaneous leishmaniasis (CL), a vector-borne infectious disease caused by protozoan parasites of the genus Leishmania, is one of the most important neglected infectious diseases worldwide. Currently, 10 million people in 82 (mostly developing) countries are infected. Those infected develop ulcerative skin lesions on exposed parts of the body, causing serious disability and permanent scarring. All mice are susceptible to infection with Leishmania major, however, the outcome of infection is different depending on the mouse strain. For example, resistant C57BL/6 mice develop lesions, which like in humans, ultimately heal. In contrast, lesions in susceptible BALB/c mice progressively worsen, ultimately resulting in mortality. Resistance or susceptibility to Leishmania parasites is largely dependent on whether the host’s CD4+ T cells develop into Th1 or Th2 effector cells, respectively. Resistant Th1 responses are typically driven by cytokines like interleukin (IL)-12 and interferon-which promotes healing and parasite clearance. In contrast, susceptible Th2 responses are marked by elevated IL-4 production which inactivates the mechanisms of effective parasite clearance and promotes disease progression through an ineffective, antibody-dominated humoral response. IL-3 is a cytokine which promotes hematopoiesis and has the ability to act on numerous cell lineages. In particular, IL-3 appears to have specialized functions in regards to the activation of basophils. For example, IL-3 has been shown to be indispensable for increases in basophil numbers in response to certain infections. Moreover, IL-3 has been shown to increase the functional ability of basophils as IL-3-stimulated basophils are shown to secrete higher levels of IL-4. IL-3 is primarily secreted by activated CD4+ effector T cells, the same cells which are so influential in determining resistance and susceptibility to CL. However, the role of IL 3 during the response to CL remains largely unknown. In the present study we show that infected mice genetically deficient in IL-3 (IL-3 -/- mice) develop smaller lesions, have a lower parasite burdens, and express lower levels of B cells in draining lymph nodes as compared to infected IL-3 +/+ mice. These data suggest IL-3 promotes susceptibility to Leishmania infection and may play an important role in the development of a Th2 immune response characteristic of susceptible BALB/c mice

Semigroups with length morphisms

The class of metrical semigroups is defined as the set consisting of those semigroups which can be homomorphically mapped into the semigroup of natural numbers (without zero) under addition. The finitely generated members of this class are characterised and the infinitely generated case is discussed. A semigroup is called locally metrical if every finitely generated subsemigroup is metrical. The classical Green's relations are trivial on any metrical semigroup. Generalisations +, + and + of the Green's relations are defined and it is shown that for any cancellative metrical semigroup, S, + is " as big as possible " if and only if S is isomorphic to a special type of semidirect product of and a group. Lyndon's characterisation of free groups by length functions is discussed andalink between length functions, metrical semigroups and semigroups embeddable into free semigroups is investigated. Next the maximal locally metrical ideal of a semigroup is discussed, and the class of t-compressible semigroups is defined as the set consisting of those semigroups that have no locally metrical ideal. The class of t-compressible semigroups is seen to contain the classes of regular and simple semigroups. Finally it is shown that a large class of semigroups can be decomposed into a chain of locally metrical ideals together with a t-compressible semigroup

A statistical framework to interpret individual response to intervention: paving the way for personalised nutrition and exercise prescription.

The concept of personalised nutrition and exercise prescription represents a topical and exciting progression for the discipline given the large inter-individual variability that exists in response to virtually all performance and health related interventions. Appropriate interpretation of intervention-based data from an individual or group of individuals requires practitioners and researchers to consider a range of concepts including the confounding influence of measurement error and biological variability. In addition, the means to quantify likely statistical and practical improvements are facilitated by concepts such as confidence intervals (CIs) and smallest worthwhile change (SWC). The purpose of this review is to provide accessible and applicable recommendations for practitioners and researchers that interpret, and report personalised data. To achieve this, the review is structured in three sections that progressively develop a statistical framework. Section 1 explores fundamental concepts related to measurement error and describes how typical error and CIs can be used to express uncertainty in baseline measurements. Section 2 builds upon these concepts and demonstrates how CIs can be combined with the concept of SWC to assess whether meaningful improvements occur post-intervention. Finally, Section 3 introduces the concept of biological variability and discusses the subsequent challenges in identifying individual response and non-response to an intervention. Worked numerical examples and interactive supplementary material are incorporated to solidify concepts and assist with implementation in practice

Camera-Based Ballot Counter

Portable ballot counters using camera technology and manual paper feed are potentially more reliable and less expensive than scanner based systems. We show that the spatial sampling rate, geometric linearity, point spread function, and photometric transfer function of off-the-shelf consumer cameras are acceptable for ballot imaging. However, scanner illumination is much more uniform than can be economically accomplished for variable size ballots. Therefore flat-field compensation must be designed into the image processing software. We illustrate the mechanical design of a prototype camera based ballot reader based on our comparative observations

Is individualization of sodium bicarbonate ingestion based on time to peak necessary?

Purpose: To describe the reliability of blood bicarbonate pharmacokinetics in response to sodium bicarbonate (SB) supplementation across multiple occasions and assess, using putative thresholds, whether individual variation indicated a need for individualised ingestion timings. Methods: Thirteen men (age 27±5 y; body mass (BM) 77.4±10.5 kg; height 1.75±0.06 m) ingested 0.3 g·kg-1BM SB in gelatine capsules on 3 occasions. One hour after a standardised meal, venous blood was obtained before and every 10 min following ingestion for 3 h, then every 20 min for a further hour. Time-to-peak (Tmax), absolute-peak (Cmax), absolute-peak-change (ΔCmax) and area under the curve (AUC) were analysed using mixed models, intraclass correlation coefficient (ICC), coefficient of variation (CV) and typical error. Individual variation in pharmacokinetic responses was assessed using Bayesian simulation with multilevel models with random intercepts. Results: No significant differences between sessions were shown for blood bicarbonate regarding Cmax, ΔCmax or AUC (p>0.05), although Tmax occurred earlier in SB2 (127±36 min) than in SB1 (169±54 min, p=0.0088) and SB3 (159±42 min, p=0.05). ICC, CV and typical error showed moderate to poor reliability. Bayesian modelling estimated that >80% of individuals from the population experience elevated blood bicarbonate levels above + 5 mmol∙L-1 between 75-240 min after ingestion, and between 90-225 min above +6 mmol∙L-1. Conclusion: Assessing SB supplementation using discrete values showed only moderate reliability at the group level, and poor reliability at the individual level, while Tmax was not reproducible. However, when analysed as modelled curves, a 0.3 g·kg-1BM dose was shown to create a long-lasting window of ergogenic potential, challenging the notion that SB ingestion individualised to time-to-peak is a necessary strategy, at least when SB is ingested in capsules

Sodium bicarbonate supplementation and the female athlete: A brief commentary with small scale systematic review and meta-analysis:Sodium bicarbonate use in women

Sodium bicarbonate (SB) is considered an effective ergogenic supplement for improving high-intensity exercise capacity and performance, although recent data suggests that women may be less amenable to its ergogenic effects than men. Currently, an apparent paucity of data on women means no consensus exists on whether women benefit from SB supplementation. The aim of the current study was to quantify the proportion of the published literature on SB supplementation that includes women, and to synthesise the evidence regarding its effects on blood bicarbonate and exercise performance in women by performing a systematic review and meta-analysis. Electronic searches of the literature were undertaken using three databases (MEDLINE, Embase, SPORTDiscus) to identify relevant articles. All meta-analyses were performed within a Bayesian framework. A total of 149 SB articles were identified, 11 of which contained individual group data for women. Results indicated a pooled blood bicarbonate increase of 7.4 [95%CrI: 4.2 to 10.4 mmol·L-1] following supplementation and a pooled standardised exercise effect size of 0.37 [95%CrI: -0.06 to 0.92]. The SB literature is skewed, with only 20% (30 studies) of studies employing female participants, of which only 11 studies (7.4%) provided group analyses exclusively in women. Despite the small amount of available data, results are consistent in showing that SB supplementation in women leads to large changes in blood bicarbonate and that there is strong evidence for a positive ergogenic effect on exercise performance that is likely to be small to medium in magnitude

Nonplacebo controls to determine the magnitude of ergogenic interventions: a systematic review and meta-analysis.

Introduction: Placebos are used as a control treatment that is meant to be indistinguishable from the active intervention. However, where substantive placebo effects may occur, studies that do not include a non-placebo control arm may underestimate the overall effect of the intervention (active plus placebo components). This study aimed to determine the relative magnitude of the placebo effect associated with nutritional supplements (caffeine and extracellular buffers) by meta-analysing data from studies containing both placebo and non-placebo control sessions. Methods: Bayesian multilevel meta-analysis models were used to estimate pooled effects and express the placebo effect as a percentage of the overall intervention effect. Results: Thirty-four studies were included, with the median pooled effect size (ES0.5) indicating a very small (ES0.5=0.09 [95%CrI:0.01 to 0.17]) improvement in performance of placebo compared to control. There was no moderating effect of exercise type (capacity or performance), exercise duration or training status. The comparison between active intervention and control indicated a small to medium effect (ES0.5=0.37 [95%CrI:0.20 to 0.56]). Expressed in relative terms, the placebo effect was equivalent to 25% [75%CrI:16 to 35%] and 59% [75%CrI:34 to 94%] of the total intervention effect for buffers and caffeine. Conclusion: These results demonstrate a very small, but potentially important placebo effect with nutritional supplementation studies. A substantive proportion of supplement effects may be due to placebo effects, with the relative proportion influenced by the magnitude of the overall ergogenic effect. Where feasible, intervention studies should employ non-placebo control-arm comparators to identify the proportion of the effect estimated to come from placebo effects and avoid underestimating the overall benefits that the physiological plus psychobiological aspects associated with an intervention provide in the real world

The Influence of Caffeine Expectancies on Simulated Soccer Performance in Recreational Individuals

Caffeine (CAF) has been reported to improve various facets associated with successful soccer play, including gross motor skill performance, endurance capacity and cognition. These benefits are primarily attributed to pharmacological mechanisms. However, evidence assessing CAF’s overall effects on soccer performance are sparse with no studies accounting for CAF’s potential psychological impact. Therefore, the aim of this study was to assess CAF’s psychological vs. pharmacological influence on various facets of simulated soccer performance. Utilising a double-dissociation design, eight male recreational soccer players (age: 22 ± 5 years, body mass: 78 ± 16 kg, height: 178 ± 6 cm) consumed CAF (3 mg/kg/body mass) or placebo (PLA) capsules, 60 min prior to performing the Loughborough Intermittent Shuttle Test (LIST) interspersed with a collection of ratings of perceived exertion (RPE), blood glucose and lactate, heart rate and performing the Loughborough Soccer Passing Test (LSPT). Whole-body dynamic reaction time (DRT) was assessed pre- and post- LIST, and endurance capacity (TLIM) post, time-matched LIST. Statistical analysis was performed using IBM SPSS (v24) whilst subjective perceptions were explored using template analysis. Mean TLIM was greatest (p < 0.001) for synergism (given CAF/told CAF) (672 ± 132 s) vs. placebo (given PLA/told PLA) (533 ± 79 s). However, when isolated, TLIM was greater (p = 0.012) for CAF psychology (given PLA/told CAF) (623 ± 117 s) vs. pharmacology (given CAF/told PLA) (578 ± 99 s), potentially, via reduced RPE. Although DRT performance was greater (p = 0.024) post-ingestion (+5 hits) and post-exercise (+7 hits) for pharmacology vs. placebo, psychology and synergism appeared to improve LSPT performance vs. pharmacology. Interestingly, positive perceptions during psychology inhibited LSPT and DRT performance via potential CAF over-reliance, with the opposite occurring following negative perceptions. The benefits associated with CAF expectancies may better suit tasks that entail lesser cognitive-/skill-specific attributes but greater gross motor function and this is likely due to reduced RPE. In isolation, these effects appear greater vs. CAF pharmacology. However, an additive benefit may be observed after combining expectancy with CAF pharmacology (i.e., synergism).N/

Effect of the overflows on the circulation in the Subpolar North Atlantic: A regional model study

An ocean circulation model for process studies of the Subpolar North Atlantic is developed based on the Geophysical Fluid Dynamics Laboratory (GFDL) Modular Ocean Model (MOM) code. The basic model configuration is identical with that of the high-resolution model (with a grid size of 1/3° × 2/5°) of the World Ocean Circulation Experiment (WOCE) Community Modeling Effort (CME), except that the domain of integration is confined to the area from 43° to 65°N. Open boundary conditions are used for the inflows and outflows across the northern and southern boundaries. A comparison with the CME model covering the whole North Atlantic (from 15°S to 65°N) shows that the regional model, with inflow conditions at 43°N from a CME solution, is able to reproduce the CME results for the subpolar area. Thus the potential of a regional model lies in its use as an efficient tool for numerical experiments aiming at an identification of the key physical processes that determine the circulation and water mass transformations in the subpolar gyre. This study deals primarily with the representation and role of the overflow waters that enter the domain at the northern boundary. Sensitivity experiments show the effect of closed versus open boundaries, of different hydrographic conditions at inflow points, and of the representation of the narrow Faeroe Bank Channel. The representation of overflow processes in the Denmark Strait is the main controlling mechanism for the net transport of the deep boundary current along the Greenland continental slope and further downstream. Changes in the Faeroe Bank Channel throughflow conditions have a comparatively smaller effect on the deep transport in the western basin but strongly affect the water mass characteristics in the eastern North Atlantic. The deep water transport at Cape Farewell and further downstream is enhanced compared to the combined Denmark Strait and Iceland-Scotland overflows. This enhancement can be attributed to a barotropic recirculation in the Irminger Basin which is very sensitive to the outflow conditions in the Denmark Strait. The representation of both overflow regions determine the upper layer circulation in the Irminger and Iceland Basins, in particular the path of the North Atlantic Current