International Society of Sports Nutrition position stand: beta-alanine

Position statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4–6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4–6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine

Family connections versus optimised treatment-as-usual for family members of individuals with borderline personality disorder: non-randomised controlled study

Background: Borderline personality disorder (BPD) is challenging for family members who are often required to fulfil multiple roles such as those of advocate, caregiver, coach and guardian. To date, two uncontrolled studies by the treatment developers suggest that Family Connections (FC) is an effective programme to support, educate and teach skills to family members of individuals with BPD. However, such studies have been limited by lack of comparison to other treatment approaches. This study aimed to compare the effectiveness of FC with an optimised treatment-as-usual (OTAU) programme for family members of individuals with BPD. A secondary aim was to introduce a long term follow-up to investigate if positive gains from the intervention would be maintained following programme completion. Methods: This study was a non-randomised controlled study, with assessment of outcomes at baseline (pre-intervention) and end of programme (post-intervention) for both FC and OTAU groups, and at follow-up (3 months post-intervention; 12 or 19 months post-intervention) for the FC group. Eighty family members participated in the FC (n = 51) and the OTAU (n = 29) programmes. Outcome measures included burden, grief, depression and mastery. Linear mixed-effects models were used to assess baseline differences in the outcome measures by gender, age group and type of relationship to the individual with BPD. Linear mixed-effects models were also used to estimate the treatment effect (FC versus OTAU) utilising all available data from baseline and end of programme. Results: The FC group showed changes indicating significant improvement with respect to all four outcome measures (p < 0.001). The OTAU group showed changes in the same direction as the intervention group but none of the changes were statistically significant. The intervention effect was statistically significant for total burden (including both subscales; p = .02 for subjective burden and p = .048 for objective burden) and grief (p = 0.013). Improvements were maintained at follow-up for FC participants. Conclusions: The findings of the current study indicate that FC results in statistically significant improvements on key measures while OTAU does not yield comparable changes. Lack of significant change on all measures for OTAU suggests that a three session psycho-education programme is of limited benefit. Further research is warranted on programme components and long-term supports for family members

Sampling constrained probability distributions using Spherical Augmentation

Statistical models with constrained probability distributions are abundant in machine learning. Some examples include regression models with norm constraints (e.g., Lasso), probit, many copula models, and latent Dirichlet allocation (LDA). Bayesian inference involving probability distributions confined to constrained domains could be quite challenging for commonly used sampling algorithms. In this paper, we propose a novel augmentation technique that handles a wide range of constraints by mapping the constrained domain to a sphere in the augmented space. By moving freely on the surface of this sphere, sampling algorithms handle constraints implicitly and generate proposals that remain within boundaries when mapped back to the original space. Our proposed method, called {Spherical Augmentation}, provides a mathematically natural and computationally efficient framework for sampling from constrained probability distributions. We show the advantages of our method over state-of-the-art sampling algorithms, such as exact Hamiltonian Monte Carlo, using several examples including truncated Gaussian distributions, Bayesian Lasso, Bayesian bridge regression, reconstruction of quantized stationary Gaussian process, and LDA for topic modeling.Comment: 41 pages, 13 figure

A Simple Iterative Model Accurately Captures Complex Trapline Formation by Bumblebees Across Spatial Scales and Flower Arrangements

PMCID: PMC3591286This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Conjugated bile acids attenuate allergen-induced airway inflammation and hyperresposiveness by inhibiting UPR transducers

© 2019 American Society for Clinical Investigation. Conjugated bile acids (CBAs), such as tauroursodeoxycholic acid (TUDCA), are known to resolve the inflammatory and unfolded protein response (UPR) in inflammatory diseases, such as asthma. Whether CBAs exert their beneficial effects on allergic airway responses via 1 arm or several arms of the UPR, or alternatively through the signaling pathways for conserved bile acid receptor, remains largely unknown. We used a house dust mite-induced (HDM-induced) murine model of asthma to evaluate and compare the effects of 5 CBAs and 1 unconjugated bile acid in attenuating allergen-induced UPR and airway responses. Expression of UPRassociated transcripts was assessed in airway brushings from human patients with asthma and healthy subjects. Here we show that CBAs, such as alanyl β-muricholic acid (AβM) and TUDCA, significantly decreased inflammatory, immune, and cytokine responses; mucus metaplasia; and airway hyperresponsiveness, as compared with other CBAs in a model of allergic airway disease. CBAs predominantly bind to activating transcription factor 6α (ATF6α) compared with the other canonical transducers of the UPR, subsequently decreasing allergen-induced UPR activation and resolving allergic airway disease, without significant activation of the bile acid receptors. TUDCA and AβM also attenuated other HDM-induced ER stress markers in the lungs of allergic mice. Quantitative mRNA analysis of airway epithelial brushings from human subjects demonstrated that several ATF6α-related transcripts were significantly upregulated in patients with asthma compared with healthy subjects. Collectively, these results demonstrate that CBA-based therapy potently inhibits the allergen-induced UPR and allergic airway disease in mice via preferential binding of the canonical transducer of the UPR, ATF6α. These results potentially suggest a novel avenue to treat allergic asthma using select CBAs

Larynx-Preserving Partial Pharyngectomy via Lateral Pharyngotomy for the Treatment of Small (T1~2) Hypopharyngeal Squamous Cell Carcinoma

ObjectivesTo evaluate the oncologic and functional results of larynx-preserving partial pharyngectomy (LPP) via lateral pharyngotomy approach as a primary treatment for small (T1 or T2) hypopharyngeal squamous cell carcinoma (HPSCC).MethodsWe performed a retrospective review of 23 patients who underwent LPP through lateral pharyngotomy approach for small HPSCC at the our department between January 1991 and June 2007. Fourteen (61%) patients had adjuvant postoperative radiotherapy.ResultsThe 2-years and 5-years disease specific survival rate was 77% and 61%, respectively. Nine patients (39%) had tumor recurrence. The most common pattern of recurrence was isolated distant failure (n=4, 44%) followed by local (n=2, 22%) and loco-regional (n=3, 34%) recurrence. The ultimate cure rate of the primary tumor was 87% (20 of 23). Twenty-two of the 23 patients (95%) could be decannulated, tolerate an oral diet, and had acceptable postoperative phonatory function.ConclusionLPP via lateral pharyngotomy approach appears to be a feasible procedure for selected small HPSCC patients in terms of both oncologic and functional outcomes

Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy

<p>Abstract</p> <p>Background</p> <p>Antisense-mediated exon skipping is currently one of the most promising therapeutic approaches for Duchenne muscular dystrophy (DMD). Using antisense oligonucleotides (AONs) targeting specific exons the DMD reading frame is restored and partially functional dystrophins are produced. Following proof of concept in cultured muscle cells from patients with various deletions and point mutations, we now focus on single and multiple exon duplications. These mutations are in principle ideal targets for this approach since the specific skipping of duplicated exons would generate original, full-length transcripts.</p> <p>Methods</p> <p>Cultured muscle cells from DMD patients carrying duplications were transfected with AONs targeting the duplicated exons, and the dystrophin RNA and protein were analyzed.</p> <p>Results</p> <p>For two brothers with an exon 44 duplication, skipping was, even at suboptimal transfection conditions, so efficient that both exons 44 were skipped, thus generating, once more, an out-of-frame transcript. In such cases, one may resort to multi-exon skipping to restore the reading frame, as is shown here by inducing skipping of exon 43 and both exons 44. By contrast, in cells from a patient with an exon 45 duplication we were able to induce single exon 45 skipping, which allowed restoration of wild type dystrophin. The correction of a larger duplication (involving exons 52 to 62), by combinations of AONs targeting the outer exons, appeared problematic due to inefficient skipping and mistargeting of original instead of duplicated exons.</p> <p>Conclusion</p> <p>The correction of DMD duplications by exon skipping depends on the specific exons targeted. Its options vary from the ideal one, restoring for the first time the true, wild type dystrophin, to requiring more 'classical' skipping strategies, while the correction of multi-exon deletions may need the design of tailored approaches.</p

Preparation, structured deliberate practice and decision making in elite level football: The case study of Gary Neville (Manchester United FC and England)

Decision making in elite level sporting competition is often regarded as distinguishing success from failure. As an intricate brain-based process it is unlike other physical processes because it is invisible and is typically only evidenced after the event. This case study shows how an individual achieved great success in elite level professional football through consistent positive decision making on and off the field of play. Through prolonged interviewing, Gary Neville, a player from Manchester United Football Club, explored personal behaviours, the structure and activities of deliberate practice and his professional choices in match preparation. His career-long devotion to purposeful organised practice was focused on cognition, physical preparation, context-relative physical action and refined repetition to optimise his mental comfort while enhancing his match day performances. This approach was underpinned by diligent personal and collective organisation and by concerted action. Results provide an insight into the categorical nature of his deliberate practice, sport-specific information processing and match-based decision making. At the operational level, his process was mediated by a complex mental representation of ongoing and anticipated game situations; these representations were continuously updated during each match. Allowing for the limitations of the design, implications are provided for developmental and educational coaching, match preparation, deliberate practice activity and improved use of the performance analysis software packages in professional football