Altitude training and individual hemoglobin mass response in athletes

Altitude training is frequently used by elite athletes to obtain potential benefits in sea-level performance. One of the main recognized physiological adaptations leading to enhanced sea- level performance is a hypoxia-induced increase in hemoglobin mass (Hbmass). During the last decades, several types of altitude training have been developed, which can be performed under either hypobaric hypoxia (HH, natural altitude) or normobaric hypoxia (NH, simulated altitude). Whether NH and HH can be used interchangeably for altitude training is still unclear. Moreover, especially from an athlete’s perspective, the individual adaptations to and the interchangeability of NH and HH are of interest. Therefore, to compare individual and mean Hbmass responses during an 18-day live hightrain low (LHTL) altitude training camp in either NH or HH, we designed a randomized matched controlled (n = 28) study and a crossover (n = 15) study with endurance athletes. To more precisely quantify the individual Hbmass response to altitude training, we implemented error- reducing duplicate Hbmass measures. Furthermore, since altitude training is primarily used by elite endurance athletes that typically present elevated Hbmass values, we tested the hypothesis that athletes with a high initial Hbmass starting an altitude sojourn will have a limited ability to further increase their post-altitude Hbmass in male endurance and team-sport athletes (n = 58). The present thesis indicates that hypobaric and normobaric LHTL camps evoke a similar mean increase in Hbmass as well as similar performance changes following an 18-day LHTL camp, suggesting that both hypoxic conditions can be used equally for an LHTL training camp. Among the mean Hbmass changes, there was a notable inter-individual variation that could not be explained by the variation in the initial Hbmass. This emphasizes the importance of individual Hbmass response evaluation for altitude training in athletes. -- L’entrainement en altitude est couramment utilisé par les sportifs d’élites afin d’obtenir des bénéfices améliorant la performance au niveau de la mer. Le mécanisme-clef réside dans l’augmentation de la masse totale en hémoglobine (Hbmass) induite par l’hypoxie. Ces dernières décennies, plusieurs méthodes d’entrainement en altitude ont été développées, soit en hypoxie hypobare (HH, altitude réelle) soit en hypoxie normobare (NH, altitude simulée). La question de savoir si HH et NH sont interchangeables n’est pas encore complètement résolue. En particulier, les effets de NH vs. HH sur les réponses individuelles de Hbmass sont encore mal connus. Par conséquent, afin de comparer les réponses de Hbmass au cours d’un stage de 18 jours "vivre en haut et s’entrainer en bas, LHTL" soit en NH ou en HH, nous avons réalisé un protocole randomisé contrôlé (n = 28) puis un protocole croisé (n = 15) avec des athlètes d’endurance. Afin de quantifier plus précisément les réponses individuelles de Hbmass et de réduire les erreurs, les mesures ont été dupliquées. De plus, comme l’entrainement en altitude est utilisé à ce jour principalement par les athlètes d’endurance ayant un niveau initial élevé de Hbmass, nous avons testé l’hypothèse que les athlètes ayant une haute valeur de Hbmass ont une augmentation limitée de celle-ci suite à un stage en altitude, que ce soit avec des sportifs d’endurance ou de sport collectif (n = 58). Le travail de doctorat réalisé montre que LHTL induit la même augmentation de Hbmass en hypoxie normobare et hypobare, ainsi qu’une amélioration similaire de la performance aérobie. Aussi, les deux conditions hypoxiques (HH et NH) peuvent être utilisées pour des stages de type LHTL. De plus, une variabilité importante interindividuelle des réponses de Hbmass a été rapportée, qui ne dépendent pas du niveau initial de Hbmass des sujets. Ceci met en évidence la nécessité de mesurer ces réponses individuelles avec précision

Controlling Big Box Retail Development in Georgia

The rise of big box retail presents a number of serious challenges that can be addressed by both state legislatures and local governments. This paper provides strategies to help communities avoid big box blight caused by retailers abandoning existing sites for new stores, leaving empty eyesores in their wake

Pharmacogenetics of antipsychotic drugs

W badaniach farmakogenetycznych analizuje się związek pomiędzy czynnikami genetycznymi a indywidualną odpowiedzią chorego na terapię określonym lekiem. W przedstawionym przeglądzie piśmiennictwa badania farmakogenetyczne leków przeciwpsychotycznych najczęściej dotyczyły analiz asocjacyjnych pojedynczych polimorfizmów genów związanych z farmakologicznym mechanizmem ich działania. Wyniki tych badań wskazują na zależność między polimorfizmami genów układu dopaminergicznego (DRD2, DRD3), serotoninergicznego (5HT2A, 5HT2C), CYP2D6 a efektem klinicznym działania leków neuroleptycznych i występowaniem objawów niepożądanych. W niewielu pracach dotyczących badań asocjacyjnych analizowano interakcję między kilkoma genami. Uwzględnienie genotypów czterech genów (5HT2A, 5HT2C, 5HTT, H2) pozwala poprawnie przewidzieć odpowiedź kliniczną dotyczącą leczenia klozapiną w ponad 76% przypadków. Ponadto wykazano znaczenie predykcyjne polimorficznych wariantów genów związanych z układem serotoninergicznym i dopaminergicznym w wypadku leczenia olanzapiną. Należy podkreślić, że efekt farmakoterapii zależy od wielu czynników niegenetycznych, takich jak na przykład: wiek, płeć, przynależność do grupy etnicznej, dieta, współwystępowanie chorób somatycznych itp.Pharmacogenetic studies concentrate on the interactions between the genetic factors and the patient’s individual response to therapy. This paper reviews the pharmacogenetic studies of antipsychotic drugs and the associations of single genes polymorphism and it influence on the pharmacotherapy. The studies revealed the interactions between the polymorphisms in the dopaminergic (DRD2, DRD3) and serotoninergic systems (5HT2A, 5HT2C), CYP2D6 and the clinical drug action profiles. Very few papers exist on the multiple gene associations studies. Four genotypes (5HT2A, 5HT2C, 5HTT, H2) enable the physician to predict the clozapine therapy outcomes in 76% of cases. The predictive significance of genes associated with dopaminergic and serotoninergic systems was revealed in olanzapine therapy. It has to be emphasised that multiple non-genetic factors contribute to the outcome of pharmacotherapy

Direct and indirect effects of the COVID-19 pandemic on mortality in Switzerland.

The direct and indirect impact of the COVID-19 pandemic on population-level mortality is of concern to public health but challenging to quantify. Using data for 2011-2019, we applied Bayesian models to predict the expected number of deaths in Switzerland and compared them with laboratory-confirmed COVID-19 deaths from February 2020 to April 2022 (study period). We estimated that COVID-19-related mortality was underestimated by a factor of 0.72 (95% credible interval [CrI]: 0.46-0.78). After accounting for COVID-19 deaths, the observed mortality was -4% (95% CrI: -8 to 0) lower than expected. The deficit in mortality was concentrated in age groups 40-59 (-12%, 95%CrI: -19 to -5) and 60-69 (-8%, 95%CrI: -15 to -2). Although COVID-19 control measures may have negative effects, after subtracting COVID-19 deaths, there were fewer deaths in Switzerland during the pandemic than expected, suggesting that any negative effects of control measures were offset by the positive effects. These results have important implications for the ongoing debate about the appropriateness of COVID-19 control measures

Feeding-induced changes in allatostatin-A and short neuropeptide F in the antennal lobes affect odor-mediated host seeking in the yellow fever mosquito, <i>Aedes aegypti</i>

Aedes aegypti is a model species in which the endogenous regulation of odor-mediated host seeking behavior has received some attention. Sugar feeding and host seeking in female A. aegypti are transiently inhibited following a blood meal. This inhibition is partially mediated by short neuropeptide F (sNPF). The paired antennal lobes (ALs), as the first processing centers for olfactory information, has been shown to play a significant role in the neuropeptidergic regulation of odor-mediated behaviors in insects. The expression of sNPF, along with other peptides in the ALs of A. aegypti, indicate parallel neuromodulatory systems that may affect olfactory processing. To identify neuropeptides involved in regulating the odor-mediated host seeking behavior in A. aegypti, we use a semi-quantitative neuropeptidomic analysis of single ALs to analyze changes in the levels of five individual neuropeptides in response to different feeding regimes. Our results show that the level of sNPF-2, allatostatin-A-5 (AstA-5) and neuropeptide-like precursor-1-5 (NPLP-1-5), but not of tachykinin-related-peptides and SIFamide (SIFa), in the AL of female mosquitoes, changes 24 h and 48 h post-blood meal, and are dependent on prior access to sugar. To assess the role of these neuropeptides in modulating host seeking behavior, when systemically injected individually, sNPF-2 and AstA-5 significantly reduced host seeking behavior. However, only the injection of the binary mixture of the two neuropeptides lead to a host seeking inhibition similar to that observed in blood fed females. We conclude that modulation of the odor mediated host seeking behavior of A. aegypti is likely regulated by a dual neuropeptidergic pathway acting in concert in the ALs

Surveillance of SARS-CoV-2 prevalence from repeated pooled testing: application to Swiss routine data.

Surveillance of SARS-CoV-2 through reported positive RT-PCR tests is biased due to non-random testing. Prevalence estimation in population-based samples corrects for this bias. Within this context, the pooled testing design offers many advantages, but several challenges remain with regards to the analysis of such data. We developed a Bayesian model aimed at estimating the prevalence of infection from repeated pooled testing data while (i) correcting for test sensitivity; (ii) propagating the uncertainty in test sensitivity; and (iii) including correlation over time and space. We validated the model in simulated scenarios, showing that the model is reliable when the sample size is at least 500, the pool size below 20, and the true prevalence below 5%. We applied the model to 1.49 million pooled tests collected in Switzerland in 2021-2022 in schools, care centres, and workplaces. We identified similar dynamics in all three settings, with prevalence peaking at 4-5% during winter 2022. We also identified differences across regions. Prevalence estimates in schools were correlated with reported cases, hospitalizations, and deaths (coefficient 0.84 to 0.90). We conclude that in many practical situations, the pooled test design is a reliable and affordable alternative for the surveillance of SARS-CoV-2 and other viruses

Are schizophrenia and bipolar disorders genetically related?

Od prawie stu lat w klasyfikacji zaburzeń psychicznych wyodrębnia się schizofrenię oraz chorobę afektywną dwubiegunową. Przyjmuje się, że schizofrenia i zaburzenia afektywne dwubiegunowe to dwie oddzielne kategorie nozologiczne (o odmiennej etiologii, specyficznym leczeniu). Wyniki badań genetycznych przeprowadzonych w ostatnich latach wskazują, że dychotomiczny podział psychoz może budzić wątpliwości. W niniejszej pracy przedstawiono dane epidemiologiczne wskazujące, że podatność do zachorowania na schizofrenię i chorobę afektywną jest w pewnym zakresie wspólna dla obydwu tych chorób. W badaniach analizy sprzężeń stwierdzono, że niektóre loci genomu wiąże się ze schizofrenią i chorobą afektywną dwubiegunową. Dotychczasowe wyniki badań wskazują także, że geny DAOA, DISC1 i COMT mogą mieć związek z patogenezą CHAD i SCH. Badania genetyczne sugerują, że podłoże genetyczne SCH i CHAD może być w pewnym zakresie wspólne.For more than hundred years research in psychiatry has proceed under the assumption that bipolar disorder and schizophrenia are distinct entities, with separate underlying disease process and treatment. It is predicted that in coming years molecular genetic studies will overturn this traditional dichotomous view. The article reviews evidence that bipolar disorder (BP) and schizophrenia (SCH) might share familial risk characteristics. Family studies of BP and SCH suggest partial overlap in familial susceptibility. Molecular linkage studies indicates that some susceptibility loci may be common for both nosological classes. Current evidence supports DAOA, DISC1 and COMT as schizophrenia and bipolar disorder susceptibility loci. Some research suggests, that there might be a genetic connection between schizophrenia and bipolar disorder. Future identification of psychosis susceptibility genes will have a major impact on our understanding of disease pathophysiology

An integrated approach to supply chain risk analysis

Despite the increasing attention that supply chain risk management is receiving by both researchers and practitioners, companies still lack a risk culture. Moreover, risk management approaches are either too general or require pieces of information not regularly recorded by organisations. This work develops a risk identification and analysis methodology that integrates widely adopted supply chain and risk management tools. In particular, process analysis is performed by means of the standard framework provided by the Supply Chain Operations Reference Model, the risk identification and analysis tasks are accomplished by applying the Risk Breakdown Structure and the Risk Breakdown Matrix, and the effects of risk occurrence on activities are assessed by indicators that are already measured by companies in order to monitor their performances. In such a way, the framework contributes to increase companies' awareness and communication about risk, which are essential components of the management of modern supply chains. A base case has been developed by applying the proposed approach to a hypothetical manufacturing supply chain. An in-depth validation will be carried out to improve the methodology and further demonstrate its benefits and limitations. Future research will extend the framework to include the understanding of the multiple effects of risky events on different processe

Beta: an experiment in funded undergraduate start up

This paper reports on an evaluation of a funded undergraduate project designed to enable student business start-up. The programme, entitled 'Beta', provides undergraduate students with £1,500 of seed-corn funding. The key objective of the project is for the participants to exit it with a viable and legal business entity through which they can start trading on completion of the course. The study adopts a case study approach and evaluates all aspects of the Beta programme, the actors involved and its processes and practices. The authors examine the development of the project and the challenges and hurdles that were identified and overcome to realize the project's goals