Ecdysteroids: A novel class of anabolic agents?

Increasing numbers of dietary supplements with ecdysteroids are marketed as “natural anabolic agents”. Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class “S1.2 Other Anabolic Agents” of the list of prohibited substances of the World Anti-Doping Agency

Systematic review of cost and cost-effectiveness of different TB-screening strategies

<p>Abstract</p> <p>Background</p> <p>Interferon-γ release assays (IGRAs) for TB have the potential to replace the tuberculin skin test (TST) in screening for latent tuberculosis infection (LTBI). The higher per-test cost of IGRAs may be compensated for by lower post-screening costs (medical attention, chest x-rays and chemoprevention), given the higher specificity of the new tests as compared to that of the conventional TST. We conducted a systematic review of all publications that have addressed the cost or cost-effectiveness of IGRAs. The objective of this report was to undertake a structured review and critical appraisal of the methods used for the model-based cost-effectiveness analysis of TB screening programmes.</p> <p>Methods</p> <p>Using Medline and Embase, 75 publications that contained the terms "IGRA", "tuberculosis" and "cost" were identified. Of these, 13 were original studies on the costs or cost-effectiveness of IGRAs.</p> <p>Results</p> <p>The 13 relevant studies come from five low-to-medium TB-incidence countries. Five studies took only the costs of screening into consideration, while eight studies analysed the cost-effectiveness of different screening strategies. Screening was performed in high-risk groups: close contacts, immigrants from high-incidence countries and healthcare workers. Two studies used the T-SPOT.TB as an IGRA and the other studies used the QuantiFERON-TB Gold and/or Gold In-Tube test. All 13 studies observed a decrease in costs when the IGRAs were used. Six studies compared the use of an IGRA as a test to confirm a positive TST (TST/IGRA strategy) to the use of an IGRA-only strategy. In four of these studies, the two-step strategy and in two the IGRA-only strategy was more cost-effective. Assumptions about TST specificity and progression risk after a positive test had the greatest influence on determining which IGRA strategy was more cost-effective.</p> <p>Conclusion</p> <p>The available studies on cost-effectiveness provide strong evidence in support of the use of IGRAs in screening risk groups such as HCWs, immigrants from high-incidence countries and close contacts. So far, only two studies provide evidence that the IGRA-only screening strategy is more cost-effective.</p

Specificity of a whole blood IGRA in German nursing students

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma release assays (IGRA) are used for tuberculosis (TB) screening in healthcare workers (HCWs). However, data on specificity of IGRA in serial testing of HCWs is sparse. Therefore the specificity and the negative predictive value of the IGRA - QuantiFERON-TB Gold In-Tube (QFT) - in German nursing students was investigated.</p> <p>Methods</p> <p>194 nursing students at the start of their professional career were tested with the QFT. 14 nursing students were excluded from the specificity analysis, due to exposure to mycobacterium tuberculosis. Two of these subjects were QFT- positive. None of them developed disease during the year of follow-up. A study group of 180 students, all with very low risk of prior TB infection, remained in the specificity analysis. Subjects were monitored for at least two years with respect to the development of active TB disease. IGRA was performed at the start of the training and after one year.</p> <p>Results</p> <p>The mean age of the study group (n = 180) was 23 years (range 18-53) with 70.9% female and 99.4% German born. The specificity of QFT was 98.9% (178/180; 95% CI 0.96-0.99); lowering the cut-off from 0.35 IU/ml to 0.1 IU/ml would have decreased specificity only slightly to 97.8% (176/180; 95% CI 0.94-0.99). Of the 154 nursing students available for re-testing, one student who initially scored positive reverted to negative, and one student initially negative converted to positive. None of the monitored group with initially negative QFT results developed TB disease, indicating a high negative predictive value of the IGRA in this population.</p> <p>Conclusions</p> <p>Following our data, QFT can serve as an effective tool in pre-employment TB screenings for HCWs. As its negative results were stable over time, specificity of the QFT in serial testing of HCWs is high. As the risk of acquiring TB infection in the German healthcare system appears to be low, our data supports the recommendation of performing TB screening only in those HCWs with known contact to TB patients or infectious materials.</p

Development of graphical time response using the OPTSYSX Program.

This thesis discusses the modification of aid additions to an existing Optimal Systems Control FORTE AN Program (OPTSYS) originally obtained from Professor Arthur E. Bryson of Stanford University and subsequently redesigned to run interactively on the IBM 33 33 VVCMS by Lieutenant Commander John G. Hoden of the Naval Postgraduate School (NPS). The modified FOBTEAN program (OPTSYSX) and the additional FOETEAN Programs (OPTCALC) and (OPTPLOT) are now designed to run interactively under VM/CMS on the IBM 3033 utilizing a library double precision numerical integration subroutine and high resolution precision plotting software to provide the user with a highly accurate time response of a system which has been designed on the OPTSYSX Program. This series of programs permits the user to rapidly design, analyze and test all types of Optimal Systems Co ntrol problems. Examples of the various types of problems are worked through to illustrate all of the capabilities available.http://archive.org/details/developmentofgra00dielCommander, United States NavyApproved for public release; distribution is unlimited

Distribuição horizontal da produtividade de soja em sistema de integração lavoura-pecuária-floresta

O sistema de integração lavoura-pecuária-floresta (ILPF) possibilita aumentar a renda da propriedade, devido a intensificação do uso da terra e o aumento da eficiência dos sistemas de produção. No entanto, com o crescimento das árvores, há uma diminuição progressiva da luminosidade disponível para o sub&#8209;bosque que pode influenciar a produtividade do componente agrícola. O objetivo do presente trabalho foi avaliar a distribuição horizontal da produtividade de soja no sistema ILPF e compará-la ao cultivo exclusivo. O experimento foi conduzido no município de Sinop/MT, avaliando-se os seguintes tratamentos: lavoura com cultivo de soja na safra e milho consorciado com Brachiaria brizantha na safrinha e o sistema de ILPF, com cultivo de eucalipto em faixas de linhas triplas (3,5 x 3,0 m orientação Leste Oeste), com soja safra na faixa de agricultura (entrerenques), seguido de milho safrinha consorciado com B. brizantha. Os tratamentos foram implantados na safra 2011/2012 sendo que as árvores foram plantadas em novembro de 2011. O experimento seguiu o delineamento de blocos casualizados (DBC) com 4 repetições. As avaliações foram realizadas no segundo ano agrícola, após implantação do experimento, na safra 2012/2013. As características agronômicas da soja foram realizadas no estágio de desenvolvimento R8, avaliando-se duas linhas de 5 m em oito posições aleatórias no cultivo exclusivo de soja. No tratamento ILPF, as duas linhas de 5 m foram avaliadas em quatro transectos equidistantes, posicionadas no sentido transversal às linhas da espécie florestal, nas distâncias de 3, 6, 10 e 15 m das florestais, para ambos os lados (face norte e face sul). Foram avaliados: número de plantas, índice de acamamento com notas de 1 a 5 (1: > 90% de plantas eretas e 5: > 80% de plantas acamadas), massa de 100 grãos e produtividade (kg ha -1 com 13% de umidade). No segundo ano agrícola, o eucalipto estava com 12 meses de idade, altura média de 4 m e DAP médio de 5,1 cm. A projeção máxima de sombra na face norte foi de 4 m às 09:30 h. Não houve diferenças significativas entre a soja cultivada em sistema exclusivo e a soja cultivada no sistema ILPF para o número de plantas (p>0,37), peso de 100 grãos (p>0,24) e índice de acamamento (p>0,24). A produtividade média de soja foi de 4.041 kg ha -1 na lavoura exclusiva e 3.999 kg ha -1 na ILPF e também não diferiu significativamente (p> 0,26). Na avaliação da distribuição horizontal, a faixa de árvores do sistema ILPF não afetou a produtividade do componente agrícola no segundo ano de condução do sistema

Distribuição horizontal e vertical de fósforo em sistemas de cultivos exclusivos de soja e de integração lavoura-pecuária-floresta.

O objetivo deste trabalho foi avaliar a distribuição horizontal e vertical do fósforo no solo e a produtividade de soja em sistemas de cultivos exclusivos e de integração lavoura-pecuária-floresta (ILPF). Foram avaliados os tratamentos: floresta plantada de eucalipto; lavoura de soja e milho safrinha consorciado com Urochloa brizantha 'Marandu'; pastagem de U. brizantha; sistema de ILPF; e duas áreas controle, com floresta nativa e pousio. O solo foi coletado nas camadas de 0-5, 5-10, 10-20 e 20-30 cm, para determinação das características químicas. As avaliações foram realizadas no segundo ano agrícola após a implantação do experimento. No sistema de ILPF, solo e produtividade foram avaliados em quatro transectos equidistantes, no centro do renque e a 3, 6, 10 e 15 m do renque, nas faces norte e sul. Os teores de P disponível (Mehlich-1) foram maiores nas camadas superficiais do solo, nos sistemas com soja/milho safrinha e com ILPF. No ILPF, os teores de P disponível não diferiram entre as distâncias do renque das árvores, e a produtividade de soja não diferiu da observada no sistema com soja/milho safrinha. Portanto, com dois anos de implantação, o sistema ILPF ainda não é capaz de interferir marcadamente nas características químicas do solo e na produtividade da soja

A novel class of anabolic agents?

Increasing numbers of dietary supplements with ecdysteroids are marketed as “natural anabolic agents”. Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class “S1.2 Other Anabolic Agents” of the list of prohibited substances of the World Anti-Doping Agency

The maximum of the local time of a diffusion process in a drifted Brownian potential

We consider a one-dimensional diffusion process $X$ in a $(-\kappa/2)$-drifted Brownian potential for $\kappa\neq 0$. We are interested in the maximum of its local time, and study its almost sure asymptotic behaviour, which is proved to be different from the behaviour of the maximum local time of the transient random walk in random environment. We also obtain the convergence in law of the maximum local time of $X$ under the annealed law after suitable renormalization when $\kappa \geq 1$. Moreover, we characterize all the upper and lower classes for the hitting times of $X$, in the sense of Paul L\'evy, and provide laws of the iterated logarithm for the diffusion $X$ itself. To this aim, we use annealed technics.Comment: 38 pages, new version, merged with hal-00013040 (arXiv:math/0511053), with some additional result

Uloga testova otpuštanja interferona gama u nadzoru nad tuberkulozom

Tuberculosis is still one of the major global public health threats. Countries with low incidence must focus on exhausting the reservoir of future cases by preventing reactivation. Therefore, it is important to identify and effectively treat those individuals who have latent tuberculosis infection and who may develop active disease. The tuberculin skin test has been the standard for detection of immune response against M. tuberculosis since the beginning of the 20th century. The new millennium has brought advancement in the diagnosis of latent tuberculosis infection. The name of the new blood test is interferon-gamma release assay (IGRA). Croatia is a middle-incidence country with a long decreasing trend and developed tuberculosis control. To reach low incidence and finally eliminate tuberculosis, its tuberculosis programme needs a more aggressive approach that would include intensive contact investigation and treatment of persons with latent tuberculosis infection. This article discusses the current uses of IGRA and its role in tuberculosis control.Tuberkuloza je i danas jedan od vodećih javnozdravstvenih problema. Zemlje s niskom incidencijom fokusiraju se na iscrpljivanje rezervoara budućih slučajeva sprječavanjem reaktivacije bolesti. To se odnosi na traženje i učinkovito liječenje infi ciranih osoba, primarno onih koje su u riziku od obolijevanja nakon infekcije. Tuberkulinski test je od početka 20. stoljeća bio standard u otkrivanju imunosnog odgovora na kontakt s Mycobacterium tuberculosis. Novo tisućljeće donijelo je određeni napredak u obliku novih testova za dijagnozu latentne tuberkulozne infekcije, krvne testove otpuštanja interferona gama. Hrvatska je zemlja srednje incidencije tuberkuloze s dugogodišnjim silaznim trendom i razvijenim protutuberkuloznim aktivnostima. U težnji prema niskoj incidenciji i u konačnici eliminaciji tuberkuloze potrebne su opsežnije aktivnosti unutar državnog programa nadzora nad tuberkulozom, uključujući intenzivnu obradu kontakata i probir na postojanje latentne tuberkulozne infekcije. Ovaj rad razmatra trenutačnu uporabu IGRE (engl. interferon - gamma release assay) i njezinu ulogu u nadzoru nad tuberkulozom

A model ensemble approach to determine the humus building efficiency of organic amendments in incubation experiments

Organic amendments are important to sustain soil organic matter (SOM) and soil functions in agricultural soils. Information about the contribution of organic amendments to SOM can be derived from incubation experiments. In this study, data from 72 incubated organic amendments including plant residues, digestates and manure were analysed. The incubation data was compiled from three experimental setups with varying incubation times, soils and incubation temperatures, in which CO2 release was measured continuously. The analysis of the incubation data was performed with an approach relying on conceptual parts of C-TOOL, CCB, Century, ICBM, RothC and Yasso which are all well-approved first-order carbon models that differ in structure and abstraction level. All models are an approximation of reality, whereby each model differs in understanding of the processes involved in soil carbon dynamics. To accumulate the advantages from each model a model ensemble was performed for each substrate. With the ability of each carbon model to compute the distribution of carbon into specific SOM pools a new approach for evaluating organic amendments in terms of humus building efficiency is presented that, depends on the weighted model fit of each ensemble member. Depending on the organic substrate added to the soil, the time course of CO2 release in the incubation studies was predicted with different accuracy by the individual model concepts. Averaging the output of the individual models leads to more robust prediction of SOM dynamics. The EHUM value is easy to interpret and the results are in accordance with the literature.Peer Reviewe