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991.
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Robert W. Smith Britta Helwig Adrie H. Westphal Eran Pel Maximilian Hörner Hannes M. Beyer Sophia L. Samodelov Wilfried Weber Matias D. Zurbriggen Jan Willem Borst Christian Fleck 《BMC systems biology》2015,10(1):110
Background
Obtaining accurate estimates of biological or enzymatic reaction rates is critical in understanding the design principles of a network and how biological processes can be experimentally manipulated on demand. In many cases experimental limitations mean that some enzymatic rates cannot be measured directly, requiring mathematical algorithms to estimate them. Here, we describe a methodology that calculates rates at which light-regulated proteins switch between conformational states. We focus our analysis on the phytochrome family of photoreceptors found in cyanobacteria, plants and many optogenetic tools. Phytochrome proteins change between active (P A ) and inactive (P I ) states at rates that are proportional to photoconversion cross-sections and influenced by light quality, light intensity, thermal reactions and dimerisation. This work presents a method that can accurately calculate these photoconversion cross-sections in the presence of multiple non-light regulated reactions.Results
Our approach to calculating the photoconversion cross-sections comprises three steps: i) calculate the thermal reversion reaction rate(s); ii) develop search spaces from which all possible sets of photoconversion cross-sections exist, and; iii) estimate extinction coefficients that describe our absorption spectra. We confirm that the presented approach yields accurate results through the use of simulated test cases. Our test cases were further expanded to more realistic scenarios where noise, multiple thermal reactions and dimerisation are considered. Finally, we present the photoconversion cross-sections of an Arabidopsis phyB N-terminal fragment commonly used in optogenetic tools.Conclusions
The calculation of photoconversion cross-sections has implications for both photoreceptor and synthetic biologists. Our method allows, for the first time, direct comparisons of photoconversion cross-sections and response speeds of photoreceptors in different cellular environments and synthetic tools. Due to the generality of our procedure, as shown by the application to multiple test cases, the photoconversion cross-sections and quantum yields of any photoreceptor might now, in principle, be obtained.994.
995.
Background
Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.Methods
We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran’s Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates.Results
Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27–0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36–1.87) or overall mortality (RR 0.95, 95% CI 0.46–1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing.Conclusions
Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals. 相似文献996.
Hyman M. Scott Risha Irvin Leo Wilton Hong Van Tieu Chauncey Watson Manya Magnus Iris Chen Charlotte Gaydos Sophia A. Hussen Sharon Mannheimer Kenneth Mayer Nancy A. Hessol Susan Buchbinder 《PloS one》2015,10(12)
Background
Black men who have sex with men (MSM) have a high prevalence of bacterial sexually transmitted infections (STIs), and individual risk behavior does not fully explain the higher prevalence when compared with other MSM. Using the social-ecological framework, we evaluated individual, social and sexual network, and structural factors and their association with prevalent STIs among Black MSM.Methods
The HIV Prevention Trials Network 061 was a multi-site cohort study designed to determine the feasibility and acceptability of a multi-component intervention for Black MSM in six US cities. Baseline assessments included demographics, risk behavior, and social and sexual network questions collected information about the size, nature and connectedness of their sexual network. Logistic regression was used to estimate the odds of having any prevalent sexually transmitted infection (gonorrhea, chlamydia, or syphilis).Results
A total of 1,553 Black MSM were enrolled in this study. In multivariate analysis, older age (aOR = 0.57; 95% CI 0.49–0.66, p<0.001) was associated with a lower odds of having a prevalent STI. Compared with reporting one male sexual partner, having 2–3 partners (aOR = 1.74; 95% CI 1.08–2.81, p<0.024) or more than 4 partners (aOR = 2.29; 95% CI 1.43–3.66, p<0.001) was associated with prevalent STIs. Having both Black and non-Black sexual partners (aOR = 0.67; 95% CI 0.45–0.99, p = 0.042) was the only sexual network factor associated with prevalent STIs.Conclusions
Age and the number and racial composition of sexual partners were associated with prevalent STIs among Black MSM, while other sexual network factors were not. Further studies are needed to evaluate the effects of the individual, network, and structural factors on prevalent STIs among Black MSM to inform combination interventions to reduce STIs among these men. 相似文献997.
The Lundehund is an old dog breed with remarkable anatomical features including polydactyly in all four limbs and extraordinary flexibility of the spine. We genotyped 28 Lundehund using the canine Illumina high density beadchip to estimate the effective population size (Ne) and inbreeding coefficients as well as to identify potential regions of positive selection. The decay of linkage disequilibrium was slow with r2 = 0.95 in 50 kb distance. The last 7-200 generations ago, Ne was at 10-13. An increase of Ne was noted in the very recent generations with a peak value of 19 for Ne at generation 4. The FROH estimated for 50-, 65- and 358-SNP windows were 0.87, 087 and 0.81, respectively. The most likely estimates for FROH after removing identical-by-state segments due to linkage disequilibria were at 0.80-0.81. The extreme loss of heterozygosity has been accumulated through continued inbreeding over 200 generations within a probably closed population with a small effective population size. The mean inbreeding coefficient based on pedigree data for the last 11 generations (FPed = 0.10) was strongly biased downwards due to the unknown coancestry of the founders in this pedigree data. The long-range haplotype test identified regions with genes involved in processes of immunity, olfaction, woundhealing and neuronal development as potential targets of selection. The genes QSOX2, BMPR1B and PRRX2 as well as MYOM1 are candidates for selection on the Lundehund characteristics small body size, increased number of digits per paw and extraordinary mobility, respectively. 相似文献
998.
Hong-Van Tieu Ting-Yuan Liu Sophia Hussen Matthew Connor Lei Wang Susan Buchbinder Leo Wilton Pamina Gorbach Kenneth Mayer Sam Griffith Corey Kelly Vanessa Elharrar Gregory Phillips Vanessa Cummings Beryl Koblin Carl Latkin HPTN 《PloS one》2015,10(8)
Background
Sexual networks may place U.S. Black men who have sex with men (MSM) at increased HIV risk.Methods
Self-reported egocentric sexual network data from the prior six months were collected from 1,349 community-recruited Black MSM in HPTN 061, a multi-component HIV prevention intervention feasibility study. Sexual network composition, size, and density (extent to which members are having sex with one another) were compared by self-reported HIV serostatus and age of the men. GEE models assessed network and other factors associated with having a Black sex partner, having a partner with at least two age category difference (age difference between participant and partner of at least two age group categories), and having serodiscordant/serostatus unknown unprotected anal/vaginal intercourse (SDUI) in the last six months.Results
Over half had exclusively Black partners in the last six months, 46% had a partner of at least two age category difference, 87% had ≤5 partners. Nearly 90% had sex partners who were also part of their social networks. Among HIV-negative men, not having anonymous/exchange/ trade partners and lower density were associated with having a Black partner; larger sexual network size and having non-primary partners were associated with having a partner with at least two age category difference; and having anonymous/exchange/ trade partners was associated with SDUI. Among HIV-positive men, not having non-primary partners was associated with having a Black partner; no sexual network characteristics were associated with having a partner with at least two age category difference and SDUI.Conclusions
Black MSM sexual networks were relatively small and often overlapped with the social networks. Sexual risk was associated with having non-primary partners and larger network size. Network interventions that engage the social networks of Black MSM, such as interventions utilizing peer influence, should be developed to address stable partnerships, number of partners, and serostatus disclosure. 相似文献999.
Xin Quan Tan Wei-Ping Goh Indumathi Venkatachalam Diana Goh Revathi Sridhar Hwang Ching Chan Sophia Archuleta 《PloS one》2015,10(1)