Logistic Curve Fitting Research Articles

Game analysis on the evolution of COVID-19 epidemic under the prevention and control measures of the government.

In this paper, the interaction strategies and the evolutionary game analysis of the actions taken by the government and the public in the early days of the epidemic are incorporated into the natural transmission mechanism model of the epidemic, and then the transmission frequency equations of COVID-19 epidemic is established. According to the cumulative confirmed cases of COVID-19 in the UK and China, the upper limit of the spread of COVID-19 in different evolutionary scenarios is set. Using SPSS to perform logistic curve fitting, the frequency fitting equations of cumulative confirmed cases under different evolution scenarios are obtained respectively. The analysis result shows that the emergency response strategy adopted by the government in the early days of the epidemic can effectively control the spread of the epidemic. Combined with the transmission frequency equation of COVID-19 epidemic, measures taken by the government are analyzed. The influence of each measure on the frequency variable is judged and then the influence on the spread of the epidemic is obtained. Finally, based on the above analysis, the government is advised to adhere to the principles of scientific, initiative and flexibility when facing major epidemics.

Effects of age on pregnancy outcomes in patients with simple tubal factor infertility receiving frozen-thawed embryo transfer

This study was to retrospectively analyze the effect of the age of embryos transfer and oocyte retrieval on the clinical pregnancy outcome in patients with simple tubal factor infertility (TFI) who received frozen-thawed embryo transfer. Patients (n = 3619) with simple TFI who underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) frozen-thawed embryo transfer at our hospital were enrolled. Univariate logistic regression analysis, categorical multivariate logistic regression analysis, curve fitting and threshold effect analysis were performed. Age of embryo transfer was a significant (P < 0.05) independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rates. The Clinical pregnancy outcome declined significantly after the age of 34 years. After limiting the female oocyte retrieval age to ≤ 34 years, no significant change was detected in the clinical pregnancy, live birth, or miscarriage rate with increase of transplantation age. In conclusion, in patients with simple TFI undergoing IVF/ICSI frozen-thawed embryo transfer, age is a significant independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rate. Aging of oocytes has a greater impact on the clinical pregnancy in women with simple TFI than the aging of the body. Patients with TFI can freeze embryos in advance to preserve fertility.

Development of Generic Equivalence Margins for Early-Stage Implementation of Equivalence Testing for Potency Assays

Relative potency assays for biological therapeutics require statistical evaluation to demonstrate similarity between the dose-response curves of a reference standard and the test samples. We developed an equivalence testing approach that can be utilized for the complete potency assay life cycle, from early development until commercialization. This approach was based on the use of generic equivalence margins to enable equivalence testing at the beginning of assay development, when the body of assay-specific data is still very limited. Generic equivalence margins for equivalence testing of four-parameter logistic curve fits were established for bioassays and binding assays spanning a variety of designs, formats, and read-outs. We also established that equivalence testing using ratios of the reference standard and test sample was superior to equivalence testing using absolute differences. Based on a large body of historical data, generic equivalence margins were determined for the curve upper asymptote, slope, and dynamic range. Furthermore, we developed a road map to guide the implementation of generic or assay-specific margins to ensure the appropriate data analysis approach is being applied during the assay life cycle.

Assessing the mitigation of greenhouse gas emissions from a green infrastructure-based urban drainage system

Green infrastructure (GI) is a low-carbon solution for urban rainwater management. Hydrological processes and the corresponding emissions of greenhouse gas (GHG) during rainfall events are optimized by GI when the latter is compared with a traditional urban drainage system. This study establishes an city-scale quantitative analysis, based on hydrological processes, with which to assess the contribution of GIs to low-carbon urban drainage systems and cities. The emission factor method is applied to measure GHG emissions. Attributable sources of emissions are wastewater treatment plants and wastewater and rainwater pumps. The amount and rate of change in GHG emissions were selected as indicators of the impacts of GI-based urban drainage systems and a case study was conducted in Dongying, China, based on 48 hydrological scenarios from 1970 to 2017. The amount of annual GHG emissions decreased by 3752.5 to 26238.9 tons of CO2 equivalent at an average of 10677.3 tons/a. The rate of annual GHG emissions decreased by 25.9–68.7% with an average reduction of 45.9%. An S-shaped logistic curve fit the data, indicated that annual rainfall is non-linearly and positively correlated with both the amount and rate of annual GHG emissions mitigated. The probability of benefits to GHG emissions in the 48 hydrological scenarios is analyzed based on a Pearson type III distribution curve. These findings can provide information that local authorities can use to guide policies towards their goals of applying GIs to mitigate GHG emissions in the urban drainage system.

The relationship and difference between delay detection ability and judgment of sense of agency.

Judgment of agency involves the comparison of motor intention and proprioceptive/visual feedback, in addition to a range of cognitive factors. However, few studies have experimentally examined the differences or correlations between delay detection ability and judgment of agency. Thus, the present study investigated the relationship between delay detection ability and agency judgment using the delay detection task and the agency attribution task. Fifty-eight participants performed the delay detection and agency attribution tasks, and the time windows of each measure were analyzed using logistic curve fitting. The results revealed that the time window of judgment of agency was significantly longer than that of delay detection, and there was a slight correlation between the time windows in each task. The results supported a two-step model of agency, suggesting that judgment of agency involved not only comparison of multisensory information but also several cognitive factors. The study firstly revealed the model in psychophysical experiments.

Electric Energy Substitution Potential Prediction Based on Logistic Curve Fitting and Improved BP Neural Network Algorithm

In order to predict the potential of electric energy substitution in the next decade in China, this paper proposes a prediction method based on Logistic curve fitting and improved BP neural network algorithm. The amount of electric energy substitution is defined to quantify the potential of electric energy substitution. Then the important influencing factors of electric energy substitution based on the Impact by Population, Affluence and Technology (IPAT) model are established and quantified. For different influencing factors, logistic curve fitting and polynomial function fitting method were used to estimate the data fitting. A two-node output layer model of BP neural network is established and improved with additional momentum factors and adaptive learning rate to learn and train the data related to electric energy substitution from 2003 to 2017, and calculate the amount of electric energy substitution which are substitution potential from 2018 to 2020, 2025 and 2030. The calculation results show that the method has higher computational accuracy and fewer iterations. The prediction results are reasonable and effective, which can be the reference of the research of energy substitution.

Leaf and male cone phenophases of Chinese pine (Pinus tabulaeformis Carr.) along a rural-urban gradient in Beijing, China

Numerous studies have shown that plant phenology has advanced due to urbanization. However, large uncertainties remain because different indicators and methods have been used to characterize plant phenology. In this study, by means of photograph identification and logistic curve fitting, the phenophases of leaves and male cones of Chinese pine (Pinus tabuliformis Carr.) were divided into seven and six phases, respectively. The rural-urban gradient in phenology of leaves and male cones varied significantly in ranges of 0.36–1.92 and 0.41–0.66 days/km, respectively, depending on the phenophase defined. Interestingly, the rural-urban gradient of leaf phenology increased with leaf development. Thus, fine separation of phenophases is necessary to provide more precise criterion for assessing urbanization-induced plant phenology across different studies or regions. For Chinese pine, the timings of maximum leaf elongation rate achievement and male cones maturation were key phenophases for investigating the effect of urbanization.

Association between Peripheral Leukocyte Telomere Length and Dietary Vitamin A and Carotenoid in U.S. Adults

To investigate the independent association between peripheral leukocyte telomere length and dietary vitamin A and carotenoid, we collected 839 participants older than 20-year from the 1999-2000 National Health and Nutrition Examination Survey. The peripheral leukocyte telomere length was obtained using the quantitative polymerase chain reaction method. Dietary information, such as alcohol, caffeine, carotenoid, folate and vitamin A/B1/B2/B6/B12/C/E was from a recall of the previous 24h taken food. Multivariable logistic regression and smooth curve fitting was conducted to analyze the independent association between telomere length and dietary vitamin A and carotenoid. Obesity was further treated as effect modification factor in the stratified analysis. After adjusting for age, race, sex, education, obesity, physical activity, PIR, smoking status, CAD history, serum concentrations of vitamin E/A/B12, folate, gamma-tocopherol, CRP, total cholesterol, cadmium and dietary intake of alcohol, caffeine, fiber, folate and vitamin B1/B2/B6/B12/C/E, the daily vitamin A and carotenoid intake was not significantly associated with telomere length in general population (vitamin A: 0.0009, 95% CI: -0.0041, 0.0058; carotenoid: 0.0040, 95% CI: -0.0458, 0.0538). In non-obesity population, the association coefficient was -0.0121 (95% CI: -0.0259, 0.0017) for vitamin A and -0.1369 (95% CI: -0.2809, 0.0070) for carotenoid. Vitamin A and carotenoid consumption was not associated with peripheral leukocyte telomere length independently in general adult population. However, in non-obese individuals, increasing vitamin A and carotenoid might tend to associate with decreasing peripheral leukocyte telomere length.

Live baby rate per oocyte with no stimulation

What is the intrinsic fecundity rate of the human oocyte in relation to age? Ovarian hyperstimulation has been found to yield a live baby rate per oocyte of only about 4 to 6%. Thus on average more than 20 to 25 oocytes would be required to produce a single live baby. But this is in stimulated cycles. The live baby rate per egg in natural cycle single embryo transfer IVF would estimate better the intrinsic fertility of the human oocyte. 13,949 oocyte retrievals were performed in a natural cycle program with single embryo transfer in an attempt to determine what is the fertility potential of a single human oocyte that has not been submitted to ovarian hyperstimulation. Infertile women undergoing natural cycle with a single embryo transfer were studied retrospectively. The primary data of live baby per oocyte were approximated with a logistic curve r+1(a+exp[b(t-c)]) where r is live baby rate per oocyte and t is age in years. The coefficients were evaluated using gradient method as implemented in statistical package R (version 3.2.5). This allowed the construction of a robust logistic curve fit. The primary outcome of interest was live baby rate per oocyte. For women ≤42 years, the overall live baby rate per oocyte was 18%, which translated into only 5.5 oocytes needed to produce one baby. For women 42 years of age, every oocyte would have a 4% chance of becoming a baby, which means for a 42 year old woman it would require 22.7 rather than 5.5 eggs to produce a baby. The drop in intrinsic fertility per oocyte is summarized remarkably robustly in a logistic curve. There is at first a steady (almost horizontal) maintenance of fertility per oocyte (26%), followed after age 34 with a sharp linear decline until age 42 (4%), with a 10% loss of fertility every year. This decline slows down after age 43, with only 3% of original fertility remaining at age 45. The logistic model explains virtually all observed variation in live baby per oocyte rate: adjusted R-square is 99%. For all transfers the basic integrity of the logistic curve was remarkably robust. Live baby rate per single unstimulated oocyte is 26% until age 35, and then declines 10% per year until age 42, when it is only 4%. This is approximately a five times greater live baby rate per egg than has been reported with stimulated cycles.

MP29-19 SIPULEUCEL-T IMMUNOTHERAPY FOR CASTRATE-RESISTANT PROSTATE CANCER MODULATES SOLUBLE B7-H3: A NOVEL MECHANISM OF ACTION

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2018MP29-19 SIPULEUCEL-T IMMUNOTHERAPY FOR CASTRATE-RESISTANT PROSTATE CANCER MODULATES SOLUBLE B7-H3: A NOVEL MECHANISM OF ACTION Andrew Chang, Smita Nair, Daniel George, and Brant Inman Andrew ChangAndrew Chang More articles by this author , Smita NairSmita Nair More articles by this author , Daniel GeorgeDaniel George More articles by this author , and Brant InmanBrant Inman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.939AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES B7-H3 is an immune checkpoint molecule widely expressed by prostate cancer, that exists in soluble form in the blood, and that impairs T cell function. We examined whether a cell-based immunotherapy for castrate-resistant prostate cancer (CRPC), sipuleucel-T, might modulate B7-H3 as part of its mechanism of action. METHODS We conducted a clinical trial (NCT02036918) where men with lymph node predominant oligometastatic CRPC were randomized to undergo either (a) sipuleucel-T immunotherapy followed by salvage lymphadenectomy (n=15) or (b) salvage lymphadenectomy followed by sipuleucel-T (n=5). Serum samples were taken at baseline, prior to each sipuleucel-T leukapheresis session (x3), and two weeks after the last sipuleucel-T infusion. Serum samples were then tested in triplicate for soluble B7-H3 using a solid phase sandwich ELISA assay. The assay was calibrated against highly purified NS0-expressed recombinant human B7-H3. ELISA was performed in 90 well microplates that were read in a SpectraMax microplate reader at 450 nm with wavelength correction set to 540 nm. B7-H3 concentrations were calculated using a 4-parameter logistic model curve fit (Hill equation). Pre- and post-intervention serum B7-H3 levels were compared with a paired T test. RESULTS The mean minimum detectable dose of B7-H3 for the assay was 0.160 ng/mL. Vaccination with sipuleucel-T resulted in significant drop in serum B7-H3 levels from a mean pre-sipuleucel-T level of 29.6 ng/mL [SD = 6.7] to a mean post-sipuleucel-T level of 24.0 ng/mL [SD = 5.5] (P <0.001). In contradistinction, pre-surgery mean serum B7-H3 was 22.1 ng/mL (SD = 5.5) and post-surgery mean serum B7-H3 was 29.2 ng/mL (SD = 9.3), a difference of 7.1 ng/mL (P = 0.002), indicating that surgery caused an increase in serum B7-H3 levels (Figure). CONCLUSIONS Sipuleucel-T immunotherapy is known to prolong survival in CRPC. Our results suggest that one potential mechanism of action of this vaccine (and possibly other prostate cancer vaccines) is to reduce the production of soluble B7-H3 by prostate cancer cells, which could lead to improved immune responsiveness of the host immune system. However, the postoperative inflammatory response may abrogate some of this benefit. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e373 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Andrew Chang More articles by this author Smita Nair More articles by this author Daniel George More articles by this author Brant Inman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A Simple Approach to Determine a Curve Fitting Model with a Correct Weighting Function for Calibration Curves in Quantitative Ligand Binding Assays.

In ligand binding assays (LBA), the concentration to response data is a nonlinear relationship driven by the law of mass action. Four parameter logistic (4PL) and five parameter logistic (5PL) curve fitting models are two widely accepted and validated models for LBA calibration curve data. Selection of the appropriate regression model and weighting function are key components of LBA development. Assessment of selected model and weighting function should be performed during assay development and confirmed later during validation. There has been limited published work on practical approaches to determining an appropriate weighting function and selection of a regression model for ligand binding assays. Herein, a structured scheme is presented to determine both. By applying commonly available software, assay performance data were analyzed to determine weighting functions and associated choice of a curve fitting model in three presented case studies. As a result, assay ranges of quantification were improved by reducing lower limit of quantification (from 1.00 to 0.317ng/mL in one case study and from 2.06 to 1.37ng/mL in another) or extending both low and upper limits of quantification(e.g., 1.04 to 48.3ng/mL improved to 0.602 to 145ng/mL). In addition, assay calibration curve performance demonstrated improved assay accuracy (%RE) and precision (%CV). Recommendations on decision flow when determining appropriate weighting function and curve fit model are presented.

Pentachlorophenol dissipation and ferrous iron accumulation in flooded paddy soils with contrasting organic matter contents and incorporation of legume green manures

The effects of different amendment rates (1 and 3%) of Chinese milk vetch (Astragalus sinicus L.) and bird vetch (Vicia cracca L.) on the dissipation of extractable pentachlorophenol (PCP) residues were investigated in two flooded paddy soils with contrasting soil organic matter (SOM) contents. Following incorporation of the legume green manures, whether acetate-extractable ferrous iron [Fe(II)NaOAc] is useful for revealing the reductive dechlorination mechanism of PCP in flooded paddy soils was verified. The kinetic parameters of PCP dissipation and Fe(II)NaOAc accumulation were estimated using logistic curve fitting. Correlation and regression analyses were performed on PCP, Fe(II)NaOAc, water-soluble organic carbon (WSOC), pH, and oxidation-reduction potential data. The kinetic parameters of PCP dissipation and Fe(II)NaOAc accumulation varied significantly with the amendment rate of legume green manure. The changes in pH value and WSOC content varied significantly with the level of SOM and with the amendment rate of legume green manure. At a low amendment rate of green manure, the pH increase and WSOC consumption greatly enhanced Fe(II)NaOAc accumulation and contributed to PCP dissipation. The rate of PCP dissipation decreased with decreasing pH and WSOC accumulation, especially in the high-SOM soil amended with the higher rate of green manure. Legume green manure species had no effect on PCP dissipation. In terms of soil chemistry, Fe(II)NaOAc was found to be the key variable that could explain the mechanisms involved in the reductive dissipation of PCP in flooded paddy soils with contrasting SOM contents and incorporation of legume green manures.

A Novel Lack-of-Fit Assessment as a System Suitability Test for Potency Assays.

Bioassay data analysis is used to determine the potency of protein therapeutics. To properly determine potency, the experimental data need to be fitted to a model that adequately describes the observed dose-response relationship. Typical models include 4-parameter logistic curve fits, 5-parameter logistic curve fits or parallel line analysis. Lack-of-fit assessment can be used as a measure of potency assay system suitability to ensure appropriate closeness of the chosen model fit to the experimental data. We present a novel lack-of-fit approach that overcomes the shortcomings of previously described lack-of-fit tests, such as the conventional analysis of variance (ANOVA) F-test and the lack-of-fit sum of squares test. Simulation studies and examples are used to assess the performance of the new lack-of-fit test. The results show that the described lack-of-fit approach can effectively reject poorly fitted data while retaining well-fitted data, and has advantages in potency assay applications where instrument-to-instrument variability in absolute readout is expected.LAY ABSTRACT: Potency assays are analytical procedures used for characterization as well as release and stability analysis in drug development and for approved products. Dose-response data generated from a drug sample and a well-characterized reference standard are evaluated to determine the potency of the drug sample relative to the reference standard. In order to obtain a potency determination, dose-response data need to be fitted to a proper model that adequately describes the observed dose-response relationship. There are different options described to assess the goodness-of-fit of the data. One approach is the goodness-of-fit assessment based on F-test. This approach compares the lack-of-fit error (representing the discrepancy between observed data and fitted curve) to the pure error (representing the random noise between replicate measurement) to determine if the observed lack-of-fit error can be attributed to random noise. A limitation of goodness of fit assessments via F-test lies in its propensity to penalize precise data (small lack-of-fit error can be considered significantly high if the assay has exceptionally low pure error) and accept undesirable noisy data (large undesirable lack-of-fit error can be considered insignificant due to large pure error). An alternative approach based on lack-of-fit sum of squares is only applicable to certain types of assays where the magnitude of measurements is consistent across different instruments given that the lack-of-fit sum of squares will increase when the magnitude of the assay signal measurements increase, even if the relative magnitude of assay data versus fitted curve remains the same. We introduce here a novel approach that overcomes the limitations of F-test and sum of squares-based approaches. This new approach will effectively reject poor data and retain good data, and it is independent of differences in absolute readout across instruments.

The Effects of Rilmenidine and Perindopril on Arousal Blood Pressure during 24 Hour Recordings in SHR.

The surge in arterial pressure during arousal in the waking period is thought to be largely due to activation of the sympathetic nervous system. In this study we compared in SHR the effects of chronic administration of the centrally acting sympatholytic agent rilmenidine with an angiotensin converting enzyme inhibitor perindopril on the rate of rise and power of the surge in mean arterial pressure (MAP) that occurs with arousal associated with the onset of night. Recordings were made using radiotelemetry in 17 adult SHR before and after treatment with rilmenidine (2mg/kg/day), perindopril (1mg/kg/day) or vehicle in the drinking water for 2 weeks. Rilmenidine reduced MAP by 7.2 ± 1.7mmHg while perindopril reduced MAP by 19 ± 3mmHg. Double logistic curve fit analysis showed that the rate and power of increase in systolic pressure during the transition from light to dark was reduced by 50% and 65%, respectively, but had no effect on diastolic pressure. Rilmenidine also reduced blood pressure variability in the autonomic frequency in the active period as assessed by spectral analysis which is consistent with reduction in sympathetic nervous system activity. Perindopril had no effect on the rate or power of the arousal surge in either systolic or diastolic pressure. These results suggest that the arousal induced surge in blood pressure can largely be reduced by an antihypertensive agent that inhibits the sympathetic nervous system and that angiotensin converting enzyme inhibition, while effective in reducing blood pressure, does not alter the rate or power of the surge associated with arousal.

Comparison of two psychometric functions in analyzing 4-AFC detection results using a task-based structured phantom for digital mammography

Introduction Detectability of spiculated and non-spiculated mass models and microcalcifications, in a structured background phantom of acrylic spheres and water, was studied for digital mammography via the four-alternative forced-choice (4-AFC) paradigm. Purpose To compare the threshold diameters for mass and microcalcification detection using two types of psychometric curves applied on the contrast-detail data. Material and methods Ten images of the structured phantom were acquired on 23 digital mammography systems under automatic exposure control. The 4-AFC study was performed with in-house developed software and 5 medical physicists as observers. Percentage correctly detected lesions (PC) was obtained for each target type. Two psychometric curves (Weibull and Logistic functions) were applied to determine the threshold diameters and number of detected targets (at PC = 62.5%). Results Both fitting procedures were successfully applied on all systems. After averaging over 23 systems, the threshold diameters for spiculated and non-spiculated masses and microcalcifications, with the Weibull psychometric curves, were 4.0 ± 0.3 mm (R2 = 0.61 ± 0.08), 4.6 ± 0.7 mm (R2 = 0.51 ± 0.11), and 0.114 ± 0.003 mm (R2 = 0.91 ± 0.03) respectively, and the values of 4.0 ± 0.4 mm (R2 = 0.61 ± 0.08), 4.7 ± 0.6 mm (R2 = 0.50 ± 0.11), and 0.114 ± 0.003 mm (R2 = 0.91 ± 0.03) were obtained with the Logistic function. The numbers of detected targets assessed from the two functions were not different (3–4 spiculated masses, 1–2 non-spiculated masses, and 4 groups of microcalcifications). If the PC values were not completely covering the lower and upper than 62.5%, there will be possibility different results occurred from these two functions. Conclusion Weibull and Logistic curve fits gave similar and reproducible threshold diameters for the structured phantom.

Forensic age prediction for dead or living samples by use of methylation-sensitive high resolution melting.

Age prediction with epigenetic information is now edging closer to practical use in forensic community. Many age-related CpG (AR-CpG) sites have proven useful in predicting age in pyrosequencing or DNA chip analyses. In this study, a wide range methylation status in the ELOVL2 and FHL2 promoter regions were detected with methylation-sensitive high resolution melting (MS-HRM) in a labor-, time-, and cost-effective manner. Non-linear-distributions of methylation status and chronological age were newly fitted to the logistic curve. Notably, these distributions were revealed to be similar in 22 living blood samples and 52 dead blood samples. Therefore, the difference of methylation status between living and dead samples suggested to be ignorable by MS-HRM. Additionally, the information from ELOVL2 and FHL2 were integrated into a logistic curve fitting model to develop a final predictive model through the multivariate linear regression of logit-linked methylation rates and chronological age with adjusted R(2)=0.83. Mean absolute deviation (MAD) was 7.44 for 74 training set and 7.71 for 30 additional independent test set, indicating that the final predicting model is accurate. This suggests that our MS-HRM-based method has great potential in predicting actual forensic age.

Differential Activity of Brain Derived Neurotrophic Factor (BDNF) and RANKL in Promoting Osteoclast Activity in Multiple Myeloma Patients with or without Bone Disease

Purpose: Brain derived neurotrophic factor (BDNF) which plays an important role in the development of neuronal cells, has a high affinity receptor TrkB and expressed in malignant plasma cells and osteoblasts.Recent reports onage related changes in human serum levels of BDNF drew our attention to further investigate whether soluble BDNF from myeloma cells contributes for the bone related osteolytic activities in MM patients. To answer this question, we analyzed samples from three group of MM patients; (a) bone related early stage, (b) late stage and (c) non-bone related early stage MM (n=10 each).Sample description and assays: Samples were obtained from patients who had given written informed consent and approved by the Institutional Review Board of NYU School of Medicineandserum samples of healthy volunteers were used for control. Multiplex luminex assay was performed to examine serum samples in triplicate (100 μl each) to measure the following analytes: BDNF, RANKL, NGF, FGF, IL-6, MIP-1α, VEGF, DKK1, OPG, and TGF-β. Immuno-profiling was performed using Luminex x-MAP technology (Luminex Corp, Austen Tx) or with Milliplex multi-analyte panels from EMD Millipore (Billerica, MA). Primary plasma cell culture supernatants were also analyzed for BDNF, NGF, FGF, IL-6, MIP-1α, OPG, RANKL and TGF-β. Data collected on a Luminex 200 instrument was further analyzed using xPONENT 3.1 software (Luminex) with 5-parameter logistic curve fitting. All standard curves generated had R2 values calculated at or close to 1 and percent recovery was between 80-120%.Results: More than 90% (9/10)of the serum samples from non-bone related and/or early stage MM patients showed an elevated level of BDNF (1135±7pg/ml) vs. control (217±7pg/ml, >5 fold) in comparison to that in bone related MM (870±12pg/ml). However, the nerve growth factor (NGF) level in the serum was found to be at a minimum detectable level of 30±3pg/ml in non-bone related MM. We observed elevated level of RANKL (305±9pg/ml, >6 fold compared to the control) in late stage bone related MM in contrast to a lesser amount in non-bone related disease (58±2pg/ml). As expected, our findings indicated a decrease in osteoprotegerin (150±9 and 115±11pg/ml) in the serum samples of early and bone related MM respectively. Although several factors were identified to be the cause for an elevated serum BDNF, in this study we asked the question of whether hypoxic conditions could influence the secretion of BDNF in MM cells. To answer this, primary plasma cells from human and mouse were exposed to hypoxia (1% oxygen level) for 24 h and the soluble BDNF measured. We found >2 fold increase in BDNF under hypoxic conditions (1530±2pg/ml) associated with an increase in RANKL (534±9pg/ml) and TGF-β (1300±23pg/ml) in non-bone related human MM. We found an increase in (>67%) differentiating preosteoclasts that are positive for TRAP activity in the presence of an exogenous source of BDNF. This effect was significantly blocked by a neutralizing BDNF antibody and/or RANKL inhibitor.Conclusion: In summary, our data provide evidence for a role of BDNF in MM patients who are presented with non-bone related MM and a risk for progressive MM. Additional experiments conducted to dissect a clear mechanism reveal a potential synergy between BDNF, TrkB and RANKL in promoting osteoclast activities. Overall, our findings provide evidence on the role for BDNF and RANKL that could synergistically interact with proinflammatory cytokines in promoting preosteoclast differentiation at early stages of MM that is not involving the bone. DisclosuresNo relevant conflicts of interest to declare.

Chronic mountain sickness in Chinese Han males who migrated to the Qinghai-Tibetan plateau: application and evaluation of diagnostic criteria for chronic mountain sickness.

BackgroundChronic mountain sickness (CMS), originally characterized by excess hemoglobin (Hb), is currently diagnosed using score-based diagnostic criteria combined with excessive erythrocytosis and clinical symptoms. However, the current criteria have limited applicability. We applied these criteria to 1,029 Chinese Han males migrated to and have been stayed at the Qinghai-Tibet plateau (3,700–5,000 m) for 2–96 months to investigate the prevalence of CMS and its correlations with Hb concentration, altitude, and the length of residence.MethodsSubjects were screened for CMS using the latest approved diagnostic criteria combined with excessive erythrocytosis and clinical symptoms. Hb concentrations were measured, and a cut-off point was determined with k-means clustering. Predisposing factors were evaluated with binary logistic analysis and curve fitting analysis.Results(1) The prevalence of CMS at the Qinghai-Tibetan plateau was 17.8% (183/1029 subjects, with CMS score ≥ 6, and Hb ≥ 210 g/L), which is higher than that previously reported. (2) While individuals were identified into two Hb clusters with a cut-off point of 200 g/L, in the low-Hb cluster (Hb < 200 g/L), the oxygen saturation remained stable as the Hb increased; in the high-Hb cluster (Hb ≥ 200 g/L), the oxygen saturation decreased as the Hb increased. (3) Two critical factors associated with CMS development were residence at an altitude of 4,500 m and a 60-month length of residence.ConclusionsOur presenting scoring system is more sensitive than previous diagnostic criteria and favors early screening and treatment of patients with CMS. Our finding suggests that an adjusted Hb threshold of 200 g/L (instead of 210 g/L) is more adaptable in Han individuals at all altitudes. The weight of Hb level should score ≥ 6 points using the CMS scoring system because of the pathophysiologic role of excessive erythrocytosis in patients with CMS. In addition, our data suggest the importance of early screening of CMS via regular medical examinations within the first 60 months of residence at high altitudes, especially >4500 m.

Assessing filter robustness at drinking water treatment plants

AbstractThis investigation explores the use of five‐parameter logistic curve fitting in quantifying turbidity robustness and risk scoring in clarification and filtrations stages of several surface water treatment works in the Anglian Water region of the United Kingdom. The approach taken reviews different scoring systems and addresses issues of weighting, averages and variability in robustness performance using turbidity robustness indices (TRIs). It also proposes an area‐based risk scoring profile to assess performance [relative area profile for T90 (RAP90)]. The metrics produced are considered to be a logical and rational way to help prioritise where resources for water treatment operation should be deployed.

Cohort Analysis of Incidence/Mortality of Liver Cancer in Japan through Logistic Curve Fitting

Incidence/mortality of liver cancer follow logistic curves because there is a limit reflecting the prevalence of hepatitis virus carriers in the cohort. The author fitted logistic curves to incidence/mortality data covering the nine five-year cohorts born in 1911-1955 of both sexes. Goodness-of-fit of logistic curves was sufficiently precise to be used for future predictions. Younger cohorts born in 1936 or later were predicted to show constant decline in incidence/mortality in the future. The male cohort born in 1931-35 showed an elevated incidence/mortality of liver cancer early in their lives supporting the previous claim that this particular cohort had suffered massive HCV infection due to nation-wide drug abuse in the 1950s. Declining case-fatality observed in younger cohorts suggested improved treatment of liver cancer. This study demonstrated that incidence/mortality of liver cancer follow logistic curves and fitted logistic formulae can be used for future prediction. Given the predicted decline of incidence/mortality in younger cohorts, liver cancer is likely to be lost to history in the not-so-distant future.