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Quantitative Finance Stack Exchange is a question and answer site for finance professionals and academics. After obtaining an accurate estimate of the model parameters I found very large 95% confidence intervals for these estimations if the sample size is about 10-15 years.
A 5-10 years period seems small since a large confidence interval means that there is a large uncertainty about the estimation. Unless it is due to random chance, there seems to be a bias in your estimation method for $\kappa$, and this bias appears to depend on the size of the sample. In practice, though, you will want to use as long a sample as possible over which you can be reasonably sure the underlying DGP has not changed. Not the answer you're looking for?Browse other questions tagged statistics estimation stochastic-volatility simulations or ask your own question.
Is the existence of a sole particle in an hypothetical infinite empty space explicitly forbidden by QM? What is the right way to think about doing lower value work when small talking with an executive? Would allowing a cantrip cast as a bonus action to be used on the same turn as a non-cantrip cast as an action break the game?
OverviewA confidence interval is a measure of estimation that is typically used in quantitative sociological research. Or, the chances are 95 out of 100 that the mean age of the population falls between 23 and 28 years.Confidence levels can be constructed for any level of confidence, however the most commonly used are 90 percent, 95 percent, and 99 percent. PhD Thesis title (Complexity Sciences and Operational Research): Efficient sequential sampling for global optimization in static and dynamic environments. Many optimization problems involve acquiring information about the underlying process to be optimized in order to identify promising solutions.
My research revolves around the topic of response surface based sequential sampling for global optimization of expensive-to-evaluate black-box functions under static and dynamic scenarios. Regarding the former scenario, it addresses the high computational cost inherent to Efficient Global Optimization (EGO), a global search algorithm that is known to work well for expensive black-box optimization problems where only few function evaluations are possible, and which uses surrogate models of the fitness landscape for deciding where to sample next.
For the latter scenario, we propose and compare four methods of incorporating old and recent information in the surrogate models of EGO in order to accelerate the search for the global optima in a dynamically changing environment.
Furthermore, using similar techniques, I explore how to incorporate information coming from models of the same system but with different fidelities. Conference talk: Morales-Enciso, Sergio, Response Surfaces with Discounted Information for Global Optima Tracking in Dynamic Environments. Conference talk: Morales-Enciso, Sergio, Sampling policies for revenue maximization through dynamic pricing under unknown market behaviour. Abstract: [Five due date prediction models are compared in a simulated self-organized manufacturing plant working under the critical ratio dispatching rule.
Abstract: [The current work addresses the use of a genetic algorithm to find a best fit for non measurable parameters in an adaptable crowd movement model. Financial Services Network Annual Conference (FSNet2010): Risk and Behaviour, October 2010.
Exposures of pregnant women to natural and manmade chemicals can lead to negative health effects in the baby, ranging from low birth weight to developmental defects.
Our goal was an initial global assessment of the fetal serum proteome and for the identification of protein biomarkers indicative of toxic in utero exposures related to maternal cigarette smoking. Drawing from a repository of 300 samples, we selected umbilical cord blood sera from 12 babies born to six smokers and six nonsmokers and analyzed both sample pools by tandem mass spectrometry in conjunction with isobaric tags (iTRAQ) for protein quantification.
We identified 203 proteins, 17 of which were differentially expressed between the cigarette smoke–exposed and control populations. This validation study provides an initial view of the proteome of human cord blood sera; it demonstrates the feasibility of identifying therein by use of proteomics, biomarkers of environmental, toxic exposures.
Citation: Colquhoun DR, Goldman LR, Cole RN, Gucek M, Mansharamani M, Witter FR, Apelberg BJ, Halden RU.
This research was supported in part by the Maryland Cigarette Restitution Program Research Grant given to the Johns Hopkins Medical Institutions and by funding from the National Institute for Occupational Safety and Health Education and Research Center for Occupational Safety and Health at the Johns Hopkins Bloomberg School of Public Health (#T42CCT310419). Environmental and occupational exposures of pregnant women may lead to negative health effects ranging from low birth weight to developmental defects in the baby (Buczynska and Tarkowski 2005). Inhaled cigarette smoke is a common and high-quantity environmental exposure involving a complex mixture of multiple toxic substances, including carcinogens and mutagens. Although genetic methods represent a relatively straightforward tool of testing for heritable diseases and susceptibility, protein biomarkers appear particularly well suited for measuring and detecting phenotypic manifestations of exposure and disease. Sample selection and collection. Samples were collected from a subset of all singleton births that occurred from November 2004 to March 2005 at the Johns Hopkins Hospital, Baltimore, Maryland. SDS-PAGE. During all steps, we assessed sample quality and reproducibility by sodium docecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) using 4–12% Tris-HCl gels (Bio-Rad, Hercules, CA). Protein digestion and iTRAQ labeling. Before analysis, two pools were formed by combining the sera of babies born to smokers and those of babies born to nonsmoking mothers. Western hybridization. Five milligrams each of samples were electrophoretically separated on a 4–12% NuPAGE gel.
Figure 1 – Gene ontology (GO) assignments for fetal proteins identified in cord blood sera.
To explore proteomic changes associated with environmental exposures, we conducted additional relative quantification analyses on sera from babies born to smokers and non-smokers.
We identified 17 candidate biomarkers of toxic in utero exposure (Table 2), 14 of which previously had been linked to cigarette smoking as determined in a literature review (Belch et al 1984; Calori et al. Figure 3 – Western blot image confirming iTRAQ observed relative increases in ?-fetoprotein levels in cord blood sera of babies born to maternal smokers versus control subjects. Table 2 – Candidate biomarkers found to be modulated in response to maternal smoking. We identified 17 candidate biomarkers of exposure and effect within the fetal blood serum proteome. Maternal smoking has been associated with low birth weight and other developmental problems, but the underlying mechanisms of these responses are not yet fully understood.
The sample selection in this study was limited by a number of variables, first and foremost the availability of a sufficient quantity of serum for proteomic analysis.
Global screening using the iTRAQ technique also led to the discovery and identification of candidate biomarkers not anticipated or predictable a priori. Overall, our work provides new evidence for important protein expression changes occurring in the fetus in response to maternal smoking. Because these analyses were conducted on pooled samples, interindividual variability may be a source of uncertainty.
When working with low-volume samples, proteomics by necessity can achieve only limited coverage of the blood proteome, which contains thousands of proteins and spans a dynamic range of > 10 orders of magnitude (Anderson and Anderson 2002).
An important yet unanswered question is whether the observed fetal responses to exposures from cigarette smoke constituents are enduring and indicative of deleterious health effects in early childhood and later in life. It has been theorized that a characterization of neonate exposures can lead to an understanding of general health outcomes (Barker et al.
Therefore, the potential exists to expand the applications of high-throughput MS techniques for the comprehensive analysis of environmental exposures, ranging from the characterization of ecotoxicologic effects to the epidemiologic analysis of chemical exposures (Dowling and Sheehan 2006; Sheehan 2007). EHP is now using Editorial Manager for manuscript submissions. All user accounts have been transferred to Editorial Manager—just log into Editorial Manager and reset your password.
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On the other hand, it appears useless to accept a sample size for which the confidence interval is small (50 years) since shorter periods provides good enough estimates.
It is an estimated range of values that is likely to include the population parameter being calculated. Moreover, in some cases obtaining this information can be expensive, which calls for a method capable of predicting promising solutions so that the global optimum can be found with as few function evaluations as possible. The proposed variant is based on partitioning the space and building local models to accelerate the selection of future sampling locations with a minimal impact on the optimization performance. As we demonstrate, exploiting old information as much as possible significantly improves the tracking behavior of the algorithm.
This is useful when dealing with expensive but very accurate simulations, and cheap but less accurate ones. Tracking global optima in dynamic environments with efficient global optimization (Submitted). The problem of generating training data from an uninformed state when using a due date dependent dispatching rule is approached by using due date setting methods not requiring any prior information of the system. The parameters must be inferred from high resolution data obtained from experiments aiming to track human movement in real non panic generic situations. The differences follow a normal distribution (as what are shown in the results of the normality test in the following SAS outputs), thus the paired t test can be used. Statistical inference and experimental design of univariate quantitative data of single-group design (part two). In some cases, diseases were postulated to have their basis in toxic exposure in utero or in early childhood. Most of the identified candidate biomarkers were biologically plausible, thereby underscoring the feasibility of screening neonates with global proteomic techniques for biomarkers of exposure and early biological effects triggered by in utero chemical exposures. Halden, Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, 1001 S.
Development of the proteomic techniques was supported in part by the National Institute of Environmental Health Sciences grant 1R01ES015445. In some cases, long-term effects, such as diabetes and chronic heart disease, are postulated to have their basis in fetal and early childhood exposure and development (Barker et al. For epidemiologic studies and clinical applications, proteomic mining strategies for biomarker discovery have focused on blood serum and plasma, because this compartment is relatively accessible and potentially provides a host of diagnostic information (Lathrop et al. Our goal was to screen neonates for candidate biomarkers indicative of early biological responses to toxic exposures from smoke constituents in utero.
This study required the collection of specimens that otherwise would have been discarded, and used information from medical records that was available to hospital personnel. Self-reported nonsmokers with cotinine levels above the limit of detection were excluded from this study.

Pooled samples were prepared in duplicate, thereby producing a total of 4 samples (2 + 2), each containing approximately 100 ?g of protein (smoker pool and nonsmoker pool). Representatives of both groups were very similar with regard to maternal gravida, age, education, marital status, and infants’ Apgar scores at 1 and 5 min.
Candidate biomarkers were identified at the ? 99% confidence level using at least two peptides. Most of these were not only biologically plausible but also confirmed by prior reports on exposure-related changes in their expression levels (Table 2).
Observed changes in ?-fetoprotein levels may be interpreted as evidence for impaired fetal growth and maturation, both known to be associated with maternal smoking (Beratis et al.
African Americans were selected as the study group because they represented nearly 70% of the population sample.
The latter include the measured reduction of adiponectin levels in the pool of babies born to smoking mothers. A fairly large increase or decrease would be required for any one individual level to affect the mean for the pool of six individuals. Thus, the total spectrum of proteins contained in human blood certainly is much larger than what is reported here. Levels of proteins also may be scrutinized on a person-by-person basis to help understand variability among individuals. Prospective cohort studies could provide answers and help to further define the value of the umbilical cord blood serum proteome as a diagnostic window into human physiology and pathology. Given the positive experiences gained from this study, we posit that the potential for global screening for protein expression differences in cord blood repositories may aid in the investigation of infant health outcomes associated with in utero exposures to environmental toxicants.
Conclusions and opinions are those of the individual authors and advertisers only and do not reflect the policies or views of the NIEHS. For instance, instead of estimating the mean age of a certain population to be a single value like 25.5 years, we could say that the mean age is somewhere between 23 and 28. For instance, when we used a 95 percent confidence level, our confidence interval was 23 – 28 years of age.
Another kind of optimization problem arises when dealing with objective functions that change over time, which requires tracking of the global optima over time. The linear computational complexity as a function of the number of observations of this extension is shown, and its performance benchmarked to both the original algorithm it extends, and state of the art algorithms.
Several replicas of the numerical experiments are performed and the results obtained are tested for statistical significance. The methodology proposed provides the means to create real size models of complete systems based on small scale experiments.
Xiao-lei Bao (Consulting Center of Biomedical Statistics, Academy of Military Medical Sciences, Beijing 100850, China ) 3.
Also, this article gives typical examples in the field of medical research as well as solutions, SAS programs, explanations and results. For example, when the two records of each pair are from the same subject before and after treatment or from two symmetric parts of one subject. Invoke the TTEST procedure to perform the t test, which, unfortunately, is not able to perform the normality test (In this case, we assume that the differences follow a normal distribution). Global Screening of Human Cord Blood Proteomes for Biomarkers of Toxic Exposure and Effect. Once obtained, an initial “snapshot” of proteins expressed in umbilical cord blood serum may serve as the starting point for developing low-cost assays for biomarkers of exposure and disease in this easily accessible and presumably information rich biofluid. Use of the GOSt tool (Gene Group Functional Profiling 2008) resulted in the assignment of none, a single, or multiple molecular functions and biological processes for each protein examined. As might be expected, infants born to smokers were on average smaller and had shorter gestational age (see footnote in Table 1 for statistical information).
Quantitative values were converted to log values and the 95% confidence interval was calculated using pairwise comparisons between controls and smokers.
Because sample volume was insufficient, data for the smoke-exposed individual 7 are missing. Detection of this relatively small number of modulated proteins (17 of 203 total; ~ 8%) demonstrates that the chosen methodology was sufficiently discriminatory and stringent.
This is intriguing because adiponectin has been implicated in metabolic syndrome in adults (Tajtakova et al. The utility of this proteome-wide approach to exploring environmental exposures is that a broad screen in tandem with quantitative analysis can reveal a broader picture of the overall exposure effects than using traditional, targeted methods; however, validation and confirmation remain critical steps in this experimental pathway. Limitations are expected to arise from using low-volume samples and blood serum as opposed to plasma. Such research could evaluate effects of confounders that were selected out of our study but which may be important for capturing the full range of protein expression. Furthermore, recently developed high-throughput protein biomarker screening methods, such as multiple reaction monitoring, could be applied to a broader cohort of samples for a further validation of the observed biological changes (Sandhu et al.
Using a well-characterized, high-magnitude exposure, differences in protein abundances related to that exposure were measured. Selected trace elements and proteins in serum of apparently healthy newborn infants of mothers who smoked during pregnancy. Annual smoking-attributable mortality, years of potential life lost, and productivity losses–United States, 1997–2001.
The effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in habitual smokers.
The effect of cigarette-smoking on cardiovascular risk factors: a study of monozygotic twins discordant for smoking. IgG subclasses in foetal cord and maternal serum: associations with infections in infancy and smoking in pregnancy. Cigarette smoking and serum lipid and lipoprotein concentrations: An analysis of published data. Serum apolipoprotein levels in relation to acute myocardial infarction and its risk factors. Technical, experimental, and biological variations in isobaric tags for relative and absolute quantitation (iTRAQ). Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. The effect of cigarette smoking during pregnancy on cord blood lipid, lipoprotein and apolipoprotein levels.
Characterization of the third component of complement (C3) after activation by cigarette smoke. Compilation of a MALDI-TOF mass spectral database for the rapid screening and characterisation of bacteria implicated in human infectious diseases. Plasma adiponectin is related to other cardiovascular risk factors in nondiabetic Korean men with CAD, independent of adiposity and cigarette smoking: cross-sectional analysis.
Comparison of alternative analytical techniques for the characterisation of the human serum proteome in HUPO. Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy. The composition of cigarette smoke: a retrospective, with emphasis on poly-cyclic components.
Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents.
Evaluation of data-dependent versus targeted shotgun proteomic approaches for monitoring transcription factor expression in breast cancer. The potential of proteomics for providing new insights into environmental impacts on human health. Evaluation of reproducibility of protein identification results after multidimensional human serum protein separation.
Changes of apolipoprotein A-IV in the human neonate: Evidence for different inductions of apolipoproteins A-IV and A-I in the postpartum period. The Baltimore THREE Study—Tracking Health Related to Environmental Exposures [accessed 6 November 2008].
Increased levels and positive correlation between erythropoietin and hemoglobin concentrations in newborn children of mothers who are smokers. Integrated pipeline for mass spectrometry-based discovery and confirmation of biomarkers demonstrated in a mouse model of breast cancer. If we use a 90 percent confidence level to calculate the confidence level for the mean age of our population, our confidence interval might be 25 – 26 years of age. However, tracking usually has to be quick, which excludes re-optimization from scratch every time the problem changes. The mathematical description of the model is provided as well as the fundamental guidelines for its practical implementation. The statement input is used to specify the observed variables x1 and x2, and the variable d is the difference between x1 and x2. Statistical inference and experimental design of univariate qualitative data of single-group design. To that end, cord blood is a readily accessible biofluid whose proteomic makeup remains mostly unexplored when compared with that of adults. Therefore, an understanding of fetal responses to environmental exposures is of increasing importance. Mass spectrometry (MS) is at the forefront of proteomic technologies for the global analysis of complex specimens such as human serum, which displays a high and thus challenging dynamic range with respect to protein abundance (Aebersold and Mann 2003; Anderson and Anderson 2002). Duplicate composite samples of exposed and controls were subjected to iTRAQ labeling to produce technical replicates.
We conducted MS using an Applied Biosystems Q-Star Pulsar with a spray voltage of 2.2 kV (Applied Biosystems, Foster City, CA). Protein coverage ranged from 84% for vitamin D–binding protein to 9.6% for immunoglobulin (Ig) heavy chainV-I region Mot. As a result of the aforementioned selection criteria, this study is not necessarily representative of a more diverse and heterogeneous population.
Sample pooling is an accepted approach in proteomics; its benefits and limitations have been discussed elsewhere (Karp et al.

Serum contains relatively fewer proteins but it is customarily collected and therefore more readily available. This validation study yielded some interesting initial information on the composition of the human umbilical cord blood serum proteome and subsequent global measures of exposure effects upon that proteome. Atlanta, GA:Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Department of Health and Human Services. The likelihood that our confidence interval will contain the population parameter is called the confidence level. Instead, it is important to make good use of the history of the search even after the environment has changed. For example, selecting two animals with similar conditions from the same litter or choosing twin siblings as a pair, and giving them different medicine or treatment. All experimental protocols were approved by the Johns Hopkins Medicine Institutional Review Board (IRB) before sample collection under IRB approval number 04-04-22-02.
A 100-?L sample was applied onto a ProteoPrep Top 20 protein immunoaffinity column (Sigma), which had previously been washed and equilibrated using PBS.
Blots were then washed three times (15 min each) in TBS-Tween, incubated with 1:5,000 dilution of horseradish peroxidase-conjugated goat anti-mouse or goat anti-rabbit antibodies (Pierce, Rockford, IL), and washed three times in TBS-Tween for 15 min each. 1994) have all been postulated as potential mechanisms for the effects of smoking-related health defects. In the past, its presence in cord blood has been associated with decreased fetal growth, a known consequence of maternal smoking (Beratis et al. Further studies of broader sample groups are required to determine whether the responses observed here can be generalized to other populations. The biological role and mechanism of this and other incompletely understood proteins warrants further investigation. To capture low-abundance proteins such as interleukins, current methods require a large starting volume and extensive prefractionation for removal of more abundant proteins. By leveraging MS technology, we demonstrated that the effects of environmental exposures at the protein level may be examined in previously unforeseen ways, giving the potential to address important biological issues from a systemwide viewpoint. For example, how confident are we that our confidence interval of 23 – 28 years of age contains the mean age of our population? Statistical inference and experimental design of univariate quantitative data of paired design.
However, because we are often most interested in effects of labile stressors at earlier stages in pregnancy (during organogenesis), the temporal aspect of toxic assault may best be dealt with by identifying biomarkers of effect that can indicate enduring biological changes that suggest both historical exposures throughout gestation and potential future adverse health outcomes.
2004), as are the health effects in neonates of mothers who smoke during pregnancy (Beratis et al. A total of 341 samples were collected, of which 300 met information and volume criteria for the larger study. Samples were incubated at room temperature for approximately 30 min, and then centrifuged at 2,000 ? g for 30 sec to elute the depleted proteins. Proteins were visualized by enhanced chemiluminescence (ECL) and exposure to Hyperfilm MP (Amersham Biosciences, Piscataway, NJ). Our data suggest that babies exposed to cigarette smoke in utero exhibit some individual protein expression patterns similar to those previously observed in adult smoke-exposed subjects and animal models. However, the strict selection criteria in this study allowed for the identification of a number of proteins whose expression is changed in response to cigarette smoke exposure. Sample pooling can address this need when working with low-volume samples, such as umbilical cord blood serum.
Because this method has been posited not to require abundant sample preparation, a prospective cohort could be rapidly assayed for the absolute presence of these biomarkers.
If this range of ages was calculated with a 95 percent confidence level, we could say that we are 95 percent confident that the mean age of our population is between 23 and 28 years.
Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) reagents (Ross et al.
Human umbilical cord serum samples were collected immediately after birth using the Witter cord cradle (Witter et al. 1993) to determine log confidence scores for protein identification and to generate iTRAQ ratios (Applied Biosystems 2006).
We measured quantitative data using ImageQuant (GE Healthcare, Piscataway, NJ) using digital images of scanned films. Because higher-order cellular processes are more varied, many proteins were assigned multiple potential biological roles in multiple processes (Figure 1B). Relative abundance of proteins in serum from babies born to maternal smokers compared with maternal nonsmokers ranged from 77% increases (hemoglobin gamma-1 subunit) to 36% decreases (complement C4-B).
Lower levels of apoliprotein A-I found among infants of smoking mothers may indicate altered lipid metabolism (Iscan et al. Furthermore, this analytical strategy may open novel avenues of investigation by generating physiologic hypotheses that later could be tested using immunoassays and other classical biochemical techniques. However, if neither of the two treatments is blank and the observed quantitative index is largely influenced by heredity factors, it is apparent that the self-paired design is not preferred, and the twin-paired design is better than the paired design of subjects with similar conditions. Survival time of advanced gastric cancer patients treated with integrated traditional Chinese and Western medicine therapy[J] J Chin Integr Med, 2010, 8(2) : 116-120.
Statistical expression and description of univariate quantitative data of single-group design (part one). 2004) make it possible to quantitatively screen the entire proteome within the detectable dynamic range for qualitative and quantitative differences in protein expression between individuals and groups differing in exposure history, health status and disease. Bound proteins (the “top 20 proteins,” not used in this study) were eluted per the manufacturer’s directions to recharge the columns.
We validated the iTRAQ labeling by searching the data against the Swiss-Prot database using Mascot selecting iTRAQ modification as a variable modification.
The pixel intensity of each individual band was determined and corrected using the gelsolin intensity for the same sample; the sum of smoker band intensities was compared with the sum of nonsmoker band intensities. Some changes were relatively small yet statistically significant, such as those observed for antithrombin-III (13% decrease) and complement C1r subcomponent (17% decrease). The paired design of subjects with similar conditions should be used only when all important non-experimental factors that have a large influence on the observed quantitative index are matched. Serum samples were centrifuged at 1,000 ? g for 15 min in a bench top centrifuge (Fisher Scientific, Palo Alto, CA). All proteins identified in our analyses were shared among babies born to smokers and nonsmokers; in other words, none of the detected proteins were unique to either study group. The observed differential levels of hemoglobin subunits may well be related to a previously described relationship between smoking and higher hemoglobin levels both in adults and in cord blood of infants of smoking mothers (D’Souza et al. Otherwise, it is not recommended to use the paired design of subjects with similar conditions.
Statistical expression and description of univariate quantitative data of single-group design (part two).
2005), the at-risk population of about 420,000 newborn infants each year is relatively high in the United States and, of course, much higher globally. We determined protein concentrations at each step using the bicinchoninic acid (BCA) assay (Pierce Biotechnology, Rockford, IL) to assess protein depletions. This is not surprising because these proteins have major structural and functional roles in human serum. In other words, if we collect a large amount of samples (say, 500) from the population of interest, 95 times out of 100, the true population mean would be included within our computed interval. Documented negative impacts on the fetus resulting from maternal cigarette smoking include preterm delivery and shortened gestation, fetal growth restriction and low birth weight, and sudden infant death syndrome (Department of Health and Human Services 2004). We assayed success of depletion (~ 98%) of major proteins by visualizing less abundant ones on silver-stained gels (data not shown).
Statistical inference and experimental design of univariate quantitative data of single-group design (part one). Other less well established adverse effects include later increased risk of type II diabetes, obesity, asthma, and impaired cognitive development (DiFranza et al. Pairwise comparisons of the technical replicates resulted in the exclusion of statistically significant changes observed in only one technical replicate.
Five times out of 100, the true population mean will not be included in our specified interval. The calculated p-values were exported into Q-value, and a false positive rate was estimated following the program’s instructions (Storey and Tibshirani 2003). Statistical inference and experimental design of univariate qualitative data of paired design. Proteins matching cytokeratin were removed from the analysis because they were identified as laboratory contaminants based upon iTRAQ quantitative ratios.
Alterations in Ig “C” chains are consistent with earlier reports that infants of smoking mothers have higher levels of IgG (Cervi and Feighery 1991). In addition, we abstracted data from medical charts of mothers and infants relevant to smoking, birth outcomes, and health problems during pregnancy, labor, and delivery (Table 1). Additionally detected were several indicators of altered lipid metabolism, specifically adiponectin (Kim et al.
Whereas cotinine in umbilical cord blood is a useful indicator for exposure to maternal active and passive smoking (Pichini et al. Additionally, Western hybridization of samples with monoclonal antibodies confirmed the qualitative and quantitative results of the iTRAQ measurements, and also produced evidence for significant inter-individual variability in fetal protein expression (Figure 3).
Interestingly, although apolipoprotein A-I was reportedly decreased in cord blood of infants of smokers in a prior study, it was found to be up-regulated here.
General issues and precautions in the design for clinical trials of investigational new drugs.

## Comments Confidence interval for quantitative data

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