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Prolactin (PRL) data from adolescents treated with olanzapine are presented.
Data from 454 adolescents (13-18, mean=15.9 yrs) with schizophrenia or bipolar mania were pooled from 4 olanzapine (2.5-20.0mg/day) studies (4-32 weeks; 2 double-blind, placebo-controlled studies [combined for acute phase endpoint PRL levels] with open-label extensions; 2 open-label studies). Age- and sex-specific Covance reference ranges defined normal PRL; categorical increases were based on multiples of the upper limit of normal (ULN). Baseline-to-endpoint PRL changes in adolescents were compared with data pooled from 84 olanzapine clinical trials in adults with schizophrenia or bipolar disorder.
Olanzapine-treated adolescents had mean PRL increases at both the acute (11.4μg/L) and open-label endpoints (4.7μg/L). Of those patients with normal PRL levels at baseline (N=311), high PRL occurred in 54.7% at anytime; 32.2% at endpoint. The percentage of patients in which PRL levels shifted from normal-to-abnormal was smaller at endpoint than at anytime during treatment; 26.7% shifted to a higher category. Among patients with normal baseline PRL, 32.7% remained <=1X ULN; 32.3% increased to 1¬<=2X; 6.0%, >2-<=3X; and 1.2%, >3X at anytime; 4.6% had at >=1 potentially PRL-related adverse event. Adolescents had significantly higher mean changes at endpoint (p=.004), and a greater incidence of high PRL levels at anytime during olanzapine treatment (p<.001) versus adults.
Incidence of high PRL was significantly higher, and mean increases in PRL were significantly greater in adolescents versus adults. Mean increases and high PRL incidence were lower at the open-label compared with the acute phase endpoint.
The changes in metabolic parameters in olanzapine-treated adolescents were examined.
Data from 454 adolescents (13–18, mean=15.9 years) with schizophrenia or bipolar I disorder were pooled from 4 olanzapine (2.5–20.0mg/day) studies (4–32 weeks). Changes in metabolic parameters in adolescents were compared with those of olanzapine-treated adults (pooled from 84 clinical trials); changes in weight and BMI were compared with US age- and sex-adjusted standardized growth curves.
Olanzapine-treated adolescents had significant increases from baseline-to-endpoint in fasting glucose (p=.021); total cholesterol, LDL, and triglycerides (p<.001); and significant decreases in HDL (p<.001). Significantly more adolescents gained >=7% of their baseline weight versus adults (65.1% vs. 35.6%, p<.001); mean change from baseline-to-endpoint in weight was significantly greater in adolescents (7.0 vs. 3.3kg, p<.001). Adolescents had significantly lower mean changes from baseline-to-endpoint in fasting glucose (0.3 vs. 0.1mmol/L, p=.002) and triglycerides (0.3 vs. 0.2mmol/L, p=.007) versus adults. Significantly more adults experienced treatment-emergent normal-to-high changes at anytime in fasting glucose (4.8% vs. 1.2%, p=.033), total cholesterol (6.9% vs. 1.1%, p=.001), LDL (5.8% vs. 1.5%, p=.014), and triglycerides (25.7% vs. 17.4%, p=.030). Compared with standardized growth curves, olanzapine-treated adolescents had greater increases from baseline-to-endpoint in weight (1.0 vs. 7.1kg, p<.001), height (0.5 vs. 0.7cm, p<.001), and BMI (0.2 vs. 2.2kg/m2, p<.001).
Olanzapine-treated adolescents may gain significantly more weight compared with adults, but may have smaller changes in other metabolic parameters. Clinicians may want to consider both efficacy and changes in metabolic parameters when selecting treatment options for individual adolescent patients.
The aim of this study was to evaluate the effects of alternative protocols to improve oocyte selection, embryo activation and genomic reprogramming on in vitro development of porcine embryos cloned by somatic cell nuclear transfer (SCNT). In Experiment 1, in vitro-matured oocytes were selected by exposure to a hyperosmotic sucrose solution prior to micromanipulation. In Experiment 2, an alternative chemical activation protocol using a zinc chelator as an adjuvant (ionomycin + N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) + N-6-dimethylaminopurine (6-DMAP)) was compared with a standard protocol (ionomycin + 6-DMAP) for the activation of porcine oocytes or SCNT embryos. In Experiment 3, presumptive cloned zygotes were incubated after chemical activation in a histone deacetylase inhibitor (Scriptaid) for 15 h, with the evaluation of embryo yield and total cell number in day 7 blastocysts. In Experiment 1, cleavage rates tended to be higher in sucrose-treated oocytes than controls (123/199, 61.8% vs. 119/222, 53.6%, respectively); however, blastocyst rates were similar between groups. In Experiment 2, cleavage rates were higher in zygotes treated with TPEN than controls but no difference in blastocyst rates between groups occurred. For Experiment 3, the exposure to Scriptaid did not improve embryo development after cloning. Nevertheless, the total number of cells was higher in cloned zygotes treated with Scriptaid than SCNT controls. In conclusion, oocyte selection by sucrose as well as treatments with zinc chelator and an inhibitor of histone deacetylases did not significantly improve blastocyst yield in cloned and parthenotes. However, the histone deacetylases inhibitor produced a significant improvement in the blastocyst quality.
The long-term effects of pediatric concussion on white matter microstructure are poorly understood. This study investigated long-term changes in white matter diffusion properties of the corpus callosum in youth several years after concussion.
Participants were 8–19 years old with a history of concussion (n = 36) or orthopedic injury (OI) (n = 21). Mean time since injury for the sample was 2.6 years (SD = 1.6). Participants underwent diffusion magnetic resonance imaging, completed cognitive testing, and rated their post-concussion symptoms. Measures of diffusivity (fractional anisotropy, mean, axial, and radial diffusivity) were extracted from white matter tracts in the genu, body, and splenium regions of the corpus callosum. The genu and splenium tracts were further subdivided into 21 equally spaced regions along the tract and diffusion values were extracted from each of these smaller regions.
White matter tracts in the genu, body, and splenium did not differ in diffusivity properties between youth with a history of concussion and those with a history of OI. No significant group differences were found in subdivisions of the genu and splenium after correcting for multiple comparisons. Diffusion metrics did not significantly correlate with symptom reports or cognitive performance.
These findings suggest that at approximately 2.5 years post-injury, youth with prior concussion do not have differences in their corpus callosum microstructure compared to youth with OI. Although these results are promising from the perspective of long-term recovery, further research utilizing longitudinal study designs is needed to confirm the long-term effects of pediatric concussion on white matter microstructure.
Early irritability predicts a broad spectrum of psychopathology spanning both internalizing and externalizing disorders, rather than any particular disorder or group of disorders (i.e. multifinality). Very few studies, however, have examined the developmental mechanisms by which it leads to such phenotypically diverse outcomes. We examined whether variation in the diurnal pattern of cortisol moderates developmental pathways between preschool irritability and the subsequent emergence of internalizing and externalizing symptoms 9 years later.
When children were 3 years old, mothers were interviewed about children's irritability and completed questionnaires about their children's psychopathology. Six years later, children collected saliva samples at wake-up and bedtime on three consecutive days. Diurnal cortisol patterns were modeled as latent difference scores between evening and morning samples. When children were approximately 12 years old, mothers again completed questionnaires about their children's psychopathology.
Among children with higher levels of irritability at age 3, a steeper diurnal cortisol slope at age 9 predicted greater internalizing symptoms and irritability at age 12, whereas a blunted slope at age 9 predicted greater externalizing symptoms at age 12, adjusting for baseline and concurrent symptoms.
Our results suggest that variation in stress system functioning can predict and differentiate developmental trajectories of early irritability that are relatively more internalizing v. those in which externalizing symptoms dominate in pre-adolescence.
Recent European studies suggest that fathers’ leave-taking may contribute to parental relationship stability. Paternity leave-taking may signal a commitment by fathers toward a greater investment in family life, which may reduce the burden on mothers and strengthen parental relationships. This study uses longitudinal data from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) to analyze the association between paternity leave-taking and relationship stability in the United States. Results indicate that paternity leave-taking, and taking relatively short leaves (i.e. two weeks or less) in particular, is associated with greater relationship stability. These findings increase our understanding of the potential benefits of paternity leave, and can inform policy decisions that aim to increase family stability.
Sugarbeet growers only recently have combined ethofumesate, S-metolachlor, and dimethenamid-P in a weed control system for waterhemp control. Sugarbeet plant density, visible stature reduction, root yield, percent sucrose content, and recoverable sucrose were measured in field experiments at five environments between 2014 and 2016. Sugarbeet stand density and stature reduction occurred in some but not all environments. Stand density was reduced with PRE application of S-metolachlor at 1.60 kg ai ha–1 and S-metolachlor at 0.80 kg ha–1 + ethofumesate at 1.68 kg ai ha–1 alone or followed by POST applications of dimethenamid-P at 0.95 kg ai ha–1. Sugarbeet visible stature was reduced when dimethenamid-P followed PRE treatments. Stature reduction was greatest with ethofumesate at 1.68 or 4.37 kg ha–1 PRE and S-metolachlor at 0.80 kg ha–1 + ethofumesate at 1.68 kg ha–1 PRE followed by dimethenamid-P at 0.95 kg ha–1 POST. Stature reduction ranged from 0 to 32% 10 d after treatment (DAT), but sugarbeet recovered quickly and visible injury was negligible 23 DAT. Although root yield and recoverable sucrose were similar across herbicide treatments and environments, we caution against the use of S-metolachlor at 0.80 kg ha–1 + ethofumesate at 1.68 kg ai ha–1 PRE followed by dimethenamid-P at 0.95 kg ha–1 in sugarbeet.
OBJECTIVES/SPECIFIC AIMS: To evaluate the ability of various techniques to track changes in body fluid volumes before and after a rapid infusion of saline. METHODS/STUDY POPULATION: Eight healthy participants (5M; 3F) completed baseline measurements of 1) total body water using ethanol dilution and bioelectrical impedance analysis (BIA) and 2) blood volume, plasma volume and red blood cell (RBC) volume using carbon monoxide rebreathe technique and I-131 albumin dilution. Subsequently, 30mL saline/kg body weight was administered intravenously over 20 minutes after which BIA and ethanol dilution were repeated. RESULTS/ANTICIPATED RESULTS: On average, 2.29±0.35 L saline was infused with an average increase in net fluid input-output (I/O) of 1.56±0.29 L. BIA underestimated measured I/O by −3.4±7.9%, while ethanol dilution did not demonstrate a measurable change in total body water. Carbon monoxide rebreathe differed from I-131 albumin dilution measurements of blood, plasma and RBC volumes by +0.6±2.8%, −5.4±3.6%, and +11.0±4.7%, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: BIA is capable of tracking modest changes in total body water. Carbon monoxide rebreathe appears to be a viable alternative for the I-131 albumin dilution technique to determine blood volume. Together, these two techniques may be useful in monitoring fluid status in patients with impaired fluid regulation.
In this article, we describe the results of the second phase of a randomized controlled trial of Minding the Baby (MTB), an interdisciplinary reflective parenting intervention for infants and their families. Young first-time mothers living in underserved, poor, urban communities received intensive home visiting services from a nurse and social worker team for 27 months, from pregnancy to the child's second birthday. Results indicate that MTB mothers' levels of reflective functioning was more likely to increase over the course of the intervention than were those of control group mothers. Likewise, infants in the MTB group were significantly more likely to be securely attached, and significantly less likely to be disorganized, than infants in the control group. We discuss our findings in terms of their contribution to understanding the impacts and import of intensive intervention with vulnerable families during the earliest stages of parenthood in preventing the intergenerational transmission of disrupted relationships and insecure attachment.
OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.
The aim of this study was to determine the feasibility and efficacy of a culturally tailored lifestyle intervention, ¡Vivir Mi Vida! (Live My Life!). This intervention was designed to improve the health and well-being of high risk late middle-aged Latino adults and to be implemented in a rural primary care system.
Rural-dwelling Latino adults experience higher rates of chronic disease compared with their urban counterparts, a disparity exacerbated by limited access to healthcare services. Very few lifestyle interventions exist that are both culturally sensitive and compatible for delivery within a non-metropolitan primary care context.
Participants were 37 Latino, Spanish-speaking adults aged 50–64-years-old, recruited from a rural health clinic in the Antelope Valley of California. ¡Vivir Mi Vida! was delivered by a community health worker-occupational therapy team over a 16-week period. Subjective health, lifestyle factors, and cardiometabolic measures were collected pre- and post-intervention. Follow-up interviews and focus groups were held to collect information related to the subjective experiences of key stakeholders and participants.
Participants demonstrated improvements in systolic blood pressure, sodium and saturated fat intake, and numerous patient-centered outcomes ranging from increased well-being to reduced stress. Although participants were extremely satisfied with the program, stakeholders identified a number of implementation challenges. The findings suggest that a tailored lifestyle intervention led by community health workers and occupational therapists is feasible to implement in a primary care setting and can improve health outcomes in rural-dwelling, late middle-aged Latinos.
While state legislative rollbacks of public-sector workers’ collective bargaining rights in Wisconsin and other US states in 2011 appeared to signal an unprecedented wave of hostility toward the public sector, such episodes have a long history. Drawing on recent work on “governance repertoires,” this article compares antistate initiatives in Wisconsin in 2011 to two previous periods of conflict over the size and shape of government: the 1930s and the 1970s. We find that while small government advocates in all three periods used similar language and emphasized comparable themes, the outcomes of their advocacy were different due to the distinct historical moments in which they unfolded and the way local initiatives were linked to political projects at the national level. We explore the relationship of local versions of small government activism to their national-level counterparts in each period to show how national-level movements and the ideological, social, and material resources they provided shaped governance repertoires in Wisconsin. We argue that the three moments of conflict over the size of government are deeply intertwined with the prehistory, emergence, and rise to dominance of neoliberal political rationality and can provide insight into how that new “governance repertoire” was experienced and built at the local level.
Correspondence analysis provides a way to summarize categorical data in a reduced number of dimensions (Clausen, 1998; Greenacre, 2007). In that sense, it is very similar to principal components analysis. Principal components is an asymmetrical analysis. We use the correlations (or covariances) between the variables as a summary of the structure in the data. The principal components represent a way of describing the correlation matrix in fewer components than variables. The analysis is asymmetrical because we focus on the relationships between variables and use the principal components to compute scores for each of the observations in the new, reduced space.
In correspondence analysis, the data usually consist of counts of different kinds of things. They could be different artifact types from a variety of sites, strata, or features or they could be different elements in the composition of artifacts. Correspondence analysis is a symmetrical analysis because we adjust the data matrix by both the rows (observations) and the columns (variables) before conducting the analysis. As a result, we can project the observations into the space defined by the variables (as with principal components) or the variables into the space defined by the observations. We can also create biplots summarizing both views.
The adjustment of the data matrix is simply a modification of the Chi-square test that we covered in Chapter 9. In the Chi-square test we compute an expected value for a particular cell by multiplying the row sum by the column sum and dividing by the total sum. The difference between the observed and expected values is squared and divided by the expected value to get the Chi-square contribution for that cell. The sum of all the Chi-square contributions is the total Chi-square value that we use to see if the observed counts are significantly different from what we would expect by chance.
To perform a correspondence analysis, we modify that procedure slightly. First, we divide every value in the table by the sum of all the entries so that each cell represents the proportion of the total found in that cell. Then we compute the expected proportions using the row and column sums of the table of proportions.
Raw data comes in many sizes and shapes and occasionally they are the wrong sizes and shapes for what we want to do with them. In those situations, it can be useful to transform them before analysis. Transforming data is often useful to balance a non-symmetric distribution or to pull in outlying observations to reduce their influence in the analysis. Transformations can be applied down columns (e.g., standard scores to weight each variable equally) or across rows (e.g., percentages to weight each assemblage equally). In general, there are four data problems that can sometimes be resolved with transformations.
First, transformations can help to produce a distribution that is closer to a normal distribution, making it possible to use parametric statistical methods (such as t-tests). In this case, we are looking at the raw data distribution and using an order-preserving transformation that makes the data more symmetrical. The alternative to transforming the data is to use nonparametric tests that do not require a normal distribution or robust statistical methods that are not as influenced by extremely large or small values.
Second, transformations can make it possible to use simple linear regression to fit nonlinear relationships between two variables. Transforming one or both variables makes the relationship between them linear. The drawback with this approach is that the errors are transformed as well so that additive errors become multiplicative errors when using a log transform. The alternative to transformation is to use nonlinear regression.
Third, transformations can be used to weight variables equally so that differences in measurement scales or variance do not give some variables more influence than others in the analysis. This is particularly important when we are using the concept of “distance” between observations (Chapter 14).
Fourth, transformations can be used to control for size differences between assemblages or specimens that we want to exclude from the analysis in order to focus on shape or relationships between variables that are independent of differences in size. In this case the transformation is applied to the rows of the data. First, we will consider a collection of R functions that are useful for a number of purposes, including transformation.
An integral aspect of archaeological data is that they come from particular places. We often want to examine the distribution of artifacts, sites, or features over space and R provides a number of tools for this purpose. We may also be interested in the direction or orientation of the object, house, or feature. This chapter will cover some of the basics, but there are specialized R packages for mapping and for analyzing gridded and point data. If most of your analysis involves spatial data it may be easier to use a geographic information system (GIS) package, but R can handle shapefiles and other data structures that are produced by those packages and it provides extensive support for statistical analysis of spatial data. In this chapter we will cover directional statistics, creating simple distribution maps based on gridded or piece plotted data.
CIRCULAR OR DIRECTIONAL STATISTICS
Circular statistics include direction and orientation (Gaile and Burt, 1980; Jammalamadaka and Sengupta, 2001; Mardia and Jupp, 2000). If we are interested in the direction of something (for example burials or rock shelter openings), then we are using directional data. In general, this is recorded in degrees measured clockwise from north, but it can also include cyclical data where the cycle repeats daily, weekly, monthly, or yearly. In other cases, we are interested in the orientation of an elongated flake, blade, or bone fragment. Orientation can be defined as north/south or east/west so we are only using half of the circle since 0° and 180° or 90° and 270° are the same orientation. With bone fragments, for example, we usually cannot identify which end is the front and which is the back so we are working with orientation. With blades, we could define the platform end as the front in which case we could measure direction rather than orientation, but often only the orientation is recorded. The research question under consideration will help to make the decision between direction and orientation. Analytically, the first step with orientation data is to double each value and analyze it as directional data.
Quantitative Methods in Archaeology Using R is the first hands-on guide to using the R statistical computing system written specifically for archaeologists. It shows how to use the system to analyze many types of archaeological data. Part I includes tutorials on R, with applications to real archaeological data showing how to compute descriptive statistics, create tables, and produce a wide variety of charts and graphs. Part II addresses the major multivariate approaches used by archaeologists, including multiple regression (and the generalized linear model); multiple analysis of variance and discriminant analysis; principal components analysis; correspondence analysis; distances and scaling; and cluster analysis. Part III covers specialized topics in archaeology, including intra-site spatial analysis, seriation, and assemblage diversity.