Retrospective investigation of sudden maternal weight loss as an indicator of impending parturition in the term gravida: a pilot study.

The aim of the study was to perform a retrospective review of records to test a possible significant association between sudden, modest weight loss (≤2 lb) between the last two prenatal appointments in the late 3rd trimester and onset of labour. Hospital and clinic records were searched for women who delivered a term baby after the onset of natural labour between 2006 and 2008, in Tulsa, OK. High-risk pregnancies were excluded. Patients were categorised by whether they lost or gained weight between their last two prenatal appointments. The groups' average times to onset of spontaneous labour were compared. A total of 149 records were obtained. Mothers who lost weight had an average onset of spontaneous labour in 2.30 days; their counterparts' average was 2.34 days. Student's t-test and Wilcoxon test p values were 0.95 and 0.61, respectively. A Kolmogorov-Smirnov test p value was 0.2139. A one-half standard deviation difference in time to delivery, approximately 2.5 days, was detectable with 0.95 probability. It was concluded that these data may be the first time this question has been investigated and provide evidence that sudden, modest weight loss at the end of pregnancy is not associated with shorter time to onset of natural labour.

Effectiveness of different corn dried distillers grains with solubles feeding strategies and increasing the time intervals between the second Improvest dose and slaughter of immunologically castrated pigs on belly and pork fat quality.

Effects of dried distillers grains with solubles (DDGS) feeding strategies (a corn-soybean meal (CS) fed continously; CS+40% DDGS fed continously; CS+40, 30, 20, or 10% DDGS in 4 phases, respectively; or CS+40% DDGS in phases 1 to 3 and CS in phase 4 before slaughter) on belly and pork fat quality of immunologically castrated (n=192) pigs were evaluated. All pigs received the first Improvest dose at 11week of age, and the second dose at 9, 7, or 5week before slaughter at 24week of age. Increasing the time interval of the second Improvest dose before slaughter reduced IV in all fat depots and increased belly thickness. Gradually decreasing dietary DDGS and DDGS withdrawal feeding strategies reduced IV in all fat depots. Calculated IV were greater using the Meadus et al. (2010) equation compared with using the AOCS (1998) equation because it includes more long-chain unsaturated fatty acids.

Growth performance of immunologically castrated pigs slaughtered at 5, 7, or 9 weeks after the second Improvest dose and fed diets containing corn dried distillers grains with solubles.

Growth performance of immunologically castrated (IC) pigs (863 total) was determined at increasing time intervals between the second Improvest (gonadotropin releasing factor analog-diphtheria toxoid conjugate; Zoetis Inc., Florham Park, NJ) dose and slaughter (TD) and with 4 different dried distillers grains with solubles (DDGS) feeding strategies (FS) in a 4 × 3 factorial arrangement of treatments. The feeding period was divided into 4 separate diet phases. Dietary treatments included 1) corn-soybean meal control diets (PCon), 2) a gradual decrease of dietary DDGS inclusion rate from 40%, 30%, 20%, and 10% in phases 1 to 4 (GD), respectively, 3) feeding 40% DDGS diets in phases 1 to 3 and removal of DDGS from the phase 4 diet (WD), and 4) feeding 40% DDGS diets in all 4 phases (NCon). Pigs received the second Improvest dose at 9 (TD9), 7 (TD7), or 5 (TD5) wk before slaughter. In each group, all pigs were slaughtered on the same day. There were no 3-way interactions among FS, TD, and week of feeding period for any measure of growth performance. Pigs fed PCon and WD had greater ( < 0.05) overall ADFI than pigs fed NCon, especially when slaughtered 9 wk after the second Improvest dose (2.45 and 2.44 vs. 2.31 ± 0.08 kg/d, respectively). This response was partly due to withdrawing DDGS from the diet at 19 wk of age (WD), which led to a tendency ( < 0.10) for increased ADFI from the wk 19 to 21 interval to the wk 21 to 24 interval (3.26 vs. 3.51 ± 0.09 kg/d, respectively). During the same time period, ADFI was unchanged ( > 0.05) in pigs fed PCon, GD, and NCon. Overall G:F was improved ( < 0.05) in TD5 pigs compared with TD9 pigs and tended ( < 0.10) to be improved compared with TD7 pigs. Final BW was similar among pigs fed GD, WD, and PCon (123.1, 122.3, and 125.3 kg, respectively), but pigs fed PCon and GD had greater ( < 0.05) BW than pigs fed NCon (120.0 kg). Throughout the growing-finishing period, BW was similar among TD treatments. The GD FS was more effective than the WD FS in maintaining overall G:F (0.424 and 0.414 ± 0.005, respectively) and ADG (0.94 and 0.93 ± 0.03 kg/d, respectively), which were similar ( > 0.05) to those of pigs fed PCon (0.427 ± 0.005 and 0.96 ± 0.03 kg/d, respectively). Growth performance of pigs fed GD more closely reflected that of pigs fed PCon than that of pigs fed WD. Delaying the second dose of Improvest from 9 to 5 wk before slaughter resulted in improved growth performance.

Effect of time interval between the second Improvest® dose and slaughter and corn dried distillers grains with solubles feeding strategies on carcass composition, primal cutout, and pork quality of immunologically castrated pigs.

Effects of dried distillers grains with solubles (DDGS) feeding strategies on carcass composition, primal cutout, and lean quality of immunologically castrated (IC; n=863) pigs were evaluated, and consisted of: 1) corn-soybean meal (CS) diet (PCon); 2) CS+40% DDGS (NCon); 3) CS+40, 30, 20, or 10% DDGS fed in phases 1 to 4, respectively (SD); or 4) CS+40% DDGS fed in phase 1 to 3 and CS in phase 4 (WD). All pigs received the first dose of Improvest® at 11weeks. of age, and the second dose was administered at either 9, 7, or 5weeks. before slaughter at 24weeks. of age. The SD and WD improved carcass dressing percentage and resulted in intermediate primal cut yields and pork loin quality compared with pigs fed PCon and NCon. Increasing the time interval between second dose of Improvest® and slaughter increased adipose tissue accretion but did not affect lean quality of pork.

Effect of Amblyomma maculatum (Acari: Ixodidae) Saliva on the Acute Cutaneous Immune Response to Rickettsia parkeri Infection in a Murine Model.

Rickettsia parkeri Luckman (Rickettsiales: Rickettsiaceae) is a pathogenic spotted fever group Rickettsia transmitted by Amblyomma maculatum Koch (Acari: Ixodidae) in the United States. The acute innate immune response to this pathogen and the effect of tick feeding or salivary components on this response is largely unknown. We hypothesized that A. maculatum saliva enhances R. parkeri infection via downregulation of the acute cellular and cytokine immune response. C3H/HeN mice were intradermally inoculated with R. parkeri both with and without A. maculatum saliva. Flow cytometry and microscopic evaluation of inoculation site skin suspensions revealed that neutrophils and macrophages predominated at 6 and 24 h post R. parkeri inoculation, respectively. This cellular influx was significantly downregulated when A. maculatum saliva was inoculated along with R. parkeri Inflammatory cytokines (interferon γ and interleukins 6 and 10) were significantly elevated after R. parkeri inoculation. However, cytokine concentration and rickettsial load were not significantly modified by A. maculatum saliva during the acute phase of infection. These results revealed that tick saliva inhibits the cutaneous cellular influx during the acute phase of rickettsial infection. Further study is needed to determine the overall impact of this effect on the establishment of rickettsiosis in the host and development of disease.

Statistical principles underlying analytic goal-setting in clinical chemistry.

The Survey programs of the College of American Pathologists (CAP) have assessed current levels of analytic variance in many biochemical measurements, and a number of clinical chemists have proposed analytic goals. The practical importance of further reductions in analytic variance depends on the specific use of the laboratory test. Three general areas of application are described: 1) surveying a population to detect disease, 2) determining whether a particular individual's level of a given analyte is above or below a predefined alarm point, 3) monitoring an individual over a period of time to detect trends. Within each of these different contests, statistical methods are proposed for judging the practical effect of improvements in current levels of analytic precision, taking into account recent estimates of biological variation within the average individual and between individuals. As might be expected, reductions in analytic variance have greatest impact in those applications where biological variance is minimal. Such reductions will generally have little effect on the efficiency of a population survey but may be extremely valuable in decision-making concerning a particular hospital patient.

Temporal changes in the concentrations of serum constituents in healthy men. Distributions of within-person variances and their relevance to the interpretation of differences between successive measurements.

The distributions of within-person variances in the concentrations of 10 commonly assayed serum constituents have been derived from data on 37 healthy male subjects studied at weekly intervals over a period of five months. All 10 distributions appear to be of log-normal form. The relevance of the findings to the interpretation of differences between serial measurements in a given individual is discussed. Examples are given to show how the information on within-person variances for a particular analyte, organised into a simple graph, may be used to test medical opinions on threshold values for serial changes in the concentration of this analyte in a given individual. In this way, biological variability as well as analytical error may be taken into account quantitatively when assessing the significance of a difference between two serial measurements.

Proposed goals for analytical precision and accuracy in single-point diagnostic testing. Theoretical basis and comparison with data from College of American Pathologists proficiency surveys.

Expressing total analytic variance as the sum of the squares of imprecision and inaccuracy, or bias, and applying the Cotlove rule recommended by the 1976 College of American Pathologists Conference on Analytical Goals in Clinical Chemistry, namely, that analytic variance should be less than one fourth of the appropriate biological variance, I derive a rule for maximum allowable imprecision in the context of single-point diagnostic testing that takes into account the bias of the test procedure. This rule may be expressed in terms of a population-based reference range (in particular, the range of test results shown in a group of healthy individuals) and the bias of the test method. The latter is required not to exceed one eighth (0.125) of the reference range. These concepts are applied to eight common analytes for which estimates of the biases of specific methods and of within-laboratory imprecision have been published for large numbers of laboratories participating in recent College of American Pathologists proficiency surveys. Results indicate that some methods widely used in 1978 fail to meet the minimum accuracy criterion, while others show negligible bias. Even neglecting bias, more recent data show that average within-laboratory imprecision is still too high for sodium, chloride, and calcium but acceptable for potassium, glucose, cholesterol, urea, and uric acid.

Impact of maternal physical activity during gestation on porcine fetal, neonatal, and adolescent ovarian development.

To determine how exercise from mid to late (days 40-104) gestation impacts offspring body, uterine and ovarian weight, and ovarian cell proliferation at three different developmental stages, Yorkshire gilts were either exercised by walking (EX) or not exercised (CON). In parity 1, ovaries and uteri were collected from the heaviest (H) and lightest (L) neonates and adolescent (6 mo) offspring. In parity 2, mothers were assigned the same treatment groups, and ovaries and uteri were collected from H and L fetuses on day 94 of gestation. Body weight was greater (P < 0.02) for H than L fetuses and neonates but not affected by EX treatment at any developmental stage. Ovarian weight in L but not H neonates was greater (P < 0.02) in EX than CON. Labeling index (LI; percentage of proliferating cells) was greater (P < 0.01) in cortex than medulla regions of fetal and neonatal ovaries. In fetal ovaries, EX enhanced LI (P < 0.01), and LI was greater (P < 0.01) in H compared with L offspring. In adolescent ovaries, LI was greatest (P < 0.01) in healthy antral and least in atretic antral follicles, and LI was greater (P < 0.01) in granulosa than theca cells of healthy antral follicles. Thus, exercise increased LI in fetal but not neonatal or adolescent ovaries. Although maternal exercise during gestation influences fetal and neonatal ovarian development, impacts on fertility remain unknown.

Effect of maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and farrowing characteristics in pigs.

Yorkshire gilts either remained in their individual stall from d 40 to term (CON; n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late gestation (EX; n = 7) to determine the impact of increased maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and parturition. In parity 1, maternal body composition (10th rib back fat and LM area), maternal behavior, and farrowing characteristics were recorded. In parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and resistance index, and umbilical blood flow were monitored beginning at d 39 of gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06) to lie down less, and had fewer postural changes (P < 0.01) compared with CON gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts. Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity compared with their second. Indices of vascular resistance were not affected (P ≥ 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index earlier than CON gilts (56.2 vs. 64.3 ± 3.6 d). Fetal weights, piglet birth weights, placental weight, interval between piglet births, and blood lactate of newborn piglets were unaffected (P ≥ 0.15) by maternal treatment. Although maternal exercise during gestation in the pig increased umbilical blood flow and appeared to reduce maternal restlessness, impacts on offspring development in postnatal life are not known.

Effects of pea chips on pig performance, carcass quality and composition, and palatability of pork.

Pea chips are produced as a by-product when field peas are processed to produce split peas for human consumption. The objective of this experiment was to test the hypothesis that inclusion of pea chips in diets fed to finishing pigs does not negatively influence pig growth performance, carcass composition, and the palatability of pork. A total of 24 barrows (initial BW: 58.0 ± 6.6 kg) were allotted to 1 of 4 treatments and fed early finishing diets for 35 d and late finishing diets for 35 d. A corn-soybean meal (SBM) control diet and 3 diets containing pea chips were formulated for each phase. Pea chips replaced 33.3, 66.6, or 100% of the SBM in the control diet. Pigs were housed individually, and all pigs were slaughtered at the conclusion of the experiment. Overall, there were no differences (P > 0.11) in final BW, ADFI, and G:F of pigs among treatments, but there was a quadratic response in ADG (P = 0.04), with the smallest value observed in pigs fed the control diet. Dressing percentage linearly decreased (P = 0.04) as pea chips replaced SBM in diets, but there were no differences (P > 0.20) among treatments in HCW, LM area, 10th-rib backfat, lean meat percentage, and marbling. Likewise, pH in loin and ham, drip loss, and purge loss were not influenced (P > 0.13) by treatment. However, there was a quadratic response (P = 0.08) in 24-h pH in the shoulder, with the smallest value present in pigs fed the diet, in which 66.6% of the SBM was replaced by pea chips. Subjective LM color and Japanese color score standard were reduced (quadratic, P = 0.03 and 0.05, respectively) and LM b* values and hue angle were increased (quadratic, P = 0.09 and 0.10, respectively) when pea chips replaced SBM in the diets. Ham L* (quadratic, P = 0.04), a* (linear, P = 0.02), b* (quadratic, P = 0.07), color saturation (linear, P = 0.02), and hue angle (quadratic, P = 0.05) were increased when pea chips replaced SBM. However, there were no differences (P > 0.16) in shoulder and fat color. Moreover, cook loss percentage, shear force, juiciness, and pork flavor of pork chops were not different (P > 0.10) among treatments, but tenderness of pork chops linearly decreased (P = 0.04) as SBM replaced pea chips. It is concluded that all the SBM in diets fed to growing-finishing pigs may be replaced by pea chips without negatively influencing growth performance or carcass composition. However, pigs fed pea chips will have pork chops and hams that are lighter, and chops may be less tender if pigs are fed pea chips rather than corn and SBM.

Some theory of reference values. I. Stratified (categorized) normal ranges and a method for following an individual's clinical laboratory values.

The conventional population-based normal range has recently been shown to be a generally defective reference criterion for assessing individual laboratory test results. Applying a previously derived formula to published data, we find that the use of age-, sex-specific normal ranges may fail to produce a substantial improvement in sensitivity over nonspecific ranges, even when age-sex differences in mean values are statistically significant. This occurs when the difference in means is not accompanied by a sufficient reduction in the variation among individuals within a given class. Turning therefore to comparison of an individual's current measurement with his own previous value(s), I suggest a simple statistical model that leads to sequential testing of each new observation against an exponentially weighted moving average of previous results. Estimates of biological and analytical components of variance are required. The ability of this method to detect trends in very short series is explored with the aid of computer-simulated laboratory data. A sample of these data is also used to illustrate the application of these estimation and testing procedures by means of a graph.

Some theory of reference values. II. Comparison of some statistical models of intraindividual variation in blood constituents.

Three models of intraindividual variation are reviewed, and statistical methods for distinguishing among them are discussed. Application of these methods to short series of observations from healthy individuals indicates that, in the large majority of cases, a strictly homeostatic model is appropriate for such constituents as serum calcium and magnesium. In less closely controlled variables, e.g., serum cholesterol and uric acid, a nonstationary, "rndom walk" model appears moresuitable in most cases. A more general autoregressive model, which includes the other models as extreme cases, could be used to describe all degrees of homeostatic control. This model is more complex, however, and requires at least 10 observations to yield estimates of acceptable precision. Moreover, it is sensitive to fluctuations in within-batch analytical variance. When biological variance is small relative to analytical variance, all three models yield essentially the same predicated values. To illustrate their use, these models have been applied to four short individual series of cholesterol observations showing increasing amounts of intrapersonal variation over long periods of time. I suggest that when less than 10 observations over time are available, the strictly homeostatic model and the nonstationary model be used to derive a "critical range" for assessing future changes. When longer series are available, the more general model might replace the other two for this purpose, if analytical variation has remained reasonably stable (within +/- 20% of its average value) during the period of observation. Much more experience with the use of all three models in health monitoring programs would be highly desirable.

On the calculation of a "reference change" for comparing two consecutive measurements.

We describe a statistical method for calculating a "reference change," defined as that difference between two consecutive test results in an individual that is statistically significant in a given proportion of all similar persons. By allowing for variation in within-person variances, this procedure computes a reference change that is more specific (i.e., less prone to false positives) than that obtained directly from the distribution of observed differences between measurements. Moreover, the method may easily be extended to a test for trend in three successive measurements. The method has been applied to semi-annual measurements of serum calcium and alkaline phosphatase in 698 men and women enrolled in a large health-maintenance program. We believe that these ideas may also be usefully applied to successive laboratory tests in carefully defined patient populations--but this introduces special problems, which are discussed briefly.

Generation and application of data on biological variation in clinical chemistry.

Most clinical chemical analytes vary in a random manner around a homeostatic set point. Replicate analyses of a series of specimens collected from a group of subjects allows estimation of analytical, within and between subject components of variation. The preferred experimental procedures and statistical methods for evaluation of data and analysis of variance are described; a detailed example is provided in the Appendix. The many uses of data on biological variation in clinical chemistry are reviewed, including setting analytical goals, deciding the significance of changes in serial results from an individual, evaluating the utility of conventional population-based reference values in patient management, and other applications.

On dividing reference data into subgroups to produce separate reference ranges.

We consider statistical criteria for partitioning a reference database to obtain separate reference ranges for different subpopulations. Using general formulas relating population variances, sample sizes, and the normal deviate test for the significance of the difference between two subgroup means, we show that partitioning into separate ranges produces little reduction in between-person variability, even when the differences between means are highly significant statistically. However, when there is a clear physiological basis for distinguishing between certain subgroups, simulation studies show that partitioning may be necessary to obtain reference limits that cut off the desired proportions of low and high values in each subgroup. Guidelines based on these results are provided to help decide whether separate ranges should be obtained for a given analyte.

On the calculation of reference change values, with examples from a long-term study.

Reference change values (sometimes called critical differences) indicate statistically important changes between test values obtained on two occasions. They are commonly computed from the median (or mean) within-subject variance observed in repeated test measurements on a number of subjects. With this computational approach, all observed within-subject variances are assumed to be estimates of a constant true variance, the same for all individuals. Moreover, any possible correlation between successive values is almost always ignored. This simplified methodology differs from the method originally proposed for computing reference change values, which accounts for variability in true variances and for serial correlation. From data obtained from repeated measurements over 2 to 5 years in 72 physically healthy subjects, we computed and compared reference change values in 18 serum analytes, using the simplified method and the originally proposed procedure. Although the original method is more complicated and requires a computer program, we believe that it produces more-reliable reference change values than those obtained by the simplified approach. The former are generally larger, but remain sensitive to clinically important changes in the individual.

Statistical criteria for separate reference intervals: race and gender groups in creatine kinase.

Previously published data confirming differences in creatine kinase (EC 2.7.3.2) among various race and gender subgroups in the Los Angeles area have been re-examined with use of recently proposed statistical criteria for defining separate reference intervals. Results indicate that one criterion may be too lenient, whereas another is clearly too restrictive in suggesting the need for separate intervals. Further experience with other analytes in both large and small population samples would be helpful.

Comparison of estimates of long-term analytical variation derived from subject samples and control serum.

Variation in the assays of uniform control serum commonly are assumed to represent day-to-day analytical variation. To test this assumption, we compared the differences between results of serum aliquots assayed immediately for 12 constituents and frozen aliquots accumulated and assayed on a single day with the results of control serum variation from the same period. One aliquot of each weekly sample was stored frozen. Eleven subjects were sampled for 12 weeks. Storage at --20 degrees C for 15 weeks had a mild destructive effect on two enzymes in serum. The control serum data revealed significant linear trends in magnesium (upwards) and alkaline phosphatase (downwards) that substantially increased the respective variances. In the other 10 constituents tested, comparison of variances indicated that long-term (weeks) variation in control serum assays is similar to the difference of variation between aliquots assayed immediately and those frozen and assayed at the same time. For these constituents, this finding justifies the use of control serum to estimate long term analytical variation.