Evaluation of applying statistical process control techniques to daily average feeding behaviors to detect disease in automatically fed group-housed preweaned dairy calves.

Group housing and computerized feeding of preweaned dairy calves are gaining in popularity among dairy producers, yet disease detection remains a challenge for this management system. The aim of this study was to investigate the application of statistical process control charting techniques to daily average feeding behavior to predict and detect illness and to describe the diagnostic test characteristics of using this technique to find a sick calf compared with detection by calf personnel. This prospective cross-sectional study was conducted on 10 farms in Minnesota (n = 4) and Virginia (n = 6) utilizing group housing and computerized feeding from February until October 2014. Calves were enrolled upon entrance to the group pen. Calf personnel recorded morbidity and mortality events. Farms were visited either every week (MN) or every other week (VA) to collect calf enrollment data, computer-derived feeding behavior data, and calf personnel-recorded calf morbidity and mortality. Standardized self-starting cumulative sum (CUSUM) charts were generated for each calf for each daily average feeding behavior, including drinking speed (mL/min), milk consumption (L/d), and visits to the feeder without a milk meal (no.). A testing subset of 352 calves (176 treated, 176 healthy) was first used to find CUSUM chart parameters that provided the highest diagnostic test sensitivity and best signal timing, which were then applied to all calves (n = 1,052). Generalized estimating equations were used to estimate the diagnostic test characteristics of a single negative mean CUSUM chart signal to detect a sick calf for a single feeding behavior. Combinations of feeding behavior signals were also explored. Single signals and combinations of signals that included drinking speed provided the most sensitive and timely signal, finding a sick calf up to an average (±SE) of 3.1 ± 8.8 d before calf personnel. However, there was no clear advantage to using CUSUM charting over calf observation for any one feeding behavior or combination of feeding behaviors when predictive values were considered. The results of this study suggest that, for the feeding behaviors monitored, the use of CUSUM control charts does not provide sufficient sensitivity or predictive values to detect a sick calf in a timely manner compared with calf personnel. This approach to examining daily average feeding behaviors cannot take the place of careful daily observation.

Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus.

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps system.

Contraception in sea-going service personnel.

The right to make an informed choice about contraception should be afforded to every individual serving within the United Kingdom (UK) Armed Forces. This article looks at the responsibilities and approach that healthcare professionals should take within a Primary Care setting, summarises the common contraceptive options available, discusses the associated advantages and disadvantages of each technique, and considers operational factors in a military environment that combine to influence the final contraceptive choice an individual makes. Case Study. A 19-year old Able Rate joined the Royal Navy (RN) and at her joining medical it was noted that she had been on Microgynon™ combined oral contraceptive pill for approximately three years. During this time, her menstrual periods remained light; she never experienced adverse effects, demonstrated good compliance, and was happy to remain on this contraceptive regimen. Over the course of the next eighteen months, she was reviewed by a number of Medical Officers and Civilian Medical Practitioners on a quarterly basis, with Microgynon™ re-prescribed on each occasion. The appropriate Defence Medical Information Capability Programme (DMICP) template was used, with weight, smoking status, compliance and any issues or comments documented accordingly. In December 2010, a discussion regarding long-acting reversible contraception (LARC) was documented for the first time. The patient agreed to give LARC some thought and a review appointment was made for one month. She was subsequently started on the progestogen-only pill Cerazette™. It was noted by the consulting doctor that both the patient's mother and grandmother had a positive history of cerebrovascular events and the combined oral contraceptive pill was discontinued. Upon review at two months, the patient reported that she was content on Cerazette™ and wished to continue with this medication. She was amenorrhoeic, highly compliant, had given up smoking and her weight and blood pressure were stable. However, due to supply issues, it was explained that Cerazette™ was no longer a viable option for her. She had no plans to start a family, and was keen to investigate other contraceptive options. Furthermore, she expressed a particular desire to remain amenorrhoeic, as she was due to deploy overseas in the coming months, and not only wanted to avoid the inconvenience of having her period, but also felt it preferable not to have to take a daily pill when considering the constantly changing time zones. She subsequently had the etonogestrel-releasing subdermal implant Nexplanon™ fitted without complication. She has remained amenorrhoeic throughout and this form of long-acting reversible contraception has particularly suited her busy working role and active lifestyle.

Effects of age and serum 25-OH-vitamin D on serum parathyroid hormone levels.

CONTEXT: Several studies define optimal serum 25-hydroxyvitamin D (25-OHD) levels based on serum PTH level reaching an asymptote. However, results differ widely, ranging from 25-OHD levels of 12-44 ng/ml: many studies are constrained by small sample size. OBJECTIVE: The objective of the study was to determine the relationship between serum PTH and 25-OHD levels and age in a very large reference laboratory database. DESIGN: This was a detailed cross-sectional analysis of 312,962 paired serum PTH and 25-OHD levels measured from July 2010 to June 2011. RESULTS: Median PTH levels and the proportion of patients (PTH > 65 pg/ml), from 63 successive 25-OHD frequency classes of 5000 patients, provide smooth, exceptionally well-fitted curves (R(2) = 0.994 and R(2) = 0.995, respectively) without discernible inflection points or asymptotes but with striking age dependencies. Serum 25-OHD was below the recent Institute of Medicine sufficiency guidance of 20 ng/ml in 27% (85,000) of the subjects. More importantly, 40 and 51% of subjects (serum 25-OHD <20 and 10 ng/ml, respectively) had biochemical hyperparathyroidism (PTH > 65 pg/ml). CONCLUSIONS: This analysis, despite inevitable inherent limitations, introduces several clinical implications. First, median 25-OHD-dependent PTH levels revealed no threshold above which increasing 25-OHD fails to further suppress PTH. Second, the large number of subjects with 25-OHD deficiency and hyperparathyroidism reinforces the Third International Workshop on Asymptomatic Primary Hyper parathyroidism's recommendations to test for, and replete, vitamin D depletion before considering parathyroidectomy. Third, strong age dependency of the PTH-25-OHD relationship likely reflects the composite effects of age-related decline in calcium absorption and renal function. Finally, this unselected large population database study could guide clinical management of patients based on an age-dependent, PTH-25-OHD continuum.

Quantitative structure-activity relationship studies of antimalarial compounds from their calculated mathematical descriptors.

A wide range of mathematical descriptors that can be calculated without the use of any other experimental data except molecular structure were used to develop models to predict binary (+/-) antimalarial activity of a set of 86 4(1H)-quinolones in two strains of parasite: D6 and TM90-C2B (chloroquine and atovaquone susceptible). The quantitative structure-activity relationship for each strain was of high quality and showed good ability in predicting activity versus inactivity when applied to a data set containing well-known antimalarial drugs.

QSPR checking and validation: a case study with hydroxy radical reaction rate constant.

Traditionally, QSAR and QSPR models have been fitted by splitting the available compounds into separate learning and validation sets. The model is then fitted to the learning set and assessed using the validation set. Cross-validation (CV) uses all available compounds for both purposes, so that the full body of available information is brought to bear on both the learning and the validation portions of the study. The price paid for this additional information is a substantially greater computational load. A common mistake in using CV is to omit some of the repetitive computations. This mistake leads to substantial bias in the assessment. A hydroxyl radical reaction rate dataset is used to illustrate the superiority of CV and the pitfalls from its improper execution when modeling using nearest neighbors, paralleling behavior in the well-studied linear model setting.

Establishing pediatric immune response zones using the Cylex ImmuKnow assay.

For all transplant patients, the transplant physician must balance the risk of rejection caused by under-immunosuppression against the risk of drug toxicity, secondary infections and post-transplant lymphoproliferative disorder with over-immunosuppression. A Food and Drug Administration (FDA)-approved in vitro assay, the Cylex ImmuKnow assay, provides a global assessment of cellular immune function to help monitor the immune status of immunosuppressed patients. This assay uses the plant lectin phytohemagglutinin to stimulate lymphocytes; an ATP assay is then used to measure the degree of activation of CD4 T cells. However, the normal values for this assay were developed with healthy adult patients. In this study, we determined the normal ranges for the ImmuKnow assay in healthy children and compared those values to levels obtained in healthy adults and in stable pediatric renal transplant patients. We found that healthy children 12 yr of age and older showed immune function levels indistinguishable from adults, while healthy children under 12 had significantly lower immune function levels than adults. For adults, the ImmuKnow assay zones (in ng/mL ATP) of strong, moderate and low immune function correspond to >525, 225 to 525, and <225. In children under 12, we found the corresponding zones to be >395, 175-395 and <175 ng/mL. The median value for normal adults is 415, whereas it is only 295 for children <12 yr of age and this value decreases to 165 in stable renal transplant patients <12 yr of age (compared with 258 for stable adult renal transplant patients). Thus, this study provides critical information necessary to utilize the ImmuKnow assay with pediatric patients. In adults, the degree of immune function as assessed by the ImmuKnow assay helps to predict patients at risk for infection or rejection. If further studies in pediatric patients document the same and is true for children, then the ImmuKnow assay will provide a useful adjunct tool to prevent over- or under-immunosuppression as newly developed drugs are utilized or drug treatment is altered because of drug side effects, toxicity, concurrent illnesses or rejection.

Bulk tank somatic cell counts analyzed by statistical process control tools to identify and monitor subclinical mastitis incidence.

The objective of this study was to examine the relationship between monthly Dairy Herd Improvement (DHI) subclinical mastitis and new infection rate estimates and daily bulk tank somatic cell count (SCC) summarized by statistical process control tools. Dairy Herd Improvement Association test-day subclinical mastitis and new infection rate estimates along with daily or every other day bulk tank SCC data were collected for 12 mo of 2003 from 275 Upper Midwest dairy herds. Herds were divided into 5 herd production categories. A linear score [LNS = ln(BTSCC/100,000)/0.693147 + 3] was calculated for each individual bulk tank SCC. For both the raw SCC and the transformed data, the mean and sigma were calculated using the statistical quality control individual measurement and moving range chart procedure of Statistical Analysis System. One hundred eighty-three herds of the 275 herds from the study data set were then randomly selected and the raw (method 1) and transformed (method 2) bulk tank SCC mean and sigma were used to develop models for predicting subclinical mastitis and new infection rate estimates. Herd production category was also included in all models as 5 dummy variables. Models were validated by calculating estimates of subclinical mastitis and new infection rates for the remaining 92 herds and plotting them against observed values of each of the dependents. Only herd production category and bulk tank SCC mean were significant and remained in the final models. High R2 values (0.83 and 0.81 for methods 1 and 2, respectively) indicated a strong correlation between the bulk tank SCC and herd's subclinical mastitis prevalence. The standard errors of the estimate were 4.02 and 4.28% for methods 1 and 2, respectively, and decreased with increasing herd production. As a case study, Shewhart Individual Measurement Charts were plotted from the bulk tank SCC to identify shifts in mastitis incidence. Four of 5 charts examined signaled a change in bulk tank SCC before the DHI test day identified the change in subclinical mastitis prevalence. It can be concluded that applying statistical process control tools to daily bulk tank SCC can be used to estimate subclinical mastitis prevalence in the herd and observe for change in the subclinical mastitis status. Single DHI test day estimates of new infection rate were insufficient to accurately describe its dynamics.

Quantitative structure-activity relationship modeling of insect juvenile hormone activity of 2,4-dienoates using computed molecular descriptors.

Juvenile hormone (JH) activity of one hundred and eighty 2,4-dienoates reported for the larvae/pupae of six insect species was modeled using 915 atom pairs and 258 global molecular descriptors (topological and geometrical). Ridge regression, principal component regression and partial least square regression methods were used to model each of the JH activities. The use of all of the available parameters did not yield any good models, and extensive predictor trimming was necessary to improve the models. Ridge regression was found to give the best results among the three statistical tools used. The top ten molecular descriptors selected based on the t-statistic for each of the six models were found to be mostly atom pairs containing heteroatoms and topochemical descriptors. This suggests the importance of the chemical nature of the ligand rather than mere space-filling as the basis of the JH bioactivity. The residual plots indicate the existence of some non-linear relations, and recursive partitioning was used to capture any nonlinear relation between the bioassays and the molecular descriptors.

A variance-stabilizing transformation for gene-expression microarray data.

MOTIVATION: Standard statistical techniques often assume that data are normally distributed, with constant variance not depending on the mean of the data. Data that violate these assumptions can often be brought in line with the assumptions by application of a transformation. Gene-expression microarray data have a complicated error structure, with a variance that changes with the mean in a non-linear fashion. Log transformations, which are often applied to microarray data, can inflate the variance of observations near background. RESULTS: We introduce a transformation that stabilizes the variance of microarray data across the full range of expression. Simulation studies also suggest that this transformation approximately symmetrizes microarray data.

Prediction of tissue-air partition coefficients: a comparison of structure-based and property-based methods.

Three linear regression methods were used to develop models for the prediction of rat tissue-air partition coefficient (P). In general, ridge regression (RR) was found to be superior to principal component regression (PCR) and partial least squares regression (PLS). A set of 46 diverse low molecular-weight volatile chemicals was used to model fat-air, liver-air and muscle-air partition coefficients for male Fischer 344 rats. Comparisons were made between models developed using descriptors based solely on molecular structure and those developed using experimental properties, including saline-air and olive oil-air partition coefficients, as independent variables, indicating that the structure-property correlations are comparable to the property-property correlations. Multiple structure-based models were developed utilizing various classes of structural descriptors based on level of complexity, i.e. topostructural (TS), topochemical (TC), 3-dimensional (3D) and calculated octanol-water partition coefficient. In most cases, the structure-based models developed using only the TC descriptors were found to be superior to those developed using other structural descriptor classes. Haloalkane subgroups were modeled separately for comparative purposes, and although models based on the congeneric compounds were superior, the models developed on the complete sets of diverse compounds were acceptable. Comparisons were also made with respect to the types of descriptors important for partitioning across the various media.

QSAR with few compounds and many features.

Fitting quantitative structure-activity relationships (QSAR) requires different statistical methodologies and, to some degree, philosophies depending on the "shape" of the data matrix. When few features are used and there are many compounds, it is a reasonable expectation that good feature subset selection may be made and that nonlinearities and nonadditivities can be detected and diagnosed. Where there are many features and few compounds, this is unrealistic. Methods such as ridge regression RR, PLS, and principal component regression PCR, which abjure feature selection and rely on linearity may provide good predictions and fair understanding. We report a development of ridge regression for the underdetermined case by using generalized cross-validation to choose the ridge constant and perform F-tests for additional information. Conventional regression diagnostics can be used in followup to identify nonlinearities and other departures from model. We illustrate the approach with QSAR models of four data sets using calculated molecular descriptors.

Some issues in resolution of diagnostic tests using an imperfect gold standard.

As a subject's true disease status is seldom known with certainty, it is necessary to compare the performance of new diagnostic tests with those of a currently accepted but imperfect 'gold standard'. Errors made by the gold standard mean that the sensitivity and specificity calculated for the new test are biased, and do not correctly estimate the new method's sensitivity and specificity. The traditional approach to this problem was 'discrepant resolution', in which the subjects for whom the two methods disagreed were subjected to a third 'resolver' test. Recent work has pointed out that this does not automatically solve the problem. A sounder approach goes beyond the discordant test results and tests at least some of the subjects with concordant results with the resolver also. This leaves some issues unresolved. One is the basic question of the direction of biases in various estimators. We point out that this question does not have a simple universal answer. Another issue, if one is to test a sample of the subjects with concordant results rather than all cases, is how to compute estimates and standard errors of the measures of test performance, notably sensitivity and specificity of the test method relative to the resolver. Expressions for these standard errors are given and illustrated with a numeric example. It is shown that using just a sample of subjects with concordant results may lead to great savings in assays. The design issue of how many concordant cells to test depends on the numbers of concordants and discordants. The formulae given show how to evaluate impact of different choices for these numbers and hence settle on a design that gives the required precision of estimates.

An invitation to join in difficulty: realizing the deeper promise of group psychotherapy.

Group psychotherapy has proven effective in treating an impressive array of specific problems. Clinical experience has also shown its utility in alleviating the more general, and very costly, alienation and pain with which the human condition is often fraught. Recent changes in health care delivery reflect a marketplace that emphasizes cost containment, brevity and specificity of treatment, and a narrowed focus of training. Techniques are often valued above relationships. In this climate, we are in danger of losing sight of group therapy's deeper promise; the experiential lesson that human beings must move toward each other with involvement and a commitment to understanding in response to the inevitable difficulties that arise as we share time, space, and resources.

Validity of an estimator of reproductive success.

Lifetime reproductive success is a major component of individual fitness and a central dependent variable for the study of natural selection. For long-lived animals, such as apes or baboons, assessment of lifetime reproductive success requires observations of identified individuals in continuous, long-term studies from which it is difficult and often impossible to obtain an adequate sample of necessary reproductive and survival data. This situation can be alleviated by the availability of a valid measure that uses incomplete reproductive histories to estimate the lifetime reproductive success of individuals. The validity of one such estimator was tested by determining if, after 10.5 years of studying free-ranging female baboons, it predicted lifetime reproductive success obtained from full reproductive histories after 21.5 years. Validity was evaluated for seven criteria of success, ranging from the number of a female's live births to the number of her offspring that reached the age of 72 months. Moderate to good prediction of lifetime reproductive success by the estimator was found for criteria of offspring living to 36 months or more. After 10.5 years, complete reproductive life spans were available for only eight females. Using the estimator, analytic potential, via sample representativeness and size, was improved at 10.5 years by an increase from a sample of eight to between 34 and 62, depending upon the criterion used, and at 21.5 years from 39 to 70. With a valid estimator, the opportunity to study lifetime reproductive success of a long-lived species is substantially improved without having to depend upon rarely available, uninterrupted data collection for 20-60 years.

Analysis of a 2(9) full factorial chemical library.

Robotic synthesis is making possible the synthesis of large, systematically designed sets of compounds. We analyze a 512-compound set that is a 2(9) full factorial experimental design using a recursive partitioning algorithm, FIRM, and a high-dimension visualization tool, TempleMVV. These techniques are used to quickly and easily identify the main trends in the data set and also identify unusual observations. We show that analytical and visualization methods can be used synergistically to analyze a large, complex, high-dimensional data set. We also show that a fractional factorial design of 128 compounds would give essentially the same information.

Applications of geostatistics in plant nematology.

The application of geostatistics to plant nematology was made by evaluating soil and nematode data acquired from 200 soil samples collected from the A(p) horizon of a reed canary-grass field in northern Minnesota. Geostatistical concepts relevant to nematology include semi-variogram modelling, kriging, and change of support calculations. Soil and nematode data generally followed a spherical semi-variogram model, with little random variability associated with soil data and large inherent variability for nematode data. Block kriging of soil and nematode data provided useful contour maps of the data. Change of snpport calculations indicated that most of the random variation in nematode data was due to short-range spatial variability in the nematode population densities.

Correlation of Edaphic Factors with Plant-parasitic Nematode Population Densities in a Forage Field.

Two hundred soil samples from the A(p) horizon of a reed canarygrass field overlaying several different but related soils in northern Minnesota were analyzed for plant-parasitic nematodes and 22 edaphic factors. Pratylenchus penetrans was the predominant nematode taxon. Others were Aglenchus agricola, Tylenchorhynchus spp., Heterodera trifolii, Paratylenchus spp., Tylenchus maius, and Criconemella sp. Five nematode taxa, P. penetrans, A, agricola, Tylenchorhynchus spp., H. trifolii, and Paratylenchus spp., were correlated with particle size, Tylenchus maius and Criconemella sp. were correlated with effective cation exchange capacity. Nematode field spatial arrangements were related to a combination of statistically significant positive and negative soil factor effects on the nematode populations. Contour maps derived by geostatistical techniques were used to visually validate statistically significant correlations of nematode and soil data. Contour mapping to supplement traditional statistical techniques can be used to achieve a more holistic approach to studies of nematode-soil interrelationships.

Cryopreservation of semen from unique lines of chicken germ plasm.

Frozen semen is a practical means of preserving valuable germ plasm. Monitored samples of semen cryopreserved with glycerol for heterozygous, dominant marker stocks and for nine chromosomal rearrangement lines had sufficiently high fertility for germ-line retrieval. The results also indicated a potential for the genetic selection of certain lines for the freezability of spermatozoa, since stock and line differences in fertility occurred when previously frozen semen was used for insemination. Freezing the semen of stocks routinely reproduced provides insurance against possible disasters.

Estimation of the relative fertilizing ability of frozen chicken spermatozoa using a heterospermic competition method.

Semen was collected from Rhode Island Red and White Leghorn roosters. After adjusting the sperm number from both breeds, half of the semen was frozen-thawed in the presence of glycerol. Frozen and unfrozen semen from both breeds was mixed 1:1 with all four possible combinations and inseminated into Rhode Island Red hens. Feather colour of chicks was used to determine which breed fertilized the eggs. Results showed that sperm cells retained 19.7% [95% confidence interval = (12.8, 30.4)] of the relative fertilizing ability after freezing. Furthermore, Rhode Island Red spermatozoa had 1.5 times [95% confidence interval = (1.1, 2.0)] higher relative fertilizing ability than did White Leghorn spermatozoa. The heterospermic competition assay method is a powerful tool for estimating the relative fertilizing ability of the sperm cells.