Out Of Range Research Articles

The application of Hoffmann method in the establishment of children's reference intervals of erythrocyte count

To verify the reliability and feasibility of Hoffmann method in establishing pediatric reference intervals (RI) of erythrocyte count. Three hundreds and ninty-two thousands of hospital-based data for erythrocyte count of children aged in 1 to 17, measured by the Sysmex Xs-800i, was collected from Beijing Children's Hospital during January to December 2014. Outliers were removed using the Dixon method, then Hoffmann method was conducted to establish the gender and age stratified pediatric RIs of erythrocyte count. The erythrocyte count of 2 217 healthy children, recruited from Beijing Children's Hospital and Liaocheng Children's Hospital in Shandong province, was conducted as normal reference to verify the reliability of Hoffmann method in establishing RIs and to compare with existing RIs. In 4 subgroups as following, male aging 1 to 12 years, male aging 13 to 17 years, female aging 1 to 12 years, female aging 13 to 17 years, the RIs of erythrocyte count established using Hoffmann method were (4.1-5.4)×10(12)/L, (4.4-5.7)×10(12)/L, (4.0-5.3)×10(12)/L, (4.0-5.3)×10(12)/L, respectively. The verification results in 2 217 healthy children showed that the proportions of out of range in four subgroups were 6.17%, 8.81%, 6.22%, 7.78%, respectively. Hoffmann method produce reliable RIs according with the actual situation in healthy children, which is also convenient and is worth popularizing in clinical practice.

Case of extremely high refractive error misdiagnosed as normal by PlusoptiX S09 photoscreener

PlusoptiX S09 (Plusoptix®GmbH,Nuremberg, Germany) is a binocular, port-able infrared video refractor which uses thedynamic photosciascopy method. As adigital photoscreener, it records digitalvideousinginfraredbeamsandanalysesdatain seconds using software installed on theminicomputer of the handpiece. At thebeginning of a measurement, the PlusoptiXcamera takes a few pictures to determinewhether the refractive error is outside meas-urement range. If it is, a ‘measurement outof range’ error message is shown on screen.In addition, the operator will find the words‘myopia’ or ‘hyperopia’ instead of refractivereadings in the output to indicate whichlimitation was exceeded. The measurementis aborted in this case and the screeningresult is ‘refer’. The method used to detectwhether the refractive error is outside themeasurement range is proprietary (RJJacobs, personal communication).Studies suggest that non-cycloplegicphotorefraction has reasonable sensitivityand specificity compared with cycloplegicretinoscopy.

PRM152 - Data Cleaning Paper Patient Reported Outcome (PRO) Data Versus Electronic Patient Reported Outcome (EPRO) Data

This conceptual paper will illustrate the impacts of low quality data, describe the requirements of the data cleaning process, compare the data cleaning process for paper versus ePRO, and provide recommendations of how ePRO can be implemented to decrease the level of effort of data cleaning. Before data can be analyzed, data cleaning must occur to ensure high data quality. Low quality data can have major impacts on data analysis/results along with cost impact. As estimated by the Data Warehousing Institute, the costs of low quality data exceeds $600 billion annually. Data cleaning process includes querying for errors, typos, outliers, out-of-range responses, missing data, deviations, etc. Paper: query data for erroneous/out-of range values; these values need to be cross-checked with original paper form to identify if error is associated with patient entry or data entry staff. If associated with patient entry, it may need to be set as missing. When original paper is lost, values may need to be set to missing as accuracy cannot be confirmed. Time/dates may be out-of-range or missing, which require cross-checking with original paper. If time/date cannot be confirmed, the entire entry may need to be set as missing. Missing values in data need to be identified and cross-checked with original paper to confirm if value was skipped by patient or by data entry staff. ePRO: can be implemented to prevent entry of out-of range values; includes time/date stamps; patient direct data entry eliminates error by data entry staff; can be programmed to not allow skipped responses to prevent missing data responses. End-of-study time is precious to the pharma industry where results need to be analyzed for submissions. Data cleaning with paper can be labor intensive and ePRO can save time with preventing errors from occurring, reducing time needed for data cleaning.

No peptide left behind: the “out of range” recovery in IPG–IEF fractionation

IEF is often used in multidimensional shotgun proteomics and the narrow range of 3.5-4.5 is the recommended pH interval for the fractionation of tryptic peptides. Usually, even if IEF is performed in IPG strip with a narrow range pH, the entire sample must be loaded onto the strip, including the "out of IPG range" peptides. We describe a simple protocol to recover at least a part of these missing peptides and show that this recovery significantly influences the overall fractionation result, increasing the number of the identified proteins and the protein coverage.

Application of zirconia modified with KOH as heterogeneous solid base catalyst to new non-edible oil for biodiesel

This study seeks to investigate zirconia modified with KOH as heterogeneous solid base catalyst for transesterification of new non-edible, Silybum marianum (oil content 46%, FFA 0.68% and linoleic acid 65.68%) oil using methanol to biodiesel. Having screened the catalytic performance of ZrO2 loaded with different K-compounds, 32% KOH loaded on ZrO2 was chosen. The catalyst was prepared using incipient wetness impregnation method. Following drying (after impregnation) and calcination at 530°C for 5h, the catalyst was characterized by means of Hammett indicators, XRD, FTIR, SEM, TGA and N2 adsorption desorption measurements. It was found that the yield of the fatty acid methyl esters (FAME) was related to the catalyst base strength. The catalyst had granular and porous structures with high basicity and superior catalytic performance for the transesterification reaction. Maximum yield (90.8%) was obtained at 15:1 methanol to oil molar ratio, 6% catalyst amount, 60°C reaction temperature in 2h. The catalyst maintained sustained activity after five times of usage. The oxidative stability and iodine value were the only unsuitable properties of the biodiesel (out of range) but can easily be improved. The cetane number, flash point and the cold flow properties among others were however, comparable to international standards. The study indicated that KOH(32%)/ZrO2-5 is an economically, suitable catalyst for producing biodiesel from S. marianum oil which is a potential new non-edible feedstock that can contribute positively to biodiesel industry as its biodiesel can be rated as promising alternate fuel.

First Definition of Reference Intervals of Liver Function Tests in China: A Large-Population-Based Multi-Center Study about Healthy Adults

BackgroundReference intervals of Liver function tests are very important for the screening, diagnosis, treatment, and monitoring of liver diseases. We aim to establish common reference intervals of liver function tests specifically for the Chinese adult population.MethodsA total of 3210 individuals (20–79 years) were enrolled in six representative geographical regions in China. Analytes of ALT, AST, GGT, ALP, total protein, albumin and total bilirubin were measured using three analytical systems mainly used in China. The newly established reference intervals were based on the results of traceability or multiple systems, and then validated in 21 large hospitals located nationwide qualified by the National External Quality Assessment (EQA) of China.ResultsWe had been established reference intervals of the seven liver function tests for the Chinese adult population and found there were apparent variances of reference values for the variables for partitioning analysis such as gender(ALT, GGT, total bilirubin), age(ALP, albumin) and region(total protein). More than 86% of the 21 laboratories passed the validation in all subgroup of reference intervals and overall about 95.3% to 98.8% of the 1220 validation results fell within the range of the new reference interval for all liver function tests. In comparison with the currently recommended reference intervals in China, the single side observed proportions of out of range of reference values from our study for most of the tests deviated significantly from the nominal 2.5% such as total bilirubin (15.2%), ALP (0.2%), albumin (0.0%). Most of reference intervals in our study were obviously different from that of other races.ConclusionThese used reference intervals are no longer applicable for the current Chinese population. We have established common reference intervals of liver function tests that are defined specifically for Chinese population and can be universally used among EQA-approved laboratories located all over China.

New diagnostic and therapeutic strategies in acute and chronic central serous corioretinopathy

AbstractPurpose Central serous chorioretinopathy (CSCR) is a disease in which a serous detachment of the neurosensory retina occurs over an area of leakage from the choriocapillaris through the retinal pigment epithelium (RPE). CSCR can be acute or chronic. Classic image studies for CSCR are Fluorescine Angiography (FA) and Optical Coherence Tomography (OCT).No medical therapy is currently indicated for CSCR despite a range of potential medical treatments evaluated in many case reports. Argon laser photocoagulation can be considered only with a single leak located more than 300 µm from the center of the fovea. Autofluorescence (AF) with ultra‐widefield scanning laser and Subthreshold Micropulse (SDM) photostimulation with true yellow 577nm diode laser are the newer diagnostic and therapeutic options.Methods AF with ultra‐widefield scanning laser (Daytona™, Optos plc UK) was performed in fifteen patients affected by acute and chronic CSCR. All the areas of serous retinal detachment visible at AF as hyperfluorescence were treated with SDM photostimulation (IQ 577™ true yellow laser, Iridex CA). Controls were made at 15 days, 1 and three months after the treatment.Results Ultra‐widefield AF allowed to identify several zones of serous detachment not detected with FA and out of range of OCT scans. In most of cases we obtained the complete resolution of serous detachment and visual acuity improvement. Gain in visual acuity was better in acute cases of CSCR.Conclusion Ultra‐widefield AF followed by SDM photostimulation can be an effective diagnostic and therapeutic option for patients with acute and chronic CSCR.

Development and Evaluation of the Innovative Smartphone Interface Bioelectrical Impedance Analyzer

Development and Evaluation of the Innovative Smartphone Interface Bioelectrical Impedance Analyzer

Sensor-Based Autonomous Robot Navigation with Distance Control

Intelligent systems to increase the road safety have been widely applied in the automotive sector; similarly, they have critical importance in the robotics to navigate the robot safely. This paper deals with an automatic distance control system, which helps to avoid collision between vehicles. We present an algorithm to maintain a distance between the robot and the object. It keeps the autonomous mobile robot at a safe distance from the object. It is implemented in a wheeled mobile robot to track the moving object. The surrounding information is obtained through the range sensors that are mounted at the front side of the robot. The central sensor gives instructions for the forward and backward motion, and the other sensors help for the left and right motion. To avoid collision, safety distance, which makes the movement easy in the out of range, stop, forward, and backward modes, is predefined in the mobile robot. Each time the range data is compared with the predefined distance measurements, and the respected function is activated. The robot is characterized due to low cost and simple control architecture. Different experiments were carried out in the indoor and outdoor environments with different objects. Simulation and experimental results have shown that the robot tracks the object correctly by maintaining a constant distance from the followed object.

MAGE-A3 expression in patients screened for the DERMA trial: A phase III trial testing MAGE-A3 immunotherapeutic in the adjuvant setting for stage IIIB-C-Tx melanoma.

8559 Background: Administration of MAGE-A3 immunotherapeutic involves the active immunization of patients (pts) with tumors expressing the MAGE-A3 protein. This new investigational approach has been previously assessed in two phase II trials, one in pts with metastatic melanoma (NCT00086866) and another in pts with completely resected non-small cell lung cancer (NCT00290355). Based on the positive responses observed in both studies, a randomized phase III placebo controlled trial assessing MAGE-A3 immunotherapeutic as adjuvant treatment in pts with resected, regionally advanced melanoma (stage IIIB-C-Tx AJCC/UICC 2010) is currently ongoing (DERMA Phase III trial, NCT00796445). Methods: Formalin-fixed, paraffin-embedded tumor tissues were prepared from surgically removed metastatic lymph nodes and tested for MAGE-A3 expression by qRT-PCR. Other baseline patient and tumor characteristics were collected during screening to further investigate factors that could potentially influence MAGE-A3 expression. Results: Between Dec 1, 2008 and Oct 25, 2011, 3917 pts were screened. Of the 3,183 valid samples (excluding the 513 inconclusive tests [66% for poor quality, 27% out-of range, 7% miscellaneous]) and the 221 missing samples, 2,092 (65.7%) were positive for MAGE-A3 expression. In these stage III melanoma pts, no difference in MAGE-A3 expression levels were identified with regard to (1) disease stage - IIIB (62.6%), IIIC (66.5%) and IIITx (66.2%); (2) gender - male (64.2%), female (68.1%); (3) age group - 18 to 39 years (63.2%), 40 to 49 years (65.3%), 50 to 59 years (66.8%), 60 to 69 years (68.1%) and 70 years and over (63.4%) and (4) region: Europe (66.1%), North America (63.0%) and rest of the world including Argentina, Brazil, Australia, Mexico, Taiwan, Japan, Korea (67.9%). Conclusions: Expression of the MAGE-A3 gene in the DERMA trial population (stage IIIB-IIIC-IIITx) was 66%. It was not correlated with age, gender, disease stage or geographic region. This expression frequency is consistent with published data in metastatic melanoma (Van den Eynde, 1997; Vourc’h-Jourdain et al, 2009) and has potentially important clinical implications.

Too Hot, Too Cold: Issues With Vaccine Storage

In the United States, infants, children, and adolescents receive ∼130 million immunizations annually as part of the recommended childhood and adolescent immunization schedule.1,2 In addition, recommendations for annual influenza immunization have become more inclusive,1,2 and new pediatric vaccines continue to be licensed.3 Each recommended vaccine has specific storage requirements that must be maintained during transport and after receipt until administration. To guide immunization programs and health care professionals, information on vaccine administration and storage is provided in the Red Book from the American Academy of Pediatrics Committee on Infectious Diseases; in the “General Recommendations on Immunization” statement from the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC)4,5; and in the CDC publication “Vaccine Management: Recommendations for Storage and Handling of Selected Biologicals.”6 Vaccine susceptibility to loss of potency from out-of range temperatures depends on … Address correspondence to Larry K. Pickering, MD, FAAP, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE, Mailstop E05, Atlanta, GA 30333. E-mail: lpickering{at}cdc.gov

Long-term follow-up in children treated for retroperitoneal malignant tumours.

Thirty-two long-term survivors after treatment with surgery, radiotherapy and chemotherapy for neuroblastoma (NRB) and Wilms' tumour (WT) were re-evaluated after a period of more than 10 years (mean 16 yr 1 mo, range 27 yr 2 mo/10 yr 5 mo). In addition to routine clinical and laboratory studies, all patients underwent auxometry, echocardiography, spinal X-ray, abdominal US and kidney radionuclide scans. Neither obvious physical signs nor cutaneous toxicity were noted at inspection. No dysmenorrhoea or sexual disorders were mentioned. Haematological data turned out to be all in the normal range, except for TIBC/UIBC ratio (out of range in 70 % of cases); gammaGt (62.5 %); A/G ratio (12.5 %); ALT (37.5 %). Auxometrical data were all in the normal range; in particular, results of mean weight and height were just slightly over the 50 degrees centile. Spinal X-rays revealed mild kyphotic deformities (68.9 %), pelvic obliquity and tilting (62.5 %), rotation of the vertebral bodies (34.3 %) and compensatory curves of the spine (21.8 %). No impairment of cardiac functions was noted at echocardiography. No alteration of the hepatic structure was detectable at US scans. Marked impairment of the renal function (20 % and 1.5 % residual function) was detected at radionuclide imaging in 2 NRB patients who had not undergone nephrectomy, with the kidney having almost disappeared in one. In conclusion, the study emphasises the need for careful and prolonged follow-up for the detection of sequelae than can appear even many years after the initial treatment, and the wisdom and the need for a continued search for less aggressive protocols; as long as the cure rate is not compromised, less aggressive protocols should aim for a satisfactory overall survival with a reduced incidence of sequelae and hence a better quality of life.

Accident on Mount McKinley

Accident on Mount McKinley

Evaluation of the CELL-DYN ® 3500 Haematology Instrument for the Analysis of the Mouse and Rat Blood

The objective of this study was to evaluate the performance of the CELL-DYN® 3500 for rat and mouse blood analysis in a routine environment. The WBC (white blood cells), RBC (red blood cells), PLT (platelets) counts and the WBC differential were determined. In addition, the following aspects were studied: within-run precision, day-to-day precision, biasfree paired difference precision; extended ranges of linearity for RBC, HCT (haematocrit), WBC, PLT; carry-over, the fffect of blood ageing, cell stability with different anticoagulants; and the normal ranges, the out of range flagging and some typical pathology cases.The CELL-DYN® 3500 is a multiparameter flow cytometer which counts and differentiates WBC, based on the principle of multi-angle polarised light scatter separation. RBC and PLT are determined by the impedance method. The WBC count is evaluated by both, optical and impedance methods. Reference methods used were according to the ICSH recommendations on blood cell analysis, including manual counts of WBC and platelets, a centrifugal microhaematocrit method and a haemoglobin measurement by spectrophotometry using the WHO haemoglobin standard. All cell counts were compared with the results obtained by our routine blood cell analyser (Contraves AL820), and the WBC differential was compared with the manual microscopic differentiation of the 400 WBC (200 cells differentiated by two technicians).The following coefficients of variation were obtained: within-run precision was 1.2% and 2.7% for WBC; 1.0% and 1.0% for RBC; 1.3% and 0.9% for haematocrit; 2.1% and 2.7% for platelets (rats and mice respectively). Day-to-day precision was performed using human trilevel control blood, and the CVs were found to be <1.7% for WBC, <1.4% for RBC, <1.2% for haemoglobin and <6.3% for platelets.The following ranges of measurement were found to be linear in the rat: WBC: 0.10–20.20×103/μl; RBC: 0.016–14.3×106/μl; haemoglobin: 0.08–26.8 g/dl; haematocrit: 5.0%–77%; platelets: 14.0–1670.0×103/μl. Equal ranges were observed for mouse blood. Carry-over in rat blood was found to be 0.12% for WBC, 0.05% for RBC, 0.15% for haemoglobin and 0.46% for platelets. In mice, similar carry-over results were obtained. The correlation coefficients (Pearson, correlation coefficient) between the CELL-DYN® 3500 and Contraves AL 820 using linear regression analysis were as follows: 0.988 and 0.997 for WBC; 0.986 and 0.920 for RBC; 0.995 and 0.984 for haemoglobin; 0.958 and 0.85 for haematocrit; 0.958 and 0.963 for platelets, for rats and mice, respectively. Correlation coefficients between the CELL-DYN® 3500 and the manual differential of NEU (neutrophils) and LYM (lymphocytes) were higher than 0.8 in rats and higher than 0.9 in mice. Due to the relatively low absolute counts of MONO (monocytes), EOS (eosinophils) and BASO (basophils), only moderate correlation of methods was found.The CELL-DYN® 3500 was judged to be reliable, accurate and easy-to-use for counting and identifying normal and most of the pathological blood specimens obtained from mice and rats. By using the CELL-DYN® 3500, the time for blood sample analysis can be shortened significantly and provides extensive opportunities to characterise pathological samples.

Evaluation of the CELL-DYN® 3500 haematology instrument for the analysis of the mouse and rat blood

The objective of this study was to evaluate the performance of the CELL-DYN® 3500 for rat and mouse blood analysis in a routine environment. The WBC (white blood cells), RBC (red blood cells), PLT (platelets) counts and the WBC differential were determined. In addition, the following aspects were studied: within-run precision, day-to-day precision, biasfree paired difference precision; extended ranges of linearity for RBC, HCT (haematocrit), WBC, PLT; carry-over, the fffect of blood ageing, cell stability with different anticoagulants; and the normal ranges, the out of range flagging and some typical pathology cases.

Interference of anti-T4 autoantibodies in the single step free T4 radioimmunoassays

The thyroid hormone profile of a hypothyroid patient, with moderate sized diffuse goiter and history of exogenous thyroid hormone therapy, was found to be highly ambiguous. The total as well as free T4 levels were consistently high (out of range) with suppressed T3 (total and free) and elevated thyrotropin levels. We incubated the serum with the radio-iodine labelled T4 and observed that the patient's serum bound about 50.5% of the total radioactivity resulting in 85.3% interference in the radioimmunoassay. On resolving the serum proteins by cellulose acetate electrophoresis, the radioactivity was detected in the gamma globulin band. The protein profile showed mildly raised levels of IgG. Therefore it was established that the patient's serum carried T4 reactive antibodies (IgG) which were interfering in the immunoassays. Elevated anti-thyroid microsomal antibodies were also present in the patient's serum. The anti-T4 antibodies were highly specific for T4 and did not show any cross reactivity with the T3 or its analogues used in the estimation of free T3. We stripped the serum by precipitating the immunoglobulins and were successful in estimating the levels of free T4 in the stripped serum by single step radioimmunoassy.

Interference of anti-T3 autoantibodies in the measurement of total and free T3 in serum

A case of anti-trilodothyronine autoantibodies is presented in this report. The thyroid hormone profile of a hypertensive patient, with multinodular goiter and history of exogenous thyroid hormone therapy, was found to be highly ambiguous. The total as well as free T3 levels were consistently high (out of range) whereas the T4 (total and free) values were always within normal limits. The thyrotropin was found to be partially suppressed. Very low T3-Uptake indicated some kind of interference in the immunoassays. We incubated the sera with the radio-iodine labelled T3 and observed that the patient's serum bound about ten times more radioactivity than a control run in parallel. On further resolving the serum proteins on cellulose acetate electrophoresis, the radioactivity was detected in the γ-globulin band. Therefore it was established that the patient's serum carried the antibodies reactive with T3 which were interfering in the immunoassays. Elevated anti-thyroid microsomal antibodies were also present in the patient's serum. The anti-T3 antibodies were highly specific for T3 and did not show any cross reactivity with the T4 or its analogues used in the estimation of free T4.

DERIVATION OF STRUCTURAL DESIGN SENSITIVITIES FROM VIBRATION TEST DATA

Structural sensitivities are often required in dynamic analyses of engineering structures, such as system identification and control, structural modification and optimization. Many different methods have been developed in the last three decades for the efficient computation of such sensitivities. Though these existing methods have proven to be very useful tools to structural analysts, they are restricted to those cases where accurate analytical or finite element models are available. In many practical applications where sensitivities are needed in the solution of troubleshooting problems only limited measured data are available; existing methods being inapplicable. In this paper, a new and effective method has been developed to derive structural design sensitivities, both frequency response function sensitivities and eigenvalue and eigenvector sensitivities, from limited vibration test data. Design sensitivities calculated directly from measured data are more accurate than those calculated from analytical or finite element models since structural modelling errors are inevitable due to the complexity of almost all engineering structures. The relationship between frequency response function sensitivities and eigenvalue and eigenvector sensitivities has been established. This relationship provides the theoretical basis for the experimental determination of eigenvalue and eigenvector sensitivities. The effect of residue (contribution of out-of range modes) upon analysis accuracy has been examined. Detailed numerical assessment based on a turbine bladed disk model as well as experimental investigation of a beam structure have been conducted and the results have demonstrated the practicality of the proposed method.

The Range of the Ancient Bow

CIRCE, WHILE WARNING ODYSSEUS of the dangers to come, told him that one might shoot an arrow across (KaL KEP 6~LoiareruEas) the strait from Scylla to Charybdis (Hom. Od. 12.102). In the Cyropaedia (1.4.23) Xenophon recounts how the Assyrians invaded Media and were met by Astyages; when he refused the conventional missile skirmish and advanced within bowshot (vras L-v6/EYvoS '6s1 875l ro~Evaros), the astonished Assyrians broke and fled. When the Ionians at the passage of the Ister were pressed by the Scythians to betray Darius, they feigned assent and destroyed the bridge, but only the north end far as an arrow reaches (6uov Tb6evya EiKVETraL, Hdt. 4.139.1). The Thracians, after butchering the people of Mycalessus in 413, fled back to the Euripus, but their ships abandoned them and anchored out of bowshot (itew OCcoteblaroS, Thuc. 7.30.2). When Agathocles was trying to land in Africa, the Carthaginians overtook him; the two fleets battled with slings and arrows until the Greeks began to prevail, whereupon the foe retired and moored a little out of range (MLKpbY w BXovs, Diod. Sic. 20.6.3). In A.D. 238 when Maximinus Thrax reached Aquileia his troops proceeded to invest the city, staying out of bowshot (telvavres Qco rotebmaros, Herodianus 8.4.6). While such passages hardly raise the bowshot to the dignity of a formal unit of length, they certainly imply an approximate measurement, howsoever empirically devised. Modern estimates range from 64 metres to 600 metres.' Surely greater precision than this can be wrung from the evidence.

The Issue Should Be Decided Now

assured. The prophetic visibility is admittedly low; few of us would pretend we can see very far into the fog of uncertainty that is even the immediate future. We badly need some intellectual counterpart of radar. Even so, certain concrete facts can be made out, not all of them pleasant. One is that our old security, the security that came in part from our two broad oceans, has been repealed by science. Whereas we have been used to thinking of ourselves as out of range and almost impossible to reach, we now realize that our old ally, geography, has taken some bad blows. We accept the sobering truth that this country can be the target of a surprise attack, and is not impossible of invasion. Whatever else may be true of the postwar world, we know that much is so.