Academic literature on the topic 'USP Reference Standards'

Abstract Background: The U.S. Pharmacopeia (USP) established microbiological procedures to evaluate nonsterile products and nutritional and dietary supplements for objectionable microorganisms of concern in the industry. A rapid method has been developed to detect the presence of microorganisms based on real-time photometric monitoring of pH, carbon dioxide, or fluorescence indicators within a novel broth/agar combination vial and accompanying reader. Objective: To validate the performance of the Neogen Rapid Microbiology System (NRMS) method against the USP reference method for the ability to detect presence or the absence of Escherichia coli, Salmonella, Staphylococcus aureus, and Pseudomonas aeruginosa in nutraceutical and dietary supplements. Methods: Over 200 samples were evaluated for the presence of objectionable microorganisms. For each specified microorganism, a minimum of 23 matrices were tested uninoculated and with a low-level inoculum of <1–27.4 CFU/g, as paired samples, by NRMS and USP methods. Results: In the four objectionable microorganism categories evaluated, 100% inclusivity, 97–100% exclusivity, 97–100% positive predictivity, 100% negative predictivity, and Kappa Indices of 0.97–1.0 were achieved following ISO 5725-6:1994 standards. Conclusions: The validation study demonstrates that NRMS is a rapid and effective method to detect objectionable microorganisms in a variety of nutraceutical and dietary supplements. Highlights: A novel method was validated against the relevant USP reference method for the detection of Escherichia coli, Salmonella, Staphylococcus aureus, and Pseudomonas aeruginosa in nutraceutical and dietary supplements. NRMS provided results statistically comparable to the USP reference method within 22 h following primary enrichment compared with 5–7 days by the reference method.

Background: Generic products must be bioequivalent to the innovator brand product. Nevertheless, in addition to meeting bioequivalence standards, attention must be paid to the content of the active substance and contaminants in generic drugs. Objective: This study compared the pharmaceutical quality of four generic losartan potassium formulations with the brand-name product: Cozaar®. Methods: The United States Pharmacopeia (USP) losartan potassium standard was used as reference material. The products tested (all 50 mg formulations) included four generic tablet formulations and the innovator brand product Cozaar®. Active substance content, organic impurities, and elemental impurities were assessed following the USP monograph for losartan potassium tablets and USP Chapter <233> on Elemental Impurities. Results: The results showed that three of the four generic products had low content of the active ingredient. The values ranged from 86.4 to 93.8%, being acceptable not below 95% of the labeled amount. Organic impurities were not detected in any of the products, and of the 13 elemental impurities tested, only four elements were detected. The elemental impurities Cr, Ni, Cu, and As were, however, in amounts within the limits established by the USP monograph. The only concern on the generic drugs analyzed was the low content of the active ingredient in 75% of the products. Conclusion: Since losartan is a drug of continuous use, lower content of the active ingredient may go unnoticed by the users of the generic product and entailed clinical consequences during long-term therapy.

Abstract Soon after the introduction of low molecular weight heparins (LMWHs) as antithrombotic agents, a LMWH standard to cross-reference the potency of commercially available LMWHs was developed. For the past 15 years, this standard has been used by manufacturers to cross-reference their branded LMWHs. The 1st LMWH standard (85/600) was produced by nitrous acid digestion of porcine mucosal heparin. This standard had characteristics that were comparable to dalteparin. Because of the widespread use of the first standard, the supplies are now depleted necessitating the introduction of new standard material. The WHO has introduced a 2nd LMWH standard which is also produced by nitrous acid digestion and which mimics the commercially available LMWH reviparin. The molecular weight profile and the biologic activities, including SERPIN affinity, of these two standards are very distinct. When used to cross-reference commercially available LMWHs such as enoxaparin, the new standard consistently overestimates the anti-Xa potency by 5–10% in comparison to the first standard. Such an overestimation may lead to a reduction in dosage and have a significant impact on the clinical dosing of LMWH in various indications. As many generic versions of LMWHs are currently being introduced, a systematic study was carried out to cross-reference three commercially available generic products from India and South America against the first and second LMWH standards using amidolytic anti-Xa and anti-IIa assays. Differences were observed in the slopes of the concentration-response curves for these standards in both the anti-Xa and anti-IIa assays. The potencies of the generic LMWHs ranged from 141 to 152 U/mg in relation to the first standard and from 132 to 143 U/mg in relation to the second standard. On average, the anti-Xa potency was 6.5% lower when calculated with the 2nd standard. The differences in anti-IIa potency were further amplified and exhibited wider variation. On average, the anti-IIa potency was 18.9% lower when calculated with the 2nd standard. These studies clearly demonstrate that the limitations in the use of the first and second LMWH standards for cross-referencing commercially available LMWHs and their potential generic versions. If the 2nd standard is used, it should first be cross-referenced against the first standard in order to properly assign the anti-Xa and anti-IIa activities. This study also underscores the need for developing individual standards for each of the branded products. Such standards should be defined in terms of not only anti-Xa and anti-IIa activity, but also in terms of anticoagulant activity in global clotting assays such as the USP assay, activated clotting time (ACT), aPTT and Heptest. Such designations will be particularly useful in evaluating the potential equivalence of generic versions of branded LMWHs.

Abstract A method for rapidly screening pharmaceuticals by thin-layer chromatography has been designed for use in areas with limited resources and by operators with limited training. An apparatus for performing the analysis in a plastic bag under equilibrium conditions was designed. Results can be reproduced by different operators and in different locations. The analysis can be performed without electricity or in a remote area, away from a laboratory. It is especially suited for field use in developing countries. The method is low cost, maintenance-free, fast, and reliable; it also uses limited volumes of solvents. The analyses can be performed without weighing if reference materials can be supplied in tablet form, provided the drug content is listed and only one unit is required for each analysis. All procedures were developed for the analysis of drugs from a partial list of essential drugs established by the World Health Organization. Three drugs were selected and prepared in the form of reference tablets. Comparisons with the analyses of the drugs in standard dosage forms were made by using reference tablets and primary USP standards. Comparable results were obtained, proving that the screening process can be conducted by using reference tablets and without weighing either the sample or the reference. The method has been successfully demonstrated and used in Swaziland, by high school teachers in the United States, and by personnel from the Ministry of Health in Saudi Arabia. Personnel can be trained in a short time to perform screening analysis of drugs.

Tuberculosisis is an infectious Neglected Tropical Disease (NTD) considered a public health problem in several countries. Rifampin (RIF) is one of the first choice drugs in the treatment of this disease since it has bactericidal action on susceptible strains of Mycobacterium tuberculosis, the etiological agent of tuberculosis affecting humans. According to the literature RIF can exist in two polymorphic forms, namely forms I and II, a penta-hydrate and an amorphous solid1. Each form has different solubility in aqueous medium affecting the bioavailability of the drug when it formulated in solid dosage forms for oral administration since they are expected to content form II2. The objective of this research is to characterize and understand in detail the pharmaceutically relevant forms of RIF. It is an important and challenging problem related to the development of formulations because the physical mixture of these forms is usually observed in raw materials from generic suppliers. Thus, the reference sample (USP standard) and two lots from different suppliers were investigated by electron microscopy, Raman and infrared spectroscopies, X-ray diffraction powder and thermal analysis. In addition, pure samples of these solid forms were produced by recrystallization under different conditions in order to establish the structural reference standards. The results of this study will be useful for the development of efficient quality control methods for a drug which is very important to the social health programs.

Abstract Objectives Turmeric (Curcuma longa) is a popular ingredient in dietary supplements (DS), promoted for a variety of health effects. FDA label regulations require information on the total weight of each botanical or extract present in a botanical DS, unless it is part of a proprietary blend. Information on the concentration of phytochemicals in extracts is voluntary. DS with turmeric rhizome powders and/or extracts were tested for curcuminoid content and the results compared to label claims and industry standards as part of the Dietary Supplement Ingredient Database (DSID) research program. The performance quality of the dosage forms was also evaluated. Methods Commonly consumed DS (n = 54 × 2 lots) with turmeric as the only or primary ingredient were analyzed for curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Certified reference materials, in-house controls and blind sample duplicates were measured to ensure the quality of results from three laboratories. Percentages of total curcuminoids (TC) and ratios of the three curcuminoids were compared to published standards. Voluntary content claims were categorized as “complete” (all listed turmeric ingredients had a TC claim) or “partial” (only one of two had a TC claim). Tablets/caplets (n = 9) and capsules (n = 39) were also tested for disintegration and soft gels (n = 4) for rupture. Results Measured TC amounts varied widely among products. At the most common labeled level of 500 mg of turmeric per day, measured TC results ranged from 16 to 554 mg (n = 12). DS with voluntary claims for TC (n = 41) had analytical content averaging 6.2% above label, and 63% within ± 10% of claims. DS with complete TC claims had significantly higher levels in mg per day than those with partial or no claims (735 ± 87, 137 ± 37, 196 ± 57; mean ± SE, respectively). The curcuminoid ratios and/or the percentages of TC differed significantly from United States Pharmacopeial (USP) standards for at least 10 DS. Most (87.5%) DS passed disintegration tests and all soft gels passed the rupture test. Conclusions Current labeling requirements for turmeric DS may be insufficient to inform researchers and consumers about the actual content of TC in DS because the extract concentrations vary widely. Voluntary claims for TC amounts were reasonably accurate. Most turmeric DS met USP disintegration and composition standards. Funding Sources NIH-ODS and USDA-ARS.

Natural polysaccharides hold advantages over synthetic polymers for conventional and novel dosage forms, because these are non-toxic, less expensive, and biodegradable. These can also be modified to tailor-made materials and thus can compete with the available synthetic excipients. Therefore, the aim of present work is to extract sodium alginate from the seaweed S. subrepandum to assess its binding property using propranolol as model drug. Sodium alginate was extracted by room-temperature alkaline extraction and high-temperature (80°C) alkaline extraction methods. Binding strength was evaluated by using two different formulations i.e., formulation 1 with sodium alginate as a binder and formulation 2 with hydroxypropylmethylcellulose (HPMC) as reference standard. The two tablet formulations were evaluated and compared for parameters such as friability, hardness and disintegration. The percentage yield was found to be 17.5% w/w by room-temperature alkaline extraction and 21%w/w by high-temperature extraction method. The results obtained for all tested parameters for tablets with sodium alginate were found within acceptable range of USP standards. It was also founded that both sodium alginate and HPMC have similar binding strength at similar concentration. So, it can be concluded that sodium alginate of S. subrepandum can be used as suitable alternative binder in tablet formulations.Keywords: Sargassum subrepandum; Sodium alginate; Hydroxypropyl methylcellulose; Friability; Hardness; Disintegration.© 2011 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi:10.3329/jsr.v3i3.6770 J. Sci. Res. 3 (3), 619-628 (2011)

The process of harmonisation of Russian and foreign approaches and requirements in the field of medicines quality assurance calls for revision of quality control procedures included in various regulations and guidelines. The monograph FS.2.5.0062.18 “Hawthorn flowers” of the State Pharmacopoeia of the Russian Federation XIV edition includes a test procedure for determination of flavonoids by a chromatospectrophotometric method. This procedure does not take into account current scientific capabilities and has a number of shortcomings, therefore it was necessary to revise the existing test procedure and develop a new approach to the standardisation of the hawthorn flower herbal substance.The objective of the study was to develop an assay method for standardisation and evaluation of hawthorn flower using high performance liquid chromatography (HPLC).Materials and methods: the study was performed using samples of hawthorn flowers by Russian manufacturers. Quercetin (USP RS) and Hyperoside (HWI, primary standard) were used as the reference standards. The HPLC analysis was performed using an Infinity II 1260 DAD LC system (Agilent), and the UV spectra were recorded on a Cary 100 Varian spectrophotometer. A TLC Visualizer (CAMAG) was used to obtain digital images of thin layer chromatography plates.Results: the authors developed an HPLC test procedure for quantitative determination of total flavonoids, expressed as hyperoside, in hawthorn flowers. The developed procedure gives reliable and reproducible results and is characterised by high sensitivity and selectivity. The results of quantitative determination of the total flavonoid content in hawthorn flowers were used to propose the standard for the total content of flavonoids, expressed as hyperoside, of “not less than 0.5%”.Conclusions: the developed assay method for determination of active pharmaceutical ingredients in hawthorn flower products by HPLC can be recommended for inclusion into the Assay part of the “Hawthorn Flowers” monograph of the State Pharmacopoeia of the Russian Federation.

Abstract Isonicotinic acid impurity in bulk niacin was detected and identified by comparison with a reference material by liquid chromatography with a diode array detector. The niacin was dissolved in dilute hydrochloric acid and chromatographed on an amine column with a mobile phase of methanol and water acidified with formic acid. Isonicotinic acid has a relative retention time of 1.5 compared with niacin (nicotinic acid), and the wavelengths of maximum ultraviolet (UV) absorbance for isonicotinic acid and niacin are 270 and 260 nm, respectively. The amount of impurity found in the niacin sample was 0.3%. Twelve formulations, including sustained-release products, one bulk material, and the United States Pharmacopeia (USP) reference standard were tested. The impurity was detected in only the bulk and USP reference material samples.

Class of 2011 Abstract<br>OBJECTIVES: To investigate if the drug content of several different antibiotic products, obtained in Mexico, fall within the USP specification range for a given drug. METHODS: Ten antibiotic products containing either amoxicillin, ampicillin, ciprofloxacin, or sulfamethoxazole/trimethoprim were obtained from three random pharmacies in Mexico. The concentrations of the active ingredient(s) in these antibiotics were determined by high performance liquid chromatography, utilizing assays from the USP monographs for each drug. Weight variation within each product was also considered. Ten units from each product were analyzed. RESULTS: More than half of the capsules for each of the amoxicillin lots analyzed were outside of the acceptable USP limits (90-120% label claim) with the average calculated % label claim for each being 89.96 and 87.25%, respectively. One lot of ampicillin had two capsules out of range, while all of the capsules tested from the second lot were within the specification range. Both lots of ciprofloxacin passed. For the sulfamethoxazole/triemthoprim tablets, the sulfamethoxazole content for each lot was in range, however 20-30% of the units analyzed were out of range for trimethoprim. Interestingly, weight variation within each product was less than 3% RSD for all products, with the exception of the ampicillin lot which had two capsules out of spec (% RSD- 6.14). CONCLUSION: Most of the Mexican acquired antibiotics had content uniformity that fit within the USP guidelines. Although amoxicillin displayed significant variability, the capsules fell outside of the USP limits by a slim margin. While these findings are not a representation of all antibiotics obtained from Mexico, they do suggest the importance of continued research of the quality of internationally obtained products.

Whether to assess the functionality of equipment or as a determinate for the accuracy of assays, reference standards are essential for the purposes of standardisation and validation. The ELISPOT assay, developed over thirty years ago, has emerged as a leading immunological assay in the development of novel vaccines for the assessment of efficacy. However, with its widespread use, there is a growing demand for a greater level of standardisation across different laboratories. One of the major difficulties in achieving this goal has been the lack of definitive reference standards. This is partly due to the ex vivo nature of the assay, which relies on cells being placed directly into the wells. Thus, the aim of this thesis was to produce an artificial reference standard using liposomes, for use within the assay. Liposomes are spherical bilayer vesicles with an enclosed aqueous compartment and therefore are models for biological membranes. Initial work examined pre-design considerations in order to produce an optimal formulation that would closely mimic the action of the cells ordinarily placed on the assay. Recognition of the structural differences between liposomes and cells led to the formulation of liposomes with increased density. This was achieved by using a synthesised cholesterol analogue. By incorporating this cholesterol analogue in liposomes, increased sedimentation rates were observed within the first few hours. The optimal liposome formulation from these studies was composed of 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and brominated cholesterol (Brchol) at a 16:4:12 µMol ratio, based on a significantly higher (p<0.01) sedimentation (as determined by a percentage transmission of 59 ± 5.9 % compared to the control formulation at 29 ± 12 % after four hours). By considering a range of liposome formulations ‘proof of principle’ for using liposomes as ELISPOT reference standards was shown; recombinant IFN? cytokine was successfully entrapped within vesicles of different lipid compositions, which were able to promote spot formation within the ELISPOT assay. Using optimised liposome formulations composed of phosphatidylcholine with or without cholesterol (16 µMol total lipid) further development was undertaken to produce an optimised, scalable protocol for the production of liposomes as reference standards. A linear increase in spot number by the manipulation of cytokine concentration and/or lipid concentrations was not possible, potentially due to the saturation that occurred within the base of wells. Investigations into storage of the formulations demonstrated the feasibility of freezing and lyophilisation with disaccharide cryoprotectants, but also highlighted the need for further protocol optimisation to achieve a robust reference standard upon storage. Finally, the transfer of small-scale production to a medium lab-scale batch (40 mL) demonstrated this was feasible within the laboratory using the optimised protocol.

Public Health<br>M.S.<br>This study compares anthropometry of rural Indian schoolchildren using national and international reference values, and explores association between demographic and socioeconomic variables and growth measures among rural children. A cross-sectional survey of height, weight, and BMI was conducted among schoolchildren (5-16 years) in Gujarat, where there were pre-established contacts who could facilitate access to schools and data collection for this study. Gender- and age-specific Z-scores were obtained for 519 children (234 girls, 285 boys) based on Indian reference values (Khadilkar et al., 2009) using an Excel® macro. Percentages of children stunted (height-for-age less than or equal to -2SD), underweight (weight-for-age less than or equal to -2SD), and wasted (BMI-for-age less than or equal to -2SD) were obtained (Khadilkar & Khadilkar, 2011). Children falling between adult Indian BMI levels 23 and 28 kg/m2 were considered overweight, and those above 28 kg/m2 were considered obese. Those stunted (height-for-age + 1SD), and obese (BMI > +2SD) were generated similarly using the WHO International Growth Standards (WHO, 2015). Regression analyses were conducted to model the relationship between growth measures, determined using national references, and predictor variables: age, gender, school, and caste. 21%, 23.1%, 8.9%, 2.7% and 0.2% of children were respectively stunted, underweight, wasted, overweight and obese based on Indian References and recommendations, and 27 %, 8.7%, 6.4% and 2.7 % respectively stunted, wasted, overweight and obese based on WHO Standards and recommendations. School was found to have significant interaction with all growth measures (P <.0001) and age had a significant interaction with height-for-age (P = 0.05). The current level of undernutrition, and emerging problems of overnutrition, in this study highlight a need to concentrate efforts to improve nutrition of Indian schoolchildren in rural areas.<br>Temple University--Theses

Thesis (MScMed)--Stellenbosch University, 2008.<br>ENGLISH ABSTRACT: Introduction: Flow cytometry has progressively replaced many traditional laboratory tests due to its greater accuracy, sensitivity and rapidity in the routine clinical settings especially clinical trails. It is a powerful tool for the measuring of chemical (the fluorochrome we add) and physical (size and complexity) characteristics of individual cells. As these instruments became major diagnostic and prognostic tools, the need for more advanced quality control, standardized procedures and proficiency testing programs increased as these instrumentations and their methodology evolve. Minor instrument settings can affect the reliability, reproducibility and sensitivity of the cytometer and should be monitored and documented in order to ensure identical conditions of measurement on a daily basis. This can be accomplished by following an Internal Quality Assurance (IQA) and/ or External Quality Assurance (EQA) program. Currently there are no such programs available in South Africa and poorer Africa countries. HIV is a global concern and the laboratories and clinics in these places are in need of such IQA programs to ensure quality of their instrumentation and accurate patient results. Quality assurance programs such as CD Chex® and UK Nequas are available but due to bad sample transport, leave the receiving laboratories with nightmares. It would be best if there was a laboratory in South Africa that could provide the surrounding laboratories with stabilized whole blood samples that can be utilized as IQA. The transport of these samples can be more efficient due to shorter distance and thus the temperature variations limited. Aims and Objectives: The aim of Chapter one is to familiarize the reader with general terminology and concepts of immunology. Chapter two describes in detail the impact stabilized whole blood had on clinical immunology concerning Quality Control and Quality Assurance. The objective of this study is to stabilize whole blood with a shelf life of greater than 30 days to serve as reference control material for South African Immunophenotyping. It is further an objective to use these in-house stabilized control samples for poorer African countries as Internal Quality Assurance reference material. It is a still further objective to stimulate various lymphocyte subsets to express activation antigens and then stabilize these cells for more specialized immunological test and can serve as a QC for those required samples. Study design: In Chapter three, the method currently used to stabilize whole blood was modified. The stability of different concentrations of a first stabilizing agent (Chromium Chloride hexahydrate) was investigated. Incubation periods and concentrations of paraformaldehyde as second stabilizing agent were investigated. Blood samples from healthy individuals (n=10) were stabilized and monitored for the routine HIV phenotypic surface antigens over a period of 40 days. These samples (n=10) were compared on the Becton Dickinson Biosciences (BD) FACSCalibur™ versus BD FACSCount™ instrumentation. Blood samples (n=3) were stabilized and monitored to identify phenotypic cell surface molecules for as long as possible. They were quantified on both flow cytrometric instruments. In addition, these stabilized samples (n=3) were investigated as control blood for calibration purposes on the BD FACSCount™ instrument. In Chapter four, lymphocytes were isolated and activated with various stimuli to express sufficient activation antigens such as CD25, CD69, HLA-DR and CD40 Ligand on the T helper cell surfaces. These activated antigens were analyzed on the BD FACSCalibur™ and further stabilized to serve as possible IQA samples in future. Results: In Chapter three, the ten individual stabilized samples had non-significant P values (P > 0.05) for CD3, CD4 and CD8 percentages and absolute values comparing day 3 until day 40. Comparing the BD FACSCalibur™ versus BD FACSCount™, resulted in a R2 = 0.9848 for CD4 absolute values and a R2 = 0.9636 for CD8 absolute values. Stabilized blood samples (n=3) were monitored for routine HIV phenotypic markers until day 84. The cells populations were easily identifiable and could be quantified on both BD FACSCalibur™ and BD FACSCount™ instruments. In Chapter four; for the activation study purposes, activated T helper lymphocytes expressed approximately 25 to 35% CD40 Ligand cell surface molecules. The stimulant of choice was Ionomycin at a 4μM concentration. Cells were incubated for four hours at 37 degree Celsius in a 5% CO2 environment. For CD69 surface expression, 6 hour incubation was optimum. The stimulus of choice in this case was 4μM Ionomycin which induced 84.21% CD69 expression in the test samples. For CD25 expression; 6 hour incubation with PHA resulted in approximately 43% of CD25 expression. For HLA-DR surface expression; 6 hour incubation with PHA resulted in approximately 43.32% of HLA-DR expression. Activated lymphocytes expressing CD40 Ligand showed stability until day 23. Activated Lymphocytes expressing CD69, CD25 and HLA-DR were stabilized in the same manner and stability could be achieved until day 16. Conclusion: This thesis was related to the preparation of control samples (IQA) designed to simulate whole blood having defined properties in clinical laboratory situations. In future kits can be developed with a low, medium and high control sample for the various immunological phenotypic determinants. Another kit can be compiled where various activation markers can be identified, quantified with a “zero”, low and high control. These whole blood IQA kits and “activation IQA kits” can be implemented for training of newly qualified staff, competency testing of staff, method development, software testing, panel settings and instrument setting testing. Control samples ideally must have a number of properties in order to be effective. For instance stability during storage times, preferably lasting more than a few weeks, reproducibility and ease of handling. These will provide the information on day-to-day variation of the technique or equipment which will enhance accuracy and improve patient care.<br>AFRIKAANSE OPSOMMING: Inleiding: Vloeisitometrie tegnologie het verskeie tradisionele laboratorium toetse vervang as gevolg van beter akuraadheid, sensitiwiteit en vinniger beskikbaarheid van resultate in ‘n kliniese omgewing, veral kliniese proewe. Vloeisitometrie is ‘n kragtige tegniek om chemiese (fluorokroom byvoeging) en fisiese (sel grote en kompleksiteit) karakter eienskappe van individuele selle te meet. Met die toename in gebruik en gewildheid van hiedie instrumente, neem die behoefde toe vir gevorderde kwaliteit kontroles, gestandardiseerde prosedures, met profesionele toets programme tesame met metode ontwikkeling. Klein verstellings aan instrument parameters beinvloed die betroubaarheid, herhaalbaarheid en sensitiwiteit van ‘n sitometer en moet gemonitor (en dokumenteer) word om identiese kondisies van leesings op ‘n daaglikse basis te verseker. Dit kan bereik word deur in te skakel met ‘n interne kwaliteits versekerings program [IQA: “Internal Quality Control”] en/of ‘n eksterne kwaliteits versekerings program [EQA: “External Quality Control”] te volg. Op die oomblik is daar geen sulke kwaliteits versekerings programme in Suid Afrika en/of in die verarmende Afrika lande beskikbaar nie. MIV is ‘n wêreldwye bekommernis en laboratoriums en klinieke in hierdie gedeeltes van die land verlang ‘n dringende behoefdte vir sulke “IQA” programme om kwaliteit van instrumentasie en akkurate pasiënt resultate te verseker wat tot beter behandeling van pasiënte lei. Kwaliteit versekerings programme soos “CD Chex®” en “UK Nequas” is beskikbaar, maar baie probleme met verwysing na monster integriteit as gevolg van tydsame vervoer en aflewering kondisies word hiermee geassosieër. Die behoefte het ontstaan vir ‘n laboratorium in Suid Afrika wat direk die omliggende laboratoriums, hospitale en klinieke kan voorsien met gestabiliseerde blood monsters wat gebruik kan word as “IQA”. Die vervoer en aflewerings kondisies van hierdie monsters sal aansienlik verbeter as gevolg van die korter aflewerings afstand wat direk die beperkte temperatuur wisseling beinvloed. Doel van studie: Die doelwit van hoofstuk een is om vir die leser ‘n inleiding te gee tot terminologie en konsepte van immunologie en die immune sisteem. Hoofstuk twee beskyf die impak wat gestabiliseerde heelbloed het op die kliniese immunologie met betrekking tot kwaliteit beheer en kwaliteit versekering. Die doelwit van hierdie studie is om heelbloed te stabiliseer sodat die rakleeftyd meer as 30 dae is en sodoende as verwysings-materiaal kontroles vir Suid Afrikaanse immunofenotipering kan dien. Dit is ‘n verdere doelwit om hierdie tuis-gestabiliseerde kontrole monsters te gebruik as “IQA” verwysings materiaal in verarmende Afrika lande. Die doelwit van hoofstuk vier is om limfosiete te stimuleer om verskeie aktiverings merkers uit te druk op hul selmembrane en dan te stabiliseer en dié te gebruik as Kwaliteits Kontroles vir die meer gespesialiseerde immunologiese toetse. Studie ontwerp: Hoofstuk drie beskryf ‘n aangepaste en verbeterde metode van heel bloed stabiliseering. Stabiliteit word ondersoek in ‘n verskyndenheid konsentrasies van ‘n primêre stabiliseerings agent (chromium chloried heksahidraat) en inkubasie periodes met paraformaldehied as tweede stabiliseerings agent word deeglik gedokumenteer. Bloedmonsters van gesonde indiwidië (n=10) was gestabiliseer en gemonitor vir roetine MIV membraanoppervlak antigene oor ‘n periode van 40 dae. Hierdie monsters (n=10) was gelees en geanaliseer op ‘n BD FACSCalibur™ en vergelyk met ‘n BD FACSCount™ vloeisitometer instrument. Drie gestabiliseerde heelbloed monsters (n=3) was gemonitor vir ‘n periode vir so lank moontlik die fenotipiese selmembraan molekules identifiseerbaar was en die kwantiteit bepaalbaar was. Hierdie drie monsters was gemeet op beide instrumente. As ‘n addisionele doelwit, was hierdie drie gestabiliseerde monsters ondersoek om as moontlike kalibrasie materiaal (verteenwoordig ‘n normale bloedmonster) te dien vir die BD FACSCount™ instrument in die oggende voor pasiënt monsters gelees kan word. In hoofstuk vier was limfosiete geϊsoleer en geaktiveer met ‘n verskyndenheid stimulante om optimale aktiveerings-antigene uit te druk op T helper selmembrane (byvoorbeeld CD25, CD69, HLA-DR en CD40 Ligand). Hierdie geaktiveerde monsters was geanaliseer op die BD FACSCalibur™ en daarna gestabiliseer. Na stabilisasie van die geaktiveerde limfosiet monsters was dit gemonitor oor ‘n tydperk so lank moontlik data plotte leesbaar en selpopulasies identifiseerbaar was. Hierdie monsters kan dien as ‘n moontlike “IQA” toets stel vir ‘n meer gespesialiseerde immunologiese aktiveerings kontrole doeleindes. Resultate: In hoofstuk drie; tien individiële gestabiliseerde heelbloed monsters het gedui op geen-beduidende P waardes (P > 0.05) vir CD3, CD4 en CD8 persentasies en absolute waardes; gemeet vanaf DAG 3 vergelykbaar tot-en-met DAG 40. Met korrelasie statistiek en vergelyking van die BD FACSCalibur™ met die FACSCount™ instrumente, is die volgende opgemerk; R2 = 0.9848 vir die CD4 absolute waardes en ‘n R2 = 0.9636 vir die CD8 absolute waardes. Drie gestabiliseerde monsters (n=3) was gemonitor vir MIV roetine fenotipeering tot en met DAG 84. Die selpopulasies was duidelik identifiseerbaar en die kwantitatief meetbaar op albei instrumente (BD FACSCalibur™ en BD FACSCount™). Hoofstuk vier: geaktiveerde T helper lymphosiete het 25 – 35% membraan CD40 Ligand uitgedruk op hul selmembrane. Die stimulant van keuse was ionomysien teen ‘n optimale konsentrasie van 4μM. Die optimale inkubasie tydperk was vier ure by 37°C in 5% CO2 kondisie. Ses uur inkubasie in 4μM ionomysien by 37°C in ‘n 5% CO2 omgewing was optimal vir die CD69 selmembraan uitdrukking en het 84.21% opgelewer. Vir CD25 selmembraan uitdrukking was die selle vir ses ure met phietoheamagglutinin (PHA) gestimuleer by 37°C in 5% CO2 kondisie en het 43% CD25 selmembraan uitdrukking opgelewer. HLA-DR selmembraan uitdrukking: selle was vir ses ure saam met PHA by 37°C in 5% CO2 kondisie inkubeer en het 43.32% opgelewer. CD40 Ligand aktivering/gestabiliseerde limfosiete het tot en met dag 23 stabiliteit getoon. Die ligand was duidelik identifiseerbaar en kwantifiseerbaar. Geaktiveerde lymphosiete wat CD69, CD25 en HLA-DR selmembraan merkers uitdruk het na die stabiliseerings proses stabiliteit getoon tot-en-met dag 16. Gevolgtrekking: Die doel van hierdie studie was om verwysingskontroles voor te berei sodat dit vars heelbloed naboots met uitkenbare eienskappe vir kliniese situasies. ‘n Toets kontrolestel met verwysings materiaal vir drie vlakke (byvoorbeeld ‘n lae, medium en hoë kontrole) absolute selwaardes en persentasies kan voorberei word vir roetine immunologiese fenotiperings merkers (CD3/CD4/CD8/CD45). Meer gespesialiseerde kontrolestelle vir meer spesifieke doeleindes kan opgemaak word wat ‘n verskydenheid van limfosiet aktiveringsmerkers bevat met byvoorbeeld ‘n “nul”, lae en hoë verwysings kontrole daarin. Hierdie heelbloed kan dien as “aktiveerde interne kwaliteits verwysings materiaal” en kan gebruik word om nuut aangestelde laboratorium werkers en nuut gekwalifiseerde studente op te lei. Hierdie verwysings materiaal / kontroles kan aangewend word vir bevoegdheids doeleindes (byvoorbeeld vir SANAS akkreditasie doeleindes), vir metode ontwikkeling, vir sagteware toetsing, vir paneel opstelling en instrument verstellings doeleindes. Die kontroles moet ‘n verskydenheid eienskappe bevat om effektief te wees. Byvoorbeeld, stabiliteit tydens storing, gewenslik meer as ‘n paar weke, herhaalbaar en maklik handteerbaar. Hierdie kontroles sal inligting voorsien op ‘n daaglikse basis tydens wisseling van tegnieke of instrumentasie wat akuraatheid beinvloed en op die ou-end direk pasiënt versorging bevoordeel.

As the argument of this thesis deals with the polarities of language usage in Jamaica, Part One presents the historical context in which a language 'continuum' came to exist in the society. Then it analyses the systemic contrasts between Jamaican Creole (JC) and Standard English (SE), and the language varieties between these two polar lects. A case history of Elementary/Primary schools in the late nineteenth and early twentieth._ centuries drew attention to the Creole-Standard debate. Educational administrators misunderstood the nature of the linguistic configuration - denying pupils' Creole the right to exist - while teachers were singularly ill-equipped to help boys and girls acquire English. Part Two deals with the empirical investigation which centres on a substantially representative sample of 530 Secondary pupils. The study seeks to determine the extent to which the Secondary sector, which is designed for the masses, can achieve two divergent linguistic goals laid down by the Ministry of Education - 'appreciation of Creole' and 'a high level of competence in English'. The study probes in some depth the concept of 'linguistic focusing' as it seeks to assess pupils' access to English through the printed word and the media. Then it closely analyses their perspectives on language use and attitudes to both languages. Finally, the assessment of two written tasks provides evidence of pupils' productive abilities in English. The data clearly reveal that they have not acquired English, even after eight years of exposure to formal teaching. Indeed, the majority leave school with negative attitudes to JC and a legacy of linguistic insecurities. The thesis concludes on a hopeful note, however, as it suggests how a new political will, the insights of linguistic scholarship and new vistas in teacher education could combine to resolve the Creole-Standard debate.

The tutorial covers the issues of building the basics of the 1C 8.3 programming language. It is intended for both beginners and advanced users. The presentation of the material is divided into two sections. The first section provides the basics of the 1C 8.3 programming language for beginners. In the second section, the use of the 1C 8.3 language is given for advanced users — in a reference form, using specific examples. Meets the requirements of the federal state educational standards of higher education of the latest generation. For students of higher educational institutions studying in all areas of training and specialties, as well as for graduate students and students of the IPK.

In the textbook, the rules of Russian spelling and punctuation are grouped by topics: "Spelling of roots", "Spelling of suffixes and endings", "Use of hyphens", "Colons and dashes", etc.&#x0D; Training exercises will help to consolidate the theoretical material. The summary tables and answers to the exercises given at the end of the book allow you to control yourself during independent classes.&#x0D; The reference nature of the book contributes to the rapid and successful preparation for control works, tests and exams in the Russian language.&#x0D; Meets the requirements of the federal state standards of secondary vocational education of the latest generation.&#x0D; For students of secondary vocational education, as well as for high school students, applicants, students and everyone who wants to master the skills of literate writing.

The textbook corresponds to the general education programs of the general courses "Hydraulics" and "Fluid Mechanics". The basic physical properties of liquids, gases, and their mixtures, including the quantum nature of viscosity in a liquid, are described; the laws of hydrostatics, their observation in natural phenomena, and their application in engineering are described. The fundamentals of the kinematics and dynamics of an incompressible fluid are given; original examples of the application of the Bernoulli equation are given. The modes of fluid motion are supplemented by the features of the transient flow mode at high local resistances. The basics of flow similarity are shown. Laminar and turbulent modes of motion in pipes are described, and the classification of flows from a creeping current to four types of hypersonic flow around the body is given. The coefficients of nonuniformity of momentum and kinetic energy for several flows of Newtonian and non-Newtonian fluids are calculated. Examples of solving problems of transient flows by hydraulic methods are given. Local hydraulic resistances, their use in measuring equipment and industry, hydraulic shock, polytropic flow of gas in the pipe and its outflow from the tank are considered. The characteristics of different types of pumps, their advantages and disadvantages, and ways of adjustment are described. A brief biography of the scientists mentioned in the textbook is given, and their contribution to the development of the theory of hydroaeromechanics is shown. The four appendices can be used as a reference to the main text, as well as a subject index. Meets the requirements of the federal state educational standards of higher education of the latest generation. For students of higher educational institutions who study full-time, part-time, evening, distance learning forms of technological and mechanical specialties belonging to the group "Food Technology".

AbstractStarting sometime in 2008/2009 one expects to be able to take a glimpse at physics at the TeV scale. This will be done through the Large Hadronic Collider (LHC) at CERN, Geneva. It will be a result of an unprecedented coordinated international scientific effort. This chapter is written in 2007. It is essentially inviting disaster to spell out in full detail what the current various theoretical speculations on the physics are, as well motivated as they may seem at this time. What I find of more value is to elaborate on some of the ideas and the motivations behind them. Some may stay with us, some may evolve and some may be discarded as the results of the experiments unfold. When the proton antiproton collider was turned on in the early eighties of the last century at Cern the theoretical ideas were ready to face the experimental results in confidence, a confidence which actually had prevailed. The emphasis was on the tremendous experimental challenges that needed to be overcome in both the production and the detection of the new particles. As far as theory was concerned this was about the physics of the standard model and not about the physics beyond it. The latter part was left safely unchallenged. That situation started changing when the large electron positron (LEP) collider experiments also at Cern were turned on as well the experiments at the Tevatron at Fermilab. Today it is with rather little, scientifically based, theoretical confidence that one is anticipating the outcome of the experiments. It is less the method and foundations that are tested and more the prejudices. It is these which are at the center of this chapter. Some claim to detect over the years an oscilatory behavior in the amount of conservatism expressed by leaders in physics. The generation in whose life time relativity and quantum mechanics were discovered remained non-conservative throughout their life. Some of the latter developed eventually such adventurous ideas as to form as a reaction a much more conservative following generation. The conservative generation perfected the inherited tools and has uncovered and constructed the Standard Model. They themselves were followed by a less conservative generation. The new generation was presented with a seemingly complete description of the known forces. In order to go outside the severe constraints of the Standard Model the new generation has drawn upon some of the more adventurous ideas of the older generation as well as created it own ideas. In a way almost all accepted notions were challenged. In the past such an attitude has led to major discoveries such as relativity and quantum mechanics. In some cases it was carried too far, the discovery of the neutrino was initially missed as energy conservation was temporarily given up.

AbstractThis paper presents the results of a pilot study carried out in cooperation between Linguistics and Mechanical Engineering, funded by the collaborative research centre (CRC) 805 “Beherrschung von Unsicherheit in lasttragenden Systemen des Maschinenbaus”. Our goal is to help improve norm compliant product development and engineering design by focusing on ambiguous language use in norm texts (= “semantic uncertainty”). Depending on the country and product under development, industry standards may be legally binding. Thus, standards play a vital role in reducing uncertainty for manufacturers and engineers by providing requirements for product development and engineering design. However, uncertainty is introduced by the standards themselves in various forms, the most notable of which are the use of underspecified concepts, modal verbs like should, and references to texts which contain semantically uncertain parts. If conformity to standards is to be ensured, the person using the standards must interpret them and document the interpretation. In order to support users in these tasks, we developed an annotation schema which allows the identification and classification of semantically uncertain segments of standards, used the schema to create a taxonomy of semantic uncertainty in standards, developed a proof-of-concept information system. The results of this project can be used as a starting point for automated annotation. The information system alerts users to semantically uncertain segments of standards, provides background information, and allows them to document their decisions how to handle the semantically uncertain parts.

This chapter gives an overview of the research in developing “minimum income standards” and “family budget standards,” “indicative budgets” and “standard budgets.” It analyzes goods and services that are considered necessary to reach a minimum standard of living for an individual or household within a given country context, region, or city. It also brings together up-to-date and accessible information and analysis in an effort to raise the profile and understanding of reference budget research. The chapter places minimum income standards at the heart of global social policy debates that focus on strengthening social protection systems. It also discusses reference budgets and minimum income standards research, covering different methodologies and approaches in relation to the implementation of policy and practice.

Developed at the request of the US Department of Transportation, Section XII-Transport Tanks, of the ASME Boiler and Pressure Vessel Code addresses rules for the construction and continued service of pressure vessels for the transportation of dangerous goods by road, air, rail, or water. The standard is intended to replace most of the vessel design rules and be referenced in the federal hazardous material regulations, Title 49 of the Code of Federal Regulations (CFR). While the majority of the current rules focus on over-the-road transport, there are rules for portable tanks which can be used in marine applications for the transport of liquefied gases, and for ton tanks used for rail and barge shipping of chlorine and other compressed gases. Rules for non-cryogenic portable tanks are currently provided in Section VIII, Division 2, but will be moved into Section XII. These portable tank requirements should also replace the existing references to the outmoded 1989 edition of ASME Section VIII, Division 1 cited in Title 46 of the CFR. Paper published with permission.

The reference stress for axial (longitudinal) surface cracks in cylinders is compared using equations from the 2016 API 579-1/ASME FFS-1 and BS 7910:2013 engineering standards, and by using J-integral values from elastic-plastic Finite Element Analysis of three-dimensional crack meshes to compute crack front reference stress. The cylinder axial surface crack reference stress solutions from the two standards differ, and further examination and comparison is desired. To evaluate if a crack is unstable and may cause catastrophic structural failure, the Failure Assessment Diagram method provides an evaluation using two ratios: brittle fracture and plastic collapse. The FAD vertical axis gives the Kr stress intensity to toughness ratio, and the FAD horizontal axis gives the Lr reference stress to yield strength ratio. The details of the FAD method are described in both standards, along with stress intensity and reference stress solutions for various geometries and crack shapes. Since the cylinder axial surface crack reference stress solutions from API 579 and BS 7910 differ, J-integral values are used to compute reference stress trends that provide additional insight and reveal if there is agreement with one or the other or neither standard. Computing reference stress from crack front J-integral results is described in API 579 Annex 9G Section 9G.4. A 3D crack mesh is created for each crack and cylinder size. Along the crack front the focused mesh pattern uses initially coincident groups of nodes at each crack front position. The group of nodes at each location on the crack front are initially coincident and can separate to help model the blunting at the crack front as the loading increases and local plasticity occurs. Post processing calculations use the J-integral versus load trend and the material specific Kr at Lr = 1 ratio to determine the reference stress geometry factor. The reference stress is computed at each crack front node to find the maximum crack front reference stress value for comparison to the engineering standards’ reference stress solutions. A range of surface crack sizes in thin to thick wall cylinders with internal pressure are used to examine reference stress trends. Standard pipe sizes and typical pipeline steel material is used in the analysis. The difference in reference stress solutions was found during an engineering critical assessment, so the J-integral approach was used to improve the solution to reduce conservatism and allow the component to remain in service.

Many end-users, specifiers, governmental agencies and testing facilities, are not fully aware of the wealth of standards available for GRP piping products and the continuing work being done in CEN &amp;ISO and other standards developing organizations. As a result the introduction of Ad-Hoc test methods, standards and obsolete requirements is, unfortunately, not uncommon. The paper will list and comment available GRP Standards that has been prepared as a reference guide to assist in the proper specification and use of GRP piping products. The primary focus is on EN and ISO standards. The work being done in CEN and ISO is closely linked, with ISO taking the lead in test method development and ISO test methods being referenced in EN standards. The work in CEN is conducted in CEN TC 155 WG14 and the work in ISO in ISO TC138 SC6. However, important standards are issued by other standards organizations and these will be also covered in the paper.

This paper presents both criticism and suggested changes to boiler efficiency standards associated with fossil-fired steam generators. These standards include the widely used ASME PTC 4.1, PTC 4 and DIN 1942, and others. The chief criticism is inconsistent application of thermodynamic principles. Specifically, conceptual errors are made with application of reference temperatures and the treatment of shaft powers. When using computed fuel flow as a touchstone, it becomes obvious that arbitrary use of reference temperatures and/or use of capricious energy credits cannot dictate a system’s computed fuel flow. Efficiency, calorific value and fuel flow must have fixed definitions concomitant with a system’s useful energy flow. Thermodynamics is not an arbitrary discipline, the computed fuel needs of a system must describe the actual. Boiler efficiency requires the same treatment, as an absolute value, as actual fuel feed and emission flow. Boiler efficiencies and associated calorific values have obvious standing when judging contractual obligations, for thermal performance monitoring, and for confirming carbon emissions. Note that a 0.5 to 1% change in efficiency may well have significant financial consequences when testing a new unit, or the on-going costs associated with fuel and carbon taxes. This paper demonstrates that errors greater than 2% are entirely possible if following the current standards. This paper appeals to the resolution of efficiency at the 0.1% level. The power plant engineer is encouraged to read the Introduction and Summary &amp; Recommendations sections while the thermodynamicist is requested to throughly review and critique the mid-sections. The author hopes such reviews will advocate for improvement of these important industrial standards.

In consultation with ASTM and other stakeholders in Tissue-Engineered Medical Products (TEMPs) industry, the National Institute of Standards and Technology (NIST) initiated a project designed to produce Reference Material scaffolds for tissue engineering. The rationale for Reference Material scaffolds was developed through several NIST/Industry workshops. In brief, Reference Material scaffolds have multiple uses: facilitating the development and the validation of new test methods that measure interactions among various components of a TEMP; comparison with other scaffolds and scaffold materials in terms of cellular responses, biodegradation, and releases of growth factors; and comparisons of responses among various cell lines. The primary customers for Reference Material scaffolds are expected to be the TEMPs industry, academic researchers, regulators, and standards developing organizations. There are many properties of a TEMP that warrant development of multiple Reference Material scaffolds. Currently, NIST is defining a set of Reference Material scaffolds based on geometric descriptors such as permeability, pore volume, pore size distribution, interconnectivity, and tortuosity. In consultation with ASTM, NIST is testing three candidate scaffolds produced by: three dimensional (3-D) printing, stereolithography, and fused deposition modeling (FDM). Scaffolds made by these methods have been obtained from Mayo Clinic (Rochester, MN), Case Western Reserve University (CWRU) (Cleveland, OH), and Osteopore International (Singapore), respectively, for structural characterization. These prototype scaffolds, with well-defined architectures, have been selected to address the following items of interest: 1) establishment of useful functional definitions of porosity content, interconnectivity, and pores; 2) evaluation of testing methods listed in the Standard Guide for the Porosity of Polymeric Scaffolds for Use in Tissue-Engineered Medical Products, which is being drafted by ASTM. Currently, NIST and the Center for Devices and Radiological Health of the Food and Drug Administration, as well as other groups from US and foreign laboratories, are actively carrying out cross-validation test of these prototype scaffolds.

Abstract Degradation of pressure equipment is becoming an important issue due to increasing asset service time in process and power plants across Europe. For this reason it is important to assess life consumption of these assets to avoid catastrophic failures. Therefore it is necessary to refer to national/international normative on this subject. At present time the Italian thermotechnical committee (CTI) has drawn up a comprehensive set of norms which help the user to set up an inspection plan to investigate and assess degradation of pressure vessels and boilers. In the first part of this paper creep damage of Steam Generators is analyzed. For this purpose results of INAIL (Istituto Nazionale per l’ Assicurazione contro gli Infortuni sul Lavoro) database of steam boilers with 100’000 service hours or more is illustrated. Critical components are identified with reference to materials, geometry and operating parameters (pressure, temperature and time). At the end of the design life cycle, components of pressure equipment operated in creep regime must subjected to specific checks to estimate their residual life and the suitability for further use in safety conditions. The procedure allows to define reinspection intervals keeping acceptable the risk associated with the further use of the component related to creep even in evidence of defects in progress. The first check must be performed after 100,000 hours of effective use. Then, residual life evaluations must be repeated according to period of time that are defined as function of the results of all the checks carried out. In the second part of this paper boiler degradation is discussed with reference to NDT results and in-field inspection campaigns which are carried out traditionally after 45 years of service time, to minimize the risk of pressure components failures. In this paper results of different case studies are discussed with reference to degradation mechanisms and applicable standards.

Long term asset management is a key issue in the high pressure industry, but only limited and somewhat fragmented guidelines exist in the form of various “New-Construction” Design Codes and Standards. The high pressure industry is a niche industry and many applications are not covered completely by existing codes and standards. The paper will cover an overview of various ASME and API documents and provide an overall methodology for the implementation of an effective and logical asset management protocol including Fitness for Service guidelines which can be referenced in lieu of a comprehensive document being available. ASME discontinued publication and distribution of the High Pressure Systems Standard (HPS-2003) [6] in September 2009. One of the most common uses for this document was the section on vessel requalification. The paper here will discuss the application of this requalification methodology, and its use in an overall high pressure asset management plan. API 510 [5] and the National Board Inspection Code (NBIC) [13] cover the in-service inspection, repair, alteration, and rerating activities for pressure vessels-including vessels constructed and approved as jurisdictional special based upon jurisdiction acceptance of particular design, fabrication, inspection, testing, and installation. However those documents reference most of the technical requirements in the ASME construction codes for design, welding, NDE, and materials as being applicable for in-service pressure vessels. Also, API 510 and NBIC recognize FFS assessments for evaluating the structural integrity of in-service damage of pressure-containing components. This paper will discuss the use of those construction codes for use in a Fitness for Service assessment and the development of a comprehensive strategy for long term asset management using these guidance documents in conjunction with the ASME/API Inspection Planning guidelines.

Fracture toughness is often described by the J-integral or crack-tip opening displacement (CTOD) for ductile materials. ASTM, BSI and ISO have developed their own standard test methods for measuring fracture initiation toughness and resistance curves in terms of the J and CTOD using bending dominant specimens in high constraint conditions. However, most actual cracks are in low constraint conditions, and the standard resistance curves may be overly conservative. To obtain more realistic fracture toughness for actual cracks in low-constraint conditions, different fracture test methods have been developed in the past decades. To facilitate understanding and use the test standards, this paper presents a critical review on commonly used fracture toughness test methods using standard and non-standard specimens in reference to the fracture parameters J and CTOD, including (1) ASTM, BSI and ISO standard test methods, (2) constraint correction methods for formulating a constraint-dependent resistance curve, and (3) direct test methods using the single edge-notched tension (SENT) specimen. This review discusses basic concepts, basic methods, estimation equations, test procedures, historical efforts and recent progresses.

Geometric Dimensioning and Tolerancing (GD&amp;T) Standards have established a language for clear and concise specification of dimensional and geometric variations on manufactured parts. The language includes symbols for tolerance type, tolerance value, datum and reference frames, diameter and material condition modifiers and associativity with geometric entities. Designers use the standard to communicate their dimensional specifications to manufacturing and inspection personnel. However, process planners appear to be less formal in how tolerances are represented in process plans. Typically, they are shown only as dimensional plus/minus values. Datum Reference Frames (DRF) and geometric tolerance symbols are absent. It is believed that the latter are implicit in the set-up and fixturing prescribed in the plan. In this paper we explore how one might extract the implicit information systematically. The motivation for this effort is to verify the consistency of manufacturing tolerances with design specs and to be able to use the same tolerance analysis tools used in design. We discuss three research issues: extracting implied DRFs from set-ups and fixtures; converting plus/minus tolerances to appropriate geometric tolerances; and dealing with transient features — which are features that do not exist on the finished part used for GDT specs by the designer. We propose a new data structure, PCTF (process oriented constraint tolerance feature graph) to facilitate mapping between design and manufacturing tolerances.

Objective: The purpose of this study was to assess the feasibility of administering the Automated Multiple-Pass Method (AMPM), a widely used tool for collecting 24-hour dietary recalls, in participants’ homes by field interviewers. Design: The design included computer-assisted personal interviews led by either a nutritionist (standard) or field interviewer. Portion estimators tested were a set of three-dimensional food models (standard), a two-dimensional food model booklet, or a tablet with digital images rendered via augmented reality. Setting: Residences in central North Carolina. Participants: English-speaking adults. Pregnant women and individuals who were fasting were excluded. Results: Among 133 interviews, most took place in living rooms (52%) or kitchens (22%). Mean interview time was 40 minutes (range 13–90), with no difference by interviewer type or portion estimator, although timing for nutritionist-led interviews declined significantly over the study period. Forty-five percent of participants referenced items from their homes to facilitate recall and portion estimation. Data entry and post-interview coding was evaluated and determined to be consistent with requirements for the National Health and Nutrition Examination Survey. Values for the number of food items consumed, food groups, energy intake (average of 3,011 kcal for men and 2,105 kcal for women), and key nutrients were determined to be plausible and within reasonably expected ranges regardless of interviewer type or portion estimator used. Conclusions: AMPM dietary recall interviews conducted in the home are feasible and may be preferable to clinical administration because of comfort and the opportunity for participants to access home items for recall. AMPMs administered by field interviewers using the food model booklet produced credible nutrition data that was comparable to AMPMs administered by nutritionists. Training field interviewers in dietary recall and conducting home interviews may be sensible choices for nutrition studies when response rates and cost are concerns.

As scientists, we aim to generate new knowledge and insights about the world around us. We often measure the impacts of our research by how many times our colleagues reference our work, an indicator that our research has contributed something new and important to our field of study. But how does our research contribute to solving the complex societal and environmental challenges facing our communities and our planet? The goal of this guidebook is to illuminate the path toward greater societal impact, with a particular focus on this work within the natural and physical sciences. We were inspired to create this guidebook after spending a collective 20+ years working in programs dedicated to moving climate science into action. We have seen firsthand how challenging and rewarding the work is. We’ve also seen that this applied, engaged work often goes unrecognized and unrewarded in academia. Projects and programs struggle with the expectation of connecting science with decision making because the skills necessary for this work aren’t taught as part of standard academic training. While this guidebook cannot close all of the gaps between climate science and decision making, we hope it provides our community of impact-driven climate scientists with new perspectives and tools. The guidebook offers tested and proven approaches for planning projects that optimize engagement with societal partners, for identifying new ways of impacting the world beyond academia, and for developing the skills to assess and communicate these impacts to multiple audiences including the general public, colleagues, and elected leaders.

The Heartland Inventory and Monitoring Network (HTLN) is a component of the National Park Service’s (NPS) strategy to improve park management through greater reliance on scientific information. The purposes of this program are to design and implement long-term ecological monitoring and provide information for park managers to evaluate the integrity of park ecosystems and better understand ecosystem processes. Concerns over declining surface water quality have led to the development of various monitoring approaches to assess stream water quality. Freshwater streams in network parks are threatened by numerous stressors, most of which originate outside park boundaries. Stream condition and ecosystem health are dependent on processes occurring in the entire watershed as well as riparian and floodplain areas; therefore, they cannot be manipulated independently of this interrelationship. Land use activities—such as timber management, landfills, grazing, confined animal feeding operations, urbanization, stream channelization, removal of riparian vegetation and gravel, and mineral and metals mining—threaten stream quality. Accordingly, the framework for this aquatic monitoring is directed towards maintaining the ecological integrity of the streams in those parks. Invertebrates are an important tool for understanding and detecting changes in ecosystem integrity, and they can be used to reflect cumulative impacts that cannot otherwise be detected through traditional water quality monitoring. The broad diversity of invertebrate species occurring in aquatic systems similarly demonstrates a broad range of responses to different environmental stressors. Benthic invertebrates are sensitive to the wide variety of impacts that influence Ozark streams. Benthic invertebrate community structure can be quantified to reflect stream integrity in several ways, including the absence of pollution sensitive taxa, dominance by a particular taxon combined with low overall taxa richness, or appreciable shifts in community composition relative to reference condition. Furthermore, changes in the diversity and community structure of benthic invertebrates are relatively simple to communicate to resource managers and the public. To assess the natural and anthropo-genic processes influencing invertebrate communities, this protocol has been designed to incorporate the spatial relationship of benthic invertebrates with their local habitat including substrate size and embeddedness, and water quality parameters (temperature, dissolved oxygen, pH, specific conductance, and turbidity). Rigid quality control and quality assurance are used to ensure maximum data integrity. Detailed standard operating procedures (SOPs) and supporting information are associated with this protocol.

This study is the latest in a series monitoring the evolution of poverty, based on data gathered by The ESRI in the Living in Ireland Surveys since 1994. These have allowed progress towards achieving the targets set out in the National Anti Poverty Strategy since 1997 to be assessed. The present study provides an updated picture using results from the 2000 round of the Living in Ireland survey. The numbers interviewed in the 2000 Living in Ireland survey were enhanced substantially, to compensate for attrition in the panel survey since it commenced in 1994. Individual interviews were conducted with 8,056 respondents. Relative income poverty lines do not on their own provide a satisfactory measure of exclusion due to lack of resources, but do nonetheless produce important key indicators of medium to long-term background trends. The numbers falling below relative income poverty lines were most often higher in 2000 than in 1997 or 1994. The income gap for those falling below these thresholds also increased. By contrast, the percentage of persons falling below income lines indexed only to prices (rather than average income) since 1994 or 1997 fell sharply, reflecting the pronounced real income growth throughout the distribution between then and 2000. This contrast points to the fundamental factors at work over this highly unusual period: unemployment fell very sharply and substantial real income growth was seen throughout the distribution, including social welfare payments, but these lagged behind income from work and property so social welfare recipients were more likely to fall below thresholds linked to average income. The study shows an increasing probability of falling below key relative income thresholds for single person households, those affected by illness or disability, and for those who are aged 65 or over - many of whom rely on social welfare support. Those in households where the reference person is unemployed still face a relatively high risk of falling below the income thresholds but continue to decline as a proportion of all those below the lines. Women face a higher risk of falling below those lines than men, but this gap was marked among the elderly. The study shows a marked decline in deprivation levels across different household types. As a result consistent poverty, that is the numbers both below relative income poverty lines and experiencing basic deprivation, also declined sharply. Those living in households comprising one adult with children continue to face a particularly high risk of consistent poverty, followed by those in families with two adults and four or more children. The percentage of adults in households below 70 per cent of median income and experiencing basic deprivation was seen to have fallen from 9 per cent in 1997 to about 4 per cent, while the percentage of children in such households fell from 15 per cent to 8 per cent. Women aged 65 or over faced a significantly higher risk of consistent poverty than men of that age. Up to 2000, the set of eight basic deprivation items included in the measure of consistent poverty were unchanged, so it was important to assess whether they were still capturing what would be widely seen as generalised deprivation. Factor analysis suggested that the structuring of deprivation items into the different dimensions has remained remarkably stable over time. Combining low income with the original set of basic deprivation indicators did still appear to identify a set of households experiencing generalised deprivation as a result of prolonged constraints in terms of command over resources, and distinguished from those experiencing other types of deprivation. However, on its own this does not tell the whole story - like purely relative income measures - nor does it necessarily remain the most appropriate set of indicators looking forward. Finally, it is argued that it would now be appropriate to expand the range of monitoring tools to include alternative poverty measures incorporating income and deprivation. Levels of deprivation for some of the items included in the original basic set were so low by 2000 that further progress will be difficult to capture empirically. This represents a remarkable achievement in a short space of time, but poverty is invariably reconstituted in terms of new and emerging social needs in a context of higher societal living standards and expectations. An alternative set of basic deprivation indicators and measure of consistent poverty is presented, which would be more likely to capture key trends over the next number of years. This has implications for the approach adopted in monitoring the National Anti-Poverty Strategy. Monitoring over the period to 2007 should take a broader focus than the consistent poverty measure as constructed to date, with attention also paid to both relative income and to consistent poverty with the amended set of indicators identified here.

1.1 Resumen macroeconómico En el segundo trimestre la economía enfrentó varios choques, principalmente de oferta y de costos, la mayoría de los cuales no fueron anticipados, o los previstos fueron más persistentes de lo esperado, y que en conjunto interrumpieron la recuperación de la actividad económica observada a comienzos de año y llevaron la inflación total a niveles superiores a la meta. La inflación básica (sin alimentos ni regulados: SAR) aumentó, pero se mantuvo baja y acorde con lo esperado por el equipo técnico. A comienzos de abril se inició una tercera ola de pandemia, más acentuada y prolongada que la anterior, con un elevado costo en vidas humanas y algún impacto negativo en la recuperación económica. Entre mayo y mediados de junio los bloqueos de las carreteras y los problemas de orden público tuvieron un fuerte efecto negativo sobre la actividad económica y la inflación. Se estima que la magnitud de estos dos choques combinados habría generado una caída en niveles en el producto interno bruto (PIB) con respecto al primer trimestre del año. Adicionalmente, los bloqueos causaron un aumento significativo de los precios de los alimentos. A estos choques se sumaron los efectos acumulados de la disrupción global en algunas cadenas de valor y el incremento en los fletes internacionales que desde finales de 2020 vienen generando restricciones de oferta y aumentos de costos. Todos estos factores, que afectaron principalmente el índice de precios al consumidor (IPC) de bienes y de alimentos, explicaron la mayor parte del error de pronóstico del equipo técnico y el aumento de la inflación total a niveles superiores a la meta del 3 %. El incremento en la inflación básica y de los precios de los regulados fue acorde con lo esperado por el equipo técnico, y se explica principalmente por la eliminación de varios alivios de precios otorgados un año atrás. A todo esto se suma la mayor percepción de riesgo soberano y las presiones al alza que esto implica sobre el costo de financiamiento externo y la tasa de cambio. A pesar de los fuertes choques negativos, el crecimiento económico esperado para la primera mitad del año (9,1%), es significativamente mayor que lo proyectado en el informe de abril (7,1%), signo de una economía más dinámica que se recuperaría más rápido de lo previsto. Desde finales de 2020 las diferentes cifras de actividad económica han mostrado un crecimiento mayor que el esperado. Esto sugiere que los efectos negativos sobre el producto de las recurrentes olas de contagio estarían siendo cada vez menos fuertes y duraderos. No obstante, la tercera ola de contagio del Covid-19, y en mayor medida los bloqueos a las vías y los problemas de orden público, habrían generado una caída del PIB durante el segundo trimestre, frente al primero. Pese a lo anterior, los datos del índice de seguimiento a la economía (ISE) de abril y mayo han resultado mayores que lo esperado, y las nuevas cifras de actividad económica sectoriales sugieren que el impacto negativo de la pandemia sobre el producto se sigue moderando, en un entorno de menores restricciones a la movilidad y de mayor avance en el ritmo de vacunación. Los registros de transporte de carga (junio) y la demanda de energía no regulada (julio), entre otros, indican una recuperación importante después de los bloqueos en mayo. Con todo lo anterior, el incremento anual del PIB del segundo trimestre se habría situado alrededor del 17,3 % (antes 15,8 %), explicado en gran parte por una base baja de comparación. Para todo 2021 el equipo técnico incrementó su proyección de crecimiento desde un 6 % hasta el 7,5 %. Este pronóstico, que está rodeado de una incertidumbre inusualmente elevada, supone que no se presentarán problemas de orden público y que posibles nuevas olas de contagio del Covid-19 no tendrán efectos negativos adicionales sobre la actividad económica. Frente al pronóstico del informe pasado, la recuperación de la demanda externa, los niveles de precios de algunos bienes básicos que exporta el país y la dinámica de las remesas de trabajadores han sido mejores que las esperadas y seguirían impulsando la recuperación del ingreso nacional en lo que resta del año. A esto se sumaría la aún amplia liquidez internacional, la aceleración en el proceso de vacunación y las bajas tasas de interés, factores que continuarían favoreciendo la actividad económica. La mejor dinámica del primer semestre, que llevó a una revisión al alza en el crecimiento de todos los componentes del gasto, continuaría hacia adelante y, antes de lo esperado en abril, la economía recuperaría los niveles de producción de 2019 a finales de 2021. El pronóstico continúa incluyendo efectos de corto plazo sobre la demanda agregada de una reforma tributaria de magnitud similar a la proyectada por el Gobierno. Con todo eso, en el escenario central de este informe, el pronóstico de crecimiento para 2021 es del 7,5 % y para 2022 del 3,1 %. A pesar de esto, el nivel de la actividad económica seguiría siendo inferior a su potencial. La mejora en estas proyecciones, sin embargo, está rodeada de una alta incertidumbre. En junio la inflación anual (3,63 %) aumentó más de lo esperado debido al comportamiento del grupo de alimentos, mientras que la inflación básica (1,87 %) fue similar a la proyectada. En lo que resta del año el mayor nivel del IPC de alimentos persistiría y contribuiría a mantener la inflación por encima de la meta. A finales de 2022 la inflación total y básica retornarían a tasas cercanas al 3 %, en un entorno de desaceleración del IPC de alimentos y de menores excesos de capacidad productiva. En los meses recientes el aumento en los precios internacionales de los fletes y de los bienes agrícolas, y las mayores exportaciones de carne y el ciclo ganadero han ejercido presiones al alza sobre el precio de los alimentos, principalmente de los procesados. A estas fuerzas persistentes se sumaron los bloqueos de las vías nacionales y los problemas de orden público en varias ciudades registrados en mayo y parte de junio, los cuales se reflejaron en una fuerte restricción en la oferta y en un aumento anual no esperado del IPC de alimentos (8,52 %). El grupo de regulados (5,93 %) también se aceleró, debido a la baja base de comparación en los precios de la gasolina y a la disolución de parte de los alivios a las tarifas de servicios públicos otorgados en 2020. Como se proyectaba, la inflación SAR repuntó al 1,87 %, debido a la reactivación de los impuestos indirectos de algunos bienes y servicios eliminados un año atrás, y por las presiones al alza que ejercieron los alimentos sobre las comidas fuera del hogar (CFH), entre otros. En lo que resta del año se espera que el aumento en los alimentos perecederos se revierta, siempre y cuando no se registren nuevos bloqueos duraderos a las vías nacionales. El mayor nivel de precios de los alimentos procesados persistiría y contribuiría a mantener la inflación por encima de la meta a finales de año. La inflación SAR continuaría con una tendencia creciente, en la medida en que los excesos de capacidad productiva se sigan cerrando y registraría un aumento transitorio en marzo de 2022, debido principalmente al restablecimiento del impuesto al consumo en las CFH. Con todo esto, para finales de 2021 y 2022 se estima una inflación total del 4,1 % y 3,1 %, y una inflación básica del 2,6 % y 3,2 %, respectivamente. El comportamiento conjunto de los precios del IPC SAR, junto con continuas sorpresas al alza en la actividad económica, son interpretados por el equipo técnico como señales de amplios excesos de capacidad productiva de la economía. Estos persistirían en los siguientes dos años, al final de los cuales la brecha del producto se cerraría. El mayor crecimiento económico sugiere una brecha del producto menos negativa que la estimada hace un trimestre. Sin embargo, el comportamiento de la inflación básica, especialmente en servicios, indica que el PIB potencial se ha recuperado de forma sorpresiva y que los excesos de capacidad siguen siendo amplios, con una demanda agregada afectada de forma persistente. Esta interpretación encuentra soporte en el mercado laboral, en donde persiste un desempleo alto y la recuperación de los empleos perdidos se estancó. Adicionalmente, los aumentos en la inflación en buena medida están explicados por choques de oferta y de costos y por la disolución de algunos alivios de precios otorgados un año atrás. Los pronósticos de crecimiento y de inflación descritos son coherentes con una brecha del producto que se cierra más rápido y es menos negativa en todo el horizonte de pronóstico con respecto al informe de abril. No obstante, la incertidumbre sobre los excesos de capacidad es muy alta y es un riesgo sobre el pronóstico. Las perspectivas de las cuentas fiscales de Colombia se deterioraron, Standard &amp; Poor’s Global Ratings (S&amp;P) y Fitch Ratings (Fitch) redujeron su calificación crediticia, los bloqueos y problemas de orden público afectaron el producto y el país enfrentó una nueva ola de contagios de Covid-19 más acentuada y prolongada que las pasadas. Todo lo anterior se ha reflejado en un aumento de las primas de riesgo y en una depreciación del peso frente al dólar. Esto ha ocurrido en un entorno favorable de ingresos externos. Los precios internacionales del petróleo, del café y de otros bienes básicos que exporta el país aumentaron y han contribuido a la recuperación de los términos de intercambio y del ingreso nacional, y han mitigado las presiones al alza sobre las primas de riesgo y la tasa de cambio. En el presente informe se incrementó el precio esperado del petróleo para 2021 a USD 68 por barril (antes USD 61 bl) y para 2022 a USD 66 bl (antes USD 60 bl). Esta mayor senda presenta una convergencia hacia precios menores que los observados recientemente, como resultado de una mayor oferta mundial esperada de petróleo, la cual más que compensaría el incremento en la demanda de este bien básico. Por ende, se supone que el aumento reciente de los precios tiene un carácter transitorio. En el escenario macroeconómico actual se espera que las condiciones financieras internacionales sean algo menos favorables, a pesar de la mejora en los ingresos externos por cuenta de una mayor demanda y unos precios del petróleo y de otros productos de exportación más altos. Frente al informe de abril el crecimiento de la demanda externa fue mejor que el esperado, y las proyecciones para 2021 y 2022 aumentaron del 5,2 % al 6,0 % y del 3,4 % al 3,5 %, respectivamente. En lo corrido del año las cifras de actividad económica muestran una demanda externa más dinámica de la esperada. En los Estados Unidos y China la recuperación del producto ha sido más rápida que la registrada en los países de la región. En estos últimos la reactivación económica ha estado limitada por los rebrotes del Covid-19, las limitaciones en la oferta de vacunas y el poco espacio fiscal para enfrentar la pandemia, entre otros factores. La buena dinámica en el comercio externo de bienes se ha dado en un entorno de deterioro en las cadenas de valor y de un aumento importante en los precios de las materias primas y en el costo de los fletes. En los Estados Unidos la inflación sorprendió al alza y su valor observado y esperado se mantiene por encima de la meta, al tiempo que se incrementó la proyección de crecimiento económico. Con esto, el inicio de la normalización de la política monetaria en ese país se daría antes de lo proyectado. En este informe se estima que el primer incremento en la tasa de interés de la Reserva Federal de los Estados Unidos se dé a finales de 2022 (antes del primer trimestre de 2023). Para Colombia se supone una mayor prima de riesgo frente al informe de abril y se sigue esperando que presente una tendencia creciente, dada la acumulación de deuda pública y externa del país. Todo esto contribuiría a un incremento en el costo del financiamiento externo en el horizonte de pronóstico. La postura expansiva de la política monetaria sigue soportando unas condiciones financieras internas favorables. En el segundo trimestre la tasa de interés interbancaria y el índice bancario de referencia (IBR) se han mantenido acordes con la tasa de interés de política. Las tasas de interés promedio de captación y crédito continuaron históricamente bajas, a pesar de algunos incrementos observados a finales de junio. La cartera en moneda nacional detuvo su desaceleración anual y, entre marzo y junio, el crédito a los hogares se aceleró, principalmente para compra de vivienda. La recuperación de la cartera comercial y de los desembolsos a ese sector fue importante, y se alcanzó de nuevo el elevado saldo observado un año atrás, cuando las empresas requirieron niveles significativos de liquidez para enfrentar los efectos económicos de la pandemia. El riesgo de crédito aumentó, las provisiones se mantienes altas y algunos bancos han retirado de su balance una parte de su cartera vencida. No obstante, las utilidades del sistema financiero se han recuperado y sus niveles de liquidez y solvencia se mantienen por encima del mínimo regulatorio. A partir de este informe se implementará una nueva metodología para cuantificar y comunicar la incertidumbre que rodea los pronósticos del escenario macroeconómico central, en un entorno de política monetaria activa. Esta metodología se conoce como densidades predictivas (DP) y se explica en detalle en el Recuadro 1. Partiendo del balance de riesgos que contiene los principales factores que, de acuerdo con el juicio del equipo técnico, podrían afectar a la economía en el horizonte de pronóstico, la metodología DP produce distribuciones de probabilidad sobre el pronóstico de las principales variables (v. g.: crecimiento, inflación). Estas distribuciones reflejan el resultado de los posibles choques (a variables externas, precios y actividad económica) que podría recibir la economía y su transmisión, considerando la estructura económica y la respuesta de política monetaria en el futuro. En este sentido, permiten cuantificar la incertidumbre alrededor del pronóstico y su sesgo. El ejercicio DP muestra un sesgo a la baja en el crecimiento económico y en la brecha del producto, y al alza en la inflación. El balance de riesgos indica que las disyuntivas para la política monetaria serán potencialmente más complejas que lo contemplado en el pasado. Por el lado de las condiciones de financiamiento externo, se considera que el mayor riesgo es que se tornen un poco menos favorables, en un escenario en el cual la Reserva Federal de los Estados Unidos incremente con mayor prontitud su tasa de interés. Esto último, ante un crecimiento económico y del empleo mayor que el esperado en los Estados Unidos que genere presiones significativas sobre la inflación de ese país. A esto se suma la incertidumbre sobre el panorama fiscal en Colombia y sus efectos sobre la prima de riesgo y el costo del financiamiento externo. En el caso del crecimiento, la mayoría de los riesgos son a la baja, destacándose los efectos de la incertidumbre política y fiscal sobre las decisiones de consumo e inversión, la aparición de nuevas olas de contagio de la pandemia del Covid-19 y sus impactos sobre la actividad económica. En el caso de la inflación, se incorporó el riesgo de una mayor persistencia de los choques asociados con la disrupción de las cadenas de valor, mayores precios internacionales de las materias primas y de los alimentos, y una recuperación más lenta que la esperada de la cadena agrícola nacional afectada por los pasados bloqueos a las vías. Estos riesgos presionarían al alza principalmente los precios de los alimentos y de los bienes. Como principal riesgo a la baja se incluyó un alza de los arriendos menor que el esperado en el escenario central, explicada por una demanda débil y por una mayor oferta en 2022 dadas las altas ventas de vivienda observadas en el presente año. Con todo, el crecimiento económico presenta un sesgo a la baja y, con el 90 % de confianza, se encontraría entre un 6,1 % y 9,1 % para 2021 y entre el 0,5 % y 4,1 % para 2022. La brecha del producto tendría un sesgo a la baja, principalmente en 2022. El sesgo de la inflación es al alza, y se encontraría entre el 3,7 % y 4,9 % en 2021, y el 2,2 % y 4,7 % en 2022, con un 90 % de probabilidad. 1.2 Decisión de política monetaria En las reuniones de junio y julio la JDBR decidió mantener la tasa de política monetaria inalterada en 1,75 %.