Measurement of anisotropic volumetric resistivity in lithium ion electrodes.

Measurements of the electronic conductivity of lithium ion coatings are an important part of electrode development, particularly for thicker electrodes and in high power applications. A resistance measurement system with 46 probes has been used to characterise lithium ion electrodes, with different formulations and coat weights. The results show that the total through plane resistance is dominated by the interface resistance between the coating and the metal foil, rather than the volumetric resistivity of the coating. For coatings containing carbon nano-tubes, the in plane resistivities in the coating and perpendicular directions are different. A finite volume model was developed to help analyse and interpret the resistivity data.

Good Practices for the Laboratory Performance Testing of Aqueous Oral Inhaled Products (OIPs): an Assessment from the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS).

Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies. As a result, there is a lack of consistency across all the recommendations, with the potential to cause confusion to those developing performance test methods. We have reviewed key methodological aspects of source guidance documents identified by a survey of the pertinent literature and evaluated the underlying evidence supporting their recommendations for the evaluation of these performance measures. We have also subsequently developed a consistent series of solutions to guide those faced with the various associated challenges when developing OIP performance testing methods for oral aqueous inhaled products.

Disparities in Use of Subspecialty Concussion Care Based on Ethnicity.

Concussion is common and subspecialty care can be essential to ensure recovery. However, barriers may exist to accessing care. This study aimed to assess disparities in subspecialty concussion care related to ethnicity, limited English proficiency (LEP), and insurance status. We utilized logistic regression to analyze 2010-2015 administrative data from four Sports Medicine clinics, comparing odds of being seen for concussion to odds of being seen for fracture by ethnicity, insurance type, and interpreter usage, controlling for demographic factors. ICD-9 codes were used to identify concussion and fracture. Our final sample contained 25,294 subjects: 5621 with concussion and 19,673 with fracture. In bivariate analysis, youth seen for concussion had 83% lower odds of being Hispanic compared with youth seen for fracture (95%CI: 75-92%). Due to interactions between ethnicity and interpreter use, we utilized a stratified multivariate model as our final model. Youth with concussion had 1.8× greater odds of having private insurance compared with youth with fracture (Hispanic OR 1.8, 95% CI 1.5-2.3; Non-Hispanic OR 1.8, 95% CI 1.7-2.0). Youth with concussion also had greater odds of not using an interpreter, though the strength of this association was weaker for Hispanic youth compared with non-Hispanic youth (Hispanic OR 1.68, 95% CI 1.30-2.17; Non-Hispanic OR 4.36, 95% CI 3.00-6.35). Age and sex were included as covariates. In conclusion, our analysis suggests disparities in subspecialty concussion care for Hispanic youth, as well as for individuals with LEP and non-private insurance. Further research should explore means for improving access to concussion care for all youth.

Non-Invasive Gene Expression Testing to Rule Out Melanoma.

The Pigmented Lesion Assay (PLA) is a gene expression test that helps rule out melanoma and has the potential to reduce the need for surgical biopsies of atypical pigmented skin lesions. Utilizing a new technological platform for the non-invasive profiling of skin, the assay analyzes samples collected from adhesive patches for expression of two key genes (PRAME and LINC00518) known to be overexpressed in melanoma. The test result is binary (positive/negative) based on the detection of one or both genes. PLA positive cases are generally biopsied to establish the histopathologic diagosis, while PLA negative cases are considered for ongoing monitoring. The combination of visual inspection with histopathology, the current gold standard for melanoma diagnosis, has a relatively low negative predictive value (NPV) of approximately 83%, meaning that 17% of melanomas will be interpreted as benign lesions. In contrast, the PLA has a very high NPV (>99%). Further, with its high specificity (69-91%), use of the PLA can reduce the number of false positive samples subjected to histopathology review. By adding the PLA to the current care pathway, the number of surgical biopsies needed to find a melanoma (number needed to biopsy) is markedly reduced from 20-25 biopsies for dermatologists and 39 biopsies for physician assistants, to an average of 2.7. To date, unnecessary surgical procedures of benign lesions have been reduced by 88% based on a sample of more than 20,000 analyzed cases. This has resulted in fewer missed melanomas and significant cost savings to health care systems.

Comprehensive microRNA expression profiling of the hematopoietic hierarchy.

The hematopoietic system produces a large number of highly specialized cell types that are derived through a hierarchical differentiation process from a common stem cell population. miRNAs are critical players in orchestrating this differentiation. Here, we report the development and application of a high-throughput microfluidic real-time quantitative PCR (RT-qPCR) approach for generating global miRNA profiles for 27 phenotypically distinct cell populations isolated from normal adult mouse hematopoietic tissues. A total of 80,000 RT-qPCR assays were used to map the landscape of miRNA expression across the hematopoietic hierarchy, including rare progenitor and stem cell populations. We show that miRNA profiles allow for the direct inference of cell lineage relations and functional similarity. Our analysis reveals a close relatedness of the miRNA expression patterns in multipotent progenitors and stem cells, followed by a major reprogramming upon restriction of differentiation potential to a single lineage. The analysis of miRNA expression in single hematopoietic cells further demonstrates that miRNA expression is very tightly regulated within highly purified populations, underscoring the potential of single-cell miRNA profiling for assessing compartment heterogeneity.

Gas chromatographic, mass spectrometric and stable carbon isotopic investigations of organic residues of plant oils and animal fats employed as illuminants in archaeological lamps from Egypt.

Man's use of illuminants in lamps or as torches to extend the working day and range of environments accessible to him would have been a major technological advance in human civilisation. The most obvious evidence for this in the archaeological record comes from pottery and stone vessels showing sooting due to the use of a wick in conjunction with a lipid-based fuel or illuminant. A wide range of potential fuels would have been exploited depending upon availability and burning requirements. Reported herein are the results of chemical investigations of a number of lamps recovered from excavations of the site of Qasr Ibrim, Egypt. Gas chromatographic, mass spectrometric and stable carbon isotopic analyses of both free (solvent extractable) and 'bound'(released from solvent extracted pottery by base treatment) lipids have revealed a wide range of saturated fatty acids, hydroxy fatty acids and alpha, omega-dicarboxylic acids. Examination of the distributions of compounds and comparisons with the fatty acid compositions of modern plant oils have allowed a range of fats and oils to be recognised. Specific illuminants identified include Brassicaceae (Cruciferae) seed oil (most likely radish oil, Raphanus sativus), castor oil (from Ricinus communis), animal fat, with less diagnostic distributions and delta(13)C values being consistent with low stearic acid plant oils, such as linseed (Linum usitatissimum) or sesame (Sesamum indicum) oils. The identifications of the various oils and fats are supported by parallel investigations of illuminant residues produced by burning various oils in replica pottery lamps. The findings are entirely consistent with the classical writers including Strabo, Pliny and Theophrastrus.

Archaeology: formulation of a Roman cosmetic.

The discovery of a small tin canister in London during archaeological excavations of a Roman temple precinct, dated to the middle of the second century AD, is a landmark in the study of this class of artefact. Such discoveries from the Roman world are rare and this is the only one to be found so far with its lid and contents--a whitish medicinal or cosmetic cream--providing a unique opportunity for us to study the ancient formulation.

Direct chemical evidence for widespread dairying in prehistoric Britain.

Domesticated animals formed an important element of farming practices in prehistoric Britain, a fact revealed through the quantity and variety of animal bone typically found at archaeological sites. However, it is not known whether the ruminant animals were raised purely for their tissues (e.g., meat) or alternatively were exploited principally for their milk. Absorbed organic residues from pottery from 14 British prehistoric sites were investigated for evidence of the processing of dairy products. Our ability to detect dairy fats rests on the observation that the delta(13)C values of the C(18:0) fatty acids in ruminant dairy fats are approximately 2.3 per thousand lower than in ruminant adipose fats. This difference can be ascribed to (i) the inability of the mammary gland to biosynthesize C(18:0); (ii) the biohydrogenation of dietary unsaturated fatty acids in the rumen; and (iii) differences (i.e., 8.1 per thousand ) in the delta(13)C values of the plant dietary fatty acids and carbohydrates. The lipids from a total of 958 archaeological pottery vessels were extracted, and the compound-specific delta(13)C values of preserved fatty acids (C(16:0) and C(18:0)) were determined via gas chromatography-combustion-isotope ratio mass spectrometry. The results provide direct evidence for the exploitation of domesticated ruminant animals for dairy products at all Neolithic, Bronze Age, and Iron Age settlements in Britain. Most significantly, studies of pottery from a range of key early Neolithic sites confirmed that dairying was a widespread activity in this period and therefore probably well developed when farming was introduced into Britain in the fifth millennium B.C.

Mycolic acids and ancient DNA confirm an osteological diagnosis of tuberculosis.

SETTING: The underlying trends in the past epidemiology of tuberculosis (TB) are obscure, requiring recourse to the archaeological record. It would therefore be of value to develop methods for reliable TB diagnosis in ancient populations. OBJECTIVE: To test the capability of two biomarkers, Mycobacterium tuberculosis complex mycolic acids and a DNA target (IS6110), for confirming an osteological diagnosis of TB in medieval individuals, based on the presence of Pott's disease and/or rib lesions. DESIGN: Osteological examination of three archaeological individuals (Medieval: approximately 1000 years old) revealed a Pott's disease case, one with no changes consistent with TB and one with rib lesions. Rib samples from these individuals were examined for the presence of Mycobacterium tuberculosis complex mycolic acids and mycobacterial DNA. RESULTS: Mycobacterium tuberculosis complex mycolic acids and the DNA target were detected in the Pott's disease case, whilst mycolic acids (insufficient for confirmation) alone were detected in the rib lesion case. CONCLUSIONS: Biomarkers provide a sensitive tool to detect ancient TB. Mycobacterium tuberculosis DNA is not distributed homogeneously, making multiple sampling essential. Mycolic acids seem more reliable for ancient TB diagnosis than IS6110. The demonstrated stability of mycolic acids show that they may be of value in tracing the palaeoepidemiology of tuberculosis back into antiquity.

Detection of palm fruit lipids in archaeological pottery from Qasr Ibrim, Egyptian Nubia.

In modern times, the trees of the palm family have been of great economic and social importance to the people in Egypt, as in other parts of the world. There are various species of palm and although different parts of the tree can be used, the fruit are of great value. In antiquity, it is expected that the palm fruit would also have been of great importance to people in the region. The chemical analysis of absorbed residues in archaeological pottery is well established, and through the investigation of ceramic vessels (via gas chromatography, gas chromatography-mass spectrometry and gas chromatography-combustion-isotope ratio mass spectrometry) saturated carboxylic acids in the range C12 to C18 have been detected (with an unusually high abundance of C12) from vessels from the Nubian site of Qasr Ibrim. This is mirrored in the saturated fatty acid distributions detected from the kernels of modern and ancient date palm (Phoenix dactylifera L.) and dom palm (Hyphaena thebaica (L.) Mart.). Mixing in some of the vessels of the palm fruit with another lipid source is indicated through the delta13C values. These results provide the first direct evidence for the exploitation of palm fruit in antiquity and the use of pottery vessels in its processing.

Environmental Protection Agency risk assessment--process and toxicologic pathology.

Risk assessment of a pesticide includes the identification of hazard, dose-response, exposure assessment, and risk characterization. Toxicology study reports undergo several levels of scientific and regulatory review in the Environmental Protection Agency's (EPA's) Office of Pesticide Programs. A Health Effects Division (HED) scientist reviews the reports. The resulting Data Evaluation Records are presented to several internal HED Peer Review committees to ensure consistency across chemicals in establishing which hazard end points to use when determining the reference dose and carcinogenicity potential for use in dietary and nondietary risk assessments. There may also be external reviews. The toxicologic pathologist can impact many steps in this process. The noncancer end points are just as important as the cancer end points when evaluating the hazard component of a pesticide. The toxicologic pathologist can assist in the hazard and risk characterization by being clear and concise, carefully defining terms and relating individual lesions to the animal, study, and database as a whole. The preceding will assist the HED in fulfilling EPA Administrator Carol Browner's guidance for risk characterizations that are transparent, clear, concise, and reasonable.

Evaluation of the carcinogenic potential of pesticides. 4. Chloroalkylthiodicarboximide compounds with fungicidal activity.

The Health Effects Division of the Office of Pesticide Programs (OPP) assessed the carcinogenic potential of three structurally related chloroalkylthiodicarboximide fungicides using a consensus peer review process and EPA's 1986 guidelines for cancer risk assessment. All of the fungicides were categorized as Group B2 (probable human) carcinogens based upon findings of an increased incidence of malignant tumors, or combined malignant and benign tumors, in multiple experiments involving different strains of mice and rats. The primary sites of tumor formation with the chloroalkylthiodicarboximide fungicides in male and/or female mice (CD-1 and B6C3F1) were the gastrointestinal tract (captan, folpet, and captafol), the lymph system (folpet and captafol), and the vascular system (captafol). The main sites of tumor formation in rats of one or both sexes (CR CD, Wistar, or F344 strains) were the kidney (Captan and captafol), uterus (captan), mammary gland and liver (captafol). In addition, positive trends for thyroid, testicular, mammary gland, and lymph node tumors were observed with folpet in the same strains of rats. All three of the compounds exhibited positive mutagenic activity in a variety of in vitro short-term tests for gene mutation, DNA repair, and chromosomal aberrations in prokaryotic and eukaryotic cells, but were not genotoxic in available studies performed under in vivo conditions. The assessment of human cancer risk for captan, folpet, and captafol was made using low-dose extrapolation models.

Evaluation of the carcinogenic potential of pesticides. 2. Methidathion.

The carcinogen potential of methidathion, a dimethoxyorganic phosphorus pesticide and cholinesterase inhibitor, was evaluated by the Health Effects Division of the Office of Pesticide Programs using a consensus peer review process and the EPA's guidelines for risk assessment. Methidathion was categorized as a Group C (possible human) carcinogen based upon evidence of an increased incidence of benign and malignant hepatocellular tumors, alone and in combination, in a single study involving male Chr-CD-1 mice. The compound was not carcinogenic in female Chr-CD-1 mice in the same study or in Sprague-Dawley rats of either sex in a second study. Methidathion was not genotoxic in a variety of in vitro or in vivo tests designed to detect DNA damage, chromosome aberrations, gene mutations, and sister chromatid exchange. Although methidathion was identified as being structurally similar to two other organophosphate insecticides, prothidathion and lythidathion, no toxicological data were available on either of these agents for comparative purposes. The biological information on methidathion was reviewed by the agency's FIFRA Scientific Advisory Panel who agreed with the category C designation for methidathion. The data were not found to be sufficient to quantify human risk to methidathion.

In vivo biochemical indices of nephrotoxicity of platinum analogs tetraplatin, CHIP, and cisplatin in the Fischer 344 rat.

In vivo biochemical indices of nephrotoxicity were investigated in Fischer 344 rats treated with a new platinum analog, tetraplatin [tetrachloro(dl-trans)1,2-diaminocyclohexane platinum(IV), NSC-363812], in comparison with rats receiving equimolar dosages of cisplatin and CHIP [cis-dichloro,trans-dihydroxybis-isopropylamine platinum(IV), NSC-256927]. The goals of this study were to assess the comparative nephrotoxicities and to determine which battery of tests might be useful for the assessment of platinum analog-induced nephrotoxicity in future clinical investigations of these drugs. An iv bolus injection of 6.7, 13.3, 26.7, and 53.3 mumol/kg of each drug in saline was administered and assessment of biochemical parameters was conducted for 15 days postinjection. A combination of urinary enzyme and protein excretion rates along with blood urea nitrogen (BUN) determinations was used to assess the nephrotoxicity of these compounds. At equimolar dosages, tetraplatin appeared to be less nephrotoxic than cisplatin, and CHIP was not nephrotoxic. At all dosages tested, cisplatin increased the rate of urinary excretion of protein, lactate dehydrogenase (LDH), and N-acetylglucosaminidase (NAG) between Days 1 and 5. Tetraplatin did not affect these parameters until the 13.3 mumol/kg dosage. Cisplatin had little effect on the excretion rates of the brush border enzymes alkaline phosphatase and maltase, whereas tetraplatin caused an initial elevation with delayed onset of peak excretion rates at 8 days postinjection. Changes in BUN were not evident until after the 13.3 mumol/kg dosage of cisplatin and the 26.7 mumol/kg dosage of tetraplatin. BUN was useful for ranking the relative toxicities of the three compounds tested, but was not as sensitive in detecting the onset of injury that correlated with early histopathological changes. Tetraplatin appeared to be less nephrotoxic than cisplatin on an equimolar basis and the specific manifestations of its toxicity were different from those observed with cisplatin. Urinary excretion rates for LDH, NAG, and protein proved to be sensitive indicators of platinum analog-induced nephrotoxicity. These indices, combined with BUN determinations and functional assessments, facilitated comparisons of the nephrotoxicity induced by cisplatin and tetraplatin in rats.

Comparative toxicity and renal distribution of the platinum analogs tetraplatin, CHIP, and cisplatin at equimolar doses in the Fischer 344 rat.

Tetraplatin [tetrachloro(dl-trans)1,2-diaminocyclohexane platinum(IV), NSC-363812] is a new anticancer platinum drug analog targeted for clinical development because of its effectiveness against cisplatin-resistant tumor cell lines and its improved formulation. The toxicity of tetraplatin was compared at equimolar doses to that of cisplatin [cis-diamminedichlorophatinum(II)] and CHIP [cis-dichloro,trans-dihydroxybis-isopropylamine platinum(IV), NSC-256927]. Adult male Fischer 344 rats received an iv bolus injection of 6.7, 13.3, 26.7, or 53.3 mumol/kg of one of these drugs in saline and were killed on Day 1, 3, 5, 8, or 15 postinjection for assessment of toxicity with emphasis on evaluation of nephrotoxicity. Rats to be killed on Day 15 were housed in metabolism cages for daily urine collection. Tetraplatin was less nephrotoxic than cisplatin at equimolar doses; CHIP was not nephrotoxic at these doses. Renal platinum contents were similar after all three drugs and did not appear to be related directly to the nephrotoxicity. Nephrotoxicity was detected 4-5 days after 6.7 mumol/kg cisplatin, was localized to the corticomedullary junction, and progressed with time and dose. Tetraplatin-induced alterations of renal function were first observed after 13.4 mumol/kg on Day 4 as an elevation of urine volume (up to 10-fold) and a smaller elevation of urinary glucose excretion. Tetraplatin lesions were localized in the mid- and outer cortex and, even at the highest dose, were less severe than those observed with cisplatin. There were other prominent toxic effects of tetraplatin, such as gastrointestinal toxicity and myelosuppression, which indicate that factors other than comparative nephrotoxicity may impact the clinical potential of this new agent.

Chronic sorrow in families of disabled children.

Among professionals who work with disabled children and their families, the need has arisen for better articulation of the concept of chronic sorrow, a bereavement process parents experience in response to life with a disabled child. This article presents information and concepts about the nature of chronic sorrow that permit clarification and understanding of the meaning of what is otherwise often confusing parent behavior. Implications for the professional in assisting the parent's movement through the bereavement process will be discussed.

Sensitivity of urinary enzymes as indicators of renal toxicity of the anticancer drug cis-platin.

Rats were intravenously injected with cis-platin in order to evaluate the sensitivity of noninvasive means of detecting renal toxicity. Doses of 8 mg/kg and 2 mg/kg were used and 7 urinary parameters (osmolality, glucose, protein, and 4 enzymes) were compared with blood urea nitrogen (BUN) and histology. Urinary enzymes usually were elevated by Day 2 posttreatment and in two cases by Day 1. Protein and glucose were elevated by Day 3 and demonstrated a greater quantitative change (10-12X control) than did urinary enzymes (2-3X controls). Enzymes, protein, and glucose all returned to control levels by Day 7 or 8, and most parameters were re-elevated again by Day 10 or 12. BUN was unaltered at the lowest dose and was increased to three times control by Day 3 after the highest dose. Cis-platin induced a mild nephrosis at the lowest dose and a proximal tubular necrosis at the highest dose. The lesion occurred at the corticomedullary junction. Biochemical changes did not correspond to the times of greatest morphological changes. Large day-day and animal-animal variation made selection of a most sensitive parameter difficult. It is concluded that one parameter is insufficient to define early renal toxicity and that a battery of several parameters would provide a better evaluation of the onset of renal toxicity.

Transformation and tumor promoter sensitive phosphoproteins in JB-6 mouse epidermal cells: one is also sensitive to heat stress.

JB-6 mouse epidermal cells undergo irreversible transformation when exposed to tumor-promoting agents such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Phosphoprotein changes related to transformation were sought in four tumor cell lines related to JB-6 cells. Two dimensional polyacrylamide gel electrophoresis showed altered abundances of five phosphoproteins in the tumor cell lines compared with five untransformed clones. The mol. wt. in Kilodaltons and isoelectric points in pH units were: 120/6.0, 80/4.5, 55/6.5, 37/5.0 and 23-25/4.5. In all four transformants pp80 was markedly decreased and the pp23-25 doublet increased. In two of the four transformants pp120 and pp55 were increased and pp37 decreased. Treatment of untransformed clones with TPA affected only one of the phosphoproteins altered in the transformants. Treatment of untransformed clones with TPA produced a 2-fold increase in pp80 after 5 h. pp80 returned to baseline levels by 24 h and changed little in the continuous presence of TPA for up to 96 h. The increase in pp80 with short term TPA treatment occurred in all of the untransformed clones but none of four transformants. Late preneoplastic (P+) JB-6 cells only require treatment with a tumor promoter to transform. Early preneoplastic (P-) JB-6 cells require prior transfection of DNA from late preneoplastic JB-6 cells to transform in response to tumor promoter treatment. Quantitative analysis of pp80 in early preneoplastic, late preneoplastic, and tumor cell lines showed an inverse relationship between the level of pp80 and degree of preneoplastic progression in these cells. pp80 represents approximately 2% of total cellular phosphoprotein in JB-6 cells, shows microheterogeneity of both mol. wt. and isoelectric point, occurs in the particulate fraction of cells and is readily solubilized by 1% Triton. pp80 is increased by heat stress and shares other properties with the recently described mammalian heat stress protein, hsp 80. pp80's decrease in four out of four tumor cell lines, inverse correlation with stage of preneoplastic progression and responsiveness to TPA in preneoplastic but not in tumor cell line suggest that pp80 may be closely linked to biochemical mechanisms underlying transformation in this cell system.