Outcome-based comparison of SMFM and ISUOG definitions of fetal growth restriction.

OBJECTIVE: The recent international guidelines by the Society for Maternal-Fetal Medicine (SMFM) and the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) differ in their definitions of fetal growth restriction (FGR). Our aim was to compare the performance of the two definitions in predicting neonatal small-for-gestational age (SGA) and composite adverse neonatal outcome (ANO). METHODS: This was a secondary analysis of data from a prospective study of women referred for fetal growth ultrasound examination between 26 + 0 and 36 + 6 weeks' gestation. The SMFM and ISUOG guidelines were used to define pregnancies with FGR. The SMFM definition of FGR is estimated fetal weight (EFW) or abdominal circumference (AC) < 10th percentile. The ISUOG-FGR definition follows the Delphi consensus criteria and includes either EFW or AC < 3rd percentile or EFW or AC < 10th percentile combined with abnormal Doppler findings or a decrease in growth centiles. The primary outcome was the prediction of neonatal SGA, defined as birth weight < 10th percentile, and a composite of ANO, which was defined as one or more of: Grade-III or -IV intraventricular hemorrhage, respiratory distress syndrome, neonatal death, cord blood pH < 7.1, seizures and admission to the neonatal intensive care unit. Test characteristics (sensitivity, specificity, positive predictive value (PPV), negative predictive value and positive (LR+) and negative likelihood ratios) and area under the receiver-operating-characteristics curve were determined. The association between FGR detected by each definition and selected adverse outcomes was assessed using logistic regression analysis. RESULTS: Of the 1054 pregnancies that met the inclusion criteria, 137 (13.0%) and 55 (5.2%) were defined as having FGR by the SMFM and ISUOG definitions, respectively. Composite ANO and SGA neonate each occurred in 139 (13.2%) pregnancies. For the prediction of neonatal SGA, the SMFM-FGR definition had a higher sensitivity (54.7%) than did the ISUOG definition (28.8%). The ISUOG-FGR definition had higher specificity (98.4% vs 93.3%), LR+ (18.0 vs 8.2) and PPV (72.7% vs 55.5%) than did the SMFM definition for the prediction of a SGA neonate. The SMFM- and ISUOG-FGR definitions had similarly poor performance in predicting composite ANO, with sensitivities of 15.1% and 10.1%, respectively. CONCLUSIONS: The SMFM definition of FGR is associated with a higher detection rate for SGA neonates but at the cost of some reduction in specificity. The ISUOG-FGR definition has a higher specificity, LR+ and PPV for the prediction of neonatal SGA. Both definitions of FGR performed poorly in predicting a composite ANO. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Endothelial chimerism in chronic sclerotic-type chronic graft-versus-host disease (GVHD) and GVHD-associated angiomatosis.

Graft-versus-host disease-associated angiomatosis (GVHD-AA) is an uncommon manifestation of chronic GVHD consisting of friable vascular proliferations. Using fluorescence in situ hybridization, we demonstrate the presence of donor-derived endothelial cells within areas of GVHD-AA. This is the first documented occurrence of a benign neoplastic growth in relationship to a form of chronic GVHD.

Biosorptive recovery of platinum from platinum group metal refining wastewaters by immobilised Saccharomyces cerevisiae.

The process of platinum group metal (PGM) refining can be up to 99.99% efficient at best, and although it may seem small, the amount of valuable metal lost to waste streams is appreciable enough to warrant recovery. The method currently used to remove entrained metal ions from refinery wastewaters, chemical precipitation, is not effective for selective recovery of PGMs. The yeast Saccharomyces cerevisiae has been found capable of sorbing numerous precious and base metals, and is a cheap and abundant source of biomass. In this investigation, S. cerevisiae was immobilised using polyethyleneimine and glutaraldehyde to produce a suitable sorbent, capable of high platinum uptake (150-170 mg/g) at low pH (<2). The sorption mechanism was found to be a chemical reaction, which made effective desorption impossible. When applied to PGM refinery wastewater, two key wastewater characteristics limited the success of the sorption process; high inorganic ion content and complex speciation of the platinum ions. The results proved the concept principle of platinum recovery by immobilised yeast biosorption and indicated that a more detailed understanding of the platinum speciation within the wastewater is required before biosorption can be applied. Overall, the sorption of platinum by the S. cerevisiae sorbent was demonstrated to be highly effective in principle, but the complexity of the wastewater requires that pretreatment steps be taken before the successful application of this process to industrial wastewater.

The implications of unconfounding multisource performance ratings.

The multifaceted structure of multisource job performance ratings has been a subject of research and debate for over 30 years. However, progress in the field has been hampered by the confounding of effects relevant to the measurement design of multisource ratings and, as a consequence, the impact of ratee-, rater-, source-, and dimension-related effects on the reliability of multisource ratings remains unclear. In separate samples obtained from 2 different applications and measurement designs (N1 [ratees] = 392, N1 [raters] = 1,495; N2 [ratees] = 342, N2 [raters] = 2,636), we, for the first time, unconfounded all systematic effects commonly cited as being relevant to multisource ratings using a Bayesian generalizability theory approach. Our results suggest that the main contributors to the reliability of multisource ratings are source-related and general performance effects that are independent of dimension-related effects. In light of our findings, we discuss the interpretation and application of multisource ratings in organizational contexts. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Intracellular movement of two mannose 6-phosphate receptors: return to the Golgi apparatus.

We have used Chinese hamster ovary (CHO) cells and a murine lymphoma cell line to study the recycling of the 215-kD and the 46-kD mannose 6-phosphate receptors to various regions of the Golgi to determine the site where the receptors first encounter newly synthesized lysosomal enzymes. For assessing return to the trans-most Golgi compartments containing sialyltransferase (trans-cisternae and trans-Golgi network), the oligosaccharides of receptor molecules on the cell surface were labeled with [3H]galactose at 4 degrees C. Upon warming to 37 degrees C, the [3H]galactose residues on both receptors were substituted with sialic acid with a t1/2 approximately 3 hrs. Other glycoproteins acquired sialic acid at least 8-10 times slower. Return of the receptors to the trans-Golgi cisternae containing galactosyltransferase could not be detected. Return to the cis/middle Golgi cisternae containing alpha-mannosidase I was measured by adding deoxymannojirimycin, a mannosidase I inhibitor, during the initial posttranslational passage of [3H]mannose-labeled glycoproteins through the Golgi, thereby preserving oligosaccharides which would be substrates for alpha-mannosidase I. After removal of the inhibitor, return to the early Golgi with subsequent passage through the Golgi complex was measured by determining the conversion of the oligosaccharides from high mannose to complex-type units. This conversion was very slow for the receptors and other glycoproteins (t1/2 approximately 20 h). Exposure of the receptors and other glycoproteins to the dMM-sensitive alpha-mannosidase without movement through the Golgi apparatus was determined by measuring the loss of mannose residues from these proteins. This loss was also slow. These results indicate that both Man-6-P receptors routinely return to the Golgi compartment which contains sialyltransferase and recycle through other regions of the Golgi region less frequently. We infer that the trans-Golgi network is the major site for lysosomal enzyme sorting in CHO and murine lymphoma cells.

Mazama ash in the northeastern pacific.

Volcanic glass in marine sediments off Oregon and Washington correlates with continental deposits of Mount Mazama ash by stratigraphic position, refractive index, and radiocarbon dating. Ash deposited in the abyssal regions by turbidity currents is used for tracing of the dispersal routes of postglacial sediments and for evaluation of marine sedimentary processes.

Lead inclusion bodies in osteoclasts.

Inclusion bodies occur frequently in the nuclei and rarely in the cytoplasm of osteoclasts in pigs with experimental lead poisoning. The light and electron microscope pictures of undemineralized sections are similar to those described for liver cord cells and renal tubular cells.

Zinc binding: a difference between human and bovine milk.

Gel chromatography indicated that most of the zinc in cow's milk was associated with high-molecular-weight fractions, whereas zinc in human milk was associated with low-molecular-weight fractions. A species difference in zinc-binding ligands may explain why symptoms of the genetic disorder of zinc metabolism, acrodermatitis enteropathica, can be alleviated by feeding human but not cow's milk.

Growth changes after inhalant abuse and toluene exposure: A systematic review and meta-analysis of human and animal studies.

Inhalant abuse is a significant public health issue, particularly for adolescents, the predominant group of inhalant users. Adolescence is a critical growth period, and inhalant abuse has been associated with growth impairments, including reduced body weight and height. However, the extent to which inhalant abuse affects growth remains unquantified, and potential moderators remain unknown. To address this knowledge gap, a systematic review and meta-analysis of clinical human and preclinical animal studies utilizing toluene exposure (the primary solvent in abused products) was conducted. Five-hundred and sixty-nine studies were screened; 31 met inclusion criteria, yielding 64 toluene-control comparisons for body weight and 6 comparisons for height. Toluene exposure was negatively associated with body weight ( d = -0.73) and height ( d = -0.69). Concentration of inhaled toluene, but not duration, moderated the effect of toluene exposure on body weight, with more severe impairments at higher concentrations. Differences in effect size for body weight were observed for study characteristic subgroups including sex, age at first exposure, administration route and species. However, these findings should be interpreted cautiously due to low study numbers. Growth impairments, particularly during adolescence, can cause long-term health consequences. These effects on growth are therefore an important clinical outcome for individuals with a history of inhalant abuse.

Biosorption of precious metals.

Biosorption has emerged as a low-cost and often low-tech option for removal or recovery of base metals from aqueous wastes. The conditions under which precious metals such as gold, platinum and palladium are sorbed by biomass are often very different to those under which base metals are sorbed. This, coupled with the increasingly high demand for precious metals, drives the increase in research into efficient recovery of precious metal ions from all waste material, especially refining wastewaters. Common biosorbents for precious metal ions include various derivatives of chitosan, as well as other compounds with relatively high surface amine functional group content. This is generally due to the ability of the positively charged amine groups to attract anionic precious metal ions at low pH. Recent research regarding the biosorption of some precious metals is reviewed here, with emphasis on the effects of the biosorption environment and the biosorption mechanisms identified.

Malignant disease in peptic ulcer surgery patients after long term follow-up: a cohort study of 1992 patients.

AIMS: To assess the effect of previous peptic ulcer surgery on subsequent malignant events, in particular in relation to previous vagotomy, a historical cohort study was conducted. METHODS: All patients undergoing surgery for peptic ulcer disease with accurate follow-up data at a large peptic ulcer clinic in the Western Infirmary, Glasgow, from 1965 to 1983 were assessed. All cancer events and specific cancer events (gastric, bronchial, laryngeal, colorectal, bladder, breast, prostate, pancreas, kidney, oesophageal cancers) were determined as outcome measures and expressed as standardised incidence ratio (SIR). RESULTS: Vagotomy and drainage accounted for 67% of all procedures for peptic ulcer disease. Eighty-three percent were habitual smokers. For all peptic ulcer surgery patients, the SIR for all cancer events was 0.86. For specific cancers, the SIRs were bronchial cancer (SIR 1.13); laryngeal cancer (SIR 2.17), colorectal cancer (SIR 0.67). For vagotomised patients the risk of gastric cancer was significantly elevated (SIR 1.50). CONCLUSIONS: An excess of cancers attributable to smoking have been found in peptic ulcer surgery patients. Vagotomised patients have a higher risk of gastric cancer after long term follow-up. This finding may have implications for screening and the safety of long term acid suppression with agents such as proton pump inhibitors.

Possible site of zinc control of hepatoma cell division in Wistar rats.

The effect of zinc on the growth of a transplantable DAB hepatoma in young male Wistar rats was determined. Both a zinc deficiency (less than 0.5 microgram/g feed) as well as high levels of dietary zinc (500 micrograms/g feed) significantly reduced tumor growth. Both high- and low-zinc diets resulted in reduced activity of the salvage pathway of thymidine synthesis as well as reduced 32PO4 incorporation into DNA and diminished DNA polymerase activity. Blockage of the de novo pathway of DNA synthesis by the folate antagonist methotrexate (MTX) resulted in greatly increased flux through the thymidine salvage pathway and increased DNA polymerase activity but decreased 32PO4 incorporation in the transplantable hepatomas in Wistar rats fed normal zinc diets (50 micrograms/g feed). MTX had the effect of reducing all these activities in the groups fed low- and high-zinc diets. These data suggested a site of action of zinc associated with the salvage pathway of thymidine synthesis.

Zinc intake, neoplastic DNA synthesis, and chemical carcinogenesis in rats and mice.

DNA synthesis in a transplanted hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene was significantly reduced (P less than 0.01) in rats maintained on diets low (0.4 mug/g) or high (greater than or equal to 500 mug/g) in zinc when compared with control animals given 60 mug zinc/g. 3-Methylcholanthrene-induced carcinogenesis was considerably lowered in mice receiving the same low or high zinc diets during the induction periods.

Indium-111-diethylenetriaminepentaacetic acid-octreotide is delivered in vivo to pancreatic, tumor cell, renal, and hepatocyte lysosomes.

To better understand the factors that govern the target-to-background ratios of 111In-diethylenetriaminepentaacetic acid (DTPA) polypeptides, we studied 111In-DTPA-octreotide and a model nontargeted compound, 111In-DTPA-poly(D)lysine-biotin. We evaluated the fate of 111In-DTPA-octreotide after it localizes in somatostatin receptor-positive tissues and sought to determine why such a large fraction of these and other 111In-DTPA-polypeptides accumulate in the liver and kidneys. Biodistribution studies in rats with an implanted pancreatic adenocarcinoma demonstrated rapid accumulation of 111In-DTPA-octreotide in the pancreas and tumor. Indium-111 also accumulated in the liver and kidneys. Subcellular fractionation of the liver, kidneys, tumor, and pancreas showed that the majority of the radioactivity copurified with lysosomal enzymes. Even at 1 h, little radioactivity was found in the fractions containing a cell surface enzyme. This suggests that in each tissue, the 111In-DTPA-octreotide was rapidly shuttled from the cell surface to lysosomes. In the liver, hepatocyte lysosomes were separated from sinusoidal and Kupffer cell lysosomes by administering chloroquine prior to sacrifice. This density shift experiment indicated that 111In-DTPA-octreotide accumulated predominantly in hepatocyte lysosomes. A low molecular weight 111In-DTPA-poly(D)lysine-biotin compound was synthesized, and biodistribution studies showed substantial renal accumulation. The poly(D)lysine backbone conferred resistance to degradation, and this fact allowed determination of the distribution of this compound at the cellular level using an antibiotin antibody and immunohistochemical techniques. These experiments, as well as subcellular fractionation studies, demonstrated that the 111In-DTPA-poly(D)lysine-biotin compound accumulated in the lysosomes of proximal renal tubular cells. These results indicate that lysosomes play a critical role in the cellular physiology of radiolabeled polypeptides. Using these data, we propose a comprehensive model that summarizes the factors that govern the target to background ratios of radiolabeled polypeptides.

Identification of metabolites of 111In-diethylenetriaminepentaacetic acid-monoclonal antibodies and antibody fragments in vivo.

The in vivo fate of various 111In-labeled polypeptides has been the subject of many investigations. Intracellular metabolism has been studied through the use of 111In-labeled glycoproteins that are concentrated in the lysosome by receptor-mediated endocytosis. These studies have indicated that the main lysosomal metabolite is 111In-chelate-epsilon-lysine, both in vitro and in vivo (Y. Arano et al., J. Nucl. Med., 35: 890-898, 1994; F. N. Franano et al., Nucl. Med. Biol., 21: 1023-1034, 1994). Since the vast majority of radiolabeled antibodies do not localize within the target tissue, an understanding of the metabolism of 111In-labeled antibodies in nontarget tissues is important for the rational design of future radiolabeled antibodies. We investigated the in vivo metabolism of 111In-DTPA3-conjugated antibody in female Sprague-Dawley rats using the anticolorectal carcinoma monoclonal antibody (MAb) 1A3 and MAb 1A3-F(ab')2. Livers and kidneys were harvested from rats injected with either intact MAb or MAb fragments and analyzed by gel filtration chromatography. Thirty-five % of the radioactivity from 111In-DTPA-1A3 MAb present in the liver was in the form of a low molecular weight species at 1 through 5 days. In contrast, 111In-DTPA-1A3-F(ab')2 was > 98% degraded to a low molecular weight species in the kidney after 1 day. In each case, the low molecular weight metabolites were collected and further analyzed by silica gel thin-layer chromatography, reversed phase high-performance liquid chromatography, and ion-exchange chromatography and compared to 111In-DTPA and 111In-DTPA-epsilon-lysine standards. In each system, the major metabolite co-eluted with 111In-DTPA-epsilon-lysine, similar to the results obtained with 111In-labeled glycoproteins that are delivered to lysosomes by receptor-mediated endocytosis. A minor metabolite that was more highly charged than 111In-DTPA was also observed. Analysis of urine and feces demonstrated that the main excretory product of both 111In-labeled intact 1A3 and 1A3-F(ab')2 was 111In-DTPA-epsilon-lysine. Based on this data, we propose that 111In-DTPA-antibodies are degraded within lysosomes of nontarget organs such as the liver and kidneys.

Everything that you have ever been told about assessment center ratings is confounded.

Despite a substantial research literature on the influence of dimensions and exercises in assessment centers (ACs), the relative impact of these 2 sources of variance continues to raise uncertainties because of confounding. With confounded effects, it is not possible to establish the degree to which any 1 effect, including those related to exercises and dimensions, influences AC ratings. In the current study (N = 698) we used Bayesian generalizability theory to unconfound all of the possible effects contributing to variance in AC ratings. Our results show that ≤1.11% of the variance in AC ratings was directly attributable to behavioral dimensions, suggesting that dimension-related effects have no practical impact on the reliability of ACs. Even when taking aggregation level into consideration, effects related to general performance and exercises accounted for almost all of the reliable variance in AC ratings. The implications of these findings for recent dimension- and exercise-based perspectives on ACs are discussed. (PsycINFO Database Record

Chronic intermittent toluene inhalation in adolescent rats results in metabolic dysfunction with altered glucose homeostasis.

BACKGROUND AND PURPOSE: Abuse of toluene-containing inhalants is an increasing public health problem, especially among adolescents. Abuse during adolescence is associated with emaciation, while industrial exposure leads to altered glycaemic control suggesting metabolic instability. However, the relationship between adolescent inhalant abuse and metabolic dysfunction remains unknown. EXPERIMENTAL APPROACH: To model human abuse patterns, we exposed male adolescent Wistar rats [postnatal day (PND) 27] to chronic intermittent inhaled toluene (CIT, 10,000 ppm) or air (control) for 1 h·day(-1) , three times a week for 4 weeks. Feeding and body composition were monitored. After 4 weeks, circulating metabolic hormone concentrations and responses to a glucose tolerance test (GTT) were measured. Dietary preference was measured by giving animals access to either a 'western diet' plus standard chow (WC + SC) or standard chow alone during 4 weeks of abstinence. Metabolic hormones and GTT were subsequently measured. KEY RESULTS: Adolescent CIT exposure significantly retarded weight gain, altered body composition, circulating metabolic hormones and responses to a GTT. While reduced body weight persisted, responses to a GTT and circulating hormones appeared to normalize for animals on standard chow following abstinence. In CIT-exposed WC + SC rats, we observed impaired glucose tolerance associated with altered metabolic hormones. Analysis of hypothalamic genes revealed differential expression profiles in CIT-exposed rats following both the exposure period and abstinence, suggesting a central contribution to inhalant-induced metabolic dysfunction. CONCLUSION AND IMPLICATIONS: CIT exposure during adolescence has long-term effects on metabolic function, which may increase the risk of disorders related to energy balance and glycaemic control.

Portal branch occlusion safely facilitates in vivo retroviral vector transduction of rat liver.

Hepatic gene therapy might correct the clinical manifestations of several genetic disorders in patients. Although retroviral vectors with a strong liver-specific promoter can result in stable and therapeutic levels of expression of genes from the liver, application of these techniques in humans is limited by the need to perform one or more invasive procedures to achieve ex vivo or in vivo transduction of hepatocytes. In vivo delivery involves injection of retrovirus into the portal vein during liver regeneration. Although transduction is efficient and specific for the liver, induction of hepatocyte replication requires a 70% partial hepatectomy or administration of a liver toxin. An alternative method for inducing hepatocyte replication is to occlude branches of the portal vein. This results in apoptosis of hepatocytes in the occluded lobes and compensatory replication of the hepatocytes in the nonoccluded lobes. We demonstrate here that portal branch occlusion is nearly as effective as partial hepatectomy at facilitating retroviral vector transduction in vivo and has a lower morbidity. Portal branch occlusion could be performed in larger animals by minimally invasive techniques and has been used safely to treat human patients with liver cancer. Portal branch occlusion might ultimately be used in humans to facilitate retroviral vector transduction in vivo for the treatment of genetic diseases.