United States' experience in nuchal translucency measurement: variation according to provider characteristics in over five million ultrasound examinations.

OBJECTIVE: The Nuchal Translucency Quality Review (NTQR) program has provided standardized education, credentialing and epidemiological monitoring of nuchal translucency (NT) measurements since 2005. Our aim was to review the effect on NT measurement of provider characteristics since the program's inception. METHODS: We evaluated the distribution of NT measurements performed between January 2005 and December 2019, for each of the three primary performance indicators of NT measurement (NT median multiples of the median (MoM), SD of log10 NT MoM and slope of NT with respect to crown-rump length (CRL)) for all providers within the NTQR program with more than 30 paired NT/CRL results. Provider characteristics explored as potential sources of variability included: number of NT ultrasound examinations performed annually (annual scan volume of the provider), duration of participation in the NTQR program, initial credentialing by an alternative pathway, provider type (physician vs sonographer) and number of NT-credentialed providers within the practice (size of practice). Each of these provider characteristics was evaluated for its effect on NT median MoM and geometric mean of the NT median MoM weighted for the number of ultrasound scans, and multiple regression was performed across all variables to control for potential confounders. RESULTS: Of 5 216 663 NT measurements from 9340 providers at 3319 sites, the majority (75%) of providers had an NT median MoM within the acceptable range of 0.9-1.1 and 85.5% had NT median MoM not statistically significantly outside this range. Provider characteristics associated with measurement within the expected range of performance included higher volume of NT scans performed annually, practice at a site with larger numbers of other NT-credentialed providers, longer duration of participation in the NTQR program and alternative initial credentialing pathway. CONCLUSIONS: Annual scan volume, duration of participation in the NTQR program, alternative initial credentialing pathway and number of other NT-credentialed providers within the practice are all associated with outcome metrics indicating quality of performance. It is critical that providers participate in ongoing quality assessment of NT measurement to maintain consistency and precision. Ongoing assessment programs with continuous feedback and education are necessary to maintain quality care. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Distinguishing Petroleum (Crude Oil and Fuel) From Smoke Exposure within Populations Based on the Relative Blood Levels of Benzene, Toluene, Ethylbenzene, and Xylenes (BTEX), Styrene and 2,5-Dimethylfuran by Pattern Recognition Using Artificial Neural Networks.

Studies of exposure to petroleum (crude oil/fuel) often involve monitoring benzene, toluene, ethylbenzene, xylenes (BTEX), and styrene (BTEXS) because of their toxicity and gas-phase prevalence, where exposure is typically by inhalation. However, BTEXS levels in the general U.S. population are primarily from exposure to tobacco smoke, where smokers have blood levels on average up to eight times higher than nonsmokers. This work describes a method using partition theory and artificial neural network (ANN) pattern recognition to classify exposure source based on relative BTEXS and 2,5-dimethylfuran blood levels. A method using surrogate signatures to train the ANN was validated by comparing blood levels among cigarette smokers from the National Health and Nutrition Examination Survey (NHANES) with BTEXS and 2,5-dimethylfuran signatures derived from the smoke of machine-smoked cigarettes. Classification agreement for an ANN model trained with relative VOC levels was up to 99.8% for nonsmokers and 100.0% for smokers. As such, because there is limited blood level data on individuals exposed to crude oil/fuel, only surrogate signatures derived from crude oil and fuel were used for training the ANN. For the 2007-2008 NHANES data, the ANN model assigned 7 out of 1998 specimens (0.35%) and for the 2013-2014 NHANES data 12 out of 2906 specimens (0.41%) to the crude oil/fuel signature category.

Nuchal Translucency Quality Review (NTQR) program: first one and half million results.

OBJECTIVE: To evaluate the performance of first-trimester nuchal translucency (NT) measurement by providers (physician-sonologists and sonographers) within the Nuchal Translucency Quality Review (NTQR) program. METHODS: After training and credentialing providers, the NTQR monitored performance of NT measurement by the extent to which an individual's median multiple of the normal median (MoM) for crown-rump length (CRL) was within the range 0.9-1.1 MoM of a published normal median curve. The SD of log10 MoM and regression slope of NT on CRL were also evaluated. We report the distribution between providers of these performance indicators and evaluate potential sources of variation. RESULTS: Among the first 1.5 million scans in the NTQR program, performed between 2005 and 2011, there were 1 485 944 with CRL in the range 41-84 mm, from 4710 providers at 2150 ultrasound units. Among the 3463 providers with at least 30 scans in total, the median of the providers' median NT-MoMs was 0.913. Only 1901 (55%) had a median NT-MoM within the expected range; there were 89 above 1.1 MoM, 1046 at 0.8-0.9 MoM, 344 at 0.7-0.8 MoM and 83 below 0.7 MoM. There was a small increase in the median NT-MoM according to providers' length of time in the NTQR program and number of scans entered annually. On average, physician-sonologists had a higher median NT-MoM than did sonographers, as did those already credentialed before joining the program. The median provider SD was 0.093 and the median slope was 13.5%. SD correlated negatively with the median NT-MoM (r = -0.34) and positively with the slope (r = 0.22). CONCLUSION: Even with extensive training, credentialing and monitoring, there remains considerable variability between NT providers. There was a general tendency towards under-measurement of NT compared with expected values, although more experienced providers had performance closer to that expected.

Fetal nuchal translucency thickness evaluation in the overweight and obese gravida.

OBJECTIVE: To evaluate the time required and failure rate for completion of nuchal translucency thickness (NT) measurements with increased maternal body mass index (BMI). METHODS: This was a retrospective review of ultrasound examinations for NT measurement in 11-14-week singleton pregnancies performed at a single site from 2004 to 2007. Women were stratified by prepregnancy BMI into normal weight (BMI, 18.5-24.9 kg/m(2)), overweight (BMI, 25.0-29.9 kg/m(2)) and obese Class I (BMI, 30.0-34.9 kg/m(2)), Class II (BMI, 35.0-39.9 kg/m(2)) and Class III (BMI >or= 40.0 kg/m(2)) groups. The failure rate, the time required for measurement, and the total study time in min were evaluated by BMI class for the first attempt and for all attempts at NT measurement. RESULTS: A total of 2508 women underwent attempted NT screening with complete data available on 1678 women (1707 examinations). The failure rate for NT screening varied significantly according to BMI (P < 0.001). At the first attempt, the median time for NT measurement varied significantly according to BMI (normal weight group, 9.7 (interquartile range (IQR) 4.4, 19.0) min; overweight group, 8.8 (4.0, 19.8) min; obese Class I, 9.6 (4.8, 20.4) min; Class II, 14.1 (5.0, 28.2) min; Class III, 12.3 (4.6, 22.7) min; P < 0.01), as did the total study time (normal group, 16.4 (10.1, 26.6) min; overweight group, 15.7 (9.8, 25.0) min, Class I, 17.3 (10.3, 29.2) min; Class II, 23.0 (12.2, 36.1) min; Class III, 18.7 (11.0, 30.8) min; P = 0.002). For all attempts also, the median time for NT measurement varied significantly according to BMI (normal weight group, 9.7 (IQR 4.4, 19.0) min; overweight group, 8.8 (4.0, 19.9) min; obese Class I, 9.6 (4.8, 21.0) min; Class II, 14.1 (5.0, 28.7) min; Class III, 12.3 (4.6, 22.5) min; P < 0.01), as did the total study time (normal weight group, 16.4 (10.2, 26.7) min; overweight group, 15.7 (9.8, 25.1) min; Class I, 17.6 (10.4, 29.9) min; Class II, 23.2 (12.0, 37.5) min; Class III, 18.7 (11.9, 31.9) min; P < 0.001). CONCLUSION: As maternal BMI increases, the time required to obtain NT measurements and the failure rate increase. Before the ultrasound examination, patients with a BMI over 30 should be counseled regarding the need for additional time and failure rates for first-trimester screening.

Fetal anatomic evaluation in the overweight and obese gravida.

OBJECTIVES: To evaluate the rate of completion of anatomic surveys of fetuses in overweight and obese gravid patients as compared with normal controls. METHODS: This was a retrospective review of anatomic ultrasound scans performed between 2004 and 2007. Women were stratified by prepregnancy body mass index (BMI) into normal weight (BMI, 18.5-24.9 kg/m(2)), overweight (BMI, 25.0-29.9 kg/m(2)) and obese Class I (BMI, 30.0-34.9 kg/m(2)), Class II (BMI, 35.0-39.9 kg/m(2)) and Class III (BMI >or= 40.0 kg/m(2)) groups. Rates of completion of basic and comprehensive scans, gestational age at completion and number of scans required were compared. RESULTS: For the 7140 patients included, completion rates for both the basic (normal weight, n = 2253 (79%); overweight, n = 1771 (76%); obese Class I, n = 767 (72%), Class II, n = 323 (61%) and Class III, n = 171 (49%)) and comprehensive (normal weight, n = 1234 (43%); overweight, n = 930 (40%); obese Class I, n = 404 (38%), Class II, n = 215 (41%) and Class III, n = 108 (31%)) surveys decreased significantly with increasing BMI (P < 0.00001). For surveys completed, the mean number of scans required was significantly higher for obese patients (basic: normal weight 1.3 vs. obese Class III 1.9; comprehensive: normal weight 1.7 vs. obese Class III, 2.2)(P < 0.00001). The overall completion rate improved at each gestational week, but was best between 20 and 23 weeks for obese patients. CONCLUSIONS: As maternal BMI increases, the rate of completion of anatomic surveys decreases and the number of scans required increases. Delaying the initial survey until 20 weeks' gestation may improve the capacity to complete the examination in a single visit. It should be noted that these results represent completion rates at a tertiary referral center, and therefore may not reflect community experience.

Sonographic birth-weight prediction in obese patients using the gestation-adjusted prediction method.

OBJECTIVES: Ultrasound birth-weight prediction may be more accurate if assessed at 34 to 36 + 6 weeks' gestation and extrapolated using the gestation-adjusted projection (GAP) method than if done at term. Because ultrasound is less accurate in women with elevated body mass index (BMI), we assessed the accuracy of GAP birth-weight prediction in obese as compared to non-obese women. METHODS: We performed a retrospective review of 1382 women with singleton pregnancies who had undergone fetal ultrasound examination at between 34 + 0 and 36 + 6 weeks, subclassified by pre-pregnancy BMI. Analysis of variance was used to compare predicted and actual birth weight. RESULTS: 1025 controls and 357 obese women were included. The obese women were divided by BMI: 159 in Class I (BMI, 30-34.9 kg/m(2)); 105 in Class II (BMI, 35-40 kg/m(2)) and 93 in Class III (BMI > 40 kg/m(2)). Mean systematic (percent) birth-weight prediction error was within 4% for all groups, with a 95% error range between - 5% and + 5%. The GAP method was able to predict actual birth weight within 20% for all groups in over 90% of cases. For all groups, the GAP method correctly excluded the presence of macrosomia with >or= 90% specificity. Negative likelihood ratios for the prediction of macrosomia were between 0.4 and 0.6 for all groups, regardless of obesity. CONCLUSIONS: The GAP method of birth-weight prediction using ultrasound measurement at 34 to 36 + 6 weeks predicts birth weight within 20% error in over 90% of cases, and is able to exclude macrosomia with over 90% accuracy regardless of maternal BMI.

A perspective on copper and liver disease in the dog.

Copper is a ubiquitous trace metal necessary for normal function of a variety of cellular proteins. Intracellular copper metabolism is complex, and only a few of the proteins/genes involved are known. Copper deficiency does not appear to be a clinical problem in dogs. Excess copper accumulation in the liver as a cause of hepatitis and cirrhosis was first demonstrated among Bedlington terriers. Subsequently, copper accumulation in the liver has been shown to occur in several other breeds of dogs. Excess hepatic copper has been found in dogs with normal liver histology, dogs with hepatitis, and dogs with end stage cirrhosis. Evidence is accumulating that copper is a cause of liver disease in breeds of dogs other than Bedlington terriers. Moreover, as more data are accumulated, the copper storage disease appears to have characteristics that are very similar among all of the affected breeds.

Mechanistic insights from the three-dimensional structure of 3-oxo-Delta(5)-steroid isomerase.

3-Oxo-Delta(5)-steroid isomerase (KSI) catalyzes the isomerization of beta,gamma-unsaturated 3-oxosteroids to their conjugated isomers through the formation of an intermediate dienolate. The three-dimensional structure of the enzyme from Pseudomonas testosteroni was solved by multidimensional heteronuclear magnetic resonance spectroscopy. This protein, a 28-kDa symmetric dimer, exhibits a three-dimensional fold with the two independently folded monomers packed together via extensive hydrophobic and electrostatic interactions. The previously identified catalytically important residues Tyr-14 (general acid) and Asp-38 (general base) are located near the bottom of a deep hydrophobic cavity and are positioned in a manner consistent with previous mechanistic hypotheses. The structure also revealed the presence of an unexpected acid group (Asp-99) located in the active site adjacent to Tyr-14. Mutagenesis and kinetic studies show that Asp-99 has an anomalously high pK(a) (>9), which allows it to contribute to catalysis by donating a hydrogen bond to the intermediate and to the transition states. In support of this hypothesis, effects on the kinetic parameters of the mutations Y14F and D99A are additive in the Y14F/D99A mutant.

Ganglions of the hand and wrist.

Ganglions of the hand and wrist are common benign lesions. They most frequently arise adjacent to joints and tendons, but may also be intratendinous or intraosseous. Treatment options include observation, aspiration, and surgical excision. Observation is acceptable in most instances. Indications for more aggressive treatment include pain, interference with activity, nerve compression, and imminent ulceration (in the case of some mucous cysts). The recurrence rate after puncture and aspiration is greater than 50% for cysts in most locations, but is less than 30% for cysts in the flexor tendon sheath. Surgical excision is effective, with a recurrence rate of only 5% if care is taken to completely excise the stalk of the cyst along with a small portion of joint capsule. Surgical treatment of occult ganglions is successful with accurate assessment of the source of the pain. Arthroscopic treatment of dorsal wrist ganglions is still experimental, but early results are encouraging. Ganglion surgery requires a formal operative environment and careful technique in order to minimize injury to adjacent structures and minimize the likelihood of recurrence.

Histomorphological and immunohistochemical studies of chronic active hepatitis in Doberman Pinschers.

Liver tissue samples were reviewed from 35 Doberman Pinschers with chronic active hepatitis in the precirrhotic stage. Thirty dogs had elevated hepatic copper concentrations, and five had normal liver copper concentrations. The earliest changes were inflammation and scar tissue deposition around the small hepatic vein branches. There was also apoptosis of scattered hepatocytes in zone 3. Inflammation consisted of macrophages, lymphocytes, and plasma cells. As the disease progressed, collagen deposition increased around the hepatic veins; in some liver specimens, thin scar tissue septa radiated from the hepatic vein branches, and inflammation spread to include the portal tracts. The sinusoids adjacent to the scar tissue were converted to endothelial-lined, thin-walled vessels. Chronic active hepatitis (commonly referred to as Doberman hepatitis or chronic active hepatitis of Dobermans) is a progressive fibrosis, inflammation and hepatocyte loss beginning among zone 3 hepatocytes around the terminal hepatic vein branches. The histomorphologic changes were the same among those Dobermans with elevated hepatic copper and those with normal hepatic copper. The cause was not determined, but these morphologic studies support the idea of immune-mediated disease.

Electrophilic assistance by Asp-99 of 3-oxo-Delta 5-steroid isomerase.

3-Oxo-Delta 5-steroid isomerase (Delta 5-3-ketosteroid isomerase, KSI; EC 5.3.3.1) catalyzes the conversion of a variety of beta, gamma-unsaturated 3-oxosteroids to their corresponding alpha, beta-unsaturated isomers at rates that approach the diffusion limit for specific substrates. The reaction proceeds through a dienolate intermediate, with two amino acid residues (Asp-38 and Tyr-14) known to be involved in catalysis. When the complete three-dimensional structure of KSI was determined recently by NMR methods, an additional polar residue (Asp-99) was found in the active site and this group was shown to be important for catalytic activity. In this work, we examine the properties of several mutant KSIs to determine the nature of catalysis by Asp-99 of KSI. The electrophoretic mobilities of wild-type (WT) KSI and several mutants (D99A, D99N, D38N, and D38N/D99A) on native gels were determined at pH values ranging from 6.0 to 8.5. The results demonstrate that the pKa of Asp-99 is >8.5 in wild-type KSI. The pH-rate profiles for the D99A, D99N, and D38H/D99A mutants of KSI were also determined. For all three mutants, kcat and kcat/KM do not decrease at high pH, in contrast to those for WT and D38H, which lose activity above pH 9 and 8, respectively. Mutation of Asp-99 to Asn decreases kcat for the substrate 5-androstene-3,17-dione by 27-fold and kcat/Km by 23-fold, substantially less than the loss of activity (3000-fold in kcat and 2200-fold in kcat/Km) observed when Asp-99 is mutated to Ala, consistent with a hydrogen bonding role for Asp-99. Taken together, these results provide evidence that Asp-99 participates in catalysis in its protonated form, with a pKa of >9 in WT and approximately 8.5 in the D38H mutant. Asp-99 likely donates a hydrogen bond to O-3 of the steroid, helping to stabilize the transition state(s) of the KSI-catalyzed reaction.

Identification of an intronic enhancer that nullifies upstream repression of SPARC gene expression.

The SPARC gene 5'flanking sequence has been shown to contain enhancer elements, but also negative control elements immediately upstream of the enhancer elements. Although these 5'enhancer elements are active in F9 and PYS-2 cells, their activities are nullified by the 5'repressor activity. In the present study we have identified within intron 1 between nucleotides (nt) +5000 and +5150 of the SPARC gene an enhancer element that bound to two transcription factors of 48 and 52 kDa and between nt +5000 and +5523 a DNase I hypersensitive site. Furthermore, a region containing the 3'intron 1 enhancer element, together with the 5'enhancer elements, neutralized the 5'repressor activity and stimulated efficient transcription. The resulting SPARC promoter activity is about equal in F9, differentiated F9 and PYS-2 cells. We consistently found that the rate of SPARC transcription is nearly the same in F9 and PYS-2 cells. Association of the 3'enhancer element in intron 1 with the DNase I hypersensitive site suggests that both play a role in regulating SPARC expression in vivo .

Solution structure of 3-oxo-delta5-steroid isomerase.

The three-dimensional structure of the enzyme 3-oxo-delta5-steroid isomerase (E.C. 5.3.3.1), a 28-kilodalton symmetrical dimer, was solved by multidimensional heteronuclear magnetic resonance spectroscopy. The two independently folded monomers pack together by means of extensive hydrophobic and electrostatic interactions. Each monomer comprises three alpha helices and a six-strand mixed beta-pleated sheet arranged to form a deep hydrophobic cavity. Catalytically important residues Tyr14 (general acid) and Asp38 (general base) are located near the bottom of the cavity and positioned as expected from mechanistic hypotheses. An unexpected acid group (Asp99) is also located in the active site adjacent to Tyr14, and kinetic and binding studies of the Asp99 to Ala mutant demonstrate that Asp99 contributes to catalysis by stabilizing the intermediate.

The relationship between hepatic copper content and morphologic changes in the liver of West Highland White Terriers.

Liver tissue from 17 West Highland White Terriers (WHWTs) with cirrhosis, subacute bridging necrosis, hepatitis, or massive necrosis were examined for the presence, composition, and distribution of inflammatory foci. Copper analysis was performed on the specimens. The foci of inflammation and necrosis composed a significant part of the lesion in 15 of the samples. The foci were of two types. One, characteristic of idiopathic chronic active hepatitis, consisted of one or two apoptotic hepatocytes attended by lymphocytes and plasma cells. These foci were found primarily in the vicinity of the portal tracts, not associated with centrolobular copper-laden hepatocytes. The other type of focus was characteristic of copper toxicosis. These foci were larger and composed of debris-filled macrophages, lymphocytes, plasma cells, and scattered neutrophils, and on occasion apoptotic hepatocytes were found at the periphery. These foci were always found around the central vein among the copper-laden hepatocytes. Such foci were found only in dogs with copper concentration > 2,000 parts/million on a dry weight basis. These morphologic studies show that clinical liver disease in WHWTs is caused by more than one etiologic agent. Among 17 WHWTs with clinical liver disease, two had copper toxicosis, five had idiopathic chronic active hepatitis, and 10 had hepatic disease of undetermined type.

When interviewing the disabled, focus on their abilities.

Thanks to the ADA, employers can capitalize on the abilities of disabled persons, rather than create barriers to employment. This article explains some common myths that have shaped hiring practices in the past and provides practical interviewing tips.

Cysteine proteinase inhibitors decrease articular cartilage and bone destruction in chronic inflammatory arthritis.

OBJECTIVE: To determine the effects of peptidyl fluoromethyl ketones on the in vitro activity of purified cathepsins B and L, on tissue cysteine proteinase activity, and on cartilage and bone destruction in experimental arthritis. METHODS: The effects of the fluoroketones on cathepsins B and L in vitro and the effects of oral administration of fluoroketones on ex vivo cysteine proteinase activity in tissue homogenates were determined by measuring the inhibition of fluorogenic substrate cleavage. To determine the effects on arthritis, animals were injected with adjuvant or type II collagen, treated orally with the fluoroketones, and the severity of arthritis was assessed by clinical, histologic, and radiologic methods. RESULTS: All of the fluoroketones tested were potent inhibitors of purified cathepsins B and L activity. Oral administration of the fluoroketones reduced tissue cysteine proteinase activity by up to 77%. In addition, fluoroketone treatment significantly reduced the severity of clinical joint disease and decreased the destruction of articular cartilage and bone. Quantitative analysis of radiographic images indicated that treatment significantly reduced soft tissue changes, periosteal proliferation, and bone erosion, but only partially reduced juxtaarticular osteoporosis. CONCLUSION: These studies suggest that cysteine proteinase inhibitors may limit tissue destruction in diseases such as rheumatoid arthritis.