Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence in the FACS randomized clinical trial.

BACKGROUND: Most guidelines recommend that patients who have undergone curative resection for primary colorectal cancer are followed up for 5 years with regular blood carcinoembryonic antigen (CEA) tests to trigger further investigation for recurrence. However, CEA may miss recurrences, or patients may have false alarms and undergo unnecessary investigation. METHODS: The diagnostic accuracy of trends in CEA measurements for recurrent colorectal cancer, taken as part of the FACS (Follow-up After Colorectal Surgery) trial (2003-2014), were analysed. Investigation to detect recurrence was triggered by clinical symptoms, scheduled CT or colonoscopy, or a CEA level of at least 7 µg/l above baseline. Time-dependent receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic accuracy of CEA trends with single measurements. CEA trends were estimated using linear regression. RESULTS: The area under the ROC curve (AUC) for CEA trend was at least 0·820 across all 5 years of follow-up. In comparison, the AUCs for single measurements ranged from 0·623 to 0·749. Improvement was most marked at the end of the first year of follow-up, with the AUC increasing from 0·623 (95 per cent c.i. 0·509 to 0·736) to 0·880 (0·814 to 0·947). However, no individual trend threshold achieved a sensitivity above 70 per cent (30 per cent missed recurrences). CONCLUSION: Interpreting trends in CEA measurements instead of single CEA test results improves diagnostic accuracy for recurrence, but not sufficiently to warrant it being used as a single surveillance strategy to trigger further investigation. In the absence of a more accurate biomarker, monitoring trends in CEA should be combined with clinical, endoscopic and imaging surveillance for improved accuracy.

Estimating gestational age at birth from fundal height and additional anthropometrics: a prospective cohort study.

OBJECTIVE: Accurate assessment of gestational age (GA) is critical to paediatric care, but is limited in developing countries without access to ultrasound. Our objectives were to assess the accuracy of prediction of GA at birth and preterm birth classification using routinely collected anthropometry measures. DESIGN: Prospective cohort study. SETTING: United States. POPULATION OR SAMPLE: A total of 2334 non-obese and 468 obese pregnant women. METHODS: Enrolment GA was determined based on last menstrual period, confirmed by first-trimester ultrasound. Maternal anthropometry and fundal height (FH) were measured by a standardised protocol at study visits; FH alone was additionally abstracted from medical charts. Neonatal anthropometry measurements were obtained at birth. To estimate GA at delivery, we developed three predictor models using longitudinal FH alone and with maternal and neonatal anthropometry. For all predictors, we repeatedly sampled observations to construct training (60%) and test (40%) sets. Linear mixed models incorporated longitudinal maternal anthropometry and a shared parameter model incorporated neonatal anthropometry. We assessed models' accuracy under varied scenarios. MAIN OUTCOME MEASURES: Estimated GA at delivery. RESULTS: Prediction error for various combinations of anthropometric measures ranged between 13.9 and 14.9 days. Longitudinal FH alone predicted GA within 14.9 days with relatively stable prediction errors across individual race/ethnicities [whites (13.9 days), blacks (15.1 days), Hispanics (15.5 days) and Asians (13.1 days)], and correctly identified 75% of preterm births. The model was robust to additional scenarios. CONCLUSIONS: In low-risk, non-obese women, longitudinal FH measures alone can provide a reasonably accurate assessment of GA when ultrasound measures are not available. TWEETABLE ABSTRACT: Longitudinal fundal height alone predicts gestational age at birth when ultrasound measures are unavailable.

Gestational weight gain, prepregnancy body mass index and offspring attention-deficit hyperactivity disorder symptoms and behaviour at age 10.

OBJECTIVE: To assess offspring attention-deficit hyperactivity disorder (ADHD) symptoms and emotional/behavioural impairments at age 10 years in relation to maternal gestational weight gain (GWG) and prepregnancy body mass index (BMI). DESIGN AND SETTING: Longitudinal birth cohort from Magee-Womens Hospital, Pittsburgh, Pennsylvania (enrolled 1983-86). POPULATION: Mother-infant dyads (n = 511) were followed through pregnancy to 10 years. METHODS: Self-reported total GWG was converted to gestational-age-standardised z-scores. Multivariable linear and negative binomial regressions were used to estimate effects of GWG and BMI on outcomes. MAIN OUTCOME MEASURES: Child ADHD symptoms were assessed with the Conners' Continuous Performance Test. Child behaviour was assessed by parent and teacher ratings on the Child Behaviour Checklist (CBCL) and Teacher Report Form, respectively. RESULTS: The mean (SD) total GWG (kg) was 14.5 (5.9), and 10% of women had a pregravid BMI ≥30 kg/m2 . Prepregnancy obesity (BMI of 30 kg/m2 ) was associated with increased offspring problem behaviours including internalising behaviours (adjusted ß 3.3 points, 95% CI 1.7-4.9), externalising behaviours (adjusted ß 2.9 points, 95% CI 1.4-4.6), and attention problems (adjusted ß 2.3 points, 95% CI 1.1-3.4) on the CBCL, compared with normal weight mothers (BMI of 22 kg/m2 ). There were nonsignificant trends towards increased offspring impulsivity with low GWG among lean mothers (adjusted incidence rate ratio 1.2, 95% CI 0.9-1.5) and high GWG among overweight mothers (adjusted incidence rate ratio 1.7, 95% CI 0.9-2.8), but additional outcomes did not differ by GWG z-score. Results were not meaningfully different after excluding high-substance users. CONCLUSIONS: In a low-income and high-risk sample, we observed a small increase in child behaviour problems among children of obese mothers, which could have an impact on child behaviour in the population. TWEETABLE ABSTRACT: Maternal obesity is associated with a small increase in child behaviour problems.

Trends in flame retardant levels in upholstered furniture and children's consumer products after regulatory action in California.

In 2013, California revised its upholstered furniture flammability standard TB 117-2013 to improve fire safety without the need for flame retardant (FR) chemicals. Subsequent legislation (SB 1019) required disclosure of FR content. In 2020 California expanded restriction on FR chemicals to include juvenile products and upholstered furniture (AB 2998). To monitor trends in FR use, and assess the effectiveness of the new regulations, we analyzed 346 samples from upholstered furniture (n = 270) and children's consumer products (n = 76), collected pre- and post-regulatory intervention for added FR chemicals (i.e., ∑FR > 1000 mg/kg). Upholstered furniture samples, collected from products before enactment of the new regulations, had a median FR concentration of 41,600 mg/kg (range: 1360-92,900 mg/kg), with 100% of the foam samples and 13.7% of the textile samples containing ∑FR > 1000 mg/kg. Firemaster formulations (FM 550 and FM 600), a mixture of triphenyl phosphate (TPHP), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (BEH-TEBP) and a mixture of isopropyl- or tert-butyl-triphenyl phosphates (ITPs or TBPPs), were the most frequently detected FR (34%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCIPP; 25%), TPHP with a mixture of polybrominated diphenyl ethers (BDE-47, 99, 100, 153 and 154; 20%) and tris(2-chloroethyl) phosphate (TCEP; 11%). Upholstered furniture components collected after enactment of the new legislation had a median FR concentration of 2600 mg/kg (range: 1160-49,800 mg/kg, outlier sample 282,200 mg/kg), with 11.9% of the foam samples and no textile samples containing ∑FR > 1000 mg/kg. Of these samples, tris(1-chloro-2-propyl) phosphate (TCIPP) was the most frequently detected FR (55%), followed by TDCIPP (30%) and Firemaster (FM 550, 15%). No PBDEs were detected in the post-regulatory intervention products. Our initial work on children's products showed 15% of the samples contained ∑FR > 1000 mg/kg. In our post- AB 2998 work, no regulated children's product components failed compliance (i.e., ∑FR > 1000 mg/kg). The data confirm successful adoption of the new regulations with most samples in compliance, demonstrating the efficacy of regulatory intervention. Given these results, environmental FR exposure is expected to decrease as older FR treated consumer products are replaced with FR free products.

Situation strength as a basis for interactions in psychological models.

One of the most important methods that psychological scientists use to understand behavior and cognition is theorizing. Increasingly, theorizing is used to support not only additive hypotheses, but also multiplicative ones. And yet, authors often struggle to provide adequate theoretical justifications for multiplicative hypotheses. In the late 1960s and early 1970s, W. Mischel averred that, in "strong" situations, behavior is relatively uniform regardless of one's personality characteristics. In "weak" situations, that is, those that lack clear behavioral expectations, behavior is not constrained by the situation and is free to covary with personality. This is the situational strength interaction, and although this reasoning has been applied to personality-behavior models, we show that it can be used to justify many interaction models in psychology more generally. In some cases, such reasoning may serve to bolster the more traditional interaction arguments. In other cases, it shows that the traditional interaction arguments must be incorrect. In this tutorial, we describe a generalized situation strength phenomenon, called the restricted variance interaction, that can be used to pinpoint the nature, direction, and even the magnitude of many interaction hypotheses in the psychological sciences. We illustrate the value and application of restricted variance reasoning using examples from the workplace mistreatment literature and then extrapolate to several other areas of psychology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The effect of dobutamine on blood flow of free tissue transfer flaps during head and neck reconstructive surgery*.

SUMMARY: In view of the controversy over the use of inotropes in free tissue transfer surgery, we assessed the effect of different intra-operative dobutamine infusion rates on blood flow in the anastomosed recipient artery. Twenty patients undergoing head and neck tumour resection and immediate reconstructive surgery with free tissue transfer were recruited. After completion of the microvascular anastomoses, patients received dobutamine infusions of 2, 4 and 6 microg x kg(-1) x min(-1) in a randomised order. After steady state dobutamine concentration was achieved, mean and maximum blood flow in the arterial anastomosis was measured at each concentration, using the Medi-Stim Butterfly Flowmeter system. Systemic haemodynamic parameters were simultaneously recorded using a pulse contour cardiac output system. Both mean and maximum blood flow increased significantly in the anastomosed artery at dobutamine infusions of 4 and 6 microg x kg(-1) x min(-1) and this was accompanied by increased cardiac output. This may improve free flap perfusion.

Trends in vaccine investment in middle income countries.

Although a proven and effective preventive health measure, childhood immunization programs remain vulnerable to budgetary pressures. Sustainable financing of immunization programs is an important issue that presents a challenge for middle-income countries (MIC) in particular, in part due to technological advances meaning more vaccines are available. This study aimed to analyse trends in immunization program investment across 15 MIC selected based on availability of data, income level classification, and regional representativeness. We assessed investment trends in relation to vaccine coverage, vaccine access, and broader health indicators. Immunization and expenditure data were obtained from the World Health Organisation (WHO) database and the WHO UNICEF Joint Reporting Form and WHO Vaccine Product, Price and Procurement from 2006-2016. We calculated a weighted average index of vaccine commitment (WAIVC) based on vaccine coverage, vaccine scope, and weighted by vaccine innovation measured by approximating vaccine expenditure. Correlation analyses were conducted between immunization expenditure per-capita and each WAIVC, infant mortality and life expectancy. Correlation analyses at a global and individual country level indicate an improvement in immunization access, vaccination commitment measured by WAIVC, and scope of available vaccines in countries with sustained increases in vaccination funding. Increases in national immunization expenditure were correlated with reduced infant mortality and increased life expectancy. Vaccine expenditure comprises a small proportion (less than 2%) of total healthcare spending and has not uniformly increased in accordance with the scope of available vaccines. The present analysis supports the premise that countries with consistent increases in vaccine expenditure have increased vaccine coverage and commitment measured by WAIVC and improved broader health outcomes, indicating the value of sustained investment in vaccination for improved population health. The benefits of vaccine expenditure in this holistic fashion are critical to inform policy decisions on national budget allocation for vaccine funding.

Looking inside and out: the impact of employee and community demographic composition on organizational diversity climate.

An organization's diversity climate refers to employees' shared perceptions of the policies and practices that communicate the extent to which fostering diversity and eliminating discrimination is a priority in the organization. The authors propose a salient element of the organizational context, the racial composition of the community where the organization is located, serves an important signaling function that shapes the formation of climate perceptions. In a study of 142 retail bank units in the United States, evidence is found for a relationship between the racial composition of an organization's workforce and diversity climate that is moderated by the racial composition of the community where the organization is located. The results suggest that when few racial minorities live in the community in which an organization is embedded, workforce diversity has an impact on employees' diversity climate perceptions. As racial minority popular share increases, workforce diversity tends to lose this signaling value.

Pharmacokinetic studies in mice of two new thioxanthenones (183577 and 232759) that showed preferential solid tumor activity.

Two new thioxanthenones, 183577 and 232759, have rekindled interest in the development of representatives from this class of structures as useful anticancer agents. Although the mechanism of action is unknown, both compounds demonstrated a similar spectrum of solid tumor selectivity. 232759 was selected for clinical development because it showed no hepatotoxicity in preliminary studies, whereas 183577 showed hepatotoxicity but only at the maximum tolerated dose (MTD). The limiting toxicity for the clinical candidate was myelosuppression in preliminary studies. Plasma and tissue drug levels, as well as protein binding, were studied in mice using optimal administration times at the MTD for each drug (for 183577, this was a 4-h infusion at 1350 mg/m2 and for 232759, it was a 5-min injection at 240 mg/m2), as well as at one-half the MTD for the clinical candidate. The drugs were 96-100% bound by plasma proteins. The peak drug concentrations, half-life, and area under the concentration-time curve in plasma for 183577 were 3483 ng/ml, 465 min, and 2018 microgram/ml. min, respectively. The peak drug concentration, half-life, and area under the concentration-time curve in plasma for 232759 were 5257 ng/ml, 44 min, and 276 microgram/ml. min, respectively, at the MTD and 2810 ng/ml, 40 min, and 110 microgram/ml. min at one-half the MTD. In all instances of simultaneous measurements, drug concentrations were equal or higher in tissues than they were in plasma. Unlike the plasma and kidney concentrations of 183577, the liver concentrations did not show a declining trend over the 8-h observation period. Declines in plasma, liver, kidney, and tumor levels of 232759 were detected over the 8-h observation period. The sustained high 183577 concentration in liver is believed to be responsible for its prolonged half-life and hepatotoxicity. Evidence for metabolism of the parent drugs was based on the finding of additional peaks on the high-pressure liquid chromatography tracings. Future studies will focus on identification and antitumor studies of these presumed metabolites in hopes of a better understanding of the solid tumor activity profiles and toxic effects of these compounds.

Exploring the role of emotions in injustice perceptions and retaliation.

Although organizational justice scholars often describe unfairness as an emotionally laden experience, the role of emotion is underresearched. In a study of individuals who experienced being laid off (N = 173), the authors found that outcome favorability interacts with both procedural and interactional justice to predict participants' emotions. The pattern of interaction differed for inward-focused (i.e., shame and guilt) and outward-focused (i.e., anger and hostility) negative emotions. Attributions of blame mediated the relationship between fairness perceptions and outward-focused negative emotion. Outward-focused emotion mediated the relationship between fairness perceptions and retaliation.

Problem of measuring the positive inotropic property of a vasodilating drug: an illustration using felodipine.

A study was undertaken to determine the presence or absence in patients of positive inotropic activity in a vasodilator drug that improves cardiac output by virtue of that vasodilatation. Felodipine is a dihydropyridine calcium antagonist that has a positive inotropic effect at low concentration in the dog in vivo. In nine patients undergoing coronary angiography in whom heart rate was kept constant by atrial pacing the solvent for the intravenous administration of the drug was infused followed by the active solution. Haemodynamic variables were measured with the Mills combined left ventricular cathetertip manometer and aortic electromagnetic blood velocity transducer. Reflex positive inotropic effects were blocked with the beta adrenergic blocking drug atenolol. An index of contractility was used to assess inotropic effects--the maximum rate of rise of left ventricular pressure measured by cathetertip micromanometry; this was an isovolumic event and therefore not sensitive to arterial pressure change, and it was unaffected by changes in left ventricular end diastolic pressure. In all patients peripheral vasodilatation was observed in the plasma felodipine concentration range of 2-40 nmol.litre-1. In eight patients this was accompanied by an 11-36% increase in maximum rate of rise of left ventricular pressure, indicating a small positive inotropic effect. Felodipine appears to show both agonist and antagonist properties in man as well as in the dog.

Validation of beat by beat pulsed Doppler measurements of ascending aortic blood velocity in man.

The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r greater than or equal to 0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (Q) measurements; this yielded the following regression equation: Doppler Q = 0.90 X thermodilution Q + 0.03 litre.min-1, r = 0.92; n = 38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man.

The effects of felodipine on left ventricular function in beta-blocked patients.

Felodipine is a dihydropyridine calcium antagonist which has a positive inotropic effect in the dog in vivo. However to date, no inotropic effects have been described in man. Thus, the solvent for the intravenous administration of the drug was infused, followed by the active solution, in 9 beta-blocked patients undergoing coronary angiography; heart rate was held constant by atrial pacing. Haemodynamic variables were measured with the Mills combined left ventricular catheter-tip manometer and aortic electromagnetic blood velocity transducer. In all patients, peripheral vasodilatation was observed. In 8 patients, this was accompanied by a 9 to 50% increase in maximum rate of rise of left ventricular pressure indicating a small positive inotropic effect.

Resorbable bioceramics based on stabilized calcium phosphates. Part II: evaluation of biological response.

Synthetic materials capable of being remodelled in vivo by the same processes responsible for natural bone turnover have long been sought for use as an artificial bone substitute. These materials must ideally combine osteoinductive capacity with the ability to withstand random dissolution at normal physiological pH, while being resorbed by natural cell-mediated processes. Resorbable calcium phosphate based coatings and bulk ceramics have been developed which promote the uniform deposition of new mineralized bone matrix thus enabling rapid integration with the surrounding host bone tissue in vivo. Furthermore, a critical result of this study is the determination that the silicon-stabilized calcium phosphate ceramics are essentially insoluble in biological media but are resorbed when acted upon by osteoclasts. In vitro biological testing and preliminary in vivo testing show that the important features of this new biomaterial are a characteristic calcium phosphate phase composition and a unique microporous morphology.

Resorbable bioceramics based on stabilized calcium phosphates. Part I: rational design, sample preparation and material characterization.

It has long been the goal of biomaterials research in the field of orthopedics to develop synthetic structures exhibiting comprehensive bioactivity. In particular, an ideal bone-biomaterial would support the activity of osteoblasts in the development of new bone, while simultaneously being resorbed by osteoclasts as part of the lifelong orderly process of bone remodelling. Such resorbable calcium phosphate-based thin films and bulk ceramics have now been created by the high-temperature processing of a fine precipitate, formed from a colloidal sol and stabilized using an additive such as silicon. The materials have two characteristic features: a phase composition which is a mixture of calcium hydroxyapatite and a silicon stabilized tricalcium phosphate, and a microporous morphology based on inter-connected particles (0.2-1 microm in diameter). X-ray diffraction, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and light scattering experiments indicate that the characteristic phase composition arises during sintering through substitution reactions where silicon enters the calcium phosphate lattice under conditions of high chemical reactivity. The crystallographic features are linked through the glaserite form of the apatite structure.

Heterotypic reactions in a radioimmunoassay for coxsackie B virus specific IgM.

IgM antibody capture radioimmunoassays were developed to detect coxsackie virus B1-B5 specific IgM. Specific IgM was detected in sera from all patients with coxsackie B virus infections proved by isolation; however, sera from 13/32 patients with rising neutralising antibody titres were negative in the assay. Frequent heterotypic responses were seen among the positive sera. Thirty seven patients with other enterovirus infections were also studied, and sera from 15 of these patients reacted in the assay, showing that heterotypic coxsackie B IgM responses occur not only in coxsackie B virus infections but also in other enterovirus infections.

Enzyme amplified immunoassay: a novel technique applied to direct detection of Chlamydia trachomatis in clinical specimens.

Endocervical swabs from 212 women and urethral swabs from 100 men were tested by the routine methods for McCoy cell culture and simultaneously by a novel enzyme amplified immunoassay test to detect chlamydia antigen. Overall correlation of the amplified test with culture was 96.5%. The test proved to be a suitable screening procedure for genital chlamydial infection, particularly for large numbers of specimens or in cases in which culture was not available.