Correction to: Assessment of individual tumor buds using keratin immunohistochemistry: moderate interobserver agreement suggests a role for machine learning.

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Assessment of individual tumor buds using keratin immunohistochemistry: moderate interobserver agreement suggests a role for machine learning.

Tumor budding is a promising and cost-effective biomarker with strong prognostic value in colorectal cancer. However, challenges related to interobserver variability persist. Such variability may be reduced by immunohistochemistry and computer-aided tumor bud selection. Development of computer algorithms for this purpose requires unequivocal examples of individual tumor buds. As such, we undertook a large-scale, international, and digital observer study on individual tumor bud assessment. From a pool of 46 colorectal cancer cases with tumor budding, 3000 tumor bud candidates were selected, largely based on digital image analysis algorithms. For each candidate bud, an image patch (size 256 × 256 µm) was extracted from a pan cytokeratin-stained whole-slide image. Members of an International Tumor Budding Consortium (n = 7) were asked to categorize each candidate as either (1) tumor bud, (2) poorly differentiated cluster, or (3) neither, based on current definitions. Agreement was assessed with Cohen's and Fleiss Kappa statistics. Fleiss Kappa showed moderate overall agreement between observers (0.42 and 0.51), while Cohen's Kappas ranged from 0.25 to 0.63. Complete agreement by all seven observers was present for only 34% of the 3000 tumor bud candidates, while 59% of the candidates were agreed on by at least five of the seven observers. Despite reports of moderate-to-substantial agreement with respect to tumor budding grade, agreement with respect to individual pan cytokeratin-stained tumor buds is moderate at most. A machine learning approach may prove especially useful for a more robust assessment of individual tumor buds.

The influence of surfactants on cell surface properties of Aeromonas hydrophila during diesel oil biodegradation.

In this study the capacity of the newly isolated environmental strain Aeromonas hydrophila was evaluated. The influence of three surfactants: rhamnolipides, saponins and Triton X-100 on cell surface properties of the A. hydrophila environmental strain and the biodegradation process of diesel oil was studied. The surface activities in water, a mineral salts medium and in the biological system of all considered surfactants were estimated by means of equilibrium surface tension experiments. The obtained results indicated that critical micellar concentration in the biological system is twice higher for saponins and Triton X-100, and three times higher for rhamnolipides. Our results indicated also, that cell surface hydrophobicity (CSH) of bacteria is correlated with carbon sources in broth medium. The mechanism of surfactant action seems to be dependent on the type and concentration of surfactant used in the studies. The best effect of saponins on diesel oil biodegradation was observed using the A. hydrophila strain, diesel oil biodegradation after 21 days was 78%.

Abnormal epithelial homeostasis in the cornea of mice with a destrin deletion.

PURPOSE: Dstn(corn1) mice lack normal destrin expression and develop corneal abnormality shortly after birth such as epithelial hyperplasia and total vascularization. Thus, the mice serve as a model for ocular surface disorders. To determine the nature of epithelial defects, we examined whether epithelial homeostasis is altered in these corneas. METHODS: Dstn(corn1) mice were crossed with ubiquitous GFP mice to generate a double homozygous line, GFP-Dstn(corn1), and cell movements were determined by whole-mount histology and in vivo time-lapse microscopy, tracking the change of epithelial GFP patterns. Rates of cell division and the presence of label-retaining cells (LRCs) were determined by systemic bromodeoxyuridine (BrdU). Epithelial expression of keratins 8, 12, and 15, and MUC5AC were determined by whole-mount immunofluorescence. RESULTS: Epithelial cells in an adult GFP-Dstn(corn1) cornea were generally immobile with no sign of directed movement for the entire life of the animal. These cells were not senescent because more than 70% of basal epithelial cells incorporated BrdU over a 24 h period. LRCs were widely distributed throughout a GFP-Dstn(corn1) cornea. The epithelium of a GFP-Dstn(corn1) cornea contained a mixed population of cells with a corneal and a conjunctival phenotype as judged by the expression of keratins and MUC5AC. CONCLUSIONS: Epithelial cells of an adult GFP-Dstn(corn1) cornea are generally stationary, mitotically active, and contain LRCs, indicating that the epithelium is self-sustained, which in turn suggests that epithelial stem cells are present within the cornea. Epithelial homeostasis of adult GFP-Dstn(corn1) corneas is abnormal, mimicking that of a normal conjunctiva or a pathological, conjunctivalized cornea.

Effects of a few food diet in attention deficit disorder.

Seventy-eight children, referred to a diet clinic because of hyperactive behaviour, were placed on a 'few foods' elimination diet. Fifty nine improved in behaviour during this open trial. For 19 of these children it was possible to disguise foods or additives, or both, that reliably provoked behavioural problems by mixing them with other tolerated foods and to test their effect in a placebo controlled double blind challenge protocol. The results of a crossover trial on these 19 children showed a significant effect for the provoking foods to worsen ratings of behaviour and to impair psychological test performance. This study shows that observations of change in behaviour associated with diet made by parents and other people with a role in the child's care can be reproduced using double blind methodology and objective assessments. Clinicians should give weight to the accounts of parents and consider this treatment in selected children with a suggestive medical history.

Alteration of vertical dimension and its effect on head and neck posture.

Previous research has shown a relationship between head posture and rest position of the mandible. Should this relationship really be an interrelationship? Does a change in mandibular posture alone also alter head and neck posture? The purpose of this article is to demonstrate how a change in mandibular posture, specifically an increase in vertical dimension, contributes to craniovertical extension leading to suboccipital compression and upsetting the postural balance between the head and neck. A model of physiologic equilibrium is presented for the craniomandibular articulation.

Cross-validation of short forms of the WISC-R in two British samples.

Short forms of the WISC-R were computed by multiple linear regression on two samples of British children aged 6 to 12 years. The predictive validity of each short form was assessed both within the sample on which it was developed and cross-validated on the other sample. The empirically determined loss of power of prediction was found to be less than expected on a priori grounds. Predictions of individual scores at the lower end of the IQ distribution were less acceptable. It is concluded that short forms are robust and of value in research and for screening purposes, but cannot be recommended for clinical purposes.

Family intervention with bereaved children.

This paper describes an intervention study carried out with 45 families (83 children) where one of the parents died, leaving a child or children under 16 years of age. The families were randomly assigned to treatment and control groups, the treatment group being seen by a family therapist for approximately six sessions within 3-5 months of bereavement. All the families were contacted approximately 1 year after and again 2 years after the bereavement and a structured interview was carried out, covering parental health and psychiatric state, the children's health and behaviour, and the death and events surrounding it. At follow-up, there was some indication that the treatment group had benefited from the brief intervention. The implications for practice are discussed.

The relationship between blood-lead concentrations, intelligence, attainment and behaviour in a school population: the second London study.

This study replicates an earlier one carried out in London in which an association was found between lead and intelligence, reading and spelling. In the present study 194 children living near an urban motorway were given the same battery of tests as well as an extensive family interview to determine background variables. Before social factors were taken into account there were no significant associations between lead and outcome variable. Possible reasons for the negative results from this study are discussed.

Automated testing of reaction time and its association with lead in children.

Following Needleman et al.'s (1979) report of a correlation between tooth lead estimates in children and reaction time as measured by Rodnick and Shakow's (1940) delayed reaction time paradigm, a version of the procedure with two delay periods of 3 s and 12 s was developed for automated presentation and scoring on a VIC-20 microcomputer. Data are presented from a study of 300 children aged 6-14 years. Mean reaction time over six trials for each delay period related in a curvilinear fashion with age, but no relationships were found with sex or intelligence. Age-adjusted reaction time related significantly with blood-lead levels, but accounted for only about 1 per cent of the variance. The effect was mainly observed in younger (6-10 years) children in whom higher lead was associated with slower reaction time.

The relationship between blood lead concentrations, intelligence and attainment in a school population: a pilot study.

One-hundred-and-sixty-six children whose blood lead levels had previously been determined were assessed on a battery of psychometric tests. Blood lead levels ranged from 7 to 33 micrograms/100 ml, and the group performed within the average range on all tests of attainment and intelligence. There were significant associations between blood lead levels and attainment scores on tests of reading, spelling and intelligence, but not on mathematics. These differences in performances largely remained after social class was partialled out. Partial correlation and multiple regression analyses suggest that while only a small proportion of the variance in intelligence is explained by blood lead levels, this relationship is independent of social class. Caution is necessary in interpreting these findings, in view of the crude measure of social factors available.

Effect of sweeteners on energy uptake and its utilization by rats.

The effect administration of saccharose, glucose and glycine in solutions of equivalent relative sweetness on the uptake and utilization of energy and on blood glucose level was studied in growing female Wistar rats. It was shown that the amount of saccharose and the remaining sweeteners added to drinks has an effect on the regulation of energy uptake from the food and on metabolic processes connected with the energy utilization.

Studies on the specific dynamic effect of proteins of different nutritional value.

Using the respiratory method the rise of metabolic rate (specific dynamic effect SDE) was determined in laboratory rats after ingestion of gluten, peas, cottage cheese and ham. The SDE was greatest after ham ingestion, which is a product of high nutritional value, while after gluten ingestion which has a low protein value, the SDE was lowest.

Feeding habits and their physiological determinants. Relationships between consumer's preference for sweetness of drinks and certain physiological parameters.

Investigations determining the preferred saccharose concentration in drinks (CP(S)), gustatory threshold values, blood glucose level, basal metabolism rate and body weight index (im) were carried out with 83 cadets, aged 21--23 years. CP(S) was directly proportional to the gustatory threshold for sweet tastee, blood glucose level and basal metabolism and the correlation found in all three cases was statistically significant (p less than 0.01). The accuracy of CP(S) estimation by cadets was strictly related to their threshold difference for sweet tast depending also on smoking.

The effect of poisoning with Dithane M-45 on oxygen uptake and energy balance in adult rats.

Adult white rats were kept on natural diet containing various doses of Dithane M-45 (Mn and Zn ethylene-bisdithiocarbamate). Oxygen uptake (VO2), metabolic rate and energy balance were determined at intervals of several days. Oxygen uptake and metabolic rate were not significantly changed in animals receiving Dithane M-45 in concentrations of 5 and 50 ppm but they were significantly decreased in the animals kept on the diet containing the preparation in concentrations of 500, 2000 and 5000 ppm. The authors conclude that changes in body weight of animals after poisoning with Dithane M-45 are due, both to reduced supply and requirements for energy.