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[Individual anatomic variability of Forel's field H].

The investigation was performed in serial frontal sections of 100 preparations of the diencephalon and midbrain made 1 mm from one another. The shape of Forel H field was found to be very variable, changing from the rectangular to triangular shape in pararubralparts, and from oval to semioval-in prerubral parts. The size and position of Forel H field proved to change in relation to intracerebral reference points: posterior comissure, medial and intercomissural planes used in stereotaxical technique.

Adult

Efficacy of cognitive/noncognitive measures in predicting resident-physician performance.

There has been relatively little research on the relationship between the clinical performance of physicians and the criteria used by medical school admissions and promotions committees. The studies which have been done primarily relate clinical performance to cognitive criteria. They have usually found only negligible relationships. By considering both cognitive and noncognitive variables, several investigators recently have improved the prediction of clinical performance in medical school. The present authors attempt to determine the increase in predictive efficiency attained by adding noncognitive variables to cognitive variables in predicting clinical performance of residents. The results of this investigation indicate that a combination of cognitive and noncognitive predictor variables functions much better than any individual variable or even any specific class of variables in predicting the postgraduate clinical performance of physicians.

Clinical Competence

Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson's disease.

Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson's disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous evaluations included whole-genome/exome sequencing, RNA sequencing, and in vivo studies, including a 39-week Good Laboratory Practice-compliant mouse safety study. While mDACs from all lines met safety criteria, mDACs from one patient failed to improve rodent behavioral outcomes, underscoring inter-individual variability. Importantly, in vitro assessments did not reliably predict in vivo efficacy, identifying dopaminergic fiber density as a key efficacy criterion. These findings support comprehensive quality control guidelines for autologous cell therapy and pave the way for a clinical trial with eight sporadic PD patients, scheduled to commence in 2025.

Humans

Relationships among measures of preferred tempo and motor rhythm.

Male and female subjects (Ns = 100) performed an accuracy task involving consecutive arm swings at a self-paced tempo. Following this, the subjects performed a motor rhythm task keeping in cadence with audio-visual stimuli presented at their preferred tempo. Previous findings regarding the magnitude of individual differences in preferred tempo and within-individual variability were replicated, as was the absence of sex differences for these attributes. With regard to motor rhythm, the findings indicated that (a) constant and variable error, and not absolute error, were the appropriate measures of performance, (b) there were no sex differences either in spatial or temporal accuracy or in trial-to-trial consistency of performance, (c) substantial individual differences were present in rhythmic accuracy, as were moderate individual differences in variability, (d) neither rhythmic accuracy nor variability was appreciably related to preferred tempo, and (e) spatial and temporal accuracy are relatively independent components of rhythmic accuracy.

Acoustic Stimulation

Quantitative analysis of mating behavior in aging male Drosophila melanogaster.

Dynamic changes in quantitative aspects of mating behavior of the male fruit fly as its life unfolds, from eclosion through maturity (peak performance) and "physiological death" (loss of fertility followed by complete loss of ability to mate), towards actual death, have been identified in this work by observations and measurements on 28 male fruit flies of the Oregon R strain studied individually. At weekly sessions from the first day of their imaginal life until their natural death, each fly was given the opportunity to mate with up to three virgin females during a one-hour period. Length of the latency period of each accomplished mating and duration of copulation were recorded. After mating the females were allowed to lay eggs for 24 hours and the number of offspring was counted 26 days later. The period between 1 and 4 weeks of age is characterized by peak and fairly constant performance: multiple matings, short latencies, long durations of copulation, and high degree of fertility (number of offspring); then a decline sets in, in some measures slower than in others, as the flies age. Large intra- and inter-individual variabilities were, however, found which obscure possible correlations between individual measures of mating ability and length of life. At the individual level, a preliminary analysis showed a good correlation (r = 0.80 and 0.79) between life span and week of last mating (onset of impotence) or week of last fertile mating (onset of sterility). At the population level it was found that a number of measures, i.e. number of remaining maters at each age, number of remaining fertile maters and total number of matings, had an age-course similar to survivorship but anticipated it by 4--6 weeks. Other measures, such as number of multiple matings and number of offspring declined with age faster than survivorship.

Aging

A method for detecting errors in data of growth studies.

The paper describes a new method used for data cleaning in growth and development studies. The method is essentially based on the assumption that an extreme value of a certain variable might be suspicious if other highly correlated variables show low compatibility with it and that, on the other hand, an extreme but possible value tends not to be erroneous if it is reinforced by another extreme but possible value of a highly correlated variable. Each variable was therefore included in at least two ratios with the highest correlated variables. A program was designed to detect extreme values of individual variables and extreme ratio values. This procedure with ratios was used to help to detect possible errors and discriminate them from true extreme values. Seen in the light of corrected data files against existing data files, the number of corrections was approximately 4.4%. If the real number of corrected errors is compared to the total number of subjects, this percentage reached 5.5%. If, when correcting, the real value was not detected with certainty, the erroneous value was then simply deleted. From our results, there is reason to believe that with this method few detectable errors will escape from the cleaning procedure. Conclusions for future correction procedures and for future growth studies in general, are also given in the paper.

Anthropometry

Assessment of the association between habitual salt intake and high blood pressure: methodological problems.

Despite the finding in cross-cultural comparisons that habitual sodium intake correlates with levels of blood pressure, similar studies from within population groups have yielded inconsistent results. The data presented in this report indicate that in industrialized societies the high degree of intra-individual variability of sodium intake, compared to much smaller inter-individual differences, may obscure potential biological correlations. A quantitative statistical method is presented to assess and minimize the effect of the large intra-individual variation in daily urinary sodium excretion.

Adult

The use of public transportation in urban areas: toward a causal model.

In this study, using the statistical models recently introduced by Goodman, we analyze the reasons why individuals choose the car or public transportation for the journey to work and draw out some of the implications of our analysis for public policy. Building on the work of Schnore, we develop a model in which both structural and individual variables are interrelated and show that the structural contexts within which individuals make decisions about their choice are crucial. We also show that, while status differentials are largely accounted for by income differences, male preferences for the automobile tend not to be due either to the structural variables or to income differences. Our findings suggest that present policies designed to induce people to shift to public transportation for the journey to work are not likely to be effective, since they do nothing to alter present cost differentials between the two modes.

Automobiles

[Specific variability in the number of cells with X-chromatin in short-term buccal epithelium cultures from women following exposure to hormones at different phases in their individual diurnal biorhythm].

Changes in the number of cells with X- and K-chromatin were studied in the buccal epithelium of 4 women in vivo for 29 h, every 2--4 h, and similarly in cultures (3 h) with and without any hormone: ACTH, insulin, thyroxin. The biorhythm of the cells with X-chromatin (established by Kanyuka in 1973) both in vivo and ie vitro within the range of from 44 to 340 0/00 per 24 h was confirmed; individual variability of the mean heterochromatin index value (X-HClm) was revealed in vitro with and without any hormones. Cell incubation with hormones at the time of minimal X-HCl in vivo led to increase in the number of cells with X-chromatin within 3 h from 50 to 240 0/00, whereas incubation at the time of maximal X-HCl in vivo--to reduction from 190 to 70 0/00. It is suggested that the specific response to the hormones is preceded by the nonspecific tissue response, determined by its condition at the time of action (by the individual X-HCl biorhythm phase) and realized in the systemic reconstruction of the number of cells at various mitotic cycle phases. Stereotypic reaction was expressed in the changes in character of the nuclear chromatin sondensation; these processes were reversible.

Adrenocorticotropic Hormone

Safe protein-calorie ratios in diets. The relative importance of protein and energy intake as causal factors in malnutrition.

There has been up to now a lack of agreement as to the way in which protein and energy requirements could be combined to give estimates of adequate dietary protein-energy ratios. In particular, the relevance of the simple ratio, average protein--average energy requirement as a basis for assessing diets, has been questioned on the grounds that it fails to take account of individual variability in needs for energy, and of the extent to which these may be independent of variability in protein requirements. The main problem is to evaluate the range over which individuals can adapt either energy intake to suit expenditure, or expenditure to suit intake, without detriment to health or growth. One solution adopted by Beaton and Swiss in a recent paper is to accept the range of observed variability of energy intakes in normal populations as a measure of this. An alterative is to make use of experimental evidence for the minimum energy intake for maintenance of body energy content. These two approaches are compared, and are shown to give quantitatively similar results. The method based on minimum maintenance requirements offers the further advantage that it allows an assessment of dietary situations in relation to the likelihood of occurrence of different forms of protein--energy malnutrition; those situations in which protein deficiency is a secondary consequence of low energy intake are differentiated from those in which the primary cause is an inadequate level of protein in the diet. The adequate "safe" level of protein-energy ratio in the diets of 2- to 3-year old children is close to 5% and since most varieties of cereal grains appear to provide utilizable protein levels of close to this amount, this lends further support to the view that primary protein deficiency is unlikely to be the main factor causing protein-energy malnutrition in communities for which cereals are the cheapest source of energy.

Breast Feeding

Carcinoma of the penis.

This study updates the experience at our hospital with cancer of the penis, which now includes 122 consecutive cases seen between 1940 and 1974 with 100 per cent followup. Historical, clinical, pathological, therapeutic and followup data were extracted for all cases in a digital code for transfer to computer storage. Life tables giving cumulative survival rates through 10 years with standard deviations and age corrections were calculated for each variable. The data were tabulated for publication to emphasize the prognostic significance of individual variables for the purpose of prospective research planning. The data were then evaluated regarding indications for prophylactic inguinal lymph node dissections, if any.

Computers

Absorption and endogenous faecal excretion of calcium by low birthweight infants on feeds with varying contents of calcium and phosphate.

Low birthweight infants aged 4-41 days were given from birth one of three experimental milk formulae varying widely in content of calcium and phosphate. Ca and P in feed, urine, and faeces were measured between carmine markers corresponding to a metabolic period of 48 hours. Calcium enriched in 46Ca to provide a marker for the dietary Ca was added to one feed and 46Ca measured in urine and faeces. True absorption of Ca and endogenous excretion into the bowel could then be inferred. True absorption of Ca was proportional to Ca intake and independent of P intake. Endogenous faecal excretion seemed to be independent of both Ca P intakes, and varied widely between different infants in the range 4-150 mg/day. Urine Ca was low and retention was essentially the difference between true absorption and endogenous faecal excretion. Retention of Ca tended to be much greater on a high Ca intake, but the variability in retention between infants on a given intake was large, paralleling the variability in endogenous faecal excretion. The variability in plasma Ca concentrations in newborn infants may in part be a consequence of wide individual variability in endogenous faecal excretion. The 46Ca marker technique provides a means of investigating the factors determining this variability.

Calcium

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment.

INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

Humans

Modifications of the pattern-evoked potential (PEP) in relation to the stimulated part of the visual field (clues for the most probable origin of each component).

A spatio-temporal analysis of the successive and simultaneous components of the pattern-evoked potential recorded on the scalp, and of their modifications according to which part of the visual field is stimulated, was carried out with 20 'normal' subjects, in order to shed some light on their most probable sites of origin. The stimulus consisted in the onset of a 20 degree checkerboard presented in runs of 75 stimuli each. Its duration was 750 msec and its frequency of occurrence was random (about 1 every 1500 msec). Twelve different visual field situations were recorded: whole field, half fields and quadrants and stimuli limited to the fovea, to the macula and to extramacular areas. Data were collected from 9 active electrodes (in line, forming a cross montage), and various reference electrodes (ear lobes, Fz, non-cephalic). Eye movements were simultaneously recorded. The electrophysiological data were digitized on line and processed by computer in the form of averaged spatio-temporal maps. In addition to the classical posterior components which peak on the midline (N 60, N 140, and P 200) or less than 4 cm away on both sides (P 90), a late negative wave (LN 210) was differentiated which peaked lower than the inion and more than 8 cm away from the midline on both hemispheres. The large inter-individual variability of the spatio-temporal organization of these components under the same conditions, as well as its very good intra-individual reproducibility, were emphasized. Interpreted on the basis of a simple dipole sheet model of the visual cortex, the changes observed for each component in the 12 experimental situations led to the following suggestions: only the first component N 60 could reflect the activity of the part of area 17 emerging on the convexity, whereas P 90 (Jeffreys' CI) is more likely to originate in area 19 and the midline components N 140 and P 200 in area 18. The topography and reactivity of LN 210 could fit with the hypothesis that it reflects activity of the infero-temporal cortex.

Adult

The effects of season and temperature on D-lactate dehydrogenase, pyruvate kinase and arginine kinase in the foot of Helix pomatia L.

The effects of pH, season, environmental and experimental temperatures on the activities and kinetic parameters of D-lactate dehydrogenase, pyruvate kinase and arginine kinase from the foot of the pulmonate snail Helix pomatia were analyzed. Both in phosphate and Tris buffers D-lactate dehydrogenase was the enzyme with the most acid maximum, arginine kinase that with the most alkaline, whilst pyruvate kinase occupied an intermediate position. Pyruvate kinase activity, measured at 20 degrees C, was positively correlated with the environmental temperature at the moment of collecting the animal, whereas neither arginine kinase nor D-lactate dehydrogenase showed such a relationship. A seasonal study based on approximately 100 specimens established that arginine kinase activity remained the same throughout the year. Pyruvate kinase activity was slightly lower, and D-lactate dehydrogenase activity significantly higher, in winter than in summer animals. Snails subjected in spring to a short warm-up period before enzyme extraction showed extreme variability and some extraordinarily high values of pyruvate kinase activity, suggesting that either season or elevated temperature may have an immediate effect on the activity of this enzyme. Individual variability of all three enzymes ranges from 300 to 400%. The activities of pyruvate kinase and D-lactate dehydrogenase are strongly correlated in summer, forming a "constant-proportion-group", whereas in winter, with D-lactate dehydrogenase activity increasing and pyruvate kinase activity decreasing these two enzymes become "uncoupled". The Km value of pyruvate kinase is independent of experimental temperature between 10 and 25 degrees C, whereas that of D-lactate dehydrogenase and arginine kinase increases about three-fold within this range. Thus the temperature relationship of a single enzymic reaction cannot be used as an arguemnt for or against the occurrence of temperature compensation of whole animal metabolism. The possibility of modulation of enzyme activity by environmental temperature is discussed.

Acclimatization

[Variability of heat resistance of frog muscle tissue in Ringer's solution].

The variability in the initial level of heat resistance of muscles was found to decrease with increase in the duration of keeping the frogs in vivarium. However, the variability in the resistance of isolated muscles kept in Ringer's solution during 90 min. is independent of this factor and lesser than the initial one. The data obtained suggest that the narrowing of the variability in the resistance of muscles kept in Ringer's solution is determined by the dispersion of the initial level of the resistance. This phenomenon is only observed when the individual variability in the resistance of muscles is sufficiently high immediately after their isolation.

Acclimatization