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PubMed1992

Correlated response in growth and body measurements accompanying selection for milk yield in Jerseys.

Growth and body measurements from a long-term selection project were analyzed to determine correlated responses to single-trait selection for milk yield. Data were from 1056 daughters (765 selection, 291 control) of 37 bulls (17 selection, 20 control) of 37 bulls (17 selection, 20 control) and included BW and measures of heart girth, chest depth, wither height, and length from withers to pins and from withers to hooks taken at 6 mo, 15 mo, first calving, end of first lactation, and maturity. Other data were birth weight, change in measurements and weights from first calving to end of first lactation, monthly rate of gain from 1 to 13 mo of age, and age reaching breeding weight (250 kg). Principal component scores were calculated from standardized measurements at each age. The first three principal components has meaning (size, length vs. girth, and height vs. girth). All analyses used linear mixed models with fixed effects of genetic group, generation within group, year-season of birth or calving, parity of dam, and birth status (multiple or single birth). Sires were assumed to be random and nested within genetic group. Mean squares for sires was used to test for group differences. Generation did not differ in any analysis and was removed from all models. Selection cows were heavier, larger in some measurements, and had greater overall size at 6 mo of age. Selection cows had greater monthly rate of gain and attained breeding weight at an earlier age. Genetic groups did not differ for any other measurement or weight. Control cows gained more weight and increased more in some measurements between first calving and end of first lactation. Selection for milk yield did not result in an undesirable correlated response in an growth or body measurement.

Animals↗

PubMed1992

Bone marrow cell differential counts obtained by multidimensional flow cytometry.

Five-dimensional flow cytometric analysis of normal bone marrow aspirates was utilized to determine the frequency of neutrophils, eosinophils, monocytes, lymphocytes, nucleated erythrocytes, reticulocytes, platelets, and a cell population that included blasts of each of the cell lineages, megakaryocytes, plasma cells, and basophils. Each of these bone marrow cell populations had unique features with respect to forward light scatter, orthogonal light scatter, and staining with Thiazole-Orange, LDS-751, and CD45 labeled with Phycoerythrin (PE). The identity of the cell populations was verified by sorting each of the cell populations and subsequent light microscopic examination of the cells. The frequencies of the nucleated bone marrow cell subpopulations of 50 normal donors were for neutrophils, mean 72.3%; SD +/- 5.1; 95% limits, 70.9-73.8%; eosinophils, mean 1.8%; SD +/- 1.3; 95% limits, 1.4-2.1%; monocytes, mean, 2.8%; SD +/- 1.2; 95% limits, 2.5-3.1%; lymphocytes, mean 12.1%; SD +/- 3.6; 95% limits 11.1-13.2%; nucleated erythrocytes, mean 8.9%; SD +/- 3.9; 95% limits, 7.8-10.1%; and the cell population that included blasts of each of the cell lineages, megakaryocytes, plasma cells, and basophils, mean 1.6%; SD +/- 1.2; 95% limits, 1.3-1.9%. The percentage of reticulocytes in bone marrow aspirates from 50 normal donors correlated with the reticulocyte frequency in the peripheral blood of these donors. However, the mean frequency of reticulocytes was significantly greater (p < 0.0001) in bone marrow (mean 2.19%; SD +/- 0.88) than in peripheral blood (mean 1.71%; SD +/- 0.88). The technique could discriminate between immature and mature reticulocytes based on the brighter staining with both Thiazole-Orange and LDS-751 of the immature reticulocytes. This was confirmed by cell sorting of both reticulocyte populations, which revealed larger clumps of New Methylene Blue staining material in the brighter Thiazole-Orange and LDS-751 stained reticulocytes. The immature reticulocytes were present in normal bone marrow, but not in normal peripheral blood. As expected, a significantly greater frequency of nucleated cells was found in bone marrow aspirates (mean 0.85%; SD +/- 0.59) than in peripheral blood (mean 0.20%; SD +/- 0.11). The frequency of platelets was significantly lower in bone marrow (mean 1.24%; SD +/- 0.69) than in peripheral blood (mean 2.94%, SD +/- 1.14). Flow cytometric bone marrow analysis can provide clinical laboratories with a technique that generates quantitative bone marrow cell differentials and potentially can reduce the need for light microscopic examination of bone marrow smears.

Benzothiazoles↗

PubMed1992

Automated detection and quantification of venous beading using Fourier analysis.

Venous beading associated with diabetic retinopathy is currently assessed by means of subjective comparison to standard photographs from the modified Airlie House classification scheme. We describe a computerized grading scheme for venous beading. The algorithm, based on Fourier analysis of vessel width measurements, generates a venous beading index (VBI) for digitized colour fundus photographs. Colour photographs of local vessel segments about 1200 microns in length were evaluated by experienced graders. A comparison between the VBI and subjective grading showed good agreement. The mean VBI values across the four levels of clinical grading were significantly different (p = 0.000). Multiple comparison testing indicated that the VBI was able to significantly differentiate between all four categories except the "questionable" (grade 1) category (p < 0.05). We also found that progression of venous beading can be followed with the VBI. The results indicate that further development of automated grading of venous beading is warranted.

Algorithms↗

PubMed2026

Pedagogical Efficacy of LLM-Generated Synthetic Data Versus Real-World Clinical Records: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND: Expert-reviewed clinical cases generated by large language models (LLMs) may supplement case resources in medical education, but their short-term educational performance relative to real-case-derived teaching materials remains uncertain. We compared immediate post-training test performance after teaching with the two types of case materials and assessed non-inferiority against a prespecified margin. METHODS: We conducted a prospective, parallel-group, randomized non-inferiority trial. Through the Wenjuanxing online platform, participants were randomized 1:1 to learn with either real-case-derived teaching cases compiled by clinicians and reviewed by experts or AI-generated clinical cases produced by Gemini 3.0 Pro from fully de-identified matched real cases and reviewed by three senior general surgery specialists with full-professor rank. The primary outcome was the total score on an independent 10-item immediate post-training test (0-10 points), with a prespecified non-inferiority margin of -0.5 points. Secondary outcomes included the training-phase performance score, learning efficiency index, single-item mental effort rating, case realism, and case-source judgment. RESULTS: A total of 403 participants were randomized, of whom 386 were included in the modified intention-to-treat analysis: 192 in the real-case group and 194 in the AI-generated case group. The mean post-training test score was 4.95 (SD, 3.35) in the real-case group and 4.61 (SD, 3.35) in the AI-generated case group. The mean difference (AI-generated minus real-case group) was -0.335 points (95% CI, -1.006 to 0.337). Because the lower bound of the confidence interval was below the prespecified non-inferiority margin of -0.5 points, non-inferiority was not demonstrated (one-sided P = 0.314). No significant between-group differences were observed in the training-phase performance score, learning efficiency index, or single-item mental effort rating. AI-generated cases received lower realism ratings for Level 3 cases. The proportion of participants with at least one high-confidence completely incorrect response was 1.6% in the real-case group and 2.1% in the AI-generated case group. CONCLUSIONS: In this short-term, text-based online case-learning setting, no statistically significant between-group difference was observed in immediate post-training test performance; however, non-inferiority of AI-generated clinical cases relative to real-case-derived teaching materials was not demonstrated.

Humans↗

PubMed2022

Genome-scale metabolic modeling reveals increased reliance on valine catabolism in clinical isolates of Klebsiella pneumoniae.

Infections due to carbapenem-resistant Enterobacteriaceae have recently emerged as one of the most urgent threats to hospitalized patients within the United States and Europe. By far the most common etiological agent of these infections is Klebsiella pneumoniae, frequently manifesting in hospital-acquired pneumonia with a mortality rate of ~50% even with antimicrobial intervention. We performed transcriptomic analysis of data collected previously from in vitro characterization of both laboratory and clinical isolates which revealed shifts in expression of multiple master metabolic regulators across isolate types. Metabolism has been previously shown to be an effective target for antibacterial therapy, and genome-scale metabolic network reconstructions (GENREs) have provided a powerful means to accelerate identification of potential targets in silico. Combining these techniques with the transcriptome meta-analysis, we generated context-specific models of metabolism utilizing a well-curated GENRE of K. pneumoniae (iYL1228) to identify novel therapeutic targets. Functional metabolic analyses revealed that both composition and metabolic activity of clinical isolate-associated context-specific models significantly differs from laboratory isolate-associated models of the bacterium. Additionally, we identified increased catabolism of L-valine in clinical isolate-specific growth simulations. These findings warrant future studies for potential efficacy of valine transaminase inhibition as a target against K. pneumoniae infection.

Humans↗

PubMed1992

Comparison of normal respiratory sounds recorded from the chest and trachea at various respiratory air flow levels.

Respiratory sounds (RS)s were recorded from the trachea and chest of 10 normal adult subjects at respiratory air flow levels of 1.6, 2.1 and 2.6 l/s using an oral flow transducer, and at approximately 2.1 l/s without the flow transducer. Tracheal RS (TRS) and chest RS (CRS) frequency spectra were generated using Fast Fourier Transform, and the peak, mean and maximum frequency parameters were derived from each spectra. Parametric analysis showed: (i) all three parameters for TRS spectra are significantly higher than those for CRS spectra; (ii) TRSs are on average eight times louder than CRSs; (iii) both TRSs and CRSs are air-flow independent over the flow range, though TRSs are significantly modified by the flow transducer while CRSs are not; and (iv) though of similar loudness, inspired and expired RSs (both TRSs and CRSs) have some significant spectral differences. To compare the complex shapes of RS spectra, each spectra was divided into narrow frequency bands (to create a feature set) and principal component analysis was performed on all spectral feature sets. TRSs and CRSs were shown to be independent biological signals with little overlap in their respective spectral characteristics.

Adult↗

PubMedDate not supplied

A prospective comparative clinical analysis of the first-generation knee replacements: polycentric vs. geometric knee arthroplasty.

A prospective study of 119 polycentric and 92 geometric knee replacements was performed to determine and compare the clinical effectiveness of these two prostheses. All kneex were followed for a minimum of 2 years and a mean time of 3 1/2 years (2--6 years). Data were collected using a specially designed proforma for subsequent computer analysis. Failure occurred in 11% of the polycentric and in 16% of the geometric knees. Males (8 of 47) and patients with osteoarthritic knees (22 of 68) failed most frequently. Both prostheses provided excellent relief of pain, the same degree of flexion and improvement in flexion contracture. However, walking, function, alignment, stability, muscle strength and patellar mobility varied as to the degree of improvement and the type of prosthesis. Present results with prosthetic knee replacement using a completely new operative technique can be used as a basis for comparison with other contemporary and future arthroplasty designs.

Adolescent↗

PubMed1975

Randomization and the analysis of variance.

This paper attempts to strengthen faith in randomization, first by defining it in general and second by showing how it is the fundamental means, in many experiments, of generating the probability space. It is defined by the natural structure of the experimental units (E.U.'s) not by a particular experimental design imposed on that structure. Three examples are given, with the same design but different E.U. structures and randomizations, to show that models developed from experimental designs are superficial, but that their randomization is fundamental.

Analysis of Variance↗

PubMed1978

[Intracellular regeneration and structuro-functional analysis of biological processes in normal cases and in pathology].

The author elucidates some problems in the history and the modern state in the doctrine on intracellular regenerative processes. Electron microscopic radioautography is considered as the most adequate method for studying intracellular regeneration. Certain examples are given to illustrate principally new possibilities of the structural-functional analysis of intracellular processes, normal and pathologic, studied by means of this method in view of the conception of intracellular generation. At the same time, new perspectives for further elaborating the problem of structural and functional integrity are stressed.

Animals↗

PubMed1992

Antibiotic prophylaxis for cardiothoracic operations. Meta-analysis of thirty years of clinical trials.

Antistaphylococcal penicillins and first-generation cephalosporins have traditionally been the prophylactic antibiotics of choice for patients undergoing cardiothoracic operations. Recently published studies have claimed improved outcomes with respect to postoperative wound infection when second-generation cephalosporins were used for prophylaxis. The purpose of this study was to critically review the infectious outcomes of prospective, randomized, and controlled studies of cardiothoracic surgery prophylaxis by means of meta-analytic techniques. For each of 28 studies meeting the meta-analysis entry criteria, odds ratios with 95% confidence intervals were calculated to compare the prophylactic efficacy of the antibiotic regimens. Odds ratios were then pooled, and a summary odds ratio was calculated for each pairing of antibiotic treatments. Placebo-controlled trials of cardiothoracic prophylaxis demonstrated a consistent benefit to the administration of antibiotic prophylaxis, with an approximate fivefold reduction in wound infection rate. The second-generation cephalosporins, cefamandole and cefuroxime, performed better than cefazolin, with an approximate one and one-half-fold reduction in wound infection rate. Administration of prophylaxis beyond 48 hours was not associated with improved infectious outcomes.

Anti-Bacterial Agents↗

PubMed1979

Clinical problem solving and clinical knowledge.

Videotape and simulated patients were used for evaluating third year medical students' performances in solving familiar and unfamiliar clinical problems. To assist the doctor to rate the students' performances by the review of videotapes, criteria were set up for students' behaviours that could be construed as evidence that the students recognized cues obtained by interviewing the patient and the information content of such cues. Criteria for data use by the students were also set. A mean of 90% of the pertinent medical history data was collected by the students. The amount of pertinent historical data collected was found to correlate very closely with student-patient interaction analysis score for the familiar and unfamiliar problems (r = 0.89 and r = 0.92, respectively). Significant differences in mean scores for data generation (P less than 0.001) and for data use (P less than 0.01) were found between those students who solved and those who failed to solve the familiar problem. With the unfamiliar problem a significant difference was found between the mean scores for data generation (P less than 0.01), but not for data use. The implications of these findings in medical education are discussed.

Clinical Competence↗

PubMed1992

Social and environmental factors in 10 aboriginal communities in the Northern Territory: relationship to hospital admissions of children.

OBJECTIVE: To identify social and environmental differences associated with differences in admission rates of children from 10 rural Aboriginal communities in the Northern Territory. DESIGN: Between March 1986 and December 1987, records of hospital admissions of the cohort of children for 1976-1985 were examined retrospectively; cross-sectional measurements of 74 historical, social and environmental characteristics of each community were collected. SAMPLE: All 1961 children born between 1 January 1976 and 31 December 1985 and still living in the 10 communities. METHOD: Scores on social and environmental factors for each community were generated by factor analysis. Generalised linear interactive modelling was used to investigate the association between these scores and admission rates. RESULTS: Mean admissions per child-year at risk were higher in Central Australian communities (range, 0.41-0.93) than Top End communities (0.26-0.38). Factor I accounted for 30% of the social and environmental differences between communities: communities with a high score on this factor had more houses, fewer shared toilets, more electrical appliances, better personal hygiene and a history of mission administration. High scores on this factor were predictive of lower admission rates and the factor explained most of the differences in admission rates between the Top End and Central Australian communities. Factor VI, correlated with dilapidated dwellings and fewer Aboriginal Health Workers, explained some differences in admission rates between six Top End communities. CONCLUSIONS: Social and environmental factors correlated with the degree of community development are associated with the health of Aboriginal children. Improved development programs should be community-controlled and evaluated to identify the social, educational, behavioural and environmental changes that are most effective in improving health.

Child, Preschool↗

PubMed2026

Intraskeletal Variation in Cortical Bone Quantity in a Medieval Italian Sample: A Multivariate Exploratory Approach.

Bioarcheologists interpret skeletal health by examining variability within and between individuals. Studies of bone loss have generated contradictory and conflicting results regarding the onset and severity of age-related bone loss on a global and temporal scale, perhaps due to mismatched methodologies. Intraskeletal comparisons of bone tissue prove challenging precisely because of heterogeneous baselines in quantity and remodeling of cortical bone throughout the skeleton, as well as evolutionary histories and environmental impacts on growth and development. Here we analyze cortical bone indicators from the rib, metacarpal, and femoral cortical bone in a subset of individuals (n = 72) regions from the medieval Italian archaeological site of Pieve di Pava. To facilitate intraskeletal comparisons across elements with different biological baselines, we standardize cortical bone parameters using z-scores. Variation in relative intraskeletal cortical bone was assessed using accessible multivariate methods (principal component analysis and hierarchical cluster analysis). Results suggest an association between femoral and metacarpal cortical bone values, with stochastic trends in metacarpal and femoral relative bone quantity in relation to the rib bone quantity at the sample level. Our study demonstrates that while intraskeletal analyses are challenging, they are made more robust by synthesizing multivariate methods alongside exploratory data analysis (EDA) methods to tack between sample-level and individual-level scales and variability. Ultimately, we advocate for leveraging multivariate techniques not as a final step, but rather as a means of generating new hypotheses and challenging tendencies to a priori establish typological groups in the research process.

Skeleton↗

PubMed1977

Genetic analysis of a strain of mice plateaued for litter size.

A strain of mice (S1) was successfully selected for large litter size for 31 generations, increasing the mean by 4.2 young per litter. After generation 31, there was no further progress and it was concluded that a selection plateau had been reached. Realized heritability decreased during the course of the experiment from 0.16+/-0.06 for the first 15 generations to 0.00+/-0.03 for generations 30 through 45.--In order to explore the nature of the selection plateau, the following groups were derived from line S1 at generation 34 or 35: Upward selection with inbreeding (SF), random (relaxed) selection (SO), and downward selection (SR). Selections were carried out for 10 to 11 generations. The means of SO and SF were similar to those of S1, ruling out any major effect of natural selection or overdominance. SR decreased, the mean averaging 2.3 young per litter below that of S1 during the last three generations. The fact that SR responded to selection indicates that genetic variance was still present in the plateaued population. The SF sublines were crossed when the inbreeding was 95% and a new line, SX, was formed. SX was maintained for three generations and the difference of +0.7 young per litter above the contemporary generations of S1 was significant. The results from this experiment suggest that the selection plateau in line S1 was caused by reduction of additive genetic variance to a very low level. Some nonadditive genetic variance remained, however, and was attributed to recessive alleles at low frequency. In agreement with results reported by Falconer (1971), inbreeding with selection followed by crossing of the inbred sublines proved to be effective in overcoming a selection plateau in litter size.

Animals↗

PubMed1992

Diagnosis of typhus infection with Rickettsia tsutsugamushi by polymerase chain reaction.

Two sets of oligonucleotide primers were used to amplify the genomic DNA of Rickettsia tsutsugamushi, the causative agent of scrub typhus (tsutsugamushi disease), by the polymerase chain reaction. Each set of primers amplified 538-bp and 109-bp products, representing part of a gene encoding a possible major 58-kDa immunogenic protein, from whole genomic DNA extracted from R. tsutsugamushi strains Karp, Kato, Gilliam, Kuroki and Kawasaki. No amplification was observed from R. sibirica, R. rickettsii, mouse and human genomic DNA. DNA amplification was observed from crude lysates of peripheral whole blood, tissue homogenates and paraffin-embedded skin biopsy sections obtained from patients with scrub typhus disease. Southern blot analysis demonstrated the specificity of the amplified DNA fragments following hybridisation with a DNA probe generated from R. tsutsugamushi strain Karp. By means of this procedure, a rapid and sensitive diagnosis of scrub typhus disease can be made during the acute stage of this infection.

Acute Disease↗

PubMed1979

Peripheral auditory input to the midbrain limbic area and related structures.

The effect of peripherally applied auditory stimulation on unit activity in midbrain limbic and related regions was investigated in the freely behaving rat. Two pure tones (1 and 10 kHz) and a noise generated by the discharge of a solenoid were used as stimuli presented randomly with 1 min mean interval between presentations. Computer-aided analysis of unit activity indicated that (1) a high proportion of neurons in the limbic midbrain region give excitatory responses to the three stimuli; (2) a majority of the responses have short latencies, especially in the dorsal raphe nucleus; (3) frequency and physical properties of the stimuli seemed not crucial for eliciting responsiveness; (4) habituation to repeated presentation of stimuli was not characteristic of the excitatory responses in the limbic midbrain region. These results are discussed in the light of possible functions of this region.

Acoustic Stimulation↗

PubMed1976

[Generation and determination of pulmonary distribution disturbances (author's transl)].

Pulmonary distribution disturbances could be generated in patients with bronchial hyperreactivity by inhalation of a Falicain aerosol (Propoxipiperocainhydrochlorid); The inhomogeneities of ventilation and mechanics of breathing were determined by means of several simple and complex methods. Comparison between these methods of analysis of distribution shows that small alterations of inhomogeneity can be indicated also by simple screening tests. The results confirm the significant relationship between ventilation disturbance and pulmonary inhomogeneity. Distribution disturbance enhances both the obstructive and the restrictive component of a ventilation disturbance. These two components cannot be separated exactly by means of the parameters of ventilation and mechanics of breathing because of the influence of inhomogeneity. The generated disturbances of distribution and ventilation became regular after inhalation of an Alupent aerosol.

Aerosols↗

PubMed1992

A clinical and biological validation of the DSM-III melancholia diagnosis in men: results of pattern recognition methods.

Pattern recognition methods were carried out on a sample of 80 depressed men, assessed by means of 14 items relevant to depressive symptomatology of the Structured Clinical Interview for DSM-III-R. 1985 edition (SCID). A cluster analysis generated two classes, which were described as a vital (n = 35) and a nonvital cluster (n = 45). Vital depressives were characterized by psychomotor disorders, loss of energy, cognitive disturbances, a distinct quality of mood, early morning awakening and nonreactivity (the "vital" symptoms). Our findings support the descriptive validity of the DSM-III melancholia diagnostic category, although the DSM-III criteria are too conservative and include nonrelevant symptoms (e.g., diurnal variation, anorexia-weight loss) whilst excluding some important items (e.g., loss of energy, cognitive disorders). Vital depressed men were significantly older, more severely depressed and they exhibited biological disturbances (abnormal dexamethasone suppression test, lower basal thyroid secreting hormone) as opposed to nonvital depressives. There are several arguments to support the possibility that both clusters constitute relevant stages in the overall severity of illness continuum, whilst showing qualitative differences with regard to the vital symptoms. In other words, both clusters are continuous categories within the overall severity of illness continuum and form discrete categories with regard to the vital symptoms. By merging the dimensional and categorical hypotheses, we were able to construct a new integrated threshold model: unipolar depression in men is probably a homogeneous disease with reference to overall severity of illness, but--as severity increases--vital symptoms emerge, grouping together into a distinct profile, i.e., vital depression.

Adult↗