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[Optical properties and clinical performance of the Topcon retinal camera TRC-FET 3 (author's transl)].

A Topcon Retinal Camera TRC-FET 3 was tested for several weeks under laboratory and clinical routine conditions. The optical properties turned out as good and meet the requirements for retinal cameras in all details. Remarkable is the high speed of the imaging system, which allows working with low flash energies and with high flash frequency. The resolving power is high (8 microns at the center) and decreases slowly to the periphery. The illumination of the fundus is fairly homogeneous. Many filters of good performance are provided. There was no problem in handling the camera, and the test photographs as well as the clinical routine photographs were of high quality.

Clinical Trials as Topic

IVF patient subgroups benefit from preimplantation genetic testing for aneuploidy: a prospective multicentre cohort study.

RESEARCH QUESTION: Can preimplantation genetic testing for aneuploidy (PGT-A) improve the ongoing pregnancy rate per transfer and reduce miscarriage rate in patients with advanced maternal age (AMA), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or both, without affecting cumulative pregnancy rate? DESIGN: Prospective cohort study of 260 patients undergoing PGT-A aged 36 years or over (AMA group), with a history of three or more blastocyst transfers without birth (RIF group), two or more early pregnancy losses (RPL group), or all. Trophectoderm biopsy was conducted day 5 or 6, and comprehensive chromosome screening was used for PGT-A before single frozen embryo transfer (PGT-A-FET). A total of 3060 patients undergoing single conventional frozen embryo transfer (FET) served as a historical reference group. RESULTS: Patients had increased odds of positive serum beta-HCG after PGT-A-FET compared with FET in the AMA (OR 1.53, 95% CI 1.06 to 2.21) and RIF (OR 2.11, 95% CI 1.41 to 3.14) groups. The PGT-A-FET group significantly improved the odds of ongoing pregnancy in the AMA (OR 2.20, 95% CI 1.52 to 3.18), RIF (OR 3.96, 95% CI 2.60 to 6.04) and RPL (OR 2.81, 95% CI 1.52 to 5.21) groups. The odds of pregnancy loss were significantly reduced with PGT-A-FET in the AMA (OR 0.36, 95% CI 0.21 to 0.64), RIF (OR 0.10, 95% CI 0.04 to 0.26) and RPL (OR 0.14, 95% CI 0.04 to 0.53) groups. Cumulative pregnancy rate did not differ between PGT-A and conventional cycles (RR 0.94, 95% CI 0.80 to 1.10). CONCLUSIONS: PGT-A improved the odds of ongoing pregnancy and reduced the odds of pregnancy loss in all groups. The cumulative pregnancy rate did not differ between PGT-A and conventional cycles. Findings should be interpreted in the context of the observational design.

Adult

The forced expiratory time as a measure of small airway resistance.

1. In five subjects, ten consecutive forced expiratory spirograms were recorded on each of 6 different days and the total forced expiratory time (FET) on each spirogram was measured. The mean overall coefficient of variation of the FET was 11.3% and of the ratio forced vital capacity (FVC)/FET was 8%. 2. Twenty-two subjects with probable small (less than 2 mm diameter) airway dysfunction as manifested by a reduced (less than 75% predicted) maximum mid-expiratory flow (MMEF) in the middle 50% of the FVC with normal FVC and FEV1 (greater than 80% predicted) were studied before and after bronchodilatation. There was no significant correlation between change in FET and change in MMEF (r = 0.36, P greater than 0.01), but between change in MMEF (deltaMMEF) and change in FVC/FET (deltaFVC/FET) there was a positive correlation (r = 0.78, P less than 0.001). 3. In six of these twenty-two subjects, the deltaFVC/FET and deltaMMEF on bronchodilatation correlated well with the change in residual volume (deltaRV). but neither measurement correlated well with the change in the 'closing volume' measurement expressed as the ratio of phase 4/VC(%). The deltaFET did not correlate well with either deltaRV or delta[phase 4/VC(%)]. 4. In eighty-one selected normal subjects (FVC, FEV1 and MMEF all greater than 80% predicted) there was better correlation of age with the FVC/FET (r = -0.676) than with the FET (r = +0.43); both correlations were significant (P less than 0.001). 5. These results do not support the use of the FET as a suitable test of small airway function; however, the mean flow rate expressed as FVC/FET may, in the presence of a normal FEV1/FVC ratio, be an adequate test of small airway function.

Adult

Enhancing detection of polygenic adaptation: a comparative study of machine learning and statistical approaches using simulated evolve-and-resequence data.

BACKGROUND: Detecting signals of polygenic adaptation remains a significant challenge in population genomics, as traditional methods often struggle to identify the associated subtle, multi-locus allele-frequency shifts. Here, we introduced and tested several novel approaches combining machine learning techniques with traditional statistical tests to detect polygenic adaptation patterns in time-series of allele frequency changes from whole genome data. We implemented a Naive Bayesian Classifier (NBC) and One-Class Support Vector Machines (OCSVM), and compared their performance against the classical Fisher's Exact Test (FET). Furthermore, we combined machine learning and statistical models (OCSVM-FET and NBC-FET), resulting in 5 competing approaches. The framework is mainly designed and validated for evolve-and-resequence (EaR) experimental designs, where defined selection pressures and temporal sampling are feasible, but might be applicable for certain natural experiments as well. RESULTS: Using a simulated dataset based on empirical C. riparius Pool-Seq data, we evaluated methods across evolutionary scenarios varying in generation, selection strength, and number of loci under selection. Our results demonstrate that the combined OCSVM-FET approach consistently outperformed competing methods, achieving the lowest false positive rate, highest area under the curve, and high accuracy. The performance peak aligned with what we term the 'late dynamic phase' of adaptation - the period after initial selection has occurred but before fixation - highlighting the method's sensitivity to ongoing selective processes. CONCLUSIONS: Furthermore, we emphasize the critical role of parameter tuning, balancing biological assumptions with methodological rigor. While broader applicability remains an important direction for future work, the present benchmarking is intentionally scoped to EaR experimental contexts.

Machine Learning

[The usefulness of ruthenium red in dye exclusion test on cultured cells (author's transl)].

QUESTION: The reliability of statements and the reproducibility of results derived from experiments on cell cultures are dependent on the use of practicable methods for most objective assay of the state of the cells. The experiments were to clarify the following questions: 1. Is it possible to assay vital and nonvital cells by use of the dye exclusion test (FET)? 2. Are intact cells also stained by FET? 3. Will there be a possibility to make FET more sensitive to obtain more reliable statements?

Cell Line

[Fetal causes of the onset of labour. A kybernetic model (author's transl)].

The question of initiation of labour is not yet solved. A fetal fixing of the date would be ingenious. On the one hand the fet is endangered by prematurity, on the other hand by placental insufficiency in postmaturity. Fetuses with comparatively lighter placenta remain in average shorter in utero until spontaneous initiation of labour than those with comparatively heavier placenta. This fact leads to the assumption of a relative placental insufficiency as a determining factor of the onset of labour. A further inquiry demonstrates, that babies born after premature termination of pregnancy about the term - either by induction of labour or by primary sectio caesarea - are heavier and longer than those born after spontaneous labour. This leads to the assumption of a prenatal weight loss of the infant before spontaneous initiation of labour. This weight loss is caused by diminution of water content and relative placental insufficiency. This relative placental insufficiency also leads to a diminution of amniotic fluid, which is swallowed by the "hungry" fet in a greater amount. Altogether a diminution of uterine volume is resulting, which is accomplished by a diminution of uterine wall tension. The coordination of uterine activity, which precedes delivery, is combined with the ripening of the cervix. The ripening of the cervix also leads to a retraction of myometrium and thus to a further diminution of uterine wall tension. It is concluded, that a diminution of uterine volume, causes by fetal weight loss and diminution of amniotic fluid, leads to a reduction of uterine wall tension, which is supported by the ripening of the cervix. This reduction of uterine wall tension is the precondition of the increasing coordination of activity, which precedes delivery.

Amniotic Fluid

Transfer learning with multiomics integration and deep neural networks reveals drug resistance mechanisms in cancer.

Drug resistance remains one of the primary challenges in effective cancer therapy. In this study, we employed a deep neural network (DNN)-based transfer learning (TL) approach to predict drug response and uncover drug resistance mechanisms. We integrated gene expression, somatic mutation, and copy number aberration (CNA) data with drug response profiles using multi-omics integration (MI). We used the Genomics of Drug Sensitivity in Cancer (GDSC) data for training and incorporated drugs with same pathways into the training models. We then evaluated drug response predictions on independent in-vivo PDX Encyclopedia (PDX) and ex-vivo the Cancer Genome Atlas (TCGA) datasets. In addition, we conducted pathway enrichment analyses to elucidate the mechanisms underlying drug resistance for paclitaxel, 5-fluorouracil (5-FU), gemcitabine, and cetuximab. We also applied Fisher's exact test (FET) to assess potential associations between drug resistance and the presence of mutations or CNAs. Our pan-drug models outperformed other methods based on the area under the precision-recall curve (AUCPR). Our pathway enrichment analyses revealed LDHB-mediated pyruvate metabolism and FYN-mediated focal adhesion might have pivotal roles in paclitaxel resistance, while PINK1-mediated mitophagy might be critical in 5-FU resistance. In addition to transcriptional activation, FET suggested that CNAs in LDHB and PINK1 may also be associated with resistance to paclitaxel and 5-FU, respectively. Furthermore, enrichment results for paclitaxel and cetuximab indicated shared resistance mechanisms between the two drugs. Importantly, our findings are consistent with prior experimental studies, providing literature-based validation of our results. Overall, our DNN-based TL approach achieved strong predictive performance across PDX & TCGA datasets and enrichment analyses provided valuable biological insights into drug resistance mechanisms.

Humans

Intrasubject variability of maximal expiratory flow volume curve.

Analysis of airflow in the terminal portion of the maximal expiratory flow volume curve has been suggested as a useful test for the early diagnosis of chronic airways obstruction. Whether such an analysis can identify early disease, and whether any subsequent action can prevent the progress of chronic airways obstruction, is unknown and will require prospective studies. As a precursor of such a study we have tried to establish the intrasubject variability of those tests of forced expiration which may be used for screening. We therefore measured expiratory flow volume curves of five healthy males and five healthy females aged 20-30 years as this is an age-group in which early detection of airways obstruction may be of value. Flow volume curves were obtained on the same day of the week for six weeks, and on three separate days during this period we carried out three flow volume curves every hour from 9 am to 6 pm. The data were subjected to analysis of variance to determine the variability of each measurement. Data were collected from forced expired volume in one second (FEV1) forced vital capacity (FVC), maximum expiratory flow rates at 50% and 75% of expired vital capacity, and forced expiratory time (FET). The results showed no consistent pattern of diurnal variation over the working day. The variation in any subject for FEV1 and FVC over the study period was considerably less than variations detected in the maximal expiratory flow rates at 50% and 75% of the expired vital capacity and FET. Our results suggest that the intrasubject variation found in flow rates of the terminal portion of the maximal expiratory flow volume curve and forced expiratory time may limit the usefulness of these tests in detecting early airways obstruction. FEV1 and FVC are more reproducible tests and are therefore particularly suited for cross-sectional screening. The more sensitive maximal expiratory flow volume curve may, however, be more useful for long-term studies in individuals when the onset of disease is sought, or for short-term challenge studies requiring the most sensitive index of change in airway characteristics.

Adult

The presence of gamma-carboxyglutamic acid-containing protein in atheromatous aortae.

It has been established that a gamma-carboxyglutamic acid-containing protein is present in rat aortae after long term atherogenic diet administration. A similar protein was proven to be present in turkey tibial tendons that are predisposed to undergo physiological calcification. The molecular weight and amino acid composition of both proteins were identical. They contained six glutamic acid residues per molecule, three of which were gamma-carboxylated. The proteins studied were also identical in their N-terminal sequence over six residues. This sequence was fully coincident with that published for osteocalcin (Price, P.A., Poser, J.W. and Raman, N. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 3374--3375). In the region corresponding to residues 20--26 in osteocalcin, a single replacement of valine for isoleucine was found in turkey tendon protein. From the physiological point of view it should be mentioned that the level of the gamma-carboxyglutamic acid containing protein in atherogenic diet fet rat aortae exceeds that found normally in bone or in tissues predisposed for physiological calcification.

1-Carboxyglutamic Acid

A 200-point analog computer of average transients for electrophysiological measurements.

A 200-point computer of average transients uses capacitors as the memory devices and MOS-FET switches. The averaged wave form is stored exponentially and the memory decays exponentially when that input is removed. The memory exponential time constant (i.e. the number of sweeps averaged) can be varied with one resistor. Read-out to an oscilloscope occurs simultaneously with read-in of each new signal. This linear circuit computes a highly accurate average, even though 10% components are used. It is more cost-effective than commercial digital averagers for many applications and can average evoked potentials, field potentials, weak single units and intracellularly recorded postsynaptic potentials.

Animals

A new method for electromyography of the female urethra.

A newly developed catheter enables the introduction of fine wire electrodes into the urethral striated sphincter muscle at predetermined locations and depths. Because of FET-probes electrode wires can be short, thus the signals show minimal artifacts owing to cable movement. The technique 1) facilitates registration of signals during coughing, walking, micturition and other activities, 2) is simple to perform and painless to the patient, 3) can be done by inexperienced personnel and 4) provides assurance that the electrodes are in the urethral sphincter muscle.

Cough

Eelectrophysiological correlates of pecking.

Electrophysiological correlates of pecking were studied in 50 freely moving pigeons. With the backward averaging technique average motor potentials (AMPs) were found in all subdivisions of the striatum. The AMPs appeared significantly earlier (40 msec before pecking) in the Wulst than in the neostriatum, ectostriatum, and archistriatum (18 to 28 msec before pecking). Their amplitude could be reduced by monocular occlusion. Average visual responses (AVRs) in the optic tectum were decreased at brief peck-flash intervals, reached maximum with 100 to 200 msec peck-flash delays and then again decreased at intervals corresponding to the occurrence of the next peck (300 msec). A head-mounted microdive system and a miniature FET probe were employed to record unit activity with glass microelectrodes. Out of 280 examined neurones, 83% were activated and 6% inhibited by pecking. The pre- and post-pecking histograms indicated that hyperstriatal neurones are activated earlier and for a longer time than the neostriatal units. It is concluded that rostral parts of striatum play an important role in the functional organisation of pecking.

Animals

Electrophysiological analysis of retrieval of conditioned taste aversion. Physiological techniques and data processing.

New techniques suitable for electrophysiological investigation of retrieval of conditioned taste aversion (CTA) were developed. The gustatory discrimination apparatus consisted of two parallel drinking spouts (20 mm apart) equipped with photoelectric lick sensors. The spouts contained water or the aversive fluid (0.15 M LiCl), respectively, and their position could be rapidly (50 ms) interchanged with a reversive electromotor. Licking at either spout and the position of the fluids were recorded on one channel of a tape recorder. Unit activity was picked up with tungsten microelectrodes (40 micrometers) inserted into the brain of a freely moving rat with a head-mounted microdrive system (weight 2 g), fixed to an implanted guiding cannula. The electrode was connected through a head-carried FET signal follower to a wide band integrated circuit amplifier and the unit activity was recorded in the other channel of the tape recorder. The records were evaluated using an off-line computer program (LINC 8) consisting of a spike detection subroutine followed by amplitude histogram analysis. The mean (M) and SD values were computed for uni- or bimodal amplitude distributions of the principal spike components. Spike falling within the M+/-2 SD range of the selected parameter were identified as single units and used for construction of post stimulus histograms triggered by licking or by spout switching.

Action Potentials

An unusual case of feline leukemia and an associated syncytium-forming virus.

A 3-year-old female Siamese cat was admitted to a local animal hospital with a history of recent extreme lethargy and anorexia. A hemorrhagic tumor was removed from an area of oral buccal skin and diagnosed histopathologically as lymphosarcoma. Rapid physical deterioration occurred, and the cat became moribund 2 weeks after surgical operation. Necropsy revealed at least 200 spherical hemorrhagic neoplastic nodules attached to the omentum, mesentery, and peritoneum. Examination of histopathologic sections confirmed the striking characteristics of an extremely vascular and highly invasive malignant lymphoma, which was designated feline tumor No. 01 (FeT-01). There was no evidence of peripheral blood leukemia. Electron microscopic examination of tumor tissue revealed numerous viral particles having characteristics common to both feline leukemia virus (FeLV) and feline syncytium-forming virus (FeSFV). Primary cells and cultures propagated from tumor tissue were found to be negative or weakly positive for group-specific (gs) antigen by radioimmunoassay but strongly positive when assayed by indirect immunofluorescence. Co-cultivation of cells from tumor tissue, with normal prescreened feline embryo cells, revealed the presence of numerous FeSFV-like viral particles in the absence of C-type virus. A FeSFV was isolated from these passaged cells, with characteristics similar to FeSFV isolates previously described in the literature. The apparent presence of FeSFV in lymphosarcomatous tissue and the apparent absence of FeLV C-type particles in passaged cells indicate the need to make a more intensive study of the FeSFV group of viruses and the possible etiologic relationship to feline malignancies.

Animals

Fabrication of pH-sensitive implantable electrode by thick film hybrid technology.

We report preliminary results of our experiments directed at fabricating pH-sensitive electrodes suitable for in vivo use by means of thick film screening techniques. Our results show that glass membranes of suitable thickness and possessing nearly theoretical sensitivity to pH can be fabricated by this process. A hybrid electrode structure permits the incorporation of a source follower FET amplifier directly adjacent to the pH membrane, significantly reducing response time and noise pick-up. Extension of the basic electrode structure to accommodate membranes sensitive to other ions is discussed.

Biomedical Engineering