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Spectral cues for sound localization in cats: a model for discharge rate representations in the auditory nerve.

Neural representations of pinna-based spectral cues for sound localization were modeled by simulating auditory nerve discharge rates to noise bursts that had been shaped by filtering properties of the cat's head-related transfer functions (HRTFs) at 179 locations in the frontal field. The auditory nerve model transformed spectral differences between HRTFs into simulated neural rate differences. Linear equations for this transformation were developed from actual auditory nerve responses to a limited subset of HRTF-filtered noise bursts [Rice et al., J. Acoust. Soc. Am. 97, 1764-1776 (1995)]. Signal detection methods were used to investigate simulated neural responses to pairwise changes between HRTFs. The quality of neural representation for these changes, in terms of d' values, declined when the reference HRTF was moved from a central location (0 degree AZ, 0 degree EL) to a large positive azimuth in the horizontal plane (75 degrees AZ, 0 degree EL) or a high elevation in the median plane (0 degree AZ, 75 degrees EL). Most simulated responses exhibited large d' values for comparisons of contralateral versus ipsilateral azimuths, or eccentric versus frontal elevations. This rate information resulted from directionally dependent changes in the overall gain of HRTFs. In addition, fibers with best frequency (BF: the frequency of greatest sensitivity for individual fibers) between 5 and 18 kHz showed large d' values for HRTF contrasts in the immediate frontal field because of the effects of spectral notches (i.e., sharp drops in gain over a narrow frequency range). Spectral notches also played a prominent role in simulations that required identification of HRTF location in the absence of a fixed reference stimulus. These modeling results correspond well with previously described patterns in the cat's localization behaviors.

Animals↗

The Continuity Trap in Data Science Health Research.

Secondary use is now the ordinary condition of data science health research rather than an exception to it. Electronic health records collected for clinical care become prediction tools and inputs for generative AI; imaging archives become foundation-model corpora; genomic datasets become resources for polygenic risk scores; and legacy biospecimens become renewable, indefinitely distributable cell lines. Governance has responded by emphasizing verifiable instruments such as provenance logs, repository approvals, broad-consent forms, data-use agreements, model cards, records of processing, and locality-preserving architectures. These instruments are necessary, and they answer real questions about lineage, privacy, institutional responsibility, and accountability, but they are not sufficient to establish that a present use remains ethically justified. We define ethical continuity as the persistence of normatively relevant relationships between the original conditions of data generation or material collection and subsequent downstream uses, such that current uses remain justifiable in light of the expectations, permissions, meanings, and relational obligations present at entrustment. We then define the Continuity Trap as a review-stage governance error in which a salient signal of continuity in one domain is treated as sufficient evidence of ethical continuity overall, causing inquiry into the remaining domains to close prematurely. The trap is not ordinary noncompliance, ethics creep, or a demand for universal rereview; it is a cross-domain inference error that can arise even in careful, good-faith review. We distinguish it from proxy closure, of which it is a continuity-specific subtype, and from Goodhart's and Campbell's laws, which describe how measures degrade once they become targets. We operationalize ethical continuity across 4 domains: provenance, semantics, authorization, and relational standing, developed in our Representational Veracity framework, and we show that these domains can diverge as data are linked, transformed, modeled, and redeployed. We identify the institutional mechanisms-provenance privilege, descriptor sedimentation, authorization fossilization, and community effacement-that cause auditable signals to be overread, and we examine how the US Health Insurance Portability and Accountability Act (HIPAA) of 1996, the General Data Protection Regulation, the European Health Data Space, US Food and Drug Administration guidance, the US National Institute of Standards and Technology (NIST) AI Risk Management Framework, and federated-learning governance can reduce risk while still inducing continuity traps. We apply the framework to consent and nonconsent settings, including public health, immunization, syndromic, and wastewater surveillance, polygenic risk scores, induced pluripotent stem cells, federated learning, and health-related large language models. The policy implication is trigger-based continuity review: rather than rereviewing every reuse, investigators and reviewers should identify the weakest continuity domain at the present data stage and impose a domain-matched safeguard, recorded in a short continuity statement. This reframing is intended for the committees, repositories, funders, and governance bodies that decide whether reuse may proceed, and it matters most in cross-border and low-resource settings. Provenance should begin ethical review; it should not end it.

Data Science↗

Oxymetholone: I. Evaluation in a comprehensive battery of genetic toxicology and in vitro transformation assays.

Oxymetholone is generally assumed to be a nongenotoxic carcinogen. This assumption is based primarily on the results of an Ames test, existing data in repeat-dose toxicology studies, and the predicted results of a 2-yr National Toxicology Program (NTP) rat carcinogenicity bioassay. To provide a comprehensive assessment of its genotoxicity in a standard battery of mutagenicity assays, oxymetholone was tested in microbial and mammalian cell gene mutation assays, in an in vitro cytogenetics assay (human lymphocytes), and in an in vivo micronucleus assay. Oxymetholone was also tested in an in vitro morphologic transformation model using Syrian hamster embryo (SHE) cells. These studies were initiated and completed prior to the disclosure of the results of the NTP bioassay. Oxymetholone was tested at doses up to 5,000 microg/plate in the bacterial plate incorporation assay using 4 Salmonella strains and the WP2 uvrA (pKM101) strain of Escherichia coil. There was no induction of revertants up to the highest dose levels, which were insoluble as well as toxic. In the L5178Y tk+/- mouse lymphoma assay, doses up to 30 microg/ml reduced relative survival to approximately 30% with no increase in mutants. Male or female human lymphocytes were exposed in vitro to oxymetholone for 24 hr without S9 or 3 hr with S9 and evaluated for the induction of chromosomal aberrations. There was no increase in aberration frequency over control levels and no difference between male and female cells. Peripheral blood from Tg.AC transgenic mice treated dermally for 20 wk with 0, 1.2, 6.0, or 12.0 mg/day of oxymetholone and from p53 transgenic mice treated orally by gavage for 26 wk with 125, 625, or 1,250 mg/kg/day of oxymetholone was evaluated for micronuclei in polychromatic and normochromatic erythrocytes. There was no difference in micronuclei frequency between control and treated animals. These results confirm that oxymetholone is not genotoxic in a comprehensive battery of mutagenicity assays. In the SHE assay, oxymetholone produced a significant increase in morphologically transformed colonies at dose levels of 13-18 microg/ml. The lack of genotoxicity of oxymetholone, the positive response in the in vitro transformation assay, and the results of transgenic mouse carcinogenicity assays will provide an interesting perspective on the results of an on-going NTP rat carcinogenicity bioassay.

Anabolic Agents↗

Tripartite and bipartite models of the photochemical apparatus of photosynthesis.

Tripartite and bipartite models for the photochemical apparatus of photosynthesis are presented and examined. It is shown that the equations for the yields of fluorescence from the different parts of the photochemical apparatus of the tripartite model transform into the simple equations of the bipartite formulation when the probability for energy transfer from the light-harvesting chlorophyll a/b complex to photosystem II is unity. The nature of the 695 and 735 nm fluorescence bands which appear in the emission spectrum of chloroplasts at low temperature is examined. It is proposed that these bands are due to fluorescence from energy-trapping centres which form in the antenna chlorophyll of photosystem II and photosystem I on cooling to low temperature. Even though these fluorescence emissions can be regarded as low temperature artifacts since they are not present at physiological temperatures, they nevertheless are proportional to the excitation energy in the two photosystems and can be used to monitor energy distribution in the photochemical apparatus. However, the question of their artifactual nature is crucial to the interpretation of fluorescence-lifetime measurements at low temperature.

Chlorophyll↗

[Gene expression profiles in early stage of BALB/c 3T3 cells' transformation promoted with 12-O-tetradecanoylphorbol-13-acetate].

OBJECTIVE: To elucidate the potential molecular mechanism responsible for the early time of tumor promotion, gene expression profile was studied in the transformed BALB/c 3T3 cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS: The two-stage cell transformation model was established by using the initiator of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promoter of TPA. Cell proliferation was measured by trypan blue staining and cell cycle analysis was carried out by flow cytometry assay. A cDNA microarray representing 1 152 genes was used to investigate the gene expression profiles of BALB/c 3T3 cells exposed to TPA at 4 h and 24 h respectively. RESULTS: TPA could effectively inhibit cell proliferation and induce the G1 and S cell cycle arrested in the early time. Moreover 19 genes were found differentially expressed at least twofold in the TPA treated cells as compared with the control cells, 9 of them were upregulated and 10 downregulated. Most of the differentially expressed genes were involved in cell proliferation, differentiation or apoptosis, and related to ras or p53 signal transduction pathway. CONCLUSION: TPA could influence the transcriptional expression of some genes related to cell cycle modulation and ultimately result in the cell growth arrest.

Animals↗

High syndecan-1 expression is associated with favourable outcome in squamous cell lung carcinoma treated with radical surgery.

Expression of syndecan-1 is down-regulated in many cellular transformation models. We studied the clinical significance of syndecan-1 expression in 116 squamous cell lung carcinomas treated with radical surgery. Paraffin-embedded tissue samples were immunostained with two antibodies against human syndecan-1 (B-B4 and 104-9). Syndecan-1 expression was higher in well differentiated cancers than in moderately or poorly differentiated cancers with either antibody (P=0.001 for B-B4, and P<0.0001 for 104-9), but no significant association was found with the primary tumour size (T-stage) or the clinical stage. When the median expression (10% of cancer cells positive in B-B4 staining) was used as the cut-off value, cancers with high expression were associated with more favourable survival than those with low expression (the 2-year survival rate corrected for intercurrent deaths 84% vs 61%, P=0.026). However, syndecan-1 expression was not an independent prognostic factor in a multivariate survival analysis. We conclude that syndecan-1 expression decreases in parallel with histological dedifferentiation in squamous cell carcinoma of the lung, and that low syndecan-1 expression is associated with unfavourable outcome.

Adult↗

Atmospheric pressure as a force that fills developing bones with marrow and air.

Many theories try to explain the existence and function of paranasal sinuses. This paper is an attempt to correlate process of paranasal sinus development in human with bone pneumatization processes in animals. It is here proposed that this mechanism starts in utero and continues after birth. During endochondral development, a solid hyaline cartilage model transforms into long bones. Central chondrocytes hypertrophy and their lacunae become confluent. Dissolving of the cartilage intercellular matrix forms a primitive marrow cavity. It is soon invaded by the periostal bud. Once circulation is established in the developing bone, the dissolved hyaline matrix can be slowly washed away from the bone cavity. Circulation in the bone cavity can develop slight subatmospheric pressures, similar to negative interstitial pressures in subcutaneous tissues. The amniotic fluid conducts atmospheric pressure to the fetal body. The pressure is trying to fill enlarging bone cavities through the existing vascular openings, or to create new openings. Bone walls of developing paranasal bones are to weak to resist the pressure gradient on their walls. New openings form on the weakest spots allowing airway mucosa to form initial paranasal sinuses. The enlarging cavities of long bones that are remote from the body surface and airway also develop a slightly subatmospheric pressure that fills them with cellular elements. These elements enter bone through the feeding vessels and form bone marrow. During after birth skeletal growth, bone remodeling shapes paranasal sinuses in a process of slow evolution that do not require measurable pressure gradients. When two sinuses come in vicinity, their growth rate declines, since the remaining thin and fragile bone lamella between them does not retract anymore.

Animals↗

The serial transformation hypothesis of vertebrate origins: comment on "The new head hypothesis revisited".

In "The New Head Hypothesis Revisited," R.G. Northcutt (2005. J Exp Zool (Mol Dev Evol) 304B:274-297) evaluates the original postulates of this hypothesis (Northcutt and Gans, 1983. Quart Rev Biol 58:1-28). One of these postulates is that the brain-particularly the forebrain-evolved at essentially the same time as many neural crest and neurogenic placode derivatives-including sensory ganglia, dermal skeleton and sensory capsules of the head, and branchial arches. Northcutt's subsequent paper in 1996 concluded with the idea that transitional forms might not have occurred at the origin of vertebrates. Butler proposed a "Serial Transformation" hypothesis in 2000, which disputed the latter idea in that paired eyes and an enlarged brain (but lacking telencephalon) were envisioned to have been gained before elaboration of most neural crest and neurogenic placodal derivatives. In 2003, J. Mallatt and J.-Y. Chen analyzed fossils of the Cambrian animal Haikouella, which strongly support its affinity to craniates and aspects of several hypotheses, including Butler's transformational model, because although branchial bars are present, most other neural crest and placodal derivatives are absent, while paired eyes and an enlarged brain (but probably without telencephalon) are present. A more complete picture of vertebrate origins can be realized when the various hypotheses are constructively reconciled.

Anatomy, Comparative↗

Caspases on the brain.

The basic mechanisms that underlie neurodegenerative diseases are unknown. Loss of function of specific regions of the brain is due to incapacitation of cells that constitute those regions. Cells can simply stop functioning normally (neurons may cease to transmit signals), or they may die. There is now evidence that the pathology of several neurodegenerative diseases is due to inappropriate apoptosis. This being the case, an understanding of the mediators of apoptosis, their identities, and their role in orchestrating death would be a vital step toward remedying the diseases. The central components of apoptotic pathways, proteases of the caspase family, are present in latent forms in all nucleated cells. Their activity is balanced by specific activation and inactivation events, and the molecular and biochemical controls have been well established in vitro and in model transformed cell lines. In this Mini-Review, we consider the current status of the basic control mechanisms and how these may be subverted during neurodegeneration.

Animals↗

Comprehensive approach for correction of motion and distortion in diffusion-weighted MRI.

Patient motion and image distortion induced by eddy currents cause artifacts in maps of diffusion parameters computed from diffusion-weighted (DW) images. A novel and comprehensive approach to correct for spatial misalignment of DW imaging (DWI) volumes acquired with different strengths and orientations of the diffusion sensitizing gradients is presented. This approach uses a mutual information-based registration technique and a spatial transformation model containing parameters that correct for eddy current-induced image distortion and rigid body motion in three dimensions. All parameters are optimized simultaneously for an accurate and fast solution to the registration problem. The images can also be registered to a normalized template with a single interpolation step without additional computational cost. Following registration, the signal amplitude of each DWI volume is corrected to account for size variations of the object produced by the distortion correction, and the b-matrices are properly recalculated to account for any rotation applied during registration. Both qualitative and quantitative results show that this approach produces a significant improvement of diffusion tensor imaging (DTI) data acquired in the human brain.

Algorithms↗

Three-dimensional metabolic and hemodynamic imaging of the normal and ischemic rat brain.

Unique insights into the topography of local metabolism/blood flow interrelationships in focal cerebral ischemia have afforded by the recent development of powerful image-processing techniques permitting three-dimensional (3D) autoradiographic image-averaging and analysis of replicate studies by a novel method termed "disparity analysis". This method, based upon a linear affine transformation model, directly estimates scaling, translation and rotation parameters simultaneously. The method was validated in awake Wister rats studied for local cerebral glucose metabolism (lCMRgl) with 14C-2-deoxyglucose. Brains were subserially sectioned, aligned by disparity analysis, and mapped into a common template so as to generate aggregate 3D data sets of the mean and standard deviation of the entire series (n = 9). Internal anatomic architecture was faithfully represented in the average image, and Fourier analysis revealed satisfactory retention of low-frequency information. The method was then applied to study metabolism/blood flow relationships in the acute focal ischemic penumbra of Sprague-Dawley rats subjected to distal photothrombotic middle cerebral artery (MCA) occlusion, coupled with permanent ipsilateral and 1 h contralateral common carotid artery occlusions. Matched series were studied for lCBF at 1.5 h and for lCMRgl at 1.25-2 h post-occlusion. The averaged lCBF image revealed the ischemic penumbra (defined as lCBF 20-40% of control) to form a "shell" around the cortical ischemic core and a confluent aggregate at the anterior and posterior poles of the core-zone. lCMRgl in the penumbra was heterogeneous, ranging from near-normal to markedly increased. An average lCMRgl/lCBF ratio data set revealed marked metabolism-flow uncoupling in penumbral pixels, averaging nearly five-fold above control ratio values. Sustained deflections of the DC potential were recorded in the penumbra, the site of marked uncoupling. This analysis defined for the first time the 3D topography of the ischemic penumbra and substantiated marked metabolism/flow dissociation, which is believed to be a metabolic consequence of the energy demand imposed by repeated peri-infarct depolarizations.

Animals↗

A reflection on the oxygen diffusion of the terminal villus of the human placenta (author's transl).

By using a simple model, transformed to cartesian coordinates, we examined the behavior of the fetal and maternal oxygen partial pressure on the terminal villus of the human placenta during a constant arteriovenous oxygen difference. For this purpose we divided the flow length of the cotyledon in central and a peripheral part. We found that the oxygen exchange takes place at a lower utero-umbilical oxygen pressure gradient it the reduction of the maternal blood flow velocity amounts to 30% of the normal value and if the diffusion distance is doubled. However under these circumstances a sufficient the oxygen supply of the fetal organism. This is the case with the total flow length of a single cotyledon, but some of the terminal villi in the periphery of the cotyledon, could receive at the same time a diminished oxygen supply leading to degenerative cell changes. At a progression of these morphological changes or during labor the oxygen transport can get insufficient.

Chorionic Villi↗

Increased parietal cell responsiveness to tetragastrin in patients with recurrent duodenal ulcer.

To clarify the contributive factors in the recurrence of duodenal ulcer, the present study was carried out on 65 male patients with active duodenal ulcers and 20 healthy male subjects. After having verified that the ulcer had healed, gastric acid secretory responses to graded doses of tetragastrin from 62.5 to 16,000 ng/kg/hr were investigated using a logarithmic transformation model. Several clinical features were also investigated. The patients were divided into three groups based on the later endoscopic follow-up study for two years. The early-recurrent group included 16 patients with recurrence occurring within three months. The late-recurrent group included 25 with recurrence occurring after three months. The nonrecurrent group included 24 patients without recurrences during the follow-up period. The 20 healthy male subjects were defined as a control group. The results were as follows: (1) Significant differences were not discerned either in basal and peak acid outputs between the three patients groups. (2) The ED50 value for tetragastrin was lower in the early-recurrent group than in the other three groups. (3) The early-recurrent group showed a higher percentage of smokers than the other patient groups. These results suggest that smoking and increased parietal cell responsiveness correlates strongly with duodenal ulcer recurrence.

Adult↗

Noninvasive detection of ventricular wall motion by electromagnetic coupling. Part 2: Experimental: cardiokymography.

The cardiokymograph or displacement cardiograph (DCG) is a noncontacting device which senses movement of the heart throughout the cardiac cycle by the interaction of a radiofrequency (10-20 MHz) electromagnetic field, generated by a sensing coil, with the thorax. In the paper three different techniques of detecting this movement will be discussed: monitoring the changes in sensing resonant frequency (FM modulation), monitoring the changes in impedance of the coil at resonant frequency (AM modulation) and a new technique which monitors the changes in coil impedance at fixed frequency. The sensitivities of these three techniques will be compared. A simplified theory of the mode of coupling between the coil and the thorax will be studied in terms of a transformer model. Preliminary clinical measurements of anterior left and right ventricular motion will be given. The presence of higher-frequency features related to atrial motion and the opening and closing of the aortic and pulmonary values will also be described.

Electromagnetic Fields↗

Study of automatic enhancement for chest radiograph.

Because of the large difference of the densities in the lung and other structures, the chest x-ray image behaves as a wide-range intensity distribution, which brings on a bit of difficulty to investigate the focus. In the paper, according to the intensity properties of the chest radiograph, the chest radiographic image is divided into three subregions, and a piecewise linear transformation model is established. An approach of automatic enhancement is presented, based on the gray-level normalization. The average enhanced ratios of three subregions of the normal and severe acute respiratory syndrome image are increased by 10.70% and 25.55%, respectively. The technique is proved to be effective through the evaluation of the improved images.

Humans↗

Advancing cancer detection and treatment using longitudinal routine clinical data.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Humans↗

Sustainability of ground water quality considering land use changes and public health risks.

One of the major environmental issues of concern to policy-makers is the increased vulnerability of ground water quality (GWQ). Another issue of equal interest is the sustainability of natural resources for future generations. To understand the sustainability of the natural resources such as water in general, one needs to understand the impact of future land use changes on the natural resources. This work proposes a methodology to address sustainability of GWQ considering land use changes, aquifer vulnerability to multiple contaminants, and public health risks. The methodology was demonstrated for the Sumas-Blaine aquifer in Washington State. The land transformation model predicted that nearly 60 percent of the land use practices would change in the Sumas-Blaine Aquifer by the year 2015. The accuracy of the LTM model predictions increased to greater levels as the spatial resolution was decreased. Aquifer vulnerability analysis was performed for major contaminants using the binary logistic regression (LR) method. The LR model, along with the predicted future land use, was used to estimate the future GWQ using two indices-carcinogenic and non-carcinogenic ground water qualities. Sustainability of GWQ was then analyzed using the concept of 'strong' sustainability. The sustainability map of GWQ showed improvements in many areas where urbanization is expected to occur. The positive impact of urbanization on GWQ is an indication of the extensive damage caused by existing agricultural activities in the study area.

Conservation of Natural Resources↗

Body mass index is not a good predictor of bone density: results from WHI, CHS, and EPIDOS.

Body mass index (BMI) is often used to predict bone mineral density (BMD). This may be flawed. Large epidemiologic studies with BMI and BMD data were analyzed. Weight alone is a better predictor of BMD than BMI. Thus, when selecting individuals for dual-energy X-ray absorptiometry, weight should be used instead of BMI. Low body mass index (BMI) is frequently suggested as one of the factors that indicates the need for bone mineral density (BMD) screening for osteoporosis. The inclusion of the height-squared term in the denominator of this predictive factor is taken on faith or from other data, but it may not be reasonable in this case. We used data from three large epidemiologic studies to test the BMI, height, and weight as predictors of BMD: (1) the Women's Health Initiative (WHI) with 11,390 women; (2) the Cardiovascular Health Study (CHS) with 1,578 men and women; (3) and EPIDOS with 7,598 women. Dual-energy X-ray absorptiometry data on one or more BMD sites, the total hip, the femoral neck, and the lumbar spine from the three studies, as well as height and weight were examined. Correlation coefficients for BMI and weight with BMD were compared. Log transformed models were evaluated to compare the strengths of the models. The result of weight alone was a much better predictor of BMD for all sites in the three studies than BMI. Taller participants had larger BMDs than would have been predicted by BMI. In conclusion, BMIs should not be used to select individuals for BMD screening. A regression model using weight alone or weight and height is a better predictor of BMD in all three populations.

Absorptiometry, Photon↗