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PubMed1993

Family functioning and injury severity as predictors of child functioning one year following traumatic brain injury.

This study examined changes in children's functioning in the year following traumatic brain injury (TBI) and the preinjury family and injury factors most predictive of children's overall adaptive functioning and social competence at 1 year. Ninety-four children with TBI (mild = 50, moderate = 25, severe = 19) and their families were consecutively enrolled from two regional medical centers. The age range was from 6 years to 15 years. Interviewer ratings and standard measures of family and child functioning were completed within 3 weeks of injury (measuring preinjury status), at 3 months and 1 year. Mean preinjury parent and teacher ratings of child functioning were within normal range. Older children (> or = 12 years) had worse preinjury functioning than younger children. Declines in child functioning were significantly associated with injury severity. Mild and moderately injured children had few declines in overall functioning. Severely injured children had the most dramatic early declines and improved only slightly between 3 months and 1 year; however, older children from poorly functioning families deteriorated in the same period. Injury severity and preinjury family functioning explained from 25% to 39% of the variation in child functioning at 1 year and up to 57% when the child's preinjury status was included. Children at risk for poorer adaptation following TBI can be identified and for optimal recovery should receive appropriate support services for optimal recovery.

Adaptation, Psychological↗
PubMed1990

Prediction of effects of therapeutic total body irradiation in man.

Total body irradiation (TBI) is an important but toxic element in the preparation of patients for bone marrow transplantation. TBI can be delivered in many different ways and analysed for many different endpoints. The published clinical and large animal experiences are reviewed to economise the search for more optimal irradiation schedules. Currently, the immunosuppressive effects and potentially lethal side effects of TBI appear to be the dominant determinants in the therapeutic ratio of TBI. Radiation survival curve parameters are estimated for bone marrow, intestines, lung and immune system in an effort to predict fractionation effects of TBI. Predictions are in reasonable agreement with retrospective clinical observations in patients and animals. High dose rate TBI, fractionated in doses greater than 2 Gy and given over 4 days or less are recommended. Further optimization attempts depend on patient's diagnosis, available bone marrow donor, lymphocyte depletion of bone marrow and prior sensitisation of recipient. Deliberate TBI dose inhomogeneities might improve the therapeutic ratio of TBI, but remain to be explored in greater detail. The proposed model for predicting TBI effects can be adapted and remain useful for future use, when more quantitative information on additional important transplant variables becomes available.

Animals↗
PubMed1987

Evaluation of multiple component relaxation training with developmentally disabled persons.

Prior studies evaluating the response of developmentally disabled persons to relaxation training procedures are largely limited to case study reports. Most often relaxation training procedures are vaguely described in these studies, and limited outcome measures are employed. In the present comparative group outcome study a specific progressive muscle relaxation training procedure was combined with auditory electromyographic (EMG) biofeedback, modeling, and reinforcement procedures in an attempt to teach relaxation skills to mentally retarded persons (N = 32) who functioned in the profound to mild range. The procedure was effective in reducing experimental group subjects' EMG levels, F (1,28) = 6.39, p less than .05, and activity level as measured with an interval recording behavior rating procedure, F (1,28) = 58.05, p less than .05. No effect was found on peripheral skin temperature. Additionally, no significant difference between the response of low functioning and high functioning subjects was seen indicating that intellectual level and adaptive behavior level failed to predict success in treatment. Scoring on a simple behavioral assessment designed to measure receptive language skills and modeling abilities thought to relate to relaxation training success also failed to correlate with outcome measures. The need to develop other predictors of relaxation training success with a mentally retarded population is discussed.

Adult↗
PubMed2006

Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF).

BACKGROUND: Although warfarin and other anticoagulants can prevent ischemic events, they can cause hemorrhage. Quantifying the rate of hemorrhage is crucial for determining the risks and net benefits of prescribing antithrombotic therapy. Our objective was to find a bleeding classification scheme that could quantify the risk of hemorrhage in elderly patients with atrial fibrillation. METHODS: We combined bleeding risk factors from existing classification schemes into a new scheme, HEMORR2HAGES, and validated all bleeding classification schemes. We scored HEMORR2HAGES by adding 2 points for a prior bleed and 1 point for each of the other risk factors: hepatic or renal disease, ethanol abuse, malignancy, older (age > 75 years), reduced platelet count or function, hypertension (uncontrolled), anemia, genetic factors, excessive fall risk, and stroke. We used data from quality improvement organizations representing 7 states to assemble a registry of 3791 Medicare beneficiaries with atrial fibrillation. RESULTS: There were 162 hospital admissions with an International Classification of Diseases, Ninth Revision, Clinical Modification code for hemorrhage. With each additional point, the rate of bleeding per 100 patient-years of warfarin increased: 1.9 for 0, 2.5 for 1, 5.3 for 2, 8.4 for 3, 10.4 for 4, and 12.3 for > or =5 points. In patients prescribed warfarin, HEMORR2HAGES had greater predictive accuracy (c statistic 0.67) than other bleed prediction schemes (P < .001). CONCLUSIONS: Adaptations of existing classification schemes, especially a new bleeding risk scheme, HEMORR2HAGES, can quantify the risk of hemorrhage and aid in the management of antithrombotic therapy.

Aged↗
PubMed2006

Left ventricular remodeling impacts the function of the Quattro stentless mitral valve bioprosthesis (a 4-year experience).

OBJECTIVE: The St Jude Quattro stentless mitral valve prosthesis (QMV) is sutured to the mitral annulus and the papillary muscle heads, thereby preserving the subvalvular apparatus. After mitral valve replacement, remodeling of the left ventricle is often observed, causing a dilated ventricle to shrink in diameter. It was our objective to assess these changes in left ventricular (LV) geometry and evaluate its effects on the function of the QMV. METHODS: From September 1997 to October 2000, 24 patients received QMV at our institution. The patients were followed up at yearly intervals (mean 4.1 +/- 2.2 years). All pre- and postoperative echocardiograms were evaluated, with attention focused on the subvalvular apparatus, leaflet morphology, and occurrence of late mitral regurgitation. In addition, all clinical outcomes and valve-related complications were recorded. RESULTS: Forty-one percent of patients (10/24) developed late mitral regurgitation (mild, n = 5; moderate, n = 5). The site of regurgitation was located at the 2 commissures in all cases. In 8 patients, changes in LV diameter had occurred. The point of leaflet coaptation had shifted away from the annulus in 4 patients. The overall mortality was 12.3%, and the postoperative stroke rate was 12.3%. CONCLUSIONS: Midterm changes in LV geometry seem to affect the competence of the QMV. Predicting these changes and subsequently adapting the sizing procedure remain a challenging task. The high rate of late valve incompetence and poor clinical outcomes has prompted us to discontinue recruitment of patients for this trial.

Bioprosthesis↗
PubMed2005

Space mediates coexistence of females and hermaphrodites.

In gynodioecious populations of flowering plants females and hermaphrodites coexist. Gynodioecy is widespread and occurs in both asexual and sexual species but does not admit a satisfactory explanation from classical sex ratio theory. In sexual populations male fertility restoring genes have evolved to counter non-nuclear male sterility mutations. In pseudogamous asexual populations pollen retention and increased self-fertilization can make male sterility costly. Both of these mechanisms can promote coexistence. However, it remains unclear how either of these mechanisms could evolve if coexistence was not initially possible. In the absence of these adaptations non-spatial models predict that females either fail to invade hermaphrodite populations or else displace them until pollen shortage drives the population to extinction. We develop a pair approximation to a probabilistic cellular automata model in which females and hermaphrodites interact on a regular lattice. The model features independent pollination and colonization processes which take place on different timescales. The timescale separation is exploited to obtain, with perturbation methods, a more manageable aggregated pair approximation. We present both the mean field model which recreates the classical non-spatial predictions and the pair approximation, which strikingly predicts different invasion criteria and coexistence under a wide range of parameters. The pair approximation is shown to correspond well qualitatively with simulation behaviour.

Models, Biological↗
PubMed2003

Methods for generating second dimension retention index data in comprehensive two-dimensional gas chromatography.

Two methods of generating transportable second dimension retention data are outlined for comprehensive two-dimensional gas chromatography (GC x GC). They are both refinements of a previously outlined procedure, which adapted 'isovolatile' curves to retention prediction maps developed in our laboratory, extended to a more polar homologous series, the linear primary alcohols. The earlier work investigated maps based on alkanes and methyl ketones and methyl esters; here the method of data collection to generate the retention map has also changed, extending the retention base range. The resulting retention map permits a retention basis to be used for GC x GC data, however, a more polar retention set than alkanes is required. The calculation of 'retention indices' is aided by the generation of 'fractional reference compound' curves, by either direct manipulation of data local to the solute, or generation of a discrete curve coincident with the retention co-ordinates of the target compound.

Alcohols↗
PubMed2026

Artificial intelligence agents and agentic artificial intelligence applied to precision medicine.

Precision medicine seeks to individualise care by integrating multimodal biomedical data, yet most deployed clinical artificial intelligence (AI) remains assistive, providing predictions without managing workflows or adapting autonomously. Agentic AI, built on large language models (LLMs), has emerged as a paradigm characterised by autonomy, goal-directed reasoning, memory, planning and tool use. This review synthesises evidence on agentic AI and LLMs applied to precision medicine, encompassing drug discovery, genomics, oncology, rare disease diagnostics and clinical pharmacology. This review also examines architectural components, recent validation milestones and emerging challenges, including hallucination, sociodemographic bias and evolving regulatory frameworks across the FDA, the EU AI Act and the WHO.

agentic AI↗
PubMedDate not supplied

Birds as long-lived animal models for the study of aging.

Despite their high lifetime energy expenditures, most birds can be characterized as long-lived homeotherms with moderately slow aging. A growing body of research confirms the prediction that birds have special adaptations for preventing aging-related oxidative and glycoxidative damage. Nonetheless, biogerontologists have been slow to develop avian laboratory models. A number of domestic poultry and cage bird species represent either established or very promising animal models for studies of basic aging processes and their prevention, including degenerative neurobiological, behavioral and reproductive processes. Several kinds of birds have also been used in studies of cellular resistance to oxidative stressors in vitro. Results of preliminary studies on chickens and quail suggest that caloric restriction may extend the reproductive life span of hens, but its long-term effects on life span remain unstudied. Birds' innate anti-aging mechanisms may actually make them more suitable in some respects as models of longevity than short-lived laboratory rodents, and bird studies may ultimately reveal routes for therapeutic intervention in diseases of human aging and infertility.

Aging↗
PubMed2005

Two different T cell receptors use different thermodynamic strategies to recognize the same peptide/MHC ligand.

A6 and B7 are two alphabeta T cell receptors (TCRs) that recognize the Tax peptide presented by the class I major histocompatibility molecule HLA-A2 (Tax/HLA-A2). Despite the fact that the two TCRs have different CDR loops and use different amino acid residues to contact their ligand, both receptors bind ligand with similar diagonal orientations. Here we show that they also bind with very similar binding affinities and kinetics (the DeltaDeltaG degrees for binding is approximately 0.3kcal/mol at 25 degrees C). The two receptors respond similarly to alterations in the MHC molecule, yet differ dramatically in their responses to ionic strength and temperature. The different responses to temperature indicate markedly different binding thermodynamics, which are not predictable from the surface area buried in the interfaces. A6 and B7 thus represent two TCRs that are both compatible with Tax/HLA-A2, although compatibility has been achieved through the use of different thermodynamic strategies. Finally, neither A6 nor B7 are predicted to undergo large conformational adaptations upon binding, distinguishing them from a number of other TCRs whose structure, thermodynamics, and kinetics have been characterized.

Gene Products, tax↗
PubMed2006

X-ray volume imaging in image-guided radiotherapy.

Treatment simulation has significantly improved the accuracy and precision of radiation therapy delivery. A new generation of therapy systems promises to take the simulation and imaging process to a new level of accuracy; however, this will require changes in the workflow process. We describe the first generation of these devices, review the various imaging options and how they might be used in the clinic to improve treatment outcomes, and suggest several workflow approaches. Workflows discussed include on-line interventional, off-line adaptive, and off-line predictive approaches, with both geometric and dosimetric considerations. These changes will place new knowledge requirements on the medical dosimetrist and will necessitate involvement in the development of new departmental processes.

Computer Simulation↗
PubMed2004

Visual perception of extent and the geometry of visual space.

The question of how perceived extents are related to the corresponding physical extents is a very old question that has not been satisfactorily answered. The common model is that perceived extent is proportional to the product of image size and perceived distance. We describe an experiment that shows that perceived extents are substantially larger than this model predicts. We propose a model that accounts for our results and a large set of other results. The principal assumption of the model is that, in the computation of perceived extent, the visual angle signal undergoes a magnifying transform. Extent is often perceived more accurately than the common model predicts, so the computation is adaptive. The model implies that, although the perception of location and the perception of extent are related, they not related by Euclidean geometry, nor by any metric geometry. Nevertheless, it is possible to describe the perception of location and extent using a simple model.

Humans↗
PubMed1997

Reproduction and host-location among the parasitic platyhelminthes.

This review examines briefly the reproductive capacity of representatives of the 4 principal groups of platyhelminths, the "Turbellaria", Monogenea, Digenea and Cestoda. Of the flatworms, 3 main groups are wholly parasitic (monogeneans; digeneans; cestodes). Among the largely free-living "Turbellaria", there are several parasitic representatives in some families (Umagillidae; Graffillidae; Pterastericolidae; Fecampiidae; Acholadidae). Endoparasitic platyhelminths with complex life-cycles produce large numbers of eggs and numbers of offspring are increased further in the digeneans and a few cestodes by asexual multiplication. Like their free-living relatives, most ectosymbiotic and ento- and ectoparasitic flatworms ("turbellarians" and monogeneans) produce, on the whole, far fewer eggs and progeny but are still successful organisms in terms of their numbers of species and diversity. Estimates of parasite fecundity from in vivo experiments are needed for representatives from all flatworm groups. For those parasites that are host-specific, the particular species of host provides a predictable target to be located. Adaptations displayed by the eggs and infective stages of some flatworms increase their chances of finding and recognising their specific host and these are reviewed: attachment of eggs to their "host"; egg hatching in response to host chemicals; rhythmical emergence; special behaviours of infective stages; host recognition.

Animals↗
PubMed2003

Calcium requirements for exocytosis do not delimit the releasable neuropeptide pool.

Recently, it was proposed that secretory vesicles have widely varying Ca(2+) thresholds for exocytosis. This model can explain adaptation of secretory responses and predicts that incomplete release is a consequence of insufficient Ca(2+). However, membrane capacitance-based measurements have not supported varying Ca(2+) thresholds. Here, Green Fluorescent Protein (GFP) imaging is used to test whether a Ca(2+) limitation determines the size of the releasable neuropeptide pool in differentiated PC12 cells. We show that depolarization-evoked release correlates with failure to sustain fully elevated [Ca(2+)](i). However, this is coincidental because release remains incomplete when [Ca(2+)](i) is maintained at a relatively high level by application of an ionophore or by dialysis with a buffered Ca(2+) solution. Furthermore, in contradiction with the existence of high threshold vesicles, stimulating maximal release with moderate [Ca(2+)](i) prevents secretory responses to large increases in [Ca(2+)](i) induced by photolysis of the caged dimethoxynitrophenyl-EGTA-4 (DMNPE-4). Thus, optical measurements show that limited capacity for neuropeptide release in response to depolarization is not caused by an insufficient duration of [Ca(2+)](i) elevation or by variation among vesicles in Ca(2+) sensitivity for exocytosis.

Action Potentials↗
PubMed2000

Flipping the oncogene switch: illumination of tumor maintenance and regression.

The genetic construction of cancer-prone mice, combined with the capacity to control transgene expression in vivo, provides new opportunities to study the role of oncogenes in the maintenance of fully formed tumors. These inducible cancer models provide a means to dissect how specific oncogenic signals influence host-tumor symbiosis, to validate the importance of a given oncogenic lesion in established advanced tumors, and to predict the biological response and adaptations to therapies targeted to that cancer-causing genetic alteration.

Animals↗
PubMed1999

Concerns about breast cancer and relations to psychosocial well-being in a multiethnic sample of early-stage patients.

Much work on psychosocial sequelae of breast cancer has been guided by the assumption that body image and partner reaction issues are focal. In a tri-ethnic sample of 223 women treated for early-stage breast cancer within the prior year, the authors assessed a wider range of concerns and relations to well-being. Strongest concerns were recurrence, pain, death, harm from adjuvant treatment, and bills. Body-image concerns were moderate; concern about rejection was minimal. Younger women had stronger sexual and partner-related concerns than older women. Hispanic women had many stronger concerns and more disruption than other women. Life and pain concerns and sexuality concerns contributed uniquely to predicting emotional and psychosexual disruption; life and pain concerns and rejection concerns contributed to predicting social disruption. In sum, adaptation to breast cancer is a process bearing on several aspects of the patient's life space.

Adaptation, Psychological↗
PubMed2002

Approaches to prokaryotic biodiversity: a population genetics perspective.

The study of prokaryotic diversity has blossomed during the last 10-15 years as a result of the introduction of molecular identification, mostly based on direct 16S rRNA gene polymerase chain reaction (PCR) amplification and sequencing from natural samples. A large amount of information exists about the diversity of this specific gene. However, data from the field of bacterial population genetics and genomics make questionable the value of information regarding just one gene. Even if we accept 16S rRNA genes as useful for species identification, intraspecific variation in bacteria is so high that species catalogues are often of little value. The gene pools represented by an operational species are yet impossible to predict. On the other hand, adaptive features in prokaryotes are often coded in gene clusters (genomic islands) that can be cloned directly from the environment, sequenced and even expressed in a surrogate host. Thus, the study of the environmental genome or metagenome appears as an alternative that could eventually lead to a more realistic understanding of prokaryotic biodiversity, provide biotechnology with new tools and maybe even contribute to develop a model of prokaryotic evolution.

Biological Evolution↗
PubMed2003

Specificity determinants and diversification of the Brassica self-incompatibility pollen ligand.

Self-incompatibility in crucifers is effected by allele-specific interactions between the highly polymorphic stigmatic S locus receptor kinase (SRK) and its pollen ligand, the S locus cysteine-rich protein (SCR). Here we show that specificity in SCR function is determined by four contiguous amino acids in one variant, indicating that the minimum sequence requirement for gaining a new specificity can be low. We also provide evidence for an extraordinarily high degree of evolutionary flexibility in SCR, whereby SCR can tolerate extensive amino acid changes within the limits of maintaining the same predicted overall structure. This remarkable adaptability suggests a hypothesis for generation of new self-incompatibility specificities by gradual modification of SRK-SCR affinities and, more generally, for functional specialization within families of homologous ligands and receptors.

Amino Acid Sequence↗