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Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice.

Dopaminergic systems are thought to mediate the rewarding and reinforcing effects of palatable food. However, the relative contribution of different dopamine receptor subtypes is not clear. We used dopamine D1 receptor deficient mice (D1 -/-) and their wild-type and heterozygous littermates to study the role of the D1 receptor in palatable food reinforced behaviour using operant responding and free access paradigms. Non-deprived mice were trained to press a lever for sucrose pellets under three schedules of reinforcement including fixed ratios (FR-1 and FR-4) and a progressive ratio (PR). Responding on one lever was reinforced by the delivery of a sucrose pellet or solution while responding on a second lever had no programmed consequences. Initially, D1 mutant mice took longer to learn to discriminate between the two levers and had significantly lower operant responding for sucrose pellets and solution than wild-type and heterozygous mice under all schedules of reinforcement. Food deprivation enhanced responding on the active lever in all mice although it remained significantly lower in D1 -/- mice than in control mice. Following extinction of sucrose reinforcement and reversal of the levers, D1 -/- mice showed deficits in extinguishing and reversing previously learned responses. Home cage intake and preference of sucrose pellets and solutions when given under free-choice access paradigms were similar among the groups. These results suggest that the dopamine D1 receptor plays a role in the motivation to work for reward (palatable food) but not in reward perception and is critical in learning new but relevant information and discontinuing previously learned responses.

Analysis of Variance↗

The Audit Commission review of diabetes services in England and Wales, 1998-2001.

UNLABELLED: AIMS OF THE AUDIT COMMISSION: The Audit Commission has a statutory duty to promote the best use of public money. It does this through value for money studies, such as that reported in Testing Times[1]. This work has been followed with a review of innovative practice in commissioning. These initiatives aim to support the implementation of the diabetes national service framework. The Audit Commission also appoints external auditors to NHS organizations who assess probity and value for money in the NHS; the latter by applying national studies locally and by carrying out local studies. METHODS: Research for Testing Times consisted of structured visits to nine acute trusts, a telephone survey of 26 health authorities and a postal survey of 1400 people with diabetes and 250 general practitioners. Local audits used a subset of the original research tools. Case studies were identified through a cascade approach to contacts established during Testing Times and through self-nomination. RESULTS: Rising numbers of people with diabetes are placing increasing pressure on hospital services. Some health authorities and primary care organizations have reviewed patterns of service provision in the light of the increasing demands. These reviews show wide variations in patterns of routine care. In addition, there is a widespread lack of data on the delivery of structured care to people with diabetes. People with diabetes report delays in gaining access to services, and insufficient time with staff. There are insufficient arrangements in place for providing information and learning opportunities to support self-management. CONCLUSION: As the number of people with diabetes continues to rise, the potential for providing more care in a primary care setting needs to be explored. This will enable specialist services to focus more effectively on those with the most complex needs.

Diabetes Mellitus↗

Core training in surgery: what does it need to include?

Core training for surgeons in any surgical specialty should include education in the relevant basic science knowledge, training in fundamental diagnostic skills, the development of surgical technical skills and considerable experience in patient care. However, for a number of reasons it is no longer acceptable to guide such training based only on such broad goals, not the least of which is the advent of resident duty-hour limitations that make it unrealistic to expect residents to simply acquire, by random observation and participation, all of the important elements of their future practices. Rather, it is necessary to provide a curriculum of learning opportunities specifically structured to allow them to gain the requisite knowledge and skills. Thus, the curriculum for the core surgical training of future vascular surgeons should be based on a very specific learning objectives, stating what information is to be learned or what action is to be done, under what conditions they are to be performed, and what criteria will be used to ascertain the acquisition of the necessary knowledge or skill. Next, the best methods of instruction, including reading materials, lectures, and exposure to specific surgical procedures must be defined and the appropriate instructional materials identified, selecting the best of existing materials or, if necessary, creating them. Finally, the residents' acquisition of knowledge and skills must be assessed. Previously this occurred through a loose combination of performance evaluations from clinical rotations, faculty group discussions, and annual in-training exams culminated in the American Board of Surgery certification process. Now evaluation must relate to specific educational objectives. This is all a daunting task currently being undertaken by vascular surgery program directors, albeit with input from the Residency Review Committee and the Vascular Surgery Board of the American Board of Surgery. Eventually, overall surgical curriculum will evolve to satisfy these educational ground rules, but currently it is very much a work in progress in most programs.

Certification↗

The shadowing experience: valuing the link between faculty practice and student learning.

Nurse faculty members, engaged in active, clinical practice roles, can enhance student learning through a shadowing experience. A shadowing, or observational, experience was designed by the writer to enhance undergraduate student learning, contribute to student socialization to the profession, and assist students to develop career goals. The shadowing experience linked an undergraduate student with the faculty member in a learning partnership in an advanced practice clinical setting. Fifteen undergraduate nursing students participated in a pilot shadowing experience with a faculty member in her private practice. Both the students and faculty reported that the experience was mutually rewarding. Students reported they were able to learn new information, apply theory from the classroom, and develop interest in graduate school. The shadowing experience provided the faculty member with an opportunity to show the value of her clinical practice within a traditional academic environment. The value of the shadowing experience for the faculty member can be enhanced by formal mechanisms that support faculty clinical practice work.

Clinical Competence↗

Storage of a sensory pattern by anti-Hebbian synaptic plasticity in an electric fish.

Synaptic plasticity occurs in several regions of the vertebrate brain and is believed to mediate the storage of behaviorally significant information during learning. Synaptic plasticity is well demonstrated in most cases, but the behavioral meaning of the relevant neural signals and the behavioral role of the plasticity are uncertain. In this paper we describe a case of synaptic plasticity which involves identifiable sensory and motor signals and which appears to mediate the storage of an image of past sensory input. Corollary discharge signals associated with the motor command that drives the electric organ are prominent in the electrosensory lobe of mormyrid electric fish. Some of these corollary discharge signals elicit a negative image or representation of the electrosensory input pattern that has followed recent motor commands. When the temporal and spatial pattern of sensory input changes, the corollary discharge effect also changes in a corresponding manner. The cellular mechanisms by which the corollary discharge-evoked representation is stored were investigated by intracellular recording from cells of the electrosensory lobe and pairing intracellular current pulses with the corollary discharge signal. The results indicate that the representation of recent sensory input is stored by means of anti-Hebbian plasticity at the synapses between corollary discharge-conveying fibers and cells of the electrosensory lobe. The results also suggest that dendritic spikes and plasticity at inhibitory synapses are involved in the phenomenon.

Animals↗

Video streaming into the mainstream.

Changes in Internet technology are making possible the delivery of a richer mixture of media through data streaming. High-quality, dynamic content, such as video and audio, can be incorporated into Websites simply, flexibly and interactively. Technologies such as G3 mobile communication, ADSL, cable and satellites enable new ways of delivering medical services, information and learning. Systems such as Quicktime, Windows Media and Real Video provide reliable data streams as video-on-demand and users can tailor the experience to their own interests. The Learning Development Centre at the University of Portsmouth have used streaming technologies together with e-learning tools such as dynamic HTML, Flash, 3D objects and online assessment successfully to deliver on-line course content in economics and earth science. The Lifesign project--to develop, catalogue and stream health sciences media for teaching--is described and future medical applications are discussed.

Computer-Assisted Instruction↗

Neuropsychological assessment of a potential "euthanasia" case: a 5 year follow up.

McMillan reported a neuropsychological assessment procedure which was used to determine whether or not there was evidence for sentience in a young woman who had been rendered tetraplegic and anarthric as a result of a road traffic accident. An application to court had been made to withdraw feeding and this was supported by medical evidence which gave the view that the individual was functioning little beyond vegetative state, had a poor quality of life and had little prospect of further recovery. Evidence for an ability to communicate reliably was found including for a wish to continue living, and as a consequence the application to court was withdrawn. This paper describes further recovery 2-4 years after the original assessment (i.e. 4-6 years post-injury). At follow-up, she remained dependent for all care, but was now feeding orally and was talking. She could learn new information, some of which she retained for at least 12 months and had greater insight into her condition. She now reported low mood and some pain. As before, she consistently reported a wish to live. The implications of the follow-up are discussed in the context of assumptions made about quality of life and decision making about euthanasia in brain injured people who are severely disabled, but are not in a vegetative state.

Adult↗

A cancer-prevention intervention for disadvantaged women: design and implementation.

A cancer-prevention mini-course was designed to increase knowledge about breast and cervical cancers as well as to improve attitudes and behaviors regarding preventive health care among minority and medically underserved women. The culturally-sensitive two-hour psycho-educational intervention was developed as an interactive curriculum in English- and Spanish-language versions for home health care attendants. After development and piloting, the course was offered as part of the weekly 40-hour training program for home attendants in Bronx, New York. After six months it was offered as in-service training for home attendants employed by a licensed home attendant-training agency. The home attendants who participated in the mini-course were primarily Hispanic (62%) and black (31%). Results of evaluation indicate that the mini-course has been remarkably successful in achieving its goals. Primary measures of its success include: 1) integration of the mini-course into the settings in which it is being offered; 2) student participation, absorption of material, and enthusiasm for the course. The mini-course has been successfully incorporated into the training agencies, with strong staff commitment to the program. Participants evince high levels of enthusiasm for the class, reporting that they have learned new information and have especially enjoyed the interactive nature of the class. Though the development of this cancer-prevention mini-course (and its materials) as well as integrating it into appropriate settings required a substantial investment of time and resources, now that it is developed, the intervention proves to be efficient and effective, and is meeting a large need.

Adult↗

Using fragment chemistry data mining and probabilistic neural networks in screening chemicals for acute toxicity to the fathead minnow.

The paper is illustrating how the general data mining methodology may be adapted to provide solutions to the problem of high throughput virtual screening of organic chemicals for possible acute toxicity to the fathead minnow fish. The present approach involves mining fragment information from chemical structures and is using probabilistic neural networks to model the relationship between structure and toxicity. Probabilistic neural networks implement a special class of multivariate non-linear Bayesian statistical models. The mathematical principles supporting their use for value prediction purposes are clarified and their peculiarities discussed. As part of the research phase of the data mining process, a dataset consisting of 800 structures and associated fathead minnow (Pimephales promelas) 96-h LC50 acute toxicity endpoint information is used for both the purpose of identifying an advantageous combination of fragment descriptors and for training the neural networks. As a result, two powerful models are generated. Model 1 implements the basic PNN with Gaussian kernel (statistical corrections included) while Model 2 implements the PNN with Gaussian kernel and separated variables. External validation is performed using a separate dataset consisting of 86 structures and associated toxicity information. Both learning and generalization capabilities of the two models are investigated and their limitations discussed.

Animals↗

Changing practice in residential aged care using participatory methods.

BACKGROUND: Residential aged care staff play a significant role in the day-to-day lives of residents yet are faced with many barriers to providing care that promotes resident wellbeing. APPROACH: Action research is a useful approach for clarifying issues, identifying education and training needs, and identifying, and in some cases overcoming, organizational barriers to change. The Well for Life project aimed to enhance the social and physical health and well being of residents of aged care settings by empowering the staff of facilities to make change. The project had a particular focus on nutrition and physical activity. This paper reports on the action research group process undertaken during Phase I of the Well for Life project. Five residential aged care settings participated in the action research process facilitated by project staff independent of the facilities. The action plan and outcomes from one of these settings is used to illustrate the process and outcomes. FINDINGS: The main findings of the project indicate that using a process that encourages staff involvement in identification of issues and actions can facilitate change in the practice of resident care. The action research groups identified specific gaps in knowledge and skill leading to targeted education that addressed areas of need. The importance of presenting information and learning opportunities for staff in a variety of formats was also recognized, as was the importance of organizational context, management support and empowerment of staff to make change.

Aged↗

HallmarkGraph: a cancer hallmark informed graph neural network for classifying hierarchical tumor subtypes.

MOTIVATION: Accurate tumor subtype diagnosis is crucial for precision oncology, yet current methodologies face significant challenges. These include balancing model accuracy with interpretability and the high costs of generating multi-omics data in clinical settings. Moreover, there is a lack of validated models capable of classifying hierarchical tumor subtypes across a comprehensive pan-cancer cohort. RESULTS: We present a graph neural network, HallmarkGraph, the first biologically informed model developed to classify hierarchical tumor subtypes in human cancer. Inspired by cancer hallmarks, the model's architecture integrates transcriptome profiles and gene regulatory interactions to perform multi-label classification. We evaluate the model on a comprehensive pan-cancer cohort comprising 11 476 samples from 26 primary cancers with 405 subtypes up to eight levels. The model demonstrates exceptional performance, achieving 5-fold cross-validation accuracy between 85% and 99% for tumor subtypes labeled with increasing details of genomic information. It also shows good generalizability on a validation dataset of 887 samples, assessed using three metrics that consider tumor subtypes at individual, combined, and sample levels. Benchmarking and ablation experiments show that hallmark-based embeddings slightly influence model performance, while the integrated multilayer perceptron plays a significant role in determining classifier accuracy. Additionally, we use the SHAP method to link cancer hallmarks with genes, identifying key features that influence model decisions. Our findings present a biologically informed machine learning framework capable of tracking tumor transcriptomic trajectories and distinguishing inter- and intra-tumor heterogeneity in pan-cancer. This approach holds promise for enhancing cancer diagnostics. AVAILABILITY AND IMPLEMENTATION: HallmarkGraph is accessible at https://github.com/laixn/HallmarkGraph.

Humans↗

ToxiVerse: chemical bioprofiling, toxicity data sharing and customizable predictive modeling.

MOTIVATION: Chemical toxicity assessment is critical for drug development and environmental safety. Computational models have emerged as a promising alternative to animal testing and now play a significant role in efficiently evaluating new chemicals. To address the urgent need for user-friendly machine learning tools in computational toxicology, we developed ToxiVerse, a public web-based platform. RESULTS: ToxiVerse provides automatic chemical bioprofiling, curated toxicity datasets, and a predictive modeling interface designed for researchers who lack programming expertise. The platform comprises three integrated modules: (i) Bioprofiler, which provides chemical descriptors by combining chemical-bioactivity data from PubChem assays with a machine learning-based data gap-filling procedure; (ii) Database, which hosts ∼50 000 curated chemicals covering diverse toxicity endpoints; and (iii) Cheminformatics, which enables dataset upload, chemical curation, and automatic generation of quantitative structure-activity relationship models for toxicity prediction. AVAILABILITY: The tool is accessible at www.toxiverse.com, and source code is available at https://github.com/zhu-research-group/toxiverse.

Quantitative Structure-Activity Relationship↗

The relationship between cognitive and physical performance: MacArthur Studies of Successful Aging.

BACKGROUND: The relationship between change in cognitive and physical performance has yet to be fully understood. Because aging decreases the ability to learn new information while preserving more established knowledge, this article examines whether the association between change in cognitive and physical performance depends on the nature of the physical task. METHODS: Data from the MacArthur Research Network on Successful Aging Community Study--a longitudinal three-site, cohort study of high-functioning, disability-free Americans aged 70 to 79 in 1988 (reinterviewed in 1991 and 1995)--are used for this investigation. We examine the association between change in cognitive performance and two categories of physical performance: novel/attentional demanding physical tasks (e.g., standing on a single leg) or routine physical tasks (e.g., walking at a normal pace). Change in physical performance (over 7 years) is regressed on change in cognitive performance (over the same period) controlling for baseline cognitive ability, demographic factors, health status, and behavioral characteristics. RESULTS: The findings suggest that declines in cognitive performance are associated with declines in both novel/attentional demanding and routine physical tasks. In addition to decline in cognition, gender, prevalent health conditions (e.g., cancer, high blood pressure, and the fracture of a hip), and smoking behavior are associated with decline in performance on some physical tasks. CONCLUSIONS: The findings suggest that the successful execution of physical tasks demands cognitive processes regardless of the nature of the task. Researchers using performance-based measures of physical functioning should pay particular attention to the cognitive capacities of their subjects and how these might influence their assessment.

Aged↗

Training skills in the psychiatrically disabled: learning coping and competence.

Social skills training methods represent a major strategy for psychiatric rehabilitation. Building skills in patients with schizophrenic and other major mental disorders is based on the assumption that coping and competence can override stress and vulnerability in reducing relapses and improving psychosocial functioning. For maximum efficiency, skills training needs to incorporate procedures and principles of human learning and information processing. Several models for skills training have been designed and evaluated, each of which has proved to be effective in raising the social competence of chronic mental patients. The "basic" model involves role playing by the patient and modeling, prompting, feedback, and reinforcement by the therapist. A "problem-solving" model of training provides general strategies for dealing with a wide variety of social situations. This model uses role playing to enhance behavioral performance but also highlights the patient's abilities to perceive and process incoming social messages and meanings. It is essential that social skills training be imbedded in a comprehensive program of rehabilitation that features continuity of care, supportive community services, therapeutic relationships, and judicious prescription of psychotropic drugs.

Activities of Daily Living↗

Cross-Cultural Cognitive Examination performance in patients with Parkinson's disease and Alzheimer's disease.

Performance profiles of patients with different dementia syndromes (Alzheimer's disease and Parkinson's disease) were compared with each other and with those of neurologically impaired and healthy individuals without dementia on a new instrument for screening dementia, the Cross-Cultural Cognitive Examination (CCCE). The CCCE measures discriminated reliably between nondemented and demented patients, regardless of etiology. Comparisons between dementia groups found that dementia patients with Parkinson's disease (PD) showed more severe psychomotor slowing and depression, compared with patients with Alzheimer's disease, who showed more impaired recall of recently learned verbal information and verbal abstract reasoning. The CCCE also distinguished between the motor and affective symptoms that are common to all PD patients and the dementia symptoms that occur in some PD patients. These results provide further support for the clinical utility of the CCCE for discriminating dementia from normal cognitive functioning and for initial identification of different dementia syndromes.

Age Factors↗

Innovative teaching of developmental themes of the elderly and the young.

The authors demonstrate how faculty members creatively designed an undergraduate course in which students learned developmental similarities and differences across the life span. Student-client interaction, involvement in practice, and inquiry strategies are used to enhance teaching and learning. Practice informed theory for students resulting ina meaningful synthesis of content.

Aged↗

Symposium on upper gastrointestinal motility disorders. Gastric motor disorders: an overview.

Disturbances of gastric emptying are being increasingly recognized as causes of clinical problems such as chronic nausea, vomiting, and abdominal pain. Although much remains to be learned, enough information is available to enable the practicing physician to develop an approach to diagnosis and management of these often difficult problems. We review here relevant physiologic concepts of gastric motor activity during fasting and feeding, as well as its controlling mechanisms. These concepts are then applied to develop a rational classification of gastric motor disorders which incorporates clinical as well as pathophysiologic information. Further, we review pertinent diagnostic studies (including gastric emptying tests, manometry, and electrophysiologic measurements) and therapeutic approaches.

Electrophysiology↗

Intergovernmental collaboration in the emergency response to HIV transmission in Chautauqua County.

New York State Department of Health (NYSDOH) staff became involved, in partnership with local county and national public health personnel, in the design and implementation of the emergency response to transmission of HIV in rural Chautauqua County, New York. Formulating plans for immediate public access to mass testing services on an uncertain time schedule and dealing with a myriad of other aspects in the context of intense media attention was an extraordinary and unprecedented experience. This case illustrated the value of intergovernmental collaboration. Lessons learned are informing development of NYSDOH guidelines.

AIDS Serodiagnosis↗