Biomedical subjects

Robert H Lee

Publications and source records attributed to Robert H Lee.

13 recordsLinked to original sources

PubMed2026

A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.

Hemostasis and thrombosis are strongly dependent on the unique ability of platelets to rapidly activate integrin receptors and to firmly adhere to sites of injury under shear stress conditions. Central to integrin activation is the small GTPase RAP1, which itself is activated by guanine nucleotide exchange factors (GEFs). CalDAG-GEFI (RASGRP2) is the highest expressed and functionally dominant platelet RAP-GEF. However, a genome-wide association study also suggested a significant role for RAPGEF2 (PDZ-GEFI), a low-expressed RAP-GEF, in human platelet aggregation. Here, we used mice deficient in RAPGEF2 (megakaryocyte-specific, Rapgef2mKO), CalDAG-GEFI (Caldaggef1-/-), or both RAPGEF2 and CalDAG-GEFI (DKO) to characterize the contribution of RAPGEF2 signaling to platelet function, hemostasis, and thrombosis. RAPGEF2 protein was detected in murine and human platelets. Compared with control or Caldaggef1-/- platelets, both RAP1 activation and integrin αIIbβ3-mediated aggregation were significantly diminished in DKO platelets. When compared with controls, Rapgef2mKO platelets exhibited reduced integrin activation, a more reversible aggregation response, and impaired adhesion under conditions of shear stress ex vivo and in vivo. Mechanistic studies strongly suggest that RAPGEF2 operates downstream of receptors coupled to the heterotrimeric G protein G13 (GNA13), such as αIIbβ3 and the thromboxane receptor. Together, our studies provide genetic evidence that RAPGEF2 in platelets operates downstream of G13 as an important regulator of RAP1 signaling and integrin activation, especially under conditions of elevated shear stress. These findings markedly improve our understanding of G protein signaling and integrin function in platelets, with potential implications for the development of improved platelet-targeted therapies for cardiovascular disease.

Animals↗

PubMed2006

Fast amplification of dynamic synaptic inputs in spinal motoneurons in vivo.

The ability of voltage-dependent inward currents (likely Na(+)) of the adult cat lumbar motoneurons to amplify rapidly changing (i.e., dynamic) synaptic inputs was investigated using in vivo intracellular recording techniques. Fast amplification was assessed by measuring the magnitude of the high-frequency (180 Hz) component of the Ia synaptic input due to tendon vibration as a function of somatic voltage and was compared with the previously observed amplification of steady inputs (steady state response of PICs to slow inputs). Data from 17 experiments show that amplification of the dynamic input indeed occurred and was directly linked to neuromodulatory drive (standard state: decerebrate with intact descending neuromodulatory systems vs. minimal state: pentobarbital with said systems significantly inhibited). Fast amplification factors averaged 2.0 +/- 0.7 (mean +/- SD) in the standard neuromodulatory state. That is, the effective synaptic current was nearly twice as large at its peak as it was at hyperpolarized levels, ranging as high as 2.6. Although fast amplification was often smaller than the amplification of steady inputs, the difference was not statistically significant. However, the voltage at which fast amplification began was approximately 10 mV more depolarized (P < 0.01). It is concluded that both dynamic and steady inputs can be amplified, but there may be differences in mechanism.

Achilles Tendon↗

PubMed2006

Reliability of the nursing home survey process: a simultaneous survey approach.

PURPOSE: We designed this study to examine the reliability of the nursing home survey process in the state of Kansas using regular and simultaneous survey teams. In particular, the study examined how two survey teams exposed to the same information at the same time differed in their interpretations. DESIGN AND METHODS: The protocol for simultaneous surveys consists of having one in-region and one out-of-region team survey a facility together. RESULTS: The regular and simultaneous survey teams generally agreed about the number of deficiencies. The intraclass correlation coefficient was 0.87 for total deficiencies and 0.76 for deficiencies with scores of G or higher. But in a substantial number of instances the teams did not agree about the scope and severity of the deficiency or about what regulation the nursing home had breached. IMPLICATIONS: The survey process is reliable when assessing aggregate results, but it is only moderately reliable when examining individual citations. Stakeholders (i.e., consumers, policy makers, nursing home administrators) should be aware of the limitations of the survey process. It needs to be modified to reduce variability.

Data Collection↗

PubMed2005

Architectures for high-performance FPGA implementations of neural models.

As the complexity of neural models continues to increase (larger populations, varied ionic conductances, more detailed morphologies, etc) traditional software-based models have difficulty scaling to reach the performance levels desired. This paper describes the use of FPGAs, or field programmable gate arrays, to easily implement a wide variety of neural models with the performance of custom analogue circuits or computer clusters, the reconfigurability of software, and at a cost rivalling personal computers. FPGAs reach this level of performance by enabling the design of neural models as parallel processed data paths. These architectures provide for a wide range of single-compartment, multi-compartment and population models to be readily converted to FPGA implementations. Generalized architectures are described for the efficient modelling of a first-order, nonlinear differential equation in throughput maximizing or latency minimizing data-path configurations. The homogeneity of population and multicompartment models is exploited to form deep pipelines for improved performance. Limitations of FPGA architectures and future research areas are explored.

Animals↗

PubMed2005

The context for nursing home resident care: the role of leaders in developing strategies.

Data obtained from three Midwestern nursing homes were used to identify and describe contextual factors that influenced resident care. A qualitative, emergent, case study design guided the study. In addition to 17 residents and 16 family members or friends of the respective residents, participants included 66 staff members and 9 managers involved in the planning and delivery of care to the participating residents. Data were collected via observation, semi-structured interview, and resident record audit. Contextual factors seemed to integrate or fragment care planning and delivery. Important integrators were shared values, the role of the Minimum Data Set coordinator, the role of other leaders, and family influence. Two fragmenting factors, competing demands for the staff members' time and a task orientation to care, appeared to be ubiquitous. External accountability also fragmented care to a discernible degree.

Aged↗

PubMed2005

Continent or incontinent? That is the question.

A qualitative, emergent, case study design guided the description of care provided to nursing home residents with urinary incontinence in three Midwestern nursing facilities. Participants included 17 residents and 16 family members or friends of the respective residents. Staff and managers involved in the planning and delivery of care to the participating residents also were included. The three facilities represented variation in size, location, ownership, and Medicare certification. Data were collected via observation, resident record audit, and semi-structured interview. Definitions of incontinence varied among staff. A collectively held expectation that residents would be toileted every 2 hours was not met. Maintaining skin integrity was the primary motivation for keeping residents clean and dry. Medical directors viewed incontinence as a nursing problem. Staff described situations in which incontinence was improved for specific residents, but there was little evidence of formal programs to maintain continence or improve incontinence.

Aged↗

PubMed2004

Estimating action potential thresholds from neuronal time-series: new metrics and evaluation of methodologies.

The estimation of action potential thresholds is a subjective process, which we quantified by surveying experienced electrophysiologists via a software application that allowed them to select action potential thresholds from several presented neuronal time series. Independent of this survey, we derived two nonparametric techniques for automating the detection of an action potential threshold from the time-series of intracellular recordings. Both methods start with a phase-space representation of the action potential (dV/dt versus V). Method I detects the maximum slope in the phase space, while Method II detects the maximum second derivative in the phase space. These two methods, as well as five additional methods in the literature, were tested on three data sets representing a variety of action potential shapes, the same three datasets that were used in the electrophysiologist survey. The database of user responses was used to provide an external benchmark against which to statistically evaluate all seven methods. Method II, as well as the curvature-based Methods VI and VII, provided the best results tracking both absolute and relative changes in threshold versus the other nonparametric methods (peak of second and third time derivatives). The one parametric method evaluated, detection of threshold crossing of the first temporal derivative, performed comparably to these methods, provided that an appropriate threshold was chosen. We conclude that Methods II, VI, and VII were the best methods evaluated due to their performance across a wide range of action potential shapes and the fact that they are nonparametric. Our user database of responses may be useful to other investigators interested in developing additional methods in that it quantifies what has often been a subjective estimate.

Action Potentials↗

PubMed2004

An FPGA-based approach to high-speed simulation of conductance-based neuron models.

The constant requirement for greater performance in neural model simulation has created the need for high-speed simulation platforms. We present a generalized, scalable field programmable gate array (FPGA)-based architecture for fast computation of neural models and focus on the steps involved in implementing a single-compartment and a two-compartment neuron model. Based on timing tests, it is shown that FPGAs can outperform traditional desktop computers in simulating these fairly simple models and would most likely provide even larger performance gains over computers in simulating more complex models. The potential of this method for improving neural modeling and dynamic clamping is discussed. In particular, it is believed that this approach could greatly speed up simulations of both highly complex single neuron models and networks of neurons. Additionally, our design is particularly well suited to automated parameter searches for tuning model behavior and to real-time simulation.

Animals↗

PubMed2004

Care planning for nursing home residents: incorporating the Minimum Data Set requirements into practice.

This study was designed to describe the care-planning process used in nursing homes and identify links among care planning, care provided, and the Resident Assessment Instrument and Minimum Data Set (MDS). Study participants in three Midwestern nursing homes included residents and family members, MDS coordinators, direct care staff, administrators, directors of nursing, and medical directors. Data were collected via semi-structured interview, observation, and resident record audit. The care-planning process differed among the three facilities despite the common MDS system structure. Care planning and the MDS system were linked to the care provided to residents through documentation in residents' records, translation of the MDS care plan to the documents used for daily care, and ongoing communication through end-of-shift report and other venues.

Aged↗

PubMed2003

Active dendritic integration of inhibitory synaptic inputs in vivo.

Synaptic integration in vivo often involves activation of many afferent inputs whose firing patterns modulate over time. In spinal motoneurons, sustained excitatory inputs undergo enormous enhancement due to persistent inward currents (PICs) that are generated primarily in the dendrites and are dependent on monoaminergic neuromodulatory input from the brain stem to the spinal cord. We measured the interaction between dendritic PICs and inhibition generated by tonic electrical stimulation of nerves to antagonist muscles during voltage clamp in motoneurons in the lumbar spinal cord of the cat. Separate samples of cells were obtained for two different states of monoaminergic input: standard (provided by the decerebrate preparation, which has tonic activity in monoaminergic axons) and minimal (the chloralose anesthetized preparation, which lacks tonic monoaminergic input). In the standard state, steady inhibition that increased the input conductance of the motoneurons by an average of 38% reduced the PIC by 69%. The range of this reduction, from <10% to >100%, was proportional to the magnitude of the applied inhibition. Thus nearly linear integration of synaptic inhibition may occur in these highly active dendrites. In the minimal state, PICs were much smaller, being approximately equal to inhibition-suppressed PICs in the standard state. Inhibition did not further reduce these already small PICs. Overall, these results demonstrate that inhibition from local spinal circuits can oppose the facilitation of dendritic PICs by descending monoaminergic inputs. As a result, local inhibition may also suppress active dendritic integration of excitatory inputs.

Animals↗

PubMed2003

Hyperexcitable dendrites in motoneurons and their neuromodulatory control during motor behavior.

Dendrites contain voltage-sensitive conductances that, in vivo, can be influenced by neuromodulatory inputs. In spinal motoneurons, dendrites have voltage-activated persistent inward currents that are facilitated by neuromodulatory input from monoaminergic axons originating in the brainstem. The highest levels of monoamine input are likely to occur during 'fight or flight' behavioral situations. At these high levels, the persistent currents are so large that the dendrites of motoneurons become hyperexcitable, enhancing ionotropic inputs by fivefold or more and allowing the firing rates required for maximal activation of muscle fibers to be generated by surprisingly small inputs. Moderate dendritic excitability (twofold to threefold enhancement) is likely to be a standard component of many normal motor behaviors, such as locomotion. Thus, during normal motor behavior, synaptic integration might be dominated by active currents intrinsic to the dendritic tree rather than by the synaptic current entering via ionotropic channels.

Animals↗

PubMedDate not supplied

Process-based costing.

Understanding how quality improvement affects costs is important. Unfortunately, low-cost, reliable ways of measuring direct costs are scarce. This article builds on the principles of process improvement to develop a costing strategy that meets both criteria. Process-based costing has 4 steps: developing a flowchart, estimating resource use, valuing resources, and calculating direct costs. To illustrate the technique, this article uses it to cost the care planning process in 3 long-term care facilities. We conclude that process-based costing is easy to implement; generates reliable, valid data; and allows nursing managers to assess the costs of new or modified processes.

Cost Allocation↗

PubMedDate not supplied

The extent of quality improvement activities in nursing homes.

The quality of nursing home care has long been a cause for concern. The federal government has recently launched the Nursing Home Quality Initiative, in which Quality Improvement Organizations assist nursing homes in quality improvement (QI) activities. In addressing how well nursing homes are prepared for QI, this article examines the sort of QI activities that nursing homes are currently undertaking and the preparation of Administrators and Directors of Nursing to lead QI efforts. Drawing on data from surveys of 2 random samples of Kansas nursing homes, the article concludes that questions about QI activities in nursing homes tend to elicit socially acceptable answers unless the questions are carefully structured; that few nursing homes appear to have functioning QI programs; and that high leadership turnover and limited leadership training make it difficult for nursing homes to sustain effective QI programs.

Humans↗