Using a human-centered design approach for collaborative decision-making in pediatric asthma care.

OBJECTIVES: Human-centered design (HCD) is a qualitative methodology that empathizes with end-users and assists in formulating preferable and practical interventions. We explored the utility of HCD in improving pediatric asthma healthcare outcomes among patient and caregiver populations within an urban academic center. STUDY DESIGN: HCD employs a multiphase process that aims to identify the needs of end users and reframe solutions around each stakeholder's preference patterns. METHODS: Ethnographic-style observations were initiated among pediatric asthma healthcare providers, community environmental activists, local government public health officials, households with a young child (<12 years of age) with asthma, and adolescent asthmatics. Common themes from the observations served as the basis for understanding users' experiences and determining actionable areas of improvement within outpatient asthma care. Multistakeholder brainstorming sessions led to the emergence of three prototypes that underwent low-fidelity field testing. RESULTS: The first prototype elucidated caregivers' preferred outpatient asthma support systems using a newly created visual decision-making aid. The second constructed prototype was a child-oriented asthma activity sheet that allowed children to better communicate their understanding and impact of asthma care. The final prototype attempted to improve interactions between providers, caregivers, and children/adolescents using visual prompts to enhance empathetic and clinically-relevant dialogue. CONCLUSION: Engaging a diverse population of relevant stakeholders in disease processes that use design thinking yield relevant solutions with enhanced community buy-in. The prototypes are continuing to undergo iterative field testing in local community and academic asthma care sites.

[Prediction of postoperative nausea and vomiting using an artificial neural network]. / Vorhersage von Ubelkeit und Erbrechen in der postoperativen Phase durch ein künstliches neuronales Netz.

OBJECTIVE: Postoperative nausea and vomiting (PONV) are still frequent side-effects after general anaesthesia. These unpleasant symptoms for the patients can be sufficiently reduced using a multimodal antiemetic approach. However, these efforts should be restricted to risk patients for PONV. Thus, predictive models are required to identify these patients before surgery. So far all risk scores to predict PONV are based on results of logistic regression analysis. Artificial neural networks (ANN) can also be used for prediction since they can take into account complex and non-linear relationships between predictive variables and the dependent item. This study presents the development of an ANN to predict PONV and compares its performance with two established simplified risk scores (Apfel's and Koivuranta's scores). METHODS: The development of the ANN was based on data from 1,764 patients undergoing elective surgical procedures under balanced anaesthesia. The ANN was trained with 1,364 datasets and a further 400 were used for supervising the learning process. One of the 49 ANNs showing the best predictive performance was compared with the established risk scores with respect to practicability, discrimination (by means of the area under a receiver operating characteristics curve) and calibration properties (by means of a weighted linear regression between the predicted and the actual incidences of PONV). RESULTS: The ANN tested showed a statistically significant ( p<0.0001) and clinically relevant higher discriminating power (0.74; 95% confidence interval: 0.70-0.78) than the Apfel score (0.66; 95% CI: 0.61-0.71) or Koivuranta's score (0.69; 95% CI: 0.65-0.74). Furthermore, the agreement between the actual incidences of PONV and those predicted by the ANN was also better and near to an ideal fit, represented by the equation y=1.0x+0. The equations for the calibration curves were: KNN y=1.11x+0, Apfel y=0.71x+1, Koivuranta 0.86x-5. CONCLUSION: The improved predictive accuracy achieved by the ANN is clinically relevant. However, the disadvantages of this system prevail because a computer is required for risk calculation. Thus, we still recommend the use of one of the simplified risk scores for clinical practice.

Visualization of the domain structure of an L-type Ca2+ channel using electron cryo-microscopy.

The three-dimensional structure of the skeletal muscle voltage-gated L-type calcium channel (Ca(v)1.1; dihydropyridine receptor, DHPR) was determined using electron cryo-microscopy and single-particle averaging. The structure shows a single channel complex with an approximate total molecular mass of 550 kDa, corresponding to the five known subunits of the DHPR, and bound detergent and lipid. Features visible in our structure together with antibody labeling of the beta and alpha(2) subunits allowed us to assign locations for four of the five subunits within the structure. The most striking feature of the structure is the extra-cellular alpha(2) subunit that protrudes from the membrane domain in close proximity to the alpha(1) subunit. The cytosolic beta subunit is located close to the membrane and adjacent to subunits alpha(1), gamma and delta. Our structure correlates well with the functional and biochemical data available for this channel and suggests a three-dimensional model for the excitation-contraction coupling complex consisting of DHPR tetrads and the calcium release channel.

[Artificial neural networks. Theory and applications in anesthesia, intensive care and emergency medicine]. / Künstliche neuronale Netze. Theorie und Anwendungen in der Anästhesie, Intensiv- und Notfallmedizin.

Artificial neural networks (ANN) are constructed to simulate processes of the central nervous system of higher creatures. An ANN consists of a set of processing units (nodes) which simulate neurons and are interconnected via a set of "weights" (analogous to synaptic connections in the nervous system) in a way which allows signals to travel through the network in parallel. The nodes (neurons) are simple computing elements. They accumulate input from other neurons by means of a weighted sum. If a certain threshold is reached the neuron sends information to all other connected neurons otherwise it remains quiescent. One major difference compared with traditional statistical or rule-based systems is the learning aptitude of an ANN. At the very beginning of a training process an ANN contains no explicit information. Then a large number of cases with a known outcome are presented to the system and the weights of the inter-neuronal connections are changed by a training algorithm designed to minimise the total error of the system. A trained network has extracted rules that are represented by the matrix of the weights between the neurons. This feature is called generalisation and allows the ANN to predict cases that have never been presented to the system before. Artificial neural networks have shown to be useful predicting various events. Especially complex, non-linear, and time depending relationships can be modelled and forecasted. Furthermore an ANN can be used when the influencing variables on a certain event are not exactly known as it is the case in financial or weather forecasts. This article aims to give a short overview on the function of ANN and their previous use and possible future applications in anaesthesia, intensive care, and emergency medicine.

Enhancement of complement-mediated lysis by a peptide derived from SCR 13 of complement factor H.

Complement factor H (fH) is an important regulator of complement activation. It contributes to protection of cells against homologous complement attack. In this study we tested the effect of fH-depletion of normal human serum (NHS) on lysis of antibody-coated sheep and human erythrocytes (EshA and EhuA). In the absence of fH, lysis of sensitised Esh and Ehu was clearly increased. Addition of fH to fH-depleted serum re-established protection of cells against complement similar to that seen with NHS. A fH-derived peptide (pepAred), covering the N-terminal half of SCR 13 in fH, was able to enhance complement-mediated lysis of EhuA significantly. However, the oxidised form of this peptide (pepAox) had no effect. Biotinylated pepAred, but not pepAox, was able to directly bind to cells. Additionally, pepAred competed with direct fH-cell interaction which was observable only after treatment of purified fH with mercaptoethanol. Only pepAred increased the amount of C3 fragments and reduced levels of fH detectable on cells as shown by FACS analysis and radio-immuno assay. Furthermore, fH and factor I (fI)-mediated cleavage of agarose bound C3b into iC3b was decreased in the presence of pepAred. These data indicate that a fH-derived peptide can enhance complement-mediated lysis. We will continue to investigate whether the use of a fH peptide can be exploited for therapeutical purposes.

A new generation of polyurethane vascular prostheses: rara avis or ignis fatuus?

Three polyurethane (PU) vascular grafts with novel designs were investigated and compared in terms of the microporous structure, reinforcement technology, polymer chemistry, microphase separation, and mechanical properties. The Corvita graft, composed of a poly(carbonate urethane) polymer, displayed a helically wound filament structure with communicating inter-fiber spaces. The reinforced model contained an external PET mesh impregnated with a protein sealant, and displayed good microphase separation, the highest Young's modulus in the longitudinal direction, and the second highest in the radial direction. The Thoratec graft was made of a polyetherurethaneurea with an average micropore size of 15 microns. Silicone was observed on both surfaces of the graft. The Thoratec device displayed a low degree of hydrogen-bonding among the urethane groups and had no well-organized hard-segment domains. Its mechanical strength was superior to that of the Pulse-Tec graft. A solid PU layer underneath the luminal surface precluded any communication between the luminal and adventitial sides. The Pulse-Tec prosthesis was composed of polyetherurethane, with an average micropore size of 28 microns. It offered the highest radial compliance, a high degree of hydrogen-bonding, a narrow molecular weight distribution, and a certain degree of microphase separation. Its tensile strength and hysteresis loss were inferior to those of the other two grafts.

Ethical issues in Alzheimer disease: the experience of a national Alzheimer society task force.

There has been increasing recognition of the ethical dilemmas that arise in the delivery of health care services and in planning and executing scientific research. Alzheimer disease (AD) and related dementias pose a particular challenge for families, care providers, and researchers because of the nature of the illness. Naturally, those at potential risk of developing the disease are eager for scientists to develop valid predictive tests for the disease. Alzheimer organizations have developed worldwide in response to the growing awareness and knowledge of the effects of dementia on individuals and their families. These organizations have played a role in advocating for research, increasing general awareness of the nature of the disease, and lobbying for more services for persons with dementia and their families. These organizations have also realized the increasing concern about the many ethical issues that arise in caring for those with AD and researching causes and cures. This paper describes a unique process one national Alzheimer society used to develop an Ethics Task Force to provide guidelines on ethical issues.

Ethical guidelines of the Alzheimer Society of Canada.

Alzheimer's disease raises numerous ethical issues which vary and evolve over the course of the illness. In recognition of the need for ongoing discussion of these issues, the Alzheimer Society of Canada established a Task Force on Ethics in 1995. Through a process of "discourse ethics" and consultation on a national scale, the Task Force produced a series of guidelines dealing with the issues of: communicating the diagnosis, driving, respecting individual choice, quality of life, participation in research, genetic testing, the use of restraints, and end-of-life care. This manuscript presents a summary of these guidelines as well as a summary of the ideas on which they were based. It was the hope of the Society that the publication of these guidelines will serve to facilitate discussion of the ethics of care of those with Alzheimer's disease.

Co-localization of the cysteine protease caspase-3 with apoptotic myocytes after in vivo myocardial ischemia and reperfusion in the rat.

The aim of our study was to characterize the temporal relationship of apoptosis to regional myocardial ischemia and reperfusion and we aimed to determine the effect of ischemia and reperfusion on the distribution of the pro-apoptotic cysteine protease caspase-3 (CPP 32, apopain, Yama) in an in vivo rat model. Male Sprague-Dawley rats (250-400 g) were anesthetized with sodium pentobarbital (65 mg/kg, i.p.), the left external carotid artery was isolated to monitor arterial pressure and a left thoracotomy was performed. Regional myocardial ischemia was induced by occluding the left main coronary artery for 45 min. The heart was reperfused for 0, 60, 120 or 180 min. TUNEL staining of formalin-fixed, paraffin-embedded left ventricle, and DNA fragmentation analysis, showed that apoptosis occurred during 45 min of ischemia alone, but further developed during the 3-h reperfusion period. Immunohistochemical analysis of ischemic/reperfused left ventricle showed caspase-3 levels were substantially elevated and localized in the ischemic/reperfused region, and that caspase-3 co-localized to TUNEL positive myocytes. Therefore, regional myocardial ischemia serves as a stimulus for myocyte apoptosis, and this form of cell death progresses time-dependently after the onset of reperfusion. Our studies implicate caspase-3 to be involved in apoptotic cell death in ischemic/reperfused rat heart.

Distribution of high-conductance Ca(2+)-activated K+ channels in rat brain: targeting to axons and nerve terminals.

Tissue expression and distribution of the high-conductance Ca(2+)-activated K+ channel Slo was investigated in rat brain by immunocytochemistry, in situ hybridization, and radioligand binding using the novel high-affinity (Kd 22 pM) ligand [3H]iberiotoxin-D19C ([3H]IbTX-D19C), which is an analog of the selective maxi-K peptidyl blocker IbTX. A sequence-directed antibody directed against Slo revealed the expression of a 125 kDa polypeptide in rat brain by Western blotting and precipitated the specifically bound [3H]IbTX-D19C in solubilized brain membranes. Slo immunoreactivity was highly concentrated in terminal areas of prominent fiber tracts: the substantia nigra pars reticulata, globus pallidus, olfactory system, interpeduncular nucleus, hippocampal formation including mossy fibers and perforant path terminals, medial forebrain bundle and pyramidal tract, as well as cerebellar Purkinje cells. In situ hybridization indicated high levels of Slo mRNA in the neocortex, olfactory system, habenula, striatum, granule and pyramidal cell layer of the hippocampus, and Purkinje cells. The distribution of Slo protein was confirmed in microdissected brain areas by Western blotting and radioligand-binding studies. The latter studies also established the pharmacological profile of neuronal Slo channels. The expression pattern of Slo is consistent with its targeting into a presynaptic compartment, which implies an important role in neural transmission.

[125I]margatoxin, an extraordinarily high affinity ligand for voltage-gated potassium channels in mammalian brain.

Monoiodotyrosine margatoxin ([125I]MgTX) specifically and reversibly labels a maximum of 0.8 pmol of sites/mg of protein in purified rat brain synaptic plasma membrane vesicles with a dissociation constant of 0.1 pM under equilibrium binding conditions. This Kd value was confirmed by kinetic experiments (Kd of 0.07 pM), competition assays employing native margatoxin (MgTX) (Ki of 0.15 pM), and receptor saturation studies (Kd of 0.18 pM). Thus, this toxin represents the highest affinity, reversible radioligand for any membrane-bound receptor or ion channel described to date. [125I]MgTX binding in this system is modulated by charybdotoxin (Ki of 5 pM), kaliotoxin (Ki of 1.5 pM), and the agitoxins I and II (Ki's of 0.1 and 0.3 pM, respectively), in a noncompetitive manner. Moreover, alpha-dendrotoxin displayed a Ki value of 0.5 pM. Iberiotoxin was without any effect, suggesting that the receptor site is likely to be associated with a voltage-gated K+ channel complex. [125I]MgTX binding is inhibited by cations that are established blockers of voltage-dependent K+ channels (Ba2+, Ca2+, Cs+). The monovalent cations Na+ and K+ stimulate binding at low concentrations before producing complete inhibition as their concentrations are increased. Stimulation of binding results from an allosteric interaction that decreases Kd, whereas inhibition is due to an ionic strength effect. Affinity labeling of the binding site in rat brain synaptic plasma membranes employing [125I]MgTX and the bifunctional cross-linking reagent, disuccinimidyl suberate, causes specific and covalent incorporation of toxin into a glycoprotein of an apparent molecular weight (M(r)) of 74,000. Deglycosylation studies reveal an M(r) for the core polypeptide of the MgTX receptor of 63,000.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of tissue-expressed alpha subunits of the high conductance Ca(2+)-activated K+ channel.

Purified high conductance calcium-activated potassium (maxi-K) channels from tracheal smooth muscle have been shown to consist of a 60-70-kDa alpha subunit, encoded by the slo gene, and a 31-kDa beta subunit. Although the size of the beta subunit is that expected for the product of the gene encoding this protein, the size of the alpha subunit is smaller than that predicted from the slo coding region. To determine the basis for this discrepancy, sequence-directed antibodies have been raised against slo. These antibodies specifically precipitate the in vitro translation product of mslo, which yields an alpha subunit of the expected molecular mass (135 kDa). Immunostaining experiments employing smooth muscle sarcolemma, skeletal muscle T-tubules, as well as membranes derived from GH3 cells reveal the presence of an alpha subunit with an apparent molecular mass of 125 kDa. The difference in size of the alpha subunit as expressed in these membranes and the purified preparations is due to a highly reproducible proteolytic decay that occurs mostly at an advanced stage of the maxi-K channel purification. In the purified maxi-K channel preparations investigated, the full-length alpha subunit, an intermediate size product of 90 kDa, and the 65-kDa polypeptide, as well as other smaller fragments can be detected using appropriate antibodies. Proteolysis occurs exclusively at two distinct positions within the long C-terminal tail of slo. In addition, evidence for the tissue expression of distinct splice variants in membrane-bound as well as purified maxi-K channels is presented.

Covalent attachment of charybdotoxin to the beta-subunit of the high conductance Ca(2+)-activated K+ channel. Identification of the site of incorporation and implications for channel topology.

Purified high conductance Ca(2+)-activated K+ (maxi-K) channels from bovine tracheal smooth muscle have been covalently labeled employing monoiodotyrosine charybdotoxin ([125I]ChTX) and different bifunctional cross-linking reagents. [125I]ChTX was specifically incorporated into the beta-subunit, which was thereafter isolated by size exclusion high performance liquid chromatography. Proteolytic fragments of the [125I]ChTX-labeled beta-subunit were generated by digestion with various endoproteinases. Glu-C or Asp-N cleavage yielded a glycosylated [125I]ChTX-labeled fragment of 13-14 kDa. A site-directed antiserum raised against residues 62-75 of the cloned beta-subunit of the maxi-K channel specifically recognizes the beta-subunit in immunostaining experiments and was capable of immunoprecipitating these ChTX-labeled peptides. Lys-C cleavage resulted in two fragments of 16 and 28 kDa, respectively, which were both precipitated by anti-beta (62-75). However, only the 28-kDa fragment was recognized by anti-beta(118-132) and shown to carry double the amount of N-linked carbohydrates. Taken together, these data restrict the site of covalent incorporation of ChTX into the beta-subunit exclusively at Lys69, confirm the predicted topology of this subunit, and indicate that both canonical N-linked glycosylation sites are occupied with complex carbohydrates of 5-6 kDa each. We propose that an extracellularly located portion of the beta-subunit is located within 7.7 A of the ChTX receptor site and could even participate in the formation of this receptor by close apposition of its extracellular domain with structural elements provided by the alpha-subunit.

The effectiveness of two sonic and two ultrasonic scaler tips in furcations.

This study compared the effectiveness of two sonic and two ultrasonic scaler tips on artificial calculus removal from the furcations of mandibular first and second molars. Twenty-four extracted mandibular molars were cleaned and randomly assigned to one of four treatment groups. Teeth were split buccal lingually, artificial calculus was placed in the furcation areas, and the teeth were photographed with a stereo camera. Teeth were reconnected with bonding material and mounted in a typodont with simulated gingiva and attached to a dental chair. Teeth were instrumented with either a Cavitron TFI10 tip, Cavitron EWPP tip, Titan-S Universal tip, or Titan-S Sickle tip by a licensed dental hygienist until each tooth was judged calculus free to the touch with a CH3 explorer. Time for each instrumentation period was recorded. Following instrumentation, the teeth were again split and photographed. Stereophotogrammetry was used to produce tracings of the teeth with initial calculus and remaining calculus. Pre-instrumentation and post-instrumentation amounts of calculus on the surface area were computed using the Bioquant system. A two factor analysis of variance was conducted followed with a Newman-Keuls Multiple Comparison Technique to test for within and between differences. Significant differences (P less than or equal to 0.01) were found between pre- and post-amounts of calculus for all tips. No significant differences (P less than or equal to 0.05) were found between the four instrument tips with respect to percentage of furcation surface with calculus remaining. No differences were found between tips with regard to the time required to clean the test surfaces.

Pediatric gunshot wounds--powder and nonpowder weapons.

A retrospective chart review of 102 consecutive cases of gunshot wound injuries in children was conducted. Victims were identified by emergency department log review and computer search for inpatient discharge diagnoses. Results are compared with other studies. Nonpowder weapons are found to be involved in a preponderance of cases. In 66% of the cases in which the weapon was known, a nonpowder weapon was used. Length of hospital stay, operations performed, and outcome were compared for the handgun and nonpowder weapon groups. Nonpowder weapons were found to have inflicted major injury in as many patients as did handguns. Methodologic problems of studying gunshot wounds in children are discussed. It is suggested that injury prevention strategies address nonpowder weapons as well as handguns.

Dentofacial trauma in children.

Most of the literature on dental injury pertains to the classification, incidence, prevalence, and treatment of fractured teeth. A major finding here is that the five leading causes of dentofacial injuries, regardless of severity, were falls, being struck by an object, bicycle accidents, assaults, and motor vehicle accidents.