Performance and usability testing of an automated tool for detection of peripheral artery disease using electronic health records.

Peripheral artery disease (PAD) is a common cardiovascular disorder that is frequently underdiagnosed, which can lead to poorer outcomes due to lower rates of medical optimization. We aimed to develop an automated tool to identify undiagnosed PAD and evaluate physician acceptance of a dashboard representation of risk assessment. Data were derived from electronic health records (EHR). We developed and compared traditional risk score models to novel machine learning models. For usability testing, primary and specialty care physicians were recruited and interviewed until thematic saturation. Data from 3168 patients with PAD and 16,863 controls were utilized. Results showed a deep learning model that utilized time engineered features outperformed random forest and traditional logistic regression models (average AUCs 0.96, 0.91 and 0.81, respectively), P < 0.0001. Of interviewed physicians, 75% were receptive to an EHR-based automated PAD model. Feedback emphasized workflow optimization, including integrating risk assessments directly into the EHR, using dashboard designs that minimize clicks, and providing risk assessments for clinically complex patients. In conclusion, we demonstrate that EHR-based machine learning models can accurately detect risk of PAD and that physicians are receptive to automated risk detection for PAD. Future research aims to prospectively validate model performance and impact on patient outcomes.

Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity.

Correct wiring in the neocortex requires that responses to an individual guidance cue vary among neurons in the same location, and within the same neuron over time. Nestin is an atypical intermediate filament expressed strongly in neural progenitors and is thus used widely as a progenitor marker. Here we show a subpopulation of embryonic cortical neurons that transiently express nestin in their axons. Nestin expression is thus not restricted to neural progenitors, but persists for 2-3 d at lower levels in newborn neurons. We found that nestin-expressing neurons have smaller growth cones, suggesting that nestin affects cytoskeletal dynamics. Nestin, unlike other intermediate filament subtypes, regulates cdk5 kinase by binding the cdk5 activator p35. Cdk5 activity is induced by the repulsive guidance cue Semaphorin3a (Sema3a), leading to axonal growth cone collapse in vitro. Therefore, we tested whether nestin-expressing neurons showed altered responses to Sema3a. We find that nestin-expressing newborn neurons are more sensitive to Sema3a in a roscovitine-sensitive manner, whereas nestin knockdown results in lowered sensitivity to Sema3a. We propose that nestin functions in immature neurons to modulate cdk5 downstream of the Sema3a response. Thus, the transient expression of nestin could allow temporal and/or spatial modulation of a neuron's response to Sema3a, particularly during early axon guidance.

On the buckling of an elastic holey column.

We report the results of a numerical and theoretical study of buckling in elastic columns containing a line of holes. Buckling is a common failure mode of elastic columns under compression, found over scales ranging from metres in buildings and aircraft to tens of nanometers in DNA. This failure usually occurs through lateral buckling, described for slender columns by Euler's theory. When the column is perforated with a regular line of holes, a new buckling mode arises, in which adjacent holes collapse in orthogonal directions. In this paper, we firstly elucidate how this alternate hole buckling mode coexists and interacts with classical Euler buckling modes, using finite-element numerical calculations with bifurcation tracking. We show how the preferred buckling mode is selected by the geometry, and discuss the roles of localized (hole-scale) and global (column-scale) buckling. Secondly, we develop a novel predictive model for the buckling of columns perforated with large holes. This model is derived without arbitrary fitting parameters, and quantitatively predicts the critical strain for buckling. We extend the model to sheets perforated with a regular array of circular holes and use it to provide quantitative predictions of their buckling.

Lightning-induced intensification of the ionospheric sporadic E layer.

A connection between thunderstorms and the ionosphere has been hypothesized since the mid-1920s. Several mechanisms have been proposed to explain this connection, and evidence from modelling as well as various types of measurements demonstrate that lightning can interact with the lower ionosphere. It has been proposed, on the basis of a few observed events, that the ionospheric 'sporadic E' layer--transient, localized patches of relatively high electron density in the mid-ionosphere E layer, which significantly affect radio-wave propagation--can be modulated by thunderstorms, but a more formal statistical analysis is still needed. Here we identify a statistically significant intensification and descent in altitude of the mid-latitude sporadic E layer directly above thunderstorms. Because no ionospheric response to low-pressure systems without lightning is detected, we conclude that this localized intensification of the sporadic E layer can be attributed to lightning. We suggest that the co-location of lightning and ionospheric enhancement can be explained by either vertically propagating gravity waves that transfer energy from the site of lightning into the ionosphere, or vertical electrical discharge, or by a combination of these two mechanisms.

Olanzapine treatment for patients with schizophrenia and substance abuse.

The objective of this study was to evaluate the efficacy and safety of olanzapine in patients with schizophrenia and comorbid substance abuse disorders. Thirty patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder as well as criteria for substance abuse or substance dependence, were treated in a 12-month prospective, open-label trial of olanzapine. Patients were evaluated with multiple efficacy and safety measures at baseline and then monthly thereafter. Statistically significant improvement was noted in psychopathology, levels of hope, and safety measures. Seventy percent (n = 21) of the patients achieved early full substance abuse remission at the end of the study period, while 30% (n = 9) achieved early partial substance abuse remission. Our results indicate that olanzapine treatment improved psychopathology, increased hopefulness, and reduced antipsychotic-associated side effects. The benefits observed with olanzapine treatment may contribute to the patients' substance abuse remission.

Switching clozapine responders to olanzapine.

BACKGROUND: Clozapine is an atypical antipsychotic indicated for the management of severely ill patients with schizophrenia who have failed to respond adequately to standard drug treatment. The significant risk of agranulocytosis and seizure associated with clozapine has led to the restrictions in its use. Additionally, drug-induced sedation, sialorrhea, enuresis, and weight gain are often cited as problematic consequences of clozapine treatment. Our primary objective was to determine the effectiveness and safety of a method of slow cross-titration from clozapine to olanzapine among patients responsive to clozapine treatment but experiencing medication-induced adverse events. METHOD: Changes in symptomatology, mood, subjective response, and safety were examined in 20 outpatients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder who converted from clozapine to olanzapine. Patients were considered clozapine-responsive as evidenced by improved social function and decreased symptoms with clozapine therapy; however, they were interested in alternative pharmacologic treatment because of clozapine-related side effects. RESULTS: Equivalent efficacy of olanzapine to clozapine was found in 90% of the patients (18/20) in the study group, without rehospitalization or suicidal behavior in any of the patients. Also notable was a reduction in drug-induced side effects and improved subjective response to pharmacotherapy. CONCLUSION: The successful conversion from clozapine to olanzapine has the potential to provide great benefits for the patient, including reducing drug-induced side effects while maintaining symptom control. These preliminary results suggest that further research on converting clozapine responders to olanzapine is warranted.

"Knock-your-socks-off" service.

The author compares customer service in industry and health care and explains what goes into delivering exceptional customer service.

Evaluating preceptorship experiences in a distance nursing program.

Clinically based education for registered nursing students is a major component of a nursing curriculum. Nursing educational programs are becoming increasingly reliant on clinicians in hospitals and health care agencies to be preceptors for their students. The concept of preceptorship in baccalaureate nursing education continues to be endorsed as a viable alternative clinical teaching strategy (Myrick & Barrett, 1994). Preceptorship programs are necessary interventions to facilitate integrating and enacting the professional nurse role (Allanach & Jennings, 1990). The educational clinical preceptorship provides the opportunity for collaboration and the development of collegial relationships between members of academia and nursing service (Patton & Dowd, 1994). The highly competitive nature of today's health care institutions and the rapid changes in health and nursing care increase the need for nurse leaders. Students must acquire leadership and management skills and be competent as the role of the nurse changes to a participant in the organizational leadership and management process. The purpose of this study was to evaluate students' experiences regarding preceptor effectiveness in upper division leadership and management courses in a Bachelor of Science in Nursing (BSN) distance nursing program. Specifically, this article describes experiences from participating students enrolled in a performance/clinical rotation in the Spring 1996 semester throughout the state of California. For a successful clinical experience, it is important to evaluate the major components of the preceptorship experience.

Synthesis, SAR and pharmacology of CP-293,019: a potent, selective dopamine D4 receptor antagonist.

A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing.

Solid-state NMR characterization of copolymers of nylon 11 and nylon 12.

Solid-state 13C and 15N NMR spectroscopy, in conjunction with differential scanning calorimetry, wide-angle X-ray diffraction and infrared spectroscopy, were used to characterize a series of nylon 11 and 12 copolymers with mole percentages of nylon 12 monomer of 0, 15, 35, 50, 65, 85, and 100%. Monotonic melting point (Tm) and heat of fusion depressions were observed for the copolymer series with the 65 mol% nylon 12 copolymer having the lowest apparent crystallinity and Tm at 148 degrees C. Solid-state 15N NMR spectra showed a smooth shift of the main peak position for the as-prepared copolymers from 84 ppm for the alpha-form of pure nylon 11 to 89 ppm for the gamma-form of pure nylon 12. Similar behavior was seen for FTIR amide V and VI modes which are also sensitive to the alpha- and gamma-crystal forms. 13C NMR T1 measurements showed that the overall most mobile sample was the 65:35 copolymer. The amide group of the 1:1 copolymer was labelled using 15N-labelled amino acids available through the Gabriel synthesis; an annealed, solution-cast film of this sample showed a T1N value of 349 s, similar to values seen for annealed nylon 11 and nylon 12 homopolymers. The WAXS pattern for the 65 mol% nylon 12 sample showed a sharp peak at 2 theta = 21.3, overlapping a broad peak centered at 2 theta = 21.0. These are consistent with the values seen for gamma-form nylon 12. The 1:1 copolymer (15N labelled) was shown to be polymorphic, like the homopolymers after specific treatments, with a gamma-like phase formed upon solvent casting, and an alpha-like phase dominating for as-polymerized material and precipitated flakes.

Combined liquid chromatography/mass spectrometry of the radical adducts of a fluorescamine-derivatized nitroxide.

Dynamic liquid secondary ion mass spectrometry (dyn-LSIMS) was employed to acquire continuous, on-line mass spectral data from the effluent of a reversed-phase high-performance liquid chromatograph (HPLC) used to separate a broad suite of carbon-centered radicals trapped as the O-alkylhydroxylamine adducts of an amino nitroxide that was subsequently derivatized with fluorescamine. Data obtained by the use of these combined techniques (LC/MS) can be employed to elucidate radical adduct structures; elemental compositions of the adducts can be confirmed by acquiring mass spectra at high resolution. At low resolution, introduction into the source of < 1 pmol of adduct yielded usable spectra. The first application of this technique to the identification of photochemically generated radicals in natural water samples is presented.

Clostridium tertium bacteremia: 2 cases and review.

Clostridium tertium bacteremia is unusual, seen most often with gastrointestinal disease and/or neutropenia. Two cases are described. The first was a 19-yr-old female with acute leukemia, who developed gastrointestinal symptoms and C. tertium bacteremia while neutropenic. The second was a 57-yr-old female with quiescent ulcerative colitis, who presented with fever, rigors and epigastric pain. Four organisms including C. tertium were isolated from blood cultures. This patient responded to broad spectrum antimicrobial therapy, whereas the first patient required the addition of specific agents to recover. C. tertium is aerotolerant and thus can be misidentified as a Bacillus or Corynebacterium spp. Our isolates had a distinctive Gram stain morphology, were catalase negative and failed to sporulate aerobically--this aided in the recognition of this significant Gram-positive bacillus.

Glutamic acid 327 in the sheep alpha 1 isoform of Na+,K(+)-ATPase is a pivotal residue for cation-induced conformational changes.

The cation binding characteristics of the mutant E327A formed in the sheep alpha 1 isoform of the Na+,K(+)-ATPase were examined using [3H]ouabain binding as a function of monovalent cation concentrations. Equilibrium competition binding assays in the presence of Mg2+, inorganic phosphate and various amounts of unlabelled ouabain indicated that both wild-type sheep alpha 1 protein and the E327A mutant expressed in 3T3 cells had similar affinities for ouabain (KD = 1.53 and 1.31 nM respectively). Sodium inhibition of ouabain binding appeared competitive in both enzymes. However, binding of three Na+ ions was required to explain the steep character of the Na+ inhibition curve for the wild-type Na+,K(+)-ATPase (Ki = 12.8 +/- 1.6 mM), whereas the binding of two Na+ ions was detected for the mutant E327A (Ki = 19.2 +/- 2.5 mM). Potassium binding of [3H]ouabain binding displayed a partially competitive nature with Hill coefficients of 2 for both wild-type sheep alpha 1 (Ki = 0.743 +/- 0.044 mM) and E327A (Ki = 0.875 +/- 0.067 mM). At concentrations of K+ above 10 mM, the sheep alpha 1 competition curve levelled off whereas the inhibition curve for E327A displayed a stimulation in ouabain binding. This stimulation in [3H]ouabain binding also occurred with Rb+, Cs+ and Li+, but was never observed with choline or Na+, suggesting that this effect was not due to ionic strength. From these [3H]ouabain-binding studies, it is obvious that the mutant enzyme E327A in the presence of Mg2+, Pi and ouabain, interacts with monovalent cations in a unique fashion. One interpretation of these data is that the glutamic acid residue at position 327 is involved in a conformational transition induced by the binding of monovalent cations to the Na+,K+-ATPase and that this transition is inhibited by the mutation of E327A.