Exploring the structural complexity of intermetallic compounds by an adaptive genetic algorithm.

Solving the crystal structures of novel phases with nanoscale dimensions resulting from rapid quenching is difficult due to disorder and competing polymorphic phases. Advances in computer speed and algorithm sophistication have now made it feasible to predict the crystal structure of an unknown phase without any assumptions on the Bravais lattice type, atom basis, or unit cell dimensions, providing a novel approach to aid experiments in exploring complex materials with nanoscale grains. This approach is demonstrated by solving a long-standing puzzle in the complex crystal structures of the orthorhombic, rhombohedral, and hexagonal polymorphs close to the Zr2Co11 intermetallic compound. From our calculations, we identified the hard magnetic phase and the origin of high coercivity in this compound, thus guiding further development of these materials for use as high performance permanent magnets without rare-earth elements.

Site Readiness Framework to Improve Health System Preparedness for a Potential New Alzheimer's Disease Treatment Paradigm.

New therapies that address the underlying pathophysiology of Alzheimer's Disease (AD), coupled with the growth of the AD population, will transform the AD care pathway and present significant challenges to health systems. We explored real-world challenges health systems may face in delivering potential new AD therapies with diverse stakeholders. Key challenges in care included integrating primary care providers into assessment and management, availability of memory care specialists, understanding payment and coverage issues and training mid-level providers to help coordinate care and serve as a shared resource across the system. This input informed a novel Site Readiness Framework for AD, comprising self-assessment exercises to identify health system capabilities and gaps and a framework of core strategies and responsive tools to help prepare to integrate new AD therapies. These resources may help health systems improve readiness to modify care pathways to integrate new therapies for AD.

Recent advances in atherectomy and devices for treatment of infra-inguinal arterial occlusive disease.

The prevalence of peripheral arterial disease (PAD) continues to rise in an ever ageing society and consumes a significant part of health resources. Percutaneous revascularization has revolutionized the treatment of lower extremity peripheral vascular disease over the past 10 years. Additionally, novel devices have allowed improved endovascular treatment of femoropopliteal as well as infrapopliteal disease. Although percutaneous transluminal angioplasty (PTA) can be an effective modality for focal lesions in the iliac arteries, the results for complex infra-inguinal arterial disease have been disappointing. One class of new technology has concentrated on debulking the plaque, while others focus to improve safety (distal embolic protection devices) or are directed to specific clinical challenges such as chronic total occlusions. However, the lack of uniform performance criteria and reporting standards for these and other devices has resulted in heterogeneous study end points, making comparative efficacy difficult. Here we review the current data for atherectomy and atheroablative technologies as well as other adjunctive devices in the treatment of lower extremity peripheral arterial disease.

Simple approaches towards the design of an attached-growth sponge bioreactor (AGSB) for wastewater treatment and reuse.

Wastewater treatment and reuse is being emphasized due to the shortage of water sources and the continuous deterioration of the aquatic environment. In this study, a novel sponge bioreactor was studied as a low cost, high efficiency alternative for an attached growth biological system. This was designed by combining of number of sponge trays. This emerging technology has many beneficial properties in wastewater treatment and reuse. The approaches towards the conditions for system design were: (i) selection of sponge types; (ii) selection of sponge shapes; and (iii) selection of designated slope of sponge tray. They were determined through a series of experiments using a laboratory-scale unit with synthetic wastewater. It was then tested with a pilot-scale unit at the predetermined optimum conditions. The results indicate that the highest biomass growth was found at the sponge type with a cell count of 70-90 cells/in(2) (6.45 cm(2)) The relationship between biomass growth and biological oxygen consumption was well established. The prism-shaped sponge (triangular polyurethane sponge of 70-90 cells/in(2) with designated slope of sponge tray at 10 degrees) led to the best performance in terms of both organic and nutrient removal efficiency.

Proton therapy for pediatric cranial tumors: preliminary report on treatment and disease-related morbidities.

PURPOSE: Accelerated protons were used in an attempt to limit treatment-related morbidity in children with tumors in or near the developing brain, by reducing the integral dose to adjacent normal tissues. METHODS AND MATERIALS: Children treated with protons at Loma Linda University Medical Center between August 1991 and December 1994 were analyzed retrospectively. Twenty-eight children, aged 1 to 18 years, were identified as at risk for brain injury from treatment. Medical records, physical examinations, and correspondence with patients, their parents, and referring physicians were analyzed. The investigators tabulated post-treatment changes in pre-treatment signs and symptoms and made judgments as to whether improvement, no change, or worsening related to disease or treatment had supervened. Magnetic resonance images were correlated with clinical findings and radiographic impressions were tabulated. RESULTS: Follow-up ranged from 7 to 49 months (median 25 months). Four instances of treatment-related morbidity were identified. Forty-one instances of site-specific, disease-related morbidity were identified: 15 improved or resolved and 26 remained unchanged after treatment. Four patients had radiographic evidence of local failure. Three of these patients, including two with high-grade glioma, have died. CONCLUSION: Early treatment-related morbidity associated with proton therapy is low. Tumor progression remains a problem when treating certain histologies such as high-grade glioma. Escalating the dose delivered to target volumes may benefit children with tumors associated with poor rates of local control. Long-term follow-up, including neurocognitive testing, is in progress to assess integral-dose effects on cognitive, behavioral and developmental outcomes in children with cranial tumors.

Long-term compliance with nasal continuous positive airway pressure therapy of obstructive sleep apnea.

In an attempt to identify predictors of long-term compliance with nasal continuous positive airway pressure (CPAP), we reviewed the records of 125 patients with obstructive sleep apnea (OSA) referred to our center for nasal CPAP trials. Severity of sleep apnea, sleep staging, daytime hypersomnolence, effectiveness of nasal CPAP, previous palatal surgery, and adverse reactions were compared in compliant and noncompliant patients. Nineteen patients did not tolerate a nasal CPAP trial in the laboratory or refused home nasal CPAP therapy. Ten patients were unavailable for follow-up. Of the remaining 96 patients, 23 (24 percent) had discontinued therapy, while 73 (76 percent) were still using nasal CPAP at 14.5 +/- 10.7 months (mean +/- SD). There were no statistically significant differences between the compliant and noncompliant patients in baseline apnea plus hypopnea index (AHI), baseline sleep staging, AHI while receiving nasal CPAP, sleep staging while receiving nasal CPAP, or frequency of adverse reactions during therapy. Severe daytime sleepiness was present in 65 of the 73 compliant patients and in 12 of the 23 noncompliant patients (p less than 0.05). Ten of 43 in the compliant group had previous palatal surgery compared with ten of 23 noncompliant patients (p less than 0.05). Our data confirm earlier observations in smaller samples that compliant and noncompliant patients have equally severe sleep apnea and good initial responses to nasal CPAP. Long-term compliance with nasal CPAP may be associated with the severity of daytime hypersomnolence on presentation. Previous palatal surgery was more frequent in patients who did not tolerate long-term nasal CPAP therapy.

Delivering drugs, via microdialysis, into the environment of extracellularly recorded hippocampal neurons in behaving primates.

Hippocampal neurons in primates have been extensively studied with electrophysiological and neuroanatomical methods. Much less effort has been devoted to examining these cells with contemporary pharmacological techniques. Therefore, we modified a recently developed integrative technique (N. Ludvig, P.E. Potter, S.E. Fox, Simultaneous single-cell recording and microdialysis within the same brain site in freely behaving rats: a novel neurobiological method, J. Neurosci. Methods 55 (1994) 31-40 [9] ) for cellular neuropharmacological studies in behaving monkeys. A driveable microelectrode-microdialysis probe guide assembly was implanted stereotaxically into the left hippocampus of squirrel monkeys (Saimiri sciureus) under isoflurane anesthesia. The assembly was covered with a protective cap. After 3 weeks of postsurgical recovery and behavioral training, the experimental subject was seated in a primate chair. For 4-5 h, single-cell recording and microdialysis were simultaneously performed in the hippocampal implantation site. The technique allowed the recording of both complex-spike cells and fast-firing neurons without the use of head restraint. The control microdialysis solution, artificial cerebrospinal fluid (ACSF), was replaced with either 1 M ethanol or 500 microM N-methyl-D-aspartate (NMDA) for 10-30 min intervals. The ethanol perfusions principally suppressed the firing of the neurons in the dialysis area. The NMDA perfusions initially increased the firing of local neurons, then caused electrical silence. These drug delivery/cell recording sessions were performed with 1-4 day intersession intervals over a 1-month period. The described method provides a tool to elaborate the pharmacology of primate hippocampal neurons during behavior and without the confounding effects of systemic drug administrations.

Diagostic value of respiratory impedance measurements in elderly subjects.

Obstructive lung disease (OLD) is highly prevalent in elderly subjects but markedly under-diagnosed. Indeed, only 40-50% of hospitalized elderly patients are able to adequately perform spirometric tests. This study aimed to evaluate, in an acute-care geriatric hospital, the diagnostic value of measuring airway impedance (Zrs) by the forced oscillation technique (FOT) for: (1) identifying OLD and (2) identifying responders vs. non-responders to bronchodilators. Sixty-seven patients (aged 82+/-8 years) underwent consecutive measurement of Zrs and forced expiratory volumes before and after bronchodilators. Zrs was measured by FOT at frequencies of 4-30 Hz. Correlations, ROC curves and logistic regression models were established to determine the sensitivity (Se) and specificity (Sp) of Zrs in identifying OLD. Significant correlations were found between spirometric and Zrs measurements. The Zrs parameters yielding the best Se and Sp for detecting OLD were: Fn (resonant frequency; Se: 76%; Sp: 78%) and R0 (resistance extrapolated for a frequency of 0: Se: 76%; Sp: 74%). Using the logistic regression models, 76% of the patients were correctly classified as having OLD or not. Zrs was however not contributive in identifying responders to bronchodilators. Zrs measurements by FOT are contributive to the diagnosis of OLD in elderly hospitalized patients.

An adaptive genetic algorithm for crystal structure prediction.

We present a genetic algorithm (GA) for structural search that combines the speed of structure exploration by classical potentials with the accuracy of density functional theory (DFT) calculations in an adaptive and iterative way. This strategy increases the efficiency of the DFT-based GA by several orders of magnitude. This gain allows a considerable increase in the size and complexity of systems that can be studied by first principles. The performance of the method is illustrated by successful structure identifications of complex binary and ternary intermetallic compounds with 36 and 54 atoms per cell, respectively. The discovery of a multi-TPa Mg-silicate phase with unit cell containing up to 56 atoms is also reported. Such a phase is likely to be an essential component of terrestrial exoplanetary mantles.

Relationships between tamoxifen use, liver fat and body fat distribution in women with breast cancer.

Tamoxifen is a nonsteroidal anti-estrogenic drug used for adjuvant treatment of breast cancer and recently as a chemopreventative agent for breast cancer and, on an investigational basis, for other cancers. To date there are case reports of hypertriglyceridemia and fatty liver disease in tamoxifen users. Fatty liver is associated with visceral obesity and other components of the metabolic syndrome. Here we evaluated steatosis and adipose tissue distribution by CT scan in a cross-sectional study of 32 women on tamoxifen and 39 control women. Tamoxifen users had more visceral adipose tissue (VAT) and more liver fat than controls. This is the first study to demonstrate that fatty liver and intra-abdominal fat accumulation are common in breast cancer patients receiving tamoxifen. Prospective studies of tamoxifen should monitor metabolic changes in obese women with or without breast cancer.

Antimalarial compounds from Rhaphidophora decursiva.

Bioassay-directed fractionation led to the isolation of 14 compounds, six of which possess antimalarial activity, from the dried leaves and stems of Rhaphidophora decursiva. Polysyphorin (1) and rhaphidecurperoxin (6) showed strong activities against Plasmodium falciparum. Rhaphidecursinol A (2), rhaphidecursinol B (3), grandisin (4), and epigrandisin (5) were less active against the same organism. Among the isolates, rhaphidecursinol A (2) and rhaphidecursinol B (3) were determined to be new neolignans, and rhaphidecurperoxin (6) is a new benzoperoxide. Known compounds isolated include polysyphorin (1), grandisin (4), epigrandisin (5), (+)-medioresinol, (-)-pinoresinol, (-)-syringaresinol, (+)-glaberide I, (+)-dehydrovomifoliol, (-)-liliolide, (-)-hydroxydihydrobovolide, and N-butylbenzamide, of which compound 1 appears worthy of further evaluation as an antimalarial agent. Structure elucidation and identification were accomplished by spectroscopic means including 1D and 2D NMR analyses.