Treatment algorithm use to optimize management of symptomatic patients with a history of mania

BACKGROUND: While monotherapy has significant limitations in bipolar disorder, few published data addressing alternatives exist. Treatment algorithms have been proposed, but none have undergone empirical evaluation. This study provides a systematic prospective, open evaluation of the effectiveness and tolerability of a treatment algorithm for patients with histories of mania. METHOD: Twenty-eight symptomatic outpatients from a public mental health facility who were diagnosed as having either bipolar I or schizoaffective illness, bipolar type, entered the study. Minimum blood levels of lithium and divalproex sodium were defined. Medications were pushed to predetermined levels (as tolerated) before proceeding to the next algorithm step. Clinical symptoms were assessed monthly using the Brief Psychiatric Rating Scale (BPRS, 27 item) and Clinical Global Impressions scale. RESULTS: Pretreatment and posttreatment clinical symptoms were compared. Over 50% of patients attained 30% improvement from baseline BPRS after 4 months. Thirty-six percent of patients (N = 10) became mood stable, 46% (N = 13) remained mood unstable, and 18% (N = 5) dropped out before completing the algorithm. Although patients who finished the algorithm were taking more medication, either dosage and/or drugs, somatic complaints did not increase. CONCLUSION: The potential benefit of a defined treatment algorithm was demonstrated for these complex and persistently ill patients. Despite long treatment histories, patients improved with more frequent visits and addition of medication(s). A randomized controlled trial comparing a similar treatment algorithm with treatment-as-usual is warranted.     

Advanced product planning: a comprehensive process for systemic definition of new product requirements

This paper reports results of research into the definition of requirements for new consumer products––specifically, electro-mechanical products. The research dealt with the derivation of design requirements that are demonstrably aligned with stakeholder needs. The paper describes a comprehensive process that can enable product development teams to deal with statements of product requirements, as originally collected through market research activities, in a systematic and traceable manner from the early, fuzzy front end, stages of the design process. The process described has been based on principles of systems engineering. A case study from its application and evaluation drawn from the power sector is described in this paper. The case study demonstrates how the process can significantly improve product quality planning practices through revision of captured product requirements, analysis of stakeholder requirements and derivation of design requirements. The paper discusses benefits and issues from the use of the process by product development teams, and identifies areas for further research. Finally, the conclusions drawn from the reported research are presented.

Towards inverse modeling of turbidity currents: The inverse lock-exchange problem

A new approach is introduced for turbidite modeling, leveraging the potential of computational fluid dynamics methods to simulate the flow processes that led to turbidite formation. The practical use of numerical flow simulation for the purpose of turbidite modeling so far is hindered by the need to specify parameters and initial flow conditions that are a priori unknown. The present study proposes a method to determine optimal simulation parameters via an automated optimization process. An iterative procedure matches deposit predictions from successive flow simulations against available localized reference data, as in practice may be obtained from well logs, and aims at convergence towards the best-fit scenario. The final result is a prediction of the entire deposit thickness and local grain size distribution. The optimization strategy is based on a derivative-free, surrogate-based technique. Direct numerical simulations are performed to compute the flow dynamics. A proof of concept is successfully conducted for the simple test case of a two-dimensional lock-exchange turbidity current. The optimization approach is demonstrated to accurately retrieve the initial conditions used in a reference calculation.     

Pan-Lysyl Oxidase Inhibitor PXS-5505 Ameliorates Multiple-Organ Fibrosis by Inhibiting Collagen Crosslinks in Rodent Models of Systemic Sclerosis

Systemic sclerosis (SSc) is characterised by progressive multiple organ fibrosis leading to morbidity and mortality. Lysyl oxidases play a vital role in the cross-linking of collagens and subsequent build-up of fibrosis in the extracellular matrix. As such, their inhibition provides a novel treatment paradigm for SSc. A novel small molecule pan-lysyl oxidase inhibitor, PXS-5505, currently in clinical development for myelofibrosis treatment was evaluated using in vivo rodent models resembling the fibrotic conditions in SSc. Both lysyl oxidase and lysyl oxidase-like 2 (LOXL2) expression were elevated in the skin and lung of SSc patients. The oral application of PXS-5505 inhibited lysyl oxidase activity in the skin and LOXL2 activity in the lung. PXS-5505 exhibited anti-fibrotic effects in the SSc skin mouse model, reducing dermal thickness and α-smooth muscle actin. Similarly, in the bleomycin-induced mouse lung model, PXS-5505 reduced pulmonary fibrosis toward normal levels, mediated by its ability to normalise collagen/elastin crosslink formation. PXS-5505 also reduced fibrotic extent in models of the ischaemia-reperfusion heart, the unilateral ureteral obstruction kidney, and the CCl4-induced fibrotic liver. PXS-5505 consistently demonstrates potent anti-fibrotic efficacy in multiple models of organ fibrosis relevant to the pathogenesis of SSc, suggesting that it may be efficacious as a novel approach for treating SSc.     

Electrochemical Synthesis of Magnetostrictive Fe–Ga/Cu Multilayered Nanowire Arrays with Tailored Magnetic Response

Arrays of nanowires are fabricated with alternating segments of the magnetostrictive alloy Fe_1–xGa_x and Cu using electrochemical deposition in nanoporous anodic aluminium oxide (AAO) templates. The difficult nature of Ga‐alloy electrochemistry is overcome by controlling mass‐transfer and hydrodynamic conditions using novel rotating disk electrode templates to obtain highly uniform segment lengths throughout the arrays. Extensive structural characterization by XRD, EBSD and TEM reveals a strong <110> textured Fe_1–xGa_x growth. Furthermore, using vibrating sample magnetometry (VSM), we demonstrate that control of magnetization reversal processes is possible once uniform aspect ratios are obtained for both the Fe–Ga and Cu segments.     

Whole grains — impact of consuming whole grains on physiological effects of dietary fiber and starch

Much of the present research on the physiological effects of dietary fiber and starch has been done on sources isolated from the parent material, and it is not clear whether they have the same effects if fed in the intact or whole grain. For dietary fiber, physiological effect depends on extent of fermentation in the large intestine, and this is influenced by chemical composition, solubility, physical form, and presence of lignin or other compounds. All of these factors are altered by isolation of a fiber source from the whole grain, and hence effects of eating fiber vary. Similarly, physical form and presence in the whole grain will affect digestibility of starch in the small intestine, which in turn influences the glycemic response and colonic effects determined by the extent of malabsorption and entry into the colon. Starch that enters the colon is fermented and produces short‐chain fatty acids, particularly butyrate, which is necessary to maintain a healthy mucosa. Hence, their presence within the whole grain may have important implications for health for both dietary fiber and starch. Evidence indicates that such effects are beneficial and that whole‐grain consumption should be encouraged.     

Plasmonic Nanoparticles as a Physically Unclonable Function for Responsive Anti‐Counterfeit Nanofingerprints

Far‐field scattering of randomly deposited Au nanoparticles (NPs) is demonstrated as a physically unclonable optical function for anti‐counterfeit applications in which the scattering patterns are easily produced yet impractical to replicate. Colloidal metal NPs are superb components for nanoscale labels owing to their small dimensions and intense far‐field scattering visible at wavelengths that depend on colloidal size, shape, composition, and their local environment. The feasibility of Au NP depositions as nanofingerprints is presented using a simple pattern matching algorithm. These NPs offer extended functionality as environmental sensors. Taking advantage of the local refractive index dependent scattering wavelengths of metal NPs, a detectable color change is also demonstrated from a nanofingerprint comprised of Au and Ag NPs when placed in media with different refractive index. The facile deposition method coupled with the intense scattering and optical response of metal NPs provides physically unclonable tags (nanofingerprints) with the ability to serve as tamper‐evident and aging labels.     

Correlation between chemical and electrical profiles in Si+, Se+ and S+ implanted bulk and epitaxial GaAs

We compare the chemical profiles of Cr, Mn, Si and Se with the electron concentration profiles in Si, Se and S implanted semi-insulating Cr-O doped bulk GaAs substrates and undoped VPE buffer layers annealed with and without a SiO₂ encapsulant in a H₂-As₄ atmosphere. A higher activation efficiency in the net electron concentration and the gateless saturated channel current is measured for SiO₂ encapsulated wafers annealed under arsine overpressure than for capless annealed ones using Cr-O doped bulk GaAs substrates. On the other hand, the net donor concentration peak is higher for implanted buffer epi layers capless annealed under arsine overpressure than for SiO₂ encapsulated ones. Secondary ion mass spectrometry (SIMS) studies of the Cr decoration of the implant damage indicate that the damage from the 100 keV Si implant anneals out at 840°C while a temperature of 900°C is required to anneal out the 260 keV Se implant damage. An explanation of these differences is provided using an impurity redistribution model and charge neutrality considerations. Excellent Hall electron mobilities at liquid nitrogen temperature of 5400–9200 cm²/V-sec are measured for Si-implanted buffer epi substrates.     

Inhibition of lipid oxidation by encapsulation of emulsion droplets within hydrogel microspheres

The purpose of this study was to assess whether the oxidation of polyunsaturated lipids could be inhibited by encapsulating them within protein-rich hydrogel microspheres (size range 1-100 μm). Filled hydrogel microspheres were fabricated as follows: (i) high methoxy pectin, sodium caseinate, and casein-coated lipid droplets were mixed at pH 7, (ii) the mixture was acidified (pH 5), (iii) casein was cross-linked using transglutaminase, (iv) the pH was adjusted to pH 7. Samples were stored in the dark at 55 °C and were monitored for lipid hydroperoxide formation and headspace propanal. Oxidation of fish oil (1% vol/vol) in the microspheres was compared with that in oil-in-water emulsions stabilised by either sodium caseinate or Tween 20. Emulsions stabilised by Tween 20 oxidised faster than either microspheres or emulsions stabilised by casein, while microspheres and the casein stabilised emulsion showed similar oxidation rates. Results highlight the natural antioxidant properties of food proteins.