Discretization-Based Feature Selection as a Bilevel Optimization Problem

Discretization-based feature selection (DBFS) approaches have shown interesting results when using several metaheuristic algorithms, such as particle swarm optimization (PSO), genetic algorithm (GA), ant colony optimization (ACO), etc. However, these methods share the same shortcoming which consists in encoding the problem solution as a sequence of cut-points. From this cut-points vector, the decision of deleting or selecting any feature is induced. Indeed, the number of generated cut-points varies from one feature to another. Thus, the higher the number of cut-points, the higher the probability of selecting the considered feature; and vice versa. This fact leads to the deletion of possibly important features having a single or a low number of cut-points, such as the infection rate, the glycemia level, and the blood pressure. In order to solve the issue of the dependency relation between the feature selection (or removal) event and the number of its generated potential cut-points, we propose to model the DBFS task as a bilevel optimization problem and then solve it using an improved version of an existing co-evolutionary algorithm, named I-CEMBA. The latter ensures the variation of the number of features during the migration process in order to deal with the multimodality aspect. The resulting algorithm, termed bilevel discretization-based feature selection (Bi-DFS), performs selection at the upper level while discretization is done at the lower level. The experimental results on several high-dimensional datasets show that Bi-DFS outperforms relevant state-of-the-art methods in terms of classification accuracy, generalization ability, and feature selection bias

MONTELUKAST SPRAY DRIED MICROPARTICLES: PREPARATION, EXCIPIENTS SELECTION AND IN VITRO PULMONARY DEPOSITION

Objective: This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted microparticles using the spray drying technique.Methods: The effect of addition of different excipients namely: mannitol, leucine and ovalbumin on the physico-chemical characteristics of MTK spray dried powders were investigated. Powder flow properties, drug association efficiency as well as microparticle size and mass median aerodynamic diameter were determined. The prepared microparticles were characterized using FT-IR and TGA. The powder crystallographic and thermal properties were studied using DSC and X-ray powder diffraction. A twin stage impinger was used to evaluate in vitro pulmonary deposition from which the inhalation indices were derived.Results: The tested excipients showed no adverse chemical interactions with the drug based on FT-IR. The best inhalation indices were obtained with powders spray dried with leucine followed by leucine/mannitol mixtures with MMAD of 1.73±0.08 and 1.36±0.16 and fine particle fraction of 60.55±1.63 and 52.31±3.52, respectively. The dried powders showed good physico-chemical stability for up to 6 mo storage.Conclusion: The developed MTK spray dried particles may offer a good platform for the targeted pulmonary delivery of MTK overcoming the major biological barriers

Liquid chromatographic-mass spectrometric method for determination of drug content uniformity of two commonly used dermatology medications in a split-tablet dosage form

Purpose: To develop and validate a simple, efficient and reliable Liquid  chromatographic-mass spectrometric (LC-MS/MS) method for the quantitative determination of two dermatological drugs, Lamisil® (terbinafine) and Proscar® (finasteride), in split tablet dosage form.Methods: Thirty tablets each of the 2 studied medications were randomly selected. Tablets were weighed and divided into 3 groups. Ten tablets of each drug were kept intact, another group of 10 tablets were manually split into halves using a tablet cutter and weighed with an analytical balance; a third group were split into quarters and weighed. All intact and split tablets were individually dissolved in a water: methanol mixture (4:1), sonicated, filtered and further diluted with mobile phase. Optimal chromatographic separation and mass spectrometric detection were achieved using an Agilent 1200 HPLC system coupled with an Agilent 6410 triple quadrupole mass spectrometer. Analytes were eluted through an Agilent eclipse plus C8 analytical column (150 mm × 4.6 mm, 5 μm) with a mobile phase composed of solvent A (water) containing 0.1% formic acid and 5mM ammonium formate pH 7.5, and solvent B (acetonitrile mixed with water in a ratio A:B 55:45) at a flow rate of 0.8 mL min-1 with a total run time of 12 min. Mass spectrometric detection was carried out using positive ionization mode with analyte quantitation monitored by multiple reaction monitoring (MRM) mode.Results: The proposed analytical method proved to be specific, robust and  adequately sensitive. The results showed a good linear fit over the concentration range of 20 - 100 ng mL-1 for both analytes, with a correlation coefficient (r2) ≥ 0.999 and 0.998 for finasteride and terbinafine, respectively. Following tablet splitting, the drug content of the split tablets fell outside of the proxy USP  specification for at least 14 halves (70 %) and 34 quarters (85 %) of FIN, as well as 16 halves (80 %) and 37 quarters (92.5 %) of TBN. Mean weight loss, after splitting, was 0.58 and 2.22 % for FIN half- and quarter tablets, respectively, and 3.96 and 4.09 % for TBN half- and quarter tablets,respectively.Conclusion: The proposed LC-MS/MS method has successfully been used to provide precise drug content uniformity of split tablets of FIN and TBN. Unequal distribution of the drug on the split tablets is indicated by the high standard deviation beyond the accepted value. Hence, it is recommended not to split non-scored tablets  especially, for those medications with significant toxicityKeywords: Tablet splitting, Finasteride, Terbinafine, Drug content uniformity,  LC-MS/M

Adaptive work in the primary health care response to domestic violence in occupied Palestinian Territory:a qualitative evaluation using Extended Normalisation Process Theory

BACKGROUND: A health system response to domestic violence against women is a global priority. However, little is known about how these health system interventions work in low-and-middle-income countries where there are greater structural barriers. Studies have failed to explore how context-intervention interactions affect implementation processes. Healthcare Responding to Violence and Abuse aimed to strengthen the primary healthcare response to domestic violence in occupied Palestinian territory. We explored the adaptive work that participants engaged in to negotiate contextual constraints. METHODS: The qualitative study involved 18 participants at two primary health care clinics and included five women patients, seven primary health care providers, two clinic case managers, two Ministry of Health based gender-based violence focal points and two domestic violence trainers. Semi-structured interviews were used to elicit participants' experiences of engaging with HERA, challenges encountered and how these were negotiated. Data were analysed using thematic analysis drawing on Extended Normalisation Process Theory. We collected clinic data on identification and referral of domestic violence cases and training attendance. RESULTS: HERA interacted with political, sociocultural and economic aspects of the context in Palestine. The political occupation restricted women's movement and access to support services, whilst the concomitant lack of police protection left providers and women feeling exposed to acts of family retaliation. This was interwoven with cultural values that influenced participants' choices as they negotiated normative structures that reinforce violence against women. Participants engaged in adaptive work to negotiate these challenges and ensure that implementation was safe and workable. Narratives highlight the use of subterfuge, hidden forms of agency, governing behaviours, controls over knowledge and discretionary actions. The care pathway did not work as anticipated, as most women chose not to access external support. An emergent feature of the intervention was the ability of the clinic case managers to improvise their role. CONCLUSIONS: Flexible use of ENPT helped to surface practices the providers and women patients engaged in to make HERA workable. The findings have implications for the transferability of evidenced based interventions on health system response to violence against women in diverse contexts, and how HERA can be sustained in the long-term

A simple lattice Boltzmann model for conjugate heat transfer research

In this paper a lattice Boltzmann (LB) model is proposed for conjugated heat transfer research. Through taking the most advantages of the standard LB method, the present model can remedy the shortcomings of the available related LB models via a simple way and meanwhile a number of intrinsic advantages of the standard LB method are preserved. It does not require any specific treatment dependent on interface topology and independent from the choice of lattice model. Moreover, it can be used for unsteady problems with complicated and time dependent interfaces. The accuracy and reliability of the present model are validated by three nontrivial benchmark tests. The good agreements between the present numerical prediction and available open data demonstrate the applicability of the present model for complicated conjugated heat transfer problems. Finally, the present model could be extended to some other important areas straightforwardly, such as fluid–solid phase change modeling

Simulated dynamics of optically pumped dilute nitride 1300 nm spin vertical-cavity surface-emitting lasers

The authors report a theoretical analysis of optically pumped 1300 nm dilute nitride spin-polarised vertical-cavity surface-emitting lasers (VCSELs) using the spin-flip model to determine the regions of stability and instability. The dependence of the output polarisation ellipticity on that of the pump is investigated, and the results are presented in twodimensional contour maps of the pump polarisation against the magnitude of the optical pump. Rich dynamics and various forms of oscillatory behaviour causing self-sustained oscillations in the polarisation of the spin-VCSEL subject to continuouswave pumping have been found because of the competition of the spin-flip processes and birefringence. The authors also reveal the importance of considering both the birefringence rate and the linewidth enhancement factor when engineering a device for high-frequency applications. A very good agreement is found with the experimental results reported by the authors' group. © The Institution of Engineering and Technology 2014

Multistage Fragmentation of Ion Trap Mass Spectrometry System and Pseudo-MS 3

A new approach was recently introduced to improve the structure elucidation power of tandem mass spectrometry simulating the MS3 of ion trap mass spectrometry system overcoming the different drawbacks of the latter. The fact that collision induced dissociation in the triple quadrupole mass spectrometer system provides richer fragment ions compared to those achieved in the ion trap mass spectrometer system utilizing resonance excitation. Moreover, extracting comprehensive spectra in the ion trap needs multistage fragmentation, whereas similar fragment ions may be acquired from one stage product ion scan using the triple quadrupole mass spectrometer. The new strategy was proven to enhance the qualitative performance of tandem mass spectrometry for structural elucidation of different chemical entities. In the current study we are endeavoring to prove our hypothesis of the efficiency of the new pseudo-MS3 technique via its comparison with the MS3 mode of ion trap mass spectrometry system. Ten pharmacologically and synthetically important (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones (enaminones 4a–j) were chosen as model compounds for this study. This strategy permitted rigorous identification of all fragment ions using triple quadrupole mass spectrometer with sufficient specificity. It can be used to elucidate structures of different unknown components. The data presented in this paper provide clear evidence that our new pseudo-MS3 may simulate the MS3 of ion trap spectrometry system

Arsenic trioxide induces accumulation of cytotoxic levels of ceramide in acute promyelocytic leukemia and adult T-cell leukemia/lymphoma cells through de novo ceramide synthesis and inhibition of glucosylceramide synthase activity

Background and Objectives Arsenic trioxide (ATO) is an effective treatment for acute promyelocytic leukemia (APL) and potentially for human T-cell leukemia virus type I (HTLV-I) associated adult T-cell leukemia/lymphoma (ATL). Many cytotoxic drugs induce apoptosis through the generation and accumulation of the sphingolipid breakdown product, ceramide, a coordinator of the cellular response to stress. We, therefore, investigated the contribution of ceramide to the mechanism of action of ATO in APL and ATL.Design and Methods A human APL-derived cell line (NB4), various ATL-derived lines and an HTLV-I-negative malignant T-cell line were cultured and treated with ATO. Growth and apoptosis assays were conducted. Measurements were made of ceramide, diacylglycerol, sphingomyelinase activity, sphingomyelin mass, glucosylceramide synthase activity and the de novo ceramide synthesis.Results Treatment of APL and ATL-derived cells with a clinically achievable concentration of ATO induced accumulation of cytotoxic levels of ceramide. The effects of ATO on ceramide levels in APL cells were more potent than those of all-trans retinoic acid (ATRA). ATO downregulated neutral sphingomyelinase activity. In contrast to the effect of ATRA, ATO-induced ceramide accumulation was not due to induction of acidic sphingomyelinase, but rather resulted from both de novo ceramide synthesis and inhibition of glucosylceramide synthase activity. Interestingly, the effects of ATO on de novo ceramide synthesis were similar in APL and ATL-derived cells despite the defective pathway in ATL cells.Interpretation and Conclusions These results indicate that ATO-induced ceramide accumulation may represent a general mediator of the effects of ATO, which paves the way for new therapeutic interventions that target the metabolic pathway of this important sphingolipid secondary messenger

Effects of Goat Manure Fertilization on Grain Nutritional Value in Two Contrasting Quinoa (Chenopodium quinoa Willd.) Varieties Cultivated at High Altitudes

In this study, the effects of goat manure fertilization (2, 4, 8, and 12 Tn/ha) on the grain yield, organic compounds, and mineral composition of two quinoa varieties (CICA-17 and Regalona Baer) were evaluated under field conditions in Northwest Argentina. The results indicate that fertilization improved the quinoa grain yield and total protein content. Low manure doses positively affected the fatty acid (FA) profile, and significant changes were determined for the monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid contents of CICA-17 and on the saturated fatty acid (SFA) contents of R. Baer seeds. The amino acid contents were positively affected in CICA-17 and negatively in R. Baer. Soluble sugars (glucose, fructose, and sucrose), major elements (K, Si, P, Mg, Ca, and Na), minor elements (Fe, Mn, Al, Zn, and Cu), and ultratrace elements (Cr and Li) were detected and discussed in terms of their impact on human nutrition and health. Conclusively, manure addition affected some essential amino acids, the desaturase activity, the n6:n3 and SFA/UFA ratios, the atherogenic index, soluble sugars, and mineral content, and the fatty acid metabolism of each variety was differently affected, especially the C16 and C18 desaturase activity, which responded differently to various manure doses. Manure addition is a promising alternative to improve the nutritional quality and functionality of quinoa grains, but the response is not linear

The future of interpretive accounting research:A Polyphonic Debate

In 1997-99 the three of us organised a series of European Commission funded conferences aimed at building a network of young researchers in the area of accounting. At the time “young” was defined by the Commission as researchers under 35 years of age (allowing for maternity leave or national service). Over the intervening years our network had grown and we wanted to try and take stock of the field in which we had now been working for a surprising number of years. To that Page 1 of 29 Accepted Manuscript 2 end we put together the above email and a broad invitation list of people who had been at those first meetings, and others of the same generation (or even younger) whom we had met since. About half of those originally contacted managed to make the meeting where we spent a stimulating couple of hours of debate on the topics raised below—so stimulating that we developed a collective desire to leave a trace of the discussion. Writing a traditional paper with so many, so widely dispersed authors was not going to work. Instead we came up with a different form of collective writing that mirrored the original debate, and that might contribute to ongoing debates in this journal concerning the nature and status of our research (e.g. Arrington, 2004; Inanga & Schneider, 2005; Macintosh, 2004). We agreed a process in which each of us in turn would have one week to add a target of 300 words to a rolling document, going through the contributors alphabetically. After two rounds we would see what we had got