An adaptive version of k-medoids to deal with the uncertainty in clustering heterogeneous data using an intermediary fusion approach

This paper introduces Hk-medoids, a modified version of the standard k-medoids algorithm. The modification extends the algorithm for the problem of clustering complex heterogeneous objects that are described by a diversity of data types, e.g. text, images, structured data and time series. We first proposed an intermediary fusion approach to calculate fused similarities between objects, SMF, taking into account the similarities between the component elements of the objects using appropriate similarity measures. The fused approach entails uncertainty for incomplete objects or for objects which have diverging distances according to the different component. Our implementation of Hk-medoids proposed here works with the fused distances and deals with the uncertainty in the fusion process. We experimentally evaluate the potential of our proposed algorithm using five datasets with different combinations of data types that define the objects. Our results show the feasibility of the our algorithm, and also they show a performance enhancement when comparing to the application of the original SMF approach in combination with a standard k-medoids that does not take uncertainty into account. In addition, from a theoretical point of view, our proposed algorithm has lower computation complexity than the popular PAM implementation

Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

<p>Abstract</p> <p>Background</p> <p>To identify the genetic defect associated with autosomal recessive congenital cataract (ARCC), mental retardation (MR) and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families.</p> <p>Methods</p> <p>We screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes <it>PAX6</it>, <it>PITX3 </it>and <it>HSF4 </it>are expressed in human brain and one gene <it>LIM2 </it>encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development. All genes were screened by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly.</p> <p>Results</p> <p>We report no mutation in the four genes of congenital cataract and its flanking regions. Only variations that did not segregate with the studied phenotypes (ARCC associated to MR, ARCC associated with MR and microcephaly) are reported. We detected three intronic variations in <it>PAX6 </it>gene: IVS4 -274insG (intron 4), IVS12 -174G>A (intron12) in the four studied families and IVS4 -195G>A (intron 4) in two families. Two substitutions polymorphisms in <it>PITX3 </it>gene: c.439 C>T (exon 3) and c.930 C>A (exon4) in one family. One intronic variation in <it>HSF4 </it>gene: IVS7 +93C>T (intron 7) identified in one family. And three intronic substitutions in <it>LIM2 </it>gene identified in all four studied families: IVS2 -24A>G (intron 2), IVS4 +32C>T (intron 4) and c.*15A>C (3'-downstream sequence).</p> <p>Conclusion</p> <p>Although the role of the four studied genes: <it>PAX6</it>, <it>PITX3</it>, <it>HSF4 </it>and <it>LIM2 </it>in both ocular and central nervous system development, we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, MR and microcephaly.</p

Synthèse, étude toxicologique et activité psychotrope de nouvelles arylidènpyridazin-3-ones N-substituées

Les d&eacute;riv&eacute;s oxyg&eacute;n&eacute;s de la pyridazine sont connus en th&eacute;rapeutique pour la richesse de leurs potentiels pharmacologiques&nbsp;: antihypertenseur et cardiotonique. Des propri&eacute;t&eacute;s antibact&eacute;riennes sont &eacute;galement mentionn&eacute;es dans la litt&eacute;rature. De ces consid&eacute;rations, r&eacute;sulte l&rsquo;id&eacute;e de synth&eacute;tiser et d&rsquo;&eacute;tudier de nouvelles s&eacute;ries d&rsquo;arylid&egrave;npyridazin-3-ones substitu&eacute;es sur le plan toxicologique, et d&rsquo;explorer leur activit&eacute; psychotrope. L'&eacute;tude de l&rsquo;activit&eacute; pharmacologique a d&eacute;montr&eacute; que ces produits ne sont pas toxiques aux doses th&eacute;rapeutiques et qu'ils sont dou&eacute;s d'effets s&eacute;datif, myorelaxant, anxiolytique mais, ne pr&eacute;sentent pas d&rsquo;effet hypnotique, ni cataleptique. Cependant, ces trois produits de synth&egrave;se potentialisent &agrave; des degr&eacute;s diff&eacute;rents l'effet hypnotique du diazepam.&nbsp;Synthesis, toxicological study and psychotropic activity of new arylidenpyridazin-3-ones N-substituted. The oxygenated derivatives of pyridazin are known into therapeutic for the richness of their pharmacological potentials: antihypertensive and cardiotonic. Properties antibacteriennes are also mentioned in the literature. From these considerations, results the idea to synthesize and study new series of arylidenpyridazin-3-ones N-substituted on the toxicological level, but also, to explore their possible activity on the central nervous system, in particular the psychotropic activity. The study of the pharmacological activity has shown that these products are not toxic at therapeutic doses and possess sedative, muscle relaxant, anxiolytic effects, but do not present any hypnotic, or catalepsy effect. However, these three products potentiate synthesis to different degrees of the hypnotic effect diazepam.&nbsp

Perception of tobacco, cannabis, and alcohol use of others is associated with one's own use.

BACKGROUND: Interventions have been developed to reduce overestimations of substance use among others, especially for alcohol and among students. Nevertheless, there is a lack of knowledge on misperceptions of use for substances other than alcohol. We studied the prevalence of misperceptions of use for tobacco, cannabis, and alcohol and whether the perception of tobacco, cannabis, and alcohol use by others is associated with one's own use. METHODS: Participants (n=5216) in a cohort study from a census of 20-year-old men (N=11,819) estimated the prevalence of tobacco and cannabis use among peers of the same age and sex and the percentage of their peers drinking more alcohol than they did. Using the census data, we determined whether participants overestimated, accurately estimated, or underestimated substance use by others. Regression models were used to compare substance use by those who overestimated or underestimated peer substance with those who accurately estimated peer use. Other variables included in the analyses were the presence of close friends with alcohol or other drug problems and family history of substance use. RESULTS: Tobacco use by others was overestimated by 46.1% and accurately estimated by 37.3% of participants. Cannabis use by others was overestimated by 21.8% and accurately estimated by 31.6% of participants. Alcohol use by others was overestimated by more than half (53.4%) of participants and accurately estimated by 31.0%. In multivariable models, compared with participants who accurately estimated tobacco use by others, those who overestimated it reported smoking more cigarettes per week (incidence rate ratio [IRR] [95% CI], 1.17 [range, 1.05, 1.32]). There was no difference in the number of cigarettes smoked per week between those underestimating and those accurately estimating tobacco use by others (IRR [95% CI], 0.99 [range, 0.84, 1.17]). Compared with participants accurately estimating cannabis use by others, those who overestimated it reported more days of cannabis use per month (IRR [95% CI], 1.43 [range, 1.21, 1.70]), whereas those who underestimated it reported fewer days of cannabis use per month (IRR [95% CI], 0.62 [range, 0.23, 0.75]). Compared with participants accurately estimating alcohol use by others, those who overestimated it reported consuming more drinks per week (IRR [95% CI], 1.57 [range, 1.43, 1.72]), whereas those who underestimated it reported consuming fewer drinks per week (IRR [95% CI], 0.41 [range, 0.34, 0.50]). CONCLUSIONS: Perceptions of substance use by others are associated with one's own use. In particular, overestimating use by others is frequent among young men and is associated with one's own greater consumption. This association is independent of the substance use environment, indicating that, even in the case of proximity to a heavy-usage group, perception of use by others may influence one's own use. If preventive interventions are to be based on normative feedback, and their aim is to reduce overestimations of use by others, then the prevalence of overestimation indicates that they may be of benefit to roughly half the population; or, in the case of cannabis, to as few as 20%. Such interventions should take into account differing strengths of association across substances

Liposomal budesonide for dry powder inhaler: Preparation and stabilization

The purpose of the study was to prepare stable liposomally entrapped budesonide (BUD) for a dry powder inhaler (DPI) formulation. BUD liposomes composed of egg phosphatidyl choline and cholesterol were prepared by lipid film hydration technique and sonicated to have the desired size (<5 μm). A rapid method was used for separation of free drug by centrifugation at a lower centrifugal force (G value). Liposomal dispersion was subjected to lyophilization after blending BUD with cryoprotectant in varying bulk and mass ratios, and percent drug remaining entrapped after lyophilization was optimized. Comparative drug retention studies on storage of DPI formulations were carried out in accordance with International Conference on Harmonization guidelines. Critical relative humidity of the formulations was determined and reported as one of the manufacturing controls. Sucrose was found to be the most effective cryoprotectant when present on both sides of the lamellae of liposomes in a bulk strength of 500 mM and mass ratio of lipid:sugar; 1∶10. Blending of sorbolac before lyophilization showed better retention of encapsulated drug (95.59%). The respirable fraction of the product (20.69±1.50%) was comparable with that of the control (26.49±1.52%), suggesting that the liposomal BUD can be successfully delivered throughout the broncho-pulmonary tree. The findings demonstrate that liposome of BUD can be prepared with a high entrapment value, stabilized by lyophilization, and delivered as an aerosolized DPI. The stability studies of lyophilized product suggests a shelf-life of one year when stored under refrigeration (2°C–8°C)