Presence Of Incompatibility Research Articles

Compatibility study of mirtazapine with several excipients used in pharmaceutical dosage forms employing thermal and non-thermal methods

AbstractMirtazapine is an atypical antidepressant used in the management of insomnia, post-traumatic stress disorder, anxiety or panic disorder, obsessive–compulsive disorder and migraines. It is used worldwide in pharmaceutical formulations alongside various excipients in its hemihydrate form. The objective of the study was the compatibility evaluation between MRTHH and ten pharmaceutical excipients. The presence of incompatibilities between the API and the selected excipients was evaluated using Fourier transform infrared spectroscopy performed on all pure samples and prepared mixtures at room temperature (23 ± 2 °C), as well as a complete thermal stress evaluation (TG—thermogravimetric/DTG—derivative thermogravimetric/DSC—differential scanning calorimetry). The results showed particularities for all analyzed mixtures, α-lactose monohydrate, starch, sorbitol, magnesium stearate, calcium lactate and magnesium citrate proving to be safe to use together with mirtazapine in binary mixtures at temperatures below 130 °C, while for polyvinylpyrrolidone K30 and aerosol precautions need to be considered at temperatures over 100 °C. The association of mirtazapine with D-mannitol or stearic acid proved to raise concerns even at room temperature, indicating possible interactions that may alter the chemical integrity of the active pharmaceutical ingredient and with it, its therapeutic effect. These findings should be taken into consideration during the selection of the technological procedures used in the manufacturing process of dosage forms that include mirtazapine alongside with any of these excipients so that unwanted chemical interactions could be avoided.

Scheduling with complete multipartite incompatibility graph on parallel machines: Complexity and algorithms

In this paper, the problem of scheduling on parallel machines with a presence of incompatibilities between jobs is considered. The incompatibility relation can be modeled as a complete multipartite graph in which each edge denotes a pair of jobs that cannot be scheduled on the same machine.The paper provides several results concerning schedules, optimal or approximate with respect to the two most popular criteria of optimality: Cmax (makespan) and ∑Cj (total completion time). The problems are considered for a variety of machine types: identical, uniform and unrelated. The results consist of delimitation of the easy (polynomial) and NP-hard problems within these constraints. Also, polynomial-time exact algorithms are provided for easier problems and algorithms with a guaranteed constant worst-case approximation ratio for harder ones.In particular, there is provided a polynomial-time approximation scheme (PTAS) for scheduling with respect to ∑Cj on uniform machines, when the number of parts (i.e. sets of vertices constituting the mentioned graph) is bounded. The problem is addressed by developing a linear programming relaxation technique with appropriate rounding. This technique together with an exhaustive search (albeit in a manner controlled by the precision parameter) allows to provide the desired algorithm. For Cmax a PTAS is provided for the case of unit time jobs, but when the number of parts is part of the input. Interestingly, the latter result shows a connection between the considered problem of scheduling and covering problems.

Scheduling with Complete Multipartite Incompatibility Graph on Parallel Machines

In this paper we consider a problem of job scheduling on parallel machines with a presence of incompatibilities between jobs. The incompatibility relation can be modeled as a complete multipartite graph in which each edge denotes a pair of jobs that cannot be scheduled on the same machine. We provide several results concerning schedules, optimal or approximate with respect to the two most popular criteria of optimality: Cmax (makespan) and ∑Cj (total completion time). We consider a variety of machine types in our paper: identical, uniform, and unrelated. Our results consist of delimitation of the easy (polynomial) and NP-hard problems within these constraints. We also provide algorithms, either polynomial exact algorithms for the easier problems, or algorithms with a guaranteed constant worst-case approximation ratio. In particular, we fill the gap on research for the problem of finding a schedule with the smallest ∑Cj on uniform machines. We address this problem by developing a linear programming relaxation technique with an appropriate rounding, which to our knowledge is a novelty for this criterion in the considered setting.

Autism: Implications for high secure psychiatric care and move towards best practice

Background/aimsTo explore the role of high secure psychiatric care (HSPC) in the assessment and management of individuals with an Autism Spectrum Disorder (ASD) using published studies and clinical experience. Key areas of exploration include the prevalence of ASD within HSPC, some autism specific issues including clinical and cognitive characteristics, psychopathy and emotional regulation, presence of incompatibilities and use of seclusion, as well as experiences of being detained in HSPC. Developing best practice and a specialist ASD service in HSPC is also discussed. MethodA discussion of available literature, supported by clinical experience. ConclusionsAlthough individuals with an ASD admitted to HSPC comprise a small group, they are likely to be overrepresented relative to the general prevalence of ASD in the population and present with specific issues. Whilst individuals report a generally positive experience of HSPC, therapeutic outcomes are variable and the factors influencing them poorly understood. Staff knowledge and application of ASD theory and practice appears to have a significant influence on outcomes. Implications: Although best practice concerning ASD secure services will continue to be improved and developed, the role of HSPC in the assessment and management of some individuals with an ASD who present with complex needs and high risk behaviours remains clear.

Instability of Incompatible Bilayered Soft Tissues and the Role of Interface Conditions.

Mechanical stability analysis is instructive in explaining biological processes like morphogenesis, organogenesis, and pathogenesis of soft tissues. Consideration of the layered, residually stressed structure of tissues, requires accounting for the joint effects of interface conditions and layer incompatibility. This paper is concerned with the influence of imposed rate (incremental) interface conditions (RICs) on critical loads in soft tissues, within the context of linear bifurcation analysis. Aiming at simplicity, we analyze a model of bilayered isotropic hyperelastic (neo-Hookean) spherical shells with residual stresses generated by "shrink-fitting" two perfectly bonded layers with radial interfacial incompatibility. This setting allows a comparison between available, seemingly equivalent, interface conditions commonly used in the literature of layered media stability. We analytically determine the circumstances under which the interface conditions are equivalent or not, and numerically demonstrate significant differences between interface conditions with increasing level of layer incompatibility. Differences of more than tenfold in buckling and 30% in inflation instability critical loads are recorded using the different RICs. Contrasting instability characteristics are also revealed using the different RICs in the presence of incompatibility: inflation instability can occur before pressure maximum, and spontaneous instability may be excluded for thin shells. These findings are relevant to the growing body of stability studies of layered and residually stressed tissues. The impact of interface conditions on critical thresholds is significant in studies that use concepts of instability to draw conclusions about the normal development and the pathologies of tissues like arteries, esophagus, airways, and the brain.

An approach via generating functions to compute power indices of multiple weighted voting games with incompatible players

We introduce a new generating function based method to compute the Banzhaf, Deegan–Packel, Public Good (a.k.a. the Holler power index) and Shapley–Shubik power indices in the presence of incompatibility among players. More precisely, given a graph $$G=\left( V,E\right) $$ with V the set of players and E the edge set, our extension involves multiple weighted voting games (MWVG’s) and incompatible players, i.e., pairs of players belonging to E are not allowed to cooperate. The route to obtain the aforementioned generating functions comprises the use of a key lemma characterizing the set of minimal winning coalitions of the game with incompatibility due to Alonso-Meijide et al. (Appl Math Comput 252(1):377–387, 2015), a tool from combinatorial analysis, namely, the Omega calculus in partition analysis, and basic tools borrowed from commutative algebra involving the computation of certain quotients of polynomial rings module polynomial ideals. Using partition analysis, we obtain new generating functions to compute the Deegan–Packel and Public Good power indices with incompatibility leading to lower time complexity than previous results of Chessa (TOP 22(2):658–673, 2014) and some results of Alonso-Meijide et al. (Appl Math Comput 219(8):3395–3402, 2012). Using a conjunction of partition analysis and commutative algebra, we extend to MWVG’s the generating function approach to compute the Banzhaf and Shapley–Shubik power indices in the presence of incompatibility. Finally, an example taken from the real-world, i.e., the European Union under the Lisbon Treaty, is used to illustrate the usefulness of the Omega package, a symbolic computational package that implements the Omega calculus in Mathematica, due to Andrews et al. (Eur J Comb 22(7):887–904, 2001) in the context of MWVG’s by computing the PG power index of the associated voting game.

High Time Resolution Time-Lapse Imaging Reveals Continuous Existence and Rotation of Stress Fibers under Cyclic Stretch in HUVEC

Cells under cyclic stretch sense their environments and induce responses such as actin stress fiber (SF) reorientation and morphological changes. These physiological responses are thought to occur when cells sense incompatibility between SF orientation and stretching direction. This hypothesis requires existence of SFs. However, such existence of SFs in cells under cyclic stretch remains unclear since few studies attempted to track the existence of SFs throughout cyclic stretch. In order to track the existence of SFs throughout cyclic stretch, high time resolution time-lapse imaging was improved in two points. First, SFs were clearly imaged with coexpression of DsRed-zyxin and GFP-actin. Second, time resolution was improved so that fluorescence images were obtained every 28 sec. With the improved high time resolution time-lapse imaging, it was revealed, for the first time, that SFs could exist continuously throughout cyclic stretch. Moreover, physiological responses including morphological change as well as SF reorientation occurred during the time when SFs formed incompatibility between SF orientation and stretching direction. These results demonstrated that SFs continuously existed in cells under cyclic stretch and in turn suggested that continuous presence of incompatibility between orientation of long-lasting SFs and the stretching direction might be important for mechanosensing which induces physiological responses.

Category-Based Screening in Choice of Complementary Products

Consumers often make complex choices involving complementary categories, such as cell phones and service plans. In the fast-growing high-tech and entertainment industries, products from complementary categories are often incompatible with one another. This research shows that when choosing a pair of such complementary products, a consumer is likely to use a two-stage decision strategy: screening by one category first to narrow down the number of pairs for further evaluation in the second stage. In the presence of incompatibility, screening by one category rather than by the other may lead to different choice outcomes. The authors develop a behavioral theory–driven choice model that accounts for both preference heterogeneity and structural heterogeneity of decision strategies to examine the extent to which consumers engage in category-based screening. Analysis of data from a 2 × 2 conjoint choice experiment reveals that consumers tend to screen a category that has higher intracategory differentiation and is congruent with their decision goals. The authors further suggest possible marketing actions a firm can take to promote the use of a specific decision strategy that leads consumers to choose its product.

Influence of manufacturing procedure on stability of Unguentum contra perniones preparations

Application of various technological procedures for the manufacture of officinal preparation ointment against chilblains (Unguentum contra perniones) produce essential variations in the quality and stability of the final product. Changing the sequence of admixing active substances into the ointment base indicated the presence of incompatibility between the active substances, as well as between the active substances and the ointment base components. The aim was to examine the influence of various technological manufacturing procedures on quality and stability of the preparation. Changes in the samples of ointments and aqueous solutions of active substances were analysed microscopically. Microscopic analysis of hydrosoluble active substance solutions demonstrated destruction of ichthammol, induced by an acidic medium due to the dissolution of tannin and resorcinol, which is well known from the literature. It also demonstrated the destruction of tannin and resorcinol in aqueous solution, which had not been described in the literature. Application of the prescribed procedure for the manufacturing of ointment against chilblains, conceals the incompatibility reactions due to a slow dissolution of the tannin suspended in the officinal ointment base Unguentum cera lanae. Admixture of an ready-made aqueous solution of tannin caused an instant contact between ichthammol and the acidic medium, which caused the destruction or the complete absence of the formation of emulsion droplets. The problem of incompatibility reactions between lanolin alcohols in the ointment base and ichthammol and resorcinol, as well as the reaction between Peruvian balsam and sulfur from the ichthammol sulfate ion was observed. Numerous incompatibility reactions of ointment against chilblains, components indicated that it was necessary to introduce alterations in both the qualitative and quantitative composition of the preparation. Excipient preparation procedure, as well as the technological procedure for incorporation of active ingredients can cause the incompatibilities and therefore the formulation stability problems.

Coevolution of the major histocompatibility complex and the t-complex in the mouse. I. Generation and maintenance of high complementarity associations.

A quantitative model is developed to explore the effects of prezygotic and postzygotic incompatibility on the origin and maintenance of associations between the major histocompatibility complex (MHC) and the t-complex in the mouse. Incompatibility is represented by a reduction in the rate of conception or gestation of offspring derived from sperm bearing MHC antigens in common with the mother. Incompatibility encourages the evolution of associations from a state of complete independence between the two complexes by promoting the invasion of all novel antigens, including those that exhibit associations with the t-complex. Incompatibility can modify the relative numbers of antigens associated with each haplotype by actively promoting the exclusion or invasion of recombinants that bear formerly +-specific or t-specific antigens on the alternative haplotype. The results of the analysis indicate that the state of complete independence between the MHC and the t-complex is not preserved over evolutionary time in the presence of incompatibility. Further, the expression of incompatibility maintains fully associated states that include a single antigen associated with the t-haplotype and up to three to five antigens associated with the +-haplotype within a single population.

ABH incompatible bone marrow transplantation: removal of erythrocytes by starch sedimentation.

Nineteen patients with acute leukaemia underwent bone marrow transplantation despite major ABH incompatibility between donor and recipient. The marrow inoculum was prepared prior to infusion by admixture with hydroxyethyl starch to sediment the incompatible erythrocytes, which were then discarded. The infusion was well tolerated with two patients developing transient haemoglobinuria, seven patients developing low grade fever and 10 experiencing no reaction. Durable haematopoietic engraftment was achieved in the 18 evaluable patients and was not influenced by pre-transplant isohaemagglutinin titres. No difference in time to engraftment, incidence of GVHD or in overall survival was found, compared to ABH compatible transplants. Therefore, the presence of incompatibility did not appear to influence transplant outcome adversely. The technique described is a rapid and safe method for overcoming the ABH barrier in marrow transplantation.