Reconstituted State Research Articles

Development and Stability Study of Oseltamivir Reconstitutable Dry Suspension from Capsules

Oseltamivir phosphate (OSEL) is recommended for the prevention and treatment of influenza virus infection. In a hospital pharmacy, OSEL liquid extemporaneous preparation is generally compounded on a case-by-case basis from the capsules because it can be stored for a certain period. Therefore, the objective of the current research was to develop an oseltamivir reconstitutable dry suspension (ORDS), and to evaluate the stability of the ORDS. The dry-suspending vehicles were first developed and subjected to stability tests. The stable vehicle was selected to mix with the content of OSEL capsules and dry powder was termed ORDS. The stability of ORDS was then tested in both dried and reconstituted states. It was found that the dry vehicle using xanthan gum as a suspending agent (at 0.25% w/v of the reconstituted suspension) was the most stable formulation at 25°C and 45°C under 75% relative humidity (RH) for 28 days. Upon mixing with OSEL capsule contents, ORDS in the dried state showed no change in either physical or chemical properties after storing at room temperature for 7 days. For the reconstituted state, the ORDS showed no change in odor and pH after storing at 2°C to 8°C in a refrigerator, and 25°C and 45°C under 75%RH for 14 days. However, its color was slightly darker after storing at 45°C. The percentage remaining OSEL at the refrigerator temperatures was 98.13% ± 1.63%, at 25°C was 100.30% ± 0.71% and at 45°C was 97.54% ± 1.38%. In conclusion, ORDS may be a convenient alternative to extemporaneous preparations. Keywords: Oseltamivir capsule, Reconstitutable dry suspension, Extemporaneous, Physico-chemical stability, Influenza

Bureaucratic fragmentation by design? the case of payroll management in the democratic Republic of Congo

ABSTRACT This paper examines the sources of bureaucratic fragmentation and coherence in the Democratic Republic of Congo by exploring the connections and tensions between interface bureaucracies and the back-office administration tasked with managing the public payroll system. Building on the ‘real governance’ literature and the notion of ‘infrastructural power’, we analyse the recent history of payroll management in Congo and especially its evolution over the last decades of state implosion and reconstruction so as to gauge the potential of different drivers of state infrastructural power. The return of the state in the first decades of the twenty-first century led to a spectacular and unprecedented growth in the number of civil servants, made possible by a reconstituted state budget and renewed donor engagement. Yet this growth largely reflects increased political competition and further disarticulated the payroll system, increasing its vulnerability to the issue of ghost workers. The case study shows important trade-offs, in processes of post-conflict reconstruction, between the triple objectives of building state infrastructural power, making use of it to improve public service delivery, and its democratization.

Interrogating Unemployment Amid Growth: Tracking Youth Unemployment in Neo-Liberal Uganda, 1990–2019

The paper interrogates the paradox of persistent youth unemployment amid an upswing of impressive economic growth after Neo-liberal reforms in Uganda. The government of Uganda undertook targeted interventions to ameliorate youth unemployment, which escalated. Why was the growing economy failing to absorb labour? Why were the interventions failing? We argue that the interplay of the skewed neo-liberal and global architecture, decline of traditional labour absorbing sectors, and the debilitating syncretic ‘informal’ sector constrained sustainable youth employment and deflated interventions. The paper opines that Uganda’s neo-liberal capitalism was unique, as it was structured in a way that did not enhance domestic actors and sectors, which would have increased sustainable labour absorption and utilisation. Otherwise, Uganda’s celebratory growth was largely aid-driven and in the controversial and constrained informal sector, limited service ‘enterprises’ and import consumerism, which undermined domestic productivity and employability. Neo-liberalism and the reconstituted state did not align the domestic and global economic structures for meaningful employment. Unemployment spiralled into the socio-political landscape, while youth agency strived for better positioning.

Structural features and stability of apo- and holo-forms of a simple iron-sulfur protein.

Iron-sulfur centers are widespread in living organisms, mostly performing electron transfer functions, either in electron transfer chains or as part of multi-enzymatic complexes, while being also present in enzyme active sites, handling substrate catalysis. Rubredoxin is the simplest iron-sulfur containing protein constituted by a single polypeptide chain of 50 to 60 amino acids, of which four cysteine residues are responsible for metal binding in a tetrahedral coordination sphere. In this manuscript we explore the structure and stability of both apo- and holo-forms of a Rubredoxin from Marinobacter hydrocarbonoclasticus using Synchrotron Radiation Circular Dichroism (SRCD) in combination with other biochemical and spectroscopic techniques. The results are consistent with a holo-protein form containing a monomeric iron center with UV-visible maxima at 760, 578, 494, 386, 356and 279nm, an intense EPR resonance with a g value around 4.3 and Mössbauer spectroscopy parameters of δ equal to 0.69mm/s and ΔEQ equal to 3.25mm/s, for the ferrous reconstituted state. SRCD data, obtained for the first time for the apo-form, show a quite defined structure with ∆ε maximum at 191nm and minima at 203 and 231nm. Most significantly, the presence of isosbestic points at 189 and 228nm made the interconversion between the two stable apo- and holo-form solution structures clear. SRCD temperature dependence data shows that for both forms the denaturation process proceeds through an intermediate species.

Marxism and the Solidarity Economy: Toward a New Theory of Revolution

In the twenty-first century, it is time that Marxists updated the conception of socialist revolution they have inherited from Marx, Engels, and Lenin. Slogans about the “dictatorship of the proletariat” “smashing the capitalist state” and carrying out a social revolution from the commanding heights of a reconstituted state are completely obsolete. In this article I propose a reconceptualization that accomplishes several purposes: first, it explains the logical and empirical problems with Marx’s classical theory of revolution; second, it revises the classical theory to make it, for the first time, logically consistent with the premises of historical materialism; third, it provides a (Marxist) theoretical grounding for activism in the solidarity economy, and thus partially reconciles Marxism with anarchism; fourth, it accounts for the long-term failure of all attempts at socialist revolution so far. In serving these functions, the revision I propose finally “modernizes” and corrects Marx’s conception of revolution.

Consolidation characteristics of a thermally cured sand–bentonite mixture

Consolidation behavior of clays and sand–clay mixtures is an important topic in environmental geotechnics, thermal geostructures and disposal of hazardous wastes. The purpose of this paper is investigation of the changes in consolidation behavior of a sand–bentonite mixture due to the pre-curing at elevated temperatures. For this reason, 1:1 mixture of sand–bentonite was used to prepare samples 100 mm in diameter and 200 mm in height. The specimens were cured at 40, 60 and 80 °C for 1, 3 and 5 days under a constant confining pressure in a modified thermal triaxial cell. Then, consolidation behavior of the prepared samples which have been named as cured samples was investigated. The results show that the cured samples shifted from a reconstituted state to a quasi-structured one. A distinct yield stress was observed in compression curves of cured samples which was not apparent for reconstituted ones. The preconsolidation pressure of cured samples increased with increase in curing temperature and curing time. Also, the coefficient of consolidation and permeability increased as temperature increased, while both values decreased with an increase in curing time. Moreover, a number of specimens were tested under cyclic thermal paths which clearly proved change in behavior of cured samples to a structured one compared to the samples without thermal curing.

Optimization, stabilization, and characterization of amphotericin B loaded nanostructured lipid carriers for ocular drug delivery.

The current study sought to formulate, optimize, and stabilize amphotericin B (AmB) loaded PEGylated nanostructured lipid carriers (NLC) and to study its ocular biodistribution following topical instillation. AmB loaded PEGylated NLC (AmB-PEG-NLC) were fabricated by hot-melt emulsification followed by high-pressure homogenization (HPH) technique. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-2K-DSPE) was used for surface PEGylation. mPEG-DSPE with different PEG molecular weight, 1 K, 2 K, 5 K, 10 K, and 20 K, were screened for formulation stability. Furthermore, the AmB loaded PEGylated (2K) NLC (AmB-PEG2K-NLC) was optimized using Box-Behnken design with respect to the amount of AmB, castor oil, mPEG-2K-DSPE, and number of high-pressure homogenization cycles as the factors; particle size, zeta potential, PDI, entrapment efficiency, and loading efficiency as responses. Stability of the optimized AmB-PEG2K-NLC was assessed over 4 weeks, at 4 °C as well as 25 °C and effect of autoclaving was also evaluated. AmB-PEG2K-NLC were tested for their in vitro antifungal activity against Candida albicans (ATCC 90028), AmB resistant Candida albicans (ATCC 200955) and Aspergillus fumigatus (ATCC 204305). Cytotoxicity of AmB-PEG2K-NLC was studied in human retinal pigmented epithelium cells. In vivo ocular biodistribution of AmB was evaluated in rabbits, following topical application of PEGylated NLCs or marketed AmB preparations. PEGylation with mPEG-2K-DSPE prevented leaching of AmB and increased the drug load significantly. The optimized formulation was prepared with a particle size of 218 ± 5 nm; 0.3 ± 0.02 PDI, 4.6 ± 0.1% w/w drug loading, and 92.7 ± 2.5% w/w entrapment efficiency. The optimized colloidal dispersions were stable for over a month, at both 4 °C and 25 °C. AmB-PEG2K-NLCs showed significantly (p < 0.05) better antifungal activity in both wild-type and AmB resistant Candida strains and, was comparable to, or better than, commercially available parenteral AmB formulations like Fungizone™ and AmBisome®. AmB-PEG2K-NLC did not show any toxicity up to a highest concentration of 1% (v/v) (percent formulation in medium). Following topical instillation, AmB was detected in all the ocular tissues tested and statistically significant (p > 0.05) difference was not observed between the formulations tested. An optimized autoclavable and effective AmB-PEG2K-NLC ophthalmic formulation with at least one-month stability, in the reconstituted state, has been developed.

Development and evaluation of taste masked dry syrup formulation of potassium chloride

Potassium chloride (KCl) syrup is widely used for the oral treatment of the hypokalemia. However, it is associated with unacceptable taste. In the present study, we sought to develop a palatable and easy to reconstitute KCl dry syrup as a commercially viable alternative to currently available KCl syrup. We explored the potential of Eudragit E100 as a taste-masking polymer to coat and improve the palatability of the KCl. With the help of fluid bed processor, KCl was coated with the solution containing varying amounts of Eudragit E100 (4, 6, 10 and 15%). Coating with 10% polymer solution enabled optimal fluid bed processing, higher entrapment of the KCl (81%) and better in vitro release profile in 0.1 N HCl and pH 6.8 phosphate buffer. A dry syrup formulation containing Eudragit E100 coated KCl with good physical and chemical stability in dry and reconstituted state was developed. The palatability of the optimized formulation and commercially available KCl syrup was evaluated using the Electronic Taste Sensing Machine. The developed formulation showed~ 2-fold better taste-masking compared to the commercial KCl syrup. Thus, present investigation describes the development of an effective alternative to the current KCl syrup that can offer better palatability, stability and patient compliance.

Compression and Strength Characteristics of Two Silts of Low and High Plasticity

AbstractThe potential for enhanced strength or stiffness arising from the microstructure of natural silty soils compared with their reconstituted state is examined using the framework for clays, to...

Characterisation of state bounding surface at low effective stresses in clayey soils having different structures

Shallow stability analysis of natural or man-made soil slopes requires accurate characterisation of soil strength at low effective stresses (5–20 kPa), corresponding to mechanisms expected at 1–2 m depth. This study focused on the intertwining effects of soil structures at different scales and low stresses on the undrained strength of fine-grained soils, by testing two natural plastic clays and a clay–sand mixed soil at different states (intact, reconstituted and compacted) in a series of constant-volume direct shear and hollow cylinder simple shear tests. The non-linearity of the Hvorslev bounding surface was expressed well by a power law function. The normalised strength and the degree of its non-linearity of the clays at intact states were higher than at equivalent reconstituted states, probably owing to true inter-particle cohesion, as confirmed by the hollow cylinder apparatus tests. The compacted states led to significantly lower normalised strength than the reconstituted state in both clays, while they did not show significant difference in the clay–sand mixed soil. This observation was explained by meso-scale discontinuities by X-ray micro-computed tomography images. Compacted clays’ shear strength is associated with a meso-fabric very different from that in more homogeneous intact and reconstituted clays, and the conventional state normalisation based on the equivalent pressure does not capture it.

Constitutive modelling of Otaniemi soft clay in both natural and reconstituted states

A rate-independent anisotropic elastoplastic constitutive model for natural soft clays is proposed, with emphasis on the effects of cementation or structure and fabric anisotropy. The characteristic non-linear normal compression line for structured soils is described by defining a variable compressibility as a function of plastic straining. No reference to the ‘intrinsic’ reconstituted state is required. The effect of plastic anisotropy is investigated from virgin constant stress ratio consolidation tests, which provide an accurate description of the equilibrium states of soil fabric. The change of fabric anisotropy is correlated with the change of inclination of the yield and plastic potential surfaces via a pair of improved rotational hardening laws. Experiments on Otaniemi clay samples in both natural and reconstituted states are simulated. Comparisons of numerical predictions with experimental data illustrate the feasibility and advantage of the proposed methodology to describe the mechanical behaviour of natural soft clays.

Microstructural changes of an undisturbed, reconstituted and compacted high plasticity clay subjected to wetting and drying

The behaviour of soil, and in particular compacted clay fill, can have significant implications on the safe and reliable operation of man-made infrastructure. The mechanical behaviour of soil (e.g. volume change and shear strength) is widely recognised as being associated with the microstructural arrangement (fabric/structure). In the case of high plasticity clays, despite the large amount of research carried out, soil microstructure and its evolution along mechanical and hydraulic paths are still not well understood. This makes incorporation of microstructural analysis difficult in engineering practice and highlights the need for further research. A comprehensive microstructural analysis of Maryland clay, a high plasticity residual soil, based on mercury intrusion porosimetry tests, is presented in this paper. Experimental results obtained from undisturbed, reconstituted and compacted specimens subjected to different hydraulic and mechanical paths are described. As with mechanical investigations, the reconstituted state is proposed to be used routinely as a reference state for comparison of undisturbed and compacted soil. The microstructural evolution of the compacted clay, prepared on the wet side of standard Proctor optimum water content, with an initially high void ratio, is examined along the main drying path. Importantly, a monotonic suction increase from the as-compacted state is shown to have negligible effect on the distribution of macro-pores. However, a new insight is provided based on the evolution of the dominant micro-pore entrance diameter which is shown to reduce with increased suction. This micro-pore entrance diameter is shown to correspond with the theoretical suction back-calculated from a simple capillary tube model, up to a limit. It is observed that, under oedometric conditions, the as-compacted microstructure is erased during saturation (soaking) and resembles the reconstituted microstructure. For this particular material and preparation conditions, it is demonstrated that a bimodal microstructure is not recovered on drying from a saturated state.

Experimental study on volumetric behaviour of Maryland clay and the role of degree of saturation

In this paper, the volume change behaviour of Maryland clay compacted on the wet side of standard Proctor optimum water content (with lower compaction energy) is studied in reference to the saturated reconstituted state. Oedometer tests over a range of suctions and vertical stresses have been carried out, and the results have shown that the compression index reaches a peak (approximately twice that of the reconstituted material) and then gradually reduces to the reconstituted value as the stress level is increased. The results are analyzed in a framework where the degree of saturation is treated as a state parameter and controls the slope of the unsaturated normal compression line. Tests conducted under constant suction and constant water content have been used to demonstrate the effectiveness of using the degree of saturation as a state variable.

Understanding Ethnic Minority Demands: A New Typology

The development of demands advanced by ethnic minorities has received broad coverage in the scholarly literature on divided societies. Current literature offers models that predict a radicalization of minority demands as the result of diverse factors, including modernization processes, discrimination, and a mother country's support for the minority's demands. The present article offers an alternative approach, one that combines the type of minority with the type of regime as fundamental elements that shape a minority's demands. The model presented in this article distinguishes between four situations in which minorities might find themselves: an indigenous minority living in a democratic regime; an immigrant minority living in a democratic regime; an indigenous minority living in an ethnocratic regime, and an immigrant minority living in an ethnocratic regime. The demands that a minority will develop in these different situations range along an axis from radical to moderate and from secession to integration on the basis of equality in a reconstituted state. As part of my analysis, I cite several examples of minority demands across the world.

Quantification of the effects of structure on the compression of a stiff clay

A detailed analysis was made of the compression behaviour of London Clay from oedometer tests, investigating the effects of the clay structure through comparisons between the behaviour of the intact soil and that of the same soil in a reconstituted state. The normalizing parameters commonly used in the literature to analyze the effects of structure on the compression behaviour of clays were found not to represent accurately the real behaviour of those clays that have a gradual yield in compression and require very high stresses to reach and cross the intrinsic compression line. For these soils, it is often difficult to identify a clear yield stress and the effects arising from the structure of the intact material may be concealed by the effects arising from the sample depth and the curvature of the intrinsic compression line at high stresses. A new normalizing parameter is introduced that refers the compression of the natural soil to the intrinsic swelling behaviour and the intrinsic compression line of the material. This was found to better represent the enhanced resistance of the intact material in compression while not requiring numerous loading and unloading stages in the oedometer tests as required by other methods.

Drained bearing response of shallow foundations on structured soils

This paper examines the drained bearing response of circular footings resting on structured soil deposits. Numerical simulations have been carried out using a finite element formulation of the Structured Cam Clay model. A parametric study was conducted by varying the parameters that govern the behaviour of structured soils and guidelines are given for designers to identify when effects of the soil structure are important. Under fully drained conditions, deformation within the structured soil supporting the footing usually occurs as a local or punching shear failure due to high compressibility of the structured soil and the mobilised bearing pressure increases with the footing movement, without reaching an ultimate value. A novel approximate method is presented to obtain the load–displacement response of a rigid circular footing resting on the surface of a structured soil deposit. This requires the properties of the soil in the reconstituted state and two additional parameters, which govern the natural structure of the soil. The proposed method has been applied to a published case study, where plate load test results are given for rigid circular steel plates resting on structured soil deposits. Fair agreement is observed between the computed and experimental results, suggesting the approximate method may be useful in design studies of foundations on structured soil deposits.

Serial Transplantation Resulting in Tolerance to an Unrelated Cord Blood Graft

Unrelated cord blood (UCB) hematopoietic stem cells were serially transplanted into two human leukocyte antigen (HLA)-identical siblings with T cell, B cell, natural killer cell severe combined immunodeficiency. Brother A received a 4/6-matched, HLA DRbeta1-identical but class I-disparate UCB graft after myeloablative dosages of busulfan, melphalan, and antithymocyte globulin. He experienced complete donor chimerism, severe acute gastrointestinal graft-versus-host disease (GVHD), and limited chronic skin GVHD that resolved with treatment. Two years later, brother B received unfractionated marrow from brother A after reduced-intensity conditioning with cyclophosphamide and antithymocyte globulin. Brother B experienced mixed-donor (i.e. original UCB) chimerism and no histologically documented GVHD. Both brothers are clinically well; brother A is in a fully immunologically reconstituted state. The uneventful course and progressive increase in donor chimerism after the second transplantation indicates that hematopoietic cells derived from the older brother's marrow engrafted without causing GVHD, suggesting that acquired tolerance to disparate unrelated HLA antigens was achieved.

Numerical Modeling of Nonhomogeneous Behavior of Structured Soils during Triaxial Tests

The nonhomogeneous behavior of structured soils during triaxial tests has been studied using a finite element model based on the Structured Cam Clay constitutive model with Biot-type consolidation. The effect of inhomogeneities caused by the end restraint is studied by simulating drained triaxial tests for samples with a height to diameter ratio of 2. It was discovered that with the increase in degree of soil structure with respect to the same soil at the reconstituted state, the inhomogeineities caused by the end restraint will increase. By loading the sample at different strain rates and assuming different hydraulic boundary conditions, inhomogeneities caused by partial drainage were investigated. It was found that if drainage is allowed from all faces of the specimen, fully drained tests can be carried out at strain rates about ten times higher than those required when the drainage is allowed only in the vertical direction at the top and bottom of the specimen, confirming the findings of previous studi...

The Barbarian Borderland and the Chinese Imagination: Travellers in Wa Country

AbstractThe Wa lands continue to be seized upon in the Chinese imagination, and elsewhere too, as representing what is dangerous and off limits. This is one important underlying reason why these lands, located in between China and Burma, have been some of the least-travelled areas on China's southwestern borders during most of the last few centuries. In fact, these areas have long been regarded as impenetrable for outsider travellers unless assisted by a full-fledged army, its gunpowder dry and its guns loaded. In the last years of the nineteenth century, the British occupation of Burma as well as increasing opium trade prompted increases in the numbers of Chinese and other visitors: officials, soldiers, traders, and so on. The first attempt at delineating a Burma-China border having failed, a second, joint British-Chinese survey was launched and almost completed in the late 1930s. These activities prompted a flurry of patriotic-scholarly efforts to claim these borderlands for the reconstituted Chinese state, which continued into the second half of the twentieth century. This brief paper explores some of the conflicting views of the various kinds of travellers and locals, including early Chinese judgements of the Wa, the nationalistic and scientistic travellers and writers of the 1930s, as well as the teams of ethnologists and soldiers dispatched there in the 1950s and 1960s – notably also Alan Winnington, the famous British correspondent for the Morning Star, and his Wa reception.

Shifting the perspective on identity discourse in Estonia

I argue that the post-socialist identity discourse in Estonia should be studied as a result of the dialectic relationship between the international context in which Estonia exists and the perceptions of history and culture that elites deploy in the public discourse of Estonia's identity. Four major narratives that compose much of the identity discourse emerge from this dialectic: Estonia as a reconstituted state and society; Estonia as European; Estonia as Finno-Ugric; and Estonia as Nordic. These narratives can be overlooked if research relies simply on “East” and “West” analytic categories or assumes that history and culture alone yield identity. Estonia provides an excellent opportunity to examine this dialectic because of the international community's role in the country's transformation into a European Union applicant state.