Hierarchical Cont-Bouchaud model

We extend the well-known Cont-Bouchaud model to include a hierarchical topology of agent's interactions. The influence of hierarchy on system dynamics is investigated by two models. The first one is based on a multi-level, nested Erdos-Renyi random graph and individual decisions by agents according to Potts dynamics. This approach does not lead to a broad return distribution outside a parameter regime close to the original Cont-Bouchaud model. In the second model we introduce a limited hierarchical Erdos-Renyi graph, where merging of clusters at a level h+1 involves only clusters that have merged at the previous level h and we use the original Cont-Bouchaud agent dynamics on resulting clusters. The second model leads to a heavy-tail distribution of cluster sizes and relative price changes in a wide range of connection densities, not only close to the percolation threshold.Comment: 10 pages, 6 figure

Observation of highly decoupled conductivity in protic ionic conductors

YesIonic liquids (ILs) are key materials for the development of a wide range of emerging technologies. Protic ionic liquids, an important class of ILs, have long been envisioned as promising anhydrous electrolytes for fuel cells. It is well known that in comparison to all other cations, protons exhibit abnormally high conductivity in water. Such superprotonic dynamics was expected in protic ionic conductors as well. However, many years of extensive studies led to the disappointing conclusion that this is not the case and most protic ionic liquids display subionic behavior. Therefore, the relatively low conductivity seems to be the main obstacle for the application of protic ionic liquids in fuel cells. Using dielectric spectroscopy, herein we report the observation of highly decoupled conductivity in a newly synthesized protic ionic conductor. We show that its proton transport is strongly decoupled from the structural relaxation, in terms of both temperature dependence and characteristic rates. This finding offers a fresh look on the charge transport mechanism in PILs and also provides new ideas for design of anhydrous materials with exceptionally high proton conductivity.National Science Centre within the framework of the Opus project (Grant No. DEC 2011/03/B/ST3/02072). Financial assistance from FNP START. The LDRD Program of ORNL, managed by UT-Battelle, LLC, for the U.S. DOE. Support from the NSF under grant CHE-1213444

Heat induced evaporative antisolvent nanoprecipitation (HIEAN) of itraconazole

YesItraconazole (ITR) is an antifungal drug with a limited bioavailability due to its poor aqueous solubility. In this study, ITR was used to investigate the impact of nanonisation and solid state change on drug’s apparent solubility and dissolution. A bottom up approach to the production of amorphous ITR nanoparticles (NPs), composed of 100% drug, with a particle diameter below 250 nm, using heat induced evaporative antisolvent nanoprecipitation (HIEAN) from acetone was developed. The NPs demonstrated improved solubility and dissolution in simulated gastrointestinal conditions when compared to amorphous ITR microparticles. NPs produced with polyethylene glycol (PEG) or its methoxylated derivative (MPEG) as a stabiliser enabled the production of smaller NPs with narrower particle size distribution and enhanced apparent solubility. MPEG stabilised NPs gave the greatest ITR supersaturation levels (up to 11.6 ± 0.5 μg/ml) in simulated gastric fluids. The stabilising polymer was in an amorphous state. Dynamic vapour sorption data indicated no solid state changes in NP samples with water vapour at 25 °C, while crystallisation was apparent at 50 °C. HIEAN proved to be an efficient method of production of amorphous ITR NPs, with or without addition of a polymeric stabiliser, with enhanced pharmaceutical properties.Libyan Ministry of Higher Education and Scientific Research through the Libyan Embassy, London and supported by the Science Foundation Ireland under Grant No. 12/RC/2275 (Synthesis and Solid State Pharmaceuticals Centre)

Synchronous borderline ovarian tumor with endometrioid endometrial carcinoma - from diagnosis to treatment. A Case study

Introduction The occurrence of two primary tumors at an interval of no more than two months is called a synchronous tumor. This also applies to female reproductive organs among which synchronous occurrence of ovarian and endometrial cancers is most frequently observed. This phenomenon is observed mainly in young women before menopause. A rare and problematic diagnostic situation is the synchronous co-occurrence of borderline ovarian carcinoma with endometrioid carcinoma of the endometrium. The diagnostic problem and treatment of this combination of cancers are presented in the following case. Case description: A 30-year-old female patient presented to the Gynecologic Oncology Department with a suspected malignant lesions of both ovaries. She underwent fertility-sparing surgery with preservation of the left ovary and uterus. Examination of the resected tissues revealed an endometrioid borderline tumor. During the next hospitalization, an excision of uterine polyps was performed, during which no neoplastic lesion of the endometrium was observed. Ultrasound examination, in which the endometrial lesion was also invisible, raised suspicion of cancer recurrence on the left ovary. The patient was scheduled for resection of the left ovary with the recurrence and hysterectomy. The histopathological examination performed confirmed the recurrence on the ovary and showed foci of G1 endometrioid carcinoma of the uterus. Conclusions Cases that meet the criteria for synchronous tumor occurrence should be considered. Appropriate diagnosis and selection of radical treatment could affect the curability of patients. Further research on rare combinations of synchronous neoplasms could be helpful in clinical practice

A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability

YesHigh-dose API powders which are to be tableted by direct compression should have high compactibility and compressibility. This note reports on a novel approach to the manufacture of crystalline powders intended for direct compaction with improved compactibility and compressibility properties. The poorly compactable API, chlorothiazide, was spray dried from a water/acetone solvent mix producing additive-free nanocrystalline microparticles (NCMPs) of median particle size 3.5 μm. Tablets compacted from NCMPs had tensile strengths ranging from 0.5 to 4.6 MPa (compared to 0.6–0.9 MPa for tablets of micronised CTZ) at compression forces ranging from 6 kN to 13 kN. NCMP tablets also had high porosities (34–20%) and large specific surface areas (4.4–4.8 m2/g). The time taken for tablets made of NCMPs to erode was not statistically longer (p > 0.05) than for tablets made of micronised CTZ. Fragmentation of NCMPs on compression was observed. The volume fraction of particles below 1 μm present in the suspension recovered after erosion of NCMP tablets was 34.8 ± 3.43%, while no nanosized particles were detected in the slurry after erosion of compacted micronised CTZ.Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/B1158

LIAISON PSYCHIATRY IN POLAND – CAN WE ACHIEVE A SUCCESSFUL HOLISTIC DIAGNOSIS?

Introduction: New decades introduce more and more new medical specialties with the inevitable progress of medical science. This is due to the increasing amount of knowledge, and in opposition to the physical and intellectual faculties of a single man. In contrast to the time of Hippocrates, today one cannot be an expert in every field of medicine. We need to consult with specialists in various fields, in order to properly diagnose the patient. Without this the final diagnosis is often impossible. Subject and methods: The objective of our survey was to check how often psychiatrists use consultation with physicians in other specialties, and whether there is a relationship between the place of work, academic degree, work experience in the profession, and the number of commissioned consultations. It was also important for us whether consultations affect the final diagnosis. Results: Most of the respondents are young doctors, specialists from big cities. They rarely consult with doctors of other specialties - 1/10 cases. However they are skeptical about the opinions of other psychiatrists. In contrast the proctologist and the pathologist are the least frequent groups of specialists who are requested for a consultation by psychiatrists. Specialists consulting the most often are internists and neurologists. Conclusions: The key to a diagnostic success is a holistic view of the patient. It is necessary therefore to develop the most effective cooperation between doctors of various specialties

Cocrystal habit engineering to improve drug dissolution and alter derived powder properties

YesObjectives: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM:4-ASA cocrystals with different habits in order to investigate the effect on dissolution, and the derived powder properties of flow and compaction. Methods: Cocrystals were prepared in a 1:1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray-drying (habit IV). Key findings: Powder X-ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate-like crystals (habit II), small cube-like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr’s compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties. Conclusions: Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behavior.Science Foundation Ireland. Grant Number: SFI/12/RC/227

Ocena skuteczności leczenia hipotensyjnego pacjentów z nadciśnieniem tętniczym i chorobą niedokrwienną serca lub ekwiwalentem wieńcowym

Introduction. Arterial hypertension (AH) is a well-known cardiovascular risk factor. Currently, in Poland, approximately 32% of adults suffer from AH, and only 26% of them are treated successfully. The study aims to determine the incidence of atherosclerosis risk factors and their influence on the effectiveness of hypotensive treatment in the population of patients with AH and coexisting coronary artery disease (CAD) or coronary equivalent. Material and methods. The study included 204 adults. The inclusion criteria were: diagnosis of AH with coexisting a diagnosis of CAD (138 people) or coronary equivalent defined as high (≥ 5%) atherosclerosis-related risk of death in 10-year prognosis, estimated using the EURO SCORE scale (66 people). During observation, pharmacological and nonpharmacological treatments were modified according to the current AH treating standards. After 6 months of observation, the effectiveness of AH control was assessed. Results. Multivariate logistic regression analysis revealed that main factors affecting poor blood pressure control after six months of observation were: obesity, age > 65 years, LDL cholesterol level > 130 mg/dL. Moreover, systolic blood pressure (SBP) < 140 mmHg was more frequent in patients with diabetes mellitus. After six months of therapy, good control of SBP was found in 42.7% of patients and normal values of diastolic blood pressure (DBP) — in 65.2 % of patients. Conclusion. Independent risk factors for poor control of blood pressure were: high level of LDL-cholesterol, age > 65 years and female sex. Paradoxically, diabetes was not a risk factor for poor control of hypertension. The introduction of combined hypotensive and lipid-lowering drugs should contribute to a better control of hypertension in Poland.Wstęp. Nadciśnienie tętnicze (AH) jest uznanym czynnikiem ryzyka schorzeń układu sercowo-naczyniowego. Obecnie 32% Polaków ma stwierdzone nadciśnienie tętnicze, z czego tylko 26% jest skutecznie leczonych. Celem pracy było określenie częstości występowania czynników ryzyka miażdżycy i ich wpływu na skuteczność leczenia hipotensyjnego w populacji pacjentów z AH i współistniejącą chorobą niedokrwienną serca (CAD) lub ekwiwalentem wieńcowym. Materiał i metody. Kryterium włączenia do badania dla 204 osób stanowiło rozpoznanie HA (204 osoby), rozpoznanie CAD (138 osób) lub obecność ekwiwalentu wieńcowego rozumianego jako wysokie (≥ 5%) ryzyko zgonu z powodu miażdżycy w ciągu najbliższych 10 lat, szacowane według skali oceny ryzyka SCORE (66 osób). W czasie obserwacji modyfikowano postępowanie niefarmakologiczne i farmakologiczne zgodnie z obowiązującymi standardami leczenia AH, ponownie oceniając uzyskaną skuteczność kontroli AH po 6 miesiącach. Wyniki. Analiza wieloczynnikowa wykazała, że niezależnymi czynnikami wpływającymi na brak prawidłowej kontroli wartości ciśnienia tętniczego po 6 miesiącach były: otyłość, wiek > 65 lat, stężenie cholesterolu frakcji LDL > 130 mg/dl. Wykazano również, że pacjenci z cukrzycą łatwiej osiągali wartości skurczowego ciśnienia tętniczego (SBP) < 140 mm Hg. Po 6 miesiącach terapii zadowalającą kontrolę SBP odnotowano u 42,7%, a rozkurczowego ciśnienia tętniczego u 65,2% pacjentów. Wnioski. Niezależnymi czynnikami ryzyka braku prawidłowej kontroli wartości ciśnienia tętniczego były: podwyższone stężenia cholesterolu frakcji LDL, otyłość, wiek > 65 lat i płeć żeńska. Paradoksalnie, cukrzyca nie była czynnikiem zwiększającym ryzyko nieprawidłowej kontroli wartości ciśnienia tętniczego. Wprowadzenie skojarzonych preparatów hipotensyjno-hipolipemizujących powinno w szczególny sposób przyczynić się do lepszej kontroli nadciśnienia tętniczego w Polsce

Impact of process variables on the micromeritic and physicochemical properties of spray-dried porous microparticles, part I: introduction of a new morphology classification system

YesObjectives This work investigated the impact of spray drying variables such as feedconcentration, solvent composition and the drying mode, on the micromeriticproperties of chlorothiazide sodium (CTZNa) and chlorothiazide potassium(CTZK).Methods Microparticles were prepared by spray drying and characterised usingthermal analysis, helium pycnometry, laser diffraction, specific surface area analysisand scanning electron microscopy.Key findings Microparticles produced under different process conditions pre-sented several types of morphology.To systematise the description of morphology ofmicroparticles, a novel morphology classification system was introduced. The shapeof the microparticles was described as spherical (1) or irregular (2) and the surfacewas classified as smooth (A) or crumpled (B). Three classes of morphology of micro-particles were discerned visually: class I, non-porous; classes II and III, comprisingdiffering types of porosity characteristics. The interior was categorised as solid/continuous (a), hollow (b), unknown (g) and hollow with microparticulate content(d). Nanoporous microparticles of CTZNa and CTZK, produced without recircula-tion of the drying gas, had the largest specific surface area of 72.3 and 90.2 m2/g,respectively, and presented morphology of class 1BIIIa.Conclusions Alteration of spray drying process variables, particularly solvent com-position and feed concentration can have a significant effect on the morphology ofspray dried microparticulate products. Morphology of spray dried particles may beusefully described using the morphology classification system.The Irish Research Council for Science and Engineering Technology (IRCSET), the Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number [07/SRC/B1158] and the Irish Drug Delivery Research Network, a Strategic Research Cluster grant (07/SRC/B1154) under the National Development Plan co-funded by EU Structural Funds and Science Foundation Ireland