Influence of crystallisation environment on the nucleation and growth of single crystals of (RS)-ibuprofen

The crystal growth of ibuprofen as a function of crystallisation environment is presented. Measurement of solubility as a function of solvent (ethanol 95%, ethyl acetate, acetonitrile and toluene) and temperature using UV/Vis spectroscopy and gravimetric analysis reveals less than ideal behaviour, consistent with strong solute-solute interactions, particularly in the case of acetonitrile. Examination of the nucleation kinetics reveals a comparatively small metastable zone width (MSZW) (ΔT = 10.0 - 13.9oC) with interfacial tensions in the range 2.56 – 5.52.10-3 (J/m2). The growth rates for the {001} and {011} faces of spontaneously nucleated single crystals are precisely measured in-situ using optical microscopy revealing that their growth rates increase with increasing supersaturation to different extents, depending on the solvent type with concomitant impact on the crystal habit. For similar supersaturations, the growth rate of {011} is lowest in ethanol and highest in acetonitrile, whilst that of {001} is lowest in toluene and highest in ethanol. The aspect ratios, as a function of supersaturation, are generally higher at the 15 mL than the 0.5 mL crystalliser scale size. The data is consistent with a 2-D Birth and Spread growth model for both surfaces and scale sizes. This is in good agreement with the calculated surface entropy α factor. The measured growth rate dispersion for these faces is much less for these spontaneously nucleated crystals in stagnant, supersaturated solutions when compared to the literature data obtained for a stirred batch crystalliser. Additional higher index re-entrant faces are found at high levels of supersaturation consistent with their alignment either parallel to the {012} or {112} face. The growth rate in the non-agitated jacketed vessel is found to be slightly higher than that for the agitated reactors with both being in quite in a good agreement with literature data suggesting that these results on single crystals will have utility in representative the growth rates of a population of crystals in an agitated crystallizer. Observations are is rationalised using molecular and crystallographic modelling revealing e.g. that polar protic solvents inhibit the growth rate of faces containing available hydrogen bonding binding sites, such as carboxylic acid groups. Molecular conformational searching reveals the molecular structure in the solid-state to be close to that of molecules minimum intra-molecular energy. Conformer population analysis as a function of solvent reveals no significant solvent effect on the low energy conformer distribution indicative a low likelihood of polymorphic behaviour for this compound in good agreement with literature

Developing a method to determine the flux of material arriving and leaving a crystal at equilibrium

It is often said that a crystal in a saturated solution neither grows nor dissolves, however, this is an equilibrium so there must be some flux between the crystal and the solution. The question is how could this be measured. The aim of this work was to develop a method to make this measurement, as a prelude to investigating the effect of ultrasound on the rate of molecular exchange between the surface layer of a growing crystal and the surrounding slightly supersaturated solution

OPTICAL BISTABILITY IN A DEGENERATE TWO-LEVEL EIT MEDIUM UNDER THE INFLUENCE OF AN EXTERNAL MAGNETIC FIELD: AN ANALYTICAL APPROACH

We investigate the behavior of optical bistability in a degenerate two-level atomic medium using an external magnetic field to separate the lower level into two distinct levels that both connect to an upper level by the probe and coupling laser fields. Based on analytical solutions, the absorption spectrum and behavior of optical bistability in an electromagnetically induced transparency regime under an external magnetic field are investigated. By controlling the external magnetic field, we find that the appearance and disappearance of the optical bistability can be easily controlled according to the strength of the magnetic field in the transparent window domain. Furthermore, the effects of the intensity of the coupling laser field and the parameters of the system on the behavior of optical bistability are also considered. The proposed model is useful for applications in all-optical switches and magneto-optic storage devices.We investigate the behavior of optical bistability in a degenerate two-level atomic medium using an external magnetic field to separate the lower level into two distinct levels that both connect to an upper level by the probe and coupling laser fields. Based on analytical solutions, the absorption spectrum and behavior of optical bistability in an electromagnetically induced transparency regime under an external magnetic field are investigated. By controlling the external magnetic field, we find that the appearance and disappearance of the optical bistability can be easily controlled according to the strength of the magnetic field in the transparent window domain. Furthermore, the effects of the intensity of the coupling laser field and the parameters of the system on the behavior of optical bistability are also considered. The proposed model is useful for applications in all-optical switches and magneto-optic storage devices

Dry Eyes Status on Des Scale and Related Factors in Outpatients at Vietnam National Institute of Ophthalmology

BACKGROUND: Dry eye (DE) can effect on quality of life by pain, inability to perform certain activities that require prolonged attention (driving, reading,…) and productivity at work and finally effect to Q0L associated with DE. OSDI is scale questionnaire is created team to measure the quality of life related to ocular surface disease. AIM: To describe the dry eye disease according to OSDI scale and related factors of this disease. METHODS: A cross-sectional descriptive study was carried out on outpatients (≥ 16-year-old) who were examined and diagnosed with dry eyes at Vietnam National Institute Of Ophthalmology from April to July 2018. Data was collected using the OSDI questionnaire. RESULTS: The average age of participants was 44.6 years; 80.9% of patients were female; 39.9% were identified having mild dry eye. The related factors have been identified that associated with severe dry eye, including age OR = 1.03 (95%CI: 1.01-1.05, p = 0.005), binocular good vision OR = 0.11 (95%CI: 0.05-0.23; p < 0.0001), medical history OR = 17.09 (95%CI: 2.24-130.25; p < 0.0001), chronic conjunctivitis OR = 0.36 (95%CI: 0.14-0.91; p = 0.027), refractive errors OR = 0.14 (95%CI: 0.04-0.48; p < 0.0001), Sjogren's syndrome OR = 31.13 (95%CI: 7.08-136.76; p < 0.0001). CONCLUSION: Several related factors have been identified associated with severe dry eye, including: age, binocular good vision, medical history, chronic conjunctivitis, refractive errors, Sjogren's syndrome

Long short-term memory (LSTM) neural networks for short-term water level prediction in Mekong river estuaries

This study firstly adopts a state-of-the-art deep learning approach based on a Long Short-Term Memory (LSTM) neural network for predicting the hourly water level of Mekong estuaries in Vietnam. The LSTM models were developed from around 8,760 hourly data points within 2018 and were evaluated using the Nash-Sutcliffe efficiency coefficient (NSE), mean absolute error (MAE), and root mean square error (RMSE). The results showed that the NSE values for the training and testing steps were both above 0.98, which can be regarded as very good performance. Furthermore, the RMSE were between 0.09 and 0.11 m for the training and between 0.10 and 0.12 m for the testing, while MAE for the training ranged from 0.07 to 0.08 m and varied from 0.08 to 0.10 m for the testing. The LSTM networks appear to enable high precision and robustness in water level time series prediction. The outcomes of this research have crucial implications in river water level predictions, especially from the viewpoint of employing deep learning algorithms

The Epidemiology of Interpandemic and Pandemic Influenza in Vietnam, 2007–2010: The Ha Nam Household Cohort Study I

Prospective community-based studies have provided fundamental insights into the epidemiology of influenza in temperate regions, but few comparable studies have been undertaken in the tropics. The authors conducted prospective influenza surveillance and intermittent seroprevalence surveys in a household-based cohort in Vietnam between December 2007 and April 2010, resulting in 1,793 person-seasons of influenza surveillance. Age- and sex-standardized estimates of the risk of acquiring any influenza infection per season in persons 5 years of age or older were 21.1% (95% confidence interval: 17.4, 24.7) in season 1, 26.4% (95% confidence interval: 22.6, 30.2) in season 2, and 17.0% (95% confidence interval: 13.6, 20.4) in season 3. Some individuals experienced multiple episodes of infection with different influenza types/subtypes in the same season (n = 27) or reinfection with the same subtype in different seasons (n = 22). The highest risk of influenza infection was in persons 5–9 years old, in whom the risk of influenza infection per season was 41.8%. Although the highest infection risk was in school-aged children, there were important heterogeneities in the age of infection by subtype and season. These heterogeneities could influence the impact of school closure and childhood vaccination on influenza transmission in tropical areas, such as Vietnam

Impact of paracetamol impurities on face properties : investigating the surface of single crystals using TOF-SIMS

Understanding the mechanism of interaction between pharmaceutical molecules (APIs) and impurities on crystal surfaces is a key concept in understanding purification and for the design of pharmaceutical crystallization processes. Several techniques may be used to study crystal surface properties, such as scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), which provide detailed imaging and elemental surface characterization. Time of flight secondary ion mass spectrometry (TOF-SIMS) is valuable in determining molecular identity and distribution. By combining TOF-SIMS, SEM, and optical (OM) and Raman microscopies, we can evaluate the usefulness of TOF-SIMS as a surface characterization technique for pharmaceutical crystals. 4-Nitrophenol has been selected as an impurity that can be incorporated during crystallization of acetaminophen (paracetamol). This study explores the distribution of impurity and its concentration on the different crystal faces of samples obtained by crystallization over a range of impurity loadings and supersaturation conditions. Raman maps of paracetamol single crystal faces were analyzed using the characteristic Raman peak intensity of 4-nitrophenol to identify regions where it accumulated; Raman maps of three single crystals produced in the presence of 4-nitrophenol using different crystallization procedures highlight how it can be difficult to detect very low concentrations of similar chemical species. In contrast, the 4-nitrophenol monoisotopic mass obtained via TOF-SIMS was shown to be detectable in all the three single crystals produced. This indicates that TOF-SIMS can be a valuable technique for single crystal impurity distribution mapping even when the impurity concentration is very low

Combination Antifungal Therapy for Cryptococcal Meningitis

Background Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. Methods We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. Results A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. Conclusions Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found