This paper examines the influence of El Niño–Southern Oscillation (ENSO) on different aspects of major stratospheric sudden warmings (SSWs), focusing on the precursor role of blocking events. The ...results reveal an ENSO modulation of the blocking precursors of SSWs. European and Atlantic blocks tend to precede SSWs during El Niño (EN), whereas eastern Pacific and Siberian blocks are the preferred precursors of SSWs during La Niña (LN) winters. This ENSO preference for different blocking precursors seems to occur through an ENSO effect on regional blocking persistence, which in turn favors the occurrence of SSWs. The regional blocking precursors of SSWs during each ENSO phase also have different impacts on the upward propagation of planetary-scale wavenumbers 1 and 2; hence, they determine ENSO differences in the wavenumber signatures of SSWs. SSWs occurring during EN are preceded by amplification of wavenumber 1, whereas LN SSWs are predominantly associated to wavenumber-2 amplification. However, there is not a strong preference for splitting or displacement SSWs during any ENSO phase. This is mainly because during EN, splitting SSWs do not show a wavenumber-2 pattern.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Amorphous nifurtimox (AM-NFX) was prepared and exhaustively characterized.•The powder dissolution rate of AM-NFX is 2.2 times that of crystalline nifurtimox.•AM-NFX is unstable, ...undergoing devitrification under mechanical and thermal stress.•Chemometric-assisted infrared spectral analysis developed for tracking devitrification.
Nifurtimox (NFX) is a nitrofuran derivative used to treat Chagas disease, a neglected disease caused by the protozoan Trypanosoma cruzi. The drug is very sparingly soluble in aqueous media and no other solid phases of NFX have been reported to date.
The preparation of the amorphous mode of NFX is reported, as well as its characterization by hot stage microscopy, thermal (differential scanning calorimetry and thermogravimetric analysis), spectroscopic (solid state nuclear magnetic resonance, mid-infrared, and near-infrared), diffractometric and functional (powder dissolution rate) means.
The stability of the new phase was investigated. This was characterized using thermal, spectroscopic, and diffractometric methods, finding out its spontaneous reversion to the crystalline state, as sign of instability. In addition, the amorphous material proved to be sensitive to temperature, pressure, and mechanical stress, all of which accelerated phase conversion. However, it was able to remain stable in a model polymeric amorphous solid dispersion with PEG 4000 for more than one month. An approach for monitoring the conversion of the amorphous phase to its crystalline counterpart under thermal stress by chemometric analysis of mid-infrared spectra at different temperatures is also disclosed.
The Northern Hemisphere (NH) polar stratospheric response to Central Pacific El Niño (CP‐El Niño) events remains unclear. Contradictory results have been reported depending on the definition and ...events considered. We show that this is due to the prominent role of Stratospheric Sudden Warmings (SSWs), whose signal dominates the NH winter polar stratospheric response to CP‐El Niño. In fact, the CP‐El Niño signal is robust when the events are classified according to the occurrence of SSWs and displays opposite response in winters with and without SSWs. In the absence of SSWs, polar stratospheric responses to Central Pacific and Eastern Pacific El Niño are clearly distinguishable in early winter, in relation to differences in the Pacific‐North American pattern. Our results demonstrate that the occurrence of SSWs needs to be taken into account when studying the stratospheric response to CP‐El Niño and explain why different responses to CP‐El Niño have been reported previously.
Key Points
SSW occurrence dominates the CP‐El Niño signal in the NH polar stratosphere
In the absence of SSWs, EP‐ and CP‐El Niño stratospheric responses are distinguishable
Robust results regardless of the CP‐El Niño index and the composite size used
The NCAR Community Earth System Model (CESM) now includes an atmospheric component that extends in altitude to the lower thermosphere. This atmospheric model, known as the Whole Atmosphere Community ...Climate Model (WACCM), includes fully interactive chemistry, allowing, for example, a self-consistent representation of the development and recovery of the stratospheric ozone hole and its effect on the troposphere. This paper focuses on analysis of an ensemble of transient simulations using CESM1(WACCM), covering the period from the preindustrial era to present day, conducted as part of phase 5 of the Coupled Model Intercomparison Project. Variability in the stratosphere, such as that associated with stratospheric sudden warmings and the development of the ozone hole, is in good agreement with observations. The signals of these phenomena propagate into the troposphere, influencing near-surface winds, precipitation rates, and the extent of sea ice. In comparison of tropospheric climate change predictions with those from a version of CESM that does not fully resolve the stratosphere, the global-mean temperature trends are indistinguishable. However, systematic differences do exist in other climate variables, particularly in the extratropics. The magnitude of the difference can be as large as the climate change response itself. This indicates that the representation of stratosphere–troposphere coupling could be a major source of uncertainty in climate change projections in CESM.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nifurtimox is a nitroheterocyclic drug employed for treatment of trypanosomiases (Chagas disease and West African sleeping sickness); its use for certain cancers has also been assessed. Despite ...having been in the market for over 50 years, knowledge of nifurtimox is still fragmentary and incomplete. Relevant aspects of the chemistry and biology of nifurtimox are reviewed to summarize the current knowledge of this drug. These comprise its chemical synthesis and the preparation of some analogues, as well as its chemical degradation. Selected physical data and physicochemical properties are also listed, along with different approaches toward the analytical characterization of the drug, including electrochemical (polarography, cyclic voltammetry), spectroscopic (ultraviolet-visible, nuclear magnetic resonance, electron spin resonance), and single crystal X-ray diffractometry. The array of polarographic, ultraviolet-visible spectroscopic, and chromatographic methods available for the analytical determination of nifurtimox (in bulk drug, pharmaceutical formulations, and biological samples), are also presented and discussed, along with chiral chromatographic and electrophoretic alternatives for the separation of the enantiomers of the drug. Aspects of the drug likeliness of nifurtimox, its classification in the Biopharmaceutical Classification System, and available pharmaceutical formulations are detailed, whereas pharmacological, chemical, and biological aspects of its metabolism and disposition are discussed.
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Vaginal candidiasis is considered a frequent opportunistic mucosal infection and the second most common cause of vaginitis after bacterial vaginosis. In this work, different vaginal ...films based on chitosan, hydroxypropyl methylcellulose and blends of these polymers containing tioconazole, were developed and thoroughly characterized to improve the conventional therapeutics of vaginal candidiasis. Mechanical properties, swelling, adhesiveness, morphology, antifungal activity, hemocompatibility and cytotoxicity were evaluated. The drug solid state in the films was analyzed by thermal and X-ray diffraction analysis. Films showed homogeneous surfaces and presented similar mechanical properties and adhesiveness. Time-kill studies displayed that films were more active than both tioconazole pure drug and traditional tioconazole ovule against Candida albicans, which is probably related to the fact that tioconazole is in amorphous state inside the films. Although all formulations proved to be hemocompatible, films based only on chitosan exhibited a certain degree of cytotoxicity and therefore they should be avoided. The system based on chitosan-hydroxypropyl methylcellulose with 40% PEG 400 as plasticizer presented fast antimicrobial activity as well as the lowest swelling. Additionally, this formulation did not produce substantial hemolytic and cytotoxic effects, indicating that films based on chitosan-hydroxypropyl methylcellulose could be a promising alternative dosage form for the treatment of vaginal candidiasis.
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•Chemometrtics-assisted methods for identification of given form in mixtures.•Monitoring of polymorphic transformations, including amorphization and ...desolvation.•Spectroscopic/chemometrics approaches to evaluate aspects of pharmaceutical polymorphism.•Classification and quantitation of solid state forms in complex pharmaceutical mixtures.•Structural polymorphism. Its quality control in pharmaceutical relevant systems.
Current regulations command to properly characterize pharmaceutically relevant solid systems. Chemometrics comprise a range of valuable tools, suitable to process large amounts of data and extract valuable information hidden in their structure. This review aims to detail the results of the fruitful association between analytical techniques and chemometrics methods, focusing on those which help to gain insight into the characteristics of drug polymorphism as an important aspect of the solid state of bulk drugs and drug products.
Hence, the combination of Raman, terahertz, mid- and near- infrared spectroscopies, as well as instrumental signals resulting from X-ray powder diffraction, 13C solid state nuclear magnetic resonance spectroscopy and thermal methods with quali-and quantitative chemometrics methodologies are examined.
The main issues reviewed, concerning pharmaceutical drug polymorphism, include the use of chemometrics-based approaches to perform polymorph classification and assignment of polymorphic identity, as well as the determination of given polymorphs in simple mixtures and complex systems. Aspects such as the solvation/desolvation of solids, phase transformation, crystallinity and the recrystallization from the amorphous state are also discussed. A brief perspective of the field for the next future is provided, based on the developments of the last decade and the current state of the art of analytical instrumentation and chemometrics methodologies.
The aim of this study was to explore the impact of the coronavirus pandemic on adolescents diagnosed with Borderline Personality Disorder (BPD) and their mothers. This exploratory study used a ...qualitative focus group approach. This study’s sample group consisted in nine participants: five adolescents diagnosed with BPD and their four mothers. Patients were recruited from a specialized BPD outpatient unit of a university hospital psychiatry department. The results are divided into two main areas, the first regarding the lockdown period and the second examining the period of gradual relaxation of lockdown restrictions. The results show that the adolescents had difficulties in the management of their interpersonal relationships, especially in striking a balance between individual and family space, as well as in communication, cohesion, and family dynamics. During the COVID lockdown, adolescents experienced a stabilization of psychopathological symptoms, but these symptoms worsened when the lockdown restrictions were lifted. Nevertheless, they reported having learned and implemented self-care strategies. The findings are discussed in terms of both individual and family impact, shedding light on some of the challenges precipitated by the COVID-19 pandemic.
This article analyses the annual mean vertical and latitudinal structure of the Brewer–Dobson circulation in the CMIP5 models. The strength of the tropical mass upwelling is found to increase at all ...altitudes throughout the stratosphere due to climate change. However, the width of the tropical upwelling region narrows below about 20 hPa, and widens above 20 hPa, suggesting different physical mechanisms may play a role in this change above and below 20 hPa. In the lower stratosphere, an equatorward shift in the stationary wave critical line allows waves to propagate further into the Tropics. However, in the upper stratosphere, where the behaviour is dominated by what happens during the winter, an increase in the extratropical zonal mean westerly jet leads to a reduced equatorward refraction of planetary waves. The seasonal cycle of the change in the Brewer–Dobson circulation is also considered, and differences are found in the latitudinal structure of the increased extratropical downwelling between the Northern and Southern Hemispheres in winter.
•Applications of NMR spectroscopy and its hyphenated derivate techniques to pharmaceutical impurities are detailed.•A wide range pharmaceutical impurities characterized by NMR spectroscopy are ...reviewed.•Advantages and disadvantages of NMR for characterization of pharmaceutical impurities are discussed.•Specific challenges of NMR with regards to different analytical problems are presented.
Current standards and regulations demand the pharmaceutical industry not only to produce highly pure drug substances, but to achieve a thorough understanding of the impurities accompanying their manufactured drug substances and products. These challenges have become important goals of process chemistry and have steadily stimulated the search of impurities after accelerated or forced degradation procedures.
As a result, impurity profiling is one of the most attractive, active and relevant fields of modern pharmaceutical analysis. This activity includes the identification, structural elucidation and quantitative determination of impurities and degradation products in bulk drugs and their pharmaceutical formulations.
Nuclear magnetic resonance (NMR) spectroscopy has evolved into an irreplaceable approach for pharmaceutical quality assessment, currently playing a critical role in unequivocal structure identification as well as structural confirmation (qualitative detection), enabling the understanding of the underlying mechanisms of the formation of process and/or degradation impurities.
NMR is able to provide qualitative information without the need of standards of the unknown compounds and multiple components can be quantified in a complex sample without previous separation. When coupled to separative techniques, the resulting hyphenated methodologies enhance the analytical power of this spectroscopy to previously unknown levels. As a result, and by enabling the implementation of rational decisions regarding the identity and level of impurities, NMR contributes to the goal of making better and safer medicines.
Herein are discussed the applications of NMR spectroscopy and its hyphenated derivate techniques to the study of a wide range pharmaceutical impurities. Details on the advantages and disadvantages of the methodology and well as specific challenges with regards to the different analytical problems are also presented.
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