Secondary transitions to aquatic environments are common among vertebrates, and aquatic lineages display several adaptations to this realm, some of which might make these transitions irreversible. At ...the same time, discussions about secondary transitions often focus only on the marine realm, comparing fully terrestrial with fully aquatic species. This, however, captures only a fraction of land-to-water transitions, and freshwater and semi-aquatic groups are often neglected in macroevolutionary studies. Here, we use phylogenetic comparative methods to unravel the evolution of different levels of aquatic adaptations across all extant mammals, testing if aquatic adaptations are irreversible and if they are related to relative body mass changes. We found irreversible adaptations consistent with Dollo's Law in lineages that rely strongly on aquatic environments, while weaker adaptations in semi-aquatic lineages, which still allow efficient terrestrial movement, are reversible. In lineages transitioning to aquatic realms, including semi-aquatic ones, we found a consistent trend towards an increased relative body mass and a significant association with a more carnivorous diet. We interpret these patterns as the result of thermoregulation constraints associated with the high thermal conductivity of water leading to body mass increase consistently with Bergmann's rule and to a prevalence of more nutritious diets.
Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which ...contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.
Introduction
Triple Network Model (TNM), which considers the dynamic interaction between Default Mode (DMN), Salience (SN), and Central Executive (CEN) networks, explains clinical features in mental ...disorders from a neurophysiological perspective. Some studies highlight the increased connectivity in TNM in adults with Borderline Personality Disorder (BPD), but little is known about adolescents.
Objectives
The aim of our preliminary study was to investigate TN functional connectivity (FC) in BPD adolescents with a history of traumatic experiences, and its correlation with dissociative symptoms.
Methods
15 BPD adolescents (DSM-5 criteria) with early traumatic experiences were compared to 15 healthy controls, matched for sex and age. Dissociation Questionnaire (DIS-Q) was administered. Eyes-closed resting-state (RS) EEG recordings were performed (19 electrodes; 10- 20 system) and analyzed using Exact Low-Resolution Electromagnetic Tomography software (eLORETA). FC was computed for all frequency bands and 9 Regions of Interest for TNM.
Results
BPD adolescents showed a hyper-connection between CEN and DMN dorso-lateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC); PCC and left posterior parietal cortex (PPC) and within the CEN (left and right PPC). The strength of PCC-dlPFC and left-right PPC connections was correlated with dissociative symptoms severity.
Conclusions
FC alterations can already be identified in BPD adolescents, supporting the need for early diagnosis. Normally DMN and CEN show opposite functioning. In our BPD adolescents, the absence of this “anti-correlation” reflects the typical confusion between internal and external mental states, which clarify their difficulties in metacognition or mentalization. Moreover, in dissociative symptoms, two CEN nodes are also involved, not only DMN as previously described.
Disclosure
No significant relationships.
An ultra high performance liquid chromatography method was developed and validated for the quantitation of triamcinolone acetonide in an injectable ophthalmic hydrogel to determine the contribution ...of analytical method error in the content uniformity measurement. During the development phase, the design of experiments/design space strategy was used. For this, the free R‐program was used as a commercial software alternative, a fast efficient tool for data analysis. The process capability index was used to find the permitted level of variation for each factor and to define the design space. All these aspects were analyzed and discussed under different experimental conditions by the Monte Carlo simulation method. Second, a pre‐study validation procedure was performed in accordance with the International Conference on Harmonization guidelines. The validated method was applied for the determination of uniformity of dosage units and the reasons for variability (inhomogeneity and the analytical method error) were analyzed based on the overall uncertainty.
•Validation of two analytical methods with different detection modes using a monoclonal antibody.•Criteria used were different in accordance to the needs and characteristics of each method.•Control ...charts and process capability index were used to monitor the methods.•The total error and β-expectation tolerance interval rules were used to assess method suitability.•It examines Arrhenius behavior and how to successfully use to estimate the shelf-life.
Size exclusion chromatography (SEC) with different detection modes was assessed as a means to characterize the type of bevacizumab aggregate that forms under thermal stress, quantitatively monitoring the aggregation kinetics.
The combination of SEC with light-scattering (SEC/LS) detection was validated using in-study validation process. This was performed by applying a strategy based on a control chart to monitor the process parameters and by inserting quality control samples in routine runs. The SEC coupled with a differential refractive-index detector (SEC/RI) was validated using a pre-study validation process in accordance with the ICH-Q2 (R1) guidelines and in-study monitoring in accordance with the Analytical Target Profile (ATP) criteria. The total error and β-expectation tolerance interval rules were used to assess method suitability and control the risk of incorrectly accepting unsuitable analytical methods.
The aggregation kinetics data were interpreted using a modified Lumry-Eyring model. The true order of the reaction was determined using the initial-rate approach. All the kinetic data show a linear Arrhenius dependence within the studied temperature range. The Arrhenius approach over-predicted the aggregation rate for 5°C, but provides an idea of the aggregation process and amount of aggregate formed. In any case, real-time stability data are necessary to establish the product shelf-life.
Overkill of large mammals is recognized as a key driver of Pleistocene megafaunal extinctions in the Americas and Australia. While this phenomenon primarily affected mega-mammals, its impact on large ...Quaternary reptiles has been debated. Freshwater turtles, due to the scarcity of giant forms in the Quaternary record, have been largely neglected in such discussions. Here we present a new giant podocnemidid turtle,
sp. nov., from the Late Pleistocene Rio Madeira Formation in the Brazilian Amazon, that challenges this assumption. Morphological and phylogenetic analyses of the holotype, a massive partial lower jaw, reveal close affinities to extant Amazonian species and suggest an omnivorous diet. Body size regressions indicate
possibly reached about 180 cm in carapace length and is among the largest freshwater turtles ever found. This finding presents the latest known occurrence of giant freshwater turtles, hinting at coexistence with early human inhabitants in the Amazon.
Drug products used for treating tuberculosis are one of the most widely reported medicines to be classified as falsified or substandard in low- and middle-income countries, representing a major ...hazard to health. The aim of this study was, firstly, to develop an ultra-performance liquid chromatography (UPLC) method which is able to analyze fixed combination tablets with up to four active pharmaceutical ingredients, including isoniazid, pyrazinamide, rifampicin, and ethambutol. Secondly, we aimed to optimize it through the design of experiments and multi-linear regression based on a central composite design and to validate it according to the guidelines of the International Conference on Harmonization. The application of this tools enabled the identification of the influential factors (flow rate, formic acid, and temperature) and their effects on the studied responses (retention factor and percentage for each drug) as part of the quality by design approach. The method proved to be to be linear in the range from 5.0 to 15 µg/mL for isoniazid, pyrazinamide, and rifampicin, being precise (<1%) and accurate (97−101%). In addition, the method validated for ethambutol proved to be linear from 1.4 to 4.2 µg/mL, as well as precise (0.54%) and accurate (97.3%). The method was stability indicated for all the active pharmaceutical ingredients studied and was able to detect two substandard formulations sampled on the African market.
We have investigated the psychotropic medications sales (i.e. benzodiazepines, mood stabilisers and selective serotonin reuptake inhibitors) during the COVID-19 pandemic in the period from March 2020 ...to February 2021 compared with the same period in the preceding year.
This was a retrospective and observational study.
Data were obtained from five pharmacies located in a working-class zone populated by approximately 150,000 people in the urban area of Rome (Italy).
A general slight increase in psychotropic medications sales was observed during the whole pandemic period compared with the previous year.
Our data showed that (1) the percentage of sales seems to vary according to the pandemic phases and related lockdowns and (2) the sales differ between the classes of medications considered.
Metal–metal oxide (MMO), graphite and laboratory-made Ag/AgCl electrodes were electrochemically characterized to be used as reference electrodes embedded in concrete structures. Electrodes were ...studied in both, aqueous solutions of pH ranging from 7 to 13.5 and embedded into cement mortars; and the electrochemical studies were carried out in the absence and presence of chloride ions. Potential evolution, polarization behaviour, galvanostatic pulse response and impedance characteristics of the electrodes were carried out in aqueous solutions. Besides, the electrochemical stability of the electrodes embedded in mortar was studied for an exposure period of 2 years. It was found that the MMO pseudo-reference electrode is pH-sensitive, the graphite pseudo-reference electrode is oxygen sensitive and the Ag/AgCl pseudo-reference electrode is chloride sensitive. In spite of the fact that any of them can be used to determine the corrosion rates of rebars because they do not depend on the absolute potential and/or the long-term stability of the reference electrode when using traditional electrochemical techniques, long-term drifts in the electrode potentials may lead to misinterpretations of the rebar state. In this context graphite electrodes are recommended because they provide conservative results regarding the active/passive state of the rebars.
•Application of the capability indices to the SEC/LS/RI method using BAS as model.•The X- and moving range chart confirmed that the method is in-control and stable.•The method meets the capability ...requirement and run under conditions preset by the analyst.•Method was used in stability study of bevacizumab pharmaceutical preparations.•Method does not comply with the specification limits and a precision control is required.
In this study, we investigated if the size-exclusion chromatography coupled with light-scattering and refractive index detection (SEC/LS/RI) method is fitted for its intended purpose and checked if the analytical method is able to provide enough conforming results. For this, the process capability indices Cp, Cpk, and Cpm were computed. The traditional X-chart and moving range (MR) chart were used by the same analyst to monitor the equipment in the laboratory over a 1-year period. For this, a bovine serum albumin (BSA) sample (0.3mgmL−1) with a nominal Mw of 66.4kDa was analyzed each working day. The results confirmed that the analytical method is in-control and stable. To determine whether the given process meets the present capability requirement and runs under the desired quality conditions, the Pearn and Shu (2003) method based on the lower confidence bound C on Cpm was used. The estimator Cpm was 1.81, and the lower confidence bound C was 1.40. We therefore conclude that the true value of the method capability Cpm is no less than 1.40 with a 95% level of confidence. This result indicates that the method is satisfactory and no stringent precision control is required. The usefulness of this method was applied in the characterization of bevacizumab commercial pharmaceutical preparations stored under different conditions that lead to aggregation. In this case, the computed Cpm index was 0.98 (0.70, 1.26), which indicates that the method does not comply with the specification limits and needs to be revised. The quality improvement effort should: (1) reduce the uncertainty in the absolute Mw determination; (2) either move the process mean closer to the target value or reduce the process variation, i.e. improve the method accuracy (μ–T) and precision (σ2). On this point, the Bayesian posterior distribution of the mean and standard deviation pointed out the need to control the precision but specially accuracy in order to reduce the overall uncertainty of analytical method and thus, the method is capable.
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