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Background: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. Outcomes: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

The region of western Georgia (Imereti) in the Southern Caucasus has been a major geographic corridor for human migrations during the Middle and Upper Paleolithic. Data of recent research and excavations in this region display its importance as a possible route for the dispersal of anatomically modern humans (AMH) into northern Eurasia. Nevertheless, within the local research context, bone-working and personal ornaments have yet contributed but little to the Upper Palaeolithic (UP) regional sequence’s characterization. Here we present an archaeozoological, technological and use-wear study of pendants from two local UP assemblages, originating in the Dzudzuana Cave and Satsurblia Cave. The ornaments were made mostly of perforated teeth, though some specimens were made on bone. Both the manufacturing marks made during preparation and use-wear traces indicate that they were personal ornaments, used as pendants or attached to garments. Detailed comparison between ornament assemblages from northern and southern Caucasus reveal that they are quite similar, supporting the observation of cultural bonds between the two regions, demonstrated previously through lithic techno-typological affinities. Furthermore, our study highlights the importance attributed to red deer (Cervus elaphus) by the UP societies of the Caucasus in sharing aesthetic values and/or a symbolic sphere.

Vibrio cholerae causes the diarrheal disease cholera which affects millions of people globally. The outer membrane protein U (OmpU) is the outer membrane protein that is most prevalent in V. cholerae and has already been recognized as a critical component of pathogenicity involved in host cell contact and as being necessary for the survival of pathogenic V. cholerae in the host body. Computational approaches were used in this study to screen a total of 37,709 natural compounds from the traditional Chinese medicine (TCM) database against the active site of OmpU. Following a sequential screening of the TCM database, we report three lead compounds—ZINC06494587, ZINC85510056, and ZINC95910434—that bind strongly to OmpU, with binding affinity values of −8.92, −8.12, and −8.78 kcal/mol, which were higher than the control ligand (−7.0 kcal/mol). To optimize the interaction, several 100 ns molecular dynamics simulations were performed, and the resulting complexes were shown to be stable in their vicinity. Additionally, these compounds were predicted to have good drug-like properties based on physicochemical properties and ADMET assessments. This study suggests that further research be conducted on these compounds to determine their potential use as cholera disease treatment.

Abstract The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of “allergy” as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence to manage mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly. In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care. We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required of physicians working with allergic patients and provides recommendations to promote harmonization of allergy training and practice worldwide.

Bloodstains found at crime scenes represent a crucial source of information for investigative purposes. However, in forensic practice, no technique is currently used to estimate the time from deposition of bloodstains. This preliminary study focuses on the age estimation of bloodstains by exploiting the color variations over time due to the oxidation of the blood. For this purpose, we used a colorimetric methodology in order to easily obtain objective, univocal and reproducible results. We developed two bloodstain age prediction algorithms: a short-term and a long-term useful model for the first 24h and 60 days, respectively. Both models showed high levels of classification accuracy, particularly for the long-term model. Although a small-scale study, these results improve the potential application of colorimetric analysis in the time-line reconstruction of violent criminal events.

This paper evaluates six soft computational models along with three statistical data-driven models for the prediction of pan evaporation (EP). Accordingly, improved kriging—as a novel statistical model—is proposed for accurate predictions of EP for two meteorological stations in Turkey. In the standard kriging model, the input data nonlinearity effects are increased by using a nonlinear map and transferring input data from a polynomial to an exponential basic function. The accuracy, precision, and over/under prediction tendencies of the response surface method, kriging, improved kriging, multilayer perceptron neural network using the Levenberg–Marquardt (MLP-LM) as well as a conjugate gradient (MLP-CG), radial basis function neural network (RBFNN), multivariate adaptive regression spline (MARS), M5Tree and support vector regression (SVR) were compared. Overall, all the applied models were highly capable of predicting monthly EP in both stations with a mean absolute error (MAE) < 0.95. Considering periodicity as an input parameter, the MLP-LM provided better results than the other methods among the soft computing models (MAE = 0.492 mm and d = 0.981). However, the improved kriging method surpassed all the other models based on the statistical measures (MAE = 0.471 mm and d = 0.983). Finally, the outcomes of the Mann–Whitney test indicated that the applied soft computational models do not have significant superiority over the statistical ones (p-value > 0.77 mm and a Willmott index (d) > 0.65 at α = 0.01 and α = 0.05).

Background: The COVID-19 crisis has caused prolonged and extreme demands on healthcare services. This study investigates the types and prevalence of occupational disruptions, and associated symptoms of mental illness, among Australian frontline healthcare workers during the COVID-19 pandemic. Methods: A national cross-sectional online survey was conducted between 27 August and 23 October 2020. Frontline healthcare workers were invited to participate via dissemination from major health organisations, professional associations or colleges, universities, government contacts, and national media. Data were collected on demographics, home and work situations, and validated scales of anxiety, depression, PTSD, and burnout. Results: Complete responses were received from 7846 healthcare workers (82.4%). Most respondents were female (80.9%) and resided in the Australian state of Victoria (85.2%). Changes to working conditions were common, with 48.5% reporting altered paid or unpaid hours, and many redeployed (16.8%) or changing work roles (27.3%). Nearly a third (30.8%) had experienced a reduction in household income during the pandemic. Symptoms of mental illness were common, being present in 62.1% of participants. Many respondents felt well supported by their workplaces (68.3%) and believed that workplace communication was timely and useful (74.4%). Participants who felt well supported by their organisation had approximately half the risk of experiencing moderate to severe anxiety, depression, burnout, and PTSD. Half (50.4%) of respondents indicated a need for additional training in using personal protective equipment and/or caring for patients with COVID-19. Conclusions: Occupational disruptions during the COVID-19 pandemic occurred commonly in health organisations and were associated with worse mental health outcomes in the Australian health workforce. Feeling well supported was associated with significantly fewer adverse mental health outcomes. Crisis preparedness focusing on the provision of timely and useful communication and support is essential in current and future crises.

The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium-and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a 'very high risk' of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate 'rapid' management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). This study is dedicated to our co-author, the late Prof. Olaf Weyl, whose sudden passing during field work in November 2020 was received by us with great sadness. This study represents a contribution to the term of reference 'd' (Advance knowledge base to further develop indicators to evaluate the status and impact of non-indigenous species in marine environments) of the ICES working group on Introductions and Transfers of Marine Organisms. The participation of GHC was supported by the Cefas Science Excellence fund. AW and AF were supported by TKP2020-NKA-16 project. Cefas Science Excellence fund; [TKP2020-NKA-16]

International audience; Video-encephalographic (vEEG) seizure recordings make essential contributions to the differentiation of epilepsy and psychogenic nonepileptic seizures (PNES). The yield of vEEG examinations can be increased through suggestive seizure manipulation (SSM) (ie, activation/provocation/cessation procedures), but its use has raised ethical concerns. In preparation for guidelines on the investigation of patients with PNES, the ILAE PNES Task Force carried out an international survey to investigate practices of and opinions about SSM. An online questionnaire was developed by the ILAE PNES Task Force. Questions were asked at clinical unit or individual respondent level. All ILAE chapters were encouraged to send questionnaires to their members. The survey was open from July 1, 2019, to August 31, 2019. A total of 487 clinicians from 411 units across 94 countries responded. Some form of SSM was used in 296/411 units (72.0%). Over 90% reported the use of verbal suggestion, over 80% the use of activation procedures also capable of eliciting epileptic activity (hyperventilation or photic stimulation). Only 26.3% of units used techniques specifically intended to provoke PNES (eg, saline injection). Fewer than 10% of units had established protocols for SSM, only 20% of units required written patient consent, in 12.2% of units patients received explicitly false information to provoke seizures. Clinicians using SSM tended to perceive no ethical problems, whereas those not using SSM were likely to have ethical concerns about these methods. We conclude that the use of invasive nocebo techniques intended to provoke PNES in diagnostic settings has declined, but SSM is commonly combined with activation procedures also capable of eliciting epileptic activity. While research suggests that openness about the use of PNES-specific nocebo techniques does not reduce diagnostic yield, very few units have suggestion protocols or seek patient consent. This could be addressed through establishing consensus guidance for the practice of SSM.