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Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons. In 25 healthy individuals, we recorded i-TEPs evoked by a single biphasic TMS pulse targeting the primary motor hand area (M1 HAND) or parietal or midline control sites. Sampling EEG at 50 kHz enabled us to reduce the duration of the TMS pulse artifact to a few milliseconds, while minor adjustments of the TMS coil tilt or position enabled us to avoid cranial muscular twitches during the experiment. We observed an early positive EEG deflection starting after approx. 2 ms followed by a series of superimposed peaks with an inter-peak interval of ∼1.1–1.4 ms in multiple electrodes surrounding the stimulated sensorimotor region. This multi-peak i-TEP response was only evoked by TMS of the M1 HAND region and was modified by changes in stimulation intensity and current direction. Single-pulse TMS of the M1 HAND evokes an immediate local multi-peak response at the cortical site of stimulation. Our results suggest that the observed i-TEP patterns are genuine cortical responses evoked by TMS caused by synchronized excitation of pyramidal neurons in the targeted precentral cortex. This notion needs to be corroborated in future studies, including further investigations into the potential contribution of instrumental or physiological artifacts. • Very early EEG responses to TMS have been obscured by artefacts. • We observed immediate transcranial evoked potentials (i-TEPs) from 2 ms after TMS. • The i-TEPs were composed of a slower positive deflection and high frequency peaks. • The i-TEPs were site-specific and only elicited by stimulation of M1. • The i-TEPs were modified by stimulation intensity and current direction. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) requiring renal-replacement therapy (RRT) after heart transplantation (OHT) is common and impairs outcomes. This study aimed to identify independent donor and recipient risk factors associated with RRT after OHT. A retrospective data analysis. Data were collected from clinical routines in a maximum-care university hospital. Patients who underwent OHT. The authors retrospectively analyzed data from 264 patients who underwent OHT between 2012 and 2021; 189 patients were eligible and included in the final analysis. The mean age was 48.0 ± 12.3 years, and 71.4% of patients were male. Ninety (47.6%) patients were on long-term mechanical circulatory support (lt-MCS). Posttransplant AKI with RRT occurred in 123 (65.1%) patients. In a multivariate analysis, preoperative body mass index >25 kg/m² (odds ratio [OR] 4.74, p < 0. 001), elevated preoperative creatinine levels (OR for each mg/dL increase 3.44, p = 0. 004), administration of red blood cell units during transplantation procedure (OR 2.31, p = 0. 041) and ischemia time (OR for each hour increase 1.77, p = 0. 004) were associated with a higher incidence of RRT. The use of renin-angiotensin-aldosterone system blockers before transplantation was associated with a reduced risk of RRT (OR 0.36, p = 0. 013). The risk of mortality was 6.9-fold higher in patients who required RRT (hazard ratio 6.9, 95% CI: 2.1-22.6 p = 0. 001). Previous lt-MCS, as well as donor parameters, were not associated with RRT after OHT. The implementation of guideline-directed medical therapy, weight reduction, minimizing ischemia time (ie, organ perfusion systems, workflow optimization), and comprehensive patient blood management potentially influences renal function and outcomes after OHT. [ABSTRACT FROM AUTHOR]

The domain of Social Collaboration Analytics (SCA) is gathering momentum due to the increasing importance of Enterprise Collaboration Systems (ECS) that are used to build performant digital workplaces. ECS collect and store large amounts of digital trace data, which reflect the collaborative work of employees. Collaborative work activity is usually supported by multiple systems, which complicates the analysis of the digital traces. The cross-system analysis of collaborative work is challenging because of the nature of the log files that are stored in heterogeneous formats and at different levels of log granularity. These challenges cannot easily be overcome with the help of existing approaches for data preprocessing. In this paper, approaches and frameworks for data mining, data preprocessing and SCA are adapted to design a special method for Social Process Mining (SPM). The DaProXSA approach was developed to obtain interpretable, high-quality event logs of multiple ECS and builds on existing literature as well as on findings from an analysis of leading ECS. DaProXSA contributes to the aim of discovering and interpreting patterns and processes that occur in computer-mediated collaborative work. [ABSTRACT FROM AUTHOR]

Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P <.05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. Retrospective design. EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma of the Bartholin's gland (ACCBG) is a rare, slowly but aggressive malignancy. We reported the case of a 31-year-old woman who was treated by local excision and then hemi-vulvectomy, with positive margins and perineural invasion. Radiation therapy (RT) was then performed delivering 45 Gy in 25 fractions in bilateral inguinal lymph nodes and 64.8 Gy in 36 fractions on the vulvar area. After 30 months, there was no local relapse (LR) but the patient presented a histologically documented lung recurrence. Genomic profiling of the tumor showed a MYB-NFIB fusion transcript and a somatic mutation of PLCG1. A treatment by Lenvatinib was started. We conducted a literature review of 100 published cases. Patients were mainly treated by radical vulvectomy (30%), hemi-vulvectomy (17%), wide or local excision (21% and 24%, respectively) or other. Forty-four percent of patients received postoperative RT, more frequently in case of positive margin (71.9% versus 29.5%). RT may reduce the risk of LR regardless of margin status, with 15.4% vs. 41.9% of LR with or without RT, respectively, in patients with negative margins, and 13% vs. 33.3% of LR with or without RT, respectively, in patients with positive margins. The risk of relapse of any type was 40.9% in patients who received adjuvant RT vs. 48.2% in patients who did not. Median time to relapse was 24 months (range 6–156 months). The most frequent metastatic sites were lung (76.7%) and bone (26.7%). Optimal treatment for ACCBG is still not clearly defined but pooling the data from published case report help us better understand this rare disease and help in the therapeutic decision. [ABSTRACT FROM AUTHOR]

Seba's short-tailed bats (Carollia perspicillata) are a frugivorous species native to Central and South America. Despite their importance as a reservoir for zoonotic pathogens and their popularity in zoological collection and as research models, there are relatively few reports on non-zoonotic diseases of bats. Mites of the genus Demodex are obligate commensals of the skin of a range of mammals, are highly host-specific and are not associated with clinical disease when present in low numbers. However, infestation with high numbers can result in severe or even fatal disease and substantially affect the well-being of the animals. The clinical, pathological and parasitological findings in 12 Seba's short-tailed bats with demodicosis from a colony kept at Munich Zoo Hellabrunn between 1992 and 2021 are described in this report. From 2002, skin lesions became apparent on the head, especially the periocular region, nose and ears, as well as the genital area of some animals. In advanced cases, skin changes were also present on the abdomen, back and extremities. Gross findings typically included alopecia and thickening of the skin, with the formation of papules, reflecting cystically dilated hair follicles containing myriads of demodecid mites. Histologically, lesions were characterized by a paucicellular lymphocytic dermatitis and folliculitis with perifollicular fibrosis, epidermal hyperplasia, orthokeratotic hyperkeratosis and disproportionately high numbers of intrafollicular arthropods. Demodex carolliae was identified morphologically by light, phase-contrast and electron microscopy. Further characterization was achieved by extraction of parasitic DNA and partial gene sequencing of two mitochondrial genes, 16S rDNA and cox1. This is the first clinicopathological description of generalized demodicosis in Seba's short-tailed bats and includes the first molecular characterization of D. carolliae with provision of a GenBank entry. [Display omitted] [ABSTRACT FROM AUTHOR]

The analysis and interpretation of collaborative work in the Digital Workplace requires an in-depth understanding of the user actions carried out in Enterprise Collaboration Systems (ECS). The academic discipline of Process Mining (PM) provides us with methods and tools for the analysis of event logs. For PM to work successfully, we need event logs that are formatted using a standard (e.g. XES) that can be processed by existing PM tools. This is a challenge for the analysis of collaborative work because collaboration processes frequently span across multiple software products, which record user activity in their own proprietary log format. The data from different systems needs to be transformed and aggregated before it can be used by PM tools. To address this issue, we developed a novel concept for the harmonisation and aggregation of log files from collaboration systems. In this concept, events are described as user actions on documents. We formalised the concept in the Collaborative Actions on Documents Ontology (ColActDOnt). ColActDOnt specifies the concepts and properties of collaboration events. The ontology has been made publicly available in a machine-readable format and provides a basis for the analysis of cross-system collaboration. [ABSTRACT FROM AUTHOR]

Mitochondrial proteostasis is critical for cellular function. The molecular chaperone HSP60 is essential for cell function and dysregulation of HSP60 expression has been implicated in cancer and diabetes. The few reported patients carrying HSP60 gene variants show neurodevelopmental delay and brain hypomyelination. Hsp60 interacts with more than 260 mitochondrial proteins but the mitochondrial proteins and functions affected by HSP60 deficiency are poorly characterized. We studied two model systems for HSP60 deficiency: (1) engineered HEK cells carrying an inducible dominant negative HSP60 mutant protein, (2) zebrafish HSP60 knockout larvae. Both systems were analyzed by RNASeq, proteomics, and targeted metabolomics, and several functional assays relevant for the respective model. In addition, skin fibroblasts from patients with disease-associated HSP60 variants were analyzed by proteomics. We show that HSP60 deficiency leads to a differentially downregulated mitochondrial matrix proteome, transcriptional activation of stress responses, and dysregulated cholesterol biosynthesis. This leads to lipid accumulation in zebrafish knockout larvae. Our data provide a compendium of the effects of HSP60 deficiency on the mitochondrial matrix proteome. We show that HSP60 is a master regulator and modulator of mitochondrial functions and metabolic pathways. HSP60 dysfunction also affects cellular metabolism and disrupts the integrated stress response. The effect on cholesterol synthesis explains the effect of HSP60 dysfunction on myelination observed in patients carrying genetic variants of HSP60. [Display omitted] • HSP60 deficiency disrupts the mitochondrial matrix proteome and activates stress responses. • Disrupted matrix proteome impairs catabolism causing acetyl-CoA shortage. • HSP60 deficiency dysregulates cytosolic cholesterol synthesis. • Dysregulated cholesterol synthesis links HSP60 deficiency to hypomyelination. [ABSTRACT FROM AUTHOR]

Significant progress has been made in recent years in the development of techniques for Next Generation Sequencing (NGS), or Massively Parallel Sequencing (MPS), of forensically relevant short tandem repeat (STR) loci. However, as these technologies are investigated and adopted by forensic laboratories, new challenges unfold that require further scrutiny. In the analysis of DNA profiles generated using the MiSeq FGx sequencing system, we have observed noise sequences with relatively high readcounts that are challenging to distinguish from genuine alleles. These high read count noise sequences appear as allele sequences with one or a few substituted bases compared to a known allele sequence within the profile. An examination of ForenSeq DNA Signature Prep Kit STR noise sequences revealed that the substituted base of a parent allele can align to the same position on the sequence across noise sequences. This suggests that these substitution events occur at specific positions within the amplicon, resulting in multiple noise reads with substitutions at the same position. Mapping of the noise events onto the original raw read positions revealed a high number of events, or "noise spikes", occurring at specific positions within a given sequencing run. These noise spikes affected reads across the entire run, agnostic of locus or sample, while the position, occurrence, and amplitude of the spikes differed across runs. The majority of noise sequences with high read counts in a DNA profile were generated from base changes at these spike positions, and could be classified as "noise spike artefacts". In this paper we present evidence of the noise spike artefacts and their genesis during the sequencing process in the sequencing-by-synthesis (SBS) cycles, as well as the methods developed to detect them. The information and methods will assist laboratories with detecting noise spikes in MiSeq FGx sequencing runs, differentiating authentic allele sequences from noise spike artefacts, and developing protocols for analyst review and handling of MiSeq FGx data. • High coverage noise sequences can be present in NGS STR data, which can complicate downstream genotyping. • These are likely generated during sequencing by unknown causes, affecting entire runs at discrete sequencing cycles. • Noise sequences manifest as spikes in substitution and indels when aligned to the positions in the original reads. • Base quality scores are associated with error spikes, but not reliable for their detection. • Library re-sequencing reduce these artefacts, and further analysis is needed for effective quality-based noise thresholds. [ABSTRACT FROM AUTHOR]

• Population density does impact on COVID-19 spread and mortality in Germany. • The effect of density on COVID-19 mortality is small and transitory. • Location has a three times greater impact on mortality than density does. • Enhancing informational connectivity is more crucial than population dispersion. • International coordination is more important than inner-city restrictions. Significant research has been devoted to understanding how environmental factors affect the COVID-19 risks local populations face. Urban density has been identified as a critical factor, posing a particular threat in densely populated countries like Germany, one of Europe's most crowded nations. Furthermore, the high degree of interconnectivity between German regions increases the risk of virus transmission from infection hotspots through regional dispersion. Our research uses linear and non-linear regression models, enhanced with longitude and latitude, to assess the relative impact of population density and regional dispersion of COVID-19 mortality across German counties. Our findings, adjusted for health-related variables, indicate that locational factors have a three times greater impact on mortality than density does. This highlights that pandemic mortality risk is shaped not only by our individual responses but also by the actions of our neighbours. Consequently, our research suggests that, given the increasing global interdependence, regional sprawl cannot be the dominant strategy for planners to avoid the consequences of a pandemic. Instead, the priority should be efficient information management to identify and mitigate interdependence with infection hotspots, which requires enhanced international cooperation. [ABSTRACT FROM AUTHOR]

To compare the efficacy, safety, and side effects of hydromorphone and morphine administered as patient-controlled analgesia (PCA) for postoperative pain therapy after cardiac surgery with median sternotomy. A retrospective analysis of data from 2 prospective, single-blinded, randomized trials. A single-center intensive care unit at a university hospital. Forty-one adult patients undergoing cardiac surgery with median sternotomy. Postoperative pain therapy at the intensive care unit was performed by PCA with intravenously administered bolus doses of 0.2 mg of hydromorphone (n = 21) or 2 mg of morphine (n = 20). Pain at rest and under deep inspiration regularly was assessed using the 11-point numerical rating scale (NRS). Blood pressure, heart rate, cardiac output, oxygen saturation, and respiratory rate were monitored, and adverse events were registered. The median (range) NRS rating at rest was 1.5 (0-5) after hydromorphone and 0.5 (0-5) after morphine, respectively (p = 0.41). The median NRS rating under deep inspiration was 3 (0-6) after hydromorphone and 4 (0-7) after morphine, respectively (p = 0.074). The dose ratio of morphine to hydromorphone during PCA was 5.7 (95% confidence interval: 2.9-7.6). Hemodynamics and respiration were stable and did not differ significantly. Postoperative nausea and vomiting were the most frequent adverse events, which were observed in 29% of the patients after hydromorphone and in 35% after morphine, respectively (p = 0.74). There were no significant differences in analgesic efficacy and safety between hydromorphone and morphine when used for postoperative pain therapy with PCA after cardiac surgery with median sternotomy. [ABSTRACT FROM AUTHOR]

Managed forests represent a major fraction of the global forest area and are known to host impoverished biodiversity compared to natural forests. The effect of forest management has focused mainly on aggregated community metrics such as species richness of single taxa and on simplistic managed vs. unmanaged comparisons. However, the effect of forest management is expected to vary among species and taxa and to be contingent on site-specific conditions. In this study, we focus on fine-scale multi-taxon biodiversity patterns to disentangle the impact of forest management on the forest structure and the abiotic soil conditions of the stands. We base our comparisons on carefully selected pairs of managed and unmanaged stands to minimize regional differences that could confound the effects of management. We found that the total effect of forest management on alpha diversity was positive on plants and rove beetles, neutral on ground beetles and mosses, and negative on crane flies, fungi, and lichens. However, using joint species distribution modeling we show that individual species' responses to the local underlying soil conditions can be as important as the forest structural changes induced by management, but this varied among the different taxa. Based on these responses we disclose synergies and trade-offs among some of the taxa. Our results indicate that the balance between forest management and abiotic conditions can shape the patterns of forest multi-taxon biodiversity. Considering these conditions can be important in predicting the response of biodiversity to forest management and act as key criteria when prioritizing areas for the conservation of biodiversity. [Display omitted] • Species richness alone provides limited insight into the effects of forest management on biodiversity. • Species-level analysis reveals the intricate relationship between forest structure, soil conditions, and species diversity. • Lichens and fungi respond positively to natural forest structures, underscoring their role as ecological indicators. • Incorporating species-level analysis unveils patterns overlooked by traditional metrics. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Because a therapeutic regimen remains scarce, the early implementation of preventive strategies is crucial. The authors investigated risk factors and the typical clinical course of CS-associated AKI (CS-AKI) to derive strategies for perioperative clinical routines. Retrospective data analysis. The data were collected from clinical routines in a maximum care university hospital. Patients. The authors retrospectively analyzed data from 538 patients who underwent CS. The median age of the 466 patients included was 66.6 years; 65.7% were men. AKI occurred in 131 (28.1%) patients, mainly (89.0%) starting postoperatively within 72 hours p. Thirty-one (6.7%) patients showed Kidney Disease Improving Global Outcome AKI stage 3. AKI was significantly more frequent in patients with chronic kidney disease (p < 0. 001), emergency admission (p < 0. 001), heart failure (p < 0. 001), and postoperative complications (p < 0. 001). In a multivariate analysis, postoperative CS-AKI risk significantly decreased with each 1 or 10 mL/min preoperative glomerular filtration rate (GFR) (odds ratio, 0.962 and 0.677; 95% confidence interval, 0.947-0.977 and 0.577-0.793; p < 0. 001 and p < 0. 0001). Only in patients who developed Kidney Disease Improving Global Outcome AKI stage 3, an early postoperative trend to decreased GFR and increased creatinine levels was observed. Especially in patients with preexisting CKD and signs of CS-AKI occurring on the day of surgery, close monitoring of renal function should be performed for at least 72 hours after CS to detect an onset of AKI early and initiate renal protective strategies. Optimal preoperative fluid management might prevent postoperative AKI. [ABSTRACT FROM AUTHOR]

MicroHapulator's empirical microhaplotype calling algorithm produces profiles well-suited for forensic analyst interpretation and probabilistic interpretation. [ABSTRACT FROM AUTHOR]

The presence of more than one DNA contributor in an evidentiary sample may preclude attempts to use forensic genetic genealogy to develop an investigative lead. To address this issue, we developed a workflow for deconvolution of SNP mixtures into single source profiles that are suitable for matching against a genealogical database. Using the method, two-contributor DNA mixtures assayed using a commercial SNP typing kit can produce informative match results for both major and minor contributors. [ABSTRACT FROM AUTHOR]

Background: Limited data are available concerning the safety, optimal administration and benefits of contemporary heart failure therapy in patients after left ventricular assist device (LVAD) implantation.Methods: Between 2015 and 2019, 257 patients underwent LVAD implantation and were included in this observational study. Oral heart failure therapy was initiated and uptitrated during the further course. After propensity matching and excluding patients with immediate postoperative treatment in an affiliated center with different medical standards, hospitalization rates and mortality within 12 months after LVAD implantation were compared between 83 patients who received medical therapy including an angiotensin receptor neprilysin inhibitor (ARNI) and 83 patients who did not receive an ARNI.Results: The overall use of heart-failure medications after 12 months was high: prescriptions: beta-blockers, 85%; angiotensin inhibiting drugs, 90% (angiotensin-converting-enzyme inhibitors 30%, angiotensin receptor blockers 23%, ARNI 37%); mineralocorticoid receptor antagonists, 80%. No serious drug-related adverse events occurred. The conditional 1-year survival in the group with ARNIs was 97% (95% CI: 94%-100%) compared to 88% in the group without an ARNI (95% CI: 80%-96%); P = 0.06.Conclusions: Contemporary heart failure therapy is safe in patients with LVADs. No increase in serious adverse events was seen in patients receiving ARNIs. No significant difference in the conditional 1-year survival was seen between the ARNI group and the nonARNI group. [ABSTRACT FROM AUTHOR]

To explore children's, parents', and healthcare professionals', experiences of anesthesia related to pediatric oncological treatment performed at the pediatric oncology ward. The study was a qualitative study. 11 children and 12 parents were recruited for individual or dyadic interviews and two focus groups with a total of 12 healthcare professionals were recruited through purposeful and convenience sampling procedures. Thematic analysis generated one main theme, the familiar in the unfamiliar, and two subthemes, the room creates an atmosphere and relational continuity. Changing the physical environment and composition of the team positively influenced the experience of anesthesia in pediatric cancer treatment for both children, parents, and healthcare professionals. Familiarity was important for all involved and familiarity was associated with continuity related to the physical environment, as well as the relational and procedural professional continuity. Parents expressed that they never felt good about anesthesia as there were feelings of leaving your child's life into the hands of others. However, familiarity in trusting relationships with healthcare professionals helped to moderate these aspects. Familiarity should be considered important with continuity in trusting relations and collaborations between nurses and families, as well as between healthcare staff. Pediatric oncology ward is a preferred safe familiar setting for procedure-related anesthesia. Parents and children value individualized flexible nursing care, that takes the child's and parents habits and preferences into account during procedure-related anesthesia in pediatric oncological treatment. • Known settings are beneficial during anesthesia in pediatric oncology for children, parents, and healthcare professionals. • Trusting relationships with healthcare professionals helped parents during anesthesia in pediatric cancer treatment. • Relational continuity increases individualized nursing care. • Staff collaboration is flexible with known team members during anesthesia in the pediatric oncology ward. [ABSTRACT FROM AUTHOR]

Les examens biologiques d'allergie contribuent de façon importante au diagnostic et au suivi des allergies respiratoires. L'augmentation de la prévalence de ces maladies dans la population française durant les dernières décennies et le recours de plus en plus fréquent au diagnostic biologique nécessite l'optimisation de l'utilisation de cet outil. Son utilisation rationnelle selon les données actualisées de la science et une démarche privilégiant le rapport coût/bénéfice sont à même de garantir l'efficience diagnostique. Consciente de cet enjeu, la Société française d'allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l'actualisation des recommandations de biologie de l'allergie, les précédentes recommandations élaborées en 2005 par la Haute Autorité de santé (HAS) étant devenues en partie obsolètes en raison de l'évolution des techniques et concepts. La méthodologie utilisée est celle des recommandations pour la pratique clinique (RPC) élaborée par la HAS, même si le texte n'a pas été labellisé par celle institution. Le groupe de travail a rédigé 11 recommandations gradées sur l'allergie respiratoire. Bien que non exhaustives, ces 11 questions répondent aux préoccupations les plus courantes des prescripteurs qu'ils soient allergologues ou non pour la prise en charge des patients ayant une suspicion d'allergie respiratoire, tout en tenant compte du contexte réglementaire français. Allergy laboratory tests provide an important contribution to the diagnosis and monitoring of respiratory allergies. The increase in the prevalence of these diseases in the French population during the last decades and the increasingly frequent use of biological diagnosis requires the optimization of the use of this tool. Its rational use according to updated scientific data and an approach favoring the cost/benefit ratio can guarantee diagnostic efficiency. Aware of this issue, the French Society of Allergology (SFA) has set up a multidisciplinary task force to update allergy biology recommendations, the previous recommendations drawn up in 2005 by the High Authority for Health (HAS) having become partly obsolete due to the evolution of techniques and concepts. The methodology used is that of the recommendations for clinical practice (RPC) developed by the HAS, even if the text has not been labeled by that institution. The working group drafted 11 graded recommendations for the management of respiratory allergy. Although not exhaustive, these 11 questions respond to the most common concerns of prescribers whether or not they are allergists for the management of patients with allergies or with a suspected respiratory allergy, while taking into account the French regulatory context. [ABSTRACT FROM AUTHOR]

Les examens biologiques d'allergie contribuent de façon importante au diagnostic et au suivi des allergies alimentaires. L'augmentation de la prévalence des allergies alimentaires dans la population française durant les dernières décennies et le recours de plus en plus fréquent au diagnostic biologique nécessite l'optimisation de l'utilisation de cet outil. Son utilisation rationnelle selon les données actualisées de la science et une démarche privilégiant le rapport coût/bénéfice sont à même de garantir l'efficience diagnostique. Le mésusage de la biologie de l'allergie et/ou son interprétation erronée risque d'aboutir à des attitudes thérapeutiques inadaptées voire dangereuses. Consciente de cet enjeu, la Société française d'allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l'actualisation des recommandations de biologie de l'allergie, les précédentes recommandations élaborées en 2005 par la Haute autorité de santé (HAS) étant devenues en partie obsolètes en raison de l'évolution des techniques et concepts. La méthodologie utilisée est celle des recommandations pour la pratique clinique (RPC) élaborée par la HAS, même si le texte n'a pas été labellisé par celle institution. Le groupe de travail a rédigé 28 recommandations gradées sur l'allergie alimentaire. Bien que non exhaustives, ces 28 questions répondent aux préoccupations les plus courantes des prescripteurs qu'ils soient allergologues ou non pour la prise en charge des allergies alimentaires avérées ou suspectées, tout en tenant compte du contexte réglementaire français. Allergy laboratory tests provide an important contribution to the diagnosis and monitoring of food allergies. The increase in the prevalence of food allergies in the French population during the last decades and the increasingly frequent use of biological diagnosis requires the optimization of the use of this tool. Its rational use according to updated scientific data and an approach favoring the cost/benefit ratio can guarantee diagnostic efficiency. The misuse of allergy biology and/or its misinterpretation may lead to inappropriate or even dangerous therapeutic attitudes. Aware of this issue, the French Society of Allergology (SFA) has set up a multidisciplinary task force to update allergy biology recommendations, the previous recommendations drawn up in 2005 by the High Authority for Health (HAS) having become partly obsolete due to the evolution of techniques and concepts. The methodology used is that of the recommendations for clinical practice (RPC) developed by the HAS, even if the text has not been labeled by that institution. The working group drafted 28 graded recommendations for the management of food allergy. Although not exhaustive, these 28 questions respond to the most common concerns of prescribers whether or not they are allergists for the care of known or suspected food allergies, while taking into account the French regulatory context. [ABSTRACT FROM AUTHOR]

Les examens biologiques d'allergie contribuent de façon significative au diagnostic et au suivi des allergies aux piqûres et morsures d'arthropodes. Les dosages d'IgE spécifiques apportent la preuve d'un mécanisme allergique IgE-dépendant. L'utilisation rationnelle des outils biologiques disponibles selon les données actualisées de la science est à même de garantir l'efficience diagnostique. Le mésusage de la biologie de l'allergie et/ou leur interprétation erronée risque d'aboutir à des attitudes thérapeutiques inadaptées. Consciente de cet enjeu, la Société française d'allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l'actualisation des recommandations de biologie de l'allergie, les précédentes recommandations élaborées en 2005 par la Haute autorité de santé (HAS) étant devenues en partie obsolètes en raison de l'évolution des techniques et concepts. La méthodologie utilisée est celle des recommandations pour la pratique clinique (RPC) élaborée par la HAS, même si le texte n'a pas été labellisé par celle institution. Le groupe de travail a rédigé 8 recommandations gradées sur l'allergie aux piqûres et morsures d'arthropodes et 5 recommandations gradées sur d'autres pathologies immuno-allergiques ou frontière. Bien que non exhaustives, ces 13 questions répondent aux préoccupations les plus courantes des prescripteurs qu'ils soient allergologues ou non, tout en tenant compte du contexte réglementaire français. Allergy laboratory tests provide a significant contribution to the diagnosis and monitoring of allergies to arthropods sting or bite. Specific IgE assays provide evidence of an IgE-dependent allergic mechanism. The rational use of the biological tools available according to updated scientific data can guarantee diagnostic efficiency. The misuse of the biology of allergy and/or their misinterpretation may lead to inappropriate therapeutic attitudes. Aware of this issue, the French Society of Allergology (SFA) has set up a multidisciplinary task force to update allergy biology recommendations, the previous recommendations drawn up in 2005 by the French High Authority for Health (HAS) having become partly obsolete due to the evolution of techniques and concepts. The methodology used is that of the recommendations for clinical practice (RPC) developed by the HAS, even if the text has not been labeled by that institution. The working group drafted 8 graded recommendations for the management of allergy to arthropods sting or bite, and 5 graded recommendations on other immuno-allergic or frontier diseases. Although not exhaustive, these 13 questions respond to the most common concerns of prescribers whether or not they are allergists, while taking into account the French regulatory context. [ABSTRACT FROM AUTHOR]

Contrairement aux allergies respiratoires, alimentaires et aux venins d'hyménoptères qui concernent des allergènes protéiques, la prise en charge des allergies aux médicaments nécessite rarement le recours aux examens biologiques pour obtenir la preuve d'un mécanisme allergique IgE-dépendant. Un nombre très restreint de dosages d'IgE spécifiques de médicaments est disponible car la grande majorité des médicaments sont des haptènes. L'utilisation rationnelle des outils biologiques disponibles selon les données actualisées de la science est à même de garantir l'efficience diagnostique. Le mésusage de la biologie de l'allergie et/ou leur interprétation erronée risque d'aboutir à des attitudes thérapeutiques inadaptées voire dangereuses. Consciente de cet enjeu, la Société française d'allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l'actualisation des recommandations de biologie de l'allergie, les précédentes recommandations élaborées en 2005 par la Haute autorité de santé (HAS) étant devenues en partie obsolètes en raison de l'évolution des techniques et concepts. La méthodologie utilisée est celle des recommandations pour la pratique clinique (RPC) élaborée par la HAS, même si le texte n'a pas été labellisé par celle institution. Le groupe de travail a rédigé 11 recommandations gradées sur l'allergie aux médicaments. Bien que non exhaustives, ces 11 questions répondent aux préoccupations les plus courantes des prescripteurs qu'ils soient allergologues ou non pour la prise en charge des patients ayant une suspicion d'allergie aux médicaments, tout en tenant compte du contexte réglementaire français. Unlike respiratory allergies, food allergies and hymenopteran venoms which involve protein allergens, the management of drug allergies rarely requires the use of laboratory tests to obtain evidence of an IgE-dependent allergic mechanism. A very small number of drug specific IgE assays are available because drugs are mostly haptens. The rational use of the biological tools available according to updated scientific data can guarantee diagnostic efficiency. The misuse of the biology of allergy and/or their misinterpretation may lead to inappropriate or even dangerous therapeutic attitudes. Aware of this issue, the French Society of Allergology (SFA) has set up a multidisciplinary task force to update allergy biology recommendations, the previous recommendations drawn up in 2005 by the High Authority for Health (HAS) having become partly obsolete due to the evolution of techniques and concepts. The methodology used is that of the recommendations for clinical practice (RPC) developed by the HAS, even if the text has not been labeled by that institution. The working group drafted 11 graded recommendations for the management of drug allergy. Although not exhaustive, these 11 questions respond to the most common concerns of prescribers whether or not they are allergists for the management of patients with suspected drug allergy, while taking into account the French regulatory context. [ABSTRACT FROM AUTHOR]

Le sésame est un allergène à connaître car présent dans notre alimentation mais aussi dans certains produits pharmaceutiques et cosmétiques. L'allergie au sésame a une prévalence faible mais est potentiellement sévère avec un risque élevé d'anaphylaxie. Les tests cutanés et les IgE spécifiques sont de valeur inconstante ; la place des allergènes recombinants reste à mieux préciser. Le test de provocation par voie orale tient une place essentielle en cas de doute diagnostique et pour évaluer une éventuelle guérison dont le taux est autour de 20 %. Il nécessite une équipe rompue à la prise en charge de l'anaphylaxie. Un prick test supérieur à 14 mm semble être associé à un taux de positivité du TPO de l'ordre de 95 %. La prise en charge repose avant tout sur l'éviction du sésame. Une liste peut être remise aux familles afin de notifier les principales sources d'exposition. L'immunothérapie orale pourrait apparaître comme une perspective intéressante mais doit être actuellement réservée aux centres experts. Sesame is an allergen to keep in mind, because it is present in usual common foods and also in some pharmaceutical and cosmetic products. Sesame allergy has a low prevalence but is potentially severe with a high risk of anaphylaxis. Skin tests and specific IgE are of inconstant value; the place of recombinant allergens remains to be better understood. The oral food challenge (OFC) plays an essential role to help diagnosis in difficult cases and/or to evaluate a tolerance, for which the rate is around of 20%. This requires a team that is experimented in anaphylaxis management. A skin test greater than 14 mm seems to be associated with a positive OFC in 95% of cases. The management of sesame allergy is primarily based on a strict avoidance. A list may be provided to families to notify them of the main sources of exposure. Oral immunotherapy appears to be an interesting prospect but should by reserved for expert centres. [ABSTRACT FROM AUTHOR]

Les allergies touchent 25 % de la population générale avec une augmentation des allergies sévères. Le développement en France de structures de soins transversales en allergologie pour une prise en charge pluridisciplinaire des patients répond à un besoin de santé publique. Notre travail a pour but de faire un état des lieux de ces structures. Enquête descriptive par questionnaire envoyé aux chefs de services de structures de soins soit avec une activité principale en allergologie, soit avec une activité variée en allergologie. L'enquête portait sur l'organisation administrative, les équipes médicales et paramédicales, l'offre de soins et les moyens techniques des structures. Trente-sept structures ont pu être analysées dont 27 avec une activité principale en allergologie et 10 avec une activité variée en allergologie. Pour les premières, le nombre de médecins varie de 1 à 16 et les équivalents temps pleins infirmier de 0,8 à 5,9. Les nombres d'hospitalisations de jour et de consultations annuelles sont respectivement de 1049 (220 à 3275) et 3561 (609 à 13 674). Un tiers du recrutement des patients est hors département. Toutes les structures avec une activité principale en allergologie réalisent des explorations sur les allergies alimentaires, médicamenteuses et aux pneumallergènes mais seulement 81 % et 74 % assurent respectivement la prise en charge des allergies aux hyménoptères et des eczémas de contact. Cette étude constitue un premier état des lieux des structures hospitalières transversales en allergologie en France afin de permettre de guider le développement d'Unités transversales d'allergologie. Allergies affect 25% of the general population with an increase in severe allergies. The development in France of cross-disciplinary allergology care structures for multidisciplinary management of patients meets a public health need. The aim of our work is to provide an overview of these structures. Descriptive survey by questionnaire sent to the heads of health care facilities either with a main activity in allergology or with a varied activity in allergology. The survey covered the administrative organisation, the medical and paramedical teams, the care offer and the technical means of the facilities. Thirty-seven facilities were analysed, 27 of which had a main activity in allergology and 10 with a varied activity in allergology. For the former, the number of doctors varies from 1 to 16 and the full-time equivalent nurses from 0.8 to 5.9. The numbers of day hospitalisations and annual consultations are respectively 1049 (220 to 3275) and 3561 (609 to 13,674). One third of patient recruitment is outside the department. All the structures with a main activity in allergology carry out investigations on food, drug and pneumallergen allergies but only 81% and 74% respectively provide care for allergies to hymenoptera and contact eczema. This study constitutes a first inventory of cross-disciplinary hospital structures in allergology in France in order to guide the development of cross-disciplinary allergy units. [ABSTRACT FROM AUTHOR]

Brass players are exposed to high musculoskeletal strains during their instrumental play. Various assessments can be used to measure these strains, whereby a targeted therapy can also be supported. The aim of this study was to review literature concerning assessments used in quantitatively based studies about the analysis of musculoskeletal loads of brass players. The Cochrane Library, PubMed, CINAHL, PEDro as well as the journal "Medical Problems of Performing Artists" were searched for relevant studies. Two reviewers independently applied the inclusion and exclusion criteria to select potential studies. A third reviewer was involved in the case of discrepancies. Two reviewers independently extracted the data. A total of 73 studies conducted between 2004 and 2019 were included. Within a total of 30 studies, 18 assessments could be found that collect 2-dimensional or 3-dimensional kinematic data using video- or image-based analysis of posture, sonographic, optoelectronic and various electromagnetic systems. In 7 studies kinetic data were measured by force-transducers, pressure platforms, stabilizer and dynamometer. Fifteen studies used clinical examinations and additional assessments to screen individual body regions and 9 studies derived electromyography measurements from a total of 25 muscles. Thirty-one partially validated questionnaires were used to record musculoskeletal pain of brass players. A variety of assessments can be used to optimize analysis and treatment procedures in research and clinical work. Future studies should both examine quality criteria of the various assessment methods and validate clinical examinations and questionnaires. [ABSTRACT FROM AUTHOR]

There is a lack of information regarding electrical properties of white matter and brain tumors. To investigate the feasibility of in-vivo measurement of electrical resistivity during brain surgery and establish a better understanding of the resistivity patterns of brain tumors in correlation to the white matter. A bipolar probe was used to measure electrical resistivity during surgery in a prospective cohort of patients with brain tumors. For impedance measurement, the probe applied a constant current of 0.7 μA with a frequency of 140 Hz. The measurement was performed in the white matter within and outside peritumoral edema as well as in non-enhancing, enhancing and necrotic tumor areas. Resistivity values expressed in ohmmeter (Ω∗m) were compared between different intracranial tissues and brain tumors. Ninety-two patients (gliomas WHO II:16, WHO III:10, WHO IV:33, metastasis:33) were included. White matter outside peritumoral edema had higher resistivity values (13.3 ± 1.7 Ω∗m) than within peritumoral edema (8.5 ± 1.6 Ω∗m), and both had higher values than brain tumors including non-enhancing (WHO II:6.4 ± 1.3 Ω∗m, WHO III:6.3 ± 0.9 Ω∗m), enhancing (WHO IV:5 ± 1 Ω∗m, metastasis:5.4 ± 1.3 Ω∗m) and necrotic tumor areas (WHO IV:3.9 ± 1.1 Ω∗m, metastasis:4.3 ± 1.3 Ω∗m), p=<0.001. No difference was found between low-grade and anaplastic gliomas, p = 0.808, while resistivity values in both were higher than the highest values found in glioblastomas, p = 0.003 and p = 0.004, respectively. The technique we applied enabled us to measure electrical resistivity of white matter and brain tumors in-vivo presumably with a significant effect with regard to dielectric polarization. Our results suggest that there are significant differences within different areas and subtypes of brain tumors and that white matter exhibits higher electrical resistivity than brain tumors. • In-vivo measurement of electrical resistivity during brain surgery is feasible. • White matter has higher electrical resistivity values than brain tumors. • Resistivity values of brain tumors seem to decrease with increasing malignancy. [ABSTRACT FROM AUTHOR]

Emerging drug-resistant strains of Candida albicans have led to the recurrence of fungal disease, rendering conventional drug therapies ineffective. Although in vitro studies on flavonoids as novel antifungal products have shown promising results, there is currently limited information regarding their in vivo effects. The aim of this review is to evaluate in vivo studies on the antifungal activity of flavonoids against C. albicans , as novel therapeutic agents. In this regard, we conducted broad searches of PubMed, Web of Science, and Embase covering the years 2009–2020. Flavonoids represent new natural therapeutic compounds to treat oral candidiasis. Among subclasses of flavonoids, flavonols and chalcones appear to have the most significant antifungal activities. Oral administration of Canthin-6-one, a flavonol, has the potential to damage fungal cell membrane while having minimal toxic effects on mice. Similarly, topical oral application of lichochalcone-A, a chalcone, reduces oral candidiasis in mice. There appears to be structural similarities in the hydroxyl residues among compounds within the same subclass of flavonoids, which may contribute to antibiofilm activity. Oral topical application of flavonoids shows low toxicity and has clinical relevance as potential novel antifungal treatments. Flavonoids are a group of natural products exhibiting antifungal activity. The subclasses flavonols and chalcones appear to have the most significant in vivo antifungal activity against C. albicans infections in mouse models. Specifically, quercetin (flavonol) has been applied via vaginal gavage in a murine vulvovaginal candidiasis model, whereas lichochalcone-A (chalcone) has shown topical oral application in C. albicans -inoculated mice. Both compounds show efficacy in fungal elimination via biofilm inhibition for their respective subclasses. The translational significance of these in vivo studies should be examined in clinical trials of selected potent compounds for the treatment of oral candidiasis. Further studies are necessary to elucidate the specific mechanisms of flavonoids as antifungal agents. • Flavonoids represent a new natural therapeutic compound to treat oral candidiasis. • Flavonols and chalcones appeared to have the most significant antifungal activity. • Topically applied lichochalcone-A (chalcones) reduced oral candidiasis in mice. • Subclasses shared hydroxyl residues and shapes contributing to anti-biofilm action. • Topical flavonoids show low toxicity and has clinical relevance for oral treatment. [ABSTRACT FROM AUTHOR]

PEDIASTHMA is a multicenter, observational, retrospective and prospective real-life study evaluating the use of dupilumab in adolescents ≥ 12 years of age with severe uncontrolled asthma. To describe characteristics of patients enrolled in PEDIASTHMA with severe asthma. This analysis presents the phenotypic characteristics of severe asthma at the initiation of dupilumab in 50 adolescents enrolled in 15 centers. Results are expressed as median [IQ25–75] or n (%). Thirty-three (66%) were males, with a median age of 14.9 [13.1–15.9] years. Patients were 8.1 [4.7–12.7] years old when they had a diagnosis of severe asthma. 27 (54.0%) had been previously treated with biotherapy, including 7 (25.9%) with ≥ 1 biotherapy. At baseline, the number of severe exacerbations in the previous year was 2.0 (1.0–5.0), pre-BD FEV1 81.0% [67.0–94.0], FEV1/FVC 80.0% [71.0–91.0], blood eosinophilia 0.38 (0.16–0–0.53) G/L, FeNO 35.8 [11.0–66.9] ppb. 33 (66%) of the patients were sensitized to ≥ 1 aeroallergen, 15 (30.0%) had food allergy, 32 (64.0%) allergic rhinitis, 28 (56.0%) atopic dermatitis, and 1 (2.0%) eosinophilic esophagitis. The expected features of severe adolescent asthma were found in this cohort. However, one in two adolescents had severe lung function impairment and one in two was prescribed dupilumab after another biotherapy. In relation to published randomized trials(ref), the follow-up of this cohort will allow us to monitor the real-world response of dupilumab on asthma control and lung function. [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• First phytochemical investigation of the roots of Myoporum insulare. • Four new and five known diterpenoids were isolated by analytical-scale HPLC. • Dual high-resolution α-glucosidase/PTP1B inhibition profiling revealed bioactivity. • The diterpene alkaloid microthecaline A found outside Eremophila for the first time. A methylene chloride extract of Myoporum insulare R. Br. (Scrophulariaceae) root material was investigated by dual high-resolution PTP1B/α-glucosidase inhibition profiling and LC-PDA-HRMS. Subsequent analytical-scale separation of the crude extract afforded serrulatanes 1 - 9 of which 2 ((1 R ,11 S ,18 R)-5,18-epoxyserrulat-3,14-dien-8,18-diol or myoporulatane A), 6 ((1 R ,4 S ,11 S)-8-hydroxy-serrulat-14-en-18,5-olide or myoporulatane B), 7 ((1 R ,4 S ,11 S)-serrulat-14-en-5,8,18-trione or myoporulatane C), and 9 ((1 S , 2 R ,4 S ,11 S)-2β-hydroxy-serrulat-14-ene or myoporulatane D) are previously unreported. The structures of all isolated compounds were established by HRMS as well as 1D and 2D NMR analysis. Relative configurations were determined from combined analyses of chemical shifts, J -coupling constants and ROESY correlations, and absolute configurations were tentatively assigned by comparison to previous studies and from biosynthetic arguments. Compounds correlated with PTP1B inhibitory activity in the high-resolution inhibition profile were tested after isolation. However, the pure compounds exhibited weak or essentially no inhibitory activity against PTP1B with IC 50 values of 97.4 μM for 2 , 3.0 mM for 4 , and > 100 μM for 7. This is the first study of the root chemistry of M. insulare. [ABSTRACT FROM AUTHOR]

L'hétérogénéité de l'asthme dans l'enfance est caractérisée par de multiples phénotypes liés à des mécanismes physiopathologiques différents qui caractérisent les endotypes. Les sensibilisations allergéniques multiples et précoces sont associées à un risque plus élevé d'exacerbations d'asthme. Le risque de persistance de l'asthme à l'âge adulte est un phénotype d'asthme sévère notamment à début précoce avec comorbiditées allergiques multiples et/ou avec mauvaise fonction respiratoire. A l'inverse, l'inflammation des voies respiratoires à neutrophile est moins fréquente chez les enfants souffrant d'asthme et n'est pas stable au cours du temps. The heterogeneity of asthma and allergic diseases in childhood is characterized by multiple phenotypes related to different pathophysiologic mechanisms or endotypes. Early multiple carry a higher risk of severe asthma phenotype, especially in terms of asthma exacerbations. Early-onset asthma with multiple allergic comorbidities and/or poor lung function entails a risk of persistent lifelong asthma. Conversely, the neutrophilic asthma phenotype is less common in children and is not stable over time. [ABSTRACT FROM AUTHOR]

Maturity and immaturity are the hallmarks of Witold Gombrowicz's literary texts. They were introduced in his first novel, Ferdydurke , and an early collection of short stories, Memoirs from a Time of Immaturity , and continued to play a central role in his fiction and nonfiction works, including the Diary , A Kind of Testament , and the penultimate novel, Pornografia. Although Gombrowicz has been widely regarded as a staunch critic of maturity and defender of immature spontaneity, playfulness, and formlessness, this view is largely based on his earlier writings. Later works offer a more complex image of Gombrowicz. Pornografia , in particular, no longer pits immaturity against maturity with the goal of discrediting the latter through humor and irony. Instead, it experiments with the possibility of a new relationship between the two, a relationship which would ameliorate the discontents that often come with aging. [ABSTRACT FROM AUTHOR]

À la suite de la reconnaissance de l'allergologie comme spécialité, la FFAL a travaillé avec le ministère des Solidarités et de la Santé dans le but d'élaborer une cartographie de l'offre de soins en allergologie en France. Un questionnaire électronique a été diffusé par le biais des newsletters des différentes instances de l'allergologie française. Les résultats de ce questionnaire sont présentés et analysés dans cet article. Following the recognition of allergy as a full specialty, the FFAL worked with the Ministry of Solidarity and Health in order to draw up a map of the supply of allergy care in France. An electronic questionnaire was disseminated through newsletters from the various authority of French allergology. The results of this questionnaire are presented and analyzed in this article. [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study examines the role of cryptocurrencies as a hedging and safe-haven instrument against stock market risk. Employing five of the largest cryptocurrencies by market capitalization: BTC, ETH, BNB, ADA, and XRP, from 2017 to 2022 in a variance-optimal hedging framework we investigate and compare the hedging effectiveness of cryptocurrencies for the developed G7 and emerging BRICS stock markets. Based on EVT we introduced a new approach to the assessment of hedging effectiveness. We found that the probability of at least 10-percent hedging effectiveness of Bitcoin is approximately equal to zero. The conditional probability that Bitcoin can reduce at least 10% of volatility given that index returns fall below the 1st percentile is higher and ranges from 2% to 28.4% depending on the stock market. The probabilities estimated for other cryptocurrencies are lower. We provide new and valuable knowledge for investors, who consider cryptocurrencies as a shelter for their investment portfolios. [Display omitted] • Effectiveness of hedging global stock markets with cryptocurrencies is verified. • New approach to assessment of hedge effectiveness based on the Extreme Value Theory is introduced. • Probability that cryptocurrencies can reduce at least 10% of volatility of global stock indices is approximately zero. • Probability that Bitcoin can reduce at least 10% of volatility when index falls below the 1st percentile is lower than 29%. • Hedging and safe-haven properties are destroyed by extreme volatility of cryptocurrencies. [ABSTRACT FROM AUTHOR]

• Larger ESG differences between acquirer and target speed up M&A closing. • This effect only occurs when acquirer exceeds target ESG performance. • Higher target ESG performance leads to longer time to completion. • The effects are driven by the environmental pillar. Sustainability is currently a major concern in business and society. As environmental, social, and governance (ESG) aspects are also considered in acquisitions, e.g., through time-consuming ESG due diligences, we investigate whether differences in ESG performance delay the closing of acquisitions. Using a sample of global M&A transactions, we measure ESG performance using the Refinitiv Eikon ESG scores and time to completion (TTC) as the number of days between the announcement and closing of a transaction. Our results show that larger differences in ESG performance between acquirer and target lead to shorter TTC when acquirer ESG performance exceeds target ESG performance. [ABSTRACT FROM AUTHOR]

Activation of the Wnt-signaling pathway is known to inhibit differentiation in adipocytes. However, there is a gap in our understanding of the transcriptional network regulated by components of the Wnt-signaling pathway during adipogenesis and in adipocytes during postnatal life. The key intracellular effectors of the Wnt-signaling pathway occur through TCF transcription factors such as TCF7L2 (transcription factor-7-like 2). Several genetic variants in proximity to TCF7L2 have been linked to type 2 diabetes through genome-wide association studies in various human populations. Our work aims to functionally characterize the adipocyte specific gene program regulated by TCF7L2 and understand how this program regulates metabolism. We generated Tcf7l2 F/F mice and assessed TCF7L2 function in isolated adipocytes and adipose specific knockout mice. ChIP-sequencing and RNA-sequencing was performed on the isolated adipocytes with control and TCF7L2 knockout cells. Adipose specific TCF7L2 knockout mice were challenged with high fat diet and assessed for body weight, glucose tolerance, and lipolysis. Here we report that TCF7L2 regulates adipocyte size, endocrine function, and glucose metabolism. Tcf7l2 is highly expressed in white adipose tissue, and its expression is suppressed in genetic and diet-induced models of obesity. Genome-wide distribution of TCF7L2 binding and gene expression analysis in adipocytes suggests that TCF7L2 directly regulates genes implicated in cellular metabolism and cell cycle control. When challenged with a high-fat diet, conditional deletion of TCF7L2 in adipocytes led to impaired glucose tolerance, impaired insulin sensitivity, promoted weight gain, and increased adipose tissue mass. This was accompanied by reduced expression of triglyceride hydrolase, reduced fasting-induced free fatty acid release, and adipocyte hypertrophy in subcutaneous adipose tissue. Together our studies support that TCF7L2 is a central transcriptional regulator of the adipocyte metabolic program by directly regulating the expression of genes involved in lipid and glucose metabolism. • Type 2 diabetes risk gene Tcf7l2 is downregulated in adipose tissue of obese mice. • TCF7L2 occupies genes involved in metabolic control and cell cycle. • Inverse correlation between Tcf7l2 expression and glucose control. • Conditional deletion of Tcf7l2 in adipocytes leads to glucose intolerance and adipocyte hypertrophy. • Tcf7l2 regulates adipose tissue lipolysis and lipogenesis. [ABSTRACT FROM AUTHOR]

Objective: To assess the general public's level of knowledge on diabetes mellitus (DM) and identify related sources of information in Cameroon.Study Design: This was a cross-sectional study conducted in 2015 in two health facilities in Yaoundé and Edéa.Methods: We included consenting adults, except health professionals. The level of knowledge on DM was evaluated on 24 points corresponding to 24 questions addressing either DM definition, signs and symptoms, risk factors or complications.Results: Overall, 1524 persons (40.2% males) were included. Almost 99% of respondents had already heard of DM, but only 16.3% had ever received education on DM. The median score for the global knowledge was 79% (IQR 67-88). A person in the close entourage (71.3%) or a health professional (58.8%) constituted the major sources of information; school (13.3%) and media (television (23.6%), newspaper/magazine (10.0%), radio (9.6%) and internet (6.8%) were less common. Younger ages (<45years), lower levels of education, semi-urban residency, were independently associated with a lower level of knowledge on DM.Conclusions: The general public's level of knowledge on DM may be satisfactory, though needing to be improved. Schools and media should be capitalized to educate people on DM, targeting especially young adults and the less educated. [ABSTRACT FROM AUTHOR]

Abstract Objective Ectopic fat deposition is associated with increased tissue production of ceramides. Recent genetic mouse studies suggest that specific sphingolipid C16:0 ceramide produced by ceramide synthase 6 (CerS6) plays an important role in the development of insulin resistance. However, the therapeutic potential of CerS6 inhibition not been demonstrated. Therefore, we pharmacologically investigated the selective ablation of CerS6 using antisense oligonucleotides (ASO) in obese insulin resistance animal models. Methods We utilized ASO as therapeutic modality, CerS6 ASO molecules designed and synthesized were initially screened for in-vitro knock-down (KD) potency and cytotoxicity. ASOs with >85% inhibition of CerS6 mRNA were selected for further investigations. Most promising ASOs verified for in-vivo KD efficacy in healthy mice. CerS6 ASO (AAGATGAGCCGCACC) was found most active with hepatic reduction of CerS6 mRNA expression. Prior to longitudinal metabolic studies, we performed a dose titration target engagement analysis with CerS6 ASO in healthy mice to select the optimal dose. Next, we utilized leptin deficiency ob/ob and high fat diet (HFD) induced obese mouse models for pharmacological efficacy study. Results CerS6 expression were significantly elevated in the liver and brown adipose, this was correlated with significantly elevated C16:0 ceramide concentrations in plasma and liver. Treatment with CerS6 ASO selectively reduced CerS6 expression by ∼90% predominantly in the liver and this CerS6 KD resulted in a significant reduction of C16:0 ceramide by about 50% in both liver and plasma. CerS6 KD resulted in lower body weight gain and accompanied by a significant reduction in whole body fat and fed/fasted blood glucose levels (1% reduction in HbA1c). Moreover, ASO-mediated CerS6 KD significantly improved oral glucose tolerance (during oGTT) and mice displayed improved insulin sensitivity. Thus, CerS6 appear to play an important role in the development of obesity and insulin resistance. Conclusions Our investigations identified specific and selective therapeutic valid ASO for CerS6 ablation in in-vivo. CerS6 should specifically be targeted for the reduction of C16:0 ceramides, that results in amelioration of insulin resistance, hyperglycemia and obesity. CerS6 mediated C16:0 ceramide reduction could be a potentially attractive target for the treatment of insulin resistance, obesity and type 2 diabetes. Highlights • Designed, screened and discovered therapeutic CerS6 ASO that specifically and selectively inhibits CerS6 in in-vivo. • Therapeutic inhibition of a selective enzyme (CerS6) ameliorate insulin resistance and hyperglycemia. • In-vivo selective ablation of CerS6 protected from body weight gain (∼25% body weight reduction in HFD obese mice). • CerS6 could be a potentially attractive target for the treatment of insulin resistance, obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract Marine debris is an economic, environmental, human health, and aesthetic problem posing a complex challenge to communities around the globe. To better document this problem in the Gulf of Mexico we monitored the occurrence and accumulation rate of marine debris at twelve sites on nine barrier islands from North Padre Island, Texas to Santa Rosa, Florida. With this information we are investigating three specific questions: (1) what are the major types/sources of marine debris; (2) does debris deposition have seasonal oscillations; and (3) how does debris deposition change spatially? Several trends emerged; plastic composed 69–95% of debris; there was a significant increase in debris accumulation during the spring and summer seasons; accumulation rates were ten times greater in Texas than the other Gulf States throughout the year; and the amount of debris accumulating along the shoreline could be predicted with high confidence in areas with high freshwater influx. Highlights • Plastic composed an average of 93% (±19%) of all marine debris collected. • There was an increase in debris accumulation during the spring and summer seasons. • Accumulation rates were 10 times greater in Texas than other Gulf states sampled. • Distance from a high-influx watershed can predict debris accumulation on beaches. [ABSTRACT FROM AUTHOR]

Abstract We assess the impact of recreational boat traffic on sensitive habitats in the Western Mediterranean using passive acoustics. We compared underwater sounds in three regulated mooring locations vs a pristine location; and temporal differences in the pristine location vs the nearest mooring between high and low touristic seasons. We measured the number of pulses/minute, fish pulse patterns, and percentage of boat noise occurrence and its relative average power level. At the pristine location, the call rates and their complexity were significantly higher and the motorboat noise was significantly lower. The temporal trend of biophonic sounds decreased significantly in the pristine location. In contrast, in the mooring sites, the motorboat noise decreased significantly and the fish calls remained at low levels in both seasons. In conclusion, motorboat noise negatively affects the complexity of the fish assemblages but could be conditioned to their historic uses. Highlights • High motorboat noise negatively affects the biophonic complexity of the fish assemblage but conditioned to the specific circumstances of each locality in terms of their historic uses. • Two dominant fish calls were described. • Passive acoustics is a useful tool to distinguish different ecological fish assemblages through sound complexity. • The different types of boating activity observed at the three mooring locations likely result in boat noise levels that mirror the boat noise occurrence pattern. [ABSTRACT FROM AUTHOR]

Urban trees often host greater insect pest abundance than trees in rural forests. This may be due, in part, to differences in tree diversity and canopy cover between these settings. Urban trees are often planted in isolation or monoculture, which favors pest accumulation. Gloomy scale, Melanaspis tenebricosa Comstock, is a pest of urban red maples (Acer rubrum L.) that is abundant where impervious surfaces dominate the local landscape. Increasing tree diversity and canopy cover around urban red maples may reduce gloomy scale abundance by supporting natural enemy communities. We investigated the effect that surrounding tree species richness and tree canopy cover had on gloomy scale abundance, natural enemy abundance, and biological control in red maple trees in Raleigh, NC, USA. We collected scales and natural enemies from red maples that spanned a gradient of tree species richness, canopy cover, and impervious surface values. We also measured gloomy scale parasitism and predation of sentinel prey in red maple canopies. Greater tree species richness and canopy cover were associated with lower gloomy scale density. Red maples in diverse settings also hosted fewer scales per natural enemy. Parasitoids were less common in maples in diverse settings, but generalist predator abundance was unaffected by tree diversity. Finally, tree species richness and canopy cover did not increase biological control of scales or sentinel prey. Our findings suggest that higher tree diversity and greater canopy cover may reduce gloomy scale density, but this is not entirely explained by the effects of natural enemies and biological control. [ABSTRACT FROM AUTHOR]

Urban areas have been subject to emergency situations with different causes and sometimes dramatic consequences. With the advent of smart cities technologies, multi-emergency detection units could be conceived and implemented taking advantage of affordable sensing technologies and efficient decision algorithms, allowing quick and distributed detection of emergencies. However, a recurrent problem has been the positioning and further deployment of such detection units in a way that the particularities of each target city are properly considered. In this sense, this article proposes the processing of geospatial data about existing urban infrastructure associated with some critical response after an emergency is detected, selecting hospitals, police stations, fire departments, and metro stations, in the target city. These infrastructures are then exploited to define the novel concept of mitigation zones, which indirectly express the perceived level of urban resilience to emergencies. Then, four positioning algorithms are proposed to exploit the mitigation zones considering a defined set of available detection units for deployment. Since the proposed approach is valid for any city, provided that geospatial data is available, it could be largely adopted to support different smart city systems, potentially bringing significant results in this area. • The positioning of emergencies detection units in cities has been a challenging task. • Some mathematical elements are defined based on geospatial data from open databases. • Distances to urban response centres are used to compute the risk level of each area. • Four positioning algorithms are proposed to exploit the risk levels of mitigation zones. • Experimental results for the cities of Paris and Porto are presented. [ABSTRACT FROM AUTHOR]

Workplace exercise has been demonstrated to improve health outcomes and productivity. Hospital staffs may have a large potential to benefit from workplace exercise; however, implementation of workplace exercise faces the challenges of the workflow in hospitals. This study aimed to explore the economic and productivity consequences of a 12-week exercise intervention for hospital health care providers in a Danish hospital department. The outcome measures included the costs of providing the intervention, sick leave, self-reported quality of life (EQ-5D-5 L), work engagement (Utrecht Work Engagement Scale), and employees' workplace social capital. Ordinary Least Squares and Generalized Linear Models were employed to assess whether the extent of participation in the intervention was associated with the outcome measures. A total of 80 participants completed an average of 9 sessions during the 12-week study period, at an estimated mean cost of €77 per person. Increasing number of exercise sessions was associated with improvements on the pain domain of the EQ-5D-5 L (mean (SD) -0.2570 (0.723), p = 0.0049), and with improved work engagement (by 4.6%) over the intervention period. We found no significant associations between exercise session participation and the other outcome measures. The pilot study demonstrates relatively high acceptance of a worksite exercise program at a hospital, at a relatively low cost, with several important directions in outcomes. Further work should explore whether these results can be replicated in a larger, randomized trial. [ABSTRACT FROM AUTHOR]

Les leçons du monde vis-à-vis de l'allergologie moléculaire montre la diversité de la réactivité des allergènes et de leurs composants en fonction de l'environnement, pour exemple les allergies prédominantes aux animaux et aux pollens en suède, à la blatte aux États-Unis, aux acariens en France et en Grande-Bretagne. L'allergie alimentaire suit ces mêmes règles, avec par exemple le problème majeur de l'arachide dans les pays anglo-saxons ou du lait de vache en France. La classification moléculaire des allergènes en différentes familles de protéines (en fonction de leur structure et de leur fonction) peut aider à prédire la probabilité de développer des réactions locales ou systémiques. En cas de séquences aminoacides et/ou structures protéiques similaires, les membres d'une même famille de protéines peuvent partager des épitopes d'IgE identiques ou similaires, il existe alors une forte probabilité de réactivité croisée. Pour l'allergie aux trophallergènes, plus le composé allergénique est stable notamment vis-à-vis de la chaleur, plus la probabilité de développer une réaction allergique sévère est importante. Pour les allergènes inhalés, les IgE spécifiques pour les composés allergéniques majeurs de l'espèce sont associées à la gravité de la maladie allergique. La sensibilisation multiple vis-à-vis des allergènes natifs mais aussi moléculaires est associée à la gravité de l'allergie pour les allergènes inhalés mais aussi alimentaires dans le monde. Molecular components of allergens shows the diversity of the reactivity of allergens and their components according to the environment, for example the main allergies are towards animal dander and pollens in Sweden, cockroach in États-Unis and house dust mites in France and in England. Food allergies follow these same rules, for example the major problem is peanut in English spoken countries and cow's milk in France. The classification of allergen molecules into different families of proteins (depending on their structure and function) can help to predict the development local or systemic reactions. Members of the same protein family can share similar IgE épitopes, with the risk of strong cross-reactivity response. For allergy to food allergens, a stable allergenic component toward the heat is associated with greater risk of development of severe allergic reaction. For inhaled allergens, specific IgE towards major allergenic compounds were associated with the severity of allergic disease. Multiple sensitizations towards native allergens but also molecular allergens are associated with the severity of the allergy for inhaled but also food allergens in the word. [ABSTRACT FROM AUTHOR]

En Europe, il y a une variabilité dans les modalités de réalisation de tests de provocation aux aliments dans les différents centres d'allergologie. La Société italienne d'allergologie et immunologie pédiatrique (SIAIP) a mené une enquête, dans plusieurs pays, pour évaluer les pratiques locales de réalisation de ces tests et rechercher les possibles différences. Nous présentons les résultats d'un questionnaire réalisé sur une plateforme en ligne par 120 centres d'allergologie, distribués en 4 pays européens différents : France, Italie, Espagne, Royaume-Uni. Malgré quelques différences, les modalités de prise en charge des patients restent assez concordantes entre les différents pays. In Europe, there is a certain variability in the way oral food challenges are performed in the different allergy centers. For such reason, the Italian Society of Pediatric Allergy and Immunology (SIAIP) decided to run a survey in different European countries, to assess local habits in performing these tests and to look for possible differences. We are here presenting the results of an online survey, to which 120 allergy centers answered, distributed in France, Italy, Spain and the UK. Even though a few differences rose from this survey, the way patients are managed seem concordant between the different European countries. [ABSTRACT FROM AUTHOR]