In this paper, we analyze the impact of the marketing authorization of EMA-approved vaccines on the returns of equity funds in the EU. Using the event study methodology, we report that the introduction of all vaccines had a positive impact on the funds' returns. Higher abnormal returns were associated with the earlier vaccines, indicating the first-mover advantage and the abnormal returns were persistent across several event windows. The findings imply that equity markets welcomed the vaccine administration as an important pharmaceutical intervention to support the quasi-revival of business activities. Consequently, there was a significant uplift in the economic bottom line.

Simple Summary The treatment outcomes in patients with head and neck cancer vary greatly, and serious side effects are often observed. Being able to predict therapy effects is therefore crucial for choosing the best treatment option for each patient. In this study, we developed an assay to evaluate how head and neck tumor cells respond to radiation and chemotherapy. Treatment of thin patient-derived cancer tissue slices in the laboratory (in vitro) resulted in large differences in individual tumor’s reactions to treatment. In the sensitive tumors, cancer cells repaired the DNA damage inflicted by therapy only partially, stopped multiplying, and showed increased levels of cell death. On the other hand, resistant tumors were able to recover from the damage caused by the treatment. The next crucial step is to investigate whether the differences we observed in vitro can indeed predict the treatment outcomes; this is currently being tested in an ongoing clinical trial. Abstract Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient. Methods: Resection material of 17 primary HNSCC patients was cultured ex vivo, irradiated or cisplatin-treated, after which the effect on tumor cell vitality was analyzed several days after treatment. Results: Ionizing radiation (IR) affected tumor cell growth and viability with a clear dose-response relationship, and marked heterogeneity between tumors was observed. After a single dose of 5Gy, proliferation in IR-sensitive tumors dropped below 30% of the untreated level, while IR-resistant tumors maintained at least 60% of proliferation. IR-sensitive tumors showed on average a twofold increase in apoptosis, as well as an increased number and size of DNA damage foci after treatment. No differences in the homologous recombination (HR) proficiency between IR-sensitive and –resistant tumors were detected. Cisplatin caused a decrease in proliferation, as well as induction of apoptosis, again with marked variation between the samples. Conclusions: Our functional ex vivo assay discriminated between IR-sensitive and IR-resistant HNSCC tumors, and may also be suitable for predicting response to cisplatin. Its predictive value is currently under investigation in a prospective clinical study.

Abstract:In order to address the research gaps on climate finance dynamics in developing countries, especially those with low governance scores, this study assesses the 2016–2020 bilateral climate finance to these countries. The total disbursed bilateral climate finance was US$1.3 billion (92 percent for mitigation, 7 percent for adaptation, and 1 percent for mitigation and adaptation simultaneously). Development-focused loans were the prevailing financial instrument cumulatively, and grants were the prevailing instrument on a per-country level. Japan was the biggest provider of bilateral climate finance (US$1 billion) to fund Uzbekistan's natural gas-fired electric power plants. All major bilateral climate finance providers ranked high on governance scores compared to the ten examined countries. Countries examined in this study will need to receive higher amounts of bilateral climate change finance in order to improve their readiness to address this issue and reduce their vulnerability to climate change impacts.

Abstract Hypoxia induces changes in the secretion of extracellular vesicles (EVs) in several non‐neuronal cells and pathological conditions. EVs are packed with biomolecules, such as microRNA(miR)‐21‐5p, which respond to hypoxia. However, the true EV association of miR‐21‐5p, and its functional or biomarker relevance, are inadequately characterised. Neurons are extremely sensitive cells, and it is not known whether the secretion of neuronal EVs and miR‐21‐5p are altered upon hypoxia. Here, we characterised the temporal EV secretion profile and cell viability of neurons under hypoxia. Hypoxia induced a rapid increase of miR‐21a‐5p secretion in the EVs, which preceded the elevation of hypoxia‐induced tissue or cellular miR‐21a‐5p. Prolonged hypoxia induced cell death and the release of morphologically distinct EVs. The EVs protected miR‐21a‐5p from enzymatic degradation but a remarkable fraction of miR‐21a‐5p remained fragile and non‐EV associated. The increase in miR‐21a‐5p secretion may have biomarker potential, as high blood levels of miR‐21‐5p in stroke patients were associated with significant disability at hospital discharge. Our data provides an understanding of the dynamic regulation of EV secretion from neurons under hypoxia and provides a candidate for the prediction of recovery from ischemic stroke.

Purpose Paediatric Type 1 Diabetes (T1D) patients are at greater risk for developing severe hypo and hyperglycaemic events due to poor glycaemic control. To reduce the risk of adverse events, patients need to achieve the best possible glycaemic management through frequent blood glucose monitoring with finger prick or Continuous Glucose Monitoring (CGM) systems. However, several non-invasive techniques have been proposed aiming at exploiting changes in physiological parameters based on glucose levels. The overall objective of this study is to validate an artificial intelligence (AI) based algorithm to detect glycaemic events using ECG signals collected through non-invasive device. Methods This study will enrol T1D paediatric participants who already use CGM. Participants will wear an additional non-invasive wearable device for recording physiological data and respiratory rate. Glycaemic measurements driven through ECG variables are the main outcomes. Data collected will be used to design, develop and validate the personalised and generalized classifiers based on a deep learning (DL) AI algorithm, able to automatically detect hypoglycaemic events by using few ECG heartbeats recorded with wearable devices. Results Data collection is expected to be completed approximately by June 2023. It is expected that sufficient data will be collected to develop and validate the AI algorithm. Conclusion This is a validation study that will perform additional tests on a larger diabetes sample population to validate the previous pilot results that were based on four healthy adults, providing evidence on the reliability of the AI algorithm in detecting glycaemic events in paediatric diabetic patients in free-living conditions. Trial registration ClinicalTrials.gov identifier: NCT03936634. Registered on 11 March 2022, retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT05278143?titles=AI+for+Glycemic+Events+Detection+Via+ECG+in+a+Pediatric+Population&draw=2&rank=1 .

Artemisia annua L. has long been known for its medicinal properties and isolation of ingredients whose derivatives are used for therapeutic purposes. The CYP2B6 and CYP3A4 enzymes belong to a large family of cytochrome P450 enzymes. These enzymes are involved in the metabolism of drugs and other xeonobiotics. It is known that various compounds can induce or inhibit the activity of these enzymes. The aim of this study was to investigate the nature of the inhibitory effect of Artemisia annua extract on CYP2B6 and CYP3A4 enzymes, as well as the type of inhibition, the presence of reversible or pseudo-irreversible inhibition, and the possible heme destruction. The methanolic extract of Artemisia annua showed an inhibitory effect on CYP2B6 (by almost 90%) and CYP3A4 enzymes (by almost 70%). A significant decrease in heme concentration by 46.8% and 38.2% was observed in different assays. These results clearly indicate that the studied plant extracts significantly inhibited the activity of CYP2B6 and CYP3A4 enzymes. Moreover, they showed irreversible inhibition, which is even more important for possible interactions with drugs and dietary supplements.

With the goal of enhancing the quality of the environment, urban green infrastructure (UGI) is an essential element in sustainable cities, and nature-based solutions (NBS) are being carried out as new infrastructure solutions that increase the resilience of cities. In this research, the method of theoretical analysis and the content analysis as the basic fact-gathering technique was applied to answer to following questions: What are the hindrances and bottlenecks in implementing NBS? Are the current decision-making mechanisms helping NBS get in route to shape cities? Is there any binding policy in practice that promotes NBS? In Belgrade is planned Type 3 of the degree of intervention/level and engineering type—Creation and new ecosystem management in the classifications of intensive urban green space management; urban planning strategies; urban water management; ecological restoration of degraded terrestrial ecosystems; and restoration and creation of semi-natural water bodies and hydrographic networks. In the future, it is essential to implement policies and incentives on national, regional, and local scales that help encourage the usage of NBS in the development of urban infrastructure.

Purpose: Total elbow arthroplasty (TEA) is rarely performed compared to other arthroplasties. For many surgical procedures, literature shows better outcomes when they are performed by experienced surgeons and in so-called ‘high-volume’ hospitals. We systematically reviewed the literature on the relationship between surgical volume and outcomes following TEA. Methods: A literature search was performed using the MEDLINE, EMBASE and CINAHL databases. The literature was systematically reviewed for original studies comparing TEA outcomes among hospitals or surgeons with different annual or career volumes. For each study, data were collected on study design, indications for TEA, number of included patients, implant types, cut-off values for volume, number and types of complications, revision rate and functional outcome measures. The methodological quality of the included studies was assessed using the Newcastle–Ottawa Scale. Results: Two studies, which included a combined 2301 TEAs, found that higher surgeon volumes were associated with lower revision rates. The examined complication rates did not differ between high- and low-volume surgeons. In one study, low-hospital volume is associated with an increased risk of revision compared to high-volume hospitals, but for other complication types, no difference was found. Conclusions: Based on the results, the evidence suggests that high-volume centers have a lower revision rate in the long term. No minimum amount of procedures per year can be advised, as the included studies have different cut-off values between groups. As higher surgeon- and center-volume, (therefore presumably experience) appear to yield better outcomes, centralization of total elbow arthroplasty should be encouraged.

ITk detector, the new ATLAS tracking system at High Luminosity LHC, will be equipped with 3D pixel sensor modules in the innermost layer (L0). The pixel cell dimensions will be either 25 × 100 μm2 (barrel) or 50 × 50 μm2 (endcap), with one read-out electrode at the centre of a pixel and four bias electrodes at the corners. Sensors from pre-production wafers (50 × 50 μm2) produced by FBK have been bump bonded to ITkPixV1.1 chips at IZM. Bare modules have been assembled in Genoa on Single Chip Cards and characterized in laboratory and on beam.

The emergence of SARS-CoV-2 variants of concern (VOC) is driven by mutations that mediate escape from neutralizing antibodies. There is also evidence that mutations can cause loss of T cell epitopes. However, studies on viral escape from T cell immunity have been hampered by uncertain estimates of epitope prevalence. Here, we map and quantify CD8 T cell responses to SARS-CoV-2-specific minimal epitopes in blood drawn from April to June 2020 from 83 COVID-19 convalescents. Among 37 HLA ligands eluted from five prevalent alleles and an additional 86 predicted binders, we identify 29 epitopes with an immunoprevalence ranging from 3% to 100% among individuals expressing the relevant HLA allele. Mutations in VOC are reported in 10.3% of the epitopes, while 20.6% of the non-immunogenic peptides are mutated in VOC. The nine most prevalent epitopes are conserved in VOC. Thus, comprehensive mapping of epitope prevalence does not provide evidence that mutations in VOC are driven by escape of T cell immunity.

Background Clinical guidelines recommend the identification of asthma comorbidities, especially treatable problems such as parental behaviours and child and parent anxiety. Purpose We aimed to (1) explore associations of asthma severity with child and parent state anxiety, trait anxiety, and asthma-related anxiety as well as with caregiver behaviours around physical activity and (2) explore if caregiver behaviours around physical activity were associated with use of inhaled β-Agonists when symptomatic, and with child and parent anxiety. Patients and methods Patients ages 3–17 years with asthma (n = 72) and their parents were recruited from the Pulmonology-Allergology Pediatric clinic University Hospital Centre Split in Split, Croatia during 2021. During a clinical visit, the pharmacological regimen was assessed and spirometry was performed. Children completed the State-Trait Anxiety Inventory for Children (STAI-C) and the Youth Asthma-Related Anxiety Scale (YASS). Parents completed the State-Trait Anxiety Inventory (STAI), the Parent Asthma-Related Anxiety Scale (PASS), and the Physical Activity Parenting Practices – Short Form (PAPP). Results Most patients had mild asthma (69.4%). Children with moderate to severe asthma had increased asthma-related anxiety (mean = 11.94 ± 6.1) compared with children with mild asthma (mean = 5.97 ± 6.39, p = 0.003). Parents of children with mild asthma reported behaviours allowing unsupervised physical activity outside more often when compared to parents of children with moderate or severe asthma. Physical activity facilitation parenting behaviour reduced the odds of a child's need for quick-reliever medication when symptomatic (OR = 0.376,95% CI = −1.885 to −0.072; p = 0.034); more coercive parenting increased the odds of a child's additional use of such medications (OR = 2.602; 95% CI = 0.005 to 1.908; p = 0.049). Parents of children in the highest quartile of trait anxiety showed less non-directive support (1.97 ± 1.01 vs. 2.89 ± 1.19, p = 0.031) and less autonomy support (3.14 ± 1.32 vs. 4.11 ± 1.23, p = 0.037) of physical activity in their children than those with less trait anxiety. Conclusion Asthma-related anxiety was an important construct in this sample of children, associated with their disease severity as well as their parent's behaviours around the child's physical activities. Current research, conducted during the COVID-19 pandemic, recognised the tangible ways that parents support or avoid the asthmatic children's physical activity participation. Child anxiety and recognised parental physical activity behaviours are potentially important factors to assess and target for intervention.

Ancient Roman concretes have survived millennia, but mechanistic insights into their durability remain an enigma. Here, we use a multiscale correlative elemental and chemical mapping approach to investigating relict lime clasts, a ubiquitous and conspicuous mineral component associated with ancient Roman mortars. Together, these analyses provide new insights into mortar preparation methodologies and provide evidence that the Romans employed hot mixing, using quicklime in conjunction with, or instead of, slaked lime, to create an environment where high surface area aggregate-scale lime clasts are retained within the mortar matrix. Inspired by these findings, we propose that these macroscopic inclusions might serve as critical sources of reactive calcium for long-term pore and crack-filling or post-pozzolanic reactivity within the cementitious constructs. The subsequent development and testing of modern lime clast–containing cementitious mixtures demonstrate their self-healing potential, thus paving the way for the development of more durable, resilient, and sustainable concrete formulations.