Bakground Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer-related death. Various molecular markers are used for early CRC diagnosis. Of these, human ephrin receptor family type-A 2 (hEphA2) oncoprotein is overexpressed significantly at the early, but not late, stages of CRC. Previously, we reported an E1 monobody that is specific for hEphA2-expressing cancer cells both in vitro and in vivo. Aim We aimed to use E1 monobody as a detection probe for hEPhA2 expressing colorectal cancer. In addition, we investigated the efficacy of E1 monobody to target on human colorectal cancer tissue. Method Here, we confirmed the expression of hEPhA2 on the surface of colorectal cancer cells by western blotting and flow cytometry. We evaluated the targeting efficacy of E1 monobody on colorectal cancer cells by flow cytometry and further confirmed with immunofluorescence staining. E1 conjugated to the Rluc8 reporter protein were used as imaging agent for in vivo imaging. Additionally, EGFP conjugated E1 monobody were used to check the targeting ability of E1 monobody on human colorectal cancer tissue. Result E1 bound efficiently to nine hEphA2-expressing CRC cell lines and E1 conjugated to the Rluc8 reporter protein targeted tumor tissues in mice transplanted with HCT115 CRC tumor cells. Finally, E1-EGFP stained tumor tissues from human CRC patients, showing a pattern similar to that of an anti-hEphA2 antibody. Conclusion These results suggest that the E1 monobody has utility as a probe to detect CRC.

Aim: This study aimed to clarify the actual status of clinical trials and translational research activities in cancer immunology in the Asia-Pacific region, the most diverse and populous region with a large number of cancer patients. Methods: This questionnaire-based survey targeted researchers and healthcare professionals in the Asia-Pacific region. The questionnaire was sent to individuals who were involved in any collaboration with the National Cancer Center, Japan, or who belonged to the Asia-Pacific Blood and Marrow Transplantation group. Results: We received 122 responses from 20 Asia-Pacific countries and regions. Approximately 58% of the respondents were currently conducting clinical trials on cancer immunotherapy, with 25% having performed >10 phase 3 trials in the last 3 years. Half of the respondents (51.7%) belonged to institutions that conducted early phase clinical trials. In clinical trials, immune checkpoint inhibitors were used in most countries (81.8%), whereas chimeric antigen receptor T-cell (CAR-T) or T-cell receptor-modified T-cell (TCR-T) therapies were used in few countries (CAR-T, 22.7%; TCR-T, 2.3%). Importantly, 18% of respondents had referred their patients to facilities conducting suitable ongoing clinical trials in foreign countries. Some institutions provided hematopoietic stem cell transplantation (HSCT), including allogeneic HSCT (55.1%) and autologous peripheral blood stem cell transplantation (81.3%). Approximately 40% of the respondents belonged to institutions that conducted translational research on cancer immunotherapy using patient-derived samples. Conclusion: This survey revealed limited cancer immunotherapy accessibility and research activities in the Asia-Pacific region, especially for CAR-T and TCR-T therapies.

Aggregation-Induced Emission (AIE) is a unique phenomenon whereby aggregation of molecules induces fluorescence emission as opposed to the more commonly known Aggregation-Caused Quenching (ACQ). AIE has the potential to be utilized in the large-scale production of AIE-active polymeric materials because of their wide range of practical applications such as stimuli-responsive sensors, biological imaging agents, and drug delivery systems. This is evident from the increasing number of publications over the years since AIE was first discovered. In addition, the ever-growing interest in this field has led many researchers around the world to develop new and creative methods in the design of monomers, initiators and crosslinkers, with the goal of broadening the scope and utility of AIE polymers. One of the most promising approaches to the design and synthesis of AIE polymers is the use of the Reversible-Deactivation Radical Polymerization (RDRP) techniques, which enabled the production of well-controlled AIE materials that are often difficult to achieve by other methods. In this review, a summary of some recent works that utilize RDRP for AIE polymer design and synthesis is presented, including (1) the design of AIE-related monomers, initiators/crosslinkers; the achievements in preparation of AIE polymers using (2) Reversible Addition-Fragmentation Chain Transfer (RAFT) technique; (3) Atom Transfer Radical Polymerization (ATRP) technique; (4) other techniques such as Cu(0)-RDRP technique and Nitroxide-Mediated Polymerization (NMP) technique; (5) the possible applications of these AIE polymers and finally (6) a summary/perspective and the future direction of AIE polymers.

Objective Methotrexate (MTX) is the cornerstone in the treatment of rheumatoid arthritis (RA) patients. However, adherence to MTX therapy is not optimal, and instruments to assess medication non-adherence are warranted. To date there is no consensus on the best method to determine adherence to MTX. The aim of this study was to assess the correlation between adherence assessed with a Medication Event Monitoring System (MEMS) versus pill count, MTX-polyglutamate (PG) concentration and Compliance-Questionnaire-Rheumatology (CQR) in patients with established RA. Second, the correlations between these methods and the Disease Activity Scores of 28 joints (DAS28) were examined. Methods Adult RA patients currently treated with MTX were included. Multivariable linear and logistic regression were used, with adherence assessed with MEMS as dependent variable versus pill count, MTX-PG concentrations, CQR as independent variables, and DAS28 versus each of the four adherence measurements. Covariates were included, such as comedication, age and use of corticosteroids. Results 190 consecutive RA patients were included. Pill count was correlated with adherence assessed with MEMS (linear regression, β = .690, p = <.001), whereas CQR and MTX-PGs were not. Logistic regression confirmed the correlation between dichotomized adherence and pill count only (β = 5.64, p= <.001). No other correlations were found, neither for all adherence outcomes and DAS28. Conclusion Measuring adherence with MEMS is correlated with pill count, whereas other methods were not correlated with MEMS, nor with DAS28. Pill count can be used to estimate adherence to MTX therapy, in case MEMS is not achievable.

Objective: This study aims to conduct a panoramic analysis of foreign and Chinese research on sports and healthy aging, and to construct a research knowledge framework based on the mechanism of the role of sports on healthy aging and the value creation of sports on healthy aging as a system. Methods: We use the literature included in the Web of Science core collection and CNKI database was used as the study sample, and bibliometric analysis was performed on the literature sample using analysis software such Bibexcel and SPSS. Results: There are links and differences between China and foreign countries in terms of the mechanisms and value creation of sport for healthy aging. While Chinese and foreign studies have focused on three aspects of physical activity behavior, health interventions for older persons, and exercise guidelines for older persons, foreign studies have focused more on individual aspects of older persons, while Chinese studies have focused more on the development of policies for older persons. Conclusions: Based on the national conditions of China, the study proposes the research idea of sports and healthy aging as an important issue to cope with population aging, as a social system project of universal health care, and as a reflection of individual quality of life. This will provide very important practical guidelines for geriatric care.

A modern healthcare system requires the right mix of clinical specialties to achieve high level of health status for its population. Despite increased availability of physicians and specialists, Türkiye still lags behind high-income countries in terms of density of medical professionals. This study attempts to understand the importance of various factors in the choice of medical specialization. A survey of 333 medical graduates was conducted to identify the potential factors. A multivariate regression model was employed to identify the statistically significant factors. Results indicate that surgical specialties show statistically significant higher likelihood of selection over other two broad specialization categories due to attractive factors (anticipated income and prestige) and lower likelihood of selection due to factors like relative ease of the training program, high work-load of specialty, medical malpractice lawsuits and risk of workplace violence. If negative factors, which can be categorized as avoidance and detrimental factors, outweigh the attractive factors, surgical specialties may not remain a highly sought-after specialization. To lower workplace violence in health sector, structural reforms and system improvements should be carried out. It is critically important to improve patient-physician trust and communications to lower the risk of malpractice and litigation.

Mismatch negativity (MMN) and P3b are well known for their clinical utility. There exists no gold standard, however, to acquire these markers. This may explain why the within-individual sensitivity of MMN/P3b is often quite poor and why seemingly identical markers can behave differently across studies. Here we compare two traditional paradigms for MMN or P3b assessment with the recently more popular local-global paradigm which promises to assess MMN and P3b orthogonally within one oddball sequence. All three paradigms were administered to healthy participants (N=15) with concurrent EEG. A clear MMN and local effect were found for 15/15 participants. The P3b and global effect were found for 14/15 and 13/15 participants, respectively. There were no systematic differences between the global effect and P3b. Indeed, P3b amplitude was highly correlated across paradigms. The local effect differed clearly from the MMN, however. It occurred earlier compared to MMN and was followed by a much more prominent P3a effect. The two sets of peak latencies and amplitudes were also not correlated across paradigms. We conclude that the local-global paradigm is effective in evoking the traditional P3b component, but it does not capture the MMN. Caution should therefore be exercised when comparing the local effect and MMN across studies. Nevertheless, the within-individual sensitivity of both MMN and the local effect was satisfactory. The within-individual sensitivity of P3b was lower than expected in a healthy control group, which may explain the often-low sensitivity of P3b in patients with disorders of consciousness.

The benefits of AI in healthcare will only be realised if we consider the whole clinical context and the AI’s role in it. The current, standard model of AI-supported decision-making in healthcare risks reducing the clinician's role to a mere ‘sense check’ on the AI, whilst at the same time leaving them to be held legally accountable for decisions made using AI. This model means that clinicians risk becoming “liability sinks”, unfairly absorbing liability for the consequences of an AI’s recommendation without having sufficient understanding or practical control over how those recommendations were reached. Furthermore, this could have an impact on the “second victim” experience of clinicians.It also means that clinicians are less able to do what they are best at, specifically exercising sensitivity to patient preferences in a shared clinician-patient decision-making process.There are alternatives to this model that can have a more positive impact on clinicians and patients alike.

Background: Colostrum contains substances such as hormones, enzymes, polyamides, nucleic acid derivatives and amino acid derivatives. Their range also includes immunomodulating substances, proline-rich polypeptides (PRP), immunoglobulins as well as bacteriostatic compounds. Based on its biological properties as well as the influence of Toll-like receptors on immune response traits of farm animals and humans, we hypothesised that gene expression for Toll-like receptors in foals is dependent on the quality of colostrum. Objectives: The aim of the study was to evaluate the impact of the quality of colostrum on the level of expression of selected Toll-like receptor genes (TLR3, TLR4, and TLR7). Study design: The experiments were conducted on 25 foals Polis Pony breed. Blood samples were collected up to 30 days of age according to the following scheme: before first suckling, at the 1st, 3rd, 5th, 10th, 20th, and 30th, day of age. Colostrum was obtained before the first suckling, 24 hr and 3 days after the delivery. Methods: Gene expression analyses were performed on Illumina Eco using a commercial kit TaqMan®MGB probes. The quality of colostrum was assessed using an optical refractometer. Total immunoglobulin level was calculated from the spectrophotometric method. Immunoglobulin G level were measured using ELISA assay Microplate Reader using 96-well plates coated with monoclonal antibodies against equine IgG. Results: The quality of colostrum significantly correlated with TLR4 and TLR7 expression. Foals that ingested colostrum with low immunoglobulin content displayed higher level of TLR4 gene expression, while in case of TLR7 the opposite trend was shown. Main limitations: It is likely that fat and the proportion of individual fatty acids in colostrum affect the action of membrane Toll-like receptors Conclusions: The expression of genes for TLR3 and TLR4 in peripheral blood is dependent on immunoglobulin concentration in mammary gland secretion suckled by foals.

The current research was designed to assess degree of sediment contamination by heavy metal in the Thamirabarani River by using pollution indicators and multivariate statistical methods. Between September 2020 and August 2021, seasonal basis sediment samples are collected from five distinct locations and subjected to standardised analysis. These statistical techniques, including Two-way ANOVA, Pearson Correlation Index, PCA and CA., were demonstrated the research. The quality of sediment needs to be better understanding about the statistical methods. Three factors that account for 95.4% of the data’s total variation were found using PCA.The sediment’s heavy metal contamination were distributed in the following sequence Fe > Mn > Cu > Zn > Al > Cd > Ni. The contamination was evaluated pollution indicators method such EF, CF, Igeo and PLI. Estimated EF values show that there is a noticeable enrichment of pollutants in copper (Cu). Therefore, river water can be used for irrigation securely, but it need to go through a lot of processing is necessary before for home uses in order to avoid negative public health effects.

Traditional molecular biology tools have elucidated the identities and functions of RNA molecules, which are essential to the understanding of gene transcription and protein translation. Deepening this research field would further require the direct visualization of RNA dynamics such as the DNA-RNA interactions and RNA-protein interactions. Towards this goal, the rise of RNA imaging tools over the past 15 years has reformed how we looked at these processes. In this emerging topic, we first highlighted recent advances on three main RNA imaging tools based on the species of interacting molecules: RNA-RNA pairing, RNA-protein binding, and small molecule-RNA complex. We introduced the advantages of these tools from a technical viewpoint, including binding affinity, fluorescent turn-on ratio, stability, and impacts on targeted RNA. Next, we discussed new rising opportunities and future directions, echoing the state-of-the-art imaging tools in the fields of fluorescent proteins and small fluorescent molecules. Together, we believe this emerging field will bring new insights on how we study RNA biology in living systems.

This paper presents a framework combining Monte Carlo Simulation (MCS) and the Newmark sliding block model with Representative slip surfaces (RSS) (model II) and Multiple response surfaces method (MRSM) to conduct seismic reliability analysis and risk assessment of soil slopes. An empirical threshold is introduced to define the limit state function to identify the failure samples in MCS and the sliding area and Newmark sliding displacement are multiplied to quantify the failure consequence. The proposed methodology is illustrated through a soil slope with multiple layers. The calculation results demonstrate that traditional Newmark sliding block model (model I) tend to underestimate the variations of yield acceleration. Both the failure probability and landslide risk exhibit decreasing trends with the increase of threshold. Significant discrepancy in failure probability and landslide risk between two models is found even for a small threshold. It is therefore, the proposed methodology is highly recommended in seismic reliability analysis and risk assessment. The contributions of RSSs to the failure probability and landslide risk are insensitive to the variation of displacement thresholds.

Background and Purpose: 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the oxoreduction of cortisone to cortisol, thereby amplifying levels of active glucocorticoids. It is considered a pharmaceutical target in metabolic disease and cognitive impairments. 11β-HSD1 also converts some 7oxo-steroids to their 7β-hydroxy forms. A recent study in mice described the ratio of tauroursodeoxycholic acid (TUDCA)/tauro-7oxolithocholic acid (T7oxoLCA) as a biomarker for decreased 11β-HSD1 oxoreductase activity. The present study aimed to evaluate the equivalent bile acid ratio glycoursodeoxycholic acid (GUDCA)/glyco-7oxolithocholic acid (G7oxoLCA) as a biomarker for pharmacological 11β-HSD1 inhibition in humans and compare it with the currently applied urinary (5α-tetrahydrocortisol+tetrahydrocortisol)/tetrahydrocortisone ((5αTHF+THF)/THE) ratio. Experimental Approach: Bile acid profiles were analyzed by ultra-HPLC tandem-MS in blood samples from two independent, double-blind placebo-controlled clinical studies on the orally administered selective 11β-HSD1 inhibitor AZD4017. The blood GUDCA/G7oxoLCA ratio was compared with the urinary tetrahydro-glucocorticoid ratio for the ability to detect 11β-HSD1 inhibition. Key Results: No significant alterations were observed in the bile acid profiles following 11β-HSD1 inhibition by AZD4017, except for an increase of the secondary bile acid G7oxoLCA. The enzyme product/substrate ratio GUDCA/G7oxoLCA was found to be more reliable to detect 11β-HSD1 inhibition than the absolute G7oxoLCA concentration in both cohorts. Comparison of the blood GUDCA/G7oxoLCA ratio with the urinary (5αTHF+THF)/THE ratio revealed that both ratios successfully detect 11β-HSD1 inhibition. Conclusion and Implications: 11β-HSD1 inhibition does not cause major alterations in bile acid homeostasis. The GUDCA/G7oxoLCA ratio represents the first blood biomarker of pharmacological 11β-HSD1 inhibition and may replace or complement the urinary (5αTHF+THF)/THE ratio biomarker.

This paper provides new information on molecular properties of the humin fraction (HM) isolated from the mollic horizons of Phaeozem and Chernozem soils developed from different parent materials in the temperate climatic zone of Poland. In our work we did not extract this fraction by dissolution but isolated it by exhaustive extraction of humic and fulvic acids with NaOH and then removing the mineral fraction with HF/HCl treatment. Obtained HM reflects the properties of this fraction that naturally occurres in the soil environment. The assessment of the structural properties of the HM was carried out using the spectroscopic methods ( 13C CP MAS NMR, FTIR, EPR), HPLC, SEM-EDX, and elemental composition analyses. The 13C CP MAS NMR spectra of the HM showed the advantage of aromatic structures over other organic components. The FTIR spectra confirmed that the content of aromatic structures dominated over the aliphatic ones, ranging from 7.05 to 10.32%. The EPR study indicated evidence of an unpaired electron situated on the condensed aromatic moieties. The HPLC investigation revealed the dominance of hydrophobic fractions, ranging from 77.41 to 80.83%. The ash content, ranging from 22.89 to 54.50%, as well as SEM-EDS study indicate that the isolated HM is not a pure organic fraction but constituted strongly bound organo-mineral compounds, resistant to further treatment with an alkali and HF/HCl mixture. This fraction represents the most resistant pool of the SOM that plays a crucial role in soil carbon sequestration and due to high functional group content contributes to the maintenance of soil and its ecosystem services.

A broadband heterogeneous circularly polarized (CP) dipole antenna with a backed cavity is presented in this letter. The proposed antenna consists of a pair of rotational symmetric short-circuited heterogeneous branches and a Γ-shaped feed structure. Each branch is designed to be axe-shaped so that the antenna can achieve a broad 3dB axial ratio (AR) bandwidth. The coupled feeding method assures the antenna is wideband, and the shorting-to-the-ground technique miniaturizes the lateral dimensions of the antenna. The profile of the proposed antenna is around 0.16λL (λL denotes the wavelength of the lower bound frequency). The introduction of a back cavity effectively enhances the boresight gain and improves the isolation level if the antenna is used to form an array. Finally, the design is prototyped, and the measurement results agree well with the simulation. The fractal -10 dB S11 bandwidth and 3dB AR bandwidths are 54.3% (2.74-4.78 GHz) and 45.9% (3.15-5.03 GHz), respectively. The antenna’s efficiency exceeds 91.5% over the target frequency band.

Covid-19 causedhospitalizations, severe disease and deaths in any age, including in the youngest children. The aim of this multicenter national study is to characterize the clinical and the prognostic role of lung ultrasound (LUS) in children with Covid-19. We enrolled children between 1 month and 18 years of age diagnosed with SARS-CoV2 infection and whounderwenta lung ultrasound within 6 hours from firstmedical evaluation. A total of 213 children were enrolled, 51.6%were male, median age was2 years and 5 months (IQR 4mm- 11 yearsand4 months).One hundred and fortyeight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit.We found an inverse correlation between the LUS score and the oxygen saturationatthe clinical evaluation (r = −0.16; p = 0.019). Moreover, LUS scores were significantly higher in patients requiring oxygen supplementation (8 (IQR 3 - 19) vs 2 (IQR 0 - 4); p= 0.001). Among LUS pathological findings, irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequentin patients whoneeded oxygen supplementation (p = 0.007; p = 0.006 andp = 0.001, respectively). This multicentric study confirmed that LUS is able to detect Covid-19 low respiratory tract involvement, which is characterized by pleural line irregularities, vertical artifacts and subpleural consolidations. Notably, children with higher LUS score have an higher risk of hospitalization or need for oxygen supplementation, supporting LUS as a valid and safe point-of-care first level tool for the clinical evaluation of children with Covid-19.

Introduced alien species have direct and indirect effects on native communities, leading to lower taxonomic diversity and negative impacts on ecosystem functioning. Moreover, other aspects of diversity could be negatively affected, through alteration of functional and phylogenetic diversity of a community. This is particularly evident in habitats where human disturbance may favour alien species, posing an additional stressor on native communities. Following the community resistance hypothesis (higher diversity, higher resistance to invasion), we hypothesized: i) higher taxonomic, functional and phylogenetic diversity (TD, FD and PD respectively) in non-invaded bird communities (i.e. no alien bird species); and, ii) lower alien species impact on all diversity metrics in less human-disturbed areas. We surveyed bird communities in a modified Mediterranean landscape subject to varying levels of human disturbance. We tested whether TD, FD and PD indices were significantly different between non-invaded and invaded bird communities, and assessed the effect of landscape composition and configuration on these indices. We found that non-invaded communities retained higher TD and FD than invaded communities. Alien birds occupied novel parts of the functional space in invaded communities, but that they did not fully compensate for the taxonomic and functional diversity loss caused by the absence of native species. These results were consistent across different habitats, suggesting weak environmental filtering of communities. Generally, both communities were negatively affected by more human-disturbed areas (e.g. agriculture and urban areas) and enhanced by forest areas and by landscape heterogeneity. Our results suggest that the occurrence of alien birds negatively affects TD and FD (but not PD) of bird community assemblages, but that this impact is stronger in human-modified landscapes. Therefore, since the conservation of biodiversity in anthropogenic habitats is a worldwide challenge, researchers should prioritize efforts to assess the effects of alien species on communities inhabiting those habitats.

Understanding how geographic range limits are shaped is a central and challenging question in ecology that has become particularly critical in the context of global environmental changes. A central hypothesis in several theories for range limitations is that the density, fitness and performance of individuals decrease towards the edge of the range as organisms become maladapted when approaching the limit of their environmental tolerance (‘Abundant-centre Hypothesis’). Energy is a critical resource, especially in winter when environmental conditions deteriorate, and this hypothesis predicts that high energy expenditure (low performance) at the range limit would lead to rapidly dwindling body mass and reduced fitness. We investigated this hypothesis in an Arctic breeding seabird wintering in the North-Atlantic, the black-legged kittiwake (Rissa tridactyla). From 2008 to 2019, we tracked 118 adult kittiwakes (n= 178 tracks) with geolocation devices and saltwater immersion sensors to estimate the time-activity budget and energy expenditure of individuals during winter, and estimated their reproductive success after their return to the colony during summer. Density was indeed higher towards the center of the range. However, contrary to the predictions, the energy expenditure of individuals was higher at the centre of the range and decreased towards the edge. In contrast, there were no spatial differences in the reproductive success of individuals wintering at the centre versus at the edge of their range. We conclude that performance and fitness did not increase towards the centre of the range, implying that although resource acquisition was likely higher at the abundant centre, energy expenditure was also higher, so that individual fitness was constant across the range.

This study demonstrates the sustainable synthesis of multifunctional CIS@MIL-101(Cr) composites for water treatment applications. The composites were prepared via hybridization of CuInS2 with MIL-101(Cr) resulting in the formation of CIS nanoplates incorporated into MIL-101(Cr). The composites exhibited high visible light photocatalytic activity due to their low band gap energy and were tested for tetracycline photodegradation achieving a degradation efficiency of 98.8%. The material showed high stability after four cycles, and the effects of reactive species on photodegradation were investigated. The kinetics and mechanism of the photocatalytic process were studied, and HPLC-MS analysis was conducted to identify intermediate products. These results demonstrate the potential of using waste PET to create new semiconductors for water pollution control, promoting a circular material pathway.

Background: Adolescents with cancer routinely report feelings of isolation and exclusion, including from medical decision-making. To address this problem and support adolescents, we designed and implemented into clinical practice the novel, virtual, weekly Teens4Teens peer support group and patient education program. Objective: We examined the views of participating adolescents, program guest speakers, and program moderators as they pertained to the need for the program and its feasibility, acceptability, and perceived impact. Methods: We recruited all available adolescents, moderators, and guest speakers who participated in Teens4Teens to take part in audio-recorded, semi-structured interviews. Interviews were transcribed, coded, and analyzed using thematic analysis. Results: We conducted 21 interviews across participant groups. We identified four broad themes: pathways into the Teen4Teens program, Teens4Teens implementation capacity, perspectives of the positive impact of Teens4Teens and suggestions to improve Teens4Teens. These themes described a perceived need for adolescent-centered psychosocial programing in pediatric cancer care, provided lessons on how best to build and apply such a program in practice, and highlighted the value of the program for both adolescents and clinicians’ acceptability, feasibility, and perceived utility. Conclusion: Adolescents, guest speakers, and moderators valued Teens4Teens and made suggestions to retain or improve capacity to routinely implement the program. Adolescent-tailored psychosocial programming such as Teens4Teens is positioned to be integrated into clinical care with relative ease and may serve to improve the cancer care experience of adolescents and their families.

Pediatric clinical practice guidelines (CPGs) on chemotherapy-induced vomiting (CIV) control were adapted for use at our institution. Palonosetron use was limited due to cost. The primary objective of this study was to determine the extent that palonosetron use was discordant with the institutional policy and CPG. We conducted a retrospective review of pediatric patients who received palonosetron when receiving chemotherapy at SickKids between July 1 st, 2019, and June 30 th, 2020. Most (72%) palonosetron doses were discordant with institutional policy; 27% were discordant with the CPG. Our institutional policy has since been updated and is now more aligned with the CPG.

Background: Data on the outcome and risk factors of pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. Objectives: We aimed to describe risk factors for a severe course and mortality. Method: In this nationwide study, data were collected retrospectively from 28 transplant centers. Results: One hundred ninety-six children [(63.8% male; median age 8.75 (IQR, 4.86-14.30)] who received allogeneic (n: 184, 93.9%) or autologous (n: 12, 6.1%) HSCT were included. The median time from HSCT to SARS-CoV-2 infection was 207.5 days (IQR, 110.2-207.5). The most common clinical manifestation was fever (58.2%), followed by cough (33.7%); 43 cases (21.9%) were asymptomatic. Lower respiratory tract disease (LRTD) and multisystem inflammatory syndrome in children (MIS-C) developed in 58 (29.6%) and 8 (4.1%) patients, respectively. Twenty-six patients (13.3%) required ICU admission. Nine patients died at a median of 17 days (min-max 1-33) after COVID-19 diagnosis, 6 of whom died due to the disease, with a COVID-19 lethality rate of 3.1%. The 6-week overall survival was 95.4% (95% CI 92.5-98.3). Multivariate analysis found that HSCT with a mismatched donor (OR, 8.98, p: 0.039) and LRTD (OR, 61.55, p: 0.001) were independent risk factors for ICU admission; MIS-C (OR, 9.55, p: 0.044) and lymphopenia (OR, 4.01, p: 0.030) at diagnosis were risk factors for mortality. Conclusion: Overall mortality was lower in children than in adult counterparts, and HSCT with a mismatched donor, lymphopenia, LRTD, MIS-C and ICU admission were important risk factors for adverse outcomes.

The robustness of a linear system in the view of parametric variations requires a stability analysis of a family of polynomials. If the parameters vary in a compact set A, then obtaining necessary and sufficient conditions to determine stability on the family F A is one of the most important tasks in the field of robust control. Two interesting classes of families arise when A is a diamond or a box of dimension n+1. These families will be denoted by F D n and F B n , respectively. In this paper a study is presented to contribute to the understanding of Hurwitz stability of families of polynomials F A . As a result of this study and the use of classical results found in the literature, it is shown the existence of an extremal polynomial f ( α ∗ , x ) whose stability determines the stability of the entire family F A . In this case f ( α ∗ , x ) comes from minimizing determinants and sometimes f ( α ∗ , x ) coincides with a Kharitonov’s polynomial. Thus another extremal property of Kharitonov’s polynomials has been found. To illustrate the versatility/generality of our approach, this is addressed to families such as F D n and F B n , when n≤5. Furthermore, the study is also used to obtain the maximum robustness of the parameters of a polynomial. To exemplify the proposed results, first, a family F D n is taken from the literature to compare and corroborate the effectiveness and the advantage of our perspective. Followed by two examples where the maximum robustness of the parameters of polynomials of degree 3 and 4 are obtained. Lastly, a family F B 5 is proposed whose extreme polynomial is not necessarily a Kharitonov’s polynomial.

some new approaches for the stability and stabilizability determination of nonlinear interval syst