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We provide a simple and intuitive theory to explain how coupling a molecule to an optical cavity can modify ground-state chemical reactivity by exploiting intrinsic quantum behaviors of light-matter interactions. Using the recently developed Polarized Fock States representation, we demonstrate that the change of the ground-state potential is achieved due to the scaling of diabatic electronic couplings with the overlap of the polarized Fock states. Our theory predicts that for a proton-transfer model system, the ground state barrier height can be modified through light-matter interactions when the cavity frequency is in the electronic excitation range. Our simple theory explains several recent computational investigations that discovered the same effect. We further demonstrate that under the deep strong coupling limit of the light and matter, the polaritonic ground and first excited eigenstates become the Mulliken-Hush diabatic states, which are the eigenstates of the dipole operator. This work provides a simple but powerful theoretical framework to understand how strong coupling between molecule and cavity can modify ground state reactivities.

Despite the modern celebrity of the fossil collector Mary Anning (1799–1847) of Lyme Regis and her frequent use as an icon in scientific education and popularization, there are few accounts of her life by her contemporaries. We report here a previously unpublished anonymous manuscript memoir of Anning's life, in the Special Collections of the University of Bristol Library. Evidence from textual analysis and handwriting corroborates its attribution to George Roberts (bap. 1804–60) of Lyme Regis, schoolmaster and historian. He wrote it at some time during 1837–47, perhaps 1839–47, by adapting a passage in his 1834 history of Lyme Regis. It was apparently intended for a new book, but was altered into an obituary after Anning's death. Evidence is presented that Roberts wrote the obituary of Anning in the Athenæum , which was widely republished in newspapers. Henry De la Beche (1796–1855) published another obituary in the Proceedings of the Geological Society . Roberts helped him to obtain information from Anning's family, but did not use this new information in his manuscript. Benjamin J.M. Donne (1831–1928), a former pupil of Roberts, painted the Society's portrait of Anning. A claim that it was commissioned by a group, mostly Fellows of the Society, remains unconfirmed.

This study reports a content analysis of the first 10 years of the Journal of Nonprofit Education and Leadership (JNEL). A team of 10 researchers spent two years piloting, and comprehensively reading and coding 97 theoretical articles published between 2010-2020. This analysis found the journal published education and leadership-focused articles with an emerging area of democracy-focused articles. The journal produced a mix of quantitative, qualitative, and mixed-methods articles, which differ from previous content analysis studies conducted in other nonprofit and philanthropic studies journals. The keywords were separated into the 16 categories of the NACC curricular guidelines, which demonstrated the variety of education and leadership-focused topics covered in the first 10 years of the journal. This study has implications for nonprofit and philanthropic studies as JNEL is a lesser-known emerging journal that caters to practitioners and scholars.

Objectives The inclusion of musculoskeletal conditions within multimorbidity research is inconsistent, and working-age populations are largely ignored. We aimed to: (1) estimate multimorbidity prevalence among working-age individuals with a range of musculoskeletal conditions; and (2) better understand the implications of decisions about the number and range of conditions constituting multimorbidity on the strength of associations between multimorbidity and burden (e.g., health status and health care utilization). Study Design and Setting Using data from the Australian National Health Survey 2007–08, the associations between burden measures and three ways of operationalizing multimorbidity (survey, policy, and research based) within the working-age (18–64 years) musculoskeletal population were estimated using multiple logistic regression (age and gender adjusted). Results Depending on definition, from 20.2% to 75.4% of working-age individuals with musculoskeletal conditions have multimorbidity. Irrespective of definition, multimorbidity was associated with increased likelihood of subjective health burden, pain or musculoskeletal medicines use, nonmusculoskeletal specialist and pharmacist (advice only) consultations, and reduced likelihood of not consulting health professionals. A group with intermediate health outcomes was considered multimorbid by some, but not all definitions. With the restrictive policy and research multimorbidity definitions, this intermediate group is included within the reference population (i.e., are considered nonmultimorbid). This worsens the reference group's apparent health status thereby leveling the comparative burden between those with and without multimorbidity. Consequently, dichotomous cut points lead to similar associations with burden measures despite the increasingly restrictive multimorbidity definitions used. Conclusions All multimorbidity definitions were associated with burden among the working-age musculoskeletal population. However, dichotomous cut points obscure the gradient of increased burden associated with restrictive definitions.

Background Health systems globally promote appropriate prescribing by healthcare providers and safe and effective medicine use by consumers. Rx for Change, a publicly available database, provides access to systematic reviews regarding best practices for prescribing and using medicines. Despite the value of the database for improving prescribing and medicine use, its use remains suboptimal. This study aimed to develop a training program for five medicine-focused organisations in Canada and Australia to facilitate the use and understanding of the Rx for Change database. Methods Four steps were undertaken: 1) key informant interviews were completed across all organisations to understand the knowledge user perspective; 2) a directed content analysis was completed of the interview transcripts and proposed training was developed; 3) a second round of feedback on the proposed training by knowledge users was gathered; and 4) feedback was integrated to develop the final training. Results Sixteen key informant interviews with knowledge users were conducted. Themes for training content included the scope of, navigation and strategies for using Rx for Change (generic content) and practical examples on incorporating evidence within their workplace context (tailored content). The final training consisted of an informational video, a 60-minute face-to-face workshop and two post-training reminders. Conclusions A method of engaging knowledge users in the development of a training program to improve the use of an on-line database of systematic reviews was established and used to design training. Next steps include the delivery and evaluation of the training.

Background The Long-ter M O U tcomes after the Multisystem Inflammatory S yndrome I n C hildren (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. Methods This multicenter observational cohort study will enroll at least 600 patients Conclusion The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

The military punishment of decimatio, the cudgelling by lot of one in ten men in a disgraced unit, often described as a cornerstone of Roman military discipline, was never practised during the third and second centuries BC. The punishment was possibly used as an extraordinary measure a couple of times in the fifth and fourth centuries BC. It soon fell into total desuetude but was cultivated as a rhetorical construct that proclaimed theoretical powers commanders no longer dared effect. It was only revived, or rather reinvented, during the Late Republic, a violent moment that saw the confluence of antiquarian enthusiasm with military dynasts whose unrestrained powers allowed them to manifest what had previously been an aristocratic talking point.

Chronic analgesic use is described in home parenteral nutrition (HPN)-dependent patients, but there are limited data on factors associated with opioid use for noncancerous pain.Patients attending a national UK intestinal failure reference center were divided in two groups according to strong opioid (SO) usage; risk factors for SO usage were analyzed using logistic regression.A total of 168 HPN-dependent patients were included. During the study period, 73 patients (43.5%) had documented SO usage (SO group), whereas the remainder did not (No-SO group). The prevalence of Crohn's disease among the No-SO group was twofold higher than among the SO group (43.2% vs 24.7%; P = 0.013), whereas those with surgical complications were twice as prevalent among the SO group (19.2% vs 8.4%, respectively; P = 0.04). The rate of working-age unemployment was significantly higher in the SO group (90.6%) than the No-SO group (55.6%; P = 0.001). Multivariate regression showed unemployment as an independent risk factor for SO usage (OR, 6.005; 95% CI, 1.435-25.134), whereas Crohn's disease (OR, 0.284; 95% CI, 0.09-0.898) and4 intravenous support (IVS) nights per week (OR, 0.113; 95% CI, 0.012-1.009) were protective factors. The life-long incidence of catheter-related bloodstream infection (CRBSI) was comparable between groups (34.2% SO vs 27.4% No-SO; P = 0.336).SO use is frequent among HPN-dependent patients and associated with high rates of unemployment and ≥4 IVS nights per week, but not with increased rate of CRBSI. The reduced usage among patients with Crohn's disease warrants further evaluation but might be due to the chronicity as compared with other IF etiologies.

This article develops economic models for a cow-calf ranching operation and an alfalfa hay operation in the Humboldt River Region (HRR) that use surface water for irrigation. The models were built and parameterized through consultation with ranchers and farmers in the HRR in order to represent typical agricultural operations in the region. The models were used to calculate the economic value to an operation of an acre-foot of water not received due to an unanticipated supply reduction. This analysis was conducted to support the conjunctive management of surface and groundwater in the HRR by providing estimates of the economic value of the water that surface water users expect but do not receive due to interference from upstream groundwater pumping. For the cow-calf ranch model, reduced water deliveries impact ranch profits by reducing the amount of low-cost feed grown on the ranch. The increase in average feed costs forces the ranch to reduce its herd size, which lowers the number of new calf births and, as a result, lowers future profits from livestock sales. The cow-calf ranching model predicts an economic value of an acre-foot of water for the cow-calf ranch in the range of $215 per acre-foot for unanticipated supply interruptions that occur in normal water years, and upwards of $290 per acre-foot for supply interruptions that occur during drought. Model results do not provide evidence that the economic value of an acre-foot of water increases with the length of the unanticipated supply reduction. For the alfalfa hay farm model, results indicate that unanticipated reduced water deliveries impact farm profits by first preventing the farm from planting a cover crop during fallow years and then, for more significant interruptions, reducing its acreage of alfalfa hay. The alfalfa hay model predicts that the economic value of an acre-foot of water increases with both the volume of water not received and the length of the unanticipated supply reduction. The economic value of water per-acre-foot predicted by the alfalfa hay model ranges from less than $10 per acre-foot for unanticipated supply interruptions that occur in normal water years, in the range of $100-$200 per acre-foot for single-year supply interruptions that occur during a below average water year, and over $300 per-acre-foot for supply interruptions that occur in successive below average water years.

BACKGROUND In an era of pay for performance metrics, we sought to increase understanding of factors driving high resource utilization (HRU) in emergent (EGS) versus same-day elective (SDGS) general surgery patients. METHODS General surgery procedures from the 2016 ACS-NSQIP public use file were grouped according to the first four digits of the primary procedure CPT code. Groups having at least 100 of both elective and emergent cases were included (22 groups; 83,872 cases). HRU patients were defined as those in-hospital >7D, returned to the OR, readmitted, and/or had morbidity likely requiring an intensive care unit (ICU)stay. Independent NSQIP predictors of HRU were identified through forward regression; P for entry 0.10. RESULTS Of all patients, 33% were HRU. The three highest HRU procedures (total colectomy, enterolysis, and ileostomy) comprised a higher proportion of EGS than SDGS cases (10.3 versus 2.6%, P < 0.001). The duration of operation was 40 Min lower in EGS after adjustment. Thirty-nine of the remaining 40 HRU predictors were higher in EGS including preoperative SIRS/Sepsis (50 versus 2%), ASA classification IV-V (31 versus 5%), albumin

John Johnstone was an Edinburgh printer and publisher, from 1849 in partnership with Robert Hunter. In 1839, Johnstone and the printer Robert Fairly established a separate firm, Johnstone & Fairly, to publish the Witness, a newspaper edited by the geologist Hugh Miller. The firm became Miller & Fairly in 1844 when Miller bought out Johnstone's share. The editorial office was in the High Street. The steam-powered printing office was in Horse Wynd, in the former gatehouse of Minto House and later also in the former house of the physician Dr John Clerk of Listonshiels. Johnstone's own publishing business specialized in religious and ecclesiastical works. Nevertheless, Miller chose that firm to publish The Old Red Sandstone (1841), and later books, until the firm ran into financial trouble in the mid-1850s, and Miller placed The testimony of the rocks (1857) with Shepherd & Elliot of Edinburgh. Miller's original choice of Johnstone was perhaps to protect the reputation of Miller and the Witness when geology was often regarded with suspicion on religious grounds. It may also have given Miller more creative freedom. Miller & Fairly printed many, but not all, impressions of Miller's books for Johnstone and other publishers. This was to Miller's, and Miller's heirs', presumed double profit as copyright holder and printer, with implications for his relationships with publishers. Miller's dual role may help explain his reluctance to resign the newspaper's editorship even at the cost of his health and life.

When molecules are coupled to an optical cavity, new light-matter hybrid states, so-called polaritons, are formed due to quantum light-matter interactions. With the experimental demonstrations of modifying chemical reactivities by forming polaritons under strong light-matter interactions, theorists have been encouraged to develop new methods to simulate these systems and discover new strategies to tune and control reactions. This review summarizes some of these exciting theoretical advances in polariton chemistry, in methods ranging from the fundamental framework to computational techniques and applications spanning from photochemistry to vibrational strong coupling. Even though the theory of quantum light-matter interactions goes back to the mid-twentieth century, the gaps in the knowledge of molecular quantum electrodynamics (QED) have only recently been filled. We review recent advances made in resolving gauge ambiguities, the correct form of different QED Hamiltonians under different gauges, and their connections to various quantum optics models. Then, we review recently developed {\it ab-initio} QED approaches which can accurately describe polariton states in a realistic molecule-cavity hybrid system. We then discuss applications using these method advancements. We review advancements in polariton photochemistry where the cavity is made resonant to electronic transitions to control molecular non-adiabatic excited state dynamics and enable new photochemical reactivities. When the cavity resonance is tuned to the molecular vibrations instead, ground-state chemical reaction modifications have been demonstrated experimentally, though its mechanistic principle remains unclear. We present some recent theoretical progress in resolving this mystery. Finally, we review the recent advances in understanding the collective coupling regime between light and matter, where many molecules can collectively couple to a single cavity mode or many cavity modes. We also lay out the current challenges in theory to explain the observed experimental results. We hope that this review will serve as a useful document for anyone who wants to become familiar with the context of polariton chemistry and molecular cavity QED and thus significantly benefit the entire community.

For imaging instruments that are in space looking toward the Earth, there are a variety of nuisance signals that can get in the way of performing certain imaging tasks, such as reflections from clouds, reflections from the ground, and emissions from the OH-airglow layer. A method for separating these signals is to perform tomographic reconstructions from the collected data. A lingering struggle for this method is altitude-axis resolution and different methods for helping with it are discussed. An implementation of the maximum likelihood expectation maximization algorithm is given and analyzed.

PurposeThe purpose of this viewpoint paper is to explore the fixation of the eyes of human resource (HR) professionals' when identifying emotions in the context of workplace research and to propose measures that might support them in their role.Design/methodology/approachThis paper combines a contemporary literature review with reflections from practice to develop more nuanced understandings of 39 HR professionals' ability to recognise emotions. This paper used eye-tracking technology more commonly used in laboratory-based students to explore the fixation of the eye when identifying emotions.FindingsThe preliminary findings suggest that HR professionals with higher levels of emotional recognition principally focus on the eyes of the recipient, whereas those with lower levels or emotional recognition focus more so the nose or the randomly across the face, depending on the level of emotional recognition. The data suggest that women are better than men, in the sample group at recognising emotions, with some variations in recognising specific emotions such as disgust.Research limitations/implicationsThe viewpoint paper proposes a number of implications for middle leaders and suggests that middle leaders should proactively seek out opportunities to be engaged in activities that support the Default Mode Network (DMN) function of the brain and subsequently the relationship-orientated aspects of leadership, for example, coaching other staff members. However, it has to be recognised that the sample size is small and further work is needed before any generalisations can be made.Originality/valueThis paper offers a contemporary review underpinned by a preliminary study into HR professionals' ability to recognise emotions.

Background Higher education is responsible for providing education that meets international benchmarks relevant to the needs of the international community. Due to the increase of digital tools in higher education, the possibility of sharing learning resources across nations has expanded. In the current project, a Norwegian university invited universities in Spain and the United Kingdom to adapt and translate e-learning resources originally developed for Norwegian nursing students for use within their respective Bachelor in Nursing programmes. Aim The aim of the current study was to gain insights into the usability and value for learning of e-compendiums shared and implemented across three European universities. Methods The study adopted a descriptive cross-sectional design and included nursing students from the University of Nottingham, Valencia Catholic University, and the University of Stavanger. Data were collected in Autumn 2017 through a questionnaire adapted from the validated “Centre for Excellence in Teaching and Learning Reusable Learning Object evaluation questionnaire” The questionnaire consisted of 19 items that included two aspects: e-compendiums’ value for learning and e-compendiums’ usability. The different study sites were compared using a binary logistic regression analysis. Subgroups of students were compared based on their gender and age. Results A total of 480 nursing students participated in the study. The e -compendiums were overall positively rated, especially for reinforcing and retaining knowledge. Compared to the students from the University of Stavanger, students from Valencia Catholic University rated the e-compendiums more positively in most aspects of learning. Students from University of Nottingham found the e-compendiums to be more important for learning engagement compared to students at the Norwegian study site, and no differences were found in any other aspects of learning. Younger students rated the interactivity and visual components as more important compared to older students. Conclusions Students from the University of Nottingham and Valencia Catholic University seem to accept the e-compendiums despite the fact that they were originally developed for use in another country. We argue that, when sharing e-learning resources across countries, an adaptation and translation process that includes a multicultural and multidisciplinary perspective should be carried out.

Osteoarthritis (OA) is one of the most prevalent conditions in the world, particularly in the developed world with a significant increase in cases and their predicted impact as we move through the twenty-first century and this will be exacerbated by the covid pandemic. The degeneration of cartilage and bone as part of this condition is becoming better understood but there are still significant challenges in painting a complete picture to recognise all aspects of the condition and what treatment(s) are most appropriate in individual causes. OA encompasses many different types and this causes some of the challenges in fully understanding the condition. There have been examples through history where much has been learnt about common disease(s) from the study of rare or extreme phenotypes, particularly where Mendelian disorders are involved. The often early onset of symptoms combined with the rapid and aggressive pathogenesis of these diseases and their predictable outcomes give an often-under-explored resource. It is these “rarer forms of disease” that William Harvey referred to that offer novel insights into more common conditions through their more extreme presentations. In the case of OA, GWAS analyses demonstrate the multiple genes that are implicated in OA in the general population. In some of these rarer forms, single defective genes are responsible. The extreme phenotypes seen in conditions such as Camptodactyly Arthropathy-Coxa Vara-pericarditis Syndrome, Chondrodysplasias and Alkaptonuria all present potential opportunities for greater understanding of disease pathogenesis, novel therapeutic interventions and diagnostic imaging. This review examines some of the rarer presenting forms of OA and linked conditions, some of the novel discoveries made whilst studying them, and findings on imaging and treatment strategies.

Background The risk of bloodstream infections may be increased in hospitalized patients receiving ready-made parenteral nutrition (PN) multichamber bags (MCBs) compared with customized PN; however, as highlighted in recent international guidelines, there are no comparable data relating to home PN (HPN). Methods Data from a prospectively maintained database were analyzed to compare incidence rates of catheter-related bloodstream infections (CRBSIs) between patients receiving customized HPN compared with MCB HPN at a national UK referral center between May 2018 and August 2020. Results Sixty patients with chronic intestinal failure were commenced on MCBs and 45 received customized HPN for a total of 5914 and 7641 catheter days, respectively. No difference in CRBSI incidence was found (0.51/1000 catheter days for MCBs, 0.39/1000 catheter days for customized HPN; incidence rate ratio, 1.29; 95% CI, 0.26-6.37). Eighteen patients were switched from customized HPN to MCB HPN. The study period covered 7401 catheter days receiving customized HPN and 4834 days on MCBs. No significant change was noted in the CRBSI rates following this switch (0.27/1000 catheter days receiving customized HPN vs 0.21/1000 catheter days on MCBs; incidence rate ratio, 1.31; 95% CI, 0.12-14.3). Conclusion The use of MCBs for HPN patients is not associated with an increased risk of CRBSI. This study will inform international guidelines and provide reassurance for the continued, safe use of MCB HPN.

In New Zealand, the introduced honey bee (Apis mellifera) is a valuable production animal, providing pollination services for horticultural crops and significant export volumes of honey, especially...

A fungal-related catheter-related bloodstream infection (CRBSI) is less frequent than those induced by bacteria. In the past, a single episode of fungal CRBSI has been used as a marker of home parenteral nutrition (HPN) failure and thus a possible indication for intestinal transplantation.Survival outcomes were assessed from a prospectively maintained database of patients initiated on HPN for underlying chronic intestinal failure between 1993 and 2018, with a censoring date of December 31, 2020. Cox regression was performed to assess predictors of mortality with univariable and multivariable analysis.A total of 1008 patients were included in the study, with a total of 1 364 595 catheter days. There were 513 CRBSI events recorded in 262 patients, equating to a CRBSI rate of 0.38/1000 catheter days. A total of 38/262 (14.5%) patients had at least one episode of fungal CRBSI, whereas 216/262 (82.4%) had at least one bacterial but no fungal CRBSI. The median time between HPN initiation and the first CRBSI episode was 20.6 months (95% confidence interval, 16.5-24.1). Episodes of fungal or bacterial CRBSI and the number of CRBSI episodes were not associated with increased mortality. Overall, 15 CRBSI-related deaths were observed in the observation period (0.01 CRBSI deaths/1000 catheter days), two of these were fungal in origin.The occurrence of a fungal CRBSI does not increase the risk of death compared with patients who have bacterial CRBSI or those without a CRBSI event.

The Single Ventricle Reconstruction (SVR) Trial was the first randomized clinical trial of a surgical approach for treatment of congenital heart disease. Infants with hypoplastic left heart syndrome (HLHS) and other single right ventricle (RV) anomalies were randomized to a modified Blalock Taussig Thomas shunt (mBTTS) or a right-ventricular-to-pulmonary-artery shunt (RVPAS) at the time of the Norwood procedure. The aim of the Long-term Outcomes of Children with HLHS and the Impact of Norwood Shunt Type (SVR III) study is to compare early adolescent outcomes including measures of cardiac function, transplant-free survival, and neurodevelopment, between those who received a mBTTS and those who received an RVPAS.Transplant-free survivors of the SVR cohort were enrolled at 10 to 15 years of age for multifaceted in-person evaluation of cardiac function (cardiac magnetic resonance [CMR], echocardiogram and exercise test) and neurodevelopmental evaluation. Right ventricular ejection fraction measured by CMR served as the primary outcome. Development of arrhythmias, protein losing enteropathy, and other comorbidities were assessed through annual medical history interview. Through the course of SVR III, protocol modifications to engage SVR trial participants were designed to enhance recruitment and retention.Evaluation of long-term outcomes will provide important data to inform decisions about the shunt type placed at the Norwood operation and will improve the understanding of cardiovascular and neurodevelopmental outcomes for early adolescents with HLHS.

An approach to adaptive optics utilizing a single-pixel camera (SPC) is proposed to maximize fiber coupling efficiency at the receiver side of an optical satellite-to-ground link perturbed by atmospheric turbulence. Using a single-pixel wavefront sensor enables operation at longer optical wavelengths, such as near and far infrared, which have advantageous propagation characteristics for free space optical communication. In this approach, a focal plane intensity image of the atmospheric-disturbed wavefront is taken via an SPC using a compressed sensing technique. An iterative speckle-based phase retrieval algorithm is then applied to infer the phase distortion corrected by a deformable mirror in a feedback loop. This computational approach to inferring the phase of the wavefront overcomes the limitations of traditional Shack–Hartman-based approaches, which are difficult to implement at high speed and at the long infrared wavelengths proposed for future optical satellite communication downlinks. It has been shown that fiber coupling efficiency is increased from less than 5% to 40%–50% in medium-to-strong turbulence scenarios with the phase retrieval algorithm proposed in this work.

Purpose: An expected outcome following germline genome sequencing in oncology is the discovery of ‘secondary findings’ (SFs). SFs comprise pathogenic(P)/likely P (LP) germline variants in cancer genes not typically associated with the presenting cancer, in addition to germline variants of uncertain significance (VUS) to the patient’s cancer. Due to the rarity of childhood cancers and a dearth of studies analyzing SFs, many pediatric SFs are categorized as VUS without clinical interpretation. Interpreting SFs poses significant challenges: VUSs and other SFs are frequently not included in clinical molecular reports, and even when reported (often through research), their clinical utility and long-term impact on patient health are unclear. However, we know VUSs can have clinical importance because some VUSs, when investigated thoroughly, have been reclassified as pathogenic predictors of significant health conditions in children. We hypothesize that an in-depth characterization of the landscape of germline SFs/VUSs across a diverse pediatric cancer cohort will reveal new roles of these genes and mutations in pediatric cancers. Methods: To explore germline SFs in pediatric cancer patients, we analyzed germline whole-genome sequencing (WGS) data for patients with rare, relapsed, refractory, and metastatic childhood cancers enrolled in the SickKids Cancer Sequencing Program (KiCS). We developed a custom analysis pipeline to identify germline single-nucleotide variants and indels deemed SFs, auto-classify their pathogenicity (ex. P, LP, or VUS) using CharGer, filter for PanCanAtlas-indicated cancer predisposition genes, and sort the remaining variants by cancer and non-cancer associations. Results: The KiCS cohort (n = 511) encompassed over 133 different tumor types; the median age of participants was 14 years (SD = 10.27) and 55% of patients were male. Ongoing work in our lab will catalogue the frequency and distribution of SFs in KiCS and analyze germline variants by subgroup (gene, tumor subtype, stage, demographics, gene function). We will also compare SF prevalence in KiCS to the general population using the gnomAD dataset. Results from preliminary analyses of this cohort will be presented. Significance: SFs/VUSs are under-utilized in cancer management. This work advances the holistic understanding of germline genomics in pediatric oncology and the roles of SFs in disease. Future studies will evaluate SFs by patient ancestry and validate cancer associations through the evaluation of allelic imbalance/loss of heterozygosity in matched tumor genomes. Citation Format: Safa Majeed, Stephenie Prokopec, Brianne Laverty, Vallijah Subasri, Michael Taylor, Yvonne Bombard, Trevor Pugh, Adam Shlien, Anita Villani, David Malkin. Investigating secondary findings in a pediatric cancer cohort: preliminary findings. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6545.

Cyclin-dependent kinases (CDK) are a family of serine/threonine kinases that heterodimerize with regulatory subunits called cyclins to drive cell cycle progression. Uncontrolled cellular proliferation is a hallmark of cancer commonly driven by dysregulated kinase activity of specific CDK family members, including cyclin-dependent kinase 2 (CDK2). Aberrant CDK2 activity most frequently occurs through amplification of CCNE1 and/or overexpression of its protein product cyclin E1, which is a canonical binding partner of CDK2. Overexpression of cyclin E1 is observed in many solid tumors including in patients with high grade serous ovarian cancer (HGSOC), gastric cancer, and ER-positive breast cancer patients whose tumors have progressed on a prior CDK4/6 inhibitor regimen. Selective inhibition of CDK2 is thus a compelling therapeutic approach to regain cell cycle control. Here, we report preclinical data supporting the development of INX-315 for patients with cancers in which proliferation is CDK2-dependent. INX-315 is a potent inhibitor of CDK2/cyclin E (0.6 nM biochemical IC50) with high selectivity over other CDK family members in both biochemical and intracellular NanoBRET assays. In CCNE1-amplified human ovarian and gastric cancer cell lines, INX-315 potently inhibited Rb phosphorylation, induced a G1 cell cycle arrest, and inhibited proliferation. INX-315 also showed potent anti-proliferative activity in luminal breast cancer cell lines that had been cultured in CDK4/6 inhibitor (+/- anti-estrogen therapy) for prolonged periods to the point of developing drug resistance. While these cell lines did not readily respond to either CDK4/6 or CDK2 inhibition alone, combination treatment again suppressed Rb phosphorylation, accompanied by G1 arrest and a senescent-like phenotype. Lastly, in CCNE1-amplified xenograft models of ovarian and gastric carcinomas, INX-315 inhibited Rb-phosphorylation and induced tumor regression. These data demonstrate INX-315 to be a potent and selective CDK2 inhibitor that may benefit patients with CDK2/cyclin E driven cancers. Citation Format: Alec G. Trub, John E. Bisi, Catherine Dietrich, Michael Taylor, Jay C. Strum, Shom Goel, Patrick J. Roberts. INX-315, a potent and selective CDK2 inhibitor, demonstrates robust antitumor activity in CCNE1-amplified cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5994.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is a life-saving therapy for patients with chronic intestinal failure but can be associated with a degree of psychological distress. The factors associated with the need for antidepressants (AD) in this cohort have not yet been described.METHODS: The study involved prospective data collection from patients attending HPN clinic at a national intestinal failure referral centre. Patients requiring HPN as a result of active malignancy were excluded. Patients were divided in two groups according to AD usage; demographic, anthropometric, socioeconomic characteristics and IVS regimens were compared between groups.RESULTS: A total of 184 patients were recruited between July 2018 and April 2019, with an overall prevalence of AD use of 41.7%. Daily mean IVS volume was significantly higher among patients taking AD ('AD' group; 2125.48±991.8 ml/day, 'no-AD' group; 1828.54±847.0 ml/day, P = 0.039) with the proportion of patients needing high volume IVS (≥3000ml/day) being three-times higher in the AD group (20.0% vs. 6.1%, P = 0.006). The average energy IVS infusion per day was similar between the two groups. Hypnotic use (25.7% vs. 5.1%, P

PurposeThis paper focusses on the leaders' ability to recognise and empathise with emotions. This is important because leadership and particularly transformational leadership are principally focussed on an individual's social interactions and their ability to identify emotions and to react empathetically to the emotions of others (Psychogios and Dimitriadis, 2020). Many leadership theorists suggest the ability to have and display empathy is an important part of leadership (Bass, 1990; Walumbwa et al., 2008).Design/methodology/approachTo examine the extent to which those who work in jobs with a significant element of leadership education can recognise and empathise with emotions, 99 part-time postgraduate executive Master of Business Administration (MBA) students took part in an emotional recognition test. First, all participants were shown a sequence of pictures portraying different human facial expressions and the electrical activity in the brain as a result of the visual stimuli were recorded using an electroencephalogram (EEG). The second stage of the research was for the participants to see the same seven randomised images, but this time, they had to report what emotion they believed they had visualised and the intensity of it on a self-reporting scale.FindingsThis study demonstrated that the ability to recognise emotions is more accurate using EEG techniques compared to participants using self-reporting surveys. The findings from this study provide academic departments with evidence that more work needs to be done with students to develop their emotional recognition skills. Particularly for those students who are or will go onto occupy leadership roles.Originality/valueThe use of neuroscientific approaches has long been used in clinical settings. However, few studies have applied these approaches to develop the authors’ understanding of their use in social sciences. Therefore, this paper provides an original and unique insight into the use of these techniques in higher education.

Cardiovascular magnetic resonance has been utilized in the management and care of pediatric patients for nearly 40 years. It has evolved to become an invaluable tool in the assessment of the littlest of hearts for diagnosis, pre-interventional management and follow-up care. Although mentioned in a number of consensus and guidelines documents, an up-to-date, large, stand-alone guidance work for the use of cardiovascular magnetic resonance in pediatric congenital 36 and acquired 35 heart disease endorsed by numerous Societies involved in the care of these children is lacking. This guidelines document outlines the use of cardiovascular magnetic resonance in this patient population for a significant number of heart lesions in this age group and although admittedly, is not an exhaustive treatment, it does deal with an expansive list of many common clinical issues encountered in daily practice.

Flooding the surgical field with dry cold COinf2/infduring open-chamber cardiac surgery has been used to mitigate air entrainment into the systemic circulation. However, exposing epithelial surfaces to cold, dry gas causes tissue desiccation. This randomized controlled study was designed to investigate whether the use of humidified warm COinf2/infinsufflation into the cardiac cavity could reduce pericardial tissue damage and the incidence of micro-emboli when compared to dry cold COinf2/infinsufflation.Forty adult patients requiring elective open-chamber cardiac surgery were randomized to have either dry cold COinf2/infinsufflation via a standard catheter or humidified warm COinf2/infinsufflation via the HumiGard device (FisherPaykel Healthcare, Panmure, Auckland, New Zealand). The primary endpoint was biopsied pericardial tissue damage, assessed using electron microscopy. We assessed the percentage of microvilli and mesothelial damage, using a damage severity score (DSS) system. We compared the proportion of patients who had less damage, defined as DSS2. Secondary endpoints included the severity of micro-emboli, by visual assessment of bubble load on transesophageal echocardiogram; lowest near infrared spectroscopy; total de-airing time; highest cardio-pulmonary bypass sweep speed; hospital length of stay and complications.A higher proportion of patients in the humidified warm COinf2/infgroup displayed conserved microvilli (47% vs. 11%, P=0.03) and preserved mesothelium (42% vs. 5%, P=0.02) compared to the control group. There were no differences in the secondary outcomes.Humidified warm COinf2/infinsufflation significantly reduced pericardial epithelial damage when compared to dry cold COinf2/infinsufflation in open-chamber cardiac surgery. Further studies are warranted to investigate its potential clinical benefits.

The attention surrounding research outputs, as partially captured by altmetrics, or alternative metrics, constitutes many varied forms of data. Each of these presents their own activity profile: varying by discipline, by year of publication and by time since published. Some attention accrues through activities that take a moment’s consideration; other attention sources take months or years of consideration and curation before being realized. These differences need to be accommodated by altmetric users. The study of temporal trends in altmetrics is under-developed, and this multi-year observation study addresses some of the deficits in our understanding of altmetric behaviour over time and the history of its development. From a set of 7739 papers sampled over the period 2008-2021 the growth of Mendeley and Twitter is confirmed, alongside an apparent decline in blogging attention. The Open Access Altmetric Advantage is seen to emerge and evolve over time, with each attention source showing different trends. The existence of late-emergent attention in all attention sources is confirmed. Policy attention is identified as the slowest form of impact studied by altmetrics, and one that strongly favours the Humanities and Social Sciences.

Although international guidelines support the use of commercially available multichamber bags (MCBs), the majority of home parenteral nutrition (HPN) in the United Kingdom has been compounded PN, tailored to the patient. However, national capacity limitations in aseptic facilities have necessitated the increased use of MCBs. There are no studies evaluating the appropriateness or benefits of using a "hybrid" regimen incorporating both MCBs and compounded PN in patients already established on compounded HPN.This was a cross-sectional audit evaluation conducted on September 1, 2021, at a national United Kingdom reference center. All HPN-dependent adults prescribed HPN for chronic intestinal failure were assessed by a multidisciplinary team for their potential of being switched to a "hybrid" regimen of MCBs and compounded PN.Of 180 patients currently receiving compounded HPN that included intravenous nitrogen with glucose ± lipid, 65 (36.1%) were deemed clinically suitable for a hybrid PN regimen, with minimal variance in PN constituents per week (volume 0%, non-nitrogen kilocalories 0%, nitrogen 0%, fat -0.2%, glucose 0%, sodium 0%, potassium 0%, calcium 0%, magnesium 0%, and phosphate -0.1%) and requiring no additional central venous catheter manipulations. The potential reduction in compounded PN would reduce by 3627 bags per year, equating to a cost saving of £141,453 per year (equivalent to $178,885).Wider use of hybrid MCB/compounded HPN regimens could lead to a reduction in the need for compounded PN to be produced by aseptic facilities. Further evaluation of acceptability and tolerance of hybrid regimens by patients already receiving compounded HPN is required.

Tropical dry forests are among the most threatened ecosystems in the world, and those occurring in the insular Caribbean are particularly vulnerable. Climate change represents a significant threat for the Caribbean region and for small islands like Jamaica. Using the Hellshire Hills protected area in Jamaica, a simple model was developed to project future abundance of arthropods and lizards based on current sensitivities to climate variables derived from rainfall and temperature records. The abundances of 20 modelled taxa were predicted more often by rainfall variables than temperature, but both were found to have strong impacts on arthropod and lizard abundance. Most taxa were projected to decrease in abundance by the end of the century under drier and warmer conditions. Where an increase in abundance was projected under a low emissions scenario, this change was reduced or reversed under a high emissions climate change scenario. The validation process showed that, even for a small population, there was reasonable skill in predicting its annual variability. Results of this study show that this simple model can be used to identify the vulnerability of similar sites to the effects of shifting climate and, by extension, their conservation needs.

Peptide-coated surfaces are widely employed in biomaterial design, but quantifiable correlation between surface composition and biological response is challenging due to, for example, instrumental limitations, a lack of suitable model surfaces or limitations in quantitatively correlating data from different surface analytical techniques. Here, we first establish a reference material that allows control over amino acid content. Reversible addition-fragmentation chain-transfer (RAFT) polymerisation is used to prepare a copolymer containing alkyne and furan units with well-defined chain length and composition. Huisgen Cu(I)-catalysed azide-alkyne cycloaddition reaction is used to attach the model azido-polyethyleneglycol-amide-modified pentafluoro-l-phenylalanine to the polymer. Different compositional ratios of the polymer provide a surface with varying amino acid content that is analysed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Nitrogen-related signals are compared with fluorine signals from both techniques. Fluorine and nitrogen signals from both techniques are found to be related to the copolymer compositions, but the homopolymer data deviate from this trend. The approach is then translated to a heparin-binding peptide that supports cell adhesion. Human embryonic stem cells cultured on copolymer surfaces presenting different amounts of heparin-binding peptide show strong cell growth while maintaining pluripotency after 72 h of culture. The early cell adhesion at 24 h can be correlated to the logarithm of the normalised CH4N+ ion intensity from ToF-SIMS data, which is established as a suitable and generalisable marker ion for amino acids and peptides. This work contributes to the ability to use ToF-SIMS in a more quantitative manner for the analysis of amino acid and peptide surfaces.