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Although primarily known as a modern and contemporary art museum the Folkwang Museum in Essen, Germany also possesses a significant anthropology collection dating from the museum’s inception which is ignored in most scholarship on the museum. Using a biography of objects approach this work analyzes the interpretation of four netsuke in the museum’s collection across three exhibitions between 2010 and 2021. By analyzing the display methods of these objects in these exhibitions, their interpretation by the museum, and utilizing theories of miniature objects I demonstrate that the small size of these objects encouraged visitors to closely examine and decode these objects. Consequently, this work provides a basis for further investigation on how museums exhibit and interpret miniature objects to construct knowledge.

As electrochemistry continues to gain broader acceptance and use within the organic chemistry community, it is important that advanced undergraduate students are exposed to fundamental and practical knowledge of electrochemical applications for chemical synthesis. Herein, we describe the development of an undergraduate laboratory experience that introduces synthetic and analytical electrochemistry concepts to an advanced organic chemistry class. Experiments focus on the electrooxidative α-functionalization of carbamates, more generally known as the Shono oxidation, and include cyclic voltammetry analysis of two cyclic carbamates and a constant current bulk electrolysis reaction. The exercise offers students an authentic experience in organic electrochemistry, lays a practical and theoretical foundation for future engagement with concepts in electrochemistry and redox chemistry, and strengthens fundamental organic chemistry skills.

Background and Objective: It is documented that some of the opioids prescribed to manage chronic pain are diverted and used for nonmedical purposes. We investigated whether a skill-based, chronic pain management (CPM) educational program could improve first-year family medicine residents’ comfort, knowledge, and concerns in assessing and managing patients who use opioids for chronic noncancer pain. Methods: A total of 72 first-year residents (four cohorts of 18) participated in a 3-month CPM training intervention that consisted of didactic lectures, objective structured clinical examination (OSCE) activities, and post-OSCE debriefing with faculty, one being a behavioral health specialist, between 2017 and 2020. We used a single-sample, pre/post design. At three points in time (baseline, 3-months, and 6-months postintervention), participants completed a set of measures assessing comfort, knowledge, and concern. We used repeated measures analyses to assess changes in outcome measures. Results: Participants reported improvements compared with baseline at both follow-up time points. At 6 months postintervention, the participants had significantly better scores on measures of comfort (F[1, 71]=65.22; P

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT.

Objectives The goals of this study were to: 1) evaluate the cardiac magnetic resonance (CMR) characteristics of pediatric cardiac masses from a large international cohort; 2) test the accuracy of previously developed CMR-based diagnostic criteria; and 3) expand diagnostic criteria using new information. Background After diagnosis of a cardiac mass, clinicians must weigh the benefits and risks of ascertaining a tissue diagnosis. Limited data are available on the accuracy of previously developed noninvasive pediatric CMR-based diagnostic criteria. Methods CMR studies (children 0-18 years of age) with confirmatory histological and/or genetic diagnosis were analyzed by 2 reviewers, without knowledge of prior diagnosis. Diagnostic accuracy was graded as: 1) single correct diagnosis; 2) correct diagnosis among a differential; or 3) incorrect diagnosis. Results Of 213 cases, 174 (82%) had diagnoses that were represented in the previously published diagnostic criteria. In 70% of 174 cases, both reviewers achieved a single correct diagnosis (94% of fibromas, 71% of rhabdomyomas, and 50% of myxomas). When ≤2 differential diagnoses were included, both reviewers reached a correct diagnosis in 86% of cases. Of 29 malignant tumors, both reviewers indicated malignancy as a single diagnosis in 52% of cases. Including ≤2 differential diagnoses, both reviewers indicated malignancy in 83% of cases. Of 6 CMR sequences examined, acquisition of first-pass perfusion and late gadolinium enhancement were independently associated with a higher likelihood of a single correct diagnosis. Conclusions CMR of cardiac masses in children leads to an accurate diagnosis in most cases. A comprehensive imaging protocol is associated with higher diagnostic accuracy.

Tumor and target volume manual delineation remains a challenging task in head and neck cancer radiation therapy. The purpose of this study was to conduct a multi-institutional evaluation of manual delineations of gross tumor volume (GTV), high-risk clinical target volume (CTV), parotids, and submandibular glands on treatment simulation magnetic resonance scans of patients with oropharyngeal cancer.We retrospectively collected pretreatment T1-weighted, T1-weighted with gadolinium contrast, and T2-weighted magnetic resonance imaging scans for 4 patients with oropharyngeal cancer under an institution review board-approved protocol. We provided the scans to 26 radiation oncologists from 7 international cancer centers that participated in this delineation study. We also provide the patients' clinical history and physical examination findings, along with a medical photographic image and radiologic results. We used both the Simultaneous Truth and Performance Level Estimation algorithm and pair-wise comparisons of the contours, using overlap/distance metrics. Lastly, to assess experience and CTV delineation institutional practices, we had participants complete a brief questionnaire.Large variability was measured between observers' delineations for GTVs and CTVs. The mean Dice similarity coefficient values across all physicians' delineations for GTVp, GTVn, CTVp, and CTVn were 0.77, 0.67, 0.77, and 0.69, respectively, for Simultaneous Truth and Performance Level Estimation algorithm comparison, and 0.67, 0.60, 0.67, and 0.58, respectively, for pair-wise analysis. Normal tissue contours were defined more consistently when considering overlap/distance metrics. The median radiation oncology clinical experience was 7 years. The median experience delineating on magnetic resonance imaging was 3.5 years. The GTV-to-CTV margin used was 10 mm for 6 of 7 participant institutions. One institution used 8 mm, and 3 participants (from 3 different institutions) used a margin of 5 mm.The data from this study suggests that appropriate guidelines, contouring quality assurance sessions, and training are still needed for the adoption of magnetic resonance-based treatment planning for head and neck cancers. Such efforts should play a critical role in reducing delineation variation and ensure standardization of target design across clinical practices.

Supplementary figures 1-4, supplementary table 1

Supplementary Table S1 and 6 Supplementary Figures, S1-6. Table S1 - Patient samples from the PredictR-HNC study. Figure S1 - CCT244747 and paclitaxel IC50 determination and analysis of CCT244747 combination therapies. Figure S2 - Investigation of triple therapies using low concentrations of CCT244747 and paclitaxel. Figure S3 - Cell morphology 48 hours after treatment. HN5 cells exhibit an early increase in the S phase population. Figure S4 - High CHK1 and p-CHK1 cytoplasmic staining correlate with recurring HPV+ HNSCC tumours. Figure S5 - High CHK1, p-CHK1 and p-ATM expression correlate with recurring tumours. Figure S6 - The HPV+ recurring cell line SCC090 is radioresistant, exhibits strong CHK1 activation after exposure to radiation, and is highly sensitive to triple therapy.

Scatter plots comparing individual MRI measurements (tumor volume, baseline R2* and percentage of fluctuating volume) against pathology (Hoechst 33342 uptake for perfusion, pimonidazole adduct formation for hypoxia) determined from the cohort of CALR xenografts.

Fluctuating volume percentages detected for HNSCC metastatic lymph node ROIs between two MR sessions 48 hours apart (solid lines - responders, dashed lines - non responders).

Examples of Ktrans and R2* distributions for fluctuating and non-fluctuating parts of human HNSCC (Patient No 5, N2). The non-enhancing part of the tumor (Ktrans = 0) is indicated with an asterisk.

Supplementary Figure Captions

Examples of R2* time series (left column, R2* range 40 s-1) and corresponding power frequency spectra (R2* power range displayed: 0 - 30) for voxels within human HNSCC classified as significantly fluctuating (tumor - top two rows) and without significant fluctuations (tumor - middle two rows, adjacent muscle - bottom row).

Supplementary Table S1. Age and gender comparison between the current study and the UK incidence data (2002-2011); Supplementary Table S2. Comparison of age distribution in cases from 2002-2006 vs. 2007-2011; Supplementary Table S3. Type-specific HPV prevalence among single infected HPV-positive tumours

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Supplementary Figures S1-S4 from Radiation-Mediated Up-Regulation of Gene Expression from Replication-Defective Adenoviral Vectors: Implications for Sodium Iodide Symporter Gene Therapy

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A rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) incidence has occurred throughout the developed world, where it has been attributed to an increasing impact of human papillomavirus (HPV) on disease etiology. This report presents the findings of a multicenter cross-sectional retrospective study aimed at determining the proportion of HPV-positive and HPV-negative OPSCC within the United Kingdom. Archival tumor tissue blocks from 1,602 patients previously diagnosed with OPSCC (2002–2011) were collated from 11 centers. HPV status was determined with three validated commercial tests to provide valid data for 1,474 cases in total. Corresponding national incidence data from the same decade were obtained from UK Cancer registries. The overall proportion of HPV+ OPSCC between 2002 and 2011 was 51.8% [95% confidence interval (CI), 49.3–54.4], and this remained unchanged throughout the decade [unadjusted RR = 1.00 (95% CI, 0.99–1.02)]. However, over the same period, the incidence of OPSCC in the broader UK population underwent a 2-fold increase [age-standardized rate 2002: 2.1 (95% CI, 1.9–2.2); 2011: 4.1 (95% CI, 4.0–4.3)]. Although the number of OPSCCs diagnosed within the United Kingdom from 2002 to 2011 nearly doubled, the proportion of HPV+ cases remained static at approximately 50%. Our results argue that the rapidly increasing incidence of OPSCC in the United Kingdom cannot be solely attributable to the influence of HPV. The parallel increase in HPV+ and HPV− cases we documented warrants further investigation, so that appropriate future prevention strategies for both types of disease can be implemented. Cancer Res; 76(22); 6598–606. ©2016 AACR.

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Purpose: To assess the effects of external beam radiotherapy (EBRT) on adenoviral-mediated transgene expression in vitro and in vivo and to define an optimal strategy for combining sodium iodide symporter (NIS)–mediated 131I therapy with EBRT.Experimental Design: Expression of reporter genes [NIS, green fluorescent protein (GFP), β-galactosidase (lacZ), and luciferase (Luc)] from replication-deficient adenoviruses was assessed in tumor cell lines under basal conditions and following irradiation. The effects of viral multiplicity of infection (MOI) and EBRT dose on the magnitude and duration of gene expression were determined. In vivo studies were done with Ad-CMV-GFP and Ad-RSV-Luc.Results: EBRT increased NIS, GFP, and β-galactosidase expression in colorectal, head and neck, and lung cancer cells. Radiation dose and MOI were important determinants of response to EBRT, with greatest effects at higher EBRT doses and lower MOIs. Radiation exerted both transductional (through increased coxsackie-adenoviral receptor and integrin αv) and nontransductional effects, irrespective of promoter sequence (CMV, RSV, hTR, or hTERT). Analysis of the schedule of EBRT followed by viral infection revealed maximal transduction at 24 hours. Radiation maintained increasing radioiodide uptake from Ad-hTR-NIS over 6 days, in direct contrast to reducing levels in unirradiated cells. The effects of EBRT in increasing and maintaining adenovirus-mediated transgene expression were also seen in vivo using GFP- and luciferase-expressing adenoviral vectors.Conclusions: Radiation increased the magnitude and duration of NIS gene expression from replication-deficient adenoviruses. The transductional effect is maximal at 24 hours, but radioiodide uptake is maintained at an elevated level over 6 days after infection.

T2*-weighted image (TE=4.9 ms) for a stage IV HNSCC patient (Pt No: 5). Marker lines represent image positions used in the assessment of motion correction. B: Time traces of nodal (LN) and primary (P) projections without (S(t)) and with motion correction (S(t)MOCO). Pronounced global motion (i.e. swallowing) is marked with an asterisk. Persistent motion artifacts present in the primary tumor are indicated with an arrow.

Purpose: To determine the safety and feasibility of combining intratumoral reovirus and radiotherapy in patients with advanced cancer and to assess viral biodistribution, reoviral replication in tumors, and antiviral immune responses.Experimental Design: Patients with measurable disease amenable to palliative radiotherapy were enrolled. In the first stage, patients received radiotherapy (20 Gy in five fractions) plus two intratumoral injections of RT3D at doses between 1 × 108 and 1 × 1010 TCID50. In the second stage, the radiotherapy dose was increased (36 Gy in 12 fractions) and patients received two, four, or six doses of RT3D at 1 × 1010 TCID50. End points were safety, viral replication, immunogenicity, and antitumoral activity.Results: Twenty-three patients with various solid tumors were treated. Dose-limiting toxicity was not seen. The most common toxicities were grade 2 (or lower) pyrexia, influenza-like symptoms, vomiting, asymptomatic lymphopenia, and neutropenia. There was no exacerbation of the acute radiation reaction. Reverse transcription-PCR (RT-PCR) studies of blood, urine, stool, and sputum were negative for viral shedding. In the low-dose (20 Gy in five fractions) radiation group, two of seven evaluable patients had a partial response and five had stable disease. In the high-dose (36 Gy in 12 fractions) radiation group, five of seven evaluable patients had partial response and two stable disease.Conclusions: The combination of intratumoral RT3D and radiotherapy was well tolerated. The favorable toxicity profile and lack of vector shedding means that this combination should be evaluated in newly diagnosed patients receiving radiotherapy with curative intent. Clin Cancer Res; 16(11); 3067–77. ©2010 AACR.

Supplementary Data from Two-Stage Phase I Dose-Escalation Study of Intratumoral Reovirus Type 3 Dearing and Palliative Radiotherapy in Patients with Advanced Cancers

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Example of coronal T2-weighted image of two simultaneously scanned mice bearing CALR HNSCC xenografts (mice IV and V, tumors are marked with arrows) and a phantom containing 1.5 mM gadoterate meglumine (Dotarem, Guerbet, Villepinte, France) in saline, acquired using the asymmetric high-resolution three element receive coil.

Purpose: Reovirus type 3 Dearing (RT3D) replicates preferentially in Ras-activated cancers. RT3D shows synergistic in vitro cytotoxicity in combination with platins and taxanes. The purpose of this phase I/II study was to assess RT3D combined with carboplatin/paclitaxel in patients with advanced cancers.Experimental Design: Patients were initially treated in a dose-escalating, phase I trial with intravenous RT3D days 1 to 5, carboplatin [area under curve (AUC) 5, day 1] and paclitaxel (175 mg/m2, day 1) 3-weekly. RT3D was escalated through three dose levels: 3 × 109, 1 × 1010, and 3 × 1010 TCID50 in cohorts of three. Primary endpoints were to define the maximum tolerated dose and dose-limiting toxicity and to recommend a dose for phase II studies. Secondary endpoints included pharmacokinetics, immune response, and antitumor activity. A subsequent phase II study using the 3 × 1010 TCID50 dose characterized the response rate in patients with head and neck cancer.Results: Thirty-one heavily pretreated patients received study therapy. There were no dose-limiting toxicities during dose-escalation and most toxicities were grade I/II. Overall effectiveness rates were as follows: one patient had a complete response (3.8%), six patients (23.1%) had partial response, two patients (7.6%) had major clinical responses clinically evaluated in radiation pretreated lesions which are not evaluable by Response Evaluation Criteria in Solid Tumors (RECIST), nine patients (34.6%) had stable disease, and eight patients (30.8%) had disease progression. Viral shedding was minimal and antiviral immune responses were attenuated compared with previous single-agent data for RT3D.Conclusions: The combination of RT3D plus carboplatin/paclitaxel is well tolerated with evidence of activity in cancer of the head and neck. A randomized phase III study is currently open for recruitment. Clin Cancer Res; 18(7); 2080–9. ©2012 AACR.

Supplementary Figures S1-S4 from Phase I/II Study of Oncolytic HSVGM-CSF in Combination with Radiotherapy and Cisplatin in Untreated Stage III/IV Squamous Cell Cancer of the Head and Neck

Examples of R2* time series (left column, R2* range 40 s-1) and corresponding power frequency spectra (R2* power range displayed: 0 - 30) for voxels within CALR HNSCC xenografts classified as significantly fluctuating (CALR tumor - top two rows) and without significant fluctuations (CALR tumor - middle two rows, adjacent muscle - bottom row).

Supplementary Figure 4 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors

Supplementary Figure 1 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors

Supplementary Figure 2 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors

Supplementary Figure 3 from Inhibition of Repair of Radiation-Induced DNA Damage Enhances Gene Expression from Replication-Defective Adenoviral Vectors

Background and purpose: A popular Normal tissue Complication (NTCP) model deployed to predict radiotherapy (RT) toxicity is the Lyman-Burman Kutcher (LKB) model of tissue complication. Despite the LKB model's popularity, it can suffer from numerical instability and considers only the generalized mean dose (GMD) to an organ. Machine learning (ML) algorithms can potentially offer superior predictive power of the LKB model, and with fewer drawbacks. Here we examine the numerical characteristics and predictive power of the LKB model and compare these with those of ML.Materials and methods: Both an LKB model and ML models were used to predict G2 Xerostomia on patients following RT for head and neck cancer, using the dose volume histogram of parotid glands as the input feature. Model speed, convergence characteristics and predictive power was evaluated on an independent training set.Results: We found that only global optimization algorithms could guarantee a convergent and predictive LKB model. At the same time our results showed that ML models remained unconditionally convergent and predictive, while staying robust to gradient descent optimization. ML models outperform LKB in Brier score and accuracy but compare to LKB in ROC-AUC.Conclusion: We have demonstrated that ML models can quantify NTCP better than or as well as LKB models, even for a toxicity that the LKB model is particularly well suited to predict. ML models can offer this performance while offering fundamental advantages in model convergence, speed, and flexibility, and so could offer an alternative to the LKB model that could potentially be used in clinical RT planning decisions.

Background and Objectives: Physicians are increasingly confronted with patients’ interrelated psychosocial and physiological issues. To assist physicians in managing the psychosocial needs of patients, integrated behavioral health (IBH) has become increasingly common. This study was completed in a large, Midwestern family medicine residency program where the authors sought to (1) identify physicians’ perceptions of IBH implementation and areas of needed IBH improvement, and (2) recognize educational needs to be addressed when providing behavioral health training to resident physicians. Methods: The authors utilized a pre/post design to measure physician perception of access and quality of an integrated behavioral health program. For quantitative data, we performed standard descriptive statistics, likelihood ratio χ2 tests, independent sample t test, and linear mixed-model analysis. For qualitative data, we completed phenomenological analysis, derived from a focus group. Results: Physician satisfaction with access and quality of behavioral health services significantly improved after the implementation of the IBH (P

Xevinapant is a first-in-class antagonist of inhibitor of apoptosis proteins, which enhances cancer cell sensitivity to chemotherapy and radiotherapy. In a phase II randomized study in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), xevinapant plus standard-of-care cisplatin-based chemoradiotherapy (CRT) showed superior efficacy versus placebo plus CRT. Here, we describe the design of TrilynX (NCT04459715), a randomized, double-blind, phase III study. In total, 700 patients with unresected LA SCCHN will be randomized 1:1 to receive xevinapant or placebo plus standard-of-care CRT followed by xevinapant monotherapy or placebo. The primary end point is event-free survival by blinded independent review committee. Secondary end points include progression-free survival, locoregional control, overall survival and safety.Xevinapant is being developed as a new type of cancer treatment. Xevinapant works by enhancing the effects of chemotherapy and radiotherapy (chemoradiotherapy), which are standard anticancer treatments. Researchers are studying whether adding xevinapant to these treatments could be helpful for people with head and neck cancers that have not spread to other parts of the body and cannot be removed by surgery. In a study of 96 people with this disease, those treated with chemoradiotherapy plus xevinapant on average lived longer than people treated with chemoradiotherapy plus placebo (liquid that looked the same but did not contain any medicine). To confirm the results, researchers have started a larger study, called TrilynX, that will compare the same treatments in around 700 people worldwide. This study will show if adding xevinapant to chemoradiotherapy can help to keep the cancer from progressing, control symptoms better and help people live longer. Clinical trial registration: NCT04459715 (ClinicalTrials.gov).

Highlights • The MR-Linac provides the tools to deliver online MR-guided Adaptive Radiotherapy • Adapt-to-Shape-Lite is a novel radiotherapy planning workflow on the Elekta Unity MR-Linac • Adapt-to-Shape-Lite generated plans that fulfilled 99.9% of mandatory dose constraints • Adapt-to-Shape-Lite workflow can generate plans in relatively short durations • Therefore, we prefer Adapt-To-Shape-Lite as the primary workflow to treat Head-and-Neck cancers, Introduction The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS). Methods Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans. Results 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s – 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s – 44 mins 27 s), respectively. Conclusions Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL.

‘Executive function’ (EF) is an umbrella term that encompasses the processes responsible for purposeful, goal-directed behaviour (Anderson, 2002; Diamond & Lee, 2011). In this study we examine the two core components of executive function that have been identified in children (Lee et al., 2013; St Clair-Thompson & Gathercole, 2004): (1) Working Memory (WM), a limited capacity system that allows the storage and manipulation of information over short time periods (Baddeley, 2010; Cowan, 2017), sometimes referred to as updating in the EF literature (2) Inhibition, which can be defined as the ability to deliberately inhibit dominant or automatic responses (Aron, 2007) We are also looking at processing speed, which relates to the speed of information processing and is normally measured using a simple reaction-time task (Coyle et al., 2011). It is well established that higher childhood socioeconomic status (SES) is associated with both higher scores on tasks of different executive functions (Lawson et al., 2018; Mooney et al., 2021, 2022), and better levels of academic attainment in childhood (Sirin, 2005; Waters et al., 2021). Higher scores on EF tasks are also associated with better academic attainment (Coyle et al., 2011; Gathercole et al., 2003; Mulder et al., 2010; St Clair-Thompson & Gathercole, 2006). More recently, some longitudinal studies have looked at whether executive functions mediate the association between SES and academic attainment. However, several of these studies used a composite measure of EF, combining tasks that measure different elements of EF, test whether the association between SES and academic attainment is mediated by ‘global’ EF (Deer et al., 2020; Ellefson et al., 2020; Lawson & Farah, 2017; Nesbitt et al., 2013). For example, Ellefson et al (2020) and Lawson & Farah (2017) found that global EF mediated the association between SES and numeracy or maths, and Nesbitt et al (2013) found that global EF mediated the association between SES and broader educational attainment. Whilst it is important to establish that EFs are mediating this association, this does not establish which of the EFs may be most important in this relationship. Only three studies have looked within different EF components to find which may be the most important mediator. In a relatively small sample of 203 children (aged 9–13 years), Albert et al (2020) found that verbal WM was the only EF measure that mediated the association between SES and both reading and maths achievement at 7th grade. Similarly, Poon et al (2022) found that WM and cognitive flexibility, but not inhibition, mediated the association between SES and a teacher report of educational attainment in a sample of 385 children aged 8 years old. Finally, in a larger study (N=1273) of infants and young children (aged 1-54 months), Waters et al (2021) found that WM was the only EF that mediated the association between SES and two subtests of the Woodcock Johnson tests of achievement battery. Therefore, when separating out different EF components, the limited studies in this area suggest that WM is the key factor mediating the relationship between SES and academic attainment. However, only one of these three studies used a measure that reflected children’s actual academic attainment on a nationally administered test (Albert et al, 2020), with the others using teacher reports (Poon et al., 2022) or the Woodcock Johnson test (Waters et al., 2021). Whilst associations between SES and tests such as the Woodcock Johnson are informative, it is important to look at the impact of SES and EF on children’s performance on nationally administered tests (e.g., Key Stage tests, A Levels). It is nationally administered tests which predicts a child’s life outcomes terms of their socioeconomic mobility (Breen & Karlson, 2014), as a child’s attainment at GCSE or A-Level determines their future chances of obtaining further qualifications in higher education, or for obtaining future employment. It is therefore important to use these types of tests as the outcome variable to fully understand how different aspects of EF mediate the relationship between SES and academic outcomes. Further, the majority of these studies lack ethnic diversity in their samples (e.g. the Deer et al., 2020 sample was 96% White). We have previously found ethnic group variation in tasks of WM in BiB (Mooney et al, 2021). It is therefore possible that the associations between SES, EF, and attainment may vary within different ethnic groups. There are fewer studies that have linked childhood SES to childhood processing speed ability. A study of 121 children aged 4-5 years tested the association between SES, EF (working memory and inhibitory control), and a proxy measure of processing speed (reaction times to the EF tasks) (St. John et al., 2019). They found that SES was related to both working memory and inhibitory control, as well as to working memory reaction times (proxy PS measure). In a study of 166 children aged 7-11, Buckhalt et al., (2007) examined whether ethnicity and SES moderated the link between children’s sleep and cognitive functioning (including processing speed), and found direct associations between SES and a standard measure of processing speed (measured via a visual matching task from Woodcock Johnson III). Several studies have directly linked processing speed to educational attainment, with some demonstrating it has distinct associations with children’s attainment that are separable from the influence that WM has with attainment (Davies et al., 2016; Mulder et al., 2010; Passolunghi & Lanfranchi, 2012). Further, Gordon et al. (2018) have proposed that processing speed within EF tasks can be used to predict academic attainment. However, in contrast to the growing body of research that examines EF as a mediator between SES and attainment, no studies have looked at whether processing speed mediates this association. In this study, we therefore test the contribution of EF versus processing speed in mediating the association between SES and children’s attainment. We also test the contribution of distinct EF’s (WM and inhibition) in mediating the association between SES and children’s attainment.

The experience of a life threatening illness not only impacts upon the patient directly but upon their close others. Partners have been identified as particularly vulnerable to the adverse responses and outcomes associated with their loved one’s diagnosis and prognosis. Research on partners’ responses to a life threatening illness has predominantly focused on negative aspects stemming from the stressors of their role of caring for the patient together with distress and pathological outcomes from their experiences. What is less known is partners’ capacity for resilience and adaptive responses to their loved one’s illness. Adopting a salutogenic perspective, this thesis explored partners’ responses to their loved one’s life threatening illness acknowledging the potential for both positive and negative outcomes. Firstly, a review of the literature regarding partners’ responses and outcomes to life threatening illnesses was undertaken to identify research deficits in this area to date. This analysis of existing literature highlighted the need for more balanced investigation of partners’ responses, finding an overemphasis on pathogenic outcomes whilst largely neglecting experiences of resilience and adaptive responses in this population. Additionally, the need for more multi-method research design and use of objective physiological measures of adaptation was deemed warranted. Based on review recommendations, an exploration of both positive and negative pre, peri, and post trauma factors known to influence adaptation was conducted with partners identified as high or low in resilience in order to determine whether these groups could be differentiated on self-report, clinical interview of post-trauma symptomatology, and physiological measures of adaptation. Study 1 explored pre trauma factors comprising optimism, mastery, and trauma history. Optimism was found to be the only factor which differentiated partners varying in their degree of resilience. High resilience partners reported greater optimism than partners identified as low in resilience. Partners’ psychophysiological and psychological responses to illness related events (diagnoses, treatment, fear of recurrence) comprised the peri traumatic exploration in Study 2. Against expectations, high and low resilience partners were unable to be differentiated in their responses on these measures. These results are the first to provide an objective measurement of partners peri-traumatic responses based on degree of resilience. An exploration of partners post trauma responses considered the factors of coping style, social support, post-traumatic stress symptomatology, and other psychological symptoms. As anticipated, partners low in resilience scored significantly higher on all negative psychological symptoms measured than partners high in resilience. In line with expectations, a strong trend was found for high resilience partners to report greater satisfaction with the social support received from family and friends. Partners satisfaction with the support received from patients was found to be indistinguishable between the resilience groups. Against expectations and findings from previous studies, however, was a failure to differentiate low and high resilient partners by their coping styles. This exploratory research reflects a novel examination of partners’ responses with consideration to resilience in both positive and negative responses to their loved ones' illness. The presented series of studies have expanded existing knowledge regarding factors influenced by partners’ resilience, and aided in identifying those struggling to adapt to the experience of their loved one’s life threatening illness. In turn, findings from these studies emphasize the need for interventions to bolster resilience, optimism, and support in low resilient partners facing the challenges experienced in their loved one’s life threatening illness. However, further research adopting similar intensive designs is warranted to determine whether the results of the current series of studies are replicated with larger scale samples.

Patients with head and neck cancer (HNC) receiving radiotherapy (RT) are at a high risk of weight loss (WL) due to a variety of nutrition impact symptoms (NISs). This prospective observational study aimed to investigate the consecutive changes of NIS during RT and analyzed its impact on body weight. The Head and Neck patient Symptom Checklist was adopted to evaluate NIS. NIS, body weight, hemoglobin and lymphocyte of 94 participants were assessed at four time points during RT and the treatment outcomes were assessed at the time of 12 months after the completion of RT. Generalised estimation equations (GEEs) and Kendall’s tau-b were used for statistical analysis. Our study found that pain, taste changes and dry mouth were the most common NIS, reported by >90% of patients and had higher interference scores (more than 85% >2) at the end of RT. The average WL was 4.22 ± 3.59 kg after treatment, and more than two-thirds of patients (67.02%, 64/94) experienced significant WL of >5%. Lack of energy, vomiting and taste changes impacted WL significantly (p < .05). Taste changes were also associated with hemoglobin and lymphocyte reduction (p = .018, p < .001). WL correlated negatively with tumor response (p = .031). In patients with HNC, taste changes, pain, dry mouth and vomiting were seen. Nutritional intervention applied as early as the first 10 days of RT could help to change the nutrition status and improve the clinical outcomes.

The experience of a life threatening illness not only impacts upon the patient directly but upon their close others. Partners have been identified as particularly vulnerable to the adverse responses and outcomes associated with their loved one's diagnosis and prognosis. Research on partners' responses to a life threatening illness has predominantly focused on negative aspects stemming from the stressors of their role of caring for the patient together with distress and pathological outcomes from their experiences. What is less known is partners' capacity for resilience and adaptive responses to their loved one's illness. Adopting a salutogenic perspective, this thesis explored partners' responses to their loved one's life threatening illness acknowledging the potential for both positive and negative outcomes. Firstly, a review of the literature regarding partners' responses and outcomes to life threatening illnesses was undertaken to identify research deficits in this area to date. This analysis of existing literature highlighted the need for more balanced investigation of partners' responses, finding an overemphasis on pathogenic outcomes whilst largely neglecting experiences of resilience and adaptive responses in this population. Additionally, the need for more multi-method research design and use of objective physiological measures of adaptation was deemed warranted. Based on review recommendations, an exploration of both positive and negative pre, peri, and post trauma factors known to influence adaptation was conducted with partners identified as high or low in resilience in order to determine whether these groups could be differentiated on self-report, clinical interview of post-trauma symptomatology, and physiological measures of adaptation. Study 1 explored pre trauma factors comprising optimism, mastery, and trauma history. Optimism was found to be the only factor which differentiated partners varying in their degree of resilience. High resilience partners reported greater optimism than partners identified as low in resilience. Partners' psychophysiological and psychological responses to illness related events (diagnoses, treatment, fear of recurrence) comprised the peri-traumatic exploration in Study 2. Against expectations, high and low resilience partners were unable to be differentiated in their responses on these measures. These results are the first to provide an objective measurement of partners peri-traumatic responses based on degree of resilience. An exploration of partners post trauma responses considered the factors of coping style, social support, post-traumatic stress symptomatology, and other psychological symptoms. As anticipated, partners low in resilience scored significantly higher on all negative psychological symptoms measured than partners high in resilience. In line with expectations, a strong trend was found for high resilience partners to report greater satisfaction with the social support received from family and friends. Partners satisfaction with the support received from patients was found to be indistinguishable between the resilience groups. Against expectations and findings from previous studies, however, was a failure to differentiate low and high resilient partners by their coping styles. This exploratory research reflects a novel examination of partners' responses with consideration to resilience in both positive and negative responses to their loved ones' illness. The presented series of studies have expanded existing knowledge regarding factors influenced by partners' resilience, and aided in identifying those struggling to adapt to the experience of their loved one's life threatening illness. In turn, findings from these studies emphasize the need for interventions to bolster resilience, optimism, and support in low resilient partners facing the challenges experienced in their loved one's life threatening illness. However, further research adopting similar intensive designs is warranted to determine whether the results of the current series of studies are replicated with larger scale samples.

The internet is a tricky and intangible place. On the one hand, it connects us with a world of knowledge and information. On the other, it allows anonymous sources to edit and post a truth that may be the furthest thing from reality. Digital folklore texts – those stories adopted by online communities for adaptation and dissemination – exploit this enigmatic aspect of online communication. Many of these stories take advantage of their audience’s wistfulness for a time that has passed and may be lost in the recesses of memory. The narrative framing of digital folklore incorporates nostalgic aesthetics to curate an unsettling but plausible representation of the past. This thesis uses Kris Straub’s short horror story ‘Candle Cove’ (2009) and its surrounding paratext to dissect how digital authors represent the past to immerse their audiences in a curated reality. Digital folklore stories focus on real or fictional pieces of lost media – texts that have left no complete copy and exist only in their paratext or audiences’ memories – and have been dissected by audiences keen to uncover or alter the truth. This thesis includes an analysis of the reception and fan contributions to the texts, such as the comment sections and online discussions. I suggest that, despite their different mediums, plots and creators, digital folklore texts demonstrate shared characteristics that highlight the potential of digital folklore to curate a past that both perverts the nostalgia of audiences and is credible enough to be immersive.

The travel journal, collecting, and exhibition of objects by museum founder, tea merchant and Member of Parliament Frederick Horniman (1835–1906) in the late nineteenth century demonstrate how material objects exemplify travel writing. Through an examination of objects he collected and later interpreted at the Horniman Free Museum, this article presents a case study of how collecting activities mirror and serve as a form of travel writing. This article presents a new model for understanding, beyond the written word, how travelers can capture the experience of a foreign expedition through the collecting and interpretation of objects.

This work examines the policies and educational programming produced by the Horniman Free Museum in London prior to its closure in 1898. Relying upon primary sources, such as the writings of tea merchant and Member of Parliament Frederick Horniman and the staff of the museum, this article refutes previous scholarship on this museum and argues that the museum possessed a clear mission, curatorial and exhibition practices, and educational practices that were derived from late nineteenth-century museum practices and theory. By examining how the Horniman Free Museum created and described its policies and programming, this article presents a basis for further work on understanding how late nineteenth-century museums interpreted museum theory for constructing and displaying knowledge about the world.

Redox reactions are ubiquitous in organic synthesis and intrinsic to organic electrosynthesis. The language and concepts used to describe reactions in these domains are sufficiently different to create barriers that hinder broader adoption and understanding of electrochemical methods. To bridge these gaps, this Synopsis compares chemical and electrochemical redox reactions, including concepts of free energy, voltage, kinetic barriers, and overpotential. This discussion is intended to increase the accessibility of electrochemistry for organic chemists lacking formal training in this area.

Background and purpose: We aimed to the genetic components and susceptibility variants associated with acute radiation-induced toxicities (RITs) in patients with head and neck cancer (HNC).Materials and methods: We performed the largest meta-GWAS of seven European cohorts (n = 4,042). Patients were scored weekly during radiotherapy for acute RITs including dysphagia, mucositis, and xerostomia. We analyzed the effect of variants on the average burden (measured as area under curve, AUC) per each RIT, and standardized total average acute toxicity (STATacute) score using a multivariate linear regression. We tested suggestive variants (p < 1.0x10-5) in discovery set (three cohorts; n = 2,640) in a replication set (four cohorts; n = 1,402). We meta-analysed all cohorts to calculate RITs specific SNP-based heritability, and effect of polygenic risk scores (PRSs), and genetic correlations among RITS.Results: From 393 suggestive SNPs identified in discovery set; 37 were nominally significant (preplication < 0.05) in replication set, but none reached genome-wide significance (pcombined < 5 × 10-8). In-silico functional analyses identified “3′-5'-exoribonuclease activity” (FDR = 1.6e-10) for dysphagia, “inositol phosphate-mediated signalling” for mucositis (FDR = 2.20e-09), and “drug catabolic process” for STATacute (FDR = 3.57e-12) as the most enriched pathways by the RIT specific suggestive genes. The SNP-based heritability (±standard error) was 29 ± 0.08 % for dysphagia, 9 ± 0.12 % (mucositis) and 27 ± 0.09 % (STATacute). Positive genetic correlation was rg = 0.65 (p = 0.048) between dysphagia and STATacute. PRSs explained limited variation of dysphagia (3 %), mucositis (2.5 %), and STATacute (0.4 %).Conclusion: In HNC patients, acute RITs are modestly heritable, sharing 10 % genetic susceptibility, when PRS explains < 3 % of their variance. We identified numerus suggestive SNPs, which remain to be replicated in larger studies.