A protocol for the longitudinal investigation of cancer related fatigue in head and neck cancer with an emphasis on the role of physical activity.

BACKGROUND AND AIM: Cancer related fatigue significantly impairs the ability to undertake sustained physical activity across the domains of daily living, work and recreation. The purpose of this study is to monitor cancer related fatigue and the factors affected or caused by it for 12 months in head and neck cancer patients following their diagnosis. Their perceptions of how fatigue might affect their activity levels in addition to identifying avenues to improve engagement with physical activity will be also explored. METHODS: A single centre longitudinal mixed-methods study will be conducted. Forty head and neck cancer patients will be recruited over 6 months following the confirmation of their treatment plan, after which fatigue and physical activity will be assessed at four time points over 12 months. Additionally, other factors which influence fatigue such as body composition, blood counts, systemic inflammation levels, haemoglobin concentration, thyroid function, sleep quality, cardiorespiratory fitness and upper and lower extremity strength will be measured to understand how the multifactorial problem of fatigue may evolve over time and influence physical activity levels. Semi-structured interviews will be conducted after treatment completion and at end of twelve months which will analyse the participants fatigue experiences, understand how their perceived fatigue may have impacted physical activity and report the factors which may improve engagement with physical activity during cancer. Quantitative data will be analysed and reported using standard descriptive statistics and post-hoc pairwise comparisons. The changes in outcome measures across time will be analysed using the MIXED procedure in SPSS software. Statistical significance will be accepted at p<0.05. Qualitative data will be analysed using the Interpretative Phenomenological Approach using the NVivo software. DISCUSSION: The results from this study may help inform the planning and delivery of appropriately timed interventions for the management of cancer related fatigue.

Anxiety, depression, and fear of cancer recurrence in head and neck cancer.

OBJECTIVE: Patients with head and neck cancer (HNC) report some of the highest levels of psychological distress amid managing their disease as well as debilitating and disfiguring treatment side effects. Fear of cancer recurrence (FCR) is a top unmet need and concern of patients with HNC. Prior research suggests elevated symptoms of anxiety and depression are potential antecedents to FCR, but findings have been limited in HNC populations. The aim of the present study was to examine the early level and change in symptoms of anxiety and depression in relation to later change in FCR among patients with HNC. METHOD: The study is a secondary analysis of data collected from 2011 to 2014 through the Head and Neck 5000 Study in the United Kingdom. A sample of 4,891 patients completed self-report longitudinal assessments of anxiety and depression symptoms at baseline, 4, and 12 months and FCR at 4 and 12 months. RESULTS: Utilizing multiple indicator latent change score modeling, results revealed baseline anxiety and increases in anxiety from baseline to 4 months were both positively associated with increases in FCR from 4 to 12 months. Neither baseline depression nor change in depression from baseline to 4 months were significantly associated with FCR change. CONCLUSIONS: Findings indicate that early level and increases in symptoms of anxiety were markers of increased FCR in patients with HNC. Future research may consider anxiety as a unique antecedent and maintaining factor of FCR and targeting anxiety early in the cancer trajectory may have downstream effects on FCR development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ductile-to-brittle transition and yielding in soft amorphous materials: perspectives and open questions.

Soft amorphous materials are viscoelastic solids ubiquitously found around us, from clays and cementitious pastes to emulsions and physical gels encountered in food or biomedical engineering. Under an external deformation, these materials undergo a noteworthy transition from a solid to a liquid state that reshapes the material microstructure. This yielding transition was the main theme of a workshop held from January 9 to 13, 2023 at the Lorentz Center in Leiden. The manuscript presented here offers a critical perspective on the subject, synthesizing insights from the various brainstorming sessions and informal discussions that unfolded during this week of vibrant exchange of ideas. The result of these exchanges takes the form of a series of open questions that represent outstanding experimental, numerical, and theoretical challenges to be tackled in the near future.

Brittle and ductile yielding in soft materials.

Many soft materials yield under mechanical loading, but how this transition from solid-like behavior to liquid-like behavior occurs can vary significantly. Understanding the physics of yielding is of great interest for the behavior of biological, environmental, and industrial materials, including those used as inks in additive manufacturing and muds and soils. For some materials, the yielding transition is gradual, while others yield abruptly. We refer to these behaviors as being ductile and brittle. The key rheological signatures of brittle yielding include a stress overshoot in steady-shear-startup tests and a steep increase in the loss modulus during oscillatory amplitude sweeps. In this work, we show how this spectrum of yielding behaviors may be accounted for in a continuum model for yield stress materials by introducing a parameter we call the brittility factor. Physically, an increased brittility decreases the contribution of recoverable deformation to plastic deformation, which impacts the rate at which yielding occurs. The model predictions are successfully compared to results of different rheological protocols from a number of real yield stress fluids with different microstructures, indicating the general applicability of the phenomenon of brittility. Our study shows that the brittility of soft materials plays a critical role in determining the rate of the yielding transition and provides a simple tool for understanding its effects under various loading conditions.

Direct-ink-write cross-linkable bottlebrush block copolymers for on-the-fly control of structural color.

Additive manufacturing capable of controlling and dynamically modulating structures down to the nanoscopic scale remains challenging. By marrying additive manufacturing with self-assembly, we develop a UV (ultra-violet)-assisted direct ink write approach for on-the-fly modulation of structural color by programming the assembly kinetics through photo-cross-linking. We design a photo-cross-linkable bottlebrush block copolymer solution as a printing ink that exhibits vibrant structural color (i.e., photonic properties) due to the nanoscopic lamellar structures formed post extrusion. By dynamically modulating UV-light irradiance during printing, we can program the color of the printed material to access a broad spectrum of visible light with a single ink while also creating color gradients not previously possible. We unveil the mechanism of this approach using a combination of coarse-grained simulations, rheological measurements, and structural characterizations. Central to the assembly mechanism is the matching of the cross-linking timescale with the assembly timescale, which leads to kinetic trapping of the assembly process that evolves structural color from blue to red driven by solvent evaporation. This strategy of integrating cross-linking chemistry and out-of-equilibrium processing opens an avenue for spatiotemporal control of self-assembled nanostructures during additive manufacturing.

Unbiased construction of constitutive relations for soft materials from experiments via rheology-informed neural networks.

The ability to concisely describe the dynamical behavior of soft materials through closed-form constitutive relations holds the key to accelerated and informed design of materials and processes. The conventional approach is to construct constitutive relations through simplifying assumptions and approximating the time- and rate-dependent stress response of a complex fluid to an imposed deformation. While traditional frameworks have been foundational to our current understanding of soft materials, they often face a twofold existential limitation: i) Constructed on ideal and generalized assumptions, precise recovery of material-specific details is usually serendipitous, if possible, and ii) inherent biases that are involved by making those assumptions commonly come at the cost of new physical insight. This work introduces an approach by leveraging recent advances in scientific machine learning methodologies to discover the governing constitutive equation from experimental data for complex fluids. Our rheology-informed neural network framework is found capable of learning the hidden rheology of a complex fluid through a limited number of experiments. This is followed by construction of an unbiased material-specific constitutive relation that accurately describes a wide range of bulk dynamical behavior of the material. While extremely efficient in closed-form model discovery for a real-world complex system, the model also provides insight into the underpinning physics of the material.

Relevance of sarcopenia in elderly patients undergoing surgery for oral squamous cell carcinoma.

In the elderly population there is increasing evidence that frailty predicts adverse outcomes better than chronological age. Sarcopenia is an important component of frailty. This study aimed to establish the relevance of sarcopenia in elderly patients with oral squamous cell carcinoma (OSCC) undergoing surgery. This retrospective, single-centre, cohort study included patients over the age of 75 years who were diagnosed with OSCC between 2007 and 2016. Cross-sectional imaging of the neck was used to predict the Skeletal Muscle Index (SMI) using validated equations. Based on established thresholds, patients were categorised as having either a normal or low SMI, indicative of sarcopenia. Sixty-nine patients met the inclusion criteria. Patients with a low SMI had a longer length of stay (16.9 days vs 9.8 days, p = 0.030); they had more severe complications, defined as Clavien-Dindo grade IIIb or higher (17.6% vs 4.0%, p = 0.042); and their mean Comprehensive Complication Index (CCI) was also higher (14.1 vs 4.7, p = 0.051). Furthermore, 2/34 patients in the low SMI group died within 30 days of surgery compared with none in the normal SMI group (5.9% vs 0%, p = 0.503). Whilst patients with a low SMI who underwent surgery had lower five-year overall survival, the difference was not statistically significant. This study shows that sarcopenia negatively influences surgical outcomes in elderly patients. Routine measurement of SMI could be an indication for a comprehensive geriatric assessment (CGA).

A critical study of the nonlinear rheological properties in major classes of foods using the Sequence of Physical Processes (SPP) method and the Fourier Transform Coupled with Chebyshev Decomposition (FTC) method.

The nonlinear rheological behaviors of three different classes of foods (emulsion, suspension, and elastic network) were studied and analyzed using the Rogers Sequence of Physical Processes (SPP) method and the Ewoldt-McKinley method of coupling Fourier Transform with Chebyshev Decomposition (FTC). SPP analysis led to instantaneous rheological parameters G't and G″t at any point in time, providing a more accurate picture of the linear viscoelastic region and crossover points by the 3D amplitude sweep. When G't is plotted against G″t, the resulting graph is a deltoid which offers a detailed and distinctive intracycle behavior of each class of food. Analyzing the revolution of deltoids with increasing strain allows for the determination of a critical strain, beyond which irreversible network breakdown occurs. The strain range between the linear viscoelastic limit and the critical strain found in SPP is comparable to the MAOS region as determined with FTC. Under increasing amplitude, predominantly elastic networks showed a gradual structural rearrangement, while more erratic and abrupt changes were observed in the suspension and emulsion we studied. Under increasing frequency, elastic responses dominate viscous responses in all samples due to the shorter experimental time, allowing less relaxation.

Impact of patient age on the functional and psychosocial outcomes of orthognathic treatment.

Orthognathic treatment has been demonstrated to enhance oral function and quality of life. In the UK, prior approval criteria have been trialled to govern the provision of orthognathic surgery within the National Health Service (NHS). These include the patient's age and presence of functional concerns. The purpose of this paper was to examine the outcomes of orthognathic treatment with respect to patient age at the start of treatment. This was a retrospective evaluation of a single surgeon's experience of patients treated for dentofacial deformity over a 17-year period. A total of 118 patients completed pre-treatment and post-treatment questionnaires. There were significant improvements (p < 0.001) in reported functional problems, and in Body Satisfaction Scale (BSS), General Health Questionnaire (GHQ-12), and in Anxiety questionnaire scores. There was no difference in outcome when younger and older patients were compared. Orthognathic treatment produced positive functional and psychosocial outcomes irrespective of the patient's age at the start of treatment.

Concerns raised by people treated for head and neck cancer: a secondary analysis of audiotaped consultations in a health services follow-up clinic.

PURPOSE: People treated for head and neck cancer (HNC) face various barriers in communicating concerns with consultants. Our aim was to investigate the number of concerns raised between patients using the Patient Concerns Inventory (PCI) and those who did not. The PCI is a 57-item prompt list used in routine HNC follow-up clinics. Additionally, we aimed to examine whether who initiated the concerns differed between groups and the factors that may predict this initiation. METHODS: Secondary data analysis included 67 participants across 15 HNC consultants from specialist cancer centres in Liverpool and Leeds. Seven consultants utilised the PCI and eight did not, assigned by preferential and random assignment. RESULTS: Patients in the PCI group raised on average 2.5 more concerns than patients in the non-PCI group (p < .001). There was no significant relationship between group and who initiated the first concern (p = .28). A mixed-effects logistic regression was found to significantly predict who initiated the first concern in consultations (p < .05). DISCUSSION: The number of concerns raised by patients increased when the PCI was introduced pre-HNC consultation. A number of factors were shown to predict the number of concerns raised in consultations by both patient and consultant. As concerns may not be raised further following the concern mentioned, we propose that the discussion of concerns needs to be maintained by the clinician throughout the consultation and not solely at the start. CONCLUSION: The PCI promoted the sharing of concerns in follow-up consultations between patient and consultant.

Treatment priorities and regret in older adults with head and neck cancer: A systematic review.

BACKGROUND: The majority of head and neck cancer (HNC) diagnoses are seen in people aged 70 and older; these numbers are set to increase. Greater understanding of treatment needs of older patients with HNC is essential. These older patients often have co-existing health conditions, are prone to frailty and may not prioritise survival when considering treatment options. This systematic review examines the current research with regard to priorities and factors influencing treatment regret in older people with HNC. METHODS: Studies were eligible for inclusion if they (i) reported data from patients with a mean age of 65 years or older who had a confirmed diagnosis of HNC and had been treated using surgery, chemotherapy and/or radiotherapy with either palliative or curative intent, (ii) considered patient's priorities or preferences or examined treatment regret as one of the primary outcomes of the study (iii) were published in English. RESULTS: Pilot search identified n = 7222 articles; however, following screening, only four papers met the inclusion criteria. Narrative synthesis was indicated to analyse quantitative and qualitative evidence in parallel, as meta-analyses were not possible. DISCUSSION: There is a paucity in the literature examining older adults with HNC. There is an indication that older adults prioritise maintaining independence when making treatment decisions and treatment regret is seen in those with high levels of depression with level of frailty also a contributing factor. Clinicians should consider patient's social circumstances, premorbid status and priorities in maintaining independence and managing symptoms when making treatment decisions in this cohort.

Extracting microscopic insight from transient dielectric measurements during large amplitude oscillatory shear.

Probing the transient microstructure of soft matter far from equilibrium is an ongoing challenge to understanding material processing. In this work, we investigate inverse worm-like micelles undergoing large amplitude oscillatory shear using time-resolved dielectric spectroscopy. By controlling the Weissenburg number, we compare the non-linear microstructure response of branched and unbranched worm-like micelles and isolate distinct elastic effects that manifest near flow reversal. We validate our dielectric measurements with small angle neutron scattering and employ sequence of physical processes to disentangle the elastic and viscous contributions of the stress.

ACTivity as medicine In Oncology for Head and Neck (ACTIOHN): Protocol for a feasibility study investigating a patient-centred approach to exercise for people with head and neck cancer.

BACKGROUND AND AIM: Attempts at personalisation of exercise programmes in head and neck cancer (HaNC) have been limited. The main aim of the present study is to investigate the feasibility and acceptability of introducing a remotely delivered, fully personalised, collaborative, and flexible approach to prescribing and delivering exercise programmes into the HaNC usual care pathway. METHODS: This is a single arm, feasibility study. Seventy patients diagnosed with HaNC will be recruited from two regional HaNC centres in the United Kingdom. Patients will undertake an 8-week exercise programme designed and delivered by cancer exercise specialists. The exercise programme will start any time between the time of diagnosis and up to 8 weeks after completing treatment, depending on patient preference. The content of the exercise programme will be primarily based on patient needs, preferences, and goals, but guided by current physical activity guidelines for people with cancer. The primary outcome measure is retention to the study. Secondary quantitative outcomes are uptake to the exercise programme, different measures of exercise adherence, pre- and post-intervention assessments of fatigue (Multidimensional Fatigue Symptom Inventory-Short Form), quality of life (SF-36), physical activity levels (International Physical Activity Questionnaire-Short Form), and various components of physical fitness. The outcomes of the nested qualitative study are acceptability and feasibility of the intervention evaluated via interviews with patients, health care professionals, and the cancer exercise specialists. Intervention and participant fidelity will be determined using checklists and scrutiny of each patient's logbook and the cancer exercise specialists' meeting notes. Analysis of quantitative data will be via standard summary statistics. Qualitative data will be analysed using thematic analysis. EXPECTED RESULTS: This feasibility study will inform the design and conduct of a future randomised controlled trial. Success will be defined according to a traffic light system for identifying the appropriateness of progression to a randomised controlled trial. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry (ISRCTN82505455).

Health-related quality of life, functional outcomes, and complications after sentinel lymph node biopsy and elective neck dissection in early oral cancer: A systematic review.

BACKGROUND: Elective neck dissection improves survival in early oral cancer. Sentinel lymph node biopsy may also do this with less morbidity. This systematic review compared health-related quality of life, functional outcomes, and complications after sentinel lymph node biopsy and elective neck dissection in early oral cancer. METHODS: PRISMA guidelines were followed. Thirteen studies met inclusion criteria. RESULTS: Results favoring sentinel lymph node biopsy were found in complications, scar length and appearance, length of hospital stay, time to drain removal, and objective shoulder measures at timepoints up to 12 months. Where differences in health-related quality of life were found, methodological issues make their clinical significance questionable. CONCLUSIONS: Sentinel lymph node biopsy was associated with fewer complications and statistically better outcomes in a number of physical measures. There is as yet no strong evidence to suggest it is associated with better health-related quality of life outcomes. While a number of health-related quality of life outcome measures show promise, their interpretation is hampered by methodological concerns. Further rigorous research is required to address this.

Barriers to and facilitators of physical activity in adults living with and beyond cancer, with special emphasis on head and neck cancer: a systematic review of qualitative and mixed methods studies.

PURPOSE: Physical activity can improve health outcomes for cancer patients; however, only 30% of patients are physically active. This review explored barriers to and facilitators of physical activity promotion and participation in patients living with and beyond cancer. Secondary aims were to (1) explore similarities and differences in barriers and facilitators experienced in head and neck cancer versus other cancers, and (2) identify how many studies considered the influence of socioeconomic characteristics on physical activity behaviour. METHODS: CINAHL Plus, MEDLINE, PsycINFO, Scopus and Cochrane (CDSR) were searched for qualitative and mixed methods evidence. Quality assessment was conducted using the Mixed Methods Appraisal Tool and a Critical Appraisal Skills Programme Tool. Thematic synthesis and frequency of reporting were conducted, and results were structured using the Capability-Opportunity-Motivation-Behaviour model and Theoretical Domains Framework. RESULTS: Thirty qualitative and six mixed methods studies were included. Socioeconomic characteristics were not frequently assessed across the included studies. Barriers included side effects and comorbidities (physical capability; skills) and lack of knowledge (psychological capability; knowledge). Having a dry mouth or throat and choking concerns were reported in head and neck cancer, but not across other cancers. Facilitators included improving education (psychological capability; knowledge) on the benefits and safety of physical activity. CONCLUSION: Educating patients and healthcare professionals on the benefits and safety of physical activity may facilitate promotion, uptakeand adherence. Head and neck cancer patients experienced barriers not cited across other cancers, and research exploring physical activity promotion in this patient group is required to improve physical activity engagement.

Alignment of multiple metabolomics LC-MS datasets from disparate diseases to reveal fever-associated metabolites.

Acute febrile illnesses are still a major cause of mortality and morbidity globally, particularly in low to middle income countries. The aim of this study was to determine any possible metabolic commonalities of patients infected with disparate pathogens that cause fever. Three liquid chromatography-mass spectrometry (LC-MS) datasets investigating the metabolic effects of malaria, leishmaniasis and Zika virus infection were used. The retention time (RT) drift between the datasets was determined using landmarks obtained from the internal standards generally used in the quality control of the LC-MS experiments. Fitted Gaussian Process models (GPs) were used to perform a high level correction of the RT drift between the experiments, which was followed by standard peakset alignment between the samples with corrected RTs of the three LC-MS datasets. Statistical analysis, annotation and pathway analysis of the integrated peaksets were subsequently performed. Metabolic dysregulation patterns common across the datasets were identified, with kynurenine pathway being the most affected pathway between all three fever-associated datasets.

TopNEXt: automatic DDA exclusion framework for multi-sample mass spectrometry experiments.

MOTIVATION: Liquid Chromatography Tandem Mass Spectrometry experiments aim to produce high-quality fragmentation spectra, which can be used to annotate metabolites. However, current Data-Dependent Acquisition approaches may fail to collect spectra of sufficient quality and quantity for experimental outcomes, and extend poorly across multiple samples by failing to share information across samples or by requiring manual expert input. RESULTS: We present TopNEXt, a real-time scan prioritization framework that improves data acquisition in multi-sample Liquid Chromatography Tandem Mass Spectrometry metabolomics experiments. TopNEXt extends traditional Data-Dependent Acquisition exclusion methods across multiple samples by using a Region of Interest and intensity-based scoring system. Through both simulated and lab experiments, we show that methods incorporating these novel concepts acquire fragmentation spectra for an additional 10% of our set of target peaks and with an additional 20% of acquisition intensity. By increasing the quality and quantity of fragmentation spectra, TopNEXt can help improve metabolite identification with a potential impact across a variety of experimental contexts. AVAILABILITY AND IMPLEMENTATION: TopNEXt is implemented as part of the ViMMS framework and the latest version can be found at https://github.com/glasgowcompbio/vimms. A stable version used to produce our results can be found at 10.5281/zenodo.7468914.

Disclosure control of machine learning models from trusted research environments (TRE): New challenges and opportunities.

Introduction: Artificial intelligence (AI) applications in healthcare and medicine have increased in recent years. To enable access to personal data, Trusted Research Environments (TREs) (otherwise known as Safe Havens) provide safe and secure environments in which researchers can access sensitive personal data and develop AI (in particular machine learning (ML)) models. However, currently few TREs support the training of ML models in part due to a gap in the practical decision-making guidance for TREs in handling model disclosure. Specifically, the training of ML models creates a need to disclose new types of outputs from TREs. Although TREs have clear policies for the disclosure of statistical outputs, the extent to which trained models can leak personal training data once released is not well understood. Background: We review, for a general audience, different types of ML models and their applicability within healthcare. We explain the outputs from training a ML model and how trained ML models can be vulnerable to external attacks to discover personal data encoded within the model. Risks: We present the challenges for disclosure control of trained ML models in the context of training and exporting models from TREs. We provide insights and analyse methods that could be introduced within TREs to mitigate the risk of privacy breaches when disclosing trained models. Discussion: Although specific guidelines and policies exist for statistical disclosure controls in TREs, they do not satisfactorily address these new types of output requests; i.e., trained ML models. There is significant potential for new interdisciplinary research opportunities in developing and adapting policies and tools for safely disclosing ML outputs from TREs.

Patient preference for commonly-used, head and neck cancer-specific quality of life questionnaires in the follow-up setting (Determin): A multi-centre randomised controlled trial and mixed methods study.

BACKGROUND: Quality of life (QoL) assessment forms an integral part of modern cancer care and research. The aim of this study is to determine patients' preferences and willingness to complete commonly used head-and-neck cancer (HNC) QoL questionnaires (QLQs) in routine follow-up clinics. METHODS: This is a randomised control trial of 583 subjects from 17 centres during follow-up after treatment for oral, oropharyngeal or laryngeal cancer. Subjects completed three structured validated questionnaires: EORTC QLQ-HN35; FACT-HN and UW-QOL, and an unstructured patient-generated list. The order of questionnaire presentation was randomised, and subjects were stratified by disease site and stage. Patients self-rated the questionnaires they found most helpful to communicate their health concerns to their clinicians. RESULTS: Of the 558 respondents, 82% (457) found QLQs useful to communicate their health concerns to their clinician (OR = 15.76; 95% CI 10.83-22.94). Patients preferred the structured disease-specific instruments (OR 8.79; 95% CI 5.99-12.91), while the open list was the most disliked (OR = 4.25; 95% CI 3.04-5.94). There was no difference in preference by treatment modality. More women preferred the FACT-HN (OR = 3.01, 95% CI 1.05-8.62), and patients under 70 preferred EORTC QLQ-HN35 (OR = 3.14, 95% CI 1.3-7.59). However, only 55% of patients expressed preference to complete questionnaires routinely at the clinic. CONCLUSIONS: Most patients found QLQs helpful during their follow-up and 55% supported routine questionnaires in follow-up clinics. Males and people over 70 years old were the least willing to complete the routine questionnaires and preferred shorter questionnaires (e.g., UW-QOL). Women preferred FACT-HN, and younger patients preferred EORTC QLQ-HN35. Reasons for the reluctance to complete questionnaires require elucidation.