The impact of multiple exposures and movement on the fear response of poultry.

Fear tests are a common research method to assess the affective state of an animal. This study aimed to assess: 1) the impact of repeated exposure to fear tests on fear response and, 2) how the addition of movement to fear stimuli during a novel object test impacts bird fear response. Over two trials, a total of 3,600 Ross 308 birds (1800 birds/trial) were raised until 42 days of age.

Transcatheter tricuspid valve intervention in the presence of a cardiac implantable electronic device; state of the art review.

A large proportion of patients referred for transcatheter tricuspid valve intervention (TTVI) will have the presence of a cardiac implantable electronic device (CIED). In such patients, surgical correction of tricuspid regurgitation (TR) is associated with high rates of morbidity and mortality. Transvenous lead extraction (TLE) could potentially ameliorate CIED-induced TR; however, it carries inherent risks and frequently does not result in TR improvement.

Multiple Valvular Heart Disease in the Transcatheter Era: A State-of-the-Art Review.

Although existing guidelines offer strong recommendations for single valvular dysfunction, the growing prevalence of multiple valvular heart disease (MVHD) in our aging population is challenging the clarity of clinical guidance. Traditional diagnostic modalities, such as echocardiography, face inherent constraints in precisely quantifying valvular dysfunction due to the hemodynamic interactions that occur with multiple valve involvement. Therefore, many patients with MVHD present at a later stage in their disease course and with an elevated surgical risk.

Evaluating the impact of gypsum as a novel bedding material on broiler performance, foot pad health, and fear response.

Flue Gas Desulfurization (FGD) gypsum is a byproduct of the coal-fired power plant process commonly used to remove sulfur dioxide emissions from the flue gas. FGD gypsum has numerous industrial, agricultural, and environmental applications. This study aimed to explore a novel approach involving the use of FGD gypsum combined with different litter treatments as bedding for broiler production.

Balloon rupture during transcatheter aortic valve replacement.

A distinctive complication with balloon-expandable (BE) THV platforms such as the Edwards Sapien (Edwards Lifescience) is the possibility of balloon rupture during THV deployment. Balloon rupture is a rare occurrence that can result in stroke due to fragment embolism, incomplete THV expansion, and/or vascular injury upon retrieval of the balloon. Careful evaluation of preoperative computed tomography is essential to identify high-risk cases.

: transmission electron microscopy simulation software for teaching and training of microscope operation.

An interactive simulation of a transmission electron microscope (TEM) called is developed here, which enables users to understand how to operate and control an electron beam without the need to access an instrument. allows users to familiarize themselves with alignment procedures offline, reducing the time and money required to become a proficient TEM operator. In addition to teaching the basics of electron beam alignments, the software enables users to create bespoke microscope configurations and develop an understanding of how to operate the configurations without sitting at a microscope.

A systematic review of biologically-informed deep learning models for cancer: fundamental trends for encoding and interpreting oncology data.

Background: There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which constrain their deployment in biomedical settings.

Methods: This systematic review discusses DL models used to support inference in cancer biology with a particular emphasis on multi-omics analysis.

Meta-analysis informed machine learning: Supporting cytokine storm detection during CAR-T cell Therapy.

Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown otherwise promising results in cancer treatment. When emerging, CRS could be identified by the analysis of specific cytokine and chemokine profiles that tend to exhibit similarities across patients. In this paper, we exploit these similarities using machine learning algorithms and set out to pioneer a meta-review informed method for the identification of CRS based on specific cytokine peak concentrations and evidence from previous clinical studies.

TEMGYM Advanced: Software for electron lens aberrations and parallelised electron ray tracing.

Characterisation of the electron beams trajectory in an electron microscope is possible in a few select commercial software packages, but these tools and their source code are not available in a free and accessible manner. This paper introduces the free and open-source software TEMGYM Advanced, which implements ray tracing methods that calculate the path of electrons through a magnetic or electrostatic lens and allow evaluation of the first-order properties and third-order geometric aberrations. Validation of the aberration coefficient calculations is performed by implementing two independent methods - the aberration integral and differential algebra (DA) methods and by comparing the results of each.

TEMGYM Advanced - NanoMi lens characterisation.

A complete analysis including finite element method (FEM) calculation, focal length properties, and thirdorder geometric aberrations of the open-source electrostatic lens from the NanoMi project is presented. The analysis is carried out by the software TEMGYM Advanced, a free package developed to carry out ray-tracing and lens characterisation in Python. Previously TEMGYM Advanced has shown how to analyse the aberrations of analytical lens fields; this paper expands upon this work to demonstrate how to apply a suitable fitting method to discrete lens fields obtained via FEM methods so that the aberrations of real lens designs can be calculated.

Digital ECMT Cancer Trial Matching Tool: an Open Source Research Application to Support Oncologists in the Identification of Precision Medicine Clinical Trials.

Purpose: Matching patients with cancer to precision medicine clinical trials on the basis of their tumor genotype has the potential to improve outcomes for patients who have exhausted standard-of-care treatment options. However, the matching process presents a substantial challenge because of the number of clinical trials available. We describe a free, open source research tool designed to extract relevant trial information to support oncologists in the matching process, and we illustrate its utility with recent case studies of patients who were matched to trials using this tool.

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic.

Patient attrition in Molecular Tumour Boards: a systematic review.

Background: Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatment.

Methods: A literature review was performed to understand patient attrition within MTBs and barriers to patients receiving treatment.

Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer.

We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment.

Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital.

Purpose: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET).

Prospective Evaluation of Autonomic Dysfunction in Post-Acute Sequela of COVID-19.

Background: Patients with post-acute sequela of COVID-19 (PASC) often report symptoms of orthostatic intolerance and autonomic dysfunction. Numerous case reports link postural orthostatic tachycardia syndrome (POTS) to PASC. No prospective analysis has been performed.

Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital.

Objectives: COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19.

Design And Setting: This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England.

Wave comparisons of clinical characteristics and outcomes of COVID-19 admissions - Exploring the impact of treatment and strain dynamics.

Objectives: Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study.

Hemodynamic Profiles of Shock in Patients With COVID-19.

Patients with serious COVID infections develop shock frequently. To characterize the hemodynamic profile of this cohort, 156 patients with COVID pneumonia and shock requiring vasopressors had interpretable echocardiography with measurement of ejection fraction (EF) by Simpson's rule and stroke volume (SV) by Doppler. RV systolic pressure (RVSP) was estimated from the tricuspid regurgitation peak velocity.

Technology clinical trials: Turning innovation into patient benefit.

Health care needs to continuously evolve and innovate to maintain the health of populations. Technology has the potential to enable better patient engagement and ownership, as well as optimise therapeutic interventions and data-science approaches to facilitate improved health care decisions. Yet, to date, technological innovation has not resulted in the rate of change that could have been predicted from other sectors.

An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancer.

Durvalumab is a programmed death-ligand 1 (PD-L1) inhibitor with clinical activity in advanced urothelial cancer (AUC). AUC is characterized by several recurrent targetable genomic alterations. This study ( NCT02546661 , BISCAY) combined durvalumab with relevant targeted therapies in biomarker-selected chemotherapy-refractory AUC populations including: (1) fibroblast growth factor receptor (FGFR) inhibitors in tumors with FGFR DNA alterations (FGFRm); (2) pharmacological inhibitor of the enzyme poly-ADP ribose polymerase (PARP) in tumors with and without DNA homologous recombination repair deficiency (HRRm); and (3) TORC1/2 inhibitors in tumors with DNA alteration to the mTOR/PI3K pathway.

Research Evaluation Alongside Clinical Treatment in COVID-19 (REACT COVID-19): an observational and biobanking study.

Introduction: The COVID-19 pandemic caused by SARS-CoV-2 places immense worldwide demand on healthcare services. Earlier identification of patients at risk of severe disease may allow intervention with experimental targeted treatments, mitigating the course of their disease and reducing critical care service demand.

Methods And Analysis: This prospective observational study of patients tested or treated for SARS-CoV-2, who are under the care of the tertiary University Hospital Southampton NHS Foundation Trust (UHSFT), captured data from admission to discharge; data collection commenced on 7 March 2020.

Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study.

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review.