**Author(s):** Perret, Cedric ; Currie, Thomas Anthropologists & archaeologists have argued that the geographical distribution of resources and barriers to dispersal can affect that the degree of inequality, e.g. mountains may limit the possibility for subordinates to run away from despots. These ideas share parallels with models from evolutionary ecology, however formals models of this process have been relatively rare and the role of dispersal and migration as a levelling mechanism in human systems is still unclear. Here we describe a model based on the reproductive skew framework, and explore the concurrent evolution of inequality in many connected groups. We use both simulations and analytical approaches to examine the role of different factors.
Our results show that (i) cost of migration, even low, can lead to high inequality, (ii) migration reduces inequality not directly but by interacting with other processes affecting inequality and (iii ) that defining circumscribed groups requires careful consideration.
Finally, we discuss what these results suggest for real-world test of the territorial circumscription theory, and how they highlight the need for comprehensive models of the evolution of inequality and socio-political organization.

Modelling the role of migration and geographical distribution of resources on the evolution of inequality in socio-political systems

Magnetorelaxometry imaging (MRXI) [1] enables a quantitative and specific localization of magnetic nanoparticles (MNPs) inside living organisms [2] which is required by several novel therapeutic approaches such as magnetic hyperthermia therapy and magnetic drug targeting. MRXI involves aligning the MNPs’ magnetic moments using electromagnetic coils and subsequently recording their decaying net magnetization (relaxation). The recorded signals are connected to the MNP iron masses inside the discretized region of interest (ROI) via a system of linear equations [3]. The MNP distribution is recovered by solving the corresponding ill-posed inverse problem. However, the ROI discretization is limited to rather large voxel sizes. Finer voxel grids increase the number of unknowns and aggravate accurate reconstructions of MNP distributions. To date, finer voxel resolutions with reliable reconstruction accuracies are still necessary to obtain clinically relevant MRXI reconstructions. Standard MRXI provides only information about the MNP distributions and every voxel can contain MNPs with equal probability. Obviously, this is not realistic in clinical practice due to the different anatomical structures inside a human body. Accompanying traditional medical imaging techniques such as CT are necessary to gain anatomical information about the ROI. Here, we develop a multimodal reconstruction using CT data as prior for MRXI reconstructions, enabling a distinction between voxels with impossible, improbable and probable MNP occurrences. We test the approach on a cylindrical ROI (see Fig. 1) containing objects that produce different radiographic density (meat, wood, water, etc.) as well as MNPs. CT and MRXI measurements were conducted and the incorporation of the CT data allows us to reconstruct MNP distributions more accurately with half the voxel edge lengths than with mere MRXI (see Fig. 2). Our multimodal approach demonstrates that resolution and quantification accuracy of MRXI substantially benefits from anatomical data provided by alternative techniques such as CT or MRI.

CT Data as A-Priori Information for Multimodal Magnetorelaxometry Imaging

Converting diagnostic developments into practice involves a complex process of invention, validation and promotion, often in the face of determined opposition from established, if inferior, approaches. I have been involved in two clinically relevant developments which offer approaches of potential broader relevance.

Both developments have had their origins at the Centre for Life where our funding to develop the complex involved a commitment to promote commercial development. I had previously been involved in “spinning out” identity testing into a company called Northgene which we moved into the Centre for Life Bioscience Incubator in 1999 as the first “occupant” on site. This company is now wholly independent and continues to trade. I proposed a technology company called Life Diagnostics which eventually became a wholly owned subsidiary of the University and Newcastle Hospitals called Newgene ltd and traded successfully until it was made quiescent by the effective nationalisation of genomic diagnostics with the creation of the Genome Laboratory Hubs. The staff, all based at the Centre for Life, were transferred into the Yorkshire North East GLH.

1. In the early 2000’s, while head of Institute at the Centre for Life, I offered lab space to a start-up biotech company I had been advising, exploring the concept of point of care genomic diagnosis. When this “spin in” was ready to launch in 2008 as QuantuMDx Ltd, I was allowed to become a shareholder and Chair by the University. The concept originally rested on use of nanowires as the primary sensor but subsequently moved to a more traditional fluorescent marker detection following a rapid “shuttle” thermal PCR. The decision to stick with thermal PCR rather than the now widely recognised isothermal technique, LAMP, was its simplicity and the option of extensive multiplexing. The general focus was infectious disease such as drug resistant tuberculosis where a molecular approach could offer identification of the organism and its drug sensitivity in a single test. A version of the device was put into trial in Peru in 2018 focused on the 14 carcinogenic forms of Human Papilloma Virus underlying cervical cancer. While reasonably successful, it exposed limitations in the resilience of the device and prompted a structural redesign to allow effective use in a wide range of settings.

The Covid19 pandemic caused a rapid realignment of assay development; a triple target SARS-CoV2 assay was developed as both a lab assay and as a new cassette. The single use disposable cassette was refined and put into manufacture while the new version of the QPoc was manufactured and completed CE-IVD testing in July 2021 in our fully accredited laboratory in central Newcastle and first sales were achieved. With a reliable PCR result in around 30 minutes, the newly established sales team are now seeking to secure a market foothold while the assay team are working on a broader respiratory panel assay including Flu A and B and a multiplex Sexually Transmitted Disease panel and the digital team are developing the interface to link directly to laboratory informatics systems.

2. My research focus has been on hereditary cancers for over 30 years with a particular interest in the most common disorder, Lynch syndrome, though to be carried by more than 1 in 300 people and amenable to preventive use of low dose aspirin based on our CAPP2 trial. Sequencing the four mismatch repair genes is expensive and limited but a key feature is the accumulation of multiple “spelling mistakes” in tumour DNA called microsatellite instability. Over more than a decade our academic consortium at the Centre for Life has developed a new form of the assay suitable for large scale analysis using high depth next generation sequencing. This has the advantage of almost unlimited scalability with minimal input from clinical scientists and pathologists and inclusion of other molecular markers such as the driver mutation BRAF V600E which helps to differentiate sporadic MSI high cancers from those likely to be the result of an inherited predisposition. We are now working to embed the new assay across the national Genomic Laboratory Hubs and commercialise with the help of Cancer Research UK the patents owned by the university. Newcastle Hospitals adopted the Newcastle MSI Plus assay in 2020 and it has been accepted as the standard of care for tumour screening in the North East. If current funding applications are successful, we will seek to commercialise through the newly created Buisness, Development and Enterprise Directorate at Newcastle Hospitals and will explore reactivating Newgene ltd to drive international sales and broaden the use of the assay to include urine screening for cancers in the renal tract for which we currently have no simple screening approach.

Despite clear progress, these two success stories are not yet complete. Diagnostics is challenging due to long lead times in research, costs of winning and defending patents, rapid technological advance, institutional preference for existing methods, international competition and short term investment decisions. The NHS and British government could do more to incorporate “social value” into procurement and strengthen policies to protect research investment. Our academic institutions and hospitals need to embrace entrepreneurship, give due credit to achievement of secure intellectual property and help promote its development.


Two journeys across the Valley of Death: QPoc and the Newcastle MSI Plus assay, Professor Sir John Burn

Precision and P4 medicine are contemporary models of healthcare that aim to deliver structured, stratified and relevant approaches to disease and well-being. It is enabled by the availability of large, rich data sets from genomics and multi-omics and a range of cell-free diagnostics (liquid biopsies). Some have predicted that with such developments in these methodologies, the role of histopathology in precision diagnostics may decline in future. Nonetheless, morphological assessment of tissue sections has contributed to a form of precision diagnostics for many decades. The development of high throughput whole slide scanners is now taking tissue-based diagnostics to the next level. Digital pathology offers advantages in workflow for histopathologists and some large departments in the UK have now converted to this platform. In addition, digitisation allows the application of adjunct techniques that enhance diagnostic capabilities for example more accurate measurements than the human eye such as cell proliferation indices. More excitingly, the application of artificial intelligence (AI) algorithms will provide further advances in precision tissue-based diagnostics. At its simplest level, machine learning approaches have been developed by which computers can essentially replicate the morphological assessment of histopathologists and with some applications can do so more accurately and reproducibly. Two such approaches for the diagnosis of breast and prostate cancer have recently been approved by the FDA for use in clinical practice in the US. Deep learning approaches offer potentially much greater information for precision diagnostics with recent studies demonstrating that scanned images of routinely stained sections can be analysed by computer to predict mutational alterations, prognosis, and response to therapy. It appears that “the demise of histopathology has been greatly exaggerated”!

Digital technologies – the coming of Age of Diagnostics, Professor Alastair Burt

Current screening procedures for lung cancer involve the use of low-dose computed tomography (LDCT). However, this approach has correlated with high false-positive rates, invasive and costly workups. In addition, 80% of diagnosed patients are unresponsive to treatment. There is a need for biomarkers with improved diagnostic accuracy and a capability of predicting response in order to improve treatment. In this study, a set of three miRNAs have been identified that can faithfully differentiate between disease free and lung cancer patients. These miRNAs have also shown to converge on pathways responsible for promoting onceogenesis pf lung cancer and mediating resistance, suggesting potential to serve as a predticitve diagnostic tools.

Multianalyte Liquid Biopsy Biomarkers for NSCLC Risk Assessment

1. Introduction Ultra-high sensitivity and micro-sized magnetic sensors are required in biomagnetic measuring devices. The GigaHertz spin rotation sensor, which is an evolution of the magneto-impedance sensor, has shown high sensitivity while transmitting GHz pulse currents [1]. Detection magnetic fields are sensed via a pickup coil wrapped around the wire when the GHz pulse currents are applied. However, the micro-mechanism in the amorphous wire, which exhibits high sensitivity, has not been characterized. Thus, we investigated the relationship between peak voltages and magnetic fields and the magnetization behavior inside the amorphous wire. 2. Calculation method and conditions The magnetization behavior was calculated using the Landau–Lifshitz–Gilbert equation, which considers eddy currents. The calculation model of the amorphous wire is shown in Fig. 1. The magnetic properties included a saturation magnetization of 1.0 T, a magnetic anisotropy constant of 250 J/m3, and exchange constants between cells in the plane and the axial direction of 1.0 × 10−11 J/m and 2.0 × 10−11 J/m, respectively. The magnetization easy axis of the amorphous wire from the outer circumference to the inside by 0.75 µm was assumed to be oriented in the circumferential direction because compressive stress is generated in the FeCoSiB amorphous wire, which is induced via rapid quenching during the fabrication processes [2]. 3. Results Fig. 2 shows the relationship between the peak voltages at the fall times of the pulse currents and magnetic fields. When the fall time was 1.0 ns, the calculated and experimental results showed the same tendency. A shorter fall time meant higher absolute values of the peak output voltages and stronger magnetic fields as shown in Fig. 2. At a fall time of 0.385 ns, only the rotations of magnetizations in the outer circumference of the amorphous wire contributed to the output voltages, whereas at a fall time of 5.0 ns, the domain wall motions inside the wire contributed to the output voltages. This was the reason why the output peak voltages increased as the fall time was shortened.

![](https://assets.underline.io/uploads/markdown_image/1/image/b0cfc2b624142dd7949f1e74c66d616b.jpg)

Fig. 1 Model of a magnetic sensor with an amorphous wire

![](https://assets.underline.io/uploads/markdown_image/1/image/fee592d4ca3a224b0b9da7393a6acba5.jpg)

Fig. 2 Relationship between peak voltages and magnetic fields

Effects of fall times of pulse currents on output voltages for amorphous-wire-based magnetic sensors

Studies have shown that relaxing music can lower a patient’s breathing rate, heart rate, and blood pressure by releasing stress or anxiety and promoting relaxation [1,2]. Based on the successful development of our magnetic respiratory monitoring technology for advanced healthcare [3], in this study we attempt to examine how the breathing pattern of a patient changes when the patient sleeps with and without a favorite music in the background. We observed that during sleep mode with music, the patient breathed more regularly and slowly (11 times per minute) compared to sleep without music (14 times per minute) and wake mode (17 times per minute). This indicated that the relaxing music helped the patient to relax and sleep better. Remarkably, while the abnormal breathing feature was observed at a certain time for all states (wake-up and sleep modes with and without music), the breathing pattern became more regular in the case of sleep with the relaxing music. Furthermore, we designed a musical biofeedback for breathing regulation. In this design, the respiratory motion of the patient was tracked and interpreted as a real-time variable for tempo adjustment to a stored musical file. The patient was able to adjust breathing to synchronize with a separate accompaniment line. When the breathing was regular and at the desired tempo, the resulting sound was synchronous and harmonious. These observations suggest a new possibility of integrating our magnetic respiratory monitoring technology with music to develop an innovative magnetic music therapy for Covid19 patients with breathing difficulty.

Magnetic Respiratory Monitoring Technology Based Music Therapy for Covid19 Patients: A New Perspective

1.Introduction The ANR RHU BioArt-Lung 2020 project aims to develop an extracorporeal artificial lung with reduced size and mass. An essential element of the system is its circulatory assist centrifugal pump, which ensures blood circulation. Our work focuses on this pump’s electric motor. Several papers present this medical technology [1-2]. In this article, we outline the electrical motor’s specifications and then present an initial dimensioning using a Design of Experiments. We then analyse the chosen structure using both 2D and 3D finite element (FE) methods. A prototype is then manufactured, and performance tests carried out. 2.Specifications and design The motor design should, therefore, be compact (adapted to the pump Fig.1 (a)). It must respect several medical, electrical, and mechanical constraints. The motor design specifications are provided in Table 1. The chosen structure is a radial flux motor with surface permanent magnets (Fig. 1 (b)). Two pairs of poles and its stator contains twelve slots with a concentrated winding. To study several structures, a method based on a Design of Experiments [3] is used. Effects of the variables (dimensions, geometrics) on the outputs: cost functions (torque, mass, efficiency) and constraints (current density, voltage level) are analysed. 3.Performance analysis The PMSM is modelled by both 2D and 3D Finite Element (FE) methods in FEMM and Comsol® Fig.1 (b). Both no-load and on-load analyses are performed. The machine can deliver torque under load with an average value of 60.9 mNm. The amplitude of the torque ripples remains acceptable (8%). The efficiency max of the PMSM is estimated to 85 %. Using iron loss model [4]. 4.PMSM prototype The prototype of the PMSM has been manufactured to test performance. Fig.1 (c) shows the active part of the engine prototype. In the final paper, a comparison will be presented to validate the simulation results. 5.Conclusion This article explores the design of a PMSM for the development of a portable artificial lung. Its pre-dimensioning is carried out using the Design of Experiments method. Details of the analysis and comparison will be described in the full paper.

Underline digital video library

Modelling the role of migration and geographical distribution of resources on the evolution of inequality in socio-political systems

CT Data as A-Priori Information for Multimodal Magnetorelaxometry Imaging

Two journeys across the Valley of Death: QPoc and the Newcastle MSI Plus assay, Professor Sir John Burn

Digital technologies – the coming of Age of Diagnostics, Professor Alastair Burt

Multianalyte Liquid Biopsy Biomarkers for NSCLC Risk Assessment

Effects of fall times of pulse currents on output voltages for amorphous-wire-based magnetic sensors

Magnetic Respiratory Monitoring Technology Based Music Therapy for Covid19 Patients: A New Perspective

Design of a Circulatory Assistance Actuator Applied to an Artificial Lung

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