University of Nottingham

The battery is mostly adopted as the load in current wireless charge applications. The wireless charger should provide configurable constant current (CC) and constant voltage (CV) outputs for the batteries. The implementation of configurable CC and CV outputs mostly rely on the additional DC-DC converter, hybrid topology, or high-order networks, resulting in complex control and poor reliability. Moreover, the battery wireless charger should also have anti-misalignment ability. To attack the above problems, a hybrid battery wireless charger is proposed for self-adapting battery charging curve and anti-misalignment. A double-solenoid quadrature coupler (DSQC) consisting of square quadrature coil and double-solenoid coil is designed, which combines the coupler with clamp circuit to switch between the two coils automatically, ensuring that the output voltage has small fluctuation within a large lateral misalignment range and inherent CC-to-CV output. The control means is relatively simple, the output threshold is not limited by the parameters of DSQC. Eventually, an experimental prototype with 100V/4.1A output is built to verify the correctness of the proposed scheme.

This paper proposes a high step-down DC-DC converter with a continuous output current. In order to obtain high efficiency, the proposed converter topology ensures zero voltage switching of the MOSFETs and zero current switching of the diodes. One of the advantages of the proposed converter is the continuity of the output current and the maintenance of the soft switching of semiconductor elements throughout a broad power range. Through the use of coupled inductors and series capacitors, the duty cycle of the converter is lengthened. As a result, the peak current of MOSFETs is reduced. Moreover, power is transmitted to the output through both switches, optimizing the converter loss distribution. With the bootstrap method, the converter's switches also are controlled, eliminating the need for gate drivers with isolated power supply. A 200W prototype converter with a 400V input voltage and 24V output voltage has been implemented to validate the theoretical analysis and confirm the topology's increased efficiency.

The phrase ‘Panta Rhei—everything flows’ by the Greek philosopher Heraclitus, a purported reference to a constantly changing flowing river, or more philosophically, ‘continual transformation’, can be aptly extended to describe the evolution of treatment strategies for many human diseases. In disappointing contrast, the drug treatment for patients with non-promyelocytic, acute myeloid leukaemia (AML) has remained essentially unchanged for over 50 years, with improved outcomes over this period, largely, a consequence of incremental improvements in supportive care and the application of allogeneic stem cell transplantation. The anti-leukaemic effectiveness of single-agent daunorubicin (D) or cytarabine (Ara-C) was first recognised over half-a-century ago, and intensified leukaemic cell kill with these genotoxic drugs (DA) became the standard approach for treating newly diagnosed AML patients. At the time of writing, induction therapy combining these two pharmacological classes of drugs, followed by intensified consolidation or allogeneic stem cell transplantation, remains the only proven strategy for curing AML. Here, through a review of the development of different anti-leukaemic drug combinations, we evaluate the effectiveness of various intensive chemotherapy platforms and the evidence for using adjunctive or sequential therapy with newer, genotoxic or non-genotoxic agents.

Background Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international guidelines. Objectives To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/dementia. Methods Guideline content was developed with input from several scientific and lay representatives’ societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert panels. Recommendations Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind–body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of evidence. Conclusions Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health.

LINKED CONTENT This article is linked to So et al papers. To view these articles, visit https://doi.org/10.1111/apt.17629 and https://doi.org/10.1111/apt.17704

Purpose of review Despite a strong consensus that treatment of hypertension is fundamental to strategies seeking to slow chronic kidney disease (CKD) progression and reduce the associated risk of cardiovascular events (CVE), controversy persists regarding optimal blood pressure (BP) targets. This article reviews the evidence for different targets, discusses associated controversies and suggests approaches to improve BP control. Recent findings Landmark clinical trials established the principle that lower BP targets are associated with slower progression of CKD in people with a greater magnitude of proteinuria and previous guidelines recommended a target BP of <130/80 mmHg for those with proteinuria. However, the Systolic Blood Pressure Intervention Trial provided new evidence that a systolic BP target of <120 mmHg was associated with a reduced risk of CVE, though there was no impact on CKD progression and there was concern about an increase in renal adverse events. Nevertheless, 2021 Kidney Disease Improving Global Outcomes guidelines recommended systolic BP <120 mmHg, though other updated guidelines did not follow this trend. All guidelines emphasise the importance of standardised BP measurement and a personalised approach. Summary An individualised and shared decision-making approach to BP target setting and management is recommended, guided by standardised BP measurement.

Cognitive impairment in multiple sclerosis (MS) can adversely impact participation in employment, activities of daily living, and wider society. It affects 40–70% of people living with MS (pwMS). There are few effective treatments for cognitive impairment in people with MS. Neuromodulation with intermittent theta-burst stimulation (iTBS) has potential for treating cognitive impairment in pwMS. This single-centre mixed-methods feasibility randomised controlled trial (NCT04931953) will assess feasibility, acceptability, and tolerability of procedures used for applying iTBS for improving cognitive performance in pwMS. Participants will be randomised into three intervention groups with varying lengths of iTBS treatment (from 1 to 4 weeks) and a sham-control group. Quantitative data will be collected at three time points (baseline, end of intervention, and 8-week follow-up). End of the intervention semi-structured interviews will explore the views and experiences of the participants receiving the intervention, analysed using framework analysis. Quantitative and qualitative data will be synthesised to explore the impact of the iTBS intervention. Ethical approval has been received from the Health Research Authority (21/LO/0506) and recruitment started in June 2022. The results will inform the design of an RCT of the efficacy of iTBS as a therapeutic intervention for cognitive impairment in pwMS.

Hormone receptor-positive (HR⁺)/human epidermal growth factor receptor 2-negative (HER2⁻) breast cancer is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. Accurate molecular classification is urgently required for guiding precision treatment. We established a large-scale multi-omics cohort of 579 patients with HR⁺/HER2⁻ breast cancer and identified the following four molecular subtypes: canonical luminal, immunogenic, proliferative and receptor tyrosine kinase (RTK)-driven. Tumors of these four subtypes showed distinct biological and clinical features, suggesting subtype-specific therapeutic strategies. The RTK-driven subtype was characterized by the activation of the RTK pathways and associated with poor outcomes. The immunogenic subtype had enriched immune cells and could benefit from immune checkpoint therapy. In addition, we developed convolutional neural network models to discriminate these subtypes based on digital pathology for potential clinical translation. The molecular classification provides insights into molecular heterogeneity and highlights the potential for precision treatment of HR⁺/HER2⁻ breast cancer.

Introduction People who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine kinase inhibitor therapy (BTKi) starting 1 week before delivery of SARS-CoV-2 vaccine booster, improves vaccine immune response when compared with continuation of BTKi. Methods and analysis An open-label, randomised controlled superiority trial will be conducted in haematology clinics in approximately 10 UK National Health Service (NHS) hospitals. The sample size is 120, randomised 1:1 to intervention and usual care arms. The primary outcome is anti-spike-receptor binding domain (RBD) antibody level at 3 weeks post-SARS-CoV-2 booster vaccination. Secondary outcomes are RBD antibody levels at 12 weeks postbooster vaccination, participant global assessments of disease activity, blood films, full blood count and lactate dehydrogenase levels, impact on quality of life, self-reported adherence with request to temporarily pause or continue BTKi, T cell response against spike protein and relative neutralising antibody titre against SARS-CoV-2 viral variants. Additionally, there will be an investigation of any effects in those given influenza vaccination contemporaneously versus COVID-19 alone. The primary analysis will be performed on the as randomised groups (‘intention to treat’). The difference between the study arms in anti-spike-RBD antibody level will be estimated using a mixed effects regression model, allowing for repeated measures clustered within participants. The model will be adjusted for randomisation factor (first line or subsequent line of therapy), and prior infection status obtained from prerandomisation antinucleocapsid antibodies as fixed effects. Ethics and dissemination This study has been approved by Leeds East Research Ethics Committee and Health Research Authority (REC Reference:22/YH/0226, IRAS ID: 319057). Dissemination will be via peer-review publications, newsletters and conferences. Results will be communicated to participants, the CLL patient and clinical communities and health policy-makers. Trial registration number ISRCTN14197181 .

Background Knowledge and attitudes of professionals both pose a potential barrier to diagnosis and treatment of mental disorders. However, knowledge and attitudes about conduct disorder in professionals working with young people are poorly understood. Little is known about the impact of occupation, direct and indirect (training and education) experience, or the interrelationship between knowledge and attitudes. Methods We conducted an online survey of 58 participants, including Psychology Staff, Teaching Staff, Care Staff, and Other Non-Clinical Staff. A questionnaire comprising three subscales (causes, treatments, and characteristics) measured knowledge. A thermometer scale measured global attitudes. Open-ended response measures were used to measure four attitude components: stereotypic beliefs (about characteristics), symbolic beliefs (about the holder’s traditions), affect, and past behaviour. Primary analysis explored the impact of occupation, direct experience, and indirect experience on outcome measures. A secondary exploratory analysis was conducted to explore the relationship between knowledge and attitudes. Results Psychology Staff had significantly more favourable global attitudes ( F = 0.49, p = 0.01) and symbolic beliefs ( F = 0.57, p = 0.02) towards those with conduct disorder than Teaching Staff; there were no other significant group differences in attitudes. Psychology staff had more knowledge about conduct disorder than other groups, though the differences were not significant. Direct and indirect experience were associated with greater knowledge (direct: d = 0.97, p = 0.002; indirect d = 0.86, p = 0.004) and favourable global attitudes (direct: d = 1.12, p < 0.001; indirect: d = 0.68, p = 0.02). Secondary exploratory analyses revealed significant positive correlations between: all knowledge variables with global attitudes; total knowledge with past behaviour; and affect and knowledge of causes with past behaviour. Conclusions Psychology-based staff may have more favourable attitudes towards children with conduct disorder than teachers, primarily due to direct and indirect experience with the disorder. Our sample may have been too small to detect overall or within-group effects of knowledge or attitudes, however exploratory analyses showing a positive correlation between knowledge and attitudes suggest education may be critical in supporting teachers and other groups in their approaches to this challenging group of young people.

Introduction/Background The objective of this non-inferiority phase III prospective randomized trial was to compare RH to SH in women with LRESCC. Methodology Women with LRESCC defined as stage IA2 or IB1 disease with lesions ≤2cm were randomized to RH or SH. The primary endpoint was pelvic recurrence rate at 3 years (PRR3). Primary intention to treat (ITT) analysis included all patients randomized. Secondary endpoints included extra-pelvic relapse-free survival (EPRFS), overall survival (OS) and patient reported outcome. Results 700 women were enrolled from December 2012 to November 2019. Median age was 44 (24-80); 91.7% were stage 1B1 and 61.7% were squamous histology. On final pathology, lymph node metastasis occurred in 3.7% (3.3% SH and 4.4% RH), positive margins in 2.5% (2.1% SH and 2.9% RH), and lesions >2cm in 4.25% (4.4% SH and 4.1% RH). A total of 8.8% of women received post-surgical adjuvant therapy (9.2% SH and 8.4% RH). With a median follow-up of 4.5 years, 21 pelvic recurrences occurred (11 SH and 10 RH). The PRR3 was 2.52% with SH and 2.17% with RH (difference 0.35% with 95% upper confidence limit 2.32%) in ITT analysis. The 3-year EPRFS and OS were respectively 98.1% and 99.1% with SH; 99.7% and 99.4% with RH. SH had less bladder (9 vs 3) and ureteral injuries (5 vs 3) and significantly less urinary incontinence (4.7% vs. 11.0%; p=0.003) and urinary retention (0.6% vs. 9.9%; p<0.0001) compared to RH. QoL scales with significant difference between the two groups over time were all in favor of SH. Conclusion The pelvic recurrence rate at 3 years in women with LRESCC who underwent SH was not inferior to RH and was associated with fewer surgical complications and better QoL.. SH should be considered the new standard of care. Disclosures None

BACKGROUND Children from pregnancies affected by preeclampsia have an increased risk of cognitive and behavioral alterations via unknown pathophysiology. We tested the hypothesis that preeclampsia generated reduced brain cortex angiogenesis in the offspring. METHODS The preeclampsia-like syndrome (PELS) mouse model was generated by administering the NO inhibitor NG-nitroarginine methyl ester hydrochloride. Confirmatory experiments were done using 2 additional PELS models. While in vitro analysis used mice and human brain endothelial cells exposed to serum of postnatal day 5 pups or umbilical plasma from preeclamptic pregnancies, respectively. RESULTS We report significant reduction in the area occupied by blood vessels in the motor and somatosensory brain cortex of offspring (postnatal day 5) from PELS compared with uncomplicated control offspring. These data were confirmed using 2 additional PELS models. Furthermore, circulating levels of critical proangiogenic factors, VEGF (vascular endothelial growth factor), and PlGF (placental growth factor) were lower in postnatal day 5 PELS. Also we found lower VEGF receptor 2 (KDR [kinase insert domain-containing receptor]) levels in mice and human endothelial cells exposed to the serum of postnatal day 5 PELS or fetal plasma of preeclamptic pregnancies, respectively. These changes were associated with lower in vitro angiogenic capacity, diminished cell migration, larger F-actin filaments, lower number of filopodia, and lower protein levels of F-actin polymerization regulators in brain endothelial cells exposed to serum or fetal plasma of offspring from preeclampsia. CONCLUSIONS Offspring from preeclampsia exhibited diminished brain cortex angiogenesis, associated with lower circulating VEGF/PlGF/KDR protein levels, impaired brain endothelial migration, and dysfunctional assembly of F-actin filaments. These alterations may predispose to structural and functional alterations in long-term brain development.

There is a consensus about the strong correlation between the elasticity of cells and tissue and their normal, dysplastic, and cancerous states. However, developments in cell mechanics have not seen significant progress in clinical applications. In this work, we explore the possibility of using phonon acoustics for this purpose. We used phonon microscopy to obtain a measure of the elastic properties between cancerous and normal breast cells. Utilising the raw time-resolved phonon-derived data (300 k individual inputs), we employed a deep learning technique to differentiate between MDA-MB-231 and MCF10a cell lines. We achieved a 93% accuracy using a single phonon measurement in a volume of approximately 2.5 μm³. We also investigated means for classification based on a physical model that suggest the presence of unidentified mechanical markers. We have successfully created a compact sensor design as a proof of principle, demonstrating its compatibility for use with needles and endoscopes, opening up exciting possibilities for future applications.

High-density phase change memory (PCM) storage is proposed for materials with multiple intermediate resistance states, which have been observed in 1T-TaS2 due to charge density wave (CDW) phase transitions. However, the metastability responsible for this behavior makes the presence of multistate switching unpredictable in TaS2 devices. Here, we demonstrate the fabrication of nanothick verti-lateral H-TaS2/1T-TaS2 heterostructures in which the number of endotaxial metallic H-TaS2 monolayers dictates the number of resistance transitions in 1T-TaS2 lamellae near room temperature. Further, we also observe optically active heterochirality in the CDW superlattice structure, which is modulated in concert with the resistivity steps, and we show how strain engineering can be used to nucleate these polytype conversions. This work positions the principle of endotaxial heterostructures as a promising conceptual framework for reliable, non-volatile, and multi-level switching of structure, chirality, and resistance.

Introduction Thoracic outlet syndrome presenting in a rheumatology clinic will challenge even the most experienced clinician. We share our experience with a patient presenting initially to the thoracic surgeons with classical symptoms of thoracic outlet obstruction. Workup (imaging) identified a bony swelling at the sternoclavicular region leading to referral to our clinic. Our working diagnosis of this being an extremely rare sole manifestation of a common rheumatological disorder was confirmed. We share our story. Case description Mrs LB, a 53 year old female was referred by her GP with a progressive swelling around the right sternoclavicular joint. On workup, we identified that she first presented to the vascular surgeons in 2008 with pain and congestion in her right arm and numbness in the fingers. MR venogram confirmed occlusion of the right subclavian with manoeuvres. She was discharged and managed conservatively with analgesia. This swelling was new, had slowly enlarged over the years and was causing pain in the anterior chest wall. On further questioning she confirmed having pustular psoriasis which was quiescent for 10 years. She denied any other articular (peripheral and spinal) or extra articular symptoms of psoriasis. She had no additional past history. Examination confirmed a hard 6 cm mass around the sternoclavicular region. The overlying skin was intact. The mass was tender only on movement of the shoulder. The rest of the examination with special focus on skin, neurovascular bundle and system review was unremarkable. Routine blood tests, inflammatory markers and detailed immunology were unremarkable other than slightly raised IgA 4.3 (range 0.7 – 4.0). X-ray clavicle and localised Computerized tomography (CT) confirmed features in keeping with hyperostosis and periostitis. Magnetic resonance imaging of the whole body identified additional involvement of the thoracic spine with endplate and vertebral body oedema at T3/4, T5/6, T6/7, T8/9 and T9/T10. Our working diagnosis of this being a rare manifestation of SAPHO was confirmed. She fulfilled the modified diagnostic criteria based on the clinical manifestations of previous pustular psoriasis and osteo-articular features on imaging. As she had been on non-steroidal anti-inflammatories for the pain around the shoulder with little effect and our workup identified additional extensive subclinical spinal involvement the patient has been started on anti-TNF therapy (adalimumab) with planned interval MRI to monitor disease and assess response. Discussion SAPHO syndrome is a rare disorder, which consists of synovitis, acne, pustulosis, hyperostosis and osteitis. As in our case, it is predominant in middle-age women. Immunological, genetic and infectious factors are underlying etiology, but the exact pathophysiological mechanisms is unknown. The innate immune system is likely to be involved via elevation of pro-inflammatory cytokines, including IL-8, IL-17 and TNF-α. The bacterial species Cutibacterium (formerly termed Propionibacterium acnes) has been identified in previous studies. Genetic factors are proposed to be involved but no specific genes have been identified. SAPHO syndrome has varied presentations. All the features of SAPHO may not be present at the same time. A high index of suspicion, careful history, radiological and skin manifestations are key to early diagnosis. As in this case, skin manifestations can predate skeletal manifestations by years. Sternoclavicular joint involvement is common (65-90%) followed by spine (32 – 52%) and pelvis (13 – 52%). On careful review of the chest x-ray from 2008 we concluded that her first presentation with thoracic outlet symptoms was due to SAPHO syndrome. Soft tissue swelling around the area of the clavicle can cause compression of structures before significant changes are seen on X Rays. MRI is recommended as this is more sensitive to pick up asymptomatic and early lesions. Even though this patient did not have any inflammatory spinal symptoms imaging identified multiple sites of active spinal disease. Until now there are no treatment guidelines for SAPHO syndrome. It is generally recommended that where NSAIDS have failed and there is axial involvement anti-TNF treatment offers better outcome compared to cDMARDS. Other treatments such as Janus kinus inhibitors, IL-17, PDE-4 inhibitors and bisphosphonates have been used. There are no agreed composite measures to assess disease activity in SAPHO and repeat imaging may be used to guide treatment. Key learning points One needs to keep a high index of suspicion of SAPHO in patients with isolated sternoclavicular joint disease especially if there is co-existant skin disease. Most commonly affected skeletal site is the anterior chest wall, including sternoclavicular, manubrosternal and costosternal joints. Axial skeleton, including the spine and sacroiliac joints are other common sites. Palmoplantar psoriasis and severe acne are the main skin manifestations of SAPHO and should act as an alert The time interval between the occurrence of initial skin and arthritis/osteitis symptoms in SAPHO can be many years. In the majority of cases this is usually within two years. Exacerbation of osteoarticular and dermatologic manifestations are often unrelated to each. Magnetic resonance imaging (MRI) is more sensitive in picking up asymptomatic and early lesions.

This feminist research explores how superstition is used by in‐law's family to subordinate women business‐owners in a highly patriarchal developing context. Whereas the exploration of gender subordination regarding women's entrepreneurship is almost exclusively confined to developed nations, little is known regarding the way women are subjugated in managing their small businesses in a patriarchal developing nation. This research generates data by conducting a case study on a woman's business in Bangladesh. This study yields unique insights by unfolding a specific form of superstition that attempts to restrain a woman from continuing her small business. The paper reveals that the male relative caused a severe adverse impact on the personal life and business of the woman by employing superstition. With particular reference to superstition, this feminist study substantially extends the theoretical understanding of gender subordination within the context of small businesses of women in a highly patriarchal developing nation. The research strongly suggests policymakers to consider familial issues of women business‐owners in designing programmes to empower them effectively.