Using digital tools in clinical, health and social care research:a mixed-methods study of UK stakeholders

Objective: The COVID-19 pandemic accelerated changes to clinical research methodology, with clinical studies being carried out via online/remote means. This mixed-methods study aimed to identify which digital tools are currently used across all stages of clinical research by stakeholders in clinical, health and social care research and investigate their experience using digital tools.Design: Two online surveys followed by semistructured interviews were conducted. Interviews were audiorecorded, transcribed and analysed thematically.Setting, participants: To explore the digital tools used since the pandemic, survey participants (researchers and related staff (n=41), research and development staff (n=25)), needed to have worked on clinical, health or social care research studies over the past 2 years (2020–2022) in an employing organisation based in the West Midlands region of England (due to funding from a regional clinical research network (CRN)). Survey participants had the opportunity to participate in an online qualitative interview to explore their experiences of digital tools in greater depth (n=8).Results: Six themes were identified in the qualitative interviews: ‘definition of a digital tool in clinical research’; ‘impact of the COVID-19 pandemic’; ‘perceived benefits/drawbacks of digital tools’; ‘selection of a digital tool’; ‘barriers and overcoming barriers’ and ‘future digital tool use’. The context of each theme is discussed, based on the interview results.Conclusions: Findings demonstrate how digital tools are becoming embedded in clinical research, as well as the breadth of tools used across different research stages. The majority of participants viewed the tools positively, noting their ability to enhance research efficiency. Several considerations were highlighted; concerns about digital exclusion; need for collaboration with digital expertise/clinical staff, research on tool effectiveness and recommendations to aid future tool selection. There is a need for the development of resources to help optimise the selection and use of appropriate digital tools for clinical research staff and participants

Role of aberrant PI3K pathway activation in gallbladder tumorigenesis

The PI3K/AKT pathway governs a plethora of cellular processes, including cell growth, proliferation, and metabolism, in response to growth factors and cytokines. By acting as a unique lipid phosphatase converting phosphatidylinositol-3,4,5,-trisphosphate (PIP3) to phosphatidylinositol-4,5,-bisphosphate (PIP2), phosphatase and tensin homolog (PTEN) acts as the major cellular suppressor of PI3K signaling and AKT activation. Recently, PI3K mutations and loss/mutation of PTEN have been characterized in human gallbladder tumors; whether aberrant PTEN/PI3K pathway plays a causal role in gallbladder carcinogenesis, however, remains unknown. Herein we show that in mice, deregulation of PI3K/AKT signaling is sufficient to transform gallbladder epithelial cells and trigger fully penetrant, highly proliferative gallbladder tumors characterized by high levels of phospho-AKT. Histopathologically, these mouse tumors faithfully resemble human adenomatous gallbladder lesions. The identification of PI3K pathway deregulation as both an early event in the neoplastic transformation of the gallbladder epithelium and a main mechanism of tumor growth in Pten heterozygous and Pten mutant mouse models provides a new framework for studying in vivo the efficacy of target therapies directed against the PI3K pathway, as advanced metastatic tumors are often addicted to “trunkular” mutations

Modulation of LISA free-fall orbits due to the Earth-Moon system

We calculate the effect of the Earth-Moon (EM) system on the free-fall motion of LISA test masses. We show that the periodic gravitational pulling of the EM system induces a resonance with fundamental frequency 1 yr^-1 and a series of periodic perturbations with frequencies equal to integer harmonics of the synodic month (9.92 10^-7 Hz). We then evaluate the effects of these perturbations (up to the 6th harmonics) on the relative motions between each test masses couple, finding that they range between 3mm and 10pm for the 2nd and 6th harmonic, respectively. If we take the LISA sensitivity curve, as extrapolated down to 10^-6 Hz, we obtain that a few harmonics of the EM system can be detected in the Doppler data collected by the LISA space mission. This suggests that the EM system gravitational near field could provide an absolute calibration for the LISA sensitivity at very low frequencies.Comment: 15 pages, 5 figure

A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer

Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten-loss driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. Conversely, this response is bypassed upon deletion of either Trp53 or Lrf together with Pten, leading to the development of castration resistant prostate cancer (CRPC). Mechanistically, the integrated acquisition of data from mouse models and patients identifies the expression patterns of XAF1-XIAP/SRD5A1 as a predictive and actionable signature for CRPC. Importantly, we show that combined inhibition of XIAP, SRD5A1, and AR pathways overcomes castration resistance. Thus, our co-clinical approach facilitates stratification of patients and the development of tailored and innovative therapeutic treatments

Optical nanofibers and spectroscopy

We review our recent progress in the production and characterization of tapered optical fibers with a sub-wavelength diameter waist. Such fibers exhibit a pronounced evanescent field and are therefore a useful tool for highly sensitive evanescent wave spectroscopy of adsorbates on the fiber waist or of the medium surrounding. We use a carefully designed flame pulling process that allows us to realize preset fiber diameter profiles. In order to determine the waist diameter and to verify the fiber profile, we employ scanning electron microscope measurements and a novel accurate in situ optical method based on harmonic generation. We use our fibers for linear and non-linear absorption and fluorescence spectroscopy of surface-adsorbed organic molecules and investigate their agglomeration dynamics. Furthermore, we apply our spectroscopic method to quantum dots on the surface of the fiber waist and to caesium vapor surrounding the fiber. Finally, towards dispersive measurements, we present our first results on building and testing a single-fiber bi-modal interferometer.Comment: 13 pages, 18 figures. Accepted for publication in Applied Physics B. Changes according to referee suggestions: changed title, clarification of some points in the text, added references, replacement of Figure 13

Health problems and help-seeking in a nationwide sample of operational Norwegian ambulance personnel

Background To estimate the prevalence of anxiety and depression symptoms, and their association with professional help-seeking, among operational ambulance personnel and a general working population, and to study the symptoms of musculoskeletal pain and disturbed sleep among ambulance personnel. Methods The results of a comprehensive nationwide questionnaire survey of operational ambulance personnel (n = 1180) were compared with the findings of a population-based Norwegian health study of working people (n = 31,987). The questionnaire included measures of help-seeking, the Hospital Anxiety and Depression Scale, the Subjective Health Complaints Questionnaire, the Karolinska Sleep Questionnaire and the Need for Recovery after Work Scale. Results Compared with those in the reference population, the mean of level anxiety symptoms in the ambulance sample was lower for men (3.5 vs. 3.9, P < 0.001) and women (4.0 vs. 4.4, P < 0.05), and the mean level of depression symptoms in ambulance workers was lower for men (2.3 vs. 2.8, P < 0.05) but not for women (2.9 vs. 3.1, P = 0.22). A model adjusted for anxiety and depression symptoms indicated that ambulance personnel had lower levels of help-seeking except for seeing a chiropractor (12% vs. 5%, P < 0.01). In the ambulance sample, symptoms of musculoskeletal pain were most consistently associated with help-seeking. In the adjusted model, only symptoms of disturbed sleep were associated with help-seeking from a psychologist/psychiatrist (total sample = 2.3%). Help-seeking was more often reported by women but was largely unaffected by age. Conclusion The assumption that ambulance personnel have more anxiety and depression symptoms than the general working population was not supported. The level of musculoskeletal pain and, accordingly, the level of help-seeking from a chiropractor were higher for ambulance workers. More research should address the physical strains among ambulance personnel

Numerical solution of a pursuit-evasion differential game involving two spacecraft in low earth orbit

This paper considers a spacecraft pursuit-evasion problem taking place in low earth orbit. The problem is formulated as a zero-sum differential game in which there are two players, a pursuing spacecraft that attempts to minimize a payoff, and an evading spacecraft that attempts to maximize the same payoff. We introduce two associated optimal control problems and show that a saddle point for the differential game exists if and only if the two optimal control problems have the same optimal value. Then, on the basis of this result, we propose two computational methods for determining a saddle point solution: a semi-direct control parameterization method (SDCP method), which is based on a piecewise-constant control approximation scheme, and a hybrid method, which combines the new SDCP method with the multiple shooting method. Simulation results show that the proposed SDCP and hybrid methodsare superior to the semi-direct collocation nonlinear programming method (SDCNLP method), which is widely used to solve pursuit-evasion problems in the aerospace field