Multiscale mechanical characterisation of the craniofacial system under external forces.

Premature fusion of craniofacial joints, i.e. sutures, is a major clinical condition. This condition affects children and often requires numerous invasive surgeries to correct. Minimally invasive external loading of the skull has shown some success in achieving therapeutic effects in a mouse model of this condition, promising a new non-invasive treatment approach. However, our fundamental understanding of the level of deformation that such loading has induced across the sutures, leading to the effects observed is severely limited, yet crucial for its scalability. We carried out a series of multiscale characterisations of the loading effects on normal and craniosynostotic mice, in a series of in vivo and ex vivo studies. This involved developing a custom loading setup as well as software for its control and a novel in situ CT strain estimation approach following the principles of digital volume correlation. Our findings highlight that this treatment may disrupt bone formation across the sutures through plastic deformation of the treated suture. The level of permanent deformations observed across the coronal suture after loading corresponded well with the apparent strain that was estimated. This work provides invaluable insight into the level of mechanical forces that may prevent early fusion of cranial joints during the minimally invasive treatment cycle and will help the clinical translation of the treatment approach to humans.

A review of pre-hospital extracorporeal cardiopulmonary resuscitation and its potential application in the North East of England.

Patients in the UK who suffer an out-of-hospital cardiac arrest are treated with cardiopulmonary resuscitation in the pre-hospital environment. Current survival outcomes are low in out-of-hospital cardiac arrest. Extracorporeal cardiopulmonary resuscitation is a technique which is offered to patients in specialised centres which provides better blood flow and oxygen delivery than conventional chest compressions. Shortening the interval between cardiac arrest and restoration of circulation is associated with improved outcomes in extracorporeal cardiopulmonary resuscitation. Delivering extracorporeal cardiopulmonary resuscitation in the pre-hospital environment can shorten this interval, improving outcomes in out-of-hospital cardiac arrest. This article will review recently published studies and summarise studies currently being undertaken in pre-hospital extracorporeal cardiopulmonary resuscitation. It will also discuss the potential application of a pre-hospital extracorporeal cardiopulmonary resuscitation programme in the North East of England.

Intake of Energy Drinks Before and During Pregnancy and Adverse Pregnancy Outcomes.

Importance: Consumption of energy drinks has increased drastically in recent years, particularly among young people. It is unknown whether intake of energy drinks is associated with health during pregnancy. Objective: To examine associations of energy drink intake before and during pregnancy with risk of adverse pregnancy outcomes (APOs). Design, Setting, and Participants: This prospective cohort study included data from women enrolled in the Nurses' Health Study 3 (NHS3) between June 1, 2010, and September 27, 2021, and the Growing Up Today Study (GUTS) who reported 1 or more singleton pregnancy from January 1, 2011, to June 1, 2019. Data were analyzed from October 1, 2021, to September 28, 2023. Exposure: Intake of energy drinks, assessed by food frequency questionnaire. Main Outcomes and Measures: The main outcomes were self-reported APOs, including pregnancy loss, gestational diabetes, gestational hypertension, preeclampsia, or preterm birth, and a composite APO, defined as development of any of the APOs. Risk of APOs was compared between consumers and nonconsumers of energy drinks. Results: This study included 7304 pregnancies in 4736 participants with information on prepregnancy energy drink intake and 4559 pregnancies in 4559 participants with information on energy drink intake during pregnancy. There were 1691 GUTS participants (mean [SD] age, 25.7 [2.9] years) and 3045 NHS3 participants (mean [SD] age, 30.2 [4.1] years). At baseline, 230 GUTS participants (14%) and 283 NHS3 participants (9%) reported any intake of energy drinks. While no associations were found for pregnancy loss (odds ratio [OR], 0.89; 95% CI, 0.71-1.11), preterm birth (OR, 1.07; 95% CI, 0.71-1.61), gestational diabetes (OR, 0.89; 95% CI, 0.58-1.35), preeclampsia (OR, 0.73; 95% CI, 0.41-1.30), or the composite APO (OR, 1.05; 95% CI, 0.87-1.26), prepregnancy energy drink use was associated with a higher risk of gestational hypertension (OR, 1.60; 95% CI, 1.12-2.29). A significant interaction was found between age and energy drink intake in relation to hypertensive disorders (P = .02 for interaction for gestational hypertension; P = .04 for interaction for any hypertensive disorders), with stronger associations for participants above the median age. No associations of energy drink intake during pregnancy with any of the APOs were found in NHS3 (eg, any APO: OR, 0.86; 95% CI, 0.41-1.79). Conclusions and Relevance: In this study, energy drink intake before pregnancy was associated with an elevated risk of gestational hypertension. Given the low prevalence of energy drink intake and low consumption levels among users, the results should be interpreted cautiously.

Finding Voices: a survey of young people's experiences of the ED.

BACKGROUND: Mental health presentations in young people are increasing. Recurrence of self-harm (SH) presentations is common and of great concern since self-harm is known to be a risk factor for suicide. Previous reports suggest that the ED experience for this group is poor. A study was carried out at the Royal Berkshire NHS Foundation Trust. The objective was to pilot new and existing measures to capture the perceived needs and expectations of young people attending ED following SH compared with those attending with suspected fractures (SFs). METHODS: Young people were approached to complete a questionnaire as they arrived in ED and again before they left. Questionnaires were a combination of pre-existing tools as well as piloting novel questions specific to the ED where no suitable tool previously existed. Satisfaction with the ED treatment was measured along with reattendance up to one year later. RESULTS: The survey was started in 2019 and suspended in March 2020 at the outset of the COVID-19 pandemic and subsequently closed, having screened 917 and recruited 104 adolescents. All the measures showed satisfactory psychometric properties with internal consistencies (alpha) of over 0.75. The two patient groups differed at baseline: it was found that the SH group had lower mood on the Short Mood and Feelings Questionnaire (p<0.001) and scored more highly on the Borderline Personality Features Scale for Children than the SF group (p<0.001) but the expectations of care across both groups was similar. Using the experience measures, the SH group was less satisfied with treatment than the SF group (p=0.0263). CONCLUSION: Our findings underline the similarities between the two groups in terms of their expectations of care. Terminating the study early at the outset of the COVID-19 pandemic has precluded any further firm conclusions to be drawn. Further research is needed.

Encouraging and Detecting Preferential Incipient Slip for Use in Slip Prevention in Robot-Assisted Surgery.

Robotic surgical platforms have helped to improve minimally invasive surgery; however, limitations in their force feedback and force control can result in undesirable tissue trauma or tissue slip events. In this paper, we investigate a sensing method for the early detection of slip events when grasping soft tissues, which would allow surgical robots to take mitigating action to prevent tissue slip and maintain stable grasp control while minimising the applied gripping force, reducing the probability of trauma. The developed sensing concept utilises a curved grasper face to create areas of high and low normal, and thus frictional, force. In the areas of low normal force, there is a higher probability that the grasper face will slip against the tissue. If the grasper face is separated into a series of independent movable islands, then by tracking their displacement it will be possible to identify when the areas of low normal force first start to slip while the remainder of the tissue is still held securely. The system was evaluated through the simulated grasping and retraction of tissue under conditions representative of surgical practice using silicone tissue simulants and porcine liver samples. It was able to successfully detect slip before gross slip occurred with a 100% and 77% success rate for the tissue simulant and porcine liver samples, respectively. This research demonstrates the efficacy of this sensing method and the associated sensor system for detecting the occurrence of tissue slip events during surgical grasping and retraction.

Towards Autonomous Robotic Minimally Invasive Ultrasound Scanning and Vessel Reconstruction on Non-Planar Surfaces.

Autonomous robotic Ultrasound (US) scanning has been the subject of research for more than 2 decades. However, little work has been done to apply this concept into a minimally invasive setting, in which accurate force sensing is generally not available and robot kinematics are unreliable due to the tendon-driven, compliant robot structure. As a result, the adequate orientation of the probe towards the tissue surface remains unknown and the anatomy reconstructed from scan may become highly inaccurate. In this work we present solutions to both of these challenges: an attitude sensor fusion scheme for improved kinematic sensing and a visual, deep learning based algorithm to establish and maintain contact between the organ surface and the US probe. We further introduce a novel scheme to estimate and orient the probe perpendicular to the center line of a vascular structure. Our approach enables, for the first time, to autonomously scan across a non-planar surface and navigate along an anatomical structure with a robotically guided minimally invasive US probe. Our experiments on a vessel phantom with a convex surface confirm a significant improvement of the reconstructed curved vessel geometry, with our approach strongly reducing the mean positional error and variance. In the future, our approach could help identify vascular structures more effectively and help pave the way towards semi-autonomous assistance during partial hepatectomy and the potential to reduce procedure length and complication rates.

A systematic review of adverse health effects associated with oral cadmium exposure.

Scientific data characterizing the adverse health effects associated with dietary cadmium (Cd) exposure were identified in order to make informed decisions about the most appropriate toxicological reference value (TRV) for use in assessing dietary Cd exposure. Several TRVs are available for Cd and regulatory organizations have used epidemiologic studies to derive these reference values; however, risk of bias (RoB) evaluations were not included in the assessments. We performed a systematic review by conducting a thorough literature search (through January 4, 2020). There were 1714 references identified by the search strings and 328 studies identified in regulatory assessments. After applying the specific inclusion and exclusion criteria, 208 studies (Human: 105, Animal: 103) were considered eligible for further review and data extraction. For the epidemiologic and animal studies, the critical effects identified for oral Cd exposure from the eligible studies were a decrease in bone mineral density (BMD) and renal tubular degeneration. A RoB analysis was completed for 49 studies (30 epidemiological and 19 animal) investigating these endpoints. The studies identified through the SR that were considered high quality and low RoB (2 human and 5 animal) can be used to characterize dose-response relationships and inform the derivation of a Cd TRV.

Mechanical loading of cranial joints minimizes the craniofacial phenotype in Crouzon syndrome.

Children with syndromic forms of craniosynostosis undergo a plethora of surgical interventions to resolve the clinical features caused by the premature fusion of cranial sutures. While surgical correction is reliable, the need for repeated rounds of invasive treatment puts a heavy burden on the child and their family. This study explores a non-surgical alternative using mechanical loading of the cranial joints to prevent or delay craniofacial phenotypes associated with Crouzon syndrome. We treated Crouzon syndrome mice before the onset of craniosynostosis by cyclical mechanical loading of cranial joints using a custom designed set-up. Cranial loading applied to the frontal bone partially restores normal skull morphology, significantly reducing the typical brachycephalic appearance. This is underpinned by the delayed closure of the coronal suture and of the intersphenoidal synchondrosis. This study provides a novel treatment alternative for syndromic craniosynostosis which has the potential to be an important step towards replacing, reducing or refining the surgical treatment of all craniosynostosis patients.

HAILO: A Sensorised Hand Splint for the Exploration of Interface Forces.

This study presents the design and development of an instrumented splint for measuring the biomechanical effects of hand splinting and for assessing interface loading characteristics for people with arthritis. Sixteen multi-axial soft load-sensing nodes were mounted on the splint-skin interface of a custom 3D printed thumb splint. The splint was used to measure the interface forces between splint and hand in 12 healthy participants in 6 everyday tasks. Forces were compared between a baseline relaxed hand position and during states of active use. These data were used to generate a measure of sensor activity across the splint surface. Through direct comparison with a commercial splint, the 3D printed splint was deemed to provide similar levels of support. Observation of the activity across the 16 sensors showed that 'active' areas of the splint surface varied between tasks but were commonly focused at the base of the thumb. Our findings show promise in the ability to detect the changing forces imparted on the hand by the splint surface, objectively characterising their behaviour. This opens the opportunity for future study into the biomechanical effects of splints on arthritic thumbs to improve this important intervention and improve quality of life.

U.S. adults noticing and using menu calorie information: Analysis of the National Cancer Institute's Health Information National Trends Survey Data.

FDA's Menu Labeling Final Rule requires covered establishments provide calorie information on menus or menu boards, among other requirements. This study describes correlates of noticing and using menu calorie information in a nationally representative sample of U.S. adults before implementation of the Final Rule in May 2018. Data from the 2018 National Cancer Institute Health Information National Trends Survey was used to assess noticing menu calorie information, using menu calorie information to change menu ordering behavior, and knowledge of daily calorie needs. Regression analysis of weighted data tested associations between individual characteristics and noticing and using menu calorie information. Nearly half of adults (44%) reported noticing menu calorie information. Women, younger individuals, those who seek health information, individuals with a BMI ≥ 30, and those with higher education or higher income were more likely to report noticing menu calorie information. Among adults who reported noticing menu calorie information, three-quarters responded by ordering less (e.g., fewer calories), which equates to about one-third of the population. About 36% of women and 42% of men lacked calorie knowledge. Men with, versus without, calorie knowledge were twice as likely to report noticing menu calorie information (adjusted OR 2.23 95% CI 1.51, 3.29). Findings suggest behavioral response to menu calorie information varies and most individuals who notice the information respond by ordering less in ways that could reduce caloric intake. Future analyses could compare noticing and using menu calorie information before and after menu labeling implementation to assess the effect of policy on population behaviors.

ß-hydroxybutyrate accumulates in the rat heart during low-flow ischaemia with implications for functional recovery.

Extrahepatic tissues which oxidise ketone bodies also have the capacity to accumulate them under particular conditions. We hypothesised that acetyl-coenzyme A (acetyl-CoA) accumulation and altered redox status during low-flow ischaemia would support ketone body production in the heart. Combining a Langendorff heart model of low-flow ischaemia/reperfusion with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), we show that ß-hydroxybutyrate (ß-OHB) accumulated in the ischaemic heart to 23.9 nmol/gww and was secreted into the coronary effluent. Sodium oxamate, a lactate dehydrogenase (LDH) inhibitor, increased ischaemic ß-OHB levels 5.3-fold and slowed contractile recovery. Inhibition of ß-hydroxy-ß-methylglutaryl (HMG)-CoA synthase (HMGCS2) with hymeglusin lowered ischaemic ß-OHB accumulation by 40%, despite increased flux through succinyl-CoA-3-oxaloacid CoA transferase (SCOT), resulting in greater contractile recovery. Hymeglusin also protected cardiac mitochondrial respiratory capacity during ischaemia/reperfusion. In conclusion, net ketone generation occurs in the heart under conditions of low-flow ischaemia. The process is driven by flux through both HMGCS2 and SCOT, and impacts on cardiac functional recovery from ischaemia/reperfusion.

Cyberpsychiatry versus COVID-19: using video consultation to improve clinical care in an in-patient psychiatric unit.

The COVID-19 pandemic has resulted in unique challenges for in-patients across the National Health Service as visitors, both family and friends, are prevented from visiting patients owing to infection prevention and control measures. The Attend Anywhere platform was used as the basis of a quality improvement project to mitigate the detrimental effects of reduced social contact for patients. The use of video conferencing led to increased subjective satisfaction for both patients and healthcare professionals, thereby providing further evidence of the benefit that this emerging technology has on healthcare delivery.

Acute mental health presentations before and during the COVID-19 pandemic.

BACKGROUND: A number of community based surveys have identified an increase in psychological symptoms and distress but there has been no examination of symptoms at the more severe end of the mental health spectrum. AIMS: We aimed to analyse numbers and types of psychiatric presentations to inform planning for future demand on mental health services in light of the COVID-19 pandemic. METHOD: We analysed electronic data between January and April 2020 for 2534 patients referred to acute psychiatric services, and tested for differences in patient demographics, symptom severity and use of the Mental Health Act 1983 (MHA), before and after lockdown. We used interrupted time-series analyses to compare trends in emergency department and psychiatric presentations until December 2020. RESULTS: There were 22% fewer psychiatric presentations the first week and 48% fewer emergency department presentations in the first month after lockdown initiated. A higher proportion of patients were detained under the MHA (22.2 v. 16.1%) and Mental Capacity Act 2005 (2.2 v. 1.1%) (χ2(2) = 16.3, P < 0.0001), and they experienced a longer duration of symptoms before seeking help from mental health services (χ2(3) = 18.6, P < 0.0001). A higher proportion of patients presented with psychotic symptoms (23.3 v. 17.0%) or delirium (7.0 v. 3.6%), and fewer had self-harm behaviour (43.8 v. 52.0%, χ2(7) = 28.7, P < 0.0001). A higher proportion were admitted to psychiatric in-patient units (22.2 v. 18.3%) (χ2(6) = 42.8, P < 0.0001) after lockdown. CONCLUSIONS: UK lockdown resulted in fewer psychiatric presentations, but those who presented were more likely to have severe symptoms, be detained under the MHA and be admitted to hospital. Psychiatric services should ensure provision of care for these patients as well as planning for those affected by future COVID-19 waves.

Adjustable Compliance Soft Sensor via an Elastically Inflatable Fluidic Dome.

Soft sensors are essential for robotic systems to safely interact with humans and the environment. Although significant research has been carried out in the field of soft tactile sensing, most of these sensors are restricted to a predefined geometry and a fixed measurement range, hence limiting their application. This paper introduces a novel approach to soft sensing by proposing a soft load-sensing unit with an adjustable mechanical compliance achieved using an elastically inflatable fluidic dome. The sensor consists of a three-dimensional Hall-effect sensor, above which is a magnet whose movement is modulated by an intermediate elastomeric dome structure. Sensor configurations were designed and fabricated using three different silicone rubbers to cover '00-10' and '20A' durometer shore hardness scales. We demonstrated that the compliance of the sensor could be dynamically tuned by changing the internal pressure of the inflatable fluidic dome in all configurations. We performed finite element simulations to determine the reaction force of the sensor under load as well as the stresses within the internal structural behavior, which are not possible to capture experimentally. The proposed soft sensor has the potential to be readily adapted for use in various soft robotic applications of differing size, compliance range, and safety requirements.

Health Disparities in Calorie Knowledge and Confidence Among the U.S. Adult Population.

PURPOSE: Obesity prevalence has reached an all-time high in the US, affecting >40% of the population. This study's objective was to evaluate associations between demographics and self-reported calorie knowledge and self-perceived confidence in calorie knowledge ("calorie confidence"). The relationships between body mass index (BMI) and calorie knowledge and confidence were also explored. METHODS: We analyzed data from participants (n = 2171) in the crosssectional, nationally representative 2019 FDA Food Safety and Nutrition Survey using logistic regression to estimate adjusted odds ratios (AORs) and confidence intervals (95% CIs) for associations between BMI and calorie knowledge (correct/incorrect), calorie confidence (confident/not confident), and demographic characteristics, and the Wald chi square test to evaluate relationships between BMI and both calorie knowledge and confidence. RESULTS: Many of the same subgroups were more likely than others to report lack of calorie knowledge and lack of confidence in knowing the typical daily calorie intake needed to maintain a healthy weight [respective AORs (95% CIs): age (years), >60 vs 51-60, 1.7 (1.1-2.5), and 1.4 (1.0-2.0); sex, male vs female, 1.7 (1.3-2.3), and 1.7 (1.3-2.1); race/ethnicity, non-Hispanic Black vs non-Hispanic white, 3.4 (2.1-5.5), and 2.4 (1.6-3.8); education, ≤high school vs college grad, 1.5 (1.0- 2.3), and 1.9 (1.3-2.7)]. BMI was significantly correlated with calorie confidence (P = .047), such that those reporting less confidence were more likely overweight or obese [underweight/healthy (BMI < 25): 29%, overweight (25 ≤ BMI < 30): 34%, obese (BMI ≥ 30): 37%]. CONCLUSION: In certain demographic subgroups associations between calorie knowledge and confidence differed. Tailored education and outreach for these groups may help to address these disparities.

Containing COVID: the establishment and management of a COVID-19 ward in an adult psychiatric hospital.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) epidemic in the UK emerged and escalated, clinicians working in mental health in-patient facilities faced unique medical, psychiatric and staffing challenges in managing and containing the impact of the virus and, in the context of legislation, enforcing social distancing. AIMS: To describe (a) the steps taken by one mental health hospital to establish a COVID-19 isolation ward for adult psychiatric in-patients and (b) how staff addressed the challenges that emerged over the period March to June 2020. METHOD: A descriptive study detailing the processes involved in changing the role of the ward and the measures taken to address the various challenges that arose. Brief clinical cases of two patients are included for illustrative purposes. RESULTS: We describe the achievements, lessons learned and outcomes of the process of repurposing a mental health triage ward into a COVID-19 isolation facility, including the impact on staff. Flexibility, rapid problem-solving and close teamwork were essential. Some of the changes made will be sustained on the ward in our primary role as a triage ward. CONCLUSIONS: Although the challenges faced were difficult, the legacy they have left is that of a range of improvements in patient care and the working environment.

IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway.

Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC. Significant inhibition of AR regulated gene expression was observed upon siRNA-mediated IKBKE depletion or pharmacological inhibition due to inhibited AR gene expression in multiple cell line models including a LNCaP derivative cell line resistant to the anti-androgen, enzalutamide (LNCaP-EnzR). Phenotypically, this resulted in significant inhibition of proliferation, migration and colony forming ability suggesting that targeting IKBKE could circumvent resistance to AR targeting therapies. Indeed, pharmacological inhibition in the CWR22Rv1 xenograft mouse model reduced tumour size and enhanced survival. Critically, this was validated in patient-derived explants where enzymatic inactivation of IKBKE reduced cell proliferation and AR expression. Mechanistically, we provide evidence that IKBKE regulates AR levels via Hippo pathway inhibition to reduce c-MYC levels at cis-regulatory elements within the AR gene. Thus, IKBKE is a therapeutic target in advanced PC suggesting repurposing of clinically tested IKBKE inhibitors could be beneficial to castrate resistant PC patients.

Design and Evaluation of Magnetic Hall Effect Tactile Sensors for Use in Sensorized Splints.

Splinting techniques are widely used in medicine to inhibit the movement of arthritic joints. Studies into the effectiveness of splinting as a method of pain reduction have generally yielded positive results, however, no significant difference has been found in clinical outcomes between splinting types. Tactile sensing has shown great promise for the integration into splinting devices and may offer further information into applied forces to find the most effective methods of splinting. Hall effect-based tactile sensors are of particular interest in this application owing to their low-cost, small size, and high robustness. One complexity of the sensors is the relationship between the elastomer geometry and the measurement range. This paper investigates the design parameters of Hall effect tactile sensors for use in hand splinting. Finite element simulations are used to locate the areas in which sensitivity is high in order to optimise the deflection range of the sensor. Further simulations then investigate the mechanical response and force ranges of the elastomer layer under loading which are validated with experimental data. A 4 mm radius, 3 mm-thick sensor is identified as meeting defined sensing requirements for range and sensitivity. A prototype sensor is produced which exhibits a pressure range of 45 kPa normal and 6 kPa shear. A proof of principle prototype demonstrates how this can be integrated to form an instrumented splint with multi-axis sensing capability and has the potential to inform clinical practice for improved splinting.

A Review of Wearable Sensor Systems to Monitor Plantar Loading in the Assessment of Diabetic Foot Ulcers.

Diabetes is highly prevalent throughout the world and imposes a high economic cost on countries at all income levels. Foot ulceration is one devastating consequence of diabetes, which can lead to amputation and mortality. Clinical assessment of diabetic foot ulcer (DFU) is currently subjective and limited, impeding effective diagnosis, treatment and prevention. Studies have shown that pressure and shear stress at the plantar surface of the foot plays an important role in the development of DFUs. Quantification of these could provide an improved means of assessment of the risk of developing DFUs. However, commercially-available sensing technology can only measure plantar pressures, neglecting shear stresses and thus limiting their clinical utility. Research into new sensor systems which can measure both plantar pressure and shear stresses are thus critical. Our aim in this paper is to provide the reader with an overview of recent advances in plantar pressure and stress sensing and offer insights into future needs in this critical area of healthcare. Firstly, we use current clinical understanding as the basis to define requirements for wearable sensor systems capable of assessing DFU. Secondly, we review the fundamental sensing technologies employed in this field and investigate the capabilities of the resultant wearable systems, including both commercial and research-grade equipment. Finally, we discuss research trends, ongoing challenges and future opportunities for improved sensing technologies to monitor plantar loading in the diabetic foot.