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The BepiColombo Mercury Imaging X-ray Spectrometer: science goals, instrument performance and operations
No full textThe Mercury Imaging X-ray Spectrometer is a highly novel instrument that is designed to map Mercury’s elemental composition from orbit at two angular resolutions. By observing the fluorescence X-rays generated when solar-coronal X-rays and charged particles interact with the surface regolith, MIXS will be able to measure the atomic composition of the upper ~10- 20 μm of Mercury’s surface on the day-side. Through precipitating particles on the night-side,MIXS will also determine the dynamic interaction of the planet’s surface with the surrounding space environment. MIXS is composed of two complementary elements: MIXS-C is a collimated instrument which will achieve global coverage at a similar spatial resolution to that achieved (in the northern hemisphere only – i.e. ~ 50 – 100 km) by MESSENGER; MIXS-T is the first ever X-ray telescope to be sent to another planet and will, during periods of high solar activity (or intense precipitation of charged particles), reveal the X-ray flux from Mercury at better than 10 km resolution. The design, performance, scientific goals and operations plans of the instrument are discussed, including the initial results from commissioning in space
Identifying suicide and self-harm research priorities in North West England: a Delphi study.
No full textBackground: Understanding and effectively managing self-harm and suicide requires collaborative research between stakeholders focused on shared priorities. Aims: To develop a consensus about suicide and self-harm research priorities in the North-West of England using the Delphi method. Method: Items for the Delphi survey were generated through group discussions at a workshop with 88 stakeholders and subsequent thematic analysis of key themes. Forty-four participants who were experts-by-experience, researchers, and clinicians based within health services including third sector organisations completed the Delphi survey. Results: A three-round survey reached consensus on 55 research priority items identifying key priorities in each of the following groups: offenders, children and young people, self-harm in community settings, and crisis care in the community. Limitation: The pool of delegates at the workshop and subsequent self-selection into the Delphi may have introduced bias into the study. Conclusion: The current paper highlights specific actionable priorities were identified in four areas that can be used to inform research efforts and future policy and practice, based on shared areas of perceived importance and concern. Future work is needed to confirm the significance of these priority areas, including the use of evidence synthesis approaches to ascertain the extent to which these priorities have already been investigated and where gaps in understanding remain
Timing of Hypoglycaemia in Patients with Hyperinsulinism (HI): Extension of the Digital Phenotype
No full textBackgroundHyperinsulinism (HI) due to excess and dysregulated insulin secretion is the most common cause of severe and recurrent hypoglycaemia in childhood. High cerebral glucose utilisation in the early hours results in high risk of hypoglycaemia for people with diabetes and carries a significant risk of brain injury. Prevention of hypoglycaemia is the cornerstone of management for HI but the risk of hypoglycaemia at night or indeed the timing of hypoglycaemia in children with HI have not been studied, and thus the digital phenotype remains incomplete and management suboptimal. ObjectiveWe aimed to quantify the timing of hypoglycaemia in patients with HI, to describe glycaemic variability and to extend the digital phenotype. This will facilitate future work using computational modelling to enable behaviour change and reduce exposure of HI patients to injurious hypoglycaemia events. MethodsPatients underwent Continuous Glucose Monitoring (CGM) with a Dexcom G4 or G6 CGM device as part of their clinical assessment for either HI (n = 23) or Idiopathic Ketotic Hypoglycaemia (IKH) (n = 24). CGM data was analysed for temporal trends. Hypoglycaemia was defined as glucose < 3.5mmol/L. Results449 hypoglycaemia events totalling 15,610 minutes were captured over a total of 237 days from 47 patients (29 male, mean age 70 months). Mean length of hypoglycaemia event was 35 minutes. There was a clear tendency to hypoglycaemia in the early hours (0300H to 0700H), particularly for those HI patients over 10 months of age where 7.6% of time (1480/19370 minutes) in this period was in hypoglycaemia compared to 2.6% (2405/92840 minutes) outside (P < .001). This tendency was less pronounced in HI patients under 10 months and those negative for genetic mutations as well as those patients with IKH. Despite real-time CGM, there were 42 hypoglycaemia events from 13 separate HI patients lasting > 30 minutes. ConclusionsIn this study, we have taken the first step in extending the digital phenotype of HI by describing the glycaemic trends and identifying the timings of hypoglycaemia measured by CGM. We have identified the early hours as a time of high hypoglycaemia risk for patients with HI and demonstrated that simple provision of CGM data to patients is not sufficient to eliminate hypoglycaemia. Future work in HI should concentrate on the early hours as a period of high risk for hypoglycaemia and must target personalised hypoglycaemia predictions. Focus must move to the human-computer interaction as an aspect of the digital phenotype that is susceptible to change rather than simple mathematical modelling to produce small improvements in hypoglycaemia prediction accuracy
How can children of imprisoned parents in the UK be supported in school?
No full textIf not supported appropriately, children of imprisoned parents face potential adverse outcomes, including difficulties with academic progress and mental health (Department for Education, 2019; Glover, 2009; Kincaid, Roberts & Kane, 2019; Murray & Farrington, 2008). This systematic literature review aims to explore ways in which children of imprisoned parents in the UK can be supported in school. Research databases and publication records from third sector organisations were searched. Eleven papers were included in the review and results highlighted a number of ways in which children of imprisoned parents can be supported in schools at a systemic, familial and individual level. Implications for schools, educational psychologists and future research are discussed
Exploring the Demographic and Situational Characteristics of Older British People experiencing Loneliness as positive within the BBC Loneliness Experiment
No full textThe aim of this study is to increase the understanding of loneliness experienced as positive, by exploring the demographic and situational characteristics of older people who experience loneliness as positive. Two binary logistic regressions were conducted using data from those aged 60+ from the BBC Loneliness Experiment (N= 5250). The first binary logistic regression compared participants who experience loneliness always as positive (N=219) to those participants who never experience loneliness as positive (N=3004). Spending time alone did not emerge as relevant to experiencing loneliness as positive, but enjoying time alone was important (OR = 1.561 (95% CI = 1.313−1.856)). The lonelier older people were, the less likely they experienced loneliness as positive (OR = 0.708 (95% CI =0.644−0.779)). Men were more likely to experience loneliness as positive compared to women (OR = 1.734 (95% CI = 1.269−2.370)). Lastly, the experience of loneliness as positive was likely to decrease when older people had more years of education (OR = 0.887 (95% CI = 0.853−0.921)) but increased with age (OR = 1.067 (95% CI = 1.037−1.098)). The results of the second binary logistic regression comparing participants who indicated loneliness purely as positive with those participants indicate to experience loneliness sometimes as positive (N=2027), are in line with the first regression analyses. The results are critically discussed by emphasizing the role of norms and cultures, gerotranscendence, and severity of loneliness, which might influence the experiences of loneliness. Further qualitative research is needed to elucidate the meanings of these positive experiences of loneliness
Cardiac Ion Channels Associated with Unexplained Stillbirth – An Immunohistochemical Study
No full textIntroductionDespite the use of post-mortem investigations, approximately 20% ofstillbirths remain unexplained. Cardiac ion channelopathies have beenidentified as a cause of death in Sudden Infant Death Syndrome (SIDS)and could be associated with unexplained stillbirths. This study aimed tounderstand if the expression or localisation of cardiac ion channelsassociated with channelopathies were altered in cases of unexplainedstillbirths.Materials and MethodsA case control study was conducted using formalin-fixed cardiac tissuefrom 20 cases of unexplained stillbirth and a control group of 20 cases ofstillbirths from intrapartum hypoxia. 4μm tissue sections were stainedusing Haematoxylin and Eosin, Masson’s Trichrome (MT) and Elastic vanGieson (EVG). Immunohistochemistry (IHC) was performed usingantibodies against CACNA1G, KCNJ2, KCNQ1, KCNH2 and KCNE1. Thecardiac conduction system in samples stained with MT and EVG could notbe identified. Therefore, the levels of immunoperoxidase staining werequantified using QuPath software.ResultsThe nuclear-cytoplasmic ratio of sections stained with haematoxylin andeosin was higher for the hypoxia group (Hypoxia median 0.13 vs. 0.04unexplained, p< 0.001). CACNA1G (Unexplained median 0.26 vs.Hypoxia 0.30, p=0.009) and KCNJ2 (Unexplained median 0.35 vs.Hypoxia 0.41, p=0.001) had lower staining intensity in the unexplainedstillbirth group. There were no statistically significant differences in thestaining intensity of KCNQ1, KCNH2 and KCNE1.DiscussionTwo ion channels associated with channelopathies demonstrated lowerlevels of expression in cases of unexplained stillbirth. Further geneticstudies using human tissue should be performed to understand theassociation between channelopathies and otherwise unexplainedstillbirths
Frequency Division Multiplexer With Directional Filters in Multilayer LCP Films at - and -Band
No full textA quasi-reflectionless frequency division multiplexer (FDM) with directional filters (DFs) in multilayer liquid crystal polymer (LCP) substrates is proposed for E- and W-band applications. The in-series cascaded DFs are designed at 74, 84, and 94 GHz, each of which comprises two microstrip lines in the first layer, two pairs of coupling slots in the second layer, and loop resonators in the third layer. The distance between DFs is optimized for suppressing reflection and insertion losses, and the asymmetric distribution of DFs is designed to obtain a low profile. The experimental data demonstrate a 3-dB passband of 8.3%, 8.8%, and 9.7% centered at 74, 84, and 94 GHz, respectively, for the proposed FDM, showing a good match with the simulation. The corresponding insertion loss is measured as 3.63, 3.4, and 2.72 dB at 74, 84, and 94 GHz, respectively. The proposed device may find many applications in multiband and ultrawideband communication and radar systems
PBPK simulation-based evaluation of ganciclovir crystalluria risk factors: effect of renal impairment, old age and low fluid intake
No full textDosing guidance is often lacking for chronic kidney disease (CKD) due to exclusion ofsuch patients from pivotal clinical trials. Physiologically-based pharmacokinetic (PBPK)modelling supports model-informed dosing when clinical data are lacking, butapplication of these approaches to patients with impaired renal function is not yet at fullmaturity. In the current study, a ganciclovir PBPK model was developed for patientswith normal renal function and extended to CKD population. CKD-related changes intubular secretion were explored in the mechanistic kidney model, implemented eitheras proportional or non-proportional decline relative to GFR. Crystalluria risk wasevaluated in different clinical settings (old age, severe CKD and low fluid intake) bysimulating ganciclovir medullary collecting duct (MCD) concentrations.The ganciclovir PBPK model captured observed changes in systemic pharmacokineticendpoints in mild-to-severe CKD; these trends were evident irrespective of assumedpathophysiological mechanism of altered active tubular secretion in the model. Minimaldifference in simulated ganciclovir MCD concentrations was noted between youngadult and geriatric populations with normal renal function and urine flow (1mL/min),with lower concentrations predicted for severe CKD patients. High crystalluria risk wasidentified at reduced urine flow (0.1mL/min) as simulated ganciclovir MCDconcentrations exceeded its solubility (2.6–6 mg/mL), irrespective of underlying renalfunction. The analysis highlighted the importance of appropriate distribution of virtualsubjects’ systems data in CKD populations. The ganciclovir PBPK model illustrates theability of this translational tool to explore individual and combined effects of age, urineflow and renal impairment on local drug renal exposure
ASSOCIATIONS WITH DIGITAL PITTING IN PATIENTS WITH SYSTEMIC SCLEROSIS: RESULTS OF A RETROSPECTIVE ANALYSIS
No full textDigital pitting (loss of tissue at the fingertip), is a cardinal feature of systemic sclerosis (SSc) (1), contributing 3 of the 9 required points to fulfill the 2013 American College of Rheumatology/ European League Against Rheumatism classification criteria (2). Digital pitting is painful and has an impact on hand function, interfering with activities of everyday living (3). We recently reported that patients with digital pitting are more likely to have ‘grossly abnormal’ capillaries on nailfold capillaroscopy than those without pitting, supporting an association between digital pitting and severity of digital vascular change (3). However, research into digital pitting has been scarce. For example, information has been lacking on whether digital pitting is associated with specific patient demographics, autoantibodies, or other SSc-related digital vascular complications, although a very recent analysis of the EUSTAR database (4) has addressed this issue. Our aim was to identify factors associated with digital pitting in patients with SSc in a retrospective cohort study. Data were extracted from a clinical database of patients with SSc attending a single tertiary referral centre between November 1994 and September 2019. Patients were sub-divided into those with and without digital pitting, as recorded at their last documented attendance. Data were collected at their first visit, or for patients attending before November 1994 at their first visit after that date, and updated if appropriate at subsequent visits. Data on the following variables were collected: age, gender, age at Raynaud’s phenomenon onset, age at SSc onset (defined using date of first non-Raynaud's clinical manifestation), limited/ diffuse cutaneous subtype, history of admission for intravenous (IV) vasodilators, history of amputations, history of surgical debridements, presence or absence of clinically apparent calcinosis, and autoantibody status (anticentromere, anti-Scl70 (anti-topoisomerase), anti-RNA polymerase and anti-RNP). <br/