King's College Research Articles

Outcomes of a mentoring scheme to improve career engagement in academia among students from minority ethnic groups

IntroductionStudent mentorship in higher education institutions is often advocated as a way to improve opportunities for students from minority ethnic groups.MethodsThis study examines this further by applying a linear regression model to explore the relationship between a 6-month pilot mentoring scheme at King's College London and career engagement in academia for students from minority ethnic groups, by investigating whether there were differential impacts by ethnic group, and by degree of exposure to mentoring, measured by the number and mode of mentoring sessions i.e., online, in-person or bimodal (a combination of online and in-person).ResultsThe results reveal that while there were no significant differences in career engagement between Asian and Black students, there were significant differences in career engagement between Black students and students who identified as Mixed or Other. Surprisingly, the number of sessions was negatively related to career engagement. However, the positive, significant interaction effect between the number and mode of sessions suggests that this relationship varies based on the mode of the sessions, with bimodal sessions leading to an increase in career engagement, in contrast to solely in-person sessions which led to a decrease in career engagement in academia.ConclusionThe results from this study point to some differential effects of mentoring by ethnic group, with Black students experiencing less gains in terms of career engagement in academia, relative to students who identified as Mixed or Other ethnic groups. This suggests that Black students may need more tailored support, in-depth mentoring or better-matched role models for improved outcomes.

HPB SO74 - Autologous Islet Transplantation combined with Pancreatic resection in Adults and Children

Abstract Background After extended pancreatic resections there is a risk of developing difficult to manage diabetes. The current NHS commissioning criteria only allows autologous islet isolation and transplantation in adult patients having total pancreatectomy for chronic pancreatitis. We present our experience of pancreatic resection combined with autologous islet transplantation (AIT) in both adults and children. Method Patients were assessed for AIT electively or as an emergency if an extended resection was required for trauma. Patients with chronic pancreatitis were assessed for Total Pancreatectomy (TP) by a multi-disciplinary team which included gastroenterologists, diabetes physicians, pain specialists, surgeons and psychiatrists. A similar approach was used in children. Patients were evaluated pre-operatively with a MMT to assess any borderline diabetes. Results 22 (20 adults and 2 children, age range 9-64 yrs) patients underwent pancreas resection with AIT. Two patients had islet isolated remotely (Edinburgh and Kings College). Five received AIT for trauma (one total and four subtotal). Other indications included Chronic Pancreatitis (n=17) one of which had Familial Hyocalciuric Hypercalcaemia. Ten had gene mutations PRSS1 (n=6) or SPINK1 (n=4). Mean number of islets transplanted were 1534 IEQ/kg ranging in total from <5000- 443,000 IEQ. Patients with mutations received lower numbers of islets. Five remained insulin independent, overall 78% had measurable C peptide. 4/17 Chronic pancreatitis still have abdominal pain. Conclusion Pancreas resection combined with AIT is a viable treatment for both adults and children, even in those presenting with severe pancreatic trauma. Achieving good islet yields in patients with gene mutation remains a problem and is related to the extent of disease and duration of symptoms. Timing of TPIAT in these patients is critical if good outcomes are to be achieved.

Outcomes of patients with acute liver failure not listed for liver transplantation: A cohort analysis.

Acute liver failure (ALF) is a rare condition leading to morbidity and mortality. Liver transplantation (LT) is often required, but patients are not always listed for LT. There is a lack of data regarding outcomes in these patients. Our aim is to describe outcomes of patients with ALF not listed for LT and to compare this with those listed for LT. Retrospective analysis of all nonlisted patients with ALF enrolled in the Acute Liver Failure Study Group (ALFSG) registry between 1998 and 2018. The primary outcome was 21-day mortality. Multivariable logistic regression was done to identify factors associated with 21-day mortality. The comparison was then made with patients with ALF listed for LT. A total of 1672 patients with ALF were not listed for LT. The median age was 41 (IQR: 30-54). Three hundred seventy-one (28.9%) patients were too sick to list. The most common etiology was acetaminophen toxicity (54.8%). Five hundred fifty-eight (35.7%) patients died at 21 days. After adjusting for relevant covariates, King's College Criteria (adjusted odds ratio: 3.17, CI 2.23-4.51), mechanical ventilation (adjusted odds ratio: 1.53, CI: 1.01-2.33), and vasopressors (adjusted odds ratio: 2.10, CI: 1.43-3.08) (p < 0.05 for all) were independently associated with 21-day mortality. Compared to listed patients, nonlisted patients had higher mortality (35.7% vs. 24.3%). Patients deemed not sick enough had greater than 95% survival, while those deemed too sick still had >30% survival. Despite no LT, the majority of patients were alive at 21 days. Survival was lower in nonlisted patients. Clinicians are more accurate in deeming patients not sick enough to require LT as opposed to deeming patients too sick to survive.

Schizophrenia and magnetic resonance imaging research: A scientometric analysis during 2014 to 2023.

Recently, magnetic resonance imaging (MRI) has emerged as a leading technique for investigating schizophrenia (SZ) pathological mechanisms, prompting an increase in related studies. This study aims to examine the field's research status and trends via bibliometric analysis. The publications on SZ and MRI over the past decade were retrieved from the Web of Science Core Collection (WOSCC) On October 15, 2023. CiteSpace and VOSviewer were used to conduct scientometric and visualized analysis, covering countries, institutions, authors, journals, co-cited literature, and keywords. A total of 4840 publications were retrieved from 2014 to 2023. The United States leads with 1863 articles, followed by China with 1127 articles. King's College London had the highest number of publications, with 332 articles. Schizophrenia Research ranks first in the journal that published the research on schizophrenia and MRI, the most published journal, Neuroimage is the most cited journal. Calhoun is the most prolific author with 145 articles, and Fischl is the most cited author, receiving 1188 citations. The literature co-citation network (2014 to 2023) revealed 16 clusters with robust structure (Q = 0.8719) and high confidence (S = 0.9421) involving MRI studies of SZ, genetic imaging and treatment of schizophrenia. Keywords include MRI, psychosis and functional magnetic resonance imaging (fMRI), MRI and neuroimaging, MRI and neuroimaging and white matter and diffusion tensor imaging. This study offers an overview of the research status and trends of publications on SZ and MRI, aiming to inspire future research directions.

Celso Arango: The future of psychiatry inevitably depends on primary prevention

Dr. Celso Arango stands as a preeminent authority in psychiatry, wielding considerable influence through his multifaceted roles. As Director of the Institute of Psychiatry and Mental Health at Hospital General Universitario Gregorio Marañón and Professor of Psychiatry at the Universidad Complutense de Madrid, he spearheads Spain's advancements in mental health research and treatment. Dr. Arango's expertise resonates globally, reflected in his visiting professorships at renowned institutions, including the University of California, San Francisco, the University of Maryland, and King's College London. His commitment to international collaboration, evidenced by partnerships with over 100 institutions worldwide, significantly propels the global psychiatric community forward. Dr. Arango's exceptional contributions have garnered prestigious accolades, notably his election as the youngest member of the Royal National Academy of Medicine in Spain and his recent induction into the National Academy of Medicine in the United States. At the core of his research efforts lies a dedicated focus on early-onset psychosis and neurodevelopmental disorders in young individuals, work that not only advances scientific understanding but also offers tangible hope for improved treatment outcomes. Dr. Arango's unique blend of clinical expertise, research acumen, and academic leadership positions him at the vanguard of innovation in mental health care, potentially revolutionizing our approach to understanding and treating psychiatric disorders across the lifespan. In this exclusive Genomic Press Interview, Dr. Arango shares insights on his life and career, offering our readers a glimpse into the mind of one of psychiatry's most influential figures.

Can edoxaban be used at extremes of bodyweight and in patients with a creatinine clearance ≥95 ml/min? – A population pharmacokinetic analysis

BackgroundClinical evidence surrounding edoxaban use in patients weighing <50 kg and >120 kg is lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee suggests avoiding edoxaban in patients >120 kg. Additionally, concerns exist regarding decreased efficacy in patients prescribed edoxaban for atrial fibrillation with a creatinine clearance (CrCl) >95 ml/min, a finding of the ENGAGE AF-TIMI 48 trial when edoxaban was compared to warfarin. ObjectiveTo derive a population pharmacokinetic (PopPK) model using clinical practice data, to understand the impact of bodyweight and renal function on edoxaban pharmacokinetics. MethodEdoxaban plasma concentrations and patient characteristics were collated from King's College Hospital anticoagulation clinics between 11/2016 and 08/2022. A PopPK model was developed using non-linear mixed effects modelling and used to simulate edoxaban concentrations at the extremes of bodyweight and with varying renal function. ResultsData from 409 patients (46 < 50 kg, 34 > 120 kg and 123 with a CrCl > 95 ml/min) provided 455 edoxaban plasma concentrations. A one-compartment model with between-subject variability on clearance with a proportional error model best described the data. The most significant covariates impacting on edoxaban exposure were CrCl and bodyweight. Our work suggests that edoxaban exposure in patients weighing up to 140 kg is comparable to those weighing 75 kg. Edoxaban exposure is reduced in patients weighing <50 kg due to the recommended dose reductions. There is also a reduction in AUCss when CrCl > 95 ml/min compared to CrCl 80 ml/min. ConclusionsOur population PK model for edoxaban suggests that renal function is a key driver for overall edoxaban exposure. Further clinical outcome data is required to understand clinical effectiveness and adverse outcomes.

Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres.

Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. A multicentre retrospective study across four major tertiary care centres. As many as 183ALF patients (median age, 23years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen percent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.

THE FORECAST STUDY: FACTORS PREDICTING PAIN PERSISTENCE IN SCIATICA. AN UPDATE ON BASELINE AND PRELIMINARY LONGITUDINAL DATA

BackgroundFORECAST is a prospective longitudinal cohort study exploring mechanism-based prognostic factors for pain persistence in sciatica. Here, we share an update on this largest deeply-phenotyped primary care sciatica cohort.Methods/resultsOur cohort includes 180 people with sciatica (score &gt;4 on Stynes’ Sum Score), aged 18–85, within 3 months of symptom onset. Psychosocial factors, self-reported sensory profiling, clinical examination, quantitative sensory testing (QST), biological samples (blood and skin samples), and Magnetic Resonance Neurography of lumbar nerve roots were collected at baseline. Pain persistence was determined at three and twelve months with the Sciatica Bothersomeness Index (SBI) and a numeric pain rating scale (NRS) as primary outcomes. Recruitment nears completion, with 160 participants enrolled to date. 127 and 96 participants have completed 3 and 12 months follow-up respectively.Overall, 56% of our cohort are female, with a mean age (SD) of 54.14yrs (16.57). Ethnicity data approximates local populations.SBI at baseline was (median [IQR]) 13[10-17], and interim longitudinal data shows stepwise improvement at 3 and 12 months. Baseline ‘average’ pain intensity was 5.56 (2.15) for leg pain, and 4.14(2.82) for low back pain (LBP). Overall, pain scores decreased at 3 and 12 months, with greater reductions in leg pain than LBP at 12 months. However, around 55–80% and 40–65% of people reported persistent pain at 3 and 12 months respectively.ConclusionLeg pain severity was moderate and higher than LBP at baseline. All primary outcome measures demonstrate improvement over time, however 40–65% of patients report persistent pain at 12 months.Conflicts of interestLR: Paid facilitation of post-graduate courses internationally. SK, MT, FP, KM, WS, CP, CR, SC: No conflicts of interest. GC: Editor in Chief of Health Psychology Review. Director of board of directors, MentalCHealth Care setting NoordWestVlaanderen. JF: Copyright holder of ODI (Oswestry Disability Index). Served on a data monitoring committee for a clinical trial of 2 different surgical approaches to cervical disc herniation (FORVAD). Member of HTA Prioritisation Committee B: Inside hospital Care from 2015-February 2019. Member of HTA Interventional Procedures Panel from 2010–2015. Trustee and board member of 3 spine related charities – Back to Back; British Scoliosis Research Foundation and BackCare. Expert instructed by both claimant and defendant solicitors in negligence and person injury cases. GB: Paid consultancy (RNA-seq) with Ivy Farm and Coding.bioABS: Paid post-graduate lecturing internationally. Co-chair NeupSig sciatica working group (unpaid).Sources of fundingThis project is funded by UKRI and Versus Arthritis as part of the UKRI Strategic Priorities Fund (SPF) Advanced Pain Discovery Platform (APDP), a co-funded initiative by UKRI (MRC, BBSRC, ESRC), Versus Arthritis, the Medical Research Foundation and Eli Lilly and Company Ltd (Grant MR/W027003/1). Additional funding has been received from the back to back charity to expand longitudinal components of the study. LR has received support with PhD fees from the CSP charitable trust. ABS is supported by a Wellcome Trust Clinical Career Development Fellowship(222101/Z/20/Z). WS is partly funded through the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King's College London. FP is funded by a Dorothy Hodgkin Career Development Fellowship in Chemistry in association with Somerville College. GB is supported by the Wellcome Trust (223149/Z/21/Z) and Diabetes UK (19/0005984). GC and KRM are partly funded by UKRI and Versus Arthritis as part of the Advanced Pain Discovery Platform (APDP) PAINSTORM (MR/W002388/1). The UKRI and Versus Arhthritis (APDP) are the major funders of FORECAST. All other funders provided either some people support, or funded projects with legacy data that we reuse.

Evidence that systemic vascular resistance is increased before the development of gestational diabetes mellitus

The ophthalmic artery, which is the first branch of the internal carotid artery, has a Doppler velocity waveform with two systolic peaks. The ratio of the peak systolic velocity (PSV) of the second wave divided by that of the first wave, reflects increased peripheral resistance. Previous studies in the first, second and third trimesters of pregnancy have reported that in pregnancies that subsequently develop preeclampsia (PE) the PSV ratio is increased. Both PE and gestational diabetes mellitus (GDM) are associated with endothelial dysfunction and an increased risk of cardiovascular diseases during the first decade following pregnancy. To compare the ophthalmic artery PSV ratio at 11-13 weeks' gestation in women who subsequently develop GDM to unaffected pregnancies and those who develop PE. This was a prospective observational study in women attending for a routine hospital visit at 11+0 - 13+6 weeks' gestation at King's College Hospital, London, UK. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries and calculation of the PSV ratio, and measurement of mean arterial pressure (MAP). Linear regression was performed for the prediction of ophthalmic artery PSV ratio, from maternal characteristics and MAP. The PSV ratio in the group with GDM was compared to that of PE and unaffected pregnancies. 3999 women were included in the study, including 375 (9.8%) who developed GDM and 101 (2.5%) who developed PE. In the GDM group, 161 (43.3%) were treated by diet alone, 130 (34,1%) were treated with metformin and 84 (22.6%) received insulin ± metformin. Significant prediction of PSV ratio was provided by development of PE, maternal age, body mass index, MAP, first degree family history of diabetes mellitus, family history of PE, Asian ethnicity, and smoking. There was no significant contribution from GDM. In women who developed GDM requiring insulin treatment, ophthalmic artery PSV ratio (0.67 ± 0.09) was higher (p <0.001) than in unaffected pregnancies (0.63 ± 0.10), but it was not significantly different from that in the PE group (0.69 ± 0.10; p=0.90). In women who develop severe GDM, requiring insulin treatment, there is evidence of increased peripheral resistance which is apparent from the first-trimester of pregnancy.

Maternal vascular – placental axis in the third trimester in women with gestational diabetes mellitus, hypertensive disorders and unaffected pregnancies.

Hypertensive disorders of pregnancy and gestational diabetes mellitus are characterized by vascular dysfunction and are associated with long term cardiovascular risks. This study aimed to compare different markers of maternal vascular function in women with gestational diabetes mellitus, preeclampsia, or gestational hypertension and in women whose pregnancies were unaffected by these complications and to assess the association between maternal vascular function and markers of placental perfusion and maternal vascular-placental axis in 4 groups of women. This was a prospective observational study of women who had routine hospital visits at 35 0/7 to 36 6/7 weeks of gestation at King's College Hospital, London, United Kingdom. The routine hospital visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, Doppler studies of the uterine arteries and ophthalmic arteries, carotid-femoral pulse wave velocity measurements, estimation of the augmentation index and total peripheral resistance, and measurements of serum placental growth factor and soluble fms-like tyrosine kinase 1. Linear regression analysis was performed for the outcomes of uterine artery pulsatility index multiple of the median, placental growth factor multiple of the median, and soluble fms-like tyrosine kinase 1 multiple of the median. The ophthalmic artery peak systolic velocity ratio, pulse wave velocity, augmentation index, and total peripheral vascular resistance were assessed as potential predictors. This analysis was performed on all women and separately in the different groups. The study population of 6502 women included 614 (9.4%) with gestational diabetes mellitus, 140 (2.1%) who subsequently developed preeclampsia, and 129 (2.0%) who developed gestational hypertension. Women with gestational diabetes mellitus had increased pulse wave velocity compared with those with pregnancies unaffected by gestational diabetes mellitus, preeclampsia, or gestational hypertension. Women with preeclampsia or gestational hypertension had lower placental growth factor multiple of the median and higher uterine artery pulsatility index multiple of the median, soluble fms-like tyrosine kinase 1 multiple of the median, augmentation index, pulse wave velocity, total peripheral resistance, and ophthalmic artery peak systolic velocity ratio than those with unaffected pregnancies. In women with unaffected pregnancies, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median, and ophthalmic artery peak systolic velocity ratio, augmentation index, total peripheral resistance, and pulse wave velocity were predictive of the placental growth factor multiple of the median and the soluble fms-like tyrosine kinase 1 multiple of the median. In women with gestational diabetes mellitus, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median; the ophthalmic artery peak systolic velocity ratio, total peripheral resistance, and pulse wave velocity were predictive of the placental growth factor multiple of the median; and total peripheral resistance was predictive of the soluble fms-like tyrosine kinase 1 multiple of the median. In women with preeclampsia, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median, placental growth factor multiple of the median, and soluble fms-like tyrosine kinase 1 multiple of the median. In women unaffected by gestational diabetes mellitus, preeclampsia, or gestational hypertension, the ophthalmic artery peak systolic velocity ratio was predictive of the uterine artery pulsatility index multiple of the median, and the augmentation index, total peripheral resistance, pulse wave velocity, and the ophthalmic artery peak systolic velocity ratio were predictive of the placental growth factor multiple of the median and the soluble fms-like tyrosine kinase 1 multiple of the median. In the third trimester of pregnancy, women with preeclampsia, gestational hypertension, and gestational diabetes mellitus present with increased arterial stiffness. In addition, women diagnosed with hypertensive complications showed increased peripheral vascular resistance. The ophthalmic artery peak systolic velocity ratio provided predictive information for placental perfusion and function in all pregnant women, whereas vascular indices were more informative for placental function in women with unaffected pregnancies and those with gestational diabetes mellitus than in those with preeclampsia or gestational hypertension. Our data suggest that vascular assessment in women during pregnancy not only may provide information about maternal vascular health but also can be used to provide information about individual risk factors for placental insufficiency. The selection of the vascular index will have to be tailored according to the maternal profile and pregnancy complication.

Soluble fms-like tyrosine kinase-1/placental growth factor ratio at 36 weeks’ gestation: association with spontaneous onset of labor and intrapartum fetal compromise in low-risk pregnancies

Previous evidence showed that placental dysfunction triggers spontaneous preterm or term births and intrapartum fetal compromise and often requires urgent delivery, thereby exposing both the fetus and the mother to significant risks. Predicting spontaneous labor onset and intrapartum fetal compromise could improve obstetrical management and outcomes, but this is currently difficult, particularly in low-risk populations. The objective of this study was to examine whether placental dysfunction, as assessed at 36 weeks' gestation by the soluble fms-like tyrosine kinase-1 to placental growth factor ratio, is associated with the interval to spontaneous onset of labor and intrapartum fetal compromise that requires cesarean delivery in a routinely examined population. This was a retrospective analysis of prospectively collected data of women with singleton pregnancies who underwent routine assessment at 35+0 to 36+6 weeks' gestation at the King's College Hospital (London, England). Using a general linear model, the study examined the outcomes related to the soluble fms-like tyrosine kinase-1/placental growth factor ratio, including the time interval from testing to spontaneous onset of labor and the subsequent rate of fetal compromise that required a cesarean delivery. Patients who underwent induction of labor or prelabor cesarean deliveries were excluded from the study. Competing risks regression and Cox regression models were used to estimate the cumulative incidence and the risk of the outcomes of interest. In the screened population of 45,375 patients, 23,831 (52.5%) had spontaneous onset of labor and were included in the analysis. Cases with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 delivered about 1 week earlier than those with a ratio of ≤50 (39.2 vs 40.0 weeks' gestation; P<.001). The general linear model showed that a larger soluble fms-like tyrosine kinase-1/placental growth factor ratio was associated with earlier spontaneous onset of labor (P<.001), particularly among multiparous women. The soluble fms-like tyrosine kinase-1/placental growth factor ratio was significantly associated, as expected, with cases of preeclampsia and advanced maternal age. The cumulative incidence of spontaneous onset of labor was significantly higher in cases with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 than in those with a ratio 50 (P<.001). Cox regression showed that the risk for spontaneous onset of labor increased with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 (hazard ratio, 1.424; 95% confidence interval, 1.253-1.618; P<.001) and, as expected, the risk was mitigated over time from when the soluble fms-like tyrosine kinase-1/placental growth factor ratio was measured to spontaneous labor onset (P<.001). Cases with intrapartum fetal compromise had a higher mean soluble fms-like tyrosine kinase-1/placental growth factor ratio than those without intrapartum fetal compromise (21.79 vs 17.67; P<.001). Qualitative addition of fetal compromise to the general linear model showed a higher soluble fms-like tyrosine kinase-1/placental growth factor ratio in cases with fetal compromise than in those without fetal compromise (P=.014). Competing risks regression showed a positive dose-response effect for fetal compromise with increasing soluble fms-like tyrosine kinase-1/placental growth factor ratios (P<.001). Above and below the optimal cutoff of 50, the quoted cumulative incidences were 6.7% and 4.7%, respectively (P<.001). The effect of the soluble fms-like tyrosine kinase-1/placental growth factor ratio remained significant even after adjusting for preeclampsia, which is a well-known major risk factor for fetal compromise. Finally, the proportion of cases with intrapartum fetal compromise who had an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 decreased from 35% to 0% with advancing gestation. This study showed that an increased soluble fms-like tyrosine kinase-1/placental growth factor ratio at 36 weeks' gestation is associated with an earlier gestational age at spontaneous onset of labor and higher rates of intrapartum fetal compromise. There are 2 major implications, namely an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 indicates imminent labor onset with about a 40% mean risk increase and immediate clinical translation for term pregnancy monitoring. In addition, an increased soluble fms-like tyrosine kinase-1/placental growth factor ratio increases the risk for intrapartum fetal compromise, although outcome variability indicates reassessment within multimarker models.

King's College Hospital Dental School Centenary Celebrations: 1923-2023.

King's College Hospital Dental School Centenary Celebrations: 1923-2023.

The people behind the papers - James O'Sullivan and Zoë Mann.

To build a functional inner ear, hair cell morphology must be precisely controlled along the proximo-distal axis. A new paper in Development shows that differential mitochondrial dynamics in proximal versus distal cells impacts on the apical cell surface area - a key aspect of morphology. To find out more about this work, we spoke to first author James O'Sullivan and senior author Zoë Mann, both at King's College London, UK.

First-trimester screening identifies maternal cardiac maladaptation in midgestation.

We have previously established that a logistic regression model, based on maternal demographic characteristics and blood pressure measured at 11-13 weeks' gestation, can identify about 70% of women who develop future chronic hypertension (CH) in the 3 years following pregnancy, at a screen-positive rate of 10%. Furthermore, in midgestation, women who subsequently develop hypertensive disorders of pregnancy (HDP) have increased peripheral vascular resistance and mild cardiac functional and morphological alterations and these cardiovascular abnormalities persist for at least 2 years after delivery. In this study, we set out to examine whether use of the first-trimester risk model for subsequent development of CH can help to identify women at high risk for cardiovascular maladaptation in midgestation. This was a prospective observational study of 3812 women with singleton pregnancy attending for a routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation and again at 19 + 1 to 23 + 3 weeks at King's College Hospital, London, UK, between December 2019 and August 2020. The first-trimester visit included recording of maternal demographic characteristics and medical history and measurement of systolic and diastolic blood pressure. In midgestation, detailed maternal cardiovascular assessment was carried out. The association between risk for development of CH, determined from first-trimester assessment, and cardiovascular indices in midgestation was examined. Women who were at high risk for development of future CH, compared to those at low risk, had a higher incidence of HDP. In addition, high-risk women had reduced systolic and diastolic function in midgestation. Among women with HDP, those who were at high risk for future CH, compared to those at low risk, had worse cardiac function in midgestation. Use of a model for first-trimester prediction of subsequent development of CH can identify women who show evidence of cardiac maladaptation in midgestation. Further studies are needed to clarify whether women who screen as high risk for future CH, compared to those at low risk, have reduced cardiac function beyond pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Progress and trends of research on mineral elements for depression

ObjectiveTo explore the research progress and trends on mineral elements and depression. MethodsAfter querying the MeSH database and referring to the search rules, the search terms were selected and optimized to obtain the target literature collection. We analyzed the general characteristics of the literature, conducted network clustering and co-occurrence analysis, and carried out a narrative review of crucial literature. ResultsBipolar disorder was a dominant topic in the retrieved literature, which saw a significant increase in 2010 and 2019–2020. Most studies focused on mineral elements, including lithium, calcium, magnesium, zinc, and copper. The majority of journals and disciplines were in the fields of psychiatry, neuropsychology, neuropharmacology, nutrition, medical informatics, chemistry, and public health. The United States had the highest proportion in terms of paper sources, most-cited articles, high-frequency citations, frontier citations, and high centrality citation. Regarding the influence of academic institutions, the top five were King's College London, the Chinese Academy of Sciences, University of Barcelona, INSERM, and Heidelberg University. Frontier keywords included bipolar disorder, drinking water, (neuro)inflammation, gut microbiota, and systematic analysis. Research on lithium response, magnesium supplementation, and treatment-resistant unipolar depression increased significantly after 2013. ConclusionGlobal adverse events may have indirectly driven the progress in related research. Although the literature from the United States represents an absolute majority, its influence on academic institutions is relatively weaker. Multiple pieces of evidence support the efficacy of lithium in treating bipolar disorder (BD). A series of key discoveries have led to a paradigm shift in research, leading to increasingly detailed studies on the role of magnesium, calcium, zinc, and copper in the treatment of depression. Most studies on mineral elements remain diverse and inconclusive. The potential toxicity and side effects of some elements warrant careful attention.

Personality traits in patients with amyotrophic lateral sclerosis

BACKGROUND: The results of several studies indicate that patients with amyotrophic lateral sclerosis (ALS) exhibit certain personality traits. However, it is currently unclear which specific traits are most typical for those patients, and whether these traits are universal across different ethno-cultural backgrounds. AIM: To analyse the personality traits of patients with ALS. MATERIALS AND METHODS: The study included patients with various forms of ALS according to the Revised El Escorial Criteria. The following data were collected: demographic information, the form of the disease, and the stage according to the King's College system. A short five-factor personality questionnaire (TIPI-RU) was used to assess personal characteristics. The statistical analysis employed non-parametric statistical methods. RESULTS: Patients with ALS had significantly higher levels of agreebleness (p=0.037). Analysis of personality traits within the group of patients with ALS showed that in patients with bulbar onset, had a significantly higher level of agreebleness — 5 (4.5–7) than in patients with spinal onset 4.5 (4–5), p=0.006. The correlation analysis revealed a direct weak relationship between the degree of extraversion and age (r=0.3; p=0.013). CONCLUSION: The analysis of the personality traits of the ALS patients showed a higher friendliness (agreeableness) compared to the control group. Future research should elucidate whether this parameter could be considered as one of the markers of increased risk of ALS development.

Maternal cardiovascular function in midgestation is related to placental angiogenesis.

To investigate whether angiogenic markers of placental function are associated with maternal cardiac function and hemodynamic responses at 19-23 weeks' gestation, controlling for maternal risk factors and pregnancy complications. This was a prospective study of women with singleton pregnancy attending King's College Hospital, London, UK, for a routine hospital visit at 19-23 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure (MAP), maternal heart rate, serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). We also performed maternal echocardiography to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function. Our cohort included 4006 women. Lower PlGF values were significantly associated with higher MAP (P < 0.0001), lower maternal heart rate (P < 0.0001), lower mitral valve s' mean velocity (P = 0.027) and higher left atrial area (P = 0.022) after adjustment for maternal characteristics and pregnancy complications. sFlt-1 was associated positively with relative wall thickness (P = 0.012), whereas sFlt-1/PlGF ratio was associated negatively with mitral valve A (P = 0.006) and positively with left atrial area (P = 0.015) and MAP (P = 0.004). The magnitude of these associations was similar in the subgroup of women without any risk factors based on their obstetric and medical history. A continuous association of moderate strength between angiogenic factors and subclinical maternal cardiac function alterations is present in midgestation, independently of pre-existing maternal risk factors and pregnancy complications. Impaired placental function appears to be related to mild systolic and diastolic dysfunction and cardiac remodeling. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Global research status of intrahepatic cholestasis of pregnancy: A bibliometric analysis of hotspots, bursts, and trends

BackgroundResearch on intrahepatic cholestasis of pregnancy (ICP) has recently gained attention. However, no bibliometric analysis was performed in the ICP research field. Therefore, the present study aimed to use bibliometric analysis to analyze the current research hotspots and identify global research status in ICP to reference for future research directions. MethodsWe comprehensively searched the Web of Science Core Collection (WoSCC) database from its inception to December 31, 2023. Articles and reviews related to ICP were downloaded as plain text file records. We used the VOSviewer and Citespace to perform the bibliometric analysis and visualization. The main bibliometric features were tabulated and calculated. ResultsA total of 1092 documents, including 921 original articles and 171 reviews, were identified in WoSCC. These publications were published in 395 journals by 4751 authors from 1250 institutions and 61 countries/regions. The global publication numbers exhibited a gradual upward trend. China, the United States, and the United Kingdom were top contributors to scientific research on ICP. King's College London, London Imperial Coll Sci Technol & Med, and Sichuan University were the most productive institutions. Catherine Williamson had published the most papers and received the most total citations. The most productive journal was Journal of Maternal-Fetal & Neonatal Medicine. The most cited paper was Beuers et al. in the Journal of Hepatology (2009). Citation burst terms showed that “risk factors” and “perinatal outcomes” were hotspots. “Inflammation”, “risk factors”, “perinatal outcomes”, and “bile acid” have gained attention in more recent research. ConclusionThe present study comprehensively summarizes the global research status and research trends in ICP. Our study identifies hotspots, collaborative networks, and trends that will provide new insights and guidance for further research in the field.

A Parkinson's Auxiliary Diagnosis Algorithm Based on a Hyperparameter Optimization Method of Deep Learning.

Parkinson's disease is a common mental disease in the world, especially in the middle-aged and elderly groups. Today, clinical diagnosis is the main diagnostic method of Parkinson's disease, but the diagnosis results are not ideal, especially in the early stage of the disease. In this paper, a Parkinson's auxiliary diagnosis algorithm based on a hyperparameter optimization method of deep learning is proposed for the Parkinson's diagnosis. The diagnosis system uses ResNet50 to achieve feature extraction and Parkinson's classification, mainly including speech signal processing part, algorithm improvement part based on Artificial Bee Colony algorithm (ABC) and optimizing the hyperparameters of ResNet50 part. The improved algorithm is called Gbest Dimension Artificial Bee Colony algorithm (GDABC), proposing "Range pruning strategy" which aims at narrowing the scope of search and "Dimension adjustment strategy" which is to adjust gbest dimension by dimension. The accuracy of the diagnosis system in the verification set of Mobile Device Voice Recordings at King's College London (MDVR-CKL) dataset can reach more than 96%. Compared with current Parkinson's sound diagnosis methods and other optimization algorithms, our auxiliary diagnosis system shows better classification performance on the dataset within limited time and resources.

Comparative physiological effects of antipsychotic drugs in children and young people: a network meta-analysis

The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions. For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393). Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6-8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from -2·00 kg (95% CI -3·61 to -0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI -0·70 kg/m2 (-1·21 to -0·19) with molindone to 2·03 kg/m2 (0·51 to 3·55) with quetiapine; total cholesterol -0·04 mmol/L (-0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol -0·12 mmol/L (-0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (-0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (-0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides -0·03 mmol/L (-0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from -0·09 mmol/L (-1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from -2·83 ng/mL (-8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from -0·20 bpm (-8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from -3·40 mm Hg (-6·25 to -0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from -0·61 ms (-1·47 to 0·26) with pimozide to 0·30 ms (-0·05 to 0·65) with ziprasidone. Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations. UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation.