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Background: Migraine is a highly prevalent neurological disease with a substantial societal burden due to lost productivity. From a societal perspective, we assessed the cost-effectiveness of eptinezumab for the preventive treatment of migraine. Methods: An individual patient simulation of discrete competing events was developed to evaluate eptinezumab cost-effectiveness compared to best supportive care for adults in the United Kingdom with ≥ 4 migraine days per month and prior failure of ≥ 3 preventive migraine treatments. Individuals with sampled baseline characteristics were created to represent this population, which comprised dedicated episodic and chronic migraine subpopulations. Clinical efficacy, utility, and work productivity inputs were based on results from the DELIVER randomised controlled trial (NCT04418765). Timing of natural history events and treatment holidays—informed by the literature—were simulated to unmask any natural improvement of the disease unrelated to treatment. The primary outcomes were monthly migraine days, migraine-associated costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and net monetary benefit, each evaluated over a 5-year time horizon from 2020. Secondary analyses explored a lifetime horizon and an alternative treatment stopping rule. Results: Treatment with eptinezumab resulted in an average of 0.231 QALYs gained at a saving of £4,894 over 5 years, making eptinezumab dominant over best supportive care (i.e., better health outcomes and less costly). This result was confirmed by the probabilistic analysis and all alternative assumption scenarios under the same societal perspective. Univariate testing of inputs showed net monetary benefit was most sensitive to the number of days of productivity loss, and monthly salary. Conclusions: This economic evaluation shows that from a societal perspective, eptinezumab is a cost-effective treatment in patients with ≥ 4 migraine days per month and for whom ≥ 3 other preventive migraine treatments have failed. Trial registration: N/A. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to describe the natural history and predictors of all‐cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM). Methods and results: This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18 years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS‐LAH)]. One hundred forty‐nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan‐like syndrome, and 3 (2%) NS‐LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36–80) mmHg, P = 0.004]. Over a median follow‐up of 197.5 [inter‐quartile range (IQR) 93.58–370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6–175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69–98.51], 90.42% (95% CI 84.04–94.33), and 84.12% (95% CI 75.42–89.94) at 1, 5, and 10 years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non‐sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all‐cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event. Conclusions: These findings highlight a distinct category of patients with Noonan‐like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy‐related HCM. [ABSTRACT FROM AUTHOR]

The digitization of natural history specimens and the popularization of citizen science are creating an unprecedented availability of large amounts of biodiversity data. These biodiversity inventories can be severely affected by species misidentification, a source of taxonomic uncertainty that is rarely acknowledged in biodiversity data management. For these reasons, taxonomists debate the use of online repositories to address biological questions at the species level. Hedera L. (ivies) provides an excellent case study as it is well represented in both herbaria and online repositories with thousands of records likely to be affected by high taxonomic uncertainty. We analyze the sources and extent of taxonomic errors in the identification of the European ivy species by reviewing herbarium specimens and find a high misidentification rate (18% on average), which varies between species (maximized in H. hibernica: 55%; H. azorica: 48%; H. iberica: 36%) and regions (maximized in the UK: 38% and Spain: 27%). We find a systematic misidentification of all European ivies with H. helix behind the high misidentification rates in herbaria and warn of even higher rates in online records. We compile a spatial database to overcome the large discrepancies we observed in species distributions between online and morphologically reviewed records. [ABSTRACT FROM AUTHOR]

Background: Metachromatic Leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease characterised by the progressive loss of motor function and severe decline in cognitive function. Limited information is available on the burden MLD places on patients and their families and the medical and social support these patients need. Three UK-based MLD patient organisations commissioned an online survey, and follow-up semi-structured interviews to describe and quantify these burdens across MLD subtypes, stage of disease (including end of life) and treatment status (untreated, gene therapy or hematopoietic stem cell transplant [HSCT]). Results: A total of 24 patients were included in the study: thirteen late infantile (LI), six early juvenile (EJ), two late juvenile (LJ) and three adult onset (AO). Six patients had received gene therapy and one had received an HSCT. MLD patients receiving no disease modifying treatment bore a high symptom burden: 94% were wheelchair dependent, 88% required tube feeding, 88% were incontinent, 82% had lost their speech and all the children were either unable to attend education or needed specialist provision. Patients were reliant on numerous medical interventions and assistive equipment. All early-onset patients (LI and EJ) were wheelchair dependent, and tube fed, with all EJ patients having lost all speech. The caregiving responsibilities of parents impacted their employment, finances, relationships and health. Patients treated with gene therapy or HSCT were more mobile and were able to eat normally and two thirds of the children were able to attend mainstream school. Conclusions: The impact of illness that patients and their caregivers faced was extensive, and the level of care, amount of medication, number of hospital visits and educational support required were substantial. Financial constraints often brought about by inability to work also placed considerable strain on families. The study increases understanding of the burden of MLD on patients and their families, and the level of unmet need in the treatment of the disease. [ABSTRACT FROM AUTHOR]

Amid growing public and academic interest in the identification and return of Aboriginal objects acquired by Britain from Australia after 1788, enquiries into the disputed origins of the British Museum's 'Gweagal shield' have highlighted the need for new and better forms of provenance research. This article explores a novel methodology and source of information: British Treasury and customs records detailing the descriptions, values, and duties paid upon a vast number of colonial collections of Aboriginal objects, human remains, and natural history specimens known to have disembarked in Britain between 1788 and 1823. By positing a new provenance for the 'Gweagal shield' – namely, that it may have accompanied Bennelong, Yemmerrawanne and Arthur Phillip on their passage to England in 1793 – the article explores the potential of such records for highlighting what, when, how, and from whom Australian collections arrived in Britain in this early and hitherto little-understood period. [ABSTRACT FROM AUTHOR]

Paranasal sinus mucocoeles can be secondary to chronic rhinosinusitis and can result in intra-orbital and intra-cranial complications requiring surgical management. The natural history of conservatively managed mucocoeles is not well established. We aimed to quantify the proportion of radiologically identified paranasal sinus mucocoeles resulting in complications over 10 years. We retrospectively reviewed anonymised data on radiologically diagnosed mucocoeles between 2011 and 2021 at two UK hospitals. We collected data on age at presentation, extent of sinus involvement, management and complications. We identified 60 patients with mucocoeles, of which 35 (58%) were incidental findings from radiological investigations. The mean age was 58 years. Fifteen patients (25%) were managed surgically and one presented with recurrence following surgery. Overall, six patients (10%) had an intra-orbital extension of their mucocoele and three (5%) had an intra-cranial extension. There was no difference in the rates of intra-cranial extension between conservative and surgical cases but surgical cases included a higher rate of intra-orbital extensions (27% vs. 4%, p = 0.01). The proportion of patients requiring surgical intervention in this study is low. Incidental and asymptomatic mucocoeles have a relatively benign disease course and selected uncomplicated cases can be considered for conservative management with serial scanning at 12 months. [ABSTRACT FROM AUTHOR]

Context: Familial partial lipodystrophy type 2 (FPLD2) results from autosomal dominant mutations in the LMNA gene, causing lack of subcutaneous fat deposition and excess ectopic fat accumulation, leading to metabolic complications and reduced life expectancy. The rarity of the condition means that the natural history of FPLD2 throughout childhood is not well understood. We report outcomes in a cohort of 12 (5M) children with a genetic diagnosis of FPLD2, under the care of the UK National Severe Insulin Resistance Service (NSIRS) which offers multidisciplinary input including dietetic, in addition to screening for comorbidities. Objective: To describe the natural history of clinical, biochemical and radiological outcomes of children with FPLD2. Design: A retrospective case note review of children with a genetic diagnosis of FPLD2 who had been seen in the paediatric NSIRS was performed. Patients: Twelve (5M) individuals diagnosed with FPLD2 via genetic testing before age 18 and who attended the NSIRS clinic were included. Measurements: Relationships between metabolic variables (HbA1c, triglycerides, fasting insulin, fasting glucose and alanine transaminase [ALT]) across time, from first visit to most recent, were explored using a multivariate model, adjusted for age and gender. The age of development of comorbidities was recorded. Results: Three patients (all female) developed diabetes between 12 and 19 years and were treated with Metformin. One female has hypertrophic cardiomyopathy and four (1M) patients developed mild hepatic steatosis at a median [range] age of 14(12–15) years. Three (1M) patients reported mental health problems related to lipodystrophy. There was no relationship between biochemical results and age. Patients with diabetes had higher concentrations of ALT than patients who did not have diabetes, adjusted for age, gender and body mass index standard deviation scores. Conclusions: Despite dietetic input, some patients, more commonly females, developed comorbidities after the age of 10. The absence of relationships between biochemical results and age likely reflects a small cohort size. We propose that, while clinical review and dietetic support are beneficial for children with FPLD2, formal screening for comorbidities before age 10 may not be of benefit. Clinical input from an multidisciplinary team including dietician, psychologist and clinician should be offered after diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. Methods: 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. Results: Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90μmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. Conclusion: We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress. [ABSTRACT FROM AUTHOR]

Long-standing overt ventriculomegaly in adults (LOVA) is a heterogenous group of conditions with differing presentations. Few studies have evaluated success rates of available surgical treatments, or ascertained the natural history. There is a need to assess the efficacy of both endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) as first-line treatments. We conducted a retrospective, single-centre study of adults with LOVA at a tertiary neurosurgery centre in England, UK, aiming to identify presentation, management strategy, and outcome following treatment. A total of 127 patients were included (mean age 48.1 years, 61/127 male). Most patients were symptomatic (73.2%, n = 93/127, median symptom duration 10 months). The most common symptoms were gait ataxia, headache, and cognitive decline (52.8%, 50.4%, and 33.9%, respectively). Fourteen patients had papilloedema. Ninety-one patients (71.7%) underwent surgery (84 ETV, 7 VPS). Over a median follow-up of 33.0 months (interquartile range [IQR] 19.0–65.7), 82.4% had a clinical improvement after surgery, and 81.3% had radiological improvement. Clinical improvement rates were similar between ETV and VP shunt groups (82.1% vs 85.7%, p = 0.812). Surgical complication rates were significantly lower in the ETV group than the VP shunt group (4.8% vs 42.9%, p < 0.001). Of the patients treated surgically, 20 (22.0%) underwent further surgery, with 14 patients improving. This study demonstrates the efficacy of ETV as a first-line treatment for LOVA. [ABSTRACT FROM AUTHOR]

Purpose: Advanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed 'Type 1'), but it is unclear how variant prevalences differ between AMD patients from different ethnicities. Methods: Collective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD). Due to a lack of available genetic data in non-European AAMD, power calculations were undertaken to estimate the AAMD population sizes required to identify statistically significant association between Type 1 CFI rare variants and disease risk in different ethnicities, using gnomAD populations as controls. Results: Type 1 CFI rare variants were enriched in all European AAMD cohorts, with odds ratios (ORs) ranging between 3.1 and 7.8, and a greater enrichment was observed in dry AMD from FINBB (OR 8.9, 95% CI 1.49–53.31). The lack of available non-European AAMD datasets prevented us exploring this relationship more globally, however a statistical association may be detectable by future sequencing studies that sample approximately 2,000 AAMD individuals from Ashkenazi Jewish and Latino/Admixed American ethnicities. Conclusions: The relationship between Type 1 CFI rare variants increasing odds of AAMD are well established in Europeans, however the lack of broader genetic data in AAMD has adverse implications for clinical development and future commercialisation strategies of targeted FI therapies in AAMD. These findings emphasise the importance of generating more diverse genetic data in AAMD to improve equity of access to new treatments and address the bias in health care. [ABSTRACT FROM AUTHOR]

Global infections with the Omicron variant of SARS-CoV-2 have now superseded all other similar variant infections we have witnessed thus far. The current global wave mainly caused by a descendant of the SARS-CoV-2 Omicron variant, called BA.2, is the most prevalent in UK, and has a natural history somewhat different from its predecessors. It also appears, that the so-called COVID-19 variant infections, in varying guises, are the harbingers of the post-COVID-19, 'new normal' world of the future, we have to live in. Here, we look at key features of SARS-CoV-2 variants, particularly BA.1 and BA.2, and the reasons for their phenomenal spread, vaccine efficacy against them, as well as the unfolding short-term outlook for the pandemic. [ABSTRACT FROM AUTHOR]

Introduction: A microsimulation model provides important references for decision-making regarding colorectal cancer (CRC) prevention strategies, yet such a well-validated model is scarce in China. Methods: We comprehensively introduce the development of MIcrosimulation Model for the prevention and Intervention of Colorectal Cancer in China (MIMIC-CRC). The MIMIC-CRC was first constructed to simulate the natural history of CRC based on the adenoma-carcinoma pathway. The parameters were calibrated and validated using data from population-based cancer registry data and CRC screening programs. Furthermore, to assess the model's external validity, we compared the model-derived results to outcome patterns of a sigmoidoscopy screening trial in the UK [UK Flexible Sigmoidoscopy Screening (UKFSS) trial]. Finally, we evaluated the application potential of the MIMIC-CRC model in CRC screening by comparing the 8 different strategies. Results: We found that most of the model-predicted colorectal lesion prevalence was within the 95% CIs of observed prevalence in a large population-based CRC screening program in China. In addition, model-predicted sex- and age-specific CRC incidence and mortality were equivalent to the registry-based data. The hazard ratios of model-estimated CRC-related incidence and mortality for sigmoidoscopy screening compared to no screening were 0.60 and 0.51, respectively, which were comparable to the reported results of the UKFSS trial. Moreover, we found that all 8 strategies could reduce CRC incidence and mortality compared to no screening. Conclusions: The well-calibrated and validated MIMIC-CRC model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies and will be useful for further decision-making to CRC prevention. [ABSTRACT FROM AUTHOR]

From the mid nineteenth into the mid twentieth centuries a significant number of British people spent their careers in India administering what was regarded as the most important territory of the British Empire. During this period, an extensive body of literature on Indian wildlife was published both in Britain and in India itself. This paper surveys the authors and the publishers of this literature and suggests that the material was shaped by the differing interests of readers in the two countries. The emergence of a community of enthusiastic naturalists among the British expatriates is contrasted with the promotion of India as an exotic location for readers in Britain itself. The role of hunting narratives in providing information for the study of natural history is explored, along with growing concerns about the need for conservation. The complexity of the relationships between expatriate British naturalists and the local populations is used to throw light on how the situation changed in the decades leading to independence. In conclusion, the publications of the Bombay Natural History Society are used to illustrate these developments [ABSTRACT FROM AUTHOR]

Objective: To analyse communication about the natural course of self-limiting illnesses, as part of shared decision-making (SDM), in general practice consultations., Methods: Natural history communication and SDM (using Observing Patient Involvement in Decision-Making (OPTION-12) and Assessing Communication about Evidence and Patient Preferences (ACEPP) items) were rated by two raters using transcripts from the UK 'One in a Million' database., Results: Of 55 eligible consultations, a 'wait and see' option was mentioned in 27 consultations (49 %), using varying terminology, with a general recovery timeframe provided in 21. Mean OPTION-12 score (of 100) was 25.2 (SD=7.4), indicating a low level of SDM. Mean ACEPP score (out of 5) was 1.2 (SD=0.5), indicating minimal communication about the options' benefits and harms. Recovery likelihood was quantified in only two consultations, while harms were quantified in none., Conclusion: Communication about the natural history of self-limiting illnesses was generally limited. The 'wait and see' approach, along with its benefits and harms, was typically not explicitly presented as an option for patients to consider., Practice Implications: Improving clinicians' awareness of the importance of and skills for communicating the natural history of self-limiting illnesses, as part of SDM, may facilitate informed decision-making in managing these conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To provide a preliminary test of the prediction that fewer former heavy drinkers will identify themselves as being in recovery in the UK versus the USA.Methods: An online cross-sectional survey was completed by a convenience sample of former heavy drinkers. This sample was identified from participants recruited to complete a questionnaire about alcohol consumption. The recruitment advertisement specified that the participants did not need to drink alcohol. The survey included items assessing self-reported current and past levels of alcohol consumption, alcohol dependence at time of heaviest alcohol consumption (ICD-10 criteria), and questions regarding identifying as currently or ever being in recovery taken from a survey by Kelly et al. (2018).Results: Out of 5002 participants who completed the questionnaire, 150 were identified as former heavy drinkers from the UK or the USA. The proportion of participants reporting alcohol dependence, and the proportion of participants reporting past year abstinence, did not differ significantly between the UK and the USA (p = .841 and 0.300 respectively). Compared to participants from the UK, participants in the USA were more likely to report that they had a problem with drinking but now no longer do (24.1 % vs. 56.0 %; p < .001), and that they currently identified (4.2 % vs. 21.2 %; p = .003) or ever identified (7.4 % vs. 30.2 %; p = .001) as being in recovery.Conclusions: Identifying as being in recovery appears more common in the USA than the UK among former heavy drinkers. This apparent difference in prevalence may reflect historic differences in treatment services offered in these countries, particularly with respect to the predominance of a 12-step approach in the USA. These findings should be replicated in a representative sample. [ABSTRACT FROM AUTHOR]

Objectives X-Linked hypophosphataemic rickets (XLH) is a rare multi-systemic disease of mineral homeostasis that has a prominent skeletal phenotype. The aim of this study was to describe additional comorbidities in XLH patients compared with general population controls. Methods The Clinical Practice Research Datalink (CPRD) GOLD was used to identify a cohort of XLH patients (1995–2016), along with a non-XLH cohort matched (1 : 4) on age, sex and GP practice. Using the CALIBER portal, phenotyping algorithms were used to identify the first diagnosis (and associated age) of 273 comorbid conditions during patient follow-up. Fifteen major disease categories were used and the proportion of patients having ≥1 diagnosis was compared between cohorts for each category and condition. Main analyses were repeated according to the Index of Multiple Deprivation (IMD). Results There were 64 and 256 patients in the XLH and non-XLH cohorts, respectively. There was increased prevalence of endocrine [OR 3.46 (95% CI: 1.44, 8.31)] and neurological [OR 3.01 (95% CI: 1.41, 6.44)] disorders among XLH patients. Across all specific comorbidities, four were at least twice as likely to be present in XLH cases, but only depression met the Bonferroni threshold: OR 2.95 (95% CI: 1.47, 5.92). Distribution of IMD among XLH cases indicated greater deprivation than the general population. Conclusion We describe a higher risk of mental illness in XLH patients compared with matched controls, and greater than expected deprivation. These findings may have implications for clinical practice guidelines and decisions around health and social care provision for these patients. [ABSTRACT FROM AUTHOR]

Summary: Systemic immunoglobulin light chain amyloidosis (AL) is an incurable disorder, and the natural history is incompletely understood. In this study, we describe its natural history based on an analysis of real‐world longitudinal data. All patients seen at the National Amyloidosis Centre, UK, between February 2010 and August 2019 and treated with up‐front bortezomib are included. In all, 1 276 patients received the first‐line treatment; 259, 85, and 32 patients received second, third, and fourth treatment lines, respectively. Among patients requiring further treatment after the first line, 77·2% started the second line within two years of the first line; 50·5%, 50·6%, 40·1% and 40·6% of patients had achieved at least very good partial response after the first, second, third and fourth treatment lines. Median overall survival (OS) from first, second, third and fourth lines was 45 months, 56 months, 37 months and not reached, respectively (P = 0·109). In summary, although relapses occur in AL amyloidosis, the outcomes and responses do not worsen with each subsequent relapse, making it attractive to design therapeutics with curative intent. [ABSTRACT FROM AUTHOR]

Objective: Autism spectrum disorder (ASD) is currently considered an early-onset neurodevelopmental condition. Follow-up studies of clinic-ascertained autism suggest that autistic symptoms typically decline with age, although symptom improvement is limited for some. To date there have been no population-based prospective studies investigating the natural history of autistic symptoms from childhood to adulthood. The aim of this study was to characterize the development and heterogeneity of autistic symptoms in a population-based cohort from childhood to age 25.Methods: Data were analyzed in a prospective U.K. population-based cohort (ALSPAC). Trajectories were derived using five assessments of the parent-rated Social and Communication Disorders Checklist (SCDC) spanning ages 7-25. Additional measures were used to validate symptom trajectories.Results: Three distinct SCDC symptom trajectory classes were identified: low (88.5%), declining (5.0%), and late-emerging (6.5%). Both the declining and late-emerging trajectory classes were associated with child and adult ASD measures, low IQ, communication problems, peer problems, and worse adult functioning compared with the low trajectory class. Male sex was associated with a higher likelihood of being in the declining trajectory class (odds ratio=2.84, 95% CI=2.19, 3.69). This sex difference was not observed in the late-emerging class (odds ratio=1.00, 95% CI=0.80, 1.24) compared with the low trajectory class.Conclusions: ASD symptom levels that emerged early tended to decline across development, although impairment was still present in adulthood for some. For others, autistic symptoms emerged across adolescence and adulthood. This challenges our current understanding that ASD symptoms inevitably first manifest early in development. [ABSTRACT FROM AUTHOR]

Objective: To investigate the demographics, natural history and treatment outcomes of non-molar gestational choriocarcinoma.Design: A retrospective national population-based study.Setting: UK 1995-2015.Population: A total of 234 women with a diagnosis of gestational choriocarcinoma, in the absence of a prior molar pregnancy, managed at the UKs two gestational trophoblast centres in London and Sheffield.Methods: Retrospective review of the patient's demographic and clinical data. Comparison with contemporary UK birth and pregnancy statistics.Main Outcomes: Incidence statistics for non-molar choriocarcinoma across the maternal age groups. Cure rates for patients by FIGO prognostic score group.Results: Over the 21-year study period, there were 234 cases of non-molar gestational choriocarcinoma, giving an incidence of 1:66 775 relative to live births and 1:84 226 to viable pregnancies. For women aged under 20, the incidence relative to viable pregnancies was 1:223 494, for ages 30-34, 1:80 227, and for ages 40-45, 1:41 718. Treatment outcomes indicated an overall 94.4% cure rate. Divided by FIGO prognostic groups, the cure rates were low-risk group 100%, high-risk group 96% and ultra-high-risk group 80.5%.Conclusions: Non-molar gestational choriocarcinoma is a very rare diagnosis with little prior detailed information on the demographics and natural history. The data in this study give age-related incidence data based on a large national population study. The results also demonstrated the widely varying natural history of this rare malignancy and the marked correlation of disease incidence with rising maternal age.Tweetable Abstract: National gestational choriocarcinoma database indicates a close association between increasing maternal age and incidence. [ABSTRACT FROM AUTHOR]

Context: Normocalcaemic hypoparathyroidism (NHYPO) is characterized by low levels of parathyroid hormone (PTH) with normal levels of calcium. There is little in the current literature on this disease, with only two studies published on its prevalence, while its natural history remains relatively unknown. Objectives: To identify the prevalence of NHYPO in a UK referral population and to study the natural history of the disorder. Design: Retrospective study. Five‐year follow‐up. Patients: 6280 patients referred for a BMD measurement in a Metabolic Bone referral centre. Measurements: Prevalence of NHYPO and variability of calcium. Results: Based on laboratory results on the index day, 22 patients with NHYPO were identified. Four patients were excluded due to non‐PTH‐induced hypocalcaemia and unconfirmed data. The final prevalence was 0.29%. Only 67% had persistent normocalcaemia, and the rest had intermittent hypocalcaemia. Two of these patients also had persistently low PTH on two occasions. Most of the patients had one PTH measurement available. No patient developed permanent hypoparathyroidism. Conclusions: The prevalence calculated from this UK referral population is lower when compared to results from previous studies. NHYPO patients often have episodes of hypocalcaemia with some cases having no apparent reason for calcium levels below the reference range. [ABSTRACT FROM AUTHOR]

Background: We determined the detection rate of monoclonal gammopathy of undetermined significance (MGUS) and follow-up of MGUS patients in a center that uses reflex testing at globulin levels outside the reference range as part of its routine service to detect monoclonal protein (M-protein). We recorded the natural history and follow-up of these patients. This is one of the first reports on the diagnosis and follow-up of MGUS patients within the UK. Patients and Methods: A total of 163 patients diagnosed in 2006 and 393 patients with M-protein on long-term follow-up in 2006 were followed over a period of 10 years (y) by community physicians with laboratory support. Results: In 2006, newly diagnosed patients with an M-protein and total number of patients as a percentage of the Worcestershire population were, respectively, 0.025%, 0.045% (at 45– 49y); 0.1%, 0.25% (at 60– 64y); and 0.26%, 1.12% (at 75– 79y). Patients with M-protein had a survival of 35.5% at 10 y and 43.5% at > 10y follow-up. Kaplan–Meier analysis of patients with an M-protein showed that lymphoplasma-cell proliferative disorders (LPD)-free survival was 91% for both 10y and > 10y follow-up. LPD-free survival decreased to approximately 73% when competing causes (death due to unrelated causes, transient M-protein, loss to follow-up) were censored. Progression to LPD occurred at initial M-protein values of 3g/L at diagnosis. During follow-up, 38.3% died without evidence of LPD, 12% were diagnosed with transient M-protein, 8.7% developed LPD, 10.9% had stable M-protein, 4.9% showed increasing M-protein, and 25.2% were lost to follow-up. Survival curves showed that M-protein isotype contributed to LPD-free survival in the order IgG=IgM>IgA>biclonal M-protein. Conclusion: Geographical variations in the diagnosis and follow-up of MGUS patients in the UK need investigation. From public health viewpoint, it is essential to determine MGUS follow-up to improve clinical care and individualise risk-based follow-up of patients. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin-G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory condition that can affect multiple organs. Despite growing interest in this condition, the natural history and management of IgG4-RD remain poorly understood. Aim To describe the clinical characteristics, treatment and outcomes of IgG4-RD in a multi-ethnic UK cohort, and investigate its possible association with malignancy. Design Retrospective analysis of case-note and electronic data. Methods Cases were identified from sub-specialty cohorts and a systematic search of an NHS trust histopathology database using 'IgG4' or 'inflammatory pseudotumour' as search terms. Electronic records, imaging and histopathology reports were reviewed. Results In total, 66 identified cases of IgG4-RD showed a similar multi-ethnic spread to the local population of North West London. The median age was 59 years and 71% of patients were male. Presenting symptoms relating to mass effect of a lesion were present in 48% of cases and the mean number of organs involved was 2.4. Total of 10 patients had reported malignancies with 6 of these being haematological. 83% of those treated with steroids had good initial response; however, 50% had relapsing-remitting disease. Rituximab was administered in 11 cases and all achieved an initial serological response. Despite this, seven patients subsequently relapsed after a mean duration of 11 months and four progressed despite treatment. Conclusions We report a large UK-based cohort of IgG4-RD that shows no clear ethnic predisposition and a wide range of affected organs. We discuss the use of serum IgG4 concentrations as a disease marker in IgG4-RD, the association with malignant disease and outcomes according to differing treatment regimens. [ABSTRACT FROM AUTHOR]

Bacterial–host interactions are non-linear and actually threefold, involving significant selection through predatory lytic bacteriophages in the host environment. In studies of human and animal gut microbiome bacteria, it is important to consider phage in all host–pathogen interactions. We use an important zoonotic pathogen, Shiga toxigenic Escherichia coli (STEC) O157:H7, to investigate this. Our study provides evidence that phage resistance profiles are well maintained at the sub-lineage level with variation in profiles within sub-lineages uncommon. This indicates that phage resistance heterogeneity happened early on in the STEC O157:H7 natural history and that occasional "wobbles" do not often outcompete the stable lineage unless combined with a competitive advantage. We discuss an example of this in the acquisition of stx2a that, while an important virulence factor, also conveys increased phage cross-resistance. We also discuss the role of phage resistance in co-occurrence of the three stable lineages worldwide and whether differing phage resistance is maintaining diversity. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a growing contributor to the global burden of noncommunicable diseases. Early diagnosis and treatment can reduce the severity of kidney damage and the need for dialysis or transplantation. It is not known whether mild-to-moderate renal pelvis dilatation (RPD) identified at 18-20 weeks gestation is an early indicator of renal pathology. The aim of this follow-up to the Welsh Study of Mothers and Babies was to assess the risk of hospital admission in children with mild-to-moderate antenatal RPD compared with children without this finding. We also examined how the natural history of the RPD (whether the dilatation persists in later pregnancy or postpartum) or its characteristics (unilateral versus bilateral) changed the risk of hospital admission.Methods/findings: This population-based cohort study included singleton babies born in Wales between January 1, 2009, and December 31, 2011 (n = 22,045). We linked ultrasound scan data to routinely available data on hospital admissions from the Patient Episode Database for Wales (PEDW). The outcome was a hospital admission for urinary tract causes (defined by an expert study steering group) in the first three years of life. We used Cox regression to model time to first hospital admission, according to whether there was evidence of RPD at the fetal anomaly scan (FAS) and/or evidence of dilatation in later investigations, adjusting for other predictors of admission. We used multiple imputation with chained equations to impute values for missing data. We included 21,239 children in the analysis. The risk of at least one hospital admission was seven times greater in those with RPD (n = 138) compared with those without (n = 21,101, conditional hazard ratio [cHR] 7.23, 95% confidence interval [CI] 4.31-12.15, p < 0.001). The risk of hospital admission was higher in children with RPD at the FAS and later dilatation (cHR 25.13, 95% CI 13.26-47.64, p < 0.001) and in children without RPD at the FAS who had later dilatation (cHR 62.06, 95% CI 41.10-93.71, p < 0.001) than in children without RPD (n = 21,057). Among children with RPD at the FAS but no dilatation in later pregnancy or postpartum, we did not find an association with hospital admissions (cHR 2.16, 95% CI 0.69-6.75, p = 0.185), except when the initial dilatation was bilateral (cHR 4.77, 95% CI 1.17-19.47, p = 0.029). Limitations of the study include small numbers in subgroups (meaning that these results should be interpreted with caution), that less severe outcomes (such as urinary tract infections [UTIs] managed in the community or in outpatients) could not be included in our analysis, and that obtaining records of radiological investigations later in pregnancy and postpartum was challenging. Our conclusions were consistent after conducting sensitivity analyses to account for some of these limitations.Conclusions: In this large population-based study, children with RPD at the FAS had higher rates of hospital admissions when there was persistent dilatation in later pregnancy or postpartum. Our results can be used to improve counselling of parents and develop care pathways for antenatal screening programmes, including protocols for reporting and further investigation of RPD. [ABSTRACT FROM AUTHOR]

Vocal fold nodules present the voice clinic team with a number of clinical dilemmas which are not as simple as previously thought. The definition, aetiology, prevalence and diagnosis are all poorly understood. Furthermore, treatment evidence for both behavioural and surgical approaches is weak. This paper reviews the published evidence pertaining to all of these aspects. Specific areas of uncertainty that remain include poorly defined nomenclature, the natural history of paediatric vocal nodules, the establishment of criteria to measure successful treatment, optimal configuration of speech therapy regimens and the rationale for surgical intervention. The authors suggest the development of evidence‐based guidelines for UK practice. [ABSTRACT FROM AUTHOR]

The early East India Company (EIC) had a profound effect on London, filling the British capital with new things, ideas and people; altering its streets; and introducing exotic plants and animals. Company commodities – from saltpetre to tea to opium – were natural products and the EIC sought throughout the period to understand how to produce and control them. In doing so, the company amassed information, designed experiments and drew on the expertise of people in the settlements and of individuals and institutions in London. Frequent collaborators in London included the Royal Society and the Society of Apothecaries. Seeking success in the settlements and patronage in London, company servants amassed large amounts of data concerning natural objects and artificial practices. Throughout the seventeenth and eighteenth centuries, company scholars and their supporters in London sought to counter critiques of the EIC by demonstrating the utility to the nation of the objects and ideas they brought home. The EIC transformed itself several times between 1600 and 1800. Nonetheless, throughout the seventeenth and eighteenth centuries, its knowledge culture was characterized by reliance on informal networks that linked the settlements with one another and with London. [ABSTRACT FROM AUTHOR]

This essay introduces a special issue of the BJHS on communities of natural knowledge and artificial practice in seventeenth- and eighteenth-century London. In seeking to understand the rise of a learned and technical culture within a growing and changing city, our approach has been inclusive in terms of the activities, people and places we consider worth exploring but shaped by a sense of the importance of collective activity, training, storage of information and identity. London's knowledge culture was formed by the public, pragmatic and commercial spaces of the city rather than by the academy or the court. In this introduction, we outline the types of group and institution within our view and acknowledge the many locations that might be explored further. Above all, we introduce a particular vision of London's potential as a city of knowledge and practice, arising from its commercial and mercantile activity and fostered within its range of corporations, institutions and associations. This was recognized and promoted by contemporary authors, including natural and experimental philosophers, practical mathematicians, artisans and others, who sought to establish a place for and recognition of their individual and collective skills and knowledge within the metropolis. [ABSTRACT FROM AUTHOR]

This article attempts to think through the logic and distinctiveness of the early Royal Society's position as a metropolitan knowledge community and chartered corporation, and the links between these aspects of its being. Among the knowledge communities of Restoration London it is one of the best known and most studied, but also one of the least typical and in many respects one of the least coherent. It was also quite unlike the chartered corporations of the City of London, exercising almost none of their ordinary functions and being granted very limited power and few responsibilities. I explore the society's imaginative and material engagements with longer-established corporate bodies, institutions and knowledge communities, and show how those encounters repeatedly reshaped the early society's internal organization, outward conduct and self-understanding. Building on fundamental work by Michael Hunter, Adrian Johns, Lisa Jardine and Jim Bennett, and new archival evidence, I examine the importance of the city to the society's foundational rhetoric and the shifting orientation of its search for patronage, the development of its charter, and how it learned to interpret the limits and possibilities of its privileges through its encounters with other chartered bodies, emphasizing the contingent nature of its early development. [ABSTRACT FROM AUTHOR]

Soil fauna constitutes one of the most abundant and richest environments on earth (Coleman et al. 2004, Fundamentals of solil ecology, 2nd ed. Elsevier Academic Press, London, UK). Different degrees of soil disturbance can affect arthropod diversity, which allows a correlation of biodiversity to quality of habitat. The present study aimed to evaluate the impact of habitat on Theraphosidae spiders, with special focus on Grammostola rosea. Slight differences in the diversity of Theraphosidae between the disturbed area of Cerro Huechuraba and the undisturbed Panul Park were found. However, a high dominance of G. rosea was observed in both study areas. G. rosea density 1,350 ind/ha in Panul Park, and 750 ind/ha in Cerro Huechuraba. UPGMA cluster analysis did not show significant differences between established environments. A standard methodology to develop inventories of Theraphosidae was proposed. The distribution of G. rosea and its natural history were reported. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • In UK children, HCV infection is transmitted by IV drug use in 53%, blood products in 24% and perinatally in 11%. • Cirrhosis occurs in 32% of patients, a median of 33 years after infection, irrespective of infection route. • Treatment impact on disease progression better if started before cirrhosis. • Anti-HCV therapy should be available in childhood to prevent long-term liver disease. Background & Aims Chronic hepatitis C virus (HCV) infection is a global health burden. Although HCV infection rarely contributes to morbidity during childhood, most HCV-infected children develop chronic HCV with a lifetime risk of liver disease. Little is known about the development of long-term liver disease and the effect of treatment in patients infected with HCV in childhood. Method This study was a retrospective review of patients infected with HCV in childhood enrolled in HCV Research UK. A total of 1,049 patients were identified and included. Results The main routes of infection were intravenous drug use (53%), blood product exposure (24%) and perinatal infection (11%). Liver disease developed in 32% of patients, a median of 33 years after infection, irrespective of the mode of infection. Therefore, patients with perinatal exposure developed cirrhosis at an earlier age than the rest of the risk groups. The incidence of hepatocellular carcinoma (HCC) was 5%, liver transplant 4% and death occurred in 3%. Overall, 663 patients were treated (55% with interferon/pegylated interferon and 40% with direct-acting antivirals). Sustained virological response (SVR) was achieved in 406 (75%). There was a higher mortality rate among patients without SVR vs. those with SVR (5% vs. 1%, p = 0.003). Treatment was more effective in patients without cirrhosis and disease progression was less frequent (13%) than in patients with cirrhosis at the time of therapy (28%) p < 0.001. Patients with cirrhosis were more likely to develop HCC, require liver transplantation, or die. Conclusion HCV infection in young people causes significant liver disease, which can now be prevented with antiviral therapy. Early treatment, especially before development of cirrhosis is essential. Detection of HCV should be aimed at relevant risk groups and antiviral therapy should be made available in childhood to prevent long-term liver disease and spread of HCV. Lay summary Chronic hepatitis C virus (HCV) infection is a global health problem, which can now be treated with potent direct-acting antiviral drugs. This study demonstrates that HCV infection in childhood causes serious liver disease in 32% of patients, a median of 33 years after infection, irrespective of age, mode and route of infection. Disease outcomes were better in patients treated before the development of advanced liver disease. Antiviral therapy should be made available in childhood to prevent long-term liver disease and the spread of HCV. [ABSTRACT FROM AUTHOR]

From walking through a park to sitting on a beach, much is known about the therapeutic potential of direct contact with natural environments. Yet routinely in the UK, millions of people encounter nature in a completely different way: through their television screens. Despite the ubiquity of natural history programming, little is understood about its impact on the restorative and affective experiences of audiences. Nowhere is this truer than in the bold orchestral scores that accompany almost all nature documentaries. Whilst considerable evidence suggests that separately, both nature and music can provide a range of psychological benefits, how their pairing might affect the wellbeing potential of virtual nature encounters remains largely unknown. Similarly, scant research has considered how viewers' own experiences, recalled through memories, might influence outcomes. To explore these areas, we formed a transdisciplinary broadcast initiative, called BBC Soundscapes for Wellbeing. Part of this project involved a randomized and controlled experiment that presented participants (n = 7636) with a dynamic nature scene accompanied by one of four acoustic tracks. Results demonstrated that whilst adding music to this scene led to increased feelings of excitement, it led to no other restorative or affective benefits when compared to silence. In contrast, the addition of natural sounds was associated with greater feelings of restorative potential, calmness, and excitement. Natural sounds also drove significant increases in the complex emotions of awe and nostalgia. Crucially, results showed the substantial moderating effects of participant memories. Those with positive memories stimulated by the experience reported significantly greater effects across all conditions and dependent variables. We find that although the acoustic design of virtual nature encounters can affect a range of emotional responses, the memories triggered by these experiences may be far more important for predicting viewer outcomes. • Nature and music-based soundscapes were systematically added to a digital nature scene. • Natural sounds increased ratings of cognitive restoration, calmness, awe, and nostalgia. • Music enhanced feelings of excitement. • Participant memories were a significant moderator of all outcome variables. • Memories were a more effective predictor of outcomes than acoustic condition. [ABSTRACT FROM AUTHOR]

The natural history of Spinal muscular atrophy (SMA) is changing rapidly due to the availability of novel medications. Nusinersen was the first treatment approved in the UK under a managed access agreement (MAA). The revised upper limb module (RULM) SMA scale is used to assess the upper limb function in the MAA. There are limited data on hand function, strength and dexterity in patients with SMA before and after starting nusinersen. The purpose of this study is to compare upper limb function, muscle strength and hand dexterity in children with SMA type 2 and 3 pre- and post- nusinersen treatment. Longitudinal data were collected from 17 children (8 with SMA 2; 9 with SMA 3, [7 ambulant]). Mean age at baseline was 10 years, range 7.1 – 13. 6 (10 girls and 7 boys). The myotools set (MyoGrip, MyoPinch and Moviplate) were used to measure hand grip, thumb pinch strength, and hand function and dexterity of the dominant side. Patients were evaluated at baseline, and six-monthly thereafter for up to 24-months after receiving nusinersen. In SMA 2, mean RULM score was 19.5 (range 13-28) at baseline and 20.4 (13-29) at 12-months; grip was 1.32 kgs/(0.31-1.81) at baseline and 1.80 kgs (1.29-2.74) at 12-months; pinch was 0.81kgs (0.3-1.5) at baseline and 0.84kgs (0.4-1.8) at 12-months dexterity was 47 (40-59) and 51 (42-55) at 12-months. In SMA 3, mean RULM score was unchanged with 33.5 (19-37) at baseline and 33.5 (22-37) at 12-months; grip was 7.5kgs (2.7 – 20.94) at baseline and 8.7kgs (3.71- 23.7) at 12-month follow up; pinch was 2.85kgs (1.5- 4.6) at baseline and 3.3kgs (1.2-6.9) at 12 months; dexterity was 59 (39-73) and 62 (48-75) at 12-months. The interim analyses at 12-months post Nusinersen treatment showed an increase in all scores for upper limb function and strength in both groups and significant difference in grip strength and RULM (p<0.05), compared to untreated SMA patients. Further data on the 24 months changes will be presented at the conference. [ABSTRACT FROM AUTHOR]

Objective: The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care., Design: Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium)., Methods: Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed., Results: Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (MRIs) [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95% CI, 4.9%-8.1%) and 14.5% (95% CI, 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95% CI, 10.4%-17.8%) and 21.3% (95% CI, 16.4%-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, and size at baseline were not predictors of enlargement/reduction. At the time of detection, 7.2%, 1.7%, and 1.5% patients had secondary hypogonadism, hypothyroidism, and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma)., Conclusions: Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance., Competing Interests: Conflicts of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)

This paper examines how communities of naturalists in mid-nineteenth-century Britain were formed and solidified around the shared practices of public meetings, the publication and reading of periodicals, and the making and printing of images. By focusing on communities of naturalists and the sites of their communication, this article undermines the distinction between amateur and professional scientific practice. Building on the notion of imagined communities, this paper also shows that in some cases the editors and illustrators utilized imagery to construct a specifically British naturalist community. Following three ‘amateur’ natural-history periodicals (Science Gossip , Midland Naturalist and the Journal of the Quekett Microscopical Club) the article demonstrates how the production and reproduction of natural history in the nineteenth century was contingent on community debate – and that this debate both was highly visual and moved across printed and geographical boundaries. This paper investigates images both for their purported success and for their ascribed value to natural history. Additionally, it considers the debates over their limitations and alleged failures of printing. Altogether, the article argues that investigating the communal practices of observation, writing, drawing and engraving allows for a better understanding of the shared practices of nineteenth-century natural history. [ABSTRACT FROM AUTHOR]

Dugald Stewart claims that conjectural history is 'the peculiar glory of the latter half of the eighteenth century'. Yet it is hard to see why, in his view, conjectural histories are not merely confabulated just-so stories. This paper examines Stewart's views about the epistemic and moral value of conjectural history. [ABSTRACT FROM AUTHOR]

This article advances a greater understanding of building materials, specifically stone, as a scientific object of experimentation that moved from the realm of natural philosophy and into architectural design and industry trades in eighteenth-century England. Revd William Borlase contemplated stone's pragmatic use in disciplinary fields that lay beyond the scientist's chemical laboratory or the antiquarian's personal collections. Cobalt, spar and other specimens of stone acted as heuristic models of architectural materials that were tested as they were being conceived in practice. These conceptions of stone gradually transformed these building materials into more industry-ready incarnations, predicted by naturalists like Borlase. [ABSTRACT FROM AUTHOR]

Objectives:The objectives of this research were: (1) to heighten awareness of Gaucher disease (GD), a rare lysosomal storage disorder with highly heterogeneous patterns of organ involvement and disease severity, to clinicians most likely to encounter these patients, and; (2) to summarize the published evidence on GD epidemiology which is essential to accurately depict the total societal burden of this rare worldwide disorder. Methods:A comprehensive literature review was undertaken to summarize the published evidence on the epidemiology of GD. MEDLINE, EMBASE, CENTRAL, and ‘grey’ literature sources published in English between January 1990 and March 2015 were searched to identify relevant publications. Results:In total, 188 full-text articles were reviewed and findings from 49 studies are summarized herein. The standardized birth incidence of GD in the general population varied from 0.39 to 5.80 per 100 000, and prevalence ranged from 0.70 to 1.75 per 100 000, respectively. Time from onset of GD symptoms to clinical diagnosis was highly variable, with median delays of up to 7 years reported. Discussion:The incidence and prevalence of GD is substantially higher among the Ashkenazi Jewish population than the general population. Limited epidemiologic information was available from Latin America, Africa, Asia, and developed nations such as the United States, Germany, and the United Kingdom. Conclusions:Signs and symptoms of GD frequently mimic more common hematologic conditions resulting in missed or delayed diagnosis. Early diagnosis and prompt initiation of treatment when indicated is crucial to prevent or minimize life-altering or life-threatening liver and skeletal complications. [ABSTRACT FROM AUTHOR]

This study explored the perceptions of ethical issues in supervision among doctoral students and supervisors. The nature of ethical issues identified by doctoral students (n = 28) and their supervisors (n = 14) is explored and the degree of fit and misfit between their perceptions in two cases representing the natural and behavioural sciences is analysed. Supervisors and students identified different ethical issues, which suggest that there are aspects in the supervisory relationship about which there is no shared understanding. There were also differences between the ethical issues emphasised in the natural sciences from those emphasised in the behavioural sciences, suggesting differences between the domains. [ABSTRACT FROM AUTHOR]

Several discrete sources have been used to compile a list of the taxidermists who were active in north east England and in Berwickshire from the 18th century to the middle of the 20th. The list, which is surprisingly large will, it is hoped, serve to underline the importance of the craft in the practise of natural history in Britain during that period. [ABSTRACT FROM AUTHOR]

Pleasantine Mill graduated in microbiology and immunology from McGill University, Montre'al, Canada, and completed her PhD in medical and molecular genetics at the University of Toronto, Canada. There, under the supervision of Chi-chung Hui, she studied Hedgehog signalling pathways in skin development and tumorigenesis. For her postdoctoral research, Pleasantine moved to Ian Jackson's laboratory at the MRC Human Genetics Unit, Edinburgh, UK, with a Natural Sciences and Engineering Research Council of Canada (NSERC) fellowship, followed by a Caledonian Research fellowship. Initially focusing on neural crest development, she identified and studied several mouse mutants that displayed defects in ciliogenesis and cilia structure that went on to be implicated in human disease. Pleasantine established her own research program at the MRC in 2014. Her group investigates the genetic programme for cilia structure and function and the links to human ciliopathies. She is the recipient of the 2019Women in Cell Biology Early Career Award Medal from the British Society for Cell Biology (BSCB). [ABSTRACT FROM AUTHOR]

Nusinersen treatment provides significant functional motor benefit in the chronic forms of spinal muscular atrophy (SMA). Less is known on respiratory outcomes in nusinersen treated patients. Only short-term results on forced vital capacity (FVC) have been reported in heterogeneous treated SMA cohorts. Aim of this study is to evaluate the impact of nusinersen on respiratory function across the iSMAC international cohort of paediatric SMA2 and non-ambulant SMA3 patients (Italian SMA network, US PNCR, UK SMA REACH) when compared to the natural history data (NH) recently published by the consortium. Five-year retrospective study of SMA2 and non-ambulant SMA3 children (age 5-16years) treated with nusinersen within iSMAc centres. We collected lung function expressed as Forced vital capacity absolute and %predicted (FVC %pred), use of non-invasive ventilation (NIV) and cough device. Data was available for 100 patients 81 SMA2, 19 SMA3. Mean (SD) age at first injection was 8(3.3) and 9.4(3.8) years in SMA2 and 3 respectively. Mean disease duration prior to treatment was 7.1(3.3) and 7.3(3.9) years. At first injection 34/65(52%) SMA2 and 2/19 SMA3(11%) were on NIV; 49/65 (75%) SMA2 and 6/20(30%) SMA3 used cough devices. Mean FVC%pred (SD) at first treatment was 53.9(25.8) and 80.6(12.0) respectively. Up to age 13 years, when the respiratory decline is steeper, in treated SMA2 FVC% declined by 2.2%/year vs 4.2% NH, in treated SMA3 FVC% declined by 1.4% vs 6.3%. In the few patients older than 13 years (13 SMA2, 7 SMA3), a clear treatment effect was not detected. One year post treatment 4/36 patients were weaned off NIV, whilst 7, who were self-ventilating at baseline, were established on NIV. This study on the largest cohort of chronic SMA reported so far, confirms the positive role of nusinersen in delaying the respiratory decline in paediatric patients with SMA2 and non-ambulant SMA3 younger than 13 years when compared to natural history. Larger cohorts and longer observation are required to evaluate the role of nusinersen on older patients. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a form of motor neuron disease caused by a mutation in the survival motor neuron 1 gene (SMN1), which results in a wide disease spectrum affecting children and adults. There are four subtypes of SMA depending on age of onset and maximum acquired motor function. The recent advances in drug development have highlighted an urgent need to establish stronger clinical networks and data collection to gain a better understanding of the impact of new drugs on the natural history of the disease. In collaboration with SMA Reach UK (paediatric and data collection network) and the UK SMA Patient Registry, the Adult SMA Reach study aims to implement a standardised dataset and use systematic data collection to generate knowledge on the natural history and the evolving phenotype of adult SMA, the impact of new treatments and management. Adult SMA REACH is a longitudinal observational study, planning to collect clinical data and outcome measures about SMA patients age ≥16 years with genetically confirmed 5q SMA, with a sample size of approximately 209 treated patients and 140 non-treated patients. A working group of UK neuromuscular clinicians and physiotherapists has designed a specific data collection form and the data collection will be performed using an online database, specifically for this study. The visit schedule will be at baseline and thereafter 4-6 monthly for Nusinersen-treated patients and a minimum of 12 monthly, for non-treated patients or treated with other SMA treatments. Data monitoring will be carried out to ensure data quality. This study will link with the UK SMA Patient Registry and collect vital Patient Reported Outcome Measures. Data from the first year of data collection will be presented in the conference. This study will help us to collect information about the natural history of the disease, the impact of new treatments, monitor the safety of treatments and the implementation of new functional scales. [ABSTRACT FROM AUTHOR]

Background: Natural history has a long tradition in the UK, dating back to before Charles Darwin. Developing from a principally amateur pursuit, natural history continues to attract both amateur and professional involvement. Within the context of citizen science and public engagement, we examine the motivations behind citizen participation in the national survey activities of the Open Air Laboratories (OPAL) programme, looking at: people's experiences of the surveys as 'project-based leisure'; their motivations for taking part and barriers to continued participation; where they feature on our continuum of engagement; and whether participation in an OPAL survey facilitated their movement between categories along this continuum. The paper focuses on a less-expected but very significant outcome regarding the participation of already-engaged amateur naturalists in citizen science. Results: Our main findings relate to: first, how committed amateur naturalists (already-engaged) have also enjoyed contributing to OPAL and the need to respect and work with their interest to encourage broader and deeper involvement; and second, how new (previously-unengaged) and relatively new participants (casually-engaged) have gained confidence, renewed their interests, refocussed their activities and/or gained validation from participation in OPAL. Overall, we argue that engagement with and enthusiasm for the scientific process is a motivation shared by citizens who, prior to participating in the OPAL surveys, were previously-unengaged, casually-engaged or already-engaged in natural history activities. Conclusions: Citizen science has largely been written about by professional scientists for professional scientists interested in developing a project of their own. This study offers a qualitative example of how citizen science can be meaningful to participants beyond what might appear to be a public engagement data collection exercise. [ABSTRACT FROM AUTHOR]

The past 15 years have seen dramatic changes in social norms around sex and sexuality in the UK and worldwide. In 2011, the London Natural History Museum (NHM) contributed to these debates by opening the temporary exhibitionSexual Nature, which aimed to provide ‘a candid exploration of sex in the natural world’ whilst also drawing in an under-represented audience of young adults.Sexual Natureprovides an opportunity to explore Macdonald's ‘politics of display’ in the mutual construction of (public) scientific knowledge, society and sexuality, at a time of intense contestation over sexual norms. WhilstSexual Natureboth reflected and contributed to major reframings of sexuality and what science can say about it, the assumption that it would be possible to present this topic as morally neutral, reliable and uncontested, in line with traditions of public science, proved to be problematic. The language of the exhibition moved back and forth between human/animal similarity and difference, and between scientific and cultural tropes as the NHM tried to maintain epistemic authority whilst also negotiating the moral boundaries of acceptable sexual behaviour. The topic of sex pushed the museum far beyond its usual expertise in the natural sciences towards the unfamiliar territory of the social and human, resulting in an ad hoc search for, and negotiation with, alternative sources of expertise. Boonet al.’s co-curation approach to exhibition building has the potential to extend the NHM's audience-driven strategy, whilst also producing a more coherent and nuanced exhibition about the science of sex. [ABSTRACT FROM PUBLISHER]

A biography of the 19th century British naturalist Mrs. Margaret Gatty is provided. She was born in Essex, England on June 3, 1809 and married Reverend Alfred Gatty in 1839. Particular focus is given to her study of sea-weeds, including her 1863 book "British Sea-Weeds: Drawn From Professor Harvey’s ‘Phycologia Britannica’ With Descriptions, an Amateur’s Synopsis, Rules for Laying out Sea-Weeds, an Order for Arranging Them in a Herbarium, and an Appendix of New Species." Her relationship with phycologist William Henry Harvey is discussed.