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The coronavirus disease 2019 pandemic has necessitated almost exclusive National Health Service focus on emergency work and cancer care. There are concerns that increased hospital and community pressures will lead to decreased referrals and worse outcomes for head and neck cancer patients.
This is a retrospective review of all cases referred for suspected head and neck cancer to our institution in January and April 2020.
There was a 55 per cent decrease in referrals but diagnostic yield rose from 2.9 per cent in January to 8.06 per cent in April. In both months, 100 per cent of patients met the 31- and 62-day targets, with similar 14-day wait time success (97.83 per cent for January vs 98.33 per cent for April). Referrals for laryngopharyngeal reflux rose from 27.5 per cent to 41.9 per cent. Referrals for those aged over 60 years fell from 42 per cent to 26 per cent.
It is suggested that further research be conducted into the reasons why fewer patients were referred, particularly elderly patients, and why laryngopharyngeal reflux is so prevalent in fast-track referrals.
Results of in situ U–Pb dating of calcite spherulites, cone-in-cone (CIC) calcite and calcite fibres from a calcareous concretion of the upper Ediacaran of Finnmark, Arctic Norway, are reported. Calcite spherulites from the innermost layers of the concretion yielded a lower intercept age of 563 ± 70 Ma, which, although imprecise, is within uncertainty of the age of sedimentation based on fossil assemblages. Non-deformed CIC calcite from the bottom part of the concretion yielded an age of 475 ± 25 Ma, which is interpreted as the age of CIC calcite formation during a period of fluid overpressure induced during burial of the sediments. Deformed CIC calcite from the top part of the concretion yielded an age of 418 ± 23 Ma, which overlaps with a known Caledonian tectono-metamorphic event, and indicates a potential post-depositional overprint at this time. Calcite fibres that grew in small fissures along spherulite rims, which are interpreted as a recrystallization feature during deformation and formation of a cleavage, gave an imprecise age of 486 ± 161 Ma. Our results show that U–Pb dating of calcite can provide age constraints for ancient carbonates and syn- to post-depositional processes that operated during burial and metamorphic overprinting.
New information on acritarchs from the Duolbagáisá Formation, Digermulen Peninsula, Arctic Norway, enable recognition of the three Cambrian Series 2 acritarch-based zones: the Skiagia ornata–Fimbriaglomerella membranacea, Heliosphaeridium dissimilare–Skiagia ciliosa and Volkovia dentifera–Liepaina plana Assemblage zones. Acritarchs of the Skiagia ornata–Fimbriaglomerella membranacea Zone (Cambrian Stage 3) appear near the base of the unit, close to an undetermined trilobite. In the Upper Member of the Duolbagáisá Formation, in levels with Kjerulfia n. sp. and Elliptocephala n. sp., appears an assemblage with abundant Skiagia ciliosa, indicative of the Heliosphaeridium dissimilare–Skiagia ciliosa Zone. A few metres higher appear Liepaina plana, Heliosphaeridium notatum and Retisphaeridium dichamerum, which indicate the Volkovia dentifera–Liepaina plana Zone (Cambrian Stage 4). The transition between the Duolbagáisá Formation and the overlying Kistedalen Formation is marked by the appearance of Comasphaeridium longispinosum, Multiplicisphaeridium llynense and Eliasum llaniscum, diagnostic of the Miaolingian Series. This coincides with the disappearance of Skiagia; occurrences of Skiagia in Miaolingian strata consist of reworked material related to the Hawke Bay regression at the Cambrian Stage 4–Wuliuan transition. The absence of Skiagia in higher levels of the Duolbagáisá Formation and Kistedalen Formation suggests that no unconformity formed during the Hawke Bay regression in this area. The chronostratigraphical significance of the Skiagia ornata–Fimbriaglomerella membranacea, Heliosphaeridium dissimilare–Skiagia ciliosa and Volkovia dentifera–Liepaina plana zones is critically analysed. Correlation of the Duolbagáisá Formation with peri-Gondwanan terrains of Avalonia and Iberia is established. The Digermulen Peninsula has great potential as a reference section for establishing a Cambrian chronostratigraphy based on acritarchs.
To investigate trends in health-related quality of life and health service use associated with diabetes and/or major depression in South Australia from 1998 to 2008.
Data analyzed were from 9,059 persons aged ≥15 years who participated in representative surveys of the South Australian population in 1998, 2004 and 2008. Major depression was determined using the mood module of the Primary Care Evaluation of Mental Disorders (PRIME-MD). Diagnosed diabetes and health service use was determined by self-report. Health-related quality of life was assessed using the 36-item Short-Form Health Survey (SF-36) and the 15-item Assessment of Quality of Life (AQoL) instruments. Weighted age-standardized and multiple-adjusted means of dependent measures were computed.
The prevalence of diabetes only, major depression only, and comorbid diabetes and major depression increased by 74%, 36% and 53% from 1998 to 2008. Mean health-related quality of life scores were 9% to 41% lower (worse), and health service use was 49% higher for persons with comorbid diabetes and major depression than for those with diabetes only (all P-values < 0.05), consistently over the 10-year period.
If past trends continue, our results suggest that the population health and economic burden of comorbid diabetes and major depression will grow similarly over the next decade or so. These trends have important implications for making health policy and resource allocation decisions.
Functional magnetic resonance imaging studies (fMRI) in children with Attention Deficit Hyperactivity Disorder (ADHD) have observed functional abnormalities in fronto-striatal and temporo-parietal brain regions during tasks of inhibitory and attention control. However, hardly any modern functional imaging studies have investigated functions of interference inhibition or attention control in adult ADHD.
We used fMRI combined with a variant of the Simon task that measures interference inhibition as well as attention allocation to compare 11 medication-naïve adults (26-30 yrs) with inattentive/hyperactive behaviours and 15 age-matched healthy controls. Patients were followed up from childhood ADHD, recruited from a 20-year prospective longitudinal epidemiological study. All met criteria for inattentive/hyperactive behaviours on an Adult Hyperactive Interview, but only 8 met clinical diagnostic criteria for ADHD. Correlation analyses were furthermore conducted within patients to correlate symptoms with brain activation. Functional connectivity analyses for group differences in fronto-striatal connectivity will be presented at the conference.
No differences were observed in task performance. During interference inhibition, adults with persistent inattentive/hyperactive compared to controls showed reduced activation in predominantly left orbitofrontal and medial cortex, caudate and putamen. During attention allocation adults with hyperactive behaviours showed dysfunction in left inferior/dorsolateral prefrontal cortex and in right inferior and superior parietal areas. Correlation analysis showed a significant negative correlation between inattentive/hyperactive behaviours and the parietal activation cluster during interference inhibition. The study demonstrates the continuity of the pattern of fronto-striatal and parietal neurofunctional abnormalities during tasks of interference inhibition and attention allocation from childhood to adult ADHD even with symptomatic improvement.
Attention Deficit Hyperactivity Disorder (ADHD) in children has been associated with functional abnormalities in fronto-striatal brain regions during tasks of inhibitory control. In adults with ADHD, however, no functional magnetic resonance imaging (fMRI) study has investigated the neurofunctional correlates of the most compromised cognitive functions of motor response inhibition or cognitive flexibility.
fMRI was used combined with a tracking Stop task of motor response inhibition and a cognitive Switch task to compare brain function between 11 medication-naïve adults (26-30 yrs) with inattentive/hyperactive behaviours and 14 age-matched healthy controls. Patients were followed up from childhood ADHD, recruited from a 20-year prospective longitudinal epidemiological study. All met criteria for inattentive/hyperactive behaviours on an Adult Hyperactive Interview, but only 8 met clinical diagnostic criteria for ADHD. Whole brain regression MR analyses were furthermore conducted within patients to correlate symptoms with brain activation. Functional connectivity analyses for group differences in fronto-striatal connectivity will be presented at the conference.
Despite comparable task performance, adults with persistent inattentive/hyperactive behaviours showed reduced activation compared to controls in inferior prefrontal cortex, caudate and thalamus during both tasks, as well as in parietal lobes during the Switch task. Regression analyses furthermore showed a linear negative correlation between behavioural symptoms and overlapping, but more extensive fronto-striatal, parietal and cerebellar brain dysfunction. The findings demonstrate for the first time the persistence of the typical childhood ADHD pattern of fronto-striatal dysfunction during tasks of cognitive control in adults with persisting behavioural symptoms, suggesting stability/continuity of neurofunctional abnormalities between childhood and early adulthood.
Cognitive Behaviour Therapy (CBT) is an effective psychological intervention for children and young people with anxiety disorders (James et al, 2013). This has led to interest in whether CBT programmes can be widely provided in schools to prevent or ameliorate anxiety symptoms in children.
Results from school based anxiety prevention trials are encouraging (Neil & Christensen 2009; Fisak, Richard, Mann 2011). Before the widespread use of school based preventive programmes can be advocated methodologically robust evaluations are required to demonstrate that they are effective when transported to everyday settings.
To undertake a pragmatic randomised controlled trial (RCT) of a universal school based CBT programme (Friends for Life) for children aged 9-10 years of age .
Three arm RCT comparing Friends for Life delivered by trained health or school leaders with usual school provision (Stallard et al,2012). Primary outcome the Revised Child Anxiety and Depression Scale (RCADS) at 12 month follow-up.
A total of 1362 children from 40 schools participated with 1257 (92%) being re-assessed at follow-up. There was a difference in adjusted mean child report RCADS scores for health-led versus school-led FRIENDS (−3.94, 95%CI −6.41 to −1.47) and health-led FRIENDS versus usual school provision (2.66, 95%CI −5.22 to −0.09). Health-led CBT resulted in greater reductions in symptoms of anxiety than the other two arms (Stallard et al 2014),
Our pragmatic trial demonstrates that universally delivered anxiety prevention programmes can be effective when transported into schools. However, effectiveness varies depending upon who delivers them.
As part of the ongoing effort to improve the Northern Hemisphere radiocarbon (14C) calibration curve, this study investigates the period of 856 BC to 626 BC (2805–2575 yr BP) with a total of 403 single-year 14C measurements. In this age range, IntCal13 was constructed largely from German and Irish oak as well as Californian bristlecone pine 14C dates, with most samples measured with a 10-yr resolution. The new data presented here is the first atmospheric 14C single-year record of the older end of the Hallstatt plateau based on an absolutely dated tree-ring chronology. The data helped reveal a major solar proton event (SPE) which caused a spike in the production rate of cosmogenic radionuclides around 2610/2609 BP. This production event is thought to have reached a magnitude similar to the 774/775 AD production event but has remained undetected due to averaging effects in the decadal calibration data. The record leading up to the 2610/2609 BP event reveals a 11-yr solar cycle with varying cyclicity. Features of the new data and the benefits of higher resolution calibration are discussed.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study with a primary focus on cognitive and brain aging in men, particularly early identification of risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). It comprises a subset of over 1600 twins from the Vietnam Era Twin Registry. Twins live all over the USA. Assessments began when participants were in their 50s. Follow-ups were conducted every 5–6 years, and wave 3 has been completed as of this writing. The age range of participants is narrow (about 10 years). An extensive neurocognitive test battery has added precision in assessing differences in middle-aged adults, and predicting progression to MCI. Young adult cognitive test data (at an average age of 20 years) provide a means of disentangling aging effects from longstanding differences. Genome wide genotyping and plasma assays of AD biomarkers from waves 1 and 3 were conducted in wave 3. These features make the VETSA ideal for studying the heterogeneity of within-individual trajectories from midlife to old age, and for early detection of risk factors for cognitive decline.
The Project Talent Twin and Sibling (PTTS) study includes 4481 multiples and their 522 nontwin siblings from 2233 families. The sample was drawn from Project Talent, a U.S. national longitudinal study of 377,000 individuals born 1942–1946, first assessed in 1960 and representative of U.S. students in secondary school (Grades 9–12). In addition to the twins and triplets, the 1960 dataset includes 84,000 siblings from 40,000 other families. This design is both genetically informative and unique in facilitating separation of the ‘common’ environment into three sources of variation: shared by all siblings within a family, specific to twin-pairs, and associated with school/community-level factors. We term this the GIFTS model for genetics, individual, family, twin, and school sources of variance. In our article published in a previous Twin Research and Human Genetics special issue, we described data collections conducted with the full Project Talent sample during 1960–1974, methods for the recent linking of siblings within families, identification of twins, and the design of a 54-year follow-up of the PTTS sample, when participants were 68–72 years old. In the current article, we summarize participation and data available from this 2014 collection, describe our method for assigning zygosity using survey responses and yearbook photographs, illustrate the GIFTS model applied to 1960 vocabulary scores from more than 80,000 adolescent twins, siblings and schoolmates and summarize the next wave of PTTS data collection being conducted as part of the larger Project Talent Aging Study.
Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.
TwinsMX is a national twin registry in Mexico recently created with institutional support from the Universidad Nacional Autónoma de México. It aims to serve as a platform to advance epidemiological and genetic research in the country and to disentangle the genetic and environmental contributions to health and disease in the admixed Mexican population. Here, we describe our recruitment and data collection strategies and discuss both the progress to date and future directions. More information about the registry is available on our website: https://twinsmxofficial.unam.mx/ (content in Spanish).
Despite the well-known relevance of twin studies in the medical and social sciences and the growing number of twin registries throughout the world, Latin America has not fully incorporated into the twin research community. We describe the first steps taken toward developing a twin registry in Mexico: its aim, organization, recruiting potential and main short-term objectives.
The Swedish Twin Registry functions as research infrastructure containing information on 216,258 twins born between 1886 and 2015, of whom 86,199 pairs have zygosity determined by DNA, an intrapair similarity algorithm, or being of opposite sex. In essence, practically all twins alive and currently 9 years or older have been invited for participation and donation of DNA on which genomewide single nucleotide polymorphisms array genotyping has been performed. Content, management and alternatives for future improvements are discussed.
Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).
We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.
There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.
These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
The Netherlands Twin Register (NTR) is a national register in which twins, multiples and their parents, siblings, spouses and other family members participate. Here we describe the NTR resources that were created from more than 30 years of data collections; the development and maintenance of the newly developed database systems, and the possibilities these resources create for future research. Since the early 1980s, the NTR has enrolled around 120,000 twins and a roughly equal number of their relatives. The majority of twin families have participated in survey studies, and subsamples took part in biomaterial collection (e.g., DNA) and dedicated projects, for example, for neuropsychological, biomarker and behavioral traits. The recruitment into the NTR is all inclusive without any restrictions on enrollment. These resources — the longitudinal phenotyping, the extended pedigree structures and the multigeneration genotyping — allow for future twin-family research that will contribute to gene discovery, causality modeling, and studies of genetic and cultural inheritance.
This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development.
The aim of the Avera Twin Register (ATR) is to establish a prospective longitudinal repository of twins, multiples, siblings and family members’ biological samples to study environmental and genetic influences on health and disease. Also, it is our intention to contribute to international genome-wide association study (GWAS) twin consortia when appropriate sample size is achieved within the ATR. The ATR is young compared with existing registers and continues to collect a longitudinal repository of biological specimens, survey data and health information. Data and biological specimens were originally collected via face-to-face appointments or the postal department and consisted of paper-informed consents and questionnaires. Enrollment of the ATR began on May 18, 2016 and is located in Sioux Falls, South Dakota, a rural and frontier area in the Central United States with a regional population of approximately 880,000. The original target area for the ATR was South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota and Nebraska. The ATR has found a need to expand that area based on twin and multiple siblings who live in various areas surrounding these states. A description of the state of the ATR today and its transition to online data collection and informed consent will be presented. The ATR collects longitudinal data on lifestyle, including diet and activity levels, aging, plus complex traits and diseases. All twins and multiples participating in the ATR are genotyped on the Illumina Global Screening Array and receive zygosity results.
The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.