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Aims: Gambling Disorder is a mental health condition in which people experience impaired ability to control or stop gambling behaviours despite adverse consequences. It is associated with psychiatric co-morbidities and risk factors for physical health conditions. There is growing exploration into physical health conditions associated with gambling disorder and this study sought to further contribute towards understanding that association. The first aim was to describe rates of physical health conditions. The second aim was to explore potential associations between physical health conditions and individuals’ sociodemographic characteristics.
Methods: Dataset one comprised aggregated anonymised subject-level data from clinical trials conducted in participants with gambling disorder (n=423). Dataset two comprised aggregated anonymised patient data from the NHS Southern Gambling Service (n=352). Descriptive characteristics of people with versus without physical health co-morbidities were presented. Statistical tests were undertaken to compare those with versus without physical health co-morbidities, independent t-tests were utilised to compare continuous variables whereas Chi Square or Fisher’s Exact test were utilised when comparing categorical variables.
Results: In dataset one 42.9% reported one or more physical health condition, the most frequent reported physical health conditions were musculoskeletal, cardiovascular, and endocrine and metabolic conditions. People in dataset one with physical health condition(s) versus without had significantly older age. In dataset two 27.1% reported one or more physical health condition, with respiratory, musculoskeletal, and endocrine and metabolic being the most reported. The presence of physical health conditions, musculoskeletal conditions, and endocrine and metabolic conditions was associated with significantly older age and female sex.
Conclusion: Increased age in individuals with gambling disorder is a crucial sociodemographic factor regarding physical health morbidity. In dataset two being female was identified as a risk factor for having physical health morbidity. Implementation of treatments targeting these risk factors may reduce the public health and individual health burden of gambling disorder.
Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
On February 2, 2023, Ilhan Omar took to the floor of the House of Representatives to address what being an American meant to her. Responding to Republican efforts to remove her from the House Committee on Foreign Affairs, the representative for Minnesota's fifth congressional district asked, “Who gets to be an American? What opinions do you have to have to be counted as American?”1 In attacking Omar for her past comments on Israel and track record of criticizing U.S. foreign policy, House Republicans were conflating progressive politics with foreignness, arguing that this combination is subversive and represents a real threat to the American government and the stability of the nation.2 Indeed, the vote to remove Omar came just a few years after President Donald J. Trump had implored Omar and her progressive allies in “The Squad”—House Democrats Alexandria Ocasio-Cortez, Ayanna Pressley, and Rashida Tlaib—to “go back” to the “crime infested places from which they came.”3 Acknowledging how her race and identity were once again being used by Republicans to question her Americanness and delegitimize her politics, Omar offered the following rebuttal:
Representation matters. Continuing to expand our ideas of who is American and who can partake in the American experiment is a good thing. I am an American … Someone who knows what it means to have a shot at a better life here in the United States. And someone who believes in the American dream, in the American possibility and the promise, and the ability to voice that in a democratic process.4
Implementation assessment plans are crucial for clinical trials to achieve their full potential. Without a proactive plan to implement trial results, it can take decades for one-fifth of effective interventions to be adopted into routine care settings. The Veterans Health Administration Office of Research and Development is undergoing a systematic transformation to embed implementation planning in research protocols through the Cooperative Studies Program, its flagship clinical research program. This manuscript has two objectives: 1) to introduce an Implementation Planning Assessment (IPA) Tool that any clinical trialist may use to facilitate post-trial implementation of interventions found to be effective and 2) to provide a case study demonstrating the IPA Tool’s use. The IPA Tool encourages study designers to initially consider rigorous data collection to maximize acceptability of the intervention by end-users. It also helps identify and prepare potential interested parties at local and national leadership levels to ensure, upon trial completion, interventions can be integrated into programs, technologies, and policies in a sustainable way. The IPA Tool can alleviate some of the overwhelming nature of implementation science by providing a practical guide based on implementation science principles for researchers desiring to scale up and spread effective, clinical trial-tested interventions to benefit patients.
Biomarkers may be useful endophenotypes for genetic studies if they share genetic sources of variation with the outcome, for example, with all-cause mortality. Australian adult study participants who had reported their parental survival information were included in the study: 14,169 participants had polygenic risk scores (PRS) from genotyping and up to 13,365 had biomarker results. We assessed associations between participants’ biomarker results and parental survival, and between biomarker results and eight parental survival PRS at varying p-value cut-offs. Survival in parents was associated with participants’ serum bilirubin, C-reactive protein, HDL cholesterol, triglycerides and uric acid, and with LDL cholesterol for participants’ fathers but not for their mothers. PRS for all-cause mortality were associated with liver function tests (alkaline phosphatase, butyrylcholinesterase, gamma-glutamyl transferase), metabolic tests (LDL and HDL cholesterol, triglycerides, uric acid), and acute-phase reactants (C-reactive protein, globulins). Association between offspring biomarker results and parental survival demonstrates the existence of familial effects common to both, while associations between biomarker results and PRS for mortality favor at least a partial genetic cause of this covariation. Identification of genetic loci affecting mortality-associated biomarkers offers a route to the identification of additional loci affecting mortality.
The COVID-19 pandemic increased population levels of depression and anxiety, and infection control measures obliged services to provide psychological therapies remotely. Evidence for the routine provision of psychological therapy via telephone and video-conferencing is limited. This study compared therapy outcomes for 5360 clients in two London Improving Access to Psychological Therapy (IAPT) services before and after homeworking produced a compete shift to remotely delivered therapy. Despite the psychological impacts of pandemic restrictions, and the use of a novel therapy modality in video-conferencing, recovery rates and net score change improved in both services, significantly in one. There was no significant worsening of outcomes for any demographic group or presenting disorder. The findings suggest that for those able to access it, therapy provided by telephone and video is a clinically effective option for IAPT services.
Key learning aims
(1) To assess the clinical effectiveness of delivering IAPT therapies remotely.
(2) To gain insight into the impacts of remote therapy on different client groups, including ethnicity, gender, age and presenting problem.
(3) To assess the impact of remote therapy on access to IAPT services.
Videoconferencing therapy (VT) has been an emerging medium of psychological therapy, and during the COVID-19 pandemic there has been substantial growth in its usage as a result of home working. However, there is a paucity of research into client and clinician perceptions of VT. This study sought to assess client and staff experiences of VT. This mixed methods study produced both quantitative and qualitative data. Seven clients who had previously received VT and 11 psychotherapists who had previously delivered VT were recruited from two NHS sites. Clients and psychotherapists took part in qualitative interviews which were analysed using thematic analysis. Quantitative surveys were developed based on themes generated from the interviews and were completed by 172 clients and 117 psychotherapists. These were analysed using simple percentages. VT often exceeded client and psychotherapist expectations and overall experiences of VT were generally positive, although there were mixed findings regarding the therapeutic alliance. Several barriers to VT were cited, such as IT issues, and challenges identified in conducting behavioural experiments, and potential exclusion of certain populations were also cited. The medium of VT was received well by both clients and clinicians, with advantages around convenience seemingly outweighing losses in quality of therapeutic relationship. Future research should focus on overcoming barriers to accessing VT in populations prone to digital exclusion. NHS services not currently employing VT may wish to reconsider their stance, expanding choice of therapy delivery and improving accessibility.
Key learning aims
(1) To gain insight into client and clinician experiences of VT during the COVID-19 pandemic.
(2) To assess the acceptability and feasibility of VT within two NHS short-term psychological support services.
(3) To identify barriers and facilitators to the implementation of VT within two NHS short-term psychological support services.
Mortality risk is known to be associated with many physiological or biochemical risk factors, and polygenic risk scores (PRSs) may offer an additional or alternative approach to risk stratification. We have compared the predictive value of common biochemical tests, PRSs and information on parental survival in a cohort of twins and their families. Common biochemical test results were available for up to 13,365 apparently healthy men and women, aged 17−93 years (mean 49.0, standard deviation [SD] 13.7) at blood collection. PRSs for longevity were available for 14,169 study participants and reported parental survival for 25,784 participants. A search for information on date and cause of death was conducted through the Australian National Death Index, with median follow-up of 11.3 years. Cox regression was used to evaluate associations with mortality from all causes, cancers, cardiovascular diseases and other causes. Linear relationships with all-cause mortality were strongest for C-reactive protein, gamma-glutamyl transferase, glucose and alkaline phosphatase, with hazard ratios (HRs) of 1.16 (95% CI [1.07, 1.24]), 1.15 (95% CI 1.04–1.21), 1.13 (95% CI [1.08, 1.19]) and 1.11 (95% CI [1.05, 1.88]) per SD difference, respectively. Significant nonlinear effects were found for urea, uric acid and butyrylcholinesterase. Lipid risk factors were not statistically significant for mortality in our cohort. Family history and PRS showed weaker but significant associations with survival, with HR in the range 1.05 to 1.09 per SD difference. In conclusion, biochemical tests currently predict long-term mortality more strongly than genetic scores based on genotyping or on reported parental survival.
Previous genetic studies on hair morphology focused on the overall morphology of the hair using data collected by self-report or researcher observation. Here, we present the first genome-wide association study (GWAS) of a micro-level quantitative measure of hair curvature. We compare these results to GWAS results obtained using a macro-level classification of observable hair curvature performed in the same sample of twins and siblings of European descent. Observational data were collected by trained observers, while quantitative data were acquired using an Optical Fibre Diameter Analyser (OFDA). The GWAS for both the observational and quantitative measures of hair curvature resulted in genome-wide significant signals at chromosome 1q21.3 close to the trichohyalin (TCHH) gene, previously shown to harbor variants associated with straight hair morphology in Europeans. All genetic variants reaching genome-wide significance for both GWAS (quantitative measure lead single-nucleotide polymorphism [SNP] rs12130862, p = 9.5 × 10–09; observational measure lead SNP rs11803731, p = 2.1 × 10–17) were in moderate to very high linkage disequilibrium (LD) with each other (minimum r2 = .45), indicating they represent the same genetic locus. Conditional analyses confirmed the presence of only one signal associated with each measure at this locus. Results from the quantitative measures reconfirmed the accuracy of observational measures.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
This article examines the border-crossing journalism of the Negro Digest, a leading African American periodical, published from 1942 to 1951. The first title produced by the Johnson Publishing Company, the Digest had an international focus that connected Jim Crow to racial oppression around the world. However, while the magazine challenged white supremacy on a local and global level, its patriotic tone and faith in American democracy occasionally restricted its global analysis of racism. Ultimately, the internationalism of the Negro Digest was quintessentially American – wedded to the exceptional status of American freedom and an overriding belief that the US could change the world for the better.
The demise of American slavery in 1865 put black Americans in motion to an unprecedented degree. Freed slaves and their descendants migrated from the plantations in the rural South to destinations around the globe. Travelling in a variety of new roles – as missionaries, journalists, agronomists, scientists, athletes, performers, entrepreneurs and political activists – African Americans gained international visibility, inspiring other oppressed populations in the colonial world to struggle for their liberation.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
This study presents new ages for the northwest section of the Laurentide Ice Sheet (LIS) glacial chronology from material recovered from two retrogressive thaw slumps exposed in the Richardson Mountains, Northwest Territories, Canada. One study site, located at the maximum glacial limit of the LIS in the Richardson Mountains, had calcite concretions recovered from aufeis buried by glacial till that were dated by U/Th disequilibrium to 18,500 cal yr BP. The second site, located on the Peel Plateau to the east yielded a fossil horse (Equus) mandible that was radiocarbon dated to ca. 19,700 cal yr BP. These ages indicate that the Peel Plateau on the eastern flanks of the Richardson Mountains was glaciated only after 18,500 cal yr BP, which is later than previous models for the global last glacial maximum (LGM). As the LIS retreated the Peel Plateau around 15,000 cal yr BP, following the age of the Tutsieta phase, we conclude that the presence of the northwestern margin of the LIS at its maximum limit was a very short event in the western Canadian Arctic.
This paper seeks to establish good practice in setting inputs for operational risk models for banks, insurers and other financial service firms. It reviews Basel, Solvency II and other regulatory requirements as well as publicly available literature on operational risk modelling. It recommends a combination of historic loss data and scenario analysis for modelling of individual risks, setting out issues with these data, and outlining good practice for loss data collection and scenario analysis. It recommends the use of expert judgement for setting correlations, and addresses information requirements for risk mitigation allowances and capital allocation, before briefly covering Bayesian network methods for modelling operational risks.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.
Aims
We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.
Method
To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance(n = 342) among healthy individuals.
Results
Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10–5). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P =3.54×10–8). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.
Conclusions
Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.
Monozygotic (MZ) twins provide a natural system for investigating developmental plasticity and the potential epigenetic origins of disease. A major difference in the intrauterine environment between MZ pairs is whether they share a common placenta or have separate placentas. Using DNA methylation measured at >400,000 points in the genome on the Illumina HumanMethylation450 array, we demonstrate that the co-twins of MZ pairs (average age of 14) that shared a common placenta (n = 18 pairs) have more similar DNA methylation levels in blood throughout the genome relative to those with separate placentas (n = 16 pairs). Functional annotation of the genomic regions that show significantly different correlation between monochorionic (MC) and dichorionic (DC) MZ pairs found an over-representation of genes involved in the regulation of transcription, neuronal development, and cellular differentiation. These results support the idea that prenatal environmental exposures may have a lasting effect on an individual's epigenetic landscape, and the potential for these changes to have functional consequences.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.