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In July 2022, a genetically linked and geographically dispersed cluster of 12 cases of Shiga toxin-producing Escherichia coli (STEC) O103:H2 was detected by the UK Health Security Agency using whole genome sequencing. Review of food history questionnaires identified cheese (particularly an unpasteurized brie-style cheese) and mixed salad leaves as potential vehicles. A case–control study was conducted to investigate exposure to these products. Case food history information was collected by telephone. Controls were recruited using a market research panel and self-completed an online questionnaire. Univariable and multivariable analyses were undertaken using Firth Logistic Regression. Eleven cases and 24 controls were included in the analysis. Consumption of the brie-style cheese of interest was associated with illness (OR 57.5, 95% confidence interval: 3.10–1,060). Concurrently, the production of the brie-style cheese was investigated. Microbiological sample results for the cheese products and implicated dairy herd did not identify the outbreak strain, but did identify the presence of stx genes and STEC, respectively. Together, epidemiological, microbiological, and environmental investigations provided evidence that the brie-style cheese was the vehicle for this outbreak. Production of unpasteurized dairy products was suspended by the business operator, and a review of practices was performed.
Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.
Method:
Older adults with major depressive disorder (N = 228, ages 65–91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning.
Results:
Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity.
Conclusions:
Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.
Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD.
Participants and Measurements:
Older adults with major depression (N = 121, Ages 65–91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aβ standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity.
Results:
Greater anxiety severity was associated with lower OFC volume (β = −68.25, t = −2.18, p = .031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety.
Conclusions:
Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Palliative care (PC) is patient and family-centered supportive care intended to improve symptom management, reduce caregiver burden, coordinate care, and improve quality of life for patients diagnosed with serious illness. Optimally, PC is begun close to initial diagnosis and delivered in synchrony with disease-specific treatment until symptom relief or patient death. The purpose of this study was to examine cancer survivors’ knowledge and perceptions of PC using a nationally representative sample of US adults from the Health Information National Trends Survey (HINTS).
Method
A total of 593 HINTS respondents reported a personal history of cancer and were included in the sample (55.56% female; mean age of 65.88 years, SD = 18.21; mean time from diagnosis 13.83 years, SD = 18.21). Weighted logistic regression models were conducted to identify correlates of PC knowledge.
Results
Of the 593 cancer survivors in the sample, 66% (N = 378) reported that they had never heard of PC, 18% (N = 112) reported knowing a little bit about PC, and 17% (N = 95) reported knowing what PC is and could explain it to someone else. In multivariable analysis, survivors of color (Hispanic/Latino, Black, Asian, American Indian, and Pacific Islander), males, and those less educated were significantly less likely to report knowledge of PC. Among survivors who did report knowledge of PC, a lack of distinction between differing modes of supportive care exists.
Significance of results
These findings suggest a need to increase PC knowledge among cancer survivors with the ultimate goal of addressing disparities in PC acceptance and utilization.
ABSTRACT IMPACT: Our research focuses on determining rural-urban disparities in chronic obstructive pulmonary disease (COPD) management to improve COPD health outcomes in rural areas. OBJECTIVES/GOALS: Several methods exist to distinguish rural from urban areas, but it is not clear which method relates most directly to rural-urban health care disparities. To address this, we compared different measures of rurality to measures of chronic obstructive pulmonary disease (COPD) processes of care among a national sample of veterans. METHODS/STUDY POPULATION: Retrospective analysis of patients with COPD (2016-2019 by ICD-10 codes) using national Veterans Affairs (VA) data. We assessed rurality by: 1) patient’s residential address, 2) assigned primary care clinic address, and 3) drive time from the patient’s residence to closest primary care clinic. Rurality designations of the residential address and primary care clinic address into urban, rural, and highly rural areas are based on the Rural Urban Commuting Area (RUCA) codes. The dependent variables were binary outcomes of: 1) documentation of a pulmonary clinic encounter and 2) evidence of spirometry to confirm the diagnosis of COPD. RESULTS/ANTICIPATED RESULTS: Of 6,765,951 veterans, 1,157,002 (17%) had COPD (Table 1). Although approximately 40% of patients with COPD reside in addresses that are rural and highly rural, a large majority are assigned to primary care clinics in urban areas (82.8%) and reside within 30 minutes to the closest primary care clinic (76.7%) (Table 2). Compared to defining rurality based on patient’s residential address or drive time to closest primary care, defining rurality based on the assigned primary care clinic address was associated with a larger disparity in rates of pulmonary encounter. In contrast, the drive time from the patient’s residence to the closest primary care was the strongest predictor of receipt of spirometry (Figure 1 and Table 3). DISCUSSION/SIGNIFICANCE OF FINDINGS: Estimates of the severity of rural-urban disparities varied based on the definition of rurality used. For two process measures, definitions of rurality based on where the patient received primary care generated more evidence of disparities than definitions based solely on the patient’s residential address.
The United Nations 2030 Agenda for Sustainable Development sets a framework of universal Sustainable Development Goals (SDGs) to address challenges to society and the planet. Island invasive species eradications have well-documented benefits that clearly align with biodiversity conservation-related SDGs, yet the value of this conservation action for socioeconomic benefits is less clear. We examine the potential for island invasive vertebrate eradications to have ecological and socioeconomic benefits. Specifically, we examine: (1) how SDGs may have been achieved through past eradications; and (2) how planned future eradications align with SDGs and associated targets. We found invasive vertebrate eradication to align with 13 SDGs and 42 associated targets encompassing marine and terrestrial biodiversity conservation, promotion of local and global partnerships, economic development, climate change mitigation, human health and sanitation and sustainable production and consumption. Past eradications on 794 islands aligned with a median of 17 targets (range 13–38) by island. Potential future eradications on 292 highly biodiverse islands could align with a median of 25 SDG targets (range 15–39) by island. This analysis enables the global community to explicitly describe the contributions that invasive vertebrate management on islands can make towards implementing the global sustainable development agenda.
Impairment in financial capacity is an early sign of cognitive decline and functional impairment in late life. Cognitive impairments such as executive dysfunction are well documented in late-life major depression; however, little progress has been made in assessing associations of these impairments with financial incapacity.
Methods:
Participants included 95 clinically depressed and 41 nondepressed older adults without dementia. Financial capacity (assessed with the Managing Money scale of the Independent Living Scale), cognitive functioning (comprehensive neuropsychological evaluation), and depression severity (Hamilton Depression Rating Scale – 24) were assessed. T tests were used to assess group differences. Linear regression was used to analyze data.
Results:
Depressed participants performed significantly lower on financial capacity (t = 2.98, p < .01). Among depressed participants, executive functioning (B = .24, p < .05) was associated with reduced financial capacity, controlling for age, gender, education, depression severity, and other cognitive domains.
Conclusions:
Our results underscore the importance of assessing financial capacity in older depressed adults as they are likely vulnerable to financial abuse even in the absence of dementia. It will be valuable to assess whether treatment for depression is an effective intervention to improve outcomes.
Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership.
Method:
Neuropsychological assessment data from 121 participants in the Alzheimer’s Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed.
Results:
A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership.
Conclusion:
LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
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.
Post-application seasonal (May-July) average concentrations of atrazine, cyanazine, and, to a lesser extent, alachlor sometimes exceed their Maximum Contaminant Levels (MCLs) (3 ug/L for atrazine and 2 ug/L for alachlor) or Maximum Contaminant Level Goal (MCLG) (1 ug/L for cyanazine) in surface waters of the Mississippi and Great Lakes Basins. These three chemicals are among the primary pre-emergent herbicides applied to corn. MCLs and MCLGs are compared to annual average concentrations for regulatory purposes. However, annual average concentrations are much less frequently reported than post-application seasonal averages. In most cases, both seasonal and annual average concentrations are substantially less than the MCLs or MCLG. However, actual and estimated annual mean concentrations occasionally exceed the MCLs or MCLG. Actual or estimated exceedences occur more frequently for atrazine and cyanazine than for alachlor, and may occur more frequently in lakes or reservoirs with long retention times than in streams and rivers. Additional year round data, and data for lakes and reservoirs, are needed to determine the extent to which such exceedences occur throughout the corn belt. The American Water Works Association (AWWA) believes that substantial numbers of Community Water Systems (CWSs) within the corn belt are currently, or will be, in violation of the revised Safe Drinking Water Act (SDWA) with respect to atrazine and cyanazine. They are concerned that such violations could result in numerous CWSs having to implement expensive tertiary treatment systems such as granular activated carbon to decrease herbicide concentrations. The United States Environmental Protection Agency, (US EPA) is continuing to review data on the pesticide concentrations in reservoirs and lakes that registrants have been submitting over the last 18 mo under the 6(a)(2) adverse impact provision of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). The US EPA is also currently using computer modeling and other methods to evaluate potential alternative and/or supplemental herbicides to reduce atrazine use. In June 1992, the US EPA approved revised labeling that is designed to reduce indirect atrazine loadings to surface waters. Additional mitigation methods have been proposed and are being considered.
We describe bright microwave events that were first detected with the Parkes 64-m telescope at 8.4 or 22 GHz from six active-chromosphere stars. In some flares spectral data were obtained over a large frequency range from simultaneous measurements with the Parkes reflector (8.4 or 22 GHz), the Tidbinbilla interferometer (8.4 and 2.29 GHz), the Fleurs synthesis telescope (1.42 GHz) and the Molonglo Observatory synthesis telescope (0.843 GHz). Data on circular polarization were obtained from the Parkes observations at 8.4 GHz.
The stars were in a wide variety of evolutionary states, ranging from a single pre-main-sequence star (HD 36705), two RS CVn binaries (HD 127535, HD 128171), an Algol (HD 132742) and two apparently single K giants (HD 32918 and HD 196818). Their high brightness temperatures, positive spectral indices and low polarization are consistent with optically thick gyrosynchrotron emission from mildly relativistic electrons with average energies 0.5 to 3 MeV gyrating in inhomogeneous magnetic fields of 5 to 100 G.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
Properties of the microwave emission from HR1099 are examined in an attempt to determine whether the emission arises as gyro-synchrotron radiation from mildly relativistic electrons trapped in magnetic fields above starspots on the active K subgiant component. It is shown that radio curves do not exhibit a systematic variation in phase with the rotation rate, as one might expect for emission from a source situated above a long-lived starspot. However, there is some evidence that the radio flaring occurs at two preferred longitude zones. Whether these zones agree with starspot locations remains to be determined by light curve modelling. What we can say with confidence is that the measured spectral index of the microwave emission does not fit a simple gyro-synchrotron source model, such as that proposed to explain the observed reversal with frequency of the sense of circular polarization.
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.
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.