Fission track dating of detrital zircons from the Scotland Sandstones, Barbados, West Indies

Results of fission track dating of detrital zircons from the Scotland sandstones, Barbados, yield a mixture of ages with several strong groupings from 20-80 Ma, 200-350 Ma, and greater than 500 Ma. Metamict grains were assumed to fall into the greater than 500 Ma population. The youngest population indicates that the Scotland beds, previously dated by paleontologic methods as Eocene, may actually be as young as late Oligocene. These ages better constrain the timing of deposition for these sediments and support the proposal that the late middle Eocene - early Oligocene Oceanic Fm has overthrust the Scotland beds. This population (20-80 Ma) may reflect material derived from the adjacent arc, the Netherland-Venezuelan Antilles arc, and the Caribbean Mountains of Venezuela. The 200-350 Ma population may reflect partially annealed cratonic material, an Andean component, and/or material associated with a Triassic rifting event. The oldest population (\u3e500 Ma) and metamict zircons were very likely derived from the South American craton. 40Ar/39Ar age spectrum analysis of detrital feldspar from sample 22 provides additional evidence of a cratonic source for these sediments. Based on results from this study, distribution of glaucophane, and paleogeographical constraints it is proposed that the source area for the Scotland sediments of Barbados was an area of the Guayana shield which was drained by the Unare (proto-Orinoco?) river system and deposited in a submarine fan north of the Unare depression

Magic in Chinese religion

This item was digitized by the Internet Archive. Thesis (M.A.)--Boston Universityhttps://archive.org/details/magicinchinesere00bal

Fission track dating of detrital zircons from the Scotland Sandstones, Barbados, West Indies

Results of fission track dating of detrital zircons from the Scotland sandstones, Barbados, yield a mixture of ages with several strong groupings from 20-80 Ma, 200-350 Ma, and greater than 500 Ma. Metamict grains were assumed to fall into the greater than 500 Ma population. The youngest population indicates that the Scotland beds, previously dated by paleontologic methods as Eocene, may actually be as young as late Oligocene. These ages better constrain the timing of deposition for these sediments and support the proposal that the late middle Eocene - early Oligocene Oceanic Fm has overthrust the Scotland beds. This population (20-80 Ma) may reflect material derived from the adjacent arc, the Netherland-Venezuelan Antilles arc, and the Caribbean Mountains of Venezuela. The 200-350 Ma population may reflect partially annealed cratonic material, an Andean component, and/or material associated with a Triassic rifting event. The oldest population (\u3e500 Ma) and metamict zircons were very likely derived from the South American craton. 40Ar/39Ar age spectrum analysis of detrital feldspar from sample 22 provides additional evidence of a cratonic source for these sediments. Based on results from this study, distribution of glaucophane, and paleogeographical constraints it is proposed that the source area for the Scotland sediments of Barbados was an area of the Guayana shield which was drained by the Unare (proto-Orinoco?) river system and deposited in a submarine fan north of the Unare depression

The Great (Immune) Escape: Unpacking breast cancer immune evasion cell by cell

The development and approval of immune checkpoint inhibitors (anti-CTLA4 and anti-PD1/PDL1) has driven a paradigm shift in cancer treatment. By blocking the T cell-suppressive interactions of CTLA4 with its ligand B7, or PD1 with PDL1/PDL2, the immune checkpoint inhibitors can induce a robust anti-tumour immune response. These therapies have achieved remarkable results in some patients with some cancers, including melanoma (Wolchok, Kluger et al. 2013) and non-small cell lung cancer (Reck, Rodríguez-Abreu et al. 2019). However, the same results have not been achieved in breast cancer. Triple negative breast cancer (TNBC), characterised by the absence of the estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor (HER2), is the most aggressive subtype of breast cancer and has the worst prognosis (Fallahpour, Navaneelan et al. 2017). For decades, surgery, chemotherapy and radiotherapy were the only approved treatment options, leaving little hope for patients who relapse on these treatments. More recently, anti-PD1 in combination with nab-paclitaxel has been approved for use in TNBC, but the vast majority of patients do not benefit from this treatment combination (Schmid, Adams et al. 2018, Schmid 2019, Schmid, Cortes et al. 2020, Schmid, Rugo et al. 2020). Given the potential of immunotherapy to induce durable anti-cancer immune responses, even in the metastatic setting, understanding why TNBC is recalcitrant to immunotherapy is crucial to improve outcomes for TNBC patients. In my doctoral studies, I have focused on understanding the immune response to breast cancer immunotherapy at the single cell level using two murine models of TNBC. I began my studies by using DNA barcoding technologies to examine the cancer cells themselves. I found two highly immune evasive cancer cell clones utilised different mechanisms of immune evasion and showed that these mechanisms were maintained simultaneously in vivo. I found one of these mechanisms could be partially restored using an epigenetic agent, providing preclinical evidence for the rational combination of an epigenetic therapy and immunotherapy in TNBC. These clones were also found to share a common gene signature that was associated with poor prognosis in two independent patient cohorts. At least one of the genes in this signature has a small molecule inhibitor available and may synergise with immunotherapy. Next, I turned to examine the immune response to breast cancer at the systems level by using single cell sequencing technologies. By utilising two mouse models of immunotherapy response, a model that responds completely and a model that does not, I generated single cell data on nearly 200,000 cells derived from the primary tumours and matching draining lymph nodes. Five treatment arms were included and all samples underwent matched T cell receptor sequencing. This not only generated a substantial resource for numerous future investigations, but also shed light on the nuanced and complex biology that governs response to immunotherapy. CD8+ T cell clonal expansion was observed in the immunotherapy responsive model, while T regulatory cell expansion dominated in the non-responsive model. This provides evidence that CD8+ T cell expansion may be a biomarker of response to immunotherapy. Overall, I provided insight into mechanisms of immune evasion and intratumoural heterogeneity (ITH) in breast cancer, and propose two candidate drugs for combination with immunotherapy in future studies. I also generated a substantial single cell dataset across multiple tissue, mouse models and single cell sequencing modalities, as well as identifying a potential biomarker of immunotherapy response in breast cancer. Together, this work shows the value of investigating cancer immunotherapy using single cell technologies, and provides further insight into cancer heterogeneity

Dissociation and Post-Traumatic Stress Disorder in Women Who Have Experienced Trauma and Sexual Assault

The relation between dissociative symptoms and posttraumatic stress disorder (PTSD) was investigated in women who had experienced trauma or sexual assault. Subjects were administered the Dissociative Experiences Scale (DES), the Sexual Experiences Scale (SES), and the PTSD Interview (PTSD-I). Subjects were grouped according to their scores on the SES and the PTSD-I. Analysis of variance revealed a relation between DES scores and PTSD symptom severity scores. Correlational analyses showed a relation between dissociative symptoms and PTSD symptom severity but not recency of trauma. Three factors from a previously published factor analysis of the DES were found to contribute to the DES scores of PTSD subjects

The impact of childhood psychological maltreatment on mental health outcomes in adulthood:A protocol for a systematic review and meta-analysis

Abstract Background Research suggests that childhood psychological maltreatment (i.e., emotional abuse and emotional neglect) is associated with mental health problems that persist into adulthood, for example anxiety, depression, post-traumatic stress disorder (PTSD), suicidal ideation, and aggression; however, a systematic review and meta-analysis of the existing literature would help clarify the magnitude and moderators of these associations, and the extent to which they may be affected by publication bias, as well as the methodological strengths and weakness of studies in this area. Method The reporting of this protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement. Searches will be carried out via several databases, including Web of Science, Medline, PubMed, PsycINFO, Applied Social Science Index and Abstract, ERIC and EMBASE. Empirical peer-reviewed research articles that fit pre-specified eligibility criteria will be included in the review. Studies will be eligible if they include participants age 18 or over at time of mental health assessment, include information on childhood psychological maltreatment (emotional abuse and/or neglect) perpetrated by a primary caregiver or adult in the same household, and provide quantitative information on the association between these factors. Studies using prospective and retrospective designs and written in either English or Chinese will be eligible. Two independent reviewers will screen and assess studies for inclusion in the review as well as extract the data, with consensus reached through discussion in cases of discrepancy. A third reviewer will be consulted to resolve any discrepancies that remain. The relevant Newcastle–Ottawa scales will be used for assessing the quality of studies. If a sufficient number of comparable studies are retrieved, a meta-analysis will be conducted using a random effects model. Study-level moderators (i.e., year of publication, quality of the study and study geographical location) will be examined in the meta-analyses. Discussion This systematic review will provide an understanding of the long-term effects of childhood psychological maltreatment on adult mental health, which adds to previous reviews focusing primarily on the effects of physical and sexual abuse. The results of the review will help inform clinical practice in approaches to treating those with a history of psychological maltreatment in childhood. The gaps and weaknesses in the evidence identified will also inform recommendations for future research

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Background: Little is known about how dependency levels have changed between generational cohorts of older people. We estimated years lived in different care states at age 65 in 1991 and 2011 and new projections of future demand for care. Methods: Two population-based studies of older people in defined geographical areas conducted two decades apart (the Cognitive Function and Ageing Studies) provided prevalence estimates of dependency in four states: high (24-hour care); medium (daily care); low (less than daily); independent. Years in each dependency state were calculated by Sullivan’s method. To project future demand, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings: Between 1991 and 2011 there were significant increases in years lived from age 65 with low (men:1·7 years, 95%CI 1·0-2·4; women:2·4 years, 95%CI 1·8-3·1) and high dependency (men:0·9 years, 95%CI 0·2-1·7; women:1·3 years, 95%CI 0·5-2·1). The majority of men’s extra years of life were independent (36%) or with low dependency (36%) whilst for women the majority were spent with low dependency (58%), only 5% being independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71,000 care home places by 2025. Interpretation: On average older men now spend 2.4 years and women 3.0 years with substantial care needs (medium or high dependency), and most will live in the community. These findings have considerable implications for older people’s families who provide the majority of unpaid care, but the findings also supply valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations

Population vs Individual Prediction of Poor Health from Results of Adverse Childhood Experiences Screening

Importance: Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems. Objective: To test the predictive accuracy of ACE screening for later health problems. Design, Setting, and Participants: This study comprised 2 birth cohorts: the Environmental Risk (E-Risk) Longitudinal Twin Study observed 2232 participants born during the period from 1994 to 1995 until they were aged 18 years (2012-2014); the Dunedin Multidisciplinary Health and Development Study observed 1037 participants born during the period from 1972 to 1973 until they were aged 45 years (2017-2019). Statistical analysis was performed from May 28, 2018, to July 29, 2020. Exposures: ACEs were measured prospectively in childhood through repeated interviews and observations in both cohorts. ACEs were also measured retrospectively in the Dunedin cohort through interviews at 38 years. Main Outcomes and Measures: Health outcomes were assessed at 18 years in E-Risk and at 45 years in the Dunedin cohort. Mental health problems were assessed through clinical interviews using the Diagnostic Interview Schedule. Physical health problems were assessed through interviews, anthropometric measurements, and blood collection. Results: Of 2232 E-Risk participants, 2009 (1051 girls [52%]) were included in the analysis. Of 1037 Dunedin cohort participants, 918 (460 boys [50%]) were included in the analysis. In E-Risk, children with higher ACE scores had greater risk of later health problems (any mental health problem: relative risk, 1.14 [95% CI, 1.10-1.18] per each additional ACE; any physical health problem: relative risk, 1.09 [95% CI, 1.07-1.12] per each additional ACE). ACE scores were associated with health problems independent of other information typically available to clinicians (ie, sex, socioeconomic disadvantage, and history of health problems). However, ACE scores had poor accuracy in predicting an individual's risk of later health problems (any mental health problem: area under the receiver operating characteristic curve, 0.58 [95% CI, 0.56-0.61]; any physical health problem: area under the receiver operating characteristic curve, 0.60 [95% CI, 0.58-0.63]; chance prediction: area under the receiver operating characteristic curve, 0.50). Findings were consistent in the Dunedin cohort using both prospective and retrospective ACE measures. Conclusions and Relevance: This study suggests that, although ACE scores can forecast mean group differences in health, they have poor accuracy in predicting an individual's risk of later health problems. Therefore, targeting interventions based on ACE screening is likely to be ineffective in preventing poor health outcomes