Flexibility in graduate careers: An exploratory study of the work careers of a sample of 1970 graduates

This thesis describes a three stage research project that explored flexibility in the career development of British graduates. Particular , attention was paid to people's subjective perceptions of their own flexibility. First, the rationale for the study is described, i. e. that the area was under researched yet new technology has created an urgent need for people to become more flexible in their careers. Then the Literature of occupational choice, career change and career development is reviewed and used to derive a typology of occupational change. The decision to use a mixture of research methods is defended. Next Stages One and Two, the Contact Survey and the Interviews, are described. 148 1970 graduates in science, techno Logy and engineering who had made voluntary occupational changes (a sub-sample from a national survey) were sent postal questionnaires, and 38 of these were subsequently I interviewed in depth about their work histories. A model was derived from the interview data of how flexibility in career development depends on a career anchor, or a set of values that a person gradually discovers that they will not give up when changing jobs. An anchor is idiosyncratic to the individual and cannot necessarily be predicted by an outsider examining work histories. It depends on experience and increasing self awareness. Stage Three involved testing some of the ideas arising from this model of a career anchor on a second sample of 1970 graduates. These respondents had recalled two of their earlier career decisions using computer programmes that elicited their values at those times. Comparisons between their earlier (pre-anchored) decisions and their Later (anchored) decisions showed support for the career anchors model. The findings and conclusions of the project are discussed in terms of five research questions: (1) How much change did they think their careers had undergone? (2) What form did any changes take? (3) Were these changes perceived as unusual in any way? (4) How far could people's views and experiences of flexibility be explained by existing psycho Logical theories about careers? (5) Any explanations of the ability to show flexibility in career development have implications for the careers counselling of adults; what would these implications be? It is concluded that the career anchors model shows promise as a supplement to existing theories of careers, and may be useful to careers counselors who deal with adults contemplating or undergoing career transitions

Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial.

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results

Impact of cyclooxygenase inhibitors in the Women\u27s Health Initiative hormone trials: secondary analysis of a randomized trial

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women\u27s Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women\u27s Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women\u27s Health Initiative hormone trial results

PAX-D:study protocol for a randomised placebo-controlled trial evaluating the efficacy and mechanism of pramipexole as add-on treatment for people with treatment resistant depression

Introduction: Clinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole versus placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task. Methods and analysis: PAX-D will assess effectiveness in the short- term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to Week 12 post-randomisation measured using the QIDS-SR. Performance on the decision-making task will be measured at Week 0, Week 2, and Week 12. Secondary outcomes include anhedonia, anxiety, and health economic measures including quality of life, capability, wellbeing, and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties. Discussion: Pramipexole is a promising augmentation agent for treatment resistant depression and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with treatment resistant depression

Can Biomarkers Identify Women at Increased Stroke Risk? The Women's Health Initiative Hormone Trials

Objective: The Women's Health Initiative hormone trials identified a 44% increase in ischemic stroke risk with combination estrogen plus progestin and a 39% increase with estrogen alone. We undertook a case-control biomarker study to elucidate underlying mechanisms, and to potentially identify women who would be at lower or higher risk for stroke with postmenopausal hormone therapy (HT). Design: The hormone trials were randomized, double-blind, and placebo controlled. Setting: The Women's Health Initiative trials were conducted at 40 clinical centers in the United States. Participants: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. Interventions: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. Outcome Measures: Stroke was ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. Results: No baseline clinical characteristics, including gene polymorphisms, identified women for whom the stroke risk from HT was higher. Paradoxically, women with higher baseline levels of some stroke-associated biomarkers had a lower risk of stroke when assigned to estrogen plus progestin compared to placebo. For example, those with higher IL-6 were not at increased stroke risk when assigned to estrogen plus progestin (odds ratio 1.28) but were when assigned to placebo (odds ratio 3.47; p for difference = 0.02). Similar findings occurred for high baseline PAP, leukocyte count, and D-dimer. However, only an interaction of D-dimer during follow-up interaction with HT and stroke was marginally significant (p = 0.03). Conclusions: Biomarkers did not identify women at higher stroke risk with postmenopausal HT. Some biomarkers appeared to identify women at lower stroke risk with estrogen plus progestin, but these findings may be due to chance

A review of the opportunities and challenges for using remote sensing for management of surface-canopy forming kelps

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cavanaugh, K. C., Bell, T., Costa, M., Eddy, N. E., Gendall, L., Gleason, M. G., Hessing-Lewis, M., Martone, R., McPherson, M., Pontier, O., Reshitnyk, L., Beas-Luna, R., Carr, M., Caselle, J. E., Cavanaugh, K. C., Miller, R. F., Hamilton, S., Heady, W. N., Hirsh, H. K., Hohman R., Lee L. C., Lorda J., Ray J., Reed D. C., Saccomanno V. R., Schroeder, S. B. A review of the opportunities and challenges for using remote sensing for management of surface-canopy forming kelps. Frontiers in Marine Science, 8, (2021): 753531, https://doi.org/10.3389/fmars.2021.753531.Surface-canopy forming kelps provide the foundation for ecosystems that are ecologically, culturally, and economically important. However, these kelp forests are naturally dynamic systems that are also threatened by a range of global and local pressures. As a result, there is a need for tools that enable managers to reliably track changes in their distribution, abundance, and health in a timely manner. Remote sensing data availability has increased dramatically in recent years and this data represents a valuable tool for monitoring surface-canopy forming kelps. However, the choice of remote sensing data and analytic approach must be properly matched to management objectives and tailored to the physical and biological characteristics of the region of interest. This review identifies remote sensing datasets and analyses best suited to address different management needs and environmental settings using case studies from the west coast of North America. We highlight the importance of integrating different datasets and approaches to facilitate comparisons across regions and promote coordination of management strategies.Funding was provided by the Nature Conservancy (Grant No. 02042019-5719), the U.S. National Science Foundation (Grant No. OCE 1831937), and the U.S. Department of Energy ARPA-E (Grant No. DE-AR0000922)

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts