The evolution and genetic basis of complex traits in Drosophila melanogaster

The current climate crisis, increasing habitat fragmentation, deforestation, the number of extreme weather events, contagious diseases, and more are major environmental stressors that threaten the survival of every species on Earth. It is necessary for organisms to evolve stress resistant traits and phenotypic plasticity to survive these catastrophic effects. To resist stress, organisms will need to invest some amount of energy, leading to trade-offs with other traits. In addition, organisms must develop behavioral adaptations to manage environmental stressors. Behaviors such as dispersal and migration, and stress-resistant traits such as starvation resistance, have evolved as a means of survival. While researchers have studied behavioral adaptations and stress-resistant traits, the genetic and evolutionary mechanisms and phenotypic plasticity of these traits are not fully known. For my dissertation research, I studied the genetic mechanisms and phenotypic plasticity of two traits: exploration behavior and starvation resistance, respectively, in evolved multiparent populations of D. melanogaster. I used a bulk-segregant analysis (BSA) approach using a multiparent population, the Drosophila Synthetic Population Resource (DSPR), to uncover the genetic basis of exploration tendency in D. melanogaster. I defined exploration as the tendency of female fruit flies to move from a starting chamber to a novel fly chamber through a narrow tube. To identify the source of genetic variability in exploration, I generated 17 pairs of "high exploration" and "low exploration" bulk segregant populations consisting of 40 - 100 female flies and performed whole genome pooled sequencing. I then compared allele frequency differences between these pools to identify regions of the genome implicated in exploration tendency. In my second chapter I studied starvation resistance in an experimentally evolved population of D. melanogaster. Our lab placed twelve replicate populations of D. melanogaster on three selection treatments: constant high nutritional diet (CHA), fluctuating nutritional diet (FA), and deteriorating nutritional diet (DA). These three treatments have been ongoing for over 50 generations. For my experiment, a duplicated set of flies from all replicates and treatments were placed on one of three diets for 10 days: high sugar, standard, and low yeast diets. After 22 days post-oviposition (p.o.), flies were placed on nutrition-less agar. Starvation resistance was measured as the time it takes for a fly to die starting the moment it is placed on nutrition-less agar. We link these phenotypic changes to variation in artificial selection pressure and environmental conditions. In my code appendix, I established a novel method of statistical error estimation due to variation in coverage in pooled sequencing experiments. Coverage is defined as the number of reads at a given location along the genome. Due to the law of large numbers, a higher sequencing coverage value leads to a more accurate allele estimation at that locus.Includes bibliographical references

Hypnosis for acute procedural pain: a critical review

Clinical evidence for the effectiveness of hypnosis in the treatment of acute procedural pain was critically evaluated based on reports from randomized controlled clinical trials (RCTs). Results from the 29 RCTs meeting inclusion criteria suggest that hypnosis decreases pain compared to standard care and attention control groups and that it is at least as effective as comparable adjunct psychological or behavioral therapies. In addition, applying hypnosis in multiple sessions prior to the day of the procedure produced the highest percentage of significant results. Hypnosis was most effective in minor surgical procedures. However, interpretations are limited by considerable risk of bias. Further studies using minimally effective control conditions and systematic control of intervention dose and timing are required to strengthen conclusions

Duration of disease does not equally influence all aspects of quality of life in Parkinson’s disease

Health related quality of life (HRQoL) is negatively impacted in patients suffering from Parkinsons disease (PD). For the specific components that comprise HRQoL, the relationship between clinical variables, such as disease duration, is not fully characterized. In this cross-sectional study (n=302), self-reported HRQoL on the Parkinsons Disease Questionnaire (PDQ-39) was evaluated as a global construct as well as individual subscale scores. HRQoL was compared in three groups: those within 5years of diagnosis, those within 6-10years of diagnosis, and those greater than 11years since diagnosis. Non-parametric analyses revealed lower HRQoL with increasing disease duration when assessed as a global construct. However, when subscales were evaluated, difficulties with bodily discomfort and cognitive complaints were comparable in individuals in the 1-5years and 6-10year duration groups. Exploratory regression analyses suggested disease duration does explain unique variance in some subscales, even after controlling for Hoehn and Yahr stage and neuropsychiatric features. Our findings show that HRQoL domains in PD patients are affected differentially across the duration of the disease. Clinicians and researchers may need to tailor interventions intended to improve HRQoL at different domains as the disease progresses

Martian Igneous Geochemistry: The Nature of the Martian Mantle

Mafic igneous rocks probe the interiors of their parent objects, reflecting the compositions and mineralogies of their source regions, and the magmatic processes that engendered them. Incompatible trace element contents of mafic igneous rocks are widely used to constrain the petrologic evolution of planets. We focus on incompatible element ratios of martian meteorites to constrain the petrologic evolution of Mars in the context of magma ocean/cumulate overturn models [1]. Most martian meteorites contain some cumulus grains, but regardless, their incompatible element ratios are close to those of their parent magmas. Martian meteorites form two main petrologic/ age groupings; a 1.3 Ga group composed of clinopyroxenites (nakhlites) and dunites (chassignites), and a <1 Ga group composed of basalts and lherzolites (shergottites)

Ross operation in children and young adults: the Alder Hey case series

BACKGROUND: The ideal prosthesis for aortic valve replacement in children and young adults has not been found yet. In recent years there has been a renewed interest in the replacement of aortic valve with the pulmonary autograft owing to its advantages of lack of anticoagulation, potential for growth and excellent haemodynamic performance. The purpose of this study was to review our institutional experience at Alder Hey hospital with the Ross procedure in children and young adults. METHODS: From November 1996 to September 2003, 38 patients (mean age, 13.1 ± 5.7 years) underwent the Ross procedure for various aortic valve diseases using the root replacement technique. Clinical and echocardiographic follow-up was performed early (within 30 days), 3 to 6 months, and yearly after surgery. Medical records of all patients were reviewed retrospectively. RESULTS: There was 1 perioperative death. The patients were followed-up for a median interval of 36 months and up to 7 years. One patient died 3 years after surgery secondary to ventricular arrhythmia with overall mortality of 5.3%. Actuarial survival at 7 years was 94 ± 2.5% and there was 100% freedom from reoperation for autograft valve dysfunction or any other cause. Balloon dilatation was required in 2 patients for pulmonary homograft stenosis. The haemodynamics at the latest follow-up were also similar to those at the time of discharge after surgery. There was no progression in the degree of aortic regurgitation for 11 patients with trivial and 3 with mild regurgitation. CONCLUSION: Our experience demonstrates that Ross operation is an attractive option for aortic valve replacement in children and young adults. Not only can the operation be accomplished with a low operative risk but the valve function stays normal over a long period of time with minimal alteration in lifestyle and no need for repeated operations to replace the valve as a result of somatic growth of the children

A Blind Search for Magnetospheric Emissions from Planetary Companions to Nearby Solar-type Stars

This paper reports a blind search for magnetospheric emissions from planets around nearby stars. Young stars are likely to have much stronger stellar winds than the Sun, and because planetary magnetospheric emissions are powered by stellar winds, stronger stellar winds may enhance the radio luminosity of any orbiting planets. Using various stellar catalogs, we selected nearby stars (<~ 30 pc) with relatively young age estimates (< 3 Gyr). We constructed different samples from the stellar catalogs, finding between 100 and several hundred stars. We stacked images from the 74-MHz (4-m wavelength) VLA Low-frequency Sky Survey (VLSS), obtaining 3\sigma limits on planetary emission in the stacked images of between 10 and 33 mJy. These flux density limits correspond to average planetary luminosities less than 5--10 x 10^{23} erg/s. Using recent models for the scaling of stellar wind velocity, density, and magnetic field with stellar age, we estimate scaling factors for the strength of stellar winds, relative to the Sun, in our samples. The typical kinetic energy carried by the stellar winds in our samples is 15--50 times larger than that of the Sun, and the typical magnetic energy is 5--10 times larger. If we assume that every star is orbited by a Jupiter-like planet with a luminosity larger than that of the Jovian decametric radiation by the above factors, our limits on planetary luminosities from the stacking analysis are likely to be a factor of 10--100 above what would be required to detect the planets in a statistical sense. Similar statistical analyses with observations by future instruments, such as the Low Frequency Array (LOFAR) and the Long Wavelength Array (LWA), offer the promise of improvements by factors of 10--100.Comment: 11 pages; AASTeX; accepted for publication in A

Racial differences in user experiences and perceived value of electronic symptom monitoring in a cohort of black and white bladder and prostate cancer patients

Purpose: Electronic patient-reported outcomes (ePROs) are increasingly being used for symptom monitoring during routine cancer care, but have rarely been evaluated in diverse patient populations. We assessed ePRO user experiences and perceived value among Black and White cancer patients. Methods: We recruited 30 Black and 49 White bladder and prostate cancer patients from a single institution. Participants reported symptoms using either a web-based or automated telephone interface over 3 months and completed satisfaction surveys and qualitative interviews focused on user experiences and value. Using a narrative mixed methods approach, we evaluated overall and race-specific differences in ePRO user experiences and perceived value. Results: Most participants selected the web-based system, but Blacks were more likely to use the automated telephone-based system than Whites. In satisfaction surveys, Whites more commonly reported ease in understanding and reporting symptoms compared with Blacks. Blacks more often reported that the ePRO system was helpful in facilitating symptom-related discussions with clinicians. During interviews, Blacks described how the ePRO helped them recognize symptoms, while Whites found value in better understanding and tracking symptoms longitudinally. Blacks also expressed preferences for paper-based ePRO options due to perceived ease in better understanding of symptom items. Conclusion: Electronic patient-reported outcomes are perceived as valuable for variable reasons by Black and White cancer populations, with greater perceived value for communicating with clinicians reported among Blacks. To optimize equitable uptake of ePROs, oncology practices should offer several ePRO options (e.g., web-based, phone-based), as well as paper-based options, and consider the e-health literacy needs of patients during implementation

Guidelines for the assessment of efficacy of clinical hypnosis applications

Research on the efficacy of hypnosis applications continues to grow, but there remain major gaps between the science and clinical practice. One challenge has been a lack of consensus on which applications of hypnosis are efficacious based on research evidence. In 2018, 6 major hypnosis organizations collaborated to form the Task Force for Establishing Efficacy Standards for Clinical Hypnosis. This paper describes a Guideline for the Assessment of Efficacy of Clinical Hypnosis Applications developed by the Task Force, which makes 10 specific recommendations. The guideline is intended to be a tool for those who want to assess the quality of existing evidence on the efficacy of clinical hypnosis for any particular indication. The paper also discusses methodological issues in the interpretation and implementation of these guidelines. Future papers will report on the other products of the Hypnosis Efficacy Task Force, such as best practice recommendations for outcomes research in hypnosis and an international survey of researchers and clinicians on current practice and attitudes about hypnosis

Geographically touring the eastern bloc: British geography, travel cultures and the Cold War

This paper considers the role of travel in the generation of geographical knowledge of the eastern bloc by British geographers. Based on oral history and surveys of published work, the paper examines the roles of three kinds of travel experience: individual private travels, tours via state tourist agencies, and tours by academic delegations. Examples are drawn from across the eastern bloc, including the USSR, Poland, Romania, East Germany and Albania. The relationship between travel and publication is addressed, notably within textbooks, and in the Geographical Magazine. The study argues for the extension of accounts of cultures of geographical travel, and seeks to supplement the existing historiography of Cold War geography

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001). INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research