Environmental variables affecting an arid coastal nebkha

Foredunes in arid coastal dune systems comprise nebkhas, which originate by interactions between vegetation and aeolian sedimentation. While continuous foredunes in temperate climates have been widely studied, knowledge of interactions between biotic and abiotic drivers in foredunes formed by nebkha is still scarce. With the aim of exploring variables affecting arid foredunes, a range of morphological, sedimentological, and vegetation characteristics were measured on a single nebkha formed by a Traganum moquinii plant located in the foredune of Caleta de Famara beach (Lanzarote, Canary Islands). Variables were sampled at 120 plots in a 0.5 × 0.5 m square grid. A two-step process using multiple linear regression (MLR) analyses was developed to characterize 1) the influence that morphological variables and distance from the sea have on plant and sediment patterns on nebkha, and 2) the influence of plants on depositional sediment characteristics. Results indicate close relationships between distance from the sea, plant coverage, and sediment patterns. Empirical results were used to develop a conceptual model that explains the spatial distribution of bio- and geo-morphological characteristics of an arid nebkha foredune.Spanish Ministry of Economy, Industry and Competitiveness contract (BES-2017-082733

A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates expansion of chronic lymphocytic leukemia cells

The signaling lymphocyte activation molecule family [SLAMF] of cell surface receptors partakes in both the development of several immunocyte lineages and innate and adaptive immune responses in humans and mice. For instance, the homophilic molecule SLAMF6 (CD352) is in part involved in natural killer T cell development, but also modulates T follicular helper cell and germinal B cell interactions. Here we report that upon transplantation of a well-defined aggressive murine B220+CD5+ Chronic Lymphocytic Leukemia (CLL) cell clone, TCL1-192, into SCID mice one injection of a monoclonal antibody directed against SLAMF6 (αSlamf6) abrogates tumor progression in the spleen, bone marrow and blood. Similarly, progression of a murine B cell lymphoma, LMP2A/λMyc, was also eliminated by αSlamf6. But, surprisingly, αSLAMF6 neither eliminated TCL1-192 nor LMP2A/λMyc cells, which resided in the peritoneal cavity or omentum. This appeared to be dependent upon the tumor environment, which affected the frequency of sub-populations of the TCL1-192 clone or the inability of peritoneal macrophages to induce Antibody Dependent Cellular Cytotoxicity (ADCC). However, co-administering αSlamf6 with the Bruton tyrosine kinase (Btk) inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the spleen, bone marrow, liver and the peritoneal cavity. Because an anti-human SLAMF6 mAb efficiently killed human CLL cells in vitro and in vivo, we propose that a combination of αSlamf6 with ibrutinib should be considered as a novel therapeutic approach for CLL and other B cell tumors

Associations of body mass and fat indexes with cardiometabolic traits

Background Body mass index (BMI) is criticized for not distinguishing fat from lean mass and ignoring fat distribution, leaving its ability to detect health effects unclear. Objectives The aim of this study was to compare BMI with total and regional fat indexes from dual-energy x-ray absorptiometry in their associations with cardiometabolic traits. Duration of exposure to and change in each index across adolescence were examined in relation to detailed traits in young adulthood. Methods BMI was examined alongside total, trunk, arm, and leg fat indexes (each in kilograms per square meter) from dual-energy x-ray absorptiometry at ages 10 and 18 years in relation to 230 traits from targeted metabolomics at age 18 years in 2,840 offspring from the Avon Longitudinal Study of Parents and Children. Results Higher total fat mass index and BMI at age 10 years were similarly associated with cardiometabolic traits at age 18 years, including higher systolic and diastolic blood pressure, higher very low-density lipoprotein and low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, higher triglycerides, and higher insulin and glycoprotein acetyls. Associations were stronger for both indexes measured at age 18 years and for gains in each index from age 10 to 18 years (e.g., 0.45 SDs [95% confidence interval: 0.38 to 0.53] in glycoprotein acetyls per SD unit gain in fat mass index vs. 0.38 SDs [95% confidence interval: 0.27 to 0.48] per SD unit gain in BMI). Associations resembled those for trunk fat index. Higher lean mass index was weakly associated with traits and was not protective against higher fat mass index. Conclusions The results of this study support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects

Survival benefits of statins for primary prevention: a cohort study

Objectives: Estimate the effect of statin prescription on mortality in the population of England and Wales with no previous history of cardiovascular disease.  Methods: Primary care records from The Health Improvement Network 1987-2011 were used.Four cohorts of participants aged 60, 65, 70, or 75 years at baseline included 118,700,199,574, 247,149, and 194,085 participants; and 1.4, 1.9, 1.8, and 1.1 million person-years of data, respectively. The exposure was any statin prescription at any time before the participant reached the baseline age (60, 65, 70 or 75) and the outcome was all-cause mortality at any age above the baseline age. The hazard of mortality associated with statin prescription was calculated by Cox's proportional hazard regressions, adjusted for sex, year of birth, socioeconomic status, diabetes,antihypertensive medication, hypercholesterolaemia, body mass index, smoking status, and general practice. Participants were grouped by QRISK2 baseline risk of afirst cardiovascular event in the next ten years of <10%, 10-19%, or ≥20%.  Results: There was no reduction in all-cause mortality for statin prescription initiated in participants with a QRISK2 score <10% at any baseline age, or in participants aged 60at baseline in any risk group. Mortality was lower in participants with a QRISK2 score≥20% if statin prescription had been initiated by age 65 (adjusted hazard ratio (HR)0.86 (0.79-0.94)), 70 (HR 0.83 (0.79-0.88)), or 75 (HR 0.82 (0.79-0.86)). Mortality reduction was uncertain with a QRISK2 score of 10-19%: the HR was 1.00 (0.91-1.11)for statin prescription by age 65, 0.89 (0.81-0.99) by age 70, or 0.79 (0.52-1.19) by age75.  Conclusions: The current internationally recommended thresholds for statin therapy for primary prevention of cardiovascular disease in routine practice may be too low and may lead to overtreatment of younger people and those at low risk

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity

Adherence to self-managed exercises for patients with persistent subacromial pain: the Ad-Shoulder feasibility study

© 2021, The Author(s). Background: Exercise is recommended for patients with subacromial pain. It has been suggested that good exercise adherence improves clinical outcomes. Despite this, little attention has been paid to the need for behavioural frameworks to enhance adherence to home exercise programmes for patients with subacromial pain. Methods: A feasibility study with pre-post design was used. Participants aged > 18 years, with subacromial pain, who had received conservative treatment during the past 6 months, were recruited. The Ad-Shoulder intervention consisted of 1–5 individual sessions provided over 3 months and was based on 5 self-management skills, which aimed to enhance the patients’ self-efficacy and adherence to self-managed exercises. The primary objectives were assessed according to predefined progression criteria: (1) the recruitment rate (10 patients enrolled within 12 weeks), (2) follow-up rate (≥ 80% on all self-reported measures), (3) objective physical activity measures (≥ 80% of participants would contribute valid data at each time point), (4) adherence with the self-managed exercises (≥ 80% of the participants would adhere to ≥ 80% of the assigned home exercise programme), (5) fidelity of the delivery of the intervention (the therapists delivered the intervention according to the protocol) and (6) adverse events (< 30% would report adverse events (including mild)). The results were reported using descriptive statistics. Results: Eleven patients were recruited during 16 weeks. Ten patients completed the self-reported measures at baseline and week 12. Objective physical activity measures were successfully obtained for 100% (11/11) at baseline, 64% (7/11) at week six and 82% at week 12. Fifty-five percent (6/11) of the participants satisfactorily completed at least 80% of their home exercise programme. All sessions were delivered according to the protocol. None of the patients reported any adverse events. Conclusions: Objective physical activity data measures at baseline and week 12, follow-up, the physiotherapists’ fidelity to the intervention and adverse events met our pre-specified progression criteria. Recruitment and adherence to the self-managed exercise programme were both below the anticipated level. Further intervention development is necessary to understand whether adherence to the self-managed exercises could be enhanced and additional methods of recruitment would need to be considered, including additional recruitment sites, in any planning for a future main trial. Trial registration: ClinicalTrials.gov, NCT04190836, Registered December 9, 2019—retrospectively registered

Low energy background in the NCD phase of the Sudbury Neutrino Observatory

The Sudbury Neutrino Observatory (SNO) was a 1 kilotonne heavy water Č{C}erenkov detector. Evidence for flavour changing neutrino oscillations was found by comparing the rate of Charged Current interactions with that of Neutral Current (NC) interactions. This thesis is concerned with the accurate determination of the NC flux in the Neutral Current Detector (NCD) phase of SNO. The measurement and understanding of radioactive backgrounds arising from decays of naturally occurring $^{232}$Th and $^{238}$U chain nuclei is crucial. This is because their daughter nuclei can produce neutrons via photodisintegration of deuterium. These would be indistinguishable from those produced by NC neutrino interactions. As the probability of neutron production was dependent upon the nature and location of activity, each contribution had to be determined separately. Of particular concern were $^{232}$Th and $^{238}$U in the D$_2$O and Neutral Current Detectors (NCDs). A maximum likelihood method was developed that exploited differences in the event isotropy and radial profile of each event class. These results were in agreement with water assay results and pre-deployment radioassays of the NCDs. An independent measurement of the $^{232}$Th content in the D$_2$O and H$_2$O was made by regularly assaying the water using filters loaded with hydrous titanium oxide. The concentration of $^{232}$Th in the water was determined by coincidence counting of the final assay sample. A new counter system was designed and built and the calibration and use of this system are presented. Two areas of increased activity were discovered on two of the NCDs deployed in the detector which would have prevented an accurate measurement of the NC flux. A method was devised to determine the composition and activity of one of these hotspots. The results were in good agreement with two independent methods and the uncertainty on the NC flux was reduced from $>7$% to $<1$%. The total number of neutrons produced per day by photodisintegration for $^{232}$Th and $^{238}$U in the D$_2$O and NCDs was measured to be $0.66^{+0.08}_{-0.07}$. This was significantly less than the expected 12.6 NC neutrino interactions per day. In the third phase, two independent data streams existed: PMT and NCD. A Monte Carlo study was undertaken to determine whether an accurate measure of the NC flux could be obtained using only PMT data. Results showed that no improvement could be made upon results from previous phases and the best measurement of the NC flux in the final phase would be made using PMT and NCD data.EThOS - Electronic Theses Online ServiceGBUnited Kingdo