Analysis of quantum semiconductor heterostructures by ballistic electron emission spectroscopy

Ph.D.Thomas K. Gaylord, Elias N. Glytsis and Phillip N. First, Co-Chairs; Gary S. May and April S. Brown, Committee Member

Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group

The impact of the lung allocation score on short-term transplantation outcomes: A multicenter study

ObjectiveThe lung allocation score restructured the distribution of scarce donor lungs for transplantation. The algorithm ranks waiting list patients according to medical urgency and expected benefit after transplantation. The purpose of this study was to evaluate the impact of the lung allocation score on short-term outcomes after lung transplantation.MethodsA multicenter retrospective cohort study was performed with data from 5 academic medical centers. Results of patients undergoing transplantation on the basis of the lung allocation score (May 4, 2005 to May 3, 2006) were compared with those of patients receiving transplants the preceding year before the lung allocation score was implemented (May 4, 2004, to May 3, 2005).ResultsThe study reports on 341 patients (170 before the lung allocation score and 171 after). Waiting time decreased from 680.9 ± 528.3 days to 445.6 ± 516.9 days (P < .001). Recipient diagnoses changed with an increase in idiopathic pulmonary fibrosis and a decrease in emphysema and cystic fibrosis (P = .002). Postoperatively, primary graft dysfunction increased from 14.1% (24/170) to 22.9% (39/171) (P = .04) and intensive care unit length of stay increased from 5.7 ± 6.7 days to 7.8 ± 9.6 days (P = .04). Hospital mortality and 1-year survival were the same between groups (5.3% vs 5.3% and 90% vs 89%, respectively; P > .6)ConclusionsThis multicenter retrospective review of short-term outcomes supports the fact that the lung allocation score is achieving its objectives. The lung allocation score reduced waiting time and altered the distribution of lung diseases for which transplantation was done on the basis of medical necessity. After transplantation, recipients have significantly higher rates of primary graft dysfunction and intensive care unit lengths of stay. However, hospital mortality and 1-year survival have not been adversely affected

Is macroporosity controlled by complexed clay and soil organic carbon?

Multi-scale evidence of rapid, climate-induced soil structural changes occurring at yearly to decadal timescales is mounting. As a result, it has become increasingly important to identify the properties and mechanisms controlling the development and maintenance of soil structure and associated macroporosity. This is especially relevant since macroporosity has disproportionate effects on saturated hydraulic conductivity ( ) which strongly influences water storage and flux, thus, affecting the water cycle. In this study, we use decision trees and piecewise linear regression to assess the influence of soil and climate properties on effective porosity (EP; a proxy of macroporosity) in both surface and subsurface horizons under varying land-use and management practices. Data from 1,491 pedons (3,679 horizons) spanning five ecoregions representing bioclimate (e.g., potential vegetation) across the conterminous US demonstrate that, at a continental scale, EP in surface (A) and subsurface (B) horizons is strongly dependent on the complexed fraction of the total mass of soil organic carbon (SOC) and clay; a combined fraction that we refer to as complexed organic carbon and clay (COCC). EP showed a slight positive response to COCC in A horizons but increased steeply with increasing COCC in B horizons. This is because the smaller values of COCC in B horizons reflect a larger pool of clay that has a greater potential to accommodate and complex additions of SOC promoting stronger organo-mineral bonds and the concomitant development and maintenance of soil structure in these horizons. In contrast, larger values of COCC in A horizons reflect conditions where all or most of the clay fraction is effectively complexed with SOC resulting in a larger pool of non-complexed soil organic matter with varying contrasting effects on macroporosity that ultimately mute the response of EP to increases in COCC. In surface horizons, indirect factors such as mean annual precipitation and land use were important predictors of EP, whereas COCC was more influential in controlling EP within the subsoil. The EP-COCC relationship also holds within ecoregions but its effect is mitigated by soil and climate interactions suggesting that the effect of climate on this relationship is indirect and complex. Plowed surface horizons and horizons underlying plowed layers showed greater homogenization (due to disturbance effects reducing heterogeneity in the soil) as well as a reduction in the magnitude and rate of change of EP as a function of COCC compared to undisturbed horizons. Our findings suggest that the complexed fraction of clay and SOC is important for controlling macroporosity and at ecoregion scales and that the EP-COCC relationship may be an important framework for understanding and predicting future land use- and climate-induced changes in soil hydraulic properties.publishedVersio

Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1·7 million individuals in Wales with 20-year follow-up: a retrospective cohort study using linked data

BACKGROUND: To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical-mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales. METHODS: In this retrospective cohort study, we used population-scale, individual-level, anonymised, linked, demographic, administrative, and electronic health record data from the Wales Multimorbidity e-Cohort. We included data on all individuals aged 25 years and older who were living in Wales on Jan 1, 2000 (the start of follow-up), with follow-up continuing until Dec 31, 2019, first break in Welsh residency, or death. Multistate models were applied to these data to model trajectories of disease in multimorbidity and their associated effect on all-cause mortality, accounting for competing risks. Life expectancy was calculated as the restricted mean survival time (bound by the maximum follow-up of 20 years) for each of the transitions from the health states to death. Cox regression models were used to estimate baseline hazards for transitions between health states, adjusted for sex, age, and area-level deprivation (Welsh Index of Multiple Deprivation [WIMD] quintile). FINDINGS: Our analyses included data for 1 675 585 individuals (811 393 [48·4%] men and 864 192 [51·6%] women) with a median age of 51·0 years (IQR 37·0-65·0) at cohort entry. The order of disease acquisition in cases of multimorbidity had an important and complex association with patient life expectancy. Individuals who developed diabetes, psychosis, and congestive heart failure, in that order (DPC), had reduced life expectancy compared with people who developed the same three conditions in a different order: for a 50-year-old man in the third quintile of the WIMD (on which we based our main analyses to allow comparability), DPC was associated with a loss in life expectancy of 13·23 years (SD 0·80) compared with the general otherwise healthy or otherwise diseased population. Congestive heart failure as a single condition was associated with mean a loss in life expectancy of 12·38 years (0·00), and with a loss of 12·95 years (0·06) when preceded by psychosis and 13·45 years (0·13) when followed by psychosis. Findings were robust in people of older ages, more deprived populations, and women, except that the trajectory of psychosis, congestive heart failure, and diabetes was associated with higher mortality in women than men. Within 5 years of an initial diagnosis of diabetes, the risk of developing psychosis or congestive heart failure, or both, was increased. INTERPRETATION: The order in which individuals develop psychosis, diabetes, and congestive heart failure as combinations of conditions can substantially affect life expectancy. Multistate models offer a flexible framework to assess temporal sequences of diseases and allow identification of periods of increased risk of developing subsequent conditions and death. FUNDING: Health Data Research UK

Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1·7 million individuals in Wales with 20-year follow-up : a retrospective cohort study using linked data

Funding: This work was supported by Health Data Research UK (HDRUK) Measuring and Understanding Multimorbidity using Routine Data in the UK (MUrMuRUK; award numbers HDR-9006 and CFC0110). HDRUK is funded by the UK Medical Research Council (MRC), Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. This work also was co-funded by the MRC and NIHR (grant number MR/S027750/1). The work was supported by the Administrative Data Research (ADR) Wales programme of work, part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1). RKO is supported by a Springboard award (SBF006\1122) funded by the Academy of Medical Sciences, Wellcome Trust, Government Department of Business, Energy and Industrial Strategy, British Heart Foundation, and Diabetes UK. SS is part funded by the NIHR Applied Research Collaboration West Midlands, the NIHR Health Protection Research Unit (HPRU) in Gastrointestinal Infections, and the NIHR HPRU in Genomics and Enabling Data.Background To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical–mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales. Methods In this retrospective cohort study, we used population-scale, individual-level, anonymised, linked, demographic, administrative, and electronic health record data from the Wales Multimorbidity e-Cohort. We included data on all individuals aged 25 years and older who were living in Wales on Jan 1, 2000 (the start of follow-up), with follow-up continuing until Dec 31, 2019, first break in Welsh residency, or death. Multistate models were applied to these data to model trajectories of disease in multimorbidity and their associated effect on all-cause mortality, accounting for competing risks. Life expectancy was calculated as the restricted mean survival time (bound by the maximum follow-up of 20 years) for each of the transitions from the health states to death. Cox regression models were used to estimate baseline hazards for transitions between health states, adjusted for sex, age, and area-level deprivation (Welsh Index of Multiple Deprivation [WIMD] quintile). Findings Our analyses included data for 1 675 585 individuals (811 393 [48·4%] men and 864 192 [51·6%] women) with a median age of 51·0 years (IQR 37·0–65·0) at cohort entry. The order of disease acquisition in cases of multimorbidity had an important and complex association with patient life expectancy. Individuals who developed diabetes, psychosis, and congestive heart failure, in that order (DPC), had reduced life expectancy compared with people who developed the same three conditions in a different order: for a 50-year-old man in the third quintile of the WIMD (on which we based our main analyses to allow comparability), DPC was associated with a loss in life expectancy of 13·23 years (SD 0·80) compared with the general otherwise healthy or otherwise diseased population. Congestive heart failure as a single condition was associated with mean a loss in life expectancy of 12·38 years (0·00), and with a loss of 12·95 years (0·06) when preceded by psychosis and 13·45 years (0·13) when followed by psychosis. Findings were robust in people of older ages, more deprived populations, and women, except that the trajectory of psychosis, congestive heart failure, and diabetes was associated with higher mortality in women than men. Within 5 years of an initial diagnosis of diabetes, the risk of developing psychosis or congestive heart failure, or both, was increased. Interpretation The order in which individuals develop psychosis, diabetes, and congestive heart failure as combinations of conditions can substantially affect life expectancy. Multistate models offer a flexible framework to assess temporal sequences of diseases and allow identification of periods of increased risk of developing subsequent conditions and death.Publisher PDFPeer reviewe

Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland

Funding: CMC: This work was supported by Health Data Research UK (HDR UK) Measuring and Understanding Multimorbidity using Routine Data in the UK (HDR-9006; CFC0110). Health Data Research UK (HDR-9006) is funded by: UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, the National Institute for Health Research (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust.There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21·3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.Publisher PDFPeer reviewe

Clustering long-Term health conditions among 67728 people with multimorbidity using electronic health records in Scotland

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21-3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: Alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-Term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-Term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.</p

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Visual impairment is associated with physical and mental comorbidities in older adults:a cross-sectional study

Background&lt;p&gt;&lt;/p&gt; Visual impairment is common in older people and the presence of additional health conditions can compromise health and rehabilitation outcomes. A small number of studies have suggested that comorbities are common in visual impairment; however, those studies have relied on self-report and have assessed a relatively limited number of comorbid conditions.&lt;p&gt;&lt;/p&gt; Methods&lt;p&gt;&lt;/p&gt; We conducted a cross-sectional analysis of a dataset of 291,169 registered patients (65-years-old and over) within 314 primary care practices in Scotland, UK. Visual impairment was identified using Read Code ever recorded for blindness and/or low vision (within electronic medical records). Prevalence, odds ratios (from prevalence rates standardised by stratifying individuals by age groups (65 to 69 years; 70 to 74; 75 to 79; 80 to 84; and 85 and over), gender and deprivation quintiles) and 95% confidence intervals (95% CI) of 37 individual chronic physical/mental health conditions and total number of conditions were calculated and compared for those with visual impairment to those without.&lt;p&gt;&lt;/p&gt; Results&lt;p&gt;&lt;/p&gt; Twenty seven of the 29 physical health conditions and all eight mental health conditions were significantly more likely to be recorded for individuals with visual impairment compared to individuals without visual impairment, after standardising for age, gender and social deprivation. Individuals with visual impairment were also significantly more likely to have more comorbidities (for example, five or more conditions (odds ratio (OR) 2.05 95% CI 1.94 to 2.18)).&lt;p&gt;&lt;/p&gt; Conclusions&lt;p&gt;&lt;/p&gt; Patients aged 65 years and older with visual impairment have a broad range of physical and mental health comorbidities compared to those of the same age without visual impairment, and are more likely to have multiple comorbidities. This has important implications for clinical practice and for the future design of integrated services to meet the complex needs of patients with visual impairment, for example, embedding depression and hearing screening within eye care services