511 research outputs found
Richard Billingham
No full textBook chapter written and illustrated with Billingham's own words and photography and one photograph from his parents family album published in 'Dream on Baby' by Gesine Borcherdt, published by Hatje Vantz, 2024, 352pp, (hb) (Billingham section Pages 62 - 71).
This book was an anthology of personal stories accompanied by previously unpublished childhood photographs and drawings.
The antholoyy revealed a multitude of ways childhood helps shape artists creative practices in later life, sheding new light on what it means to make art.
Besides Billingham, Gesine Borcherdt asked 33 artists, including Ai Weiwei, Marina Abramović, Lynda Benglis, Vaginal Davis, Marcel Dzama, Mona Hatoum, Jeff Koons, Gregor Schneider, and Jordan Wolfson, about the impact of their earliest experiences on being an artist today.
Gesine Borcherdt is a Berlin-based curator, art critic and author for Art Review, Ursula, Welt am Sonntag, ART, and AD Germany.
The book was printed in both German and English editions
Public health priorities - The cost-effectiveness of HIV control: Getting the priorities right
No full textNo abstract available
Der Bruch der Theorie in der Praxis durch Not
No full textSome Remarks on Lujo Brentano's View of Labor Market Problems
Lujo Brentano (1844-1931) aimed for "realism" in economics. Regarding labor market theory, two topics are of particular interest: His investigations on "Hours and Wages in Relation to Production" (Scribner's 1894) and his analysis "On the History and Development of Gilds and the Origins of Trade Unions" (Trubner 1870). The topics of are discussed with a view on recent developments in labor economics.Lujo Brentano (1844-1931) hat sich als "realistischen" Ökonomen verstanden. Im Bereich der Arbeitsmarkttheorie sind zwei Bereiche von besonderem Interesse: Seine Untersuchungen über den Zusammenhang zwischen Lohn, Arbeitszeit und Arbeitsleistung und seine Überlegungen zur Bildung von kollektiven Formen der Lohnsetzung. Diese beiden Themen werden unter Einbeziehung gesamtwirtschaftlicher und methodischer Aspekte und einiger moderner Gesichtspunkte diskutiert
The role of endothelial proteoglycans and extracellular matrix for the flow- dependent dilatation of isolated normal and atherosclerotic human coronary arteries
No full text0 Titelblatt, Inhaltsverzeichnis, Abkürzungen
1 Einleitung 7
1.1 Geschichte 8
1.2 Fluß und Scherkraft - Begriffsbestimmung und Meßbereiche 9
1.2.1 Laminare Scherkraft 10
1.2.2 Turbulente Scherkraft 10
1.3 Wandaufbau humaner Koronararterien 11
1.3.1 Endothel 11
1.3.2 Extrazelluläre Matrix 13
1.3.3 Endotheliale Proteoglycane als Fluß-Sensoren 15
1.4 Mechanismen der Vasomotorik 16
1.4.1 Vasokonstriktion 16
1.4.2 Flußabhängige Vasodilatation 17
1.5 Desiderate 21
1.6 Ziel der Arbeit 22
2 Methoden 23
2.1 Präparation 23
2.1.1 Explantation 23
2.1.2 Feinpräparation und Äquilibrierung 23
2.1.3 Lösungen und Substanzen 23
2.2 Messung der Flußrate 25
2.3 Messung der Kraftentwicklung 25
2.4 Messung des Membranpotentials 25
2.4.1 Mikroelektroden 25
2.4.2 Meßverstärker und Datenaufnahme 26
2.4.3 Einstiche 26
2.5 Versuchsdurchführung 27
2.6 Korrektur der 'stress relaxation' 27
2.7 Auswertung 28
2.7.1 Auswertungsmodell 28
2.7.2 Statistische Methoden 29
3 Ergebnisse 30
3.1 Kraft- und Potentialentwicklung von unbehandelten normalen Gefäßen 30
3.2 Kraft- und Potentialentwicklung von deendothelialisierten normalen
Gefäßen 30
3.3 Kraft- und Potentialentwicklung von trypsinisierten normalen Gefäßen 33
3.4 Kraft- und Potentialentwicklung von unbehandelten arteriosklerotischen
Gefäßen 33
3.5 Kraft- und Potentialentwicklung von deendothelialisierten
arteriosklerotischen Gefäßen 36
3.6 Kraft- und Potentialentwicklung von trypsinisierten arteriosklerotischen
Gefäßen 36
3.7 Kraftentwicklung in Abhängigkeit vom Sensor in normalen Gefäßen 38
3.8 Kraftentwicklung in Abhängigkeit von der Matrix in normalen Gefäßen 40
3.9 Kraftentwicklung in Abhängigkeit vom Sensor in arteriosklerotischen
Gefäßen 40
3.10 Kraftentwicklung in Abhängigkeit von der Matrix in arteriosklerotischen
Gefäßen 42
4 Diskussion 43
4.1 Elektromechanische Kopplung in humanen Koronararterien 43
4.2 Trypsinisierung 45
4.2.1 Auswirkung in normalen Gefäßen 46
4.2.2 Auswirkung in arteriosklerotischen Gefäßen 47
4.3 Deendothelialisierung 47
4.4 Mechanosensorik und Mechanotransduktion in normalen Gefäßen 47
4.4.1 Anforderungen 48
4.4.2 Kandidaten 48
4.5 Mechanosensorik und -transduktion bei Arteriosklerose 51
4.5.1 Endotheliale Dysfunktion 52
4.5.2 Matrixveränderungen bei Arteriosklerose 53
4.6 Einfluß von endothelständigem Sensor und subendothelialer Matrix auf die
Kraftentwicklung bei verschiedenen Flußraten in normalen Gefäßen 54
4.7 Einfluß von endothelständigem Sensor und subendothelialer Matrix auf die
Kraftentwicklung bei verschiedenen Flußraten in arteriosklerotischen Gefäßen
55
5 Literatur 56
6 Zusammenfassung, Danksagung, Lebenslauf 71
Danksagung 73Die Bedeutung eines intakten Endothels für die flußabhängige Dilatation
arterieller Gefäße ist unbestritten und methodologisch befriedigend
untersucht. Weniger Aufmerksamkeit wurde der Rolle der extrazellulären Matrix
bei der Vermittlung des Flussreizes gewidmet sowie dem Anteil, den beide,
Endothel und Matrix, an Membranpotential und Gefäßtonus arteriosklerotischer
Gefäße haben. Diese Arbeit stellt eine erste systematische vergleichende
Untersuchung des Beitrags von Endothel und Matrix zu Membranpotential- und
Tonusentwicklung in Abhängigkeit von systematisch variierten Flußraten in
normalen und arteriosklerotischen Gefäßen unter jeweils identischen
Versuchsbedingungen dar. Hierzu wurden unbehandelte, intakte humane Koronar-
Präparate wurden mit mechanisch deendothelialisierten Präparaten verglichen
sowie mit Präparaten, die zuvor mit einer niedrig-konzentrierten Trypsinlösung
inkubiert worden waren. Die Trypsinbehandlung führte zur Lösung der Ektodomäne
des endothelialen transmembranalen Proteoglykans Syndecan sowie zur
Desintegration von Teilen der subendothelialen Matrix. Das Membranpotential
wurde intrazellulär mit Glaskapillar-Mikroelektroden, die Kraftentwicklung mit
einem induktiven Kraftaufnehmer gemessen. Mit zunehmender Flußrate von 3
ml/min auf 100 ml/min hyperpolarisierte die glattmuskuläre Zellmembran
unbehandelten nicht-arteriosklerotischen Präparate. Hiermit ging eine
Tonusabnahme in Höhe von 0,512 g einher. Die deendothelialisierten nicht-
arteriosklerotischen Präparate wiesen eine deutlich geringfügigere
Hyperpolarisation und eine Relaxation um lediglich 0,280 g auf. Trypsinisierte
nicht-arteriosklerotische Gefäße zeigten eine Depolarisation sowie eine
Kontraktion von 0,391 g. Unbehandelte arteriosklerotische Präparate wiesen
gegenüber unbehandelten nicht-arteriosklerotischen Präparaten eine
Hyperpolarisation und eine signifikant geringfügigere Abnahme der Wandspannung
um 0,102 g auf. Deendothelialisierte arteriosklerotische Präparate zeigten
eine flußabhängige Hyperpolarisierung mit einer minimalen flußabhängigen
Relaxation um 0,070 g. Trypsinisierte arteriosklerotische Präparate zeigten
eine ausgeprägte flußabhängige Tonusabnahme von 0,612 g. Hieraus lässt sich
ableiten, dass bei physiologischen Flußraten zwischen 20 ml/min und 40 ml/min
das endotheliale Kompartiment normaler humaner Koronararterien zu etwa 65% an
der flußabhängigen Relaxation beteiligt ist, während bei Flußraten von 100
ml/min die flußabhängige Tonusabnahme zu 72% von der subendothelialen Matrix
getragen wird. In arteriosklerotisch veränderten Gefäßen kommt es zu einer
flußabhängigen Kontraktion, an der das endotheliale Kompartiment ab einer
Flußrate von 20 ml/min in zunehmendem Maß beteiligt ist. Bei Flußraten von 100
ml/min vermittelt das endotheliale Kompartiment eine Kontraktion in Höhe von
44% der maximalen Dilatation eines normalen Gefäßes; diese Kontraktion wird
zum größeren Teil von einer matrixvermittelten flußabhängigen Relaxation in
Höhe von 27% der maximalen Tonusabnahme eines normalen Gefäßes aufgehoben.
Diese Ergebnisse weisen auf das Ausmaß der durch Arteriosklerose induzierten
endothelialen Dysfunktion in den untersuchten Gefäßen hin und unterstreichen
die vitale Bedeutung einer intakten subendothelialen Matrix für die
Aufrechterhaltung physiologischer Flußmuster in arteriosklerotisch veränderten
Koronararterien.Despite its clinical importance and augmented research activity, the exact
mechanisms of mechanoperception at the luminal surface of the coronary artery
endothelium and of mechanotransduction on to the arterial smooth muscle cell
remain elusive. This research quantifies the impact of the luminal
proteoglycan syndecan as a potential mechanosensor, and the subendothelial
matrix as the site of mechanotransduction, in maintaining flow-dependent
vasodilatation in healthy and atherosclerotic human coronary arteries. We
measured the development of membrane potential and tension in non-
atherosclerotic and atherosclerotic segments of human coronary arteries under
flow rates of between 5 and 100 ml/min and compared these with the development
in de-endothelialised and trypsinised non-atherosclerotic and atherosclerotic
segments. Trypsinisation lead to the cleavage of the ectodomain of the luminal
proteoglycan syndecan as well as to the interruption of matrix integrity. The
membrane potential was measured intermittently with glass electrodes; vascular
wall tension was measured continuously by mounting the segment in the force
transduction unit of a flow chamber supplied with aerated, heated Krebs
solution at regularly increased flow rates. Untreated non-atherosclerotic
vessel segments showed a marked flow-dependent hyperpolarisation and a
relaxation of 0.512 g. In de-endothelialised non-atherosclerotic vessel
segments, membrane potential and tension were higher at baseline and decreased
less under flow, with a net relaxation of 0.280. Trypsinised non-
atherosclerotic vessel segments had still higher membrane potential and
tension at baseline and showed a marked flow-dependent depolarisation and
contraction of 0.391 g. In untreated atherosclerotic vessel segments, baseline
values for membrane potential and tension were higher than in healthy vessel
segments; under flow conditions, these segments exhibited a stunted
hyperpolarisation and relaxation at low flow rates, with subsequent
depolarisation and contraction under higher flow rates (net relaxation 0.102
g). De-endothelialised atherosclerotic vessel segments had higher baseline
values than de-endothelialised non-atherosclerotic vessel segments and showed
a minimal hyperpolarisation after initial depolarisation as well as a minimal
relaxation (0.070 g). Trypsinised atherosclerotic vessel segments had a
significantly lower baseline membrane potential and tension than untreated
atherosclerotic as well as trypsinised non-atherosclerotic vessel segments and
showed a marked flow-dependent relaxation (0.612). Based on these values, we
calculated the contribution of the luminal flow-sensor syndecan and the
subendothelial matrix to overall vasomotion to be 47% vs. 11% at flow rates of
5 ml/min, 65% vs. 25% at 20 ml/min, 65% vs. 38% at 40 ml/min, and 28% vs. 72%
at 100 ml/min in non-atherosclerotic vessels. In atherosclerotic vessels,
endothelium-induced contraction was 18% at 20 ml/min rising to 43,8% at 100
ml/min, with the matrix partly compensating this with a relaxation of 13% at 5
ml/min and 26% to 27% between 20 and 100 ml/min (100% = 0.461g, maximal net
relaxation of non-atherosclerotic, intact vessel segments)
The economics of antiretroviral therapy in South Africa: The role of budget impact modelling in changing policy
No full textSouth Africa is home to the largest number of people living with HIV in the world, as well as the world’s largest public-sector antiretroviral treatment (ART) programme. Despite the absolute majority of it being domestically funded, planning and budgeting for this programme has in the past been based on assumptions regarding target population and unit cost and on politically expedient coverage targets. The aim of this thesis was to improve on this situation by developing a budget impact model that could project the number of adults and children in treatment based on sound epidemiological methods, and calculate the cost of treating them based on the results of detailed bottom-up cost analyses at relevant clinics and hospitals in South Africa. The thesis describes the methods used in generating the inputs for the model, including the outpatient and inpatient cost of ART provision to adults and children of different ages, and the rates of CD4 cell count development, mortality, loss to follow-up, treatment failure, and regimen switches that were used in the model.The model was used to illustrate the budget impact of a number of guideline changes under discussion by the South African government in 2009/10, including 1.) expanding eligibility to all adults with CD4 cell counts <350 cells/microl, as well as to all TB co-infected and pregnant patients and all children under the age of 12 months regardless of immunological status, and 2.) replacing stavudine in first-line regimens with tenofovir for adults and with abacavir for children, with concomitant changes to second-line regimens. Both 1.) and 2.) had been suggested by the 2009 World Health Organization (WHO) guidelines (“Full WHO guidelines”). A second scenario was considered that expanded eligibility at 350 CD4 cells/microl only to those adults who were pregnant or had active TB at initiation while also replacing the current drug regimens as under 2.) (“New guidelines”). Additional factors with an impact on cost that were considered in the model were a) the introduction of a task-shifting policy that allowed antiretroviral drugs to be prescribed by nurses instead of doctors, and dispensed by pharmacy assistants instead of pharmacists, and b) replacing the existing system of antiretroviral drug procurement via government tenders that favour domestic production with drugs sourced globally at ceiling prices based on the cheapest internationally available price for each drug, including fixed-dose combinations (FDCs) wherever possible. Combining all the inputs, the model showed that while the Full WHO guidelines scenario would increase total cost over the next two mid-term expenditure framework periods (2010/11 to 2016/17) by 35% to USD 19.1 billion, and the New Guidelines scenario by 19%, this increase could be more than offset by introducing the two additional policies. In this case, the total cost of the ART programme under the New Guidelines would be 32% less than under the Old Guidelines without FDCs and task-shifting (taken as government’s revealed willingness-to-pay), while reaching 14% more patients, and implementing the Full WHO Guidelines would still be 23% less costly than continuing the Old Guidelines, while reaching 23% more patients. Based in part on this analysis, the South African government increased treatment eligibility in two steps in April 2010 and in August 2011, introduced the improved drug regimens, established task shifting, and, using the proposed reference price list, negotiated significant drug price reductions for both the December 2010 and the December 2012 ARV drug tender. The budget impact model, named the National ART Cost Model, has been used in budget planning processes for the last seven financial years and, based in part on it, the government’s Conditional Grant for HIV/AIDS, the main vehicle for ART funding, was more than doubled in real terms over this time period. The thesis ends by presenting the results of a cost-benefit analysis of an alternative funding mechanism to public-sector funding, the provision of ART at the workplace, which was found from the company perspective to be cost-saving over no provision of ART, reducing the total cost due to HIV by 5%, and the cost per HIV-infected employee by 14%, over 20 years
Posttraumatic Stress Disorder (PTSD) Patients Exhibit a Blunted Parasympathetic Response to an Emotional Stressor
No full textDiminished parasympathetic reactivity is a physiological feature of posttraumatic stress disorder (PTSD). The objective of this study was to compare female PTSD patients with non-traumatized healthy women with respect to autonomic cardiovascular regulation during exposure to two stressors. Hospitalized PTSD patients (n = 52) and controls (n = 37) completed standardized laboratory-based stress testing including a mental arithmetic test and a standardized audiotape recording of a crying infant. Controls and PTSD patients both showed a significantly increased heart rate and reduced pre-ejection period from baseline rest to the arithmetic stressor. However, as judged from nonsignificant changes in baroreflex sensitivity, parasympathetic activation caused by the crying infant stressor was blunted in PTSD patients as compared to healthy individuals. Under the crying infant condition, a vagal dominance was observed only in controls, and not in PTSD patients. Our data demonstrate that, in PTSD patients, diminished parasympathetic reactivity is not restricted to trauma-related events but can also be observed in response to a social stimulus such as listening to a crying infant. This finding suggests that the altered vagal reactivity in PTSD patients reflects the physiological consequences of a generally disturbed autonomous response to emotionally relevant stressors
The cost effectiveness of integrated care for people living with HIV including antiretroviral treatment in a primary health care centre in Bujumbura, Burundi
No full textThe incremental cost effectiveness of an integrated care package (i.e., medical care including antiretroviral therapy (ART) and other services such as psychological and social support) for people living with HIV/AIDS was calculated in a not-for-profit primary health care centre in Bujumbura run by Society of Women against AIDS-Burundi (SWAA-Burundi), an African non-governmental organisation (NGO). Results are expressed as cost-effectiveness ratio 2007, constant US per DALY averted. The package of care provided by SWAA-Burundi is therefore a very cost-effective intervention in comparison with other interventions against HIV/AIDS that include ART. It is however, less cost effective than other types of interventions against HIV/AIDS, such as preventive activities
Abstract Wed149: Cardiac Fibrosis and Senescence in Engineered Human Myocardium
No full textIntroduction: Engineered Human Myocardium (EHM) is presently used for drug discovery and modeling of monogenic cardiomyopathy. Notably, standard four- to six-week EHM cultures exhibit characteristics similar to juvenile ventricular myocardium. We hypothesize, that prolonged culture of EHM recapitulates pathological cardiac remodeling and aging processes. Methods and Results: We generated EHM (n=240) from human iPSC-derived cardiomyocytes and stromal cells in a collagen hydrogel. To assess spontaneous tissue contractions, we employed a video-optic recording system and observed stable contractions (force of contraction [FOC] in mN/mm2: 0.34 ± 0.01; n=240) in all EHM at 5 weeks of culture. Spontaneous contractions remained intact until 4 months (FOC in mN/mm2: 0.91 ± 0.06; n=159), after which they declined until 50% of the cohort lost spontaneous contractility at 6 months (FOC in mN/mm2: 0.35 ± 0.02; n=112). By 12 months, only 2 EHM showed macroscopically visible contractions (FOC in mN/mm2: 0.16; n=2). Diastolic tissue tension (resting tension [RT]), as a marker of fibroblast activity, remained stable until 8 weeks in culture (RT in mN/mm2: 0.6 ± 0.05; n=238), but increased significantly between 3 and 6 months (RT in mN/mm2: 2.5 ± 0.1 vs 10.0 ± 0.2; p<0.0001). In predefined endpoint measurements including RNA and single-nucleus sequencing, we observed development of a “myofibroblast signature” at 3 and 6 months with enrichment of transcripts encoding for ACTA2, POSTN and COL1A1. At 12 months, transcriptome signals indicative of cellular senescence (CDKN1A, SERPINE1) and inflammation (LIF, NFKB2) became apparent. Furthermore, analysis of medium supernatant by proximity extension assays (OLink) revealed increased abundance of aging-related proteins in older EHM cultures. Conclusion: EHM exhibit stable contractile function and tissue tension from 1 to 3 months, serving as a model for the healthy myocardium within this timespan. Between 3 and 6 months, EHM show increased tissue tension and expression of myofibroblast markers, accompanied by decreased spontaneous contractility. Further cultivation up to 12 months accumulates transcriptome markers of cardiac senescence and secretion of aging-related proteins. These findings suggest that EHM can serve as a model for cardiac fibrosis and aging
HIV treatment as prevention: modelling the cost of antiretroviral treatment--state of the art and future directions.
No full textPolicy discussions about the feasibility of massively scaling up antiretroviral therapy (ART) to reduce HIV transmission and incidence hinge on accurately projecting the cost of such scale-up in comparison to the benefits from reduced HIV incidence and mortality. We review the available literature on modelled estimates of the cost of providing ART to different populations around the world, and suggest alternative methods of characterising cost when modelling several decades into the future. In past economic analyses of ART provision, costs were often assumed to vary by disease stage and treatment regimen, but for treatment as prevention, in particular, most analyses assume a uniform cost per patient. This approach disregards variables that can affect unit cost, such as differences in factor prices (i.e., the prices of supplies and services) and the scale and scope of operations (i.e., the sizes and types of facilities providing ART). We discuss several of these variables, and then present a worked example of a flexible cost function used to determine the effect of scale on the cost of a proposed scale-up of treatment as prevention in South Africa. Adjusting previously estimated costs of universal testing and treatment in South Africa for diseconomies of small scale, i.e., more patients being treated in smaller facilities, adds 42% to the expected future cost of the intervention
HIV Treatment as Prevention: Modelling the Cost of Antiretroviral Treatment—State of the Art and Future Directions
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