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Additional file 2: Supplementary Figure 1. Interview Vignettes.

Groß, R., 2020. Ein neuer (grüner) Marshall-Plan für Europa? Konzepte des Wiederaufbaus aus umwelthistorischer Perspektive.Input zur Paneldiskussion “Wirtschaftliche Perspektiven – ein Round Table” mit Exenberger, A; Ohndorf, M; und Momsen, K

Energy, food, or mobility can be conceptualized as provisioning systems which are decisive to sustainability transformations in how they shape resource use and because of emissions resulting from them. To curb environmental pressures and improve societal well-being, fundamental changes to existing provisioning systems are necessary. In this article, we propose that provisioning systems be conceptualized as featuring integrated socio-metabolic and political-economic dimensions. In socio-metabolic terms, material stocks—buildings, infrastructures, and machines, for example—are key components of provisioning systems and transform flows of energy and materials into goods and services. In political-economic terms, provisioning systems are formed by actors, institutions, and capital. We loosely identify and closely analyze, from sociometabolic and political-economic perspectives, five phases along which provisioning systems are shaped and in which specific opportunities for interventions exist. Relying mainly on examples from the fossil-fueled electricity system, we argue that an integrated conceptualization of provisioning systems can advance understanding of these systems in two essential ways: by (1) facilitating a more encompassing perspective on current forms of provisioning as relying on capitalist regulation and on material stocks and flows and by (2) embedding provisioning systems within their historical context, making it possible to conceive of more sustainable and just forms of provisioning under (radically) altered conditions.

Groß, R., 2021. Der Marshall Plan. Eine Bedingung der Möglichkeit der „Großen Beschleunigung“ in Westeuropa?

Groß, R., 2020. Gegen den Strich gebürstet: Überlegungen zur Umweltgeschichte des Marshallplan.

Loss of nigrostriatal dopaminergic projection neurons is a key pathology in Parkinson's disease, leading to abnormal function of basal ganglia motor circuits and the accompanying characteristic motor features. A number of intraparenchymally delivered gene therapies designed to modify underlying disease and/or improve clinical symptoms have shown promise in preclinical studies and subsequently were evaluated in clinical trials. Here we review the challenges with surgical delivery of gene therapy vectors that limited therapeutic outcomes in these trials, particularly the lack of real-time monitoring of vector administration. These challenges have recently been addressed during the evolution of novel techniques for vector delivery that include the use of intraoperative MRI. The preclinical development of these techniques are described in relation to recent clinical translation in an adeno-associated virus serotype 2-mediated human aromatic L-amino acid decarboxylase gene therapy development programme. This new paradigm allows visualisation of the accuracy and adequacy of viral vector delivery within target structures, enabling intertrial modifications in surgical approaches, cannula design, vector volumes and dosing. The rapid, data-driven evolution of these procedures is unique and has led to improved vector delivery.

ObjectiveTo determine whether regulatory variations in the heme oxygenase-1 (HO-1) promoter (GT) n dinucleotide repeat length could identify unique population genetic risks for neurocognitive impairment (NCI) in persons living with HIV (PLWH), we genotyped 528 neurocognitively assessed PLWH of European American and African American descent and linked genotypes to cognitive status.MethodsIn this cross-sectional study of PLWH (the CNS HIV Antiretroviral Therapy Effect Research cohort), we determined HO-1 (GT) n repeat lengths in 276 African Americans and 252 European Americans. Using validated criteria for HIV-associated NCI (HIV NCI), we found associations between allele length genotypes and HIV NCI and between genotypes and plasma markers of monocyte activation and inflammation. For comparison of HO-1 (GT) n allele frequencies with another population of African ancestry, we determined HO-1 (GT) n allele lengths in African PLWH from Botswana (n = 428).ResultsPLWH with short HO-1 (GT) n alleles had a lower risk for HIV NCI (OR = 0.63, 95% CI: 0.42-0.94). People of African ancestry had a lower prevalence of short alleles and higher prevalence of long alleles compared with European Americans, and in subgroup analyses, the protective effect of the short allele was observed in African Americans and not in European Americans.ConclusionsOur study identified the short HO-1 (GT) n allele as partially protective against developing HIV NCI. It further suggests that this clinical protective effect is particularly relevant in persons of African ancestry, where the lower prevalence of short HO-1 (GT) n alleles may limit induction of HO-1 expression in response to inflammation and oxidative stress. Therapeutic strategies that enhance HO-1 expression may decrease HIV-associated neuroinflammation and limit HIV NCI.

Learning to control a safety-critical system with latent dynamics (e.g. for deep brain stimulation) requires taking calculated risks to gain information as efficiently as possible. To address this problem, we present a probabilistically-safe, meta-active learning approach to efficiently learn system dynamics and optimal configurations. We cast this problem as meta-learning an acquisition function, which is represented by a Long-Short Term Memory Network (LSTM) encoding sampling history. This acquisition function is meta-learned offline to learn high quality sampling strategies. We employ a mixed-integer linear program as our policy with the final, linearized layers of our LSTM acquisition function directly encoded into the objective to trade off expected information gain (e.g., improvement in the accuracy of the model of system dynamics) with the likelihood of safe control. We set a new state-of-the-art in active learning for control of a high-dimensional system with altered dynamics (i.e., a damaged aircraft), achieving a 46% increase in information gain and a 20% speedup in computation time over baselines. Furthermore, we demonstrate our system's ability to learn the optimal parameter settings for deep brain stimulation in a rat's brain while avoiding unwanted side effects (i.e., triggering seizures), outperforming prior state-of-the-art approaches with a 58% increase in information gain. Additionally, our algorithm achieves a 97% likelihood of terminating in a safe state while losing only 15% of information gain., Comment: 9 pages

BackgroundPeople living with HIV (PLWH) commonly report marijuana use for chronic pain, although there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation).MethodsParticipants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation.ResultsOf 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (interquartile range 4.7-8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity, and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation.ConclusionsWe did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana.

Presentation at theLunchtime Colloquium of the Rachel Carson Center for Environment and Society, LMU Munich,31.10.2019

BackgroundChronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes.MethodsThis was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site.ResultsAmong 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03).ConclusionsChronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration.

PurposeAmong patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death.MethodsWe conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs.ResultsOver 7033 person-years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person-years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person-years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1-11mo: HR, 1.79 [95% confidence interval (CI), 0.74-4.31]; 12-35mo: HR, 1.39 [95% CI, 0.68-2.87]; 36-71mo: HR, 2.27 [95% CI, 0.92-5.60]; >71mo: HR, 4.66 [95% CI, 1.04-20.83]; P=.045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1-11mo: HR, 2.24 [95% CI, 1.04-4.81]; 12-35mo: HR, 2.05 [95% CI, 0.68-6.20]; 36-71mo: HR, 3.04 [95% CI, 1.12-8.26]; >71mo: HR, 3.93 [95% CI, 0.75-20.50]; P=.030).ConclusionsThese findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients.

Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

The present thesis essays to ascertain and research problems that concern the social requirements and the iconography of Hellenistic royal portraiture in glyptics. Throughout I employ a methodology established by H. Kyrieleis and R. Fleischer that defined anew the study of the numismatic evidence, recognizing in the obverse typology programs of a dynastic iconography.The analysis of the royal iconography is pursued in the second through the fourth chapters, which in their organization take account of the distribution of the material evidence. Leaving aside the late Ptolemaic dynasty, for which the numismatic evidence remains silent, over two-thirds of the portraits surveyed represent the types of the regnal emissions or are associated with them in iconography. For the complement of anonymous portraits the I attempt to establish a relative chronology based on correlations educed in the stylistic properties of the obverse types. Whereas some new attributions are proposed, the arguments are equally directed to an assessment of the stylistic idioms in which the iconography is couched. I submit that if judiciously applied against the numismatic criteria, this approach can at least suggest the probable dynastic affiliation or regional origin of a given portrait. The first chapter addresses the social requirements of the glyptic portraiture in the courts. Principally, it introduces arguments that stand counter to the scholarly consensus. I mount a case to refute the judgement that portrait cameos may have functioned as the ornamental devices of crowns awarded to the priests attending the eponymous dynastic cults. The weight of the evidence presumes that medallions fulfilled this purpose. Further, I would contend that the extended relationship of the glyptic iconography to the obverse types contradicts the theory that the royal house or its commissioners imposed in the aulic environment an iconography of divinized kingship, ideologically separate from that sanctioned for the official, public representation of the dynasty.

Multiple regression and frequency analysis of average month, peak month, peak day, and instantaneous water use by various water supply systems in Utah and Colorado are used to develop water demand functions. The research objective was to predict water demand as a function of a small number of independent variables for which data were easily obtainable and thereby provide an attractive method for use by consulting engineers inf uture planning studies. The independent variables in landscaped area and accounts for use of supplementary ditch or pressure irrigation systems. The demand functions were developed with data from a sample of 14 systems varying in size from very small low density rural systems to Salt Lake City's water system. The correlation coefficients (R^2) vary from 0.80 to 0.95. The demand fucntions were validated by comparing calculated to measured water use for more than 40 other Utah systems. Instantaneous demands are determined for any desired recurrence interval as a function of number of connections. The demand functions are presented both at best fit (expected value) levels for average month, peak month, and peak day and at recommended design levels for the same time durations. The design levels were calculated by adding to expected values an increment which was based upon standard deviation of the samples. Instanataneous demand peaks which can be expecte donce in about 30 years in Utah systems are under 2 gpm per connection for lines serving more than 50 families, 3 gpm for lines serving 10 families, and 5 gpm for lines serving 4 connections.

Society's dependence on weather systems has broadened to include electricity generation from wind turbines and solar PV systems. Climate change is altering energy flows in the atmosphere, which will affect the economic potential of wind and solar power outputs. This thesis presents a framework to assess the economic impact of climate change on annual average wind and solar power generation. This thesis highlights the knowledge gaps in economic analysis of future wind and solar resource assessments which consider climate change. It presents an interdisciplinarity framework which combines climate model outputs with technoeconomic modelling of financial metrics. This thesis outlines the proof of concept for this framework, exploring the limitations of global climate models for assessing wind and solar resources, and presents a novel bias-adjustment method to create future projected time series. CMIP5 and MERRA(2) datasets are used due to their accessibility and global scale, enabling results to be produced for anywhere on the globe. The framework is demonstrated with three case studies which focus on the cost of wind power in the UK, changing icing related losses in the northern hemisphere, and future impacts of climate change on solar PV in China. In all case studies, climate change impacts are projected under low and extreme climate forcing scenarios from the early to the late 21st century. Results are mixed. The relative change in average-annual capacity factors and levelised cost of energy is between ±2% under low scenarios of climate change and within ±5% for more extreme climate change. The change is also more pronounced later into the 21st century. These results show assessments of future wind and solar power are possible, highlighting that wind and solar power generation remains an attractive investment under all scenarios of climate change. Open Access

The cost of addressing climate change by reducing greenhouse gas emissions is heavily dependent on the future costs of low-carbon energy technologies. Yet many of these technologies are still relatively immature, with potentially significant room for further innovation and cost reduction. Estimating future technology costs is therefore critical yet challenging. This thesis investigates how different drivers of innovation and cost reduction, such as technological improvements, material inputs and manufacturing scale can be considered in tandem to better understand the future cost ranges of energy technologies. The thesis presents a first-of-a-kind assessment of organic solar photovoltaic modules using a bottom-up engineering model of material and manufacturing costs, with a stochastic analysis to understand the range of cost outcomes and the principal drivers of those outcomes. It also includes a first-of-a-kind expert elicitation of lithium ion battery packs for off-grid applications, further developing and enhancing existing best-practice expert elicitation protocols to account for different drivers of cost-reduction, including R&D, learning-by-doing and economies of scale. The thesis explores the implications of the future cost estimates of these technologies at two geographical scales: the first by considering the costs of off-grid solar and battery systems in rural communities currently reliant on diesel generators, using a bespoke model; the second by considering the potential impact of future solar photovoltaic and battery storage costs on global mitigation costs to meet a 2oC climate target, using an integrated assessment model. The thesis finds that disaggregation of technological innovation and cost reduction drivers provides important insights into how future cost reductions are likely to come about, including the role of specific policy support. In addition, the influence of solar photovoltaic and battery storage costs on mitigation costs is significant, since these technologies are making renewable-generated electricity at a variety of scales cost-competitive with fossil fuel electricity generation. Open Access

This thesis is concerned with the history of electricity generation costs, how they have changed over time, and the accuracy of forecasts of future costs. These costs are a critical input to policy, yet both estimates and forecasts have frequently proved to be wrong or have changed dramatically over relatively short timescales. The thesis presents evidence from three technology case studies (offshore wind, nuclear power and solar PV), supported by a review of the range of cost measures used in the economic, business and policy spheres, and the methodologies used to understand the factors that bear upon cost trajectories and approaches to forecasting future costs. Drawing upon the evidence from the case studies, the thesis examines how cost forecasts have changed over time, the (frequently wide) range of forecasts, the sources of errors, and how policy has responded to uncertainty and changes in both cost estimates and forecasts. The findings address the limitations of commonly used cost metrics, challenge assumptions that costs will necessarily fall, discuss the meaning of regulatory certainty in the face of uncertain future costs, and emphasise the importance of context (why estimates are commissioned, and by whom, and also who they are undertaken by). The evidence suggests that the co-presentation and use of estimates and forecasts for technologies with very different technical and financial characteristics implies significantly more comparability between them than is wise, and can convey the message that the underlying uncertainties are similar, when in fact the reasons may be fundamentally different in character. This highlights how important an understanding of technology characteristics is when deriving estimates and forecasts, not simply because those characteristics bear upon the numerical values of the results, but because of the influence they have on the nature of the uncertainty of those results. Open Access

The UK’s commitments to addressing climate change require a radical restructuring of the electricity sector. This thesis examines what role the electricity transmission networks could play in this transformation. In order to examine the possible role of policy making within a socio-technical system under conditions of long-term uncertainty, a novel scenario method is developed which accounts for political values, actor dynamics and technological networks. The approach is used to examine possible pathways for the electricity transmission network within alternative policy value-sets, which are defined by the level of locational signal provided to generators in respect of their network usage, and the degree of anticipatory or strategic planning involved in network policy. The scenarios emphasise the importance of a locational signal which acts at the operational timescale as well as the investment timescale. They also suggest a role for strategic coordination, particularly to join up planning across onshore, offshore and interconnector regimes. However, due to the range of possible generation and network configurations the scenarios span, they do not support the idea of a central design authority working to a single network blueprint. Specific policy recommendations aim to incorporate these suggestions within the grain of the existing policy trajectory and its prevailing value system. The two principle policy recommendations are therefore, the inclusion of a locational signal within the BSUoS charge in order to better reflect network usage at the operational timescale, and the establishment of an independent body with a remit to identify and contribute needs cases for cross-regime strategic coordination opportunities. The latter recommendation could be achieved with some adaption and clarification of the remit of the ENSG. Open Access

There is a longstanding debate about the future availability of energy resources, and a significant literature has developed around the issues of oil availability in particular. More recently, the availability of lesser-known critical metals, such as lithium and indium, has been called into question. These metals are key components in low-carbon energy technologies and a new evidence base that questions their future availability is emerging. Much of this research applies methods and techniques also applied to the analysis of oil resources, with the implicit assumption that these resources are in some way analogous. However, although there are similarities, there are also structural differences and the appropriateness of the assumed analogy has not been sufficiently tested. This thesis explores the similarities and differences in the structure of the oil, lithium and indium resource systems, examining the likely response of these systems to availability constraints and testing the appropriateness of this assumed analogy. The systems that define the market for resources are dynamically complex and involve a number of different interlinked variables. The way in which these resource systems respond to changes in surrounding conditions arises from the structure of these variables and their linkages. However, much of the existing analysis of critical metals relies on simplistic assumptions regarding the structure and function of these systems. To address this knowledge gap, this thesis first presents case studies of the three resource systems. The case studies are then used to develop three system dynamics models. This thesis finds that, while there are many similarities in the structure of the three resource systems modelled, the differences between them have a significant impact on their dynamic system behaviour. Analysis which overlooks these differences is likely to draw inaccurate conclusions. In particular, the resilience of metals to periods of constrained availability is potentially greater than that of oil if metal recycling is taken into account. However, metals recovered as by-products are potentially limited in their ability to resist constrained availability. Open Access