Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: For example, flood walls should be built, and in numerous cases, it is probably advisable to move human settlements out of flood plains and other low-lying areas…” (Framework on Climate Change—2015); over “a process by which strategies to moderate, cope with, and take advantage of the consequences of climatic events are enhanced, developed, and implemented” (Development Programme—UNDP, 2012); to “The process or outcome of a process that leads to a reduction in harm or risk of harm, or realisation of benefits associated with climate variability and climate change” (Programme—UKCIP). This latter definition is comparable to the definition offered by IPCC (Levina & Tirpak, 2006, 2005. These natural hazards, which collectively fed the first media hype on climate change (Schmidt-Thomé, Klein, Nockert, Donges, & Haller, 2013), caused a general perception that climate change was a principal causative agent for many such disasters. Also the 3rd and 4th IPCC synthesis report (IPCC, 2001, 2007a) postulated general relationships between higher frequencies and occurrences of certain disasters and climate change, even though these generalized relationships still remain under debate (e. g. , Pielke, Gratz, Landsea, Collins, Saunders, & Musulin, 2008; Barredo, 2009, 2010). Perhaps the most prominent report that contributed to the shift towards climate change adaptation was the Review on Economics of Climate Change, by (2006, known as the “Stern Review”), which pointed out the importance of economic aspects in dealing with climate change. The report focused on the costs of inaction of climate change mitigation, but it also clearly showed the need for adaptation, especially by poorer countries. It was this combination of the IPCC reports, the Stern Review, and media attention on the disasters caused by natural hazards that led to political action on climate change adaptation on the transnational level. In the European Union, this was evidenced by the on climate change adaptation (COM, 2007), which was soon followed by the EU on climate change adaptation (COM, 2009). These policy documents highlight the need for climate change adaptation and point out that adaptation must be implemented at the local level. Several other initiatives on transnational and national scales have led to the preparation of climate change adaptation strategies at different scales, from national to local. [SEP] Justify:

Output: The text contrasts the claim by emphasizing that climate adaptation is necessary but not sufficient on its own to counteract climate change. References to the need for building flood walls, moving settlements, and strategic coping methods underline the complexity of addressing climate change, suggesting that adaptation strategies are a response to the consequences rather than a complete solution. Additionally, the acknowledgment of the importance of mitigation and the costs of inaction suggests that both adaptation and mitigation are required to effectively tackle climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: The 443 reaction were methodically classified into three different categories 1) reactions that use no co-substrates or co-factors, 2) reactions that are anabolic conversions (merging the substrate with a co-substrate), and 3) reactions that are catabolic conversions where the substrate breaks down into corresponding product and co-product. Additionally, thermodynamic analysis was performed for each reaction, calculating ΔG (KJ/MOL), as was a promiscuity analysis (determining if an enzyme could accept multiple substrates). Subsequently, GEM-Path implemented a pathway predictor algorithm, which works by 1) designating a target compound and setting predictor constraints (maximal pathway length, metabolites to compute at each iteration, thermodynamic threshold, and reaction promiscuity threshold), 2) applying reactions to the target in a retrosynthetic manner for generating the corresponding substrates, and 3) checking if the substrate matches a compound in the Escherichia coli metabolome. Subsequently, if a pathway is found FBA is run to validate production. GEM-Path is not available for public use and there are other differences between the two software. GEM-Path integrates more detailed reaction parameters when predicting a pathway (i. e. ΔG and promiscuity) than RetSynth uses to identify optimal solutions. This subsequently makes GEM-Path’s metabolic database substantially smaller than RetSynth and therefore is missing many synthetic pathway opportunities. Additionally, GEM-Path’s algorithm does not allow multiple pathways per target to be identified, limiting the potential pathways provided to the researcher. MetaRouteMetaRoute is a web-based tool that finds pathways between two specified compounds using a graph-based searching algorithm [5]. Specifically, this tool uses Eppstein’s k-shortest path algorithm to find the shortest distance between two nodes in a graph. The graph representing a metabolic network was built by 1) using pre-calculated and concise atom mapping rules in which two successive reactions are represented by a single edge, 2) removing irrelevant reaction conversions (i. e. glucose 6 phosphate to ATP to AMP), and 3) using an updated weighting schema which decreased weights on edges through frequently used metabolites which traditionally had higher weights. [SEP] Justify:

Output: The text does not address the use of chassis organisms like E. coli in synthetic gene construction. It focuses on the classification of reactions, thermodynamic analysis, and specific metabolic pathway algorithms, which do not relate to the claim about E. coli's role in gene construction.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine tailors treatments to individuals based on genetic information. [SEP] Text: Analyzing a unique dataset linking medical claims, cancer registry data and proxies for income between 2004 and 2015, we find that lower-income patients are more likely to be diagnosed with later stages of breast cancer, and this pattern renders NHI coverage of anti-HER2 therapy pro-poor even before full coverage of the diagnostic tests. Moreover, the expansion of NHI coverage—including the FISH diagnostic test and trastuzumab for early-stage breast cancer—strengthened the pro-poor distribution of genetic testing and target treatment, albeit only marginally. The extent of pharmaceutical company coverage of testing and its impact on patient access are topics of our ongoing research, contrasting breast cancer with colorectal cancer. (pages 237 - 272)This 10. 7208/chicago/9780226611235. 003. 0010[pharmacogenomics;cost-effectiveness;Clopidogrel]Dual antiplatelet therapy, combining a P2Y12 inhibitor and aspirin, is central to management of patients with acute coronary syndromes. Clopidogrel is a commonly prescribed thienopyridine P2Y12 inhibitor used to prevent secondary events following a myocardial infarction/percutaneous coronary intervention. Clopidogrel effectiveness has been linked to proper function of metabolic enzyme cytochrome P450 2C19 (CYP2C19). Testing for CYP2C19 genetic changes that result in decreased activity has been proposed as a mechanism by which to identify clopidogrel non-responders a priori. Robust real-world studies evaluating the impact of genotype-guided antiplatelet selection on clinical, utilization and outcome metrics are lacking. We linked clinical and financial data on 2,595 Geisinger patients prescribed antiplatelet therapy without pharmacogenomic insight. Leveraging post-hoc, research-generated pharmacogenomic information, we describe the potential value of pharmacogenomic information in the selection of clopidogrel as the P2Y12 inhibitor therapy. Among patients examined, CYP2C19 loss of function did not predict the probability of later adverse events, clinical utilization or total medical costs within the 12 months after clopidogrel initiation. [SEP] Justify:

Output: The text corroborates the claim by discussing how pharmacogenomic testing, specifically the testing for CYP2C19 genetic changes, can help identify clopidogrel non-responders. This indicates that treatments can be tailored to individuals based on their genetic makeup, supporting the concept of personalized medicine.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: To support least developed countries (LDC’s) in their efforts, the UNFCC created the process of the programs of Action (NAPAs). Within this process, the LDCs identify the most imminent climate change adaptation needs, identifying those needs that should not be delayed either because of an increase in vulnerabilities or an increase in costs related to climate change impacts. Once an LDC submits a NAPA, that country is eligible for funding allocated under the (LDCF), managed by the Facility (GEF). By the end of 2013, 50 countries had submitted NAPAs to secure appropriate funding (information on the website). Even though large uncertainties remain about the speed and the impacts of human-induced climate change, changes in climate zones, and subsequently in habitats, are continuously proven scientifically and mapped (e. g. , Chen & Chen, 2013; Gerstengarbe & Werner, 2009). Following the logic that anthropogenic GHG emissions contribute to climate change, and since these emissions continue to increase (Mundaca, Markandya, & Nørgaard, 2013), it is quite clear that humans need to improve their adaptation to variances in the climate system and extreme events. The IPCC has published a comprehensive overview on climate change adaptation needs in its 5th Assessment Report, stating that “Adaptation requires adequate information on risks and vulnerabilities in order to identify needs and appropriate adaptation options to reduce risks and build capacity” (IPCC, 2014, p. 840). The identified needs comprise six categories: Biophysical and and Resources. Biophysical and Environmental adaptation needs can be addressed mainly by protecting habitats in their adaptation process. Social adaptation needs focus strongly on engaging different social groups, while respecting those most in need, including minority groups. Institutional adaptation needs address structures and their further development, as well as the importance of cooperation among different levels in developing and applying adaptation measures. Although higher-level institutions commonly set out regulations and incentives for adaptation, local level institutions need to translate those into locally applicable solutions—because it is at the local level where adaptation takes place in practice. From the Private Sector, stronger engagement in climate change adaptation can take place, not only by private firms understanding and protecting their holdings from emerging climate-related risks, but also by supporting the protection of their markets and clients. Information is most vital in understanding adaptation needs and their prioritization, which leads to overall Capacity needs. [SEP] Justify:

Output: The text contrasts with the claim by emphasizing the multifaceted approach required to address the impacts of climate change. It discusses the limitations of adaptation alone, stating that adaptation needs are categorized into biophysical, social, institutional, and capacity needs. Moreover, the text indicates the necessity for effective information on risks and vulnerabilities for identifying adequate adaptation options. This suggests adaptation is one part of a larger strategy that must include mitigation efforts, which contradicts the claim that adaptation alone can fully counteract the effects of climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: The graph of reactions and compounds MetaRoute uses was built using several metabolic repositories including BN++ (a biological information system), BNDB (biochemical network database) and KEGG. There are several key differences between this web-based tool and RetSynth, one being that a source compound must be specified instead of a chassis organism, which limits the number of pathways that can be discovered. While a user could perform a pathway search between every internal chassis compound and the target, this would take an extraordinary amount of time to get all optimal pathways and require the user to further sort through the pathways and identify the best route. Additionally, this is not a tool that can find sub-optimal pathways or evaluate the effectiveness of pathways through FBA. RetSynth’s capabilities far exceed MetaRoute’s including being a stand-alone software package that does not require a webservice like MetaRoute. RouteSearchRouteSearch is a module of the software utilizing the EcoCyc and MetaCyc databases for synthetic pathway identification [9]. This tool uses the branch-and-bound search algorithm on atom mapping rules to find optimal pathways between a set of starting compounds (or a specified source compound) and a target compound. Users can specify the weights (costs) of identifying pathways with reactions native to the chassis organism and those external to the organism. Additionally, multiple optimal pathways as well as higher cost or length sub-optimal pathways can be identified by RouteSearch. The user must specify how many pathways they want to examine, and if there are fewer optimal pathways than the user specified, then RouteSearch will give longer (sub-optimal) pathways. When identifying pathways by RouteSearch using the BioCyc web-browser a set of source compounds can be used to find pathways to an individual target compound. Additionally, a number of external bacterial organisms can be set by the user in which to search for optimal pathways. When using all bacterial organisms, however, RouteSearch freezes and is unusable. In addition to the web browser, RouteSearch can be used through the software suite, which allows all MetaCyc reactions to be loaded quickly and efficiently. When using RouteSearch through only a single source compound can be set and optimal pathways cannot be identified from an entire set of source compounds. Thus a rapid search for an optimal and sub-optimal pathway using all native chassis organism metabolites cannot be rapidly or efficiently achieved. [SEP] Justify:

Output: The text is irrelevant to the claim because it discusses the capabilities and limitations of tools like MetaRoute and RetSynth in metabolic pathway identification. It does not mention E. coli or chassis organisms directly in relation to synthetic gene construction.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine tailors treatments to individuals based on genetic information. [SEP] Text: . Nevzat Tarhan: "Genetic treatments provide personalized medicine. " Prof. Nevzat Tarhan: "Genetic treatments provide personalized medicine. " 12. 08. 2024 - 10:34 Haber ile ilişkili SDG etiketleri DOI : Noting that medication and psychotherapy are generally used together in the initial stage of psychiatric disorders, Psychiatrist Prof. expressed that "The role of the brain is critical in treatment. Drug treatment is the gold standard because psychiatric disorders cause disorders in the electrical and chemical communication of the brain. " Stating that the personalization of psychiatric treatments will play an important role in achieving more effective and safe results, Prof. Tarhan said that "Genetic treatments provide personalized treatment. It may be important to perform genetic evaluations, especially in cases where improvement cannot be achieved. " President of Üsküdar University and Psychiatrist Prof. evaluated current approaches in psychiatric diagnosis and treatment methods. Psychiatric illness is often called "disorders". . . Reminding that classical diagnostic methods were used in psychiatry diagnosis and treatment methods, especially in diagnosis, Prof. Tarhan noted that in these methods, the person is examined and diagnosed according to the symptoms and checklists, and the reason why psychiatric illness is generally called "disorders" is that biological evidence and their counterparts in the brain have not been fully confirmed. Stating that although there is a pathology in the brain, this pathology cannot be fully defined as a disease and therefore the term "disorder" is used, Prof. Tarhan said that "For example, terms such as depressive disorder, schizophrenic disorder and bipolar disorder are used in this way. Neuropathological evidence had to be present to identify a condition as a disease. However, in recent years, laboratory evidence has increased. Thanks to neuroimaging, neurobiological and neurophysiological studies, brain functions have been measured and the causality link between disorders has been revealed. Addiction is called ‘reward failure syndrome’, which is caused by an inadequate functioning of the reward area of the brain. Depression, on the other hand, can be defined as the asymmetrical functioning of the frontal region of the brain and the incompatible functioning of the pleasure and depression areas. In the future, diagnoses based on connectivity disorders of certain brain regions will be able to be made. [SEP] Justify:

Output: The text corroborates the claim by stating that 'Genetic treatments provide personalized medicine.' Prof. Nevzat Tarhan emphasizes the importance of personalization in psychiatric treatments and suggests conducting genetic evaluations, particularly when standard treatments are ineffective. This aligns with the claim's focus on how personalized medicine leverages genetic information to tailor healthcare treatments to the individual.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: The latter include Resources, that is, available means (mainly finances) that enable the development and implementation of adaptation projects. Based on established adaptation needs, adaptation options then are set out. These are grouped by IPCC (2014) as Structural/Physical, Social, and Institutional, each of which has several subgroups. Structural/Physical adaptation options are mainly composed of engineering and technological solutions (e. g. , dams for flood protection, or changes in fruits and crops) that speak to ecosystem needs (environmental protection and conservation) and services (e. g. , water and sanitation). Social adaptation options comprise education (from pre-school to adult education, as well as raising awareness on all levels), information (from hazard mapping to local scenario building), and behavior (from adapting life styles and agricultural patterns to evacuation planning). Institutional adaptation options address economic issues (e. g. , fund incentives), laws and regulations (e. g. , zoning, building standards and environmental protection), and government policies and programs (e. g. , adaptation plans on all levels). Several climate change adaptation measures appear comparatively easy to implement (e. g. , by integrating information and rising awareness into school and university curricula), other requirements are rather complex and challenging. This is especially true for the justification for investments and/or restrictions for possible future developments and events versus short-term investment and benefit interests and the overall uncertainty of climate change impacts on the living environment, its different habitats, and extreme events. Climate change adaptation is closely linked to societal resilience. To successfully implement climate change adaptation, it is therefore necessary not only to seek for technological solutions (e. g. , flood protection), but to embed the concept of (continuous) adaptation to changing climatic conditions into societal and organizational structures (e. g. , Agder, Arnell, & Tompkins, 2005; Berkhout, 2012; Collins & Ison, 2009). Since human beings have lived throughout the quaternary glaciations (which included rather warm, interglacial, periods) it is obvious that climate change adaptation can occur “unintentionally. ” But in a deeply interlinked modern society, with limited space and political barriers that challenge free migration from one place to another, it is preferred to seek for purposeful adaptation concepts. [SEP] Justify:

Output: The text contrasts the claim by indicating that while climate adaptation is essential, it cannot fully counteract the effects of climate change on its own. The text discusses the multifaceted nature of climate adaptation, detailing various structural, social, and institutional options. It emphasizes that adaptation must be embedded within societal and organizational structures and acknowledges the complex challenges of implementing effective adaptation measures. The mention of the need for 'purposeful adaptation concepts' suggests that adaptation alone is insufficient without comprehensive strategies addressing the broader impacts of climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: While RouteSearch can perform similar functions to RetSynth the usability and system-wide analysis that RetSynth provides cannot be matched. RetrobiosynthesisRetrobiosynthesis is a synthetic biology tool that can build novel synthetic pathways for compound production. This tool, which was developed by the Institute of Technology [24], first implements a network generation algorithm that compiles a list of all theoretically possible enzymatic transformations. A pathway reconstruction algorithm, using either a graph-based search or optimization-based methods, then builds all possible pathways from a source compound to a target. After implementation of these algorithms, reduction steps are taken to decrease the amount of information which include: 1) sorting through the list of possible enzymatic transformations and comparing what is known vs novel using repositories such as and ChEBI, and 2) sifting through the pathways and selecting ones based on thermodynamic feasibility, number of enzymatic transformations in a pathway and maximum target yield. Although the Retrobiosynthesis tool performs many of the same functions as RetSynth, and can predict novel enzymatic transformations, its ability to be used by independent researchers is limited. It requires setting up a collaboration with the Institute of Technology and having them run the analysis. Retrobiosynthesis requires a designation of a source compound, making it likely that identifying all pathways to a target in a chassis organism would require a large amount of time, although we could not test this as we do not have access to the tool. RetSynth is a stand-alone software with a graphical user interface that researchers can download and use independently, making identifying pathways less reliant on the developers. Overall the software is quicker and easier to use for researchers to find optimal pathways. RetroPathRetroPath is a synthetic pathway finding tool used to identify pathways between a set of source compounds and a target compound [8]. RetroPath uses a database (database named RetroRules) of external metabolic reactions which was constructed using reaction information collected from and MetaCyc. Reactions are represented by reaction which facilitates the ability for potential novel enzymatic transformations to be predicted. Pathways between source and target compounds are calculated by identifying the shortest hyperpath in a larger weighted hypergraph (constructed using the database of external reactions) using the FindPath algorithm [25, 26]. [SEP] Justify:

Output: The text does not directly address the claim about chassis organisms like E. coli being used for synthetic gene construction. Instead, it discusses synthetic biology tools such as RetSynth and Retrobiosynthesis, focusing on their functionalities and comparisons, without mentioning E. coli or any other chassis organisms.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine tailors treatments to individuals based on genetic information. [SEP] Text: ” Tarhan also explained that “Such findings show that the disease occurs outside the will or control of the person and is caused by disorders that occur in certain regions of the brain. To tell someone to ‘look alive' or ‘do not overthink it’ in relation to depression or other psychiatric disorders would be to ignore disturbances in their brain chemistry or function. " Tarhan emphasized that such situations may be too complex to be overcome by will or control on their own, therefore, it is important to create appropriate treatment plans by understanding the biological and chemical condition of the individual in the treatment of psychiatric disorders. Not being understood contributes to the pain. . . Noting that people with psychiatric disorders suffer and not being understood increases the pain even more, Prof. Tarhan said that "There are patients who cry because the reason is understood. They blame themselves. They say, 'Why am I like this? ' However, the serotonin stores in the brain are empty, and the person is exhausted. Therefore, it is involuntary. " With newly developed technologies, it is becoming possible to repair disrupted networks in the brain Prof. Tarhan said that "With newly developing technologies, it is possible to repair and correct the damaged networks in the brain with methods such as brain modulation treatments. For example, magnetic stimulation therapy can correct receptors and open ion channels by delivering magnetic impulses to specific areas in the brain. This can enable drugs to reach the brain better and support the treatment process. " Noting that pharmacogenetic studies determine which drugs may be more effective by looking at the genetic structure of individuals, Prof. Tarhan stated that "Genetic information can help personalized treatment plans to the person and achieve more effective results. In this way, drug doses and duration of treatment can be determined based on the individual genetic profiles of individuals, thus increasing response to treatment and tolerance. " Personalized treatment gives more effective and safe results. . . Stating that the personalization of psychiatric treatments will play an important role in achieving more effective and safe results, Prof. Tarhan said that "Genetic treatments provide personalized treatment. Especially in cases where improvement cannot be achieved, genetic evaluations may be important. In both the elderly and children, when there is no response to treatment or when drugs do not work, evaluation of genetic factors can help identify new treatment options. [SEP] Justify:

Output: The text corroborates the claim by detailing how genetic information can inform personalized treatment plans. Prof. Tarhan mentions that 'pharmacogenetic studies determine which drugs may be more effective by looking at the genetic structure of individuals,' and that this allows for the determination of 'drug doses and duration of treatment… based on the individual genetic profiles of individuals.' This underscores the role of genetic information in tailoring treatments to individuals, thereby supporting the claim.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: Independent of scales, such planned adaptation is based on three cornerstones to cope with climatic changes (Agder, Arnell, & Tompkins, 2005): reduction of the overall sensitivity, alteration of the exposure, and increase of the resilience. Limitations to climate change are not only born by geographical or political obstacles, such limitations are also deeply rooted in our societal structures and behavior (Biesbroek, Klostermann, Termeer, & Kabat, 2013; Eisenack et al. , 2014; Moser & Ekstrom, 2010). Such social limitations, or constraints, to adaptation might be born on ethics (e. g. , values), comprehension (knowledge), risk (perception), and social structures (cultures) (Adger, Arnell, & Tompkins, 2005; Grothmann & Patt, 2005). Society’s response to climatic changes is very much influenced by local cultural dimensions and inherited structures (political, economical, religious, etc. ). Since risks are perceived differently among societies, and climate change adaptation mainly addresses risks, cultures respond in different ways. Therefore cultural structures may support or challenge both planned and spontaneous adaptation efforts and processes (Adger, Barnett, Brown, Marshall, & O’Brien, 2013), and the challenge is to identify pathways to embed climate change adaptation into societal structures, also under varying cultural settings. The following sections review the applicability of climate change adaptation measures and their implementation from a practical point of view. to PracticeTaking coastal zone management as one example for climate change adaptation, options to adapt to sea level rise are either to accommodate, protect, or retreat (IPCC, 1990, and see Figure 1 below). Since 1990, these three options have become more complex and have been subdivided into several measures (e. g. , IPCC, 2007a), but the underlying three options still remain valid as the basic attitude to (changing) climatic conditions and extreme weather event patterns. In fact, they are derivable also to extreme events, such as floods, droughts, storms, etc. , as the human being always has the option to safely accommodate people, their assets and economic structures (e. g. , agriculture), and/or to protect those (e. g. , by technological solutions such levees (floods) and water storage (droughts), and/or to retreat (partly or totally). Open in new tabFigure 1. [SEP] Justify:

Output: The text contrasts the claim by suggesting that climate adaptation has its limitations due to societal structures and various constraints. It emphasizes that adaptation is influenced by cultural dimensions and recognizes that societal responses to climate change are not uniform, indicating that adaptation alone may not fully counteract the effects of climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: To compare synthetic pathways between RetSynth and RetroPath we first retrieved the reaction available for the MetaCyc repository from the RetroRules full database ( A RetSynth database was then built to match the reactions that were in the RetroPath MetaCyc reaction rules database so an equal comparison between the tools could be run. Extra RetroPath parameters such as maximum and minimum diameter and maximum molecular weight for source were all kept at their default values of 1000, 0 and 1000 respectively. Diameter is a measure of the depth and detail of the molecular reaction signatures (reaction ) used to identify pathways in RetroPath. The larger diameter the more detailed and strict the reaction are and therefore are less able to predict novel reactions. Because RetSynth cannot predict novel reactions and we want to do a strict comparison between the two tools the maximum diameter of 1000 keeps the reaction sufficiently strict to prevent novel reactions from being identified by RetroPath. Additionally, source compounds (metabolites native to Escherichia coli K-12 M1655) were also the same for the two tools. Using RetroPath, which was run with the KNIME analytics platform with the pathway limit being 10 reaction steps (which matched the default pathway limit of RetSynth) we attempted to identify pathways for all MetaCyc compounds not in Escherichia coli. This query, however, was too large for RetroPath to handle, and subsequently RetroPath was employed to find pathways for a smaller set of target compounds including methyl acetate, pterostilbene (Fig. 2), 2-propanol, butanol, sabinene, 2-methylbutanal and isobutanol. RetSynth with this smaller database was able to identify pathways for all compounds in this smaller set while RetroPath was only able to find optimal and sub-optimal pathways for 2-methylbutanal, isobutanol and 2-propanol (Fig. 6). Fig. 6RetSynth vs RetroPath2. 0. Optimal and sub-optimal pathways identified by RetSynth and RetroPath for 2-propanol (a), 2-methylbutanal (b) and isobutanol (c). [SEP] Justify:

Output: The text is irrelevant (pass) to the claim as it discusses the comparison of synthetic pathways using the RetSynth and RetroPath tools without specifically mentioning the use of chassis organisms like E. coli for synthetic gene construction. It focuses on the details of database comparisons and pathway identification, which do not directly support or refute the claim.


Input: Task: corroborate the claim using the given text. Claim: Pharmacogenomics studies how genes affect a person's response to drugs. [SEP] Text: IntroductionDrug toxicity and associated adverse events are critical issues in drug development: by a general estimate, 20–40% of novel drug candidates fail because of safety issues. 1, 2, 3 Over the past 10 years, gene expression profiling has been introduced into drug development to predict and understand toxicity in pre-clinical settings, either as a stand-alone method4, 5, 6, 7 or integrated within systematic approaches. 8, 9, 10, 11, 12, 13In this work, we focus on the problem of identifying transcriptomics signatures that (a) predict toxicity prior to histopathological observations and (b) extrapolate between in vitro and in vivo settings and across species. Several studies have undertaken this task:14, 15, 16, 17 while making remarkable progress, they have illustrated two major challenges caused by limited data availability. 18 First, most studies have derived signatures from small-scale experiments with one or few compounds. Such signatures suffer both from limited statistical power and from limited translatability to other compounds. At the same time, it is difficult to interpret ‘black-box’ signatures, which are statistically significant but not associated with biological function. Second, most studies have sought late-time signatures (≥24 h). Such signatures are likely to be downstream effectors of signalling networks, which are compound specific and highly dependent on the specific cellular context and the availability of complex regulatory elements, as recently revealed by the project. 19 In contrast, early-response genes (<24 h) may be less context specific and more generic, because many of them are essential transcription factors or regulators of stress response,20 and they are closer to the core machineries of ‘bow-tie’-like signalling networks. 21It is not feasible to identify early-response toxicity signatures from large-scale experiments with current bottom–up practices. 22 Therefore, we took a top–down approach by analysing TG-GATEs (Toxicogenomics Project-system), a toxicogenomics database covering 170 compounds (1). The data comprise time-series gene expression, cell-based assay readouts and pathological records (Figure 1a). TG-GATEs is publicly available and is one of the most comprehensive data sets up to date. [SEP] Justify:

Output: The text corroborates the claim by discussing gene expression profiling and its integration into drug development. It emphasizes the role of transcriptomics in predicting drug toxicity, which is directly related to how genes influence drug responses. The mention of 'early-response toxicity signatures' and the identification of genetic factors that predict toxicity underscores the relevance of pharmacogenomics in understanding drug effects.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: Climate change adaptation options from coastal protection perspective (modified, based on IPCC, 1990). Examples for all these concepts can be found from historical settlements towards modern climate change adaptation policies and implementations. Observing the location of the original nuclei of historical old towns, it is noticeable that these were originally accommodated to respect extreme events. For example, only the ports of the important coastal cities in were located at the seashore—but not the city centers, as a safety distance from the shoreline was kept to prevent from diseases (e. g. , malaria) and floods. Ancient churches and other buildings remain standing, despite earthquakes, because they were built on hard rock, instead of soft soil (liquefaction). Coastal settlements, such as Castro, on the Island of Chiloe (Chile), and in the (Cambodia), are still built on high pillars to give room to daily or periodically changing tides and floods. There is a globally observable pattern that many modern buildings (often 20th or 21st century) are situated on soft soils and in or near flood prone areas, while the old city foundations are located on hard rock and/or above flood prone areas. The pressure of a growing population to move into hazardous areas is only partly true, as hazardous areas are also being built up in Europe, which actually faces population decrease. One major problem is the steady population increase in urban areas, especially coastal urban areas (United Nations, 2014). Staying with the example of coastal protection, modern policies or strategies react differently to adapt to extreme events and climate change impacts. The city of Hamburg, Germany actively discusses accommodation with the support of different flood compartments (Knieling & Schaerffer, 2013). However, the first master plan for coastal and flood protection of the State of Mecklenburg-Vorpommern acknowledges that retreat is an option, as it mentions that the coastline is a mosaic in space and time, its character is variation (Ministerium für Bau, Landesentwicklung und Umwelt Mecklenburg-Vorpommern, 1993). Indeed, in some areas of Mecklenburg-Vorpommern, sea walls are removed, re-creating salt marshes as flood retention areas. for Rebuilding and Resiliency (2013) on the other hand states that “The city cannot, and will not, retreat” (p. 7). [SEP] Justify:

Output: The text contrasts the claim by discussing various aspects of climate adaptation and emphasizing that adaptation strategies such as retreat and accommodation are necessary to respond to climate change impacts. For example, the mention of the State of Mecklenburg-Vorpommern acknowledging retreat as an option, indicates that adaptation alone is not sufficient to fully counteract climate change effects. Furthermore, the discussion of historical approaches to settlement and modern strategies illustrates that while adaptation efforts are critical, they cannot solely address the challenges posed by climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: Additionally, RetSynth is able to rank pathways based on maximum theoretical yield which is calculated by flux balance analysis. Our tool exceeds the capabilities of any other current software available because it includes a graphical user interface, providing the ability for RetSynth to be used by scientists without a programming background, the capability to add new and proprietary biological reactions as well as synthetic chemical databases, efficient identification of optimal and sub-optimal pathways and clear images of pathways via our visualization module to allow quick interpretation of results. Availability and requirementsProject name: RetSynthProject home page: system(s): Mac, Windows and LinuxProgramming language: Python and JavaOther requirements: (v4. 64), libSMBLLicense: BSD 2-clause license Availability of data and materials All software and data are available at AbbreviationsEMP: Enzyme and metabolic pathways FBA: Flux balance analysis GUI: : Kyoto encyclopedia of genomes and genes MILP: Mixed integer linear program MINE: Metabolic in-silico network expansion UM-BBD: University of Minnesota Biocatalyst/Biodegradation database 15. 8. 121. 76. 9. 58. 74. 2. 0: A retrosynthesis workflow for metabolic engineers. Metab Eng. 2018; 45:158–70. 50. 42. 8. 1318. 9. 30. 44. 66. 2. 1, a selective chemical synthesis and reaction database. J Model. 2005; 45(5):1470–3. 74. 1. 24. 9. 5482. 5. 104. 122. 10. 3525. FundingThis research was conducted as part of the Co-Optimization of Fuels and Engines (Co-Optima) project sponsored by the U. S. Department of Energy (DOE) Office of (EERE), Offices. Co-Optima is a collaborative project of multiple national laboratories initiated to simultaneously accelerate the introduction of affordable, scalable, and sustainable biofuels and high-efficiency, low-emission vehicle engines. The DOE was not involved in the design of study, collection, analysis, interpretation of data or the writing of this manuscript. Author informationAuthors and 94550, USALeanne S. & Corey M. HudsonAuthorsLeanne S. WhitmoreView author publicationsYou can also search for this author in PubMed 4. [SEP] Justify:

Output: The text does not discuss or provide any information related to chassis organisms such as E. coli or their use in synthetic gene construction. Instead, it focuses on the capabilities of the RetSynth tool for metabolic engineering and related projects, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine can help reduce adverse drug reactions. [SEP] Text: Skip to main content Explore journals Get published About BMC My account Search all BMC 1. There is evidence suggesting that particular HLA alleles may be risk factors for skin reactions to additional drugs, but problems with small numbers of cases for individual drugs have limited the ability to obtain statistically significant associations in some recent candidate gene and GWA studies [36–38]. Underlying mechanism for HLA associations with adverse drug reactionsUp to recently, two main mechanisms for the observed HLA associations with adverse drug reactions affecting skin and liver were postulated. One involved formation of a covalent complex between the drug or a metabolite and cellular proteins [39]. This complex could then be presented to T cells by particular HLA molecules, resulting in an inappropriate local T-cell response and cellular damage. An alternative mechanism proposed that drugs interact directly with HLA molecules, resulting in a T-cell response without the need to form a covalent complex (p-I concept) [40]. However, recent data on T-cell responses to abacavir are more consistent with a third mechanism. Using several different approaches, three independent groups of investigators have suggested that abacavir binds to the B*57:01 gene product and induces a conformational change. This results in incorrect recognition of self-peptides as foreign by the immune system, which triggers an inappropriate immune response [41–43]. However, flucloxacillin, which may give rise to DILI in B*57:01-positive individuals, did not induce inappropriate recognition of self-peptides [42]. Instead, flucloxacillin appears to induce cell proliferation in T cells that are B*57:01-positive when covalently bound to peptides [44]. Similarly, carbamazepine also appears to interact covalently with peptides with the B*15:02 gene product [45]. It has also been proposed recently that the available T-cell repertoire, which could also be genetically determined, may be an additional factor to HLA genotype in determining whether an adverse drug reaction occurs [46]. There are currently no data showing an association between susceptibility to HLA-associated adverse drug reactions and the T-cell receptor gene, but it would be of interest to investigate this further. [SEP] Justify:

Output: The text supports the claim by discussing specific genetic factors, particularly HLA alleles, that are implicated in adverse drug reactions. It presents evidence that understanding the interaction between drugs and these genetic factors can provide insights into preventing adverse reactions, which aligns with the principles of personalized medicine. The mention of different mechanisms by which HLA associations can lead to adverse reactions highlights the potential for personalized approaches in mitigating such risks.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: On the other hand City does not aim for complete protection, as the report also outlines concepts of “living with water. ” Due to the rather short time span (less than a decade) of recent climate change adaptation strategies, the concrete implementation of climate change adaptation measures at local levels is often still lagging. The problem with many politically and institutionally demanded climate change adaptation measures is their lack of practical applicability at the local level. Another challenge is the inherent uncertainties in emission scenarios and climate models. One argument, often mentioned by stakeholders and decision makers, involves our need to react and adapt “now” and “before it is too late”—a near mantra that has infused the basic content of most discussion about climate change and its effects. Climate change impact assessments usually conclude that there are far more negative than positive impacts (e. g. , Hitz & Smith, 2004; IPCC, 2014). However, measurements show that anthropogenic GHG emissions had already surpassed “worst case” IPCC emission scenarios by 2004 (Le Quéré et al. , 2009; Raupach et al. , 2007) (see also below). 2015, the (NOAA) and the Agency (EPA, 2015) reported that the global GHG concentration in the earth’s atmosphere surpassed 400 ppm (from 280ppm in 1850). Following the argumentation that anthropogenic GHG emissions strongly increase the atmosphere’s greenhouse effect, this means that continuous global warming will continue, for several decades at least (e. g. , Archer & Brovkin, 2008). Humans will inevitably have to adapt to rising temperatures and the consequences (IPCC, 2001, 2014). The comparatively small amount of literature on the benefits of global warming (for example in the respective IPCC assessment report 2015. This phenomenon was not included in any climate change model issued by IPCC, which, in 2001, portrayed several models with steadily increasing rates in global warming throughout the 21st century. In its 5th assessment report, IPCC stated that the continuous warming trend had been much slower between 1998 and 2014, the so-called hiatus of global warming, than over the time span of the past 60 years (IPCC, 2014). Several scientists promptly retro-analyzed the hiatus (e. g. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and challenges of climate adaptation measures. It indicates that adaptation strategies are often lagging in implementation and not aimed at complete protection from climate change effects. The text highlights that climate change impact assessments generally reveal more negative than positive impacts and that adaptation is not a complete solution, as continuous global warming will still persist due to anthropogenic greenhouse gas emissions. This suggests that adaptation alone is insufficient to fully counteract the effects of climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: AbstractSulforhodamine 101 (SR101) is a preferential astrocyte marker widely used in 2-photon microscopy experiments. Here we show, that topical loading of two commonly used SR101 concentrations, 100 μM and 250 μM when incubated for 10 min, can induce seizure-like local field potential (LFP) activity in both anaesthetized and awake mouse sensori-motor cortex. This cortical seizure-like activity develops in less than ten minutes following topical loading and when applied longer, these neuronal discharges reliably evoke contra-lateral hindlimb muscle contractions. Short duration (<1 min) incubation of 100 μM and 250 μM SR101 or application of lower concentrations 25 μM and 50 μM of SR101, incubated for 30 and 20 min, respectively, did not induce abnormal LFP activity in sensori-motor cortex, but did label astrocytes and may thus be considered more appropriate concentrations for in vivo astrocyte labeling. In addition to label astrocytes SR101 may, at 100 μM and 250 μM, induce abnormal neuronal activity and interfere with cortical circuit activity. SR101 concentration of 50 μM or lower did not induce abnormal neuronal activity. We advocate that, to label astrocytes with SR101, concentrations no higher than 50 μM should be used for in vivo experiments. Similar content being viewed by others Astrocytes modulate sensory-evoked neuronal network activity 6. When used for in vivo microscopy, SR101 is routinely applied topically to the exposed cortex, from where it is taken up by astrocytes7 and diffuses through the astrocyte syncytium via gap junctions, brightly labelling astrocyte somata, processes and perivascular end-feet8. SR101 has in particular been used in combination with loading of chemical Ca2+ indicators such as 488 BAPTA-1 AM to unambiguously distinguishing between neuronal and astrocytic Ca2+ signals1,3. We and others have previously described bioactive effects of SR101 on excitatory neuronal activity9,10. In hippocampal slices, pyramidal CA1 neurones showed long-term potentiation of intrinsic excitability and enhanced synaptic efficacy following a short period of SR101 application9. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of sulforhodamine 101 (SR101) on neuronal activity and labeling of astrocytes, and does not mention E. coli or synthetic gene construction. Therefore, it does not provide any support or contradiction to the claim.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine can help reduce adverse drug reactions. [SEP] Text: Non-HLA genetic associations in adverse drug reactionsIn addition to HLA, a number of genetic risk factors for idiosyncratic adverse drug reactions have been identified, though only a few of these have been well replicated. Idiosyncratic adverse drug reactions are often considered to be concentration-independent, but genetic factors that affect drug concentration by their role in drug disposition also make a contribution to susceptibility to some adverse drug reactions. Other genetic risk factors identified include polymorphisms affecting the innate immune system and in genes that protect the cell against oxidative stress. Cardiotoxicity reactions are different to other forms of adverse drug reaction in that polymorphisms in cardiac ion channels are the best described genetic risk factors currently and there appears to be no overlap with genetic risk factors for other adverse drug reactions. As the area of non-HLA genetic associations in adverse reactions covers a wide range of different types of genes, this section will consider in separate subsections the contribution of genes affecting drug disposition to adverse drug reactions, the contribution of innate immune system and oxidative stress genes, and finally the role of cardiac ion channel polymorphisms in cardiotoxicity reactions. Idiosyncratic adverse drug reactions and genes affecting drug dispositionWell-replicated associations have been described for SLCO1B1 with statin myopathy and for NAT2 with isoniazid-induced DILI. There are also a number of other more poorly replicated associations particularly involving the transporter ABCC2 and various UGT isoforms. Table 2 summarizes current data in this area. Table 2 Drug disposition genes and adverse drug reactionsFull size tableThough they are very effective drugs, statins can cause muscle toxicity in some individuals. This is usually seen as an asymptomatic rise in creatine phosphokinase levels, which is reversible by drug discontinuation but can be more serious on rare occasions with a more severe form of disease resulting in rhabdomyolysis followed by possible death (for review, see [47]). A GWA study involving 85 cases of simvastatin-induced myopathy found a significant signal for a single SNP in the gene SLCO1B1, which encodes a transporter expressed at high levels in hepatocytes [48]. The transporter is located on the sinusoidal membrane and transports statins and various other drugs into hepatocytes from the general circulation. [SEP] Justify:

Output: The text corroborates the claim by discussing various genetic associations with adverse drug reactions, such as those involving the SLCO1B1 and NAT2 genes. By identifying these genetic risk factors and their implications for drug safety, personalized medicine can tailor drug prescriptions to individuals based on their genetic profiles, potentially reducing the risk and severity of adverse drug reactions.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: , Fučkar, Volpi, Guemas, & Doblas-Reyes, 2014; Guemas, Doblas-Reyes, Andreu-Burillo, & Asif, 2013), delivering explanations as to why this slowdown in global warming was not seen as possible by earlier modeling efforts. These explanations were issued retrospectively and included calculations on a restart of the warming process. Karl et al. (2015) published a recalculation of global temperature trends postulating that this so-called hiatus of global warming in fact never occurred, and that it was a wrong interpretation of data based on biases. It is certainly scientifically correct to calculate and publish modeling and data interpretation results, including critical reviews, modifications, and corrections. But the back-and-forth of information on how much the planet heats up, or does not—or again does—emphasizes the uncertainties in climate change data, the models, and their interpretations. These discussions and uncertainties do not remain within the scientific community; they find entrance into the media, where they are noticed by decision makers, stakeholders, and the private sector. By demanding the need for adaptation to uncertain climate changes, the debate on the local level quickly turns into questions of conducting or prohibiting investments that might be, or might as well not be, affected by climate change impacts. From the perspective of municipalities and investors, a horizon, for example, of 17 years (the yearly measure of the hiatus period in global warming) covers approximately three election periods, and extends beyond the profit horizon of many investments (e. g. , of the tourist industry in coastal areas that might be affected by sea level rise). Why would a municipality forbid such investments in its own area when an investor might be given the permission in a neighboring municipality? Stakeholders and decision makers of all kinds, as well as investors and representatives of the private sector, tend to ask these questions in climate change adaptation meetings: How reliable are the emission scenarios and climate change models, and how high are the uncertainties? How reliable are derived climate change impacts on the living environment and hydro-meteorological extreme events? One aspect of the uncertainties is that IPCC reports (2007, 2014) usually state what impacts might happen, underlying the statements with high, medium, or low likelihoods, certainties, and agreements. However, the reports seldom state that these effects might as well not happen. [SEP] Justify:

Output: The text contrasts the claim by highlighting the uncertainties in climate change data and the limitations of climate adaptation. It emphasizes that despite discussions on climate change adaptation, there remain significant uncertainties regarding the effectiveness of emission scenarios and climate models. Furthermore, the text notes that IPCC reports often outline potential impacts with varying degrees of likelihood, indicating that these effects might not occur at all. This suggests that climate adaptation alone may not be sufficient to fully counteract the effects of climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: Intra-neuronal recordings indicated that the increased excitability was a consequence of lowering the threshold for evoking action potentials and was observed following application of just 1 μM SR101 for ten minutes. The original publication by Nimmerjahn and colleagues reported that SR101 does not induce phototoxicity over hours, days and weeks8. Here we have combined SR101 loading with recordings of the local field potential (LFP) during the labeling period to interrogate if SR101 causes changes in cortical neuronal activity in vivo. We explored the effects of topical SR101 application on neuronal activity in layer II of primary sensori-motor cortical areas (S1-M1) of adult anaesthetized or awake mice. We show that spontaneous seizure-like LFP activity develops within less than ten minutes following cortical exposure to 100 μM SR101 for ten minutes, a commonly used dosage for astrocyte labelling (see S1). This S1-M1 seizure-like neuronal activity was accompanied with a reduction in low-frequency power and simultaneous increase in higher-frequency power in the LFP. When exposing the cortex to 250 μM SR101 for ten minutes the seizure-like activity developed within five minutes and ceased after about 45 minutes. In addition, we show that SR101-induced seizure-like activity in S1-M1 is sufficiently potent to drive a motor output, recorded as compound action potentials in the sciatic nerve of the contra-lateral hindlimb or by observation of movement. Finally, we show that 25 μM and 50 μM SR101 application, incubated for 30 or 20 minutes respectively, or 100 μM and 250 μM incubated for one minute, does not induce abnormal cortical LFP activity and may thus be considered as safe dosages. ResultsSR101 can induce seizure-like LFP activity in anaesthetised miceWe first recorded LFPs in S1-M1 of ketamine (120 mg kg–1) and xylazine (10 mg kg–1) (KX) anesthetized mice while topically applying 100 μM or 250 μM SR101 for 10 minutes (Fig. 1a). In a subset of experiments, we included recordings of the electroneurogram (ENG) from the contra-lateral sciatic nerve, to provide a measure of cortical-evoked motor output (Fig. [SEP] Justify:

Output: The text is irrelevant to the claim regarding the use of chassis organisms like E. coli in synthetic gene construction. Instead, it discusses the effects of SR101 on neuronal activity in mice, which does not relate to the claim about E. coli or synthetic gene construction.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine can help reduce adverse drug reactions. [SEP] Text: In a recent GWA study involving DILI cases caused by a variety of different drugs, when polymorphisms relevant to drug disposition only were considered, an apparent association between a polymorphism in UGT1A and susceptibility to DILI associated with fluoroquinolone antimicrobials was detected, though this could not be confirmed in a replication cohort [18]. Drug transporter genes of the ABC transporter superfamily are biologically plausible candidates for a role in DILI susceptibility, especially because some ABC transporter family gene products transport bile acids in addition to drugs [58]. Also, some inherited forms of cholestasis have been demonstrated to result from specific mutations in the ABCB4 (MDR3) and ABCB11 (BSEP) genes [59]. Some evidence for an association between cholestatic liver injury due to a range of drugs and a polymorphism in exon 13 of ABCB11 that had previously been reported to be associated with cholestasis of pregnancy was reported [60]. The association could not be confirmed in a larger cohort of predominantly cholestatic DILI cases [61] or in a GWA study involving DILI caused by a range of drugs [18]. ABCC2 (MRP2) has a major role in the biliary excretion of a variety of glucuronide conjugates. There is evidence that polymorphisms in this gene may be risk factors for some forms of DILI, though effect sizes are unlikely to be very large. In the candidate gene study on diclofenac DILI already discussed above, carriage of an upstream polymorphism in ABCC2 (C-24T) was found to be significantly more common among hepatotoxicity cases [57]. This finding is consistent with increased levels of the reactive diclofenac acyl glucuronide being associated with toxicity since there is evidence that C-24T results in lower production of the MRP2 protein, which would favor cellular accumulation of the glucuronide [62, 63]. [SEP] Justify:

Output: The text corroborates the claim by discussing the relevance of genetic polymorphisms, such as those in UGT1A and ABCC2, in relation to drug disposition and adverse drug reactions (DILI). It highlights how understanding these genetic factors can inform personalized medicine strategies, ultimately suggesting that personalized approaches could help mitigate the risk of adverse drug reactions by tailoring medication choices based on individual genetic profiles.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: Even though there is a so-called scientific consensus (IPCC, 2014) that human GHG-induced climate change appears to lead to unprecedented rates of climatic changes, these must still be seen in the human (geologically very short term) perspective—because there is also evidence of natural rapid climatic changes (Rial et al. , 2004). Meanwhile, any abrupt climate changes most likely have a strong impact on socio-economic systems (Claussen, 2008); the timeframe of such (geologically rapid) changes are yet not comparable to the even shorter timeframes of day-to-day politics, decision making, and investments. Investments lead to jobs and, subsequently, tax income—on which municipalities eventually depend. Decision makers, stakeholders, and local private sector actors certainly also want to protect their communities and areas as well as their investments from potential damages. But they are also in a constant competition with other municipalities and need to remain attractive for investments to secure their own socio-economic development. Many discussions with local stakeholders have shown that there certainly is awareness of climate change and its potential impacts. But there is also knowledge about the uncertainties and the time span perspectives. It definitely plays a major role for a municipality when investments to prevent potential future hazard patterns are politically or scientifically required on the one hand, but the municipality encounters financial thresholds or resistance on the other hand. The question is how adaptation to climate change can be planned and implemented, respecting both inert uncertainties and economic developments. There are, however, numerous examples of mal-adaptation practices, not only to climate change impacts, but also to current extreme event patterns, scarce natural resources, and agricultural practices. An appropriate recommendation, therefore, is to analyze human vulnerabilities and adaptabilities to local climates from a general perspective, with examples of mal-adaptations, before developing and implementing climate change adaptation measures. Human Adaptability, Mal-Adaptation, and As a species, humans are spread more widely across the climate zones of this world than any other mammalian species. Humans have been permanently and self-sufficiently settling into all climate zones and on all but one continent, from the Arctic over all climate zones, north and south of the equator, and in nearly all altitudes, from below sea level (e. g. , Dead Sea) to over 4,000 m above sea level (e. g. , Andes). [SEP] Justify:

Output: The text contrasts the claim by emphasizing that while there is awareness of climate change and its impacts, adaptation measures must be planned with consideration of both uncertainties and socio-economic factors. It points out that there are examples of mal-adaptation practices and highlights the need to analyze human vulnerabilities and adaptabilities before implementing adaptation measures, implying that adaptation alone may not be sufficient to fully counteract the effects of climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: 1a), in addition video recordings were obtained to document the motor activity (see S1–S3). Following topical application of SR101, astrocytes exhibited a time-dependent increase in SR101 fluorescent intensity, with a marked increase occurring ~10–20 minutes following application (Fig. 1b). Simultaneous LFP recordings in S1-M1 layer II revealed that large synchronized potentials, mimicking epileptic seizure activity in terms of individual event amplitude11,12,13 and event interval14,15,16, appeared within 5–10 minutes following topical 100 μM SR101 application (Fig. 1c). Figure 1SR101 can induce seizure-like activity in anaesthetized mice. (a) Experimental setup and craniotomy above primary sensori-motor cortex (S1-M1). (b) Astrocytic SR101 uptake time course. (c) Upper, LFP during development of seizure-like activity in S1-M1 following 100 μM SR101 loading (10 min incubation). Lower, frequency power spectrograms from period 1 and 2 from LFP above. (d) Histograms showing individual seizure-like event amplitudes and intervals. (e) Graph showing dose-dependency of seizure-like activity onset and cessation. Statistical difference was assessed using an unpaired Welch’s t-test. (f) Left, simultaneous S1-M1 LFP and ENG following 250 μM SR101 application (10 min incubation). Right, graph showing cumulative number of ENG events as a function of seizure-like LFP events. Correlation was assessed using a Pearson’s correlations test. Full size imageThe seizure-like activity was correlated with a reduction in low-frequency power (1–4 Hz) and a slight increase in higher-frequency power (12–30 Hz) (Fig. 1c and Supplementary Fig. S1). Such increases in higher-frequency power bands have previously been showed in animal models using kainate or optogenetics to evoke epileptic acivity13,17. Similar changes in cortical LFP activity were not recorded under control conditions (see Supplementary Fig. S2). An example of a non-filtered recording displaying the artefacts evoked by application and wash out of SR101 10 min later is provided in Supplementary Fig. S3. [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of a compound (SR101) on astrocytes and seizure-like activity in mice, providing no information about chassis organisms like E. coli or their use in synthetic gene construction.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine can help reduce adverse drug reactions. [SEP] Text: In a Korean candidate gene study on DILI caused by a range of drugs, a polymorphism at position -1,549 of ABCC2, which is in linkage disequilibrium with C-24T, was a significant risk factor for the development of hepatocellular toxicity, whereas a second polymorphism at position -1,774 was a risk factor for cholestatic or mixed disease [63]. Further evidence of a modest contribution by ABCC2 to DILI susceptibility is provided from a large GWA study. Though polymorphisms in ABCC2 did not show genome-wide significance, when a subgroup of genes relevant to drug disposition was investigated, a significant association for a number of polymorphisms in ABCC2, including a non-synonymous polymorphism (C1515Y), was seen [18]. Some recent data suggest that genotype for pregnane × receptor (PXR), a transcriptional regulator for various metabolism and transporter genes that are relevant to disposition of both drugs and endogenous factors such as bile acids, may also be a predictor for DILI relating to flucloxacillin [64]. Though the effect size was relatively small, the association involved a polymorphism for which functional significance is well established [65]. Because other drugs are known to act as PXR agonists, the gene encoding PXR has potential as a more general risk factor for DILI. The relevance of polymorphisms affecting drug disposition to skin reactions has also been assessed, but generally findings are negative. For example, the possible role of microsomal epoxide hydrolase in carbamazepine-induced skin rash has been investigated in considerable detail but with entirely negative results [66, 67]. For sulfamethoxazole-induced skin rash, NAT2 and CYP2C9, which both contribute to metabolism, were found not to be risk factors [68, 69]. There is some borderline significant data for GSTP1 in relation to sulfamethoxazole skin reactions but the biological basis for this association is not clear [69]. Polymorphisms relevant to innate immunityA number of candidate gene studies have reported that cytokine polymorphisms that may contribute to inflammatory and innate immune responses are predictors for DILI (Table 3). The majority of these reports find relatively small effects that have not been replicated, though the genes involved are biologically plausible risk factors. [SEP] Justify:

Output: The text discusses various genetic polymorphisms and their associations with drug-induced liver injury (DILI) and adverse drug reactions (ADRs). It highlights specific polymorphisms that serve as risk factors in drug metabolism, indicating that understanding these genetic factors can lead to more personalized approaches in medicine. The mention of genotype influences on DILI suggests that personalized medicine informed by genetic profiling could indeed help mitigate adverse drug responses.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: Since the first appearance of humans, climate has undergone several changes, including several Quaternary glaciation cycles. For humans to survive and thrive across such diverse environments and climates, adaptability is necessary. One contemporary example of the capacity for humans to adapt to different climates is displayed by the daily mortality rates versus temperature effects for the age group of 65 and above in Europe. Temperatures of around 25 °C and above in northern Finland lead to the highest mortality rates of that age group, whereas these temperatures bear the lowest mortality rate of the same age group in Greece. For the same age group, temperatures of around 5°C in the lead to the highest mortality and to the lowest in northern Finland (Keatinge et al. , 2000). It might be deduced that humans as a species will adjust to changing temperatures, at least in the course of generations. This means that, as long as climatic conditions on planet Earth are such that human life is possible, humans will adjust and adapt. The IPCC definitions of climate change adaptation are based on human-induced climate change and are certainly justifiable within the concept of recent climate changes in the Holocene, especially in connection with anthropogenic GHG emissions. But it can be argued that these definitions do not fully grasp adaptation in its entire complexity. The overall definition mentions the “moderation of harm” or the exploitation of “beneficial opportunities,” which presupposes that humans have a clear knowledge of both the climatic changes to be expected and their potential impacts. This definition somehow skips one of the most essential parts of adaptation to climatic stimuli: the ability of nature and humans to spontaneously and promptly adjust to (changing) climatic and environmental conditions and maintain a living environment, including necessary food supplies. The mention of “various types of adaptation” (IPCC, see above) even more strongly presupposes human knowledge about potential impacts in climatic changes and optimal adaptation measures, whether these be anticipated, planned, or spontaneous. From a purely theoretical point of view, these definitions might be correct. But as humans adapt to be able to live in certain climate settings, they all too often increase their own vulnerabilities by putting their assets and lives, as well as vital natural resources at risk by mal-adaptation practices. Examples can be found in nearly all climate zones and cultures, and independently from economic conditions. [SEP] Justify:

Output: The text contrasts the claim by arguing that while adaptation is necessary for humans to survive changing climates, it does not fully counteract the effects of climate change. It highlights that definitions of climate adaptation often presuppose knowledge of climatic changes and their impacts, which may not always be present, leading to potential mal-adaptation practices that increase vulnerabilities. This suggests that adaptation is not sufficient on its own to address the complex challenges posed by climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: The seizure-like activity displayed a gradual build-up in amplitude, similar to prevously shown during 4-AP-induced epilepsy15, with the individual seizure-like events exhibiting an average amplitude of 1. 64 ± 0. 67 mV and average event interval of 1. 01 ± 0. 88 s (Fig. 1d), similar to previous reports using caged 4-AP, kainate or optogenetics to evoke seizures11,12,13. The term “seizure-like” was chosen based on the LFP’s resembles to previously published LFP activity during epileptiform activity (i. e. event amplitude, event frequency and 12–30 Hz LFP power band increase), induced by commonly used epilepsy models such as kainate, 4-AP or kindling12,15,18. However, due to the lack of mechanistic insight to what is triggering the abnormal neuronal discharges following SR101 application, we chose “seizure-like”, as opposed to simply “epileptiform” or “seizure”. In many publications, SR101 is applied topically at concentrations ranging from 1 μM to 1 mM (see S1), most commonly between 100–300 μM4,15,19,20 and incubated for 1–60 minutes (see S1), often for 10–30 minutes15,20,21. SR101 induced a dose-dependent onset and cessation of the cortical seizure-like LFP activity (Fig. 1e); at a loading concentration of 250 μM (incubated for 10 min), seizure-like activity appeared at 5. 16 ± 3. 41 min, but first 10. 31 ± 5. 1 min after application of 100 μM (incubated for 10 min) SR101 (Unpaired Welch’s t-test, t = 2. 819 df = 9. 771, P = 0. 0186). The seizure-like LFP activity disappeared after 47. 50 ± 19. 41 min and 32. 83 ± 12. 38 min following SR101 application, for 250 μM and 100 μM SR101, respectively (Unpaired Welch’s t-test, t = 2. 292 df = 15. 91, P = 0. 0359). [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the seizure-like activity induced by SR101 and the properties of that activity, without mentioning chassis organisms or E. coli in the context of synthetic gene construction.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine can help reduce adverse drug reactions. [SEP] Text: The first GWA study on drug-induced QT-prolongation involved 183 patients in a phase III clinical trial of the antipsychotic drug iloperidone who had QT measurements performed 14 days after the start of drug treatment [85]. No genome-wide significant signals were detected but relatively low P values were obtained for several novel loci. No trends towards significance with the SNPs in either ion channels or NOS1AP relevant to QT length in the previous studies were detected. Another recent GWA study examined a cohort of 783 schizophrenia patients taking antipsychotic drugs frequently associated with QT prolongation [86]. Significant effects were seen for SNPs in NOS1AP and NUBPL, a gene concerned with mitochondrial function. In addition, evidence for a role for the transporter gene SLC22A23 in relation to the effect of the drug quetiapine on prolongation was obtained. Consistent associations with certain genes have started to emerge for drug-induced cardiotoxicity but overall effects are small. The possibility that rare variants are more important contributors requires further investigation. Though genes relevant to drug disposition are plausible candidates for contributors to drug-induced cardiotoxicity and a number of studies have been performed, findings on these have generally been negative. Concluding remarks and future prospectsAs reviewed recently by others [87], considerable progress has been made in understanding the genetics of adverse drug reactions with particular progress made using both candidate gene and GWA approaches in understanding idiosyncratic adverse drug reactions where HLA genotype is a risk factor. Two of these associations that show very high sensitivity and specificity for abacavir hypersensitivity and B*57:01 and carbamazepine toxicity and B*15:02 have been translated to the clinic. There is also potential for translating some of the other associations such as that between A*31:01 and carbamazepine-induced skin rash, and that between B*58:01 and allopurinol-induced skin rash. Most of these advances have been achieved through candidate gene association studies rather than GWA studies. There has been slower progress on understanding the genetic basis for adverse drug reactions where HLA does not contribute. One success story is the association between SLCO1B1 and statin myopathy. [SEP] Justify:

Output: The text corroborates the claim by outlining advancements in understanding the genetics of adverse drug reactions, specifically mentioning that considerable progress has been made in identifying genetic factors that can predict responses to drugs. It highlights successful associations, such as between HLA genotypes and specific drug hypersensitivities, which illustrates how personalized medicine can leverage genetic information to reduce the risk of adverse drug reactions. The mention of translating these findings to clinical practice supports the claim that personalized medicine has the potential to improve patient outcomes regarding drug safety.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: Examples include settlements in hazardous areas, mal-adapted agricultural practices, and overuse of natural resources. These examples enlarge the contextual frame of climate change adaptation and interlink it with vulnerability and risk, especially with the concept of acceptable risk. Over millennia any human society in any part of the world has somehow adapted to a certain climate and climatic changes. Despite excellent information, experiences, statistical records, and scientific knowledge on underlying hazards, vulnerabilities, and resulting risks, examples of mal-adaptation are continuously found within nearly all societies. Presently, climate change adaptation is mainly discussed in the context of recent Holocene climatic changes, but it should be analyzed and understood in a broader context. This broader context should include earlier (rapid) climate changes, human reactions to those, as well as adaptation to extreme events, scarce natural resources, and respective mal-adaptation practices. Human vulnerabilities, and their exposure to adverse characteristics of their living environment and extreme events, play a key role in understanding risks. To understand risk patterns, it is crucial to assess social vulnerabilities and their many variables (Cutter, Boruff, & Shirley, 2003), as well as the motivations and capabilities of local actors and networks (Schmidt-Thomé & Peltonen, 2006). Most importantly, these vulnerabilities need to be assessed on several levels, from the national to the local level (Cutter, Mitchell, & Scott, 2000), and they should be assessed not just from a purely damage-oriented approach (e. g. , losses calculated by insurance companies). When analyzing and developing climate change adaptation options and strategies one question needs to be asked. Adapted to the of a Specific Region, Events? Before analyzing the ability to adapt to changing climatic stimuli, both the resilience of societies and the vulnerability to extreme events should be analyzed. Factors such as availability and use of natural resources should be taken in to consideration. Human beings tend to blame disasters related to mal-adaptation practices on other reasons or circumstances besides their own mismanagement. Growing overall losses and rising local vulnerabilities related to natural hazards and subsequent disasters (e. g. , Munich Re, 2015) cannot be attributed only to climate change impacts (e. g. , Barredo, 2009, 2010; IPCC, 2012). Losses grow because people continue to settle and expand settlements in hazardous areas, not only in poor regions with a potential shortage of land due to expanding populations, but also in richer countries. [SEP] Justify:

Output: The text contrasts the claim by elaborating on the complexities of climate adaptation. It mentions examples of mal-adaptation and emphasizes that growing losses and rising local vulnerabilities are influenced by factors beyond climate change, such as human behavior and settlement practices. This indicates that adaptation alone is insufficient to counteract climate change effects, as historical patterns of mal-adaptation are prevalent and human societal resilience and vulnerabilities must also be considered.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: Muscle twitches occurring in the contra-lateral hindlimb was observed ~20 minutes following topical SR101 application (see S1–S3). To assess whether the movement of the contra-lateral hindlimb originated from S1-M1, we obtained simultaneous LFP recordings in S1-M1 and ENG from the contra-lateral sciatic nerve (Fig. 1a). These recordings showed that S1-M1 SR101 application (250 μM, ten minute incubation) correlated with arrival of compound action potentials in the sciatic nerve and that individual seizure-like LFP events and ENG compound action potential events were almost perfectly matched in a 1:1 ratio (Fig. 1f) (Pearsons’s correlation test, R2 = 0. 99). An example of a longer recording is provided in Supplementary Fig. S4. A compound structurally similar to SR101, but with a SO3H group replaced by SO2NHNH222, is Texas Red, also used to label astrocytes8,23. Opposite to SR101 did topical application (100 μM and 500 μM, 15 min and 10 min incubation time, respectively) not evoke any seizure-like LFP activity (see Supplementary Fig. S6). Taken together, these experiments show that topical SR101 application can have pronounced effects on cortical neuronal activity when applied at commonly used loading concentrations, i. e. 100 μM and 250 μM, in anaesthetized mice. SR101 can induce seizure-like LFP activity in awake miceAnesthesia is known to have anti-epileptic effects24 and anesthesia markedly changes the membrane potential dynamics of neurones25. Moreover, in vivo 2-photon microscopy experiments are increasingly based on analysis of awake animals4. We therefore analyzed the effects of SR101 application in awake non-anaesthetized mice (Fig. 2a). Following preparation of the cranial window the mice were allowed to wake up from the anesthesia for 1 hour and wakefulness was then confirmed by decreased 1–4 Hz power and increased 12–30 Hz power in the LFP26 as well as by visual confirmation (Fig. 2b,c and Supplementary Fig. 7a–c). [SEP] Justify:

Output: The text is irrelevant to the claim as it discusses the effects of topical SR101 application on neuronal activity and does not mention E. coli or the use of chassis organisms in synthetic gene construction.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine can help reduce adverse drug reactions. [SEP] Text: Though the predictive value is probably insufficient for widespread clinical translation and it is likely that the contribution by SLCO1B1 genotype varies between different statins, the finding has increased understanding of the mechanism for this toxicity and genotyping could be beneficial in certain situations. Otherwise, GWA studies have not identified novel genes to any great extent. This may be due to insufficient numbers of cases being studied. Continuing efforts by international consortia to increase cohort sizes for various adverse drug reactions may still enable further progress to be made using a GWA approach. The availability of cohorts of well-phenotyped cases will also be helpful for whole genome sequencing, which is likely to become more routine as processing costs fall and methods for data analysis improve. Performing genetic association studies on idiosyncratic adverse drug reactions is of particular value because of the lack of animal models for most of the common reactions and also the difficulty in obtaining material from the target organ for most types of reaction. One interesting recent development is the possibility of using induced pluripotent stem (iPS) cells from individuals who have suffered adverse drug reactions to model the reaction. This has been proposed as a means of studying congenital long QT syndrome [88], but should be equally applicable to drug-induced long QT and also to other adverse drug reactions such as DILI since it is now possible to derive hepatocyte-like cells from human iPS cells [89]. In addition to the adverse drug reactions discussed in detail in this 1298. 10. 1136/bmj. 316. 7140. 1295. 473. 10. 1517/17425250902927386. CAS PubMed 2658. 10. 1182/blood-2011-06-360313. CAS PubMed 75. 889. 10. 1038/ng. 2344. 310. 10. 1007/s00125-012-2756-1. 363. 10. 1055/s-0029-1240004. PubMed 202. 10. 1146/annurev. pharmtox. 45. 120403. 100058. CAS PubMed 501. 10. 1111/j. 1399-6576. 1985. tb02242. x. CAS PubMed 432. CAS PubMed 680. 10. 3109/00365529309098271. CAS PubMed 606. 10. 1002/hep. [SEP] Justify:

Output: The text supports the claim by discussing the potential benefits of genotyping in understanding the mechanisms of adverse drug reactions and highlights the value of personalized approaches, such as using induced pluripotent stem (iPS) cells to model reactions to study adverse drug reactions. It indicates that these personalized methods are likely to allow for a better understanding and potentially lower the risks of adverse reactions.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: Despite knowledge of rising sea levels, urban agglomerations continue to grow strongly in coastal areas globally (United Nations, 2014). After a disaster, the one to blame is searched for—it is usually not found to be one’s own wrongdoing. Interestingly, the one to blame has changed over the centuries, as the following example displays. It is well documented that tropical cyclones occasionally run up the East coast of the and lead to severe flood events in New England. Following a hurricane landfall in September 1815, and associated devastating floods that engulfed and destroyed vast areas and took many lives, the blame for the disaster was attributed either to god’s will, or the will of his opponent (Whipple, 1983). When a similar storm hit 100 years later, in September 1938, the then recently created U. S. Meteorological service was blamed for not issuing timely warnings (Whipple, 1983). And when hurricane Sandy hit the East coast of the in 2013, the blame was primarily put on climate change (see various newspapers and blogs published after the storm, and Sobel, 2014). Due to its morphology and experiences of historically recorded events, is considered to be flood prone. Despite this knowledge, the blame for the mentioned disasters is always attributed to something other—today climate change—than the simple fact of people exposing themselves and their assets to extreme events. It is also interesting to observe that flood-prone areas are continuously further developed and densely settled, despite the existence of climate change adaptation strategies. Finland was the first country to adopt a for Adaptation to in 2005 (Ministry of Agriculture and Forestry, 2005), and the adaptation policies and measures were evaluated for implementation in 2009 and 2013 (Ministry of Agriculture and Forestry, 2009, 2013). This led to an updated national climate change adaptation strategy, a draft version of which was published in 2014 (Ministry of Agriculture and Forestry, 2014). developed a climate change adaptation strategy in 2012 (HSY, 2013). Earlier, the city of Helsinki had developed strategies for floods (City of Helsinki, 2010) and a flood risk management act (620/2010), both of which were based on the EU floods directive (2007/60/EY). Despite guidelines available to the public, recommending that the lowest elevation of the ground floor of buildings in coastal areas should not be located below 2. [SEP] Justify:

Output: The text contrasts the claim by illustrating that despite the existence of climate change adaptation strategies, urban areas continue to develop in flood-prone regions, leading to increased vulnerability to climate-related events. The text emphasizes that adaptation measures have been implemented, yet the persistence of risky development in these areas suggests that adaptation alone is insufficient to fully counteract the effects of climate change.


Input: Task: pass the claim using the given text. Claim: Chassis organisms like E. coli are commonly used for synthetic gene construction. [SEP] Text: When we recorded LFPs in S1-M1 of awake mice we again observed large synchronised seizure-like potentials occuring following 100 μM (10 min incubation) SR101 application (Fig. 2d). Note that movement artefacts were not removed from the LFP trace shown in Fig. 2d. This seizure-like activity was correlated with a drop in low-frequency power (1–4 Hz) and an increase in higher-frequency power (12–30 Hz) (Fig. 2d and Supplementary Fig. S1) similar to seen in Fig. 1b and previous epilepsy publications13,17. The individual seizure-like events in awake mice exhibited an average amplitude of 1. 4 ± 0. 82 mV and average event intervals of 0. 83 ± 0. 75 s (Fig. 2e). Thus, the average seizure-like event amplitude was 0. 24 mV smaller (Unpaired Welch’s t-test, t = 1. 632 df = 8. 605, P = 0. 1387) and the event interval 0. 16 s shorter (Unpaired Welch’s t-test, t = 2. 181 df = 9. 934, P = 0. 0543) than in anaesthetized mice. Overall, this experiment expands the finding that SR101 evoke seizure-like cortical activity to awake animals, potentially making it useful as an epileptogenic agent for future in vivo experiments investigating cortical epilepsy, conditioned that SR101’s mechanism of action will be revealed in future experiments. Figure 2SR101 can induce seizure-like activity in awake mice. (a) Experimental setup. (b) LFP recordings from the same mouse during ketamine/xylazine (KX) anaesthesia and wakefulness. (c) Frequency-domain spectra showing change in power distribution between KX anaesthesia and awake LFP from (b). (d) Upper, LFP recording showing development of seizure-like activity in primary sensori-motor cortex following 100 μM SR101 loading (10 min incubation). Note that movement artefacts have not been removed from the LFP. Lower, frequency power spectrograms from period 1 and 2 from LFP above. (e) Histograms showing individual seizure-like activity event amplitudes and intervals. [SEP] Justify:

Output: The text is irrelevant to the claim as it focuses on experimental results related to seizure-like activity in awake mice and the effects of SR101. There is no mention of E. coli or synthetic gene construction, making it a 'pass' regarding relevance to the claim.


Input: Task: corroborate the claim using the given text. Claim: Personalized medicine can help reduce adverse drug reactions. [SEP] Text: Academy of Enter your Email address: Subscribe to eTOC Home >. . . the 7, 2006 —As drug reimbursement under D becomes a reality, medical groups are grappling not only with how to get the right drugs to all Medicare beneficiaries who need them, but also with how to make sure all patients takes their medications without adverse drug reactions or interactions. At a meeting here in November on drug discovery, development, and translation convened by the Institute of Medicine (IOM), invited speakers addressed the role of health-care professionals and consumers in reducing adverse drug events. The IOM Forum was held shortly after the FDA announced on Nov. 2 its requirement that drug makers submit prescription drug label information to the agency in a new electronic formatwas held shortly before the Nov. 8 announcement that the Institute for Practices, headquartered in Huntingdon, PA, is partnering with the FDA on an educational campaign to eliminate potentially harmful, error-prone medical abbreviations such as HCT for hydrocortisone, which could be mistaken for hydrochlorothiazide. The new joint educational campaign will be launched in the first half of 2006. speakers cited statistics from the 1999 IOM report, Is Human, that estimated that up to 98,000 Americans die each year from medical errors, many from adverse drug reactions and drug-drug interactions. Those statistics, they said, were good reason for establishing a national database that would include drug-drug interactions, adverse drug reactions, as well as misuse and underuse. “Drug databases have focused on misuse in the past, but I think we're going to see more drug databases that address drug underuse based on evidence-based practices,” said Scott Weingarten, MD, President and CEO of Zynx Health, citing the failure to prescribe long-term aspirin therapy after a heart attack. Dr. Weingarten is also of Medicine at the University of California-School of Medicine and Director of Research at Cedars-SystemSidney N. of Pharmacovigilance & Inc, a Huntington Valley, PA-based firm that provides advice on drug safety and risk assessment to the pharmaceutical industry, said that drug labeling is now little more than a “laundry list” of adverse drug reactions. “You end up with screen after screen of information, but what does it tell the clinician to do? ” asked Dr. Kahn. “There is limited information useful to prescribers. [SEP] Justify:

Output: The text supports the claim by discussing the importance of addressing adverse drug reactions and the potential role of health-care professionals and consumers in reducing these incidents. It emphasizes the need for a national database that includes information on drug-drug interactions and adverse drug reactions, which aligns with the idea that personalized medicine can help tailor treatments to individual patients and therefore minimize the risk of adverse effects.


Input: Task: contrast the claim using the given text. Claim: Climate adaptation alone can fully counteract the effects of climate change. [SEP] Text: 6 m above mean sea level (Ollila, 2002), several new town areas were planned and built below this level, after the publication of the guidelines in flood-prone areas, within the Area (Schmidt-Thomé & Klein, 2011). These developments continued until the Gudrun hit Helsinki in January 2005, flooding several newly built houses. This extreme event contributed to the further development and implementation of the climate change adaptation strategies mentioned above. A newer guide, by Parjanne and Huokuna (2014), raises the minimum elevation to 2. 8 m. Nonetheless, in 2014, houses continued to be built on the Area shorelines, often less than 1 m above sea level. According to the architects responsible for issuing building permits, the investors building close to sea level were informed that these buildings are located in flood-prone areas. Despite these guidelines, and knowing that they were building in a flood prone area, private investors perceived that the benefit of living on the shoreline outweighed the risks to which they exposed their assets. The cooperation of the private sector in developing and implementing climate change adaptation strategies in urban areas Finland is rather weak (Klein, Mäntysalo, & Juhola, 2015). According to Finnish insurance companies, many wealthy persons do not mind that their flood prone assets are not insurable. In the case of flood events, assets are protected with sand bags. Afterwards, the flood damages are repaired at the owner’s expense. In some cases, repairs are necessary annually, but the fact of living close to the sea outweighs risks and costs. Per definition, extreme events occur only seldom (from a human perspective). Still, their impacts are often disastrous. The problems, obstacles, and/or negligence in adapting to such events lead to the conclusion that it should be feasible to discuss (mal-)adaptation to the (current) climate and its extremes first, before heading straightforward into climate change adaptation. The message on climate change conveyed by IPCC’s summary for policy makers (IPCC, 2007b, 2014) is that hydro-meteorological natural hazards will, with high confidence, increase on nearly all continents, in both intensities and frequencies. Therefore the statement above might also be asked the other way round: in the Words: by Nowadays? [SEP] Justify:

Output: The text contrasts the claim by highlighting the inadequacies of climate adaptation strategies in Finland, where despite guidelines, houses continue to be built in flood-prone areas, exposing them to significant risks. It states that private investors are aware of the flood risks but still choose to build close to the sea, indicating that climate adaptation alone is not sufficient to mitigate the effects of climate change. The text also emphasizes the weak cooperation in developing adaptation strategies and the recurring damages from floods, suggesting that adaptation measures are inadequate without addressing the underlying risks and behaviors.