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Public service announcements (PSAs) or campaigns aimed at preventing harm can inadvertently risk creating additional harms. It remains unclear whether these unintended effects are considered during campaign development, if risk mitigation strategies are implemented, or how professionals involved perceive these issues. It is in the context of illicit drug use prevention PSAs that our research investigates and explores the perspectives of practitioners—health support professionals and advertising campaign designers and creators. Semi-structured expert interviews were conducted to capture and synthesize practitioners' perspectives which were then analysed by applying a framework to address the unintended effects of public health interventions. The results indicated that practitioners from both sectors are aware of unintended harms but place varying levels of importance on different aspects. In the case of illicit drug prevention PSAs, incorporating practitioners' perspectives in campaign development may result in mitigating the risk of potential unintended harmful effects. [ABSTRACT FROM AUTHOR]

Background People need critical thinking skills to make well-informed health choices and avoid waste and unnecessary suffering. However, educational interventions can have adverse effects, which is often overlooked. We created a framework of potential harms of interventions to improve critical thinking about health choices. The objective was to identify potential effects and articulate potential mechanisms. We intended to use the framework to inform the development and evaluation of an intervention in Kenya, Rwanda, and Uganda. Methods We created an initial framework drawing on two earlier frameworks. We surveyed external experts using Likert-scale and open-ended items, including researchers, educators, and others, in a variety of relevant fields. We emailed the survey to an international advisory network, and all other experts recommended by respondents. We analyzed the quantitative data using descriptive statistics. We conducted a thematic analysis of the qualitative data. We revised the framework based on those results. To identify any effects missing from the revised framework, we individually interviewed a convenience sample of one teacher from each of Kenya, Rwanda, and Uganda. Results We received responses from 38 of 70 external experts (54%). The quantitative survey data suggested respondents agreed with the initial framework overall. However, the qualitative data led to substantial revisions. The revised framework consists of categories of adverse outcomes; outcomes within each category; sub-outcomes; individuals, groups, and populations that might experience each adverse outcome; beneficial outcomes corresponding with adverse outcomes; and potential mechanisms of adverse effects. There are six categories: decision-making harms, psychological harms, equity harms, group and social harms, waste, and other harms. In the interviews with teachers, we did not identify any effects missing from the revised framework. Conclusions As far as we know, the framework is the first tool of its kind for education research. It can be improved upon and adapted.

The main objectives were to evaluate the substantial equivalence of metabolite composition in transgenic rice and its parents, and assess the risk factors in rice from two aspects of metabolomic variation and mycotoxin content. High performance liquid chromatography-mass spectrometry (HPLC-MS) was used to analyze Japonica rice varieties Nip-ponbare (FP1) and PJ574(FP2) and their corresponding transgenic lines (FT16 and FT23). The results were as follows: multivariate statistical methods such as principal component analysis and partial least squares discriminant analysis were used to detect 448 metabolites from rice samples. Different metabolites were screened and it was found that the concentration variations of zearalenone, L-lactate, 10@, 12Z-octadecanodienoic acid and spermine were significantly affected by gene modification or variety differences. There were 9, 23 and 13 unique differential metabolites in group FP1-FP2, FP1-FT16 and FP2-FT23, respectively, with the highest variation in FP1-FT16. The unique differential metabolites of group FP1-FT16 mainly included deoxyguanolate, coffee salt and gluconic acid. The distinct metabolites of FP2-FT23 were mainly prostaglandin B2, L-cystine, 16-hydroxypalmitic acid. The unique differential metabolites of FP1-FP2 consisted of inositol and stearate amides. The effects of transgenic breeding and variety differences were similar, both of which affect arginine biosynthesis and multiple amino acid metabolic pathways to a certain extent, but the variation of metabolic pathways in different varieties of transgenic rice was different. Enzyme-linked immunoassay (ELISA) showed that the zearalenone content in rice samples ranged from 4.2 to 6 !g/kg, with a significant difference between the two parent varieties (A<0.01), but the content of zearalenone in transgenic rices was substantial equivalence to that in the parents. Fusarium was found to be a common endophytic fungus in rice by high-throughput sequencing. Conclusions: Although the variation of metabolic components and metabolic pathways induced by transgenic breeding may affect the nutritional quality of rice, the extent of variation is not greater than that of rice varieties, and it is within the safe range. A low dose (less than 6 g/kg) of Fusarium toxin zearalenone was detected in rice samples from four rice samples by untargeted metabolomic analysis technique. Although lower than the national standard (60 g/kg), Fusarium toxin may be synthesized by endophytic Fusarium fungi in rice, and there is a risk of fungal outbreaks under certain conditions with significant accumulation of toxicity. [ABSTRACT FROM AUTHOR]

Aid localisation is a decades-old endeavour recently catalysed by the 2016 Grand Bargain agreement. However, localisation's unintended effects have yet to be assessed systematically. This study typologises five unintended effects in the context of Cordaid's partnerships within the Just Future program: competition, administration, value, civic space, and climate effects. Through literature reviews and 15 key informant interviews, it finds most frequently and impactfully that localisation risks perpetuating hierarchies, as international NGOs favour partnerships with larger local NGOs that manage to meet donor requirements at the expense of community-based organisations (competition effect). In addition, it risks disproportionately increasing local administrative burdens due to donors' low risk appetite and mistrustful perceptions of local capacities (administration effect). Localisation furthermore risks diverging from certain values, such as gender-related and LGBTQ+ rights, which are a priority for many international NGOs (value effect). Recommendations focus on adaptive management and providing technical assistance to smaller local NGOs. [ABSTRACT FROM AUTHOR]

ABSTRACTUnintended effects of gene edit crops may pose safety issues. Omics is a useful tool for researchers to evaluate these unexpected effects. Transcriptome and proteomics analyses were performed for two gene editors, CRISPR-Cas9 and adenine base editor (ABE) gene edit rice, as well as corresponding wild-type plants (Nipponbare). Transcriptome revealed 520 and 566 rice differentially expressed genes (DEGs) in the Cas9/Nip and ABE/Nip comparisons, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most DEGs participated in metabolism of terpenoids and polyketones, plant–pathogen interactions, and plant signal transduction. It mainly belongs to environmental adaptation. Proteomics revealed 298 and 54 rice differentially expressed proteins (DEPs) in the Cas9/Nip and ABE/Nip comparisons, respectively. KEGG pathway enrichment analysis showed that most DEPs participated in the biosynthesis of secondary metabolite and metabolic pathways.According to integrated transcriptomes and proteomics analysis, the results showed that no newly generated genes were identified as new transcripts of these differentially expressed genes, and gene edit tools had little effect on rice transcription levels and no new proteins were generated in the gene-edited rice.

Abstract Background Betalain is a natural pigment with important nutritional value and broad application prospects. Previously, we produced betanin biosynthesis transgenic carrots via expressing optimized genes CYP76AD1S, cDOPA5GTS and DODA1S. Betanin can accumulate throughout the whole transgenic carrots. But the effects of betanin accumulation on the metabolism of transgenic plants and whether it produces unexpected effects are still unclear. Results The accumulation of betanin in leaves can significantly improve its antioxidant capacity and induce a decrease of chlorophyll content. Transcriptome and metabolomics analysis showed that 14.0% of genes and 33.1% of metabolites were significantly different, and metabolic pathways related to photosynthesis and tyrosine metabolism were markedly altered. Combined analysis showed that phenylpropane biosynthesis pathway significantly enriched the differentially expressed genes and significantly altered metabolites. Conclusions Results showed that the metabolic status was significantly altered between transgenic and non-transgenic carrots, especially the photosynthesis and tyrosine metabolism. The extra consumption of tyrosine and accumulation of betanin might be the leading causes.

The safety and unintended effects of genetically modified (GM) crops have been the focus of public attention. Transcriptome analysis is a powerful tool to assess the potential impact of genetic modification on plant genomes. In this study, three transgenic (KMD, KF6, and TT51-1) and three non-transgenic (XS11, MH86, and MH63) rice varieties were assessed at the genomic and protein levels. The results of polymerase chain reaction (PCR) and Cry1Ab/1Ac speed test strips showed that the Bt gene was successfully expressed in transgenic rice. The results of RNA-seq analysis to analyze the unintended effects of transgenic Bt rice showed fewer differentially expressed genes (DEGs) between the transgenic and non-transgenic rice varieties than among the different varieties. Meanwhile, the results of principal component analysis and cluster analysis found no significant genetic variation between the transgenic and non-transgenic rice varieties, except for the presence of Bt in transgenic rice. There were only two co-upregulated DEGs and no co-downregulated DEGs among three comparison groups. Although there were various DEGs among the groups, the two co-upregulated DEGs were not related to any significantly enriched gene ontology (GO) term or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, indicating that the differences among the subgroups were more likely caused by complex environmental or genetic factors, rather than unintended effects due to Bt expression. This study provides useful information to further explore the unexpected effects and safety of GM rice. [ABSTRACT FROM AUTHOR]

There is widespread recognition among scholars, international aid providers and evaluators of the need to take into account the unintended outcomes of international development efforts. Practitioners have also signed on to charters that promise they will do their utmost best to 'do no harm'. This article focusses on the often overlooked unintended gender effects. A rigorous literature review was conducted to reveal some of the most prominent unintended consequences as documented in primary research in development studies. Five prevalent unintended gender effects were identified: (1) household dynamics, (2) anti-foreign backfire, (3) overburdening of women, (4) human trafficking and sexual exploitation and (5) hype. While not all of the unintended gender effects are negative, most of the reported unintended effects jeopardise the intended outcomes of the interventions. This research provides both a call and a tool to analyse more systematically the unintended gender effects of international development efforts. [ABSTRACT FROM AUTHOR]

The miraculin transgenic tomato is a genetically modified (GM) crop that can be used as an alternative for low calories food and a natural non-sugar sweetener. Before the release and distribution, transgenic crop needs to go through an environmental risk assessment (ERA) as a backbone to achieve biosafety. Comparative analysis is a general principle of ERA to identify differences between transgenic crop and its non-transgenic counterpart which may indicate substantial equivalence and unintended effects. This experiment was aimed to compare the agronomic, compositional, and physiological characteristics of miraculin transgenic tomato cv. Moneymaker with non-transgenic tomato. The data obtained were plant height, stem diameter, relative growth rate, chlorophyll content, stomatal conductance, days to 50% flowering, days to fruit maturity, a number of flowers per cluster, a number of fruits per cluster, a number of fruits per plant, fruit weight, fruit diameter, harvest index, total dissolved solids, fructose, glucose, and sucrose contents, and total carotenoids, lycopene, and β-carotene contents. This study found that there were no significant differences between miraculin transgenic and non-transgenic tomato in all variables observed. It suggests that miraculin transgenic tomato is equivalent to its counterpart and unintended effects are not detected as.

Background: Betalain is a natural pigment with important nutritional value and broad application prospects. Previously, we produced betanin biosynthesis transgenic carrots via expressing optimized genes CYP76AD1S, cDOPA5GTS and DODA1S. Betanin can accumulate throughout the whole transgenic carrots. But the effects of betanin accumulation on the metabolism of transgenic plants and whether it produces unexpected effects are still unclear. Results: The accumulation of betanin in leaves can significantly improve its antioxidant capacity and induce a decrease of chlorophyll content. Transcriptome and metabolomics analysis showed that 14.0% of genes and 33.1% of metabolites were significantly different, and metabolic pathways related to photosynthesis and tyrosine metabolism were markedly altered. Combined analysis showed that phenylpropane biosynthesis pathway significantly enriched the differentially expressed genes and significantly altered metabolites. Conclusions: Results showed that the metabolic status was significantly altered between transgenic and non-transgenic carrots, especially the photosynthesis and tyrosine metabolism. The extra consumption of tyrosine and accumulation of betanin might be the leading causes. [ABSTRACT FROM AUTHOR]

Stable and high expression of introduced genes is a prerequisite for using transgenic trees. Transgene stacking enables combining several valuable traits, but repeated transformation increases the risk of unintended effects. This work studied the stability and intron-mediated enhancement of uidA gene expression in leaves and different anatomical parts of pear fruits during field trials over 14 years. The stability of reporter and herbicide resistance transgenes in retransformed pear plants, as well as possible unintended effects using high-throughput phenotyping tools, were also investigated. The activity of β-glucuronidase (GUS) varied depending on the year, but silencing did not occur. The uidA gene was expressed to a maximum in seeds, slightly less in the peel and peduncles, and much less in the pulp of pear fruits. The intron in the uidA gene stably increased expression in leaves and fruits by approximately twofold. Retransformants with the bar gene showed long-term herbicide resistance and exhibited no consistent changes in leaf size and shape. The transgenic pear was used as rootstock and scion, but grafted plants showed no transport of the GUS protein through the graft in the greenhouse and field. This longest field trial of transgenic fruit trees demonstrates stable expression under varying environmental conditions, the expression-enhancing effect of intron and the absence of unintended effects in single- and double-transformed woody plants. [ABSTRACT FROM AUTHOR]

Main conclusion: Transcriptomics and methylomics were used to identify the potential effects resulting from GM rice breeding stacks, which provided scientific data for the safety assessment strategy of stacked GM crops in China. Gene interaction is one of the main concerns for stacked genetically modified crop safety. With the development of technology, the combination of omics and bioinformatics has become a useful tool to evaluate the unintended effects of genetically modified crops. In this study, transcriptomics and methylomics were used as molecular profiling techniques to identify the potential effects of stack through breeding. Stacked transgenic rice En-12 × Ec-26 was used as material, which was obtained through hybridization using parents En-12 and Ec-26, in which the foreign protein can form functional EPSPS protein by intein-mediated trans-splitting. Differentially methylated region (DMR) analysis showed that the effect of stacking breeding on methylation was less than that of genetic transformation at the methylome level. Differentially expressed gene (DEG) analysis showed that the DEGs between En-12 × Ec-26 and its parents were far fewer than those between transgenic rice and Zhonghua 11 (ZH11), and no unintended new genes were found in En-12 × Ec-26. Statistical analysis of gene expression and methylation involved in shikimic acid metabolism showed that there was no difference in gene expression, although there were 16 and 10 DMR genes between En-12 × Ec-26 and its parents (En and Ec) in methylation, respectively. The results indicated that the effect of stacking breeding on gene expression and DNA methylation was less than the effect of genetic transformation. This study provides scientific data supporting safety assessments of stacked GM crops in China. [ABSTRACT FROM AUTHOR]

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The quality of transgenic fruits was studied only for apple, plum and citrus. We first evaluated the transgenic fruit characteristics of pear, which is one of the most consumed fruit crops. The size, shape and biochemical composition of fruits from field-grown pear trees with marker genes were analyzed for 5 years. Soluble solids, vitamin C, and phenolic compounds varied significantly between transgenic lines, but these deviations were inconsistent. Arbutin content and sugar:acidity ratio were the most stable parameters. One transgenic line showed a stable increase in fruit weight (by 12.2–21.2%). The extremely dry and hot season increased the total phenolics (2.6–3.6 times) and tannin (3.2–3.6 times) levels, but not flavonoids. The harvest year had a stronger effect on analyzed fruit parameters than the genotype. Our study found no unintended effects of genetic transformation on pear fruit quality and confirms the importance of long-term field tests for perennial transgenic plants. [ABSTRACT FROM AUTHOR]

Compensation packages including incentives tied to a company's stock price can be powerful motivators for corporate leaders. But the authors' study also showed that these motivations can produce some serious unintended consequences. Equity incentives can tempt CMOs to engage in short-sighted marketing management such as cutting R&D and advertising spending in an effort to inflate current earnings and enhance the company's stock price. This myopic management boosts their personal earnings at the expense of their company's long-term performance. Our findings highlight the pitfalls and limitations of overreliance on equity in managerial compensation packages. Companies could continue to pay their C-level executives based on stock price performance but defer the payout to the future until the long-term consequences of their decisions become apparent. This would reduce the temptation to act on short-term impulses to boost equity compensation. [ABSTRACT FROM AUTHOR]

Abstract Background There is increasing awareness among researchers and policymakers of the potential for healthcare interventions to have consequences beyond those initially intended. These unintended consequences or “spillover effects” result from the complex features of healthcare organisation and delivery and can either increase or decrease overall effectiveness. Their potential influence has important consequences for the design and evaluation of implementation strategies and for decision-making. However, consideration of spillovers remains partial and unsystematic. We develop a comprehensive framework for the identification and measurement of spillover effects resulting from changes to the way in which healthcare services are organised and delivered. Methods We conducted a scoping review to map the existing literature on spillover effects in health and healthcare interventions and used the findings of this review to develop a comprehensive framework to identify and measure spillover effects. Results The scoping review identified a wide range of different spillover effects, either experienced by agents not intentionally targeted by an intervention or representing unintended effects for targeted agents. Our scoping review revealed that spillover effects tend to be discussed in papers only when they are found to be statistically significant or might account for unexpected findings, rather than as a pre-specified feature of evaluation studies. This hinders the ability to assess all potential implications of a given policy or intervention. We propose a taxonomy of spillover effects, classified based on the outcome and the unit experiencing the effect: within-unit, between-unit, and diagonal spillover effects. We then present the INTENTS framework: Intended Non-intended TargEted Non-Targeted Spillovers. The INTENTS framework considers the units and outcomes which may be affected by an intervention and the mechanisms by which spillover effects are generated. Conclusions The INTENTS framework provides a structured guide for researchers and policymakers when considering the potential effects that implementation strategies may generate, and the steps to take when designing and evaluating such interventions. Application of the INTENTS framework will enable spillover effects to be addressed appropriately in future evaluations and decision-making, ensuring that the full range of costs and benefits of interventions are correctly identified.

Background: To address concerns that healthy weight and lifestyle campaigns (HWLCs) could have unintended psychological or behavioral consequences, this study tested reactions to TV advertisements from two HWLCs: LiveLighter ® (employs graphic health effects messaging) and Swap It Don't Stop It (employs animation and light-hearted messaging). Methods: An online between-subjects experiment tested reactions to one of five advertisements: "Toxic Fat"; "Sugary Drinks" (both from LiveLighter); "Become a Swapper"; "How to Swap It" (both from Swap It); and "HSBC Bank" (control) among 2,208 adults from Western Australia and Victoria, Australia. Responses assessed were cognitive and emotional reactions, behavioral intentions, internalized weight bias, antifat attitudes, self-esteem and body dissatisfaction. Results: The HWLC advertisements prompted favorable cognitive reactions and weak to neutral positive and negative emotional responses. HWLC advertisements promoted stronger intentions to engage in adaptive lifestyle behaviors compared with the control advertisement. Intention to engage in maladaptive behaviors (e.g., skipping meals) was low overall and did not differ by condition. Compared with the control condition, participants who saw LiveLighter "Sugary Drinks" showed weaker disagreement with antifat attitudes; however, mean antifat attitude scores were still at the low end of the scale. HWLC advertisements did not promote internalized weight bias, reduced self-esteem or body dissatisfaction compared with the control advertisement. Conclusions: Overall, HWLC advertisements performed favorably compared with the control advertisement and showed no clear evidence of adverse impacts. Findings suggest HWLC advertisements may not promote negative psychological and behavioral consequences and can continue to be used in obesity prevention efforts. [ABSTRACT FROM AUTHOR]

The miraculin transgenic tomato is a genetically modified (GM) crop that can be used as an alternative for low calories food and a natural non-sugar sweetener. Before the release and distribution, transgenic crop needs to go through an environmental risk assessment (ERA) as a backbone to achieve biosafety. Comparative analysis is a general principle of ERA to identify differences between transgenic crop and its non-transgenic counterpart which may indicate substantial equivalence and unintended effects. This experiment was aimed to compare the agronomic, compositional, and physiological characteristics of miraculin transgenic tomato cv. Moneymaker with non-transgenic tomato. The data obtained were plant height, stem diameter, relative growth rate, chlorophyll content, stomatal conductance, days to 50% flowering, days to fruit maturity, a number of flowers per cluster, a number of fruits per cluster, a number of fruits per plant, fruit weight, fruit diameter, harvest index, total dissolved solids, fructose, glucose, and sucrose contents, and total carotenoids, lycopene, and ß-carotene contents. This study found that there were no significant differences between miraculin transgenic and non-transgenic tomato in all variables observed. It suggests that miraculin transgenic tomato is equivalent to its counterpart and unintended effects are not detected as. [ABSTRACT FROM AUTHOR]

Unintended effects of gene edit crops may pose safety issues. Omics is a useful tool for researchers to evaluate these unexpected effects. Transcriptome and proteomics analyses were performed for two gene editors, CRISPR-Cas9 and adenine base editor (ABE) gene edit rice, as well as corresponding wild-type plants (Nipponbare). Transcriptome revealed 520 and 566 rice differentially expressed genes (DEGs) in the Cas9/Nip and ABE/Nip comparisons, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most DEGs participated in metabolism of terpenoids and polyketones, plant–pathogen interactions, and plant signal transduction. It mainly belongs to environmental adaptation. Proteomics revealed 298 and 54 rice differentially expressed proteins (DEPs) in the Cas9/Nip and ABE/Nip comparisons, respectively. KEGG pathway enrichment analysis showed that most DEPs participated in the biosynthesis of secondary metabolite and metabolic pathways. According to integrated transcriptomes and proteomics analysis, the results showed that no newly generated genes were identified as new transcripts of these differentially expressed genes, and gene edit tools had little effect on rice transcription levels and no new proteins were generated in the gene-edited rice. [ABSTRACT FROM AUTHOR]

Background: The literature on start-up subsidies (SUS) for the unemployed finds positive effects on objective outcome measures such as employment or income. However, little is known about effects on subjective well-being of participants. Knowledge about this is especially important because subsidizing the transition into self-employment may have unintended adverse effects on participants' well-being due to its risky nature and lower social security protection, especially in the long run. Objective: We study the long-term effects of SUS on subjective outcome indicators of well-being, as measured by the participants' satisfaction in different domains. This extends previous analyses of the current German SUS program ("Gründungszuschuss") that focused on objective outcomes—such as employment and income—and allows us to make a more complete judgment about the overall effects of SUS at the individual level. Research design: Having access to linked administrative-survey data providing us with rich information on pretreatment characteristics, we base our analysis on the conditional independence assumption and use propensity score matching to estimate causal effects within the potential outcomes framework. We perform several sensitivity analyses to inspect the robustness of our findings. Results: We find long-term positive effects on job satisfaction but negative effects on individuals' satisfaction with their social security situation. Supplementary findings suggest that the negative effect on satisfaction with social security may be driven by negative effects on unemployment and retirement insurance coverage. Our heterogeneity analysis reveals substantial variation in effects across gender, age groups, and skill levels. Estimates are highly robust. [ABSTRACT FROM AUTHOR]

The exponential advancement of health technologies has led to an increasing need for awareness and critical thinking about the potential unintended consequences and ethical dilemmas that may arise from using new technologies. Unfortunately, many ethical issues arise post-implementation. Few researchers preemptively consider the ethical implications of health technologies. The current study located more than 24 million articles in PubMed that discussed common health technologies. Of these, 0.07% (n = 17,816) articles deeply considered the technology's potential ethical implications. Critical thinking and ethics are the mainstays of nursing practice. Thus, critically thinking about the potential ethical implications of relevant technologies should be at the forefront of research; we contend that this is not common practice. We hope to shed light on this issue to remind researchers to think like nurses when researching new health technologies. [ABSTRACT FROM AUTHOR]

Abstract Background Widely targeted metabolomics was applied to estimate the differences in the metabolite profiles of maize seeds from 3 natural genotypic varieties and 4 genetically modified (GM) lines. Results Pairwise comparison with their isogenic controls revealed 71, 121, 43 and 95 differentially accumulated metabolites (DAMs) in GM maize seeds of C0030.2.4, C0030.3.5, C0010.1.1 and C0010.3.1, respectively. KEGG pathway enrichment analysis showed that most of these DAMs participated in the biosynthesis of secondary metabolites and purine metabolism in GM maize C0030.2.4 and C0030.3.5, but participated in tryptophan metabolism and 2-oxocarboxylic acid metabolism in C0010.3.1 seeds and in metabolic pathways and the biosynthesis of secondary metabolites in C0010.1.1 seeds. The data also showed that the differences in metabolite accumulation, both total DAMs and co-DAMs, among the different natural genotypic varieties (418 DAMs and 39 co-DAMs) were greater than those caused by genetic modification (330 DAMs and 3 co-DAMs). Conclusions None of the DAMs were identified as new or unintended, showing only changes in abundance in the studied maize seeds. The metabolite profile differences among the 3 non-GM lines were more notable than those among GM lines. Different genetic backgrounds affect metabolite profiling more than gene modification itself. Graphic abstract

Scholars examining the effects of collective action on public policy have predominantly analyzed policy outcomes with respect to the stated goals of collective actors. This approach to the political influence of collective action not only limits our analytical scope, but also makes the field vulnerable to the criticism that outcome research may be overly deterministic in attributing observed changes to collective action, especially if it utilizes an atemporal logic. This article offers an alternative approach by analyzing a change in legislation that can be considered an unintended consequence of collective action. It examines the decision to introduce a police identification statute after the violent NoG20 protests in Hamburg in 2017 and asks how the protests were consequential for a policy that collective actors had neither initially addressed, nor intended to change. Policy making is conceptualized as a contingent, non-linear process that is best understood from a "processual" perspective. Based on parliamentary documents and semi-structured interviews, the article temporally reconstructs a policy process that had its beginning well before the NoG20 protests. The long-term analysis shows that instead of initiating policy change, the protests created a "window of opportunity" for the members of parliament to push for a proposal they had previously introduced. Police identification was raised after multiple, contingent processes converged after the protests that enabled the members of parliament to point to a factual necessity for policy change. Activists only had a passive role in this change as they had lost credibility during the violent protests. This study emphasizes the centrality of temporality for understanding policy effects of collective action and argues that a processual perspective allows for contextualizing the influence of collective actors both in time and in concert with other actors.

Collaboration is one of the defining features of work and learning in the 21st century. Yet despite the proliferation of Google apps and devices for collaboration across North American school systems, the scope of research on student collaboration using Google technologies in elementary school settings is limited. This paper presents findings from two cases in grade five classrooms where teachers were experimenting with using Google Docs and Chromebooks in their literacy programs. Drawing on a conceptual framework of sociomaterial, complexity, and affect theories, the study offers insights for teachers to understand the complexities of collaboration with these technologies, and pedagogical implications for working with the magic and monsters of unintended effects in collaborative literacy practices. [ABSTRACT FROM AUTHOR]

Collaboration is one of the defining features of work and learning in the 21st century. Yet despite the proliferation of Google apps and devices for collaboration across North American school systems, the scope of research on student collaboration using Google technologies in elementary school settings is limited. This paper presents findings from two cases in grade five classrooms where teachers were experimenting with using Google Docs and Chromebooks in their literacy programs. Drawing on a conceptual framework of sociomaterial, complexity, and affect theories, the study offers insights for teachers to understand the complexities of collaboration with these technologies, and pedagogical implications for working with the magic and monsters of unintended effects in collaborative literacy practices.

The Environmental Risk Assessment (ERA) of genetically modified (GM) crops in Argentina is carried out by the National Advisory Commission on Agricultural Biotechnology (CONABIA) and the Innovation and Biotechnology Coordination (CIyB). Both have a large experience with this assessment, since 1991, when CONABIA was created. The continuous support to biotechnology as a state policy and as part of the decision to encourage developers in the regulatory process has helped make progress in the revision of the regulations. The experience gained during the last 30 years and the worldwide scientific advances supported the bases to update the regulatory framework. Focusing on the biosafety strengthening and the improvement of the applicant’s experience in the GM crops evaluation process, during 2020 and 2021, the ERA went through a reviewing process. Some important modifications were made, such as (i) the assessment of stacked GM crops with focus on the possible interactions between transgenes and the expression products, (ii) the strengthening of the ERA taking into account the transportability of data and conclusions from the Confined Field Trials (CFTs), (iii) the adoption of Familiarity and History of Safe Use (HOSU) concepts on the risk assessment of the expression products, (iv) the special considerations for the unintended effects of insertional sites, and (v) as a post commercial release of GM crops, the Insect Resistance Management Plan (IRMP) was reformulated. These novel approaches enhance the ERA; they make it more efficient by applying the science criteria and the accumulated experience and scientific bibliography on the topic.

Background: Widely targeted metabolomics was applied to estimate the differences in the metabolite profiles of maize seeds from 3 natural genotypic varieties and 4 genetically modified (GM) lines. Results: Pairwise comparison with their isogenic controls revealed 71, 121, 43 and 95 differentially accumulated metabolites (DAMs) in GM maize seeds of C0030.2.4, C0030.3.5, C0010.1.1 and C0010.3.1, respectively. KEGG pathway enrichment analysis showed that most of these DAMs participated in the biosynthesis of secondary metabolites and purine metabolism in GM maize C0030.2.4 and C0030.3.5, but participated in tryptophan metabolism and 2-oxocarboxylic acid metabolism in C0010.3.1 seeds and in metabolic pathways and the biosynthesis of secondary metabolites in C0010.1.1 seeds. The data also showed that the differences in metabolite accumulation, both total DAMs and co-DAMs, among the different natural genotypic varieties (418 DAMs and 39 co-DAMs) were greater than those caused by genetic modification (330 DAMs and 3 co-DAMs). Conclusions: None of the DAMs were identified as new or unintended, showing only changes in abundance in the studied maize seeds. The metabolite profile differences among the 3 non-GM lines were more notable than those among GM lines. Different genetic backgrounds affect metabolite profiling more than gene modification itself. [ABSTRACT FROM AUTHOR]

Over the past years, there has been increasing public criticism of international volunteering. Yet, the academic literature has so far given limited insight into the diversity of this complex and 'liquid' field. To fill this gap, this article develops a taxonomy of volunteering providers with different goals and behaviours. The value of this new taxonomy is illustrated by applying the analytical framework to 'orphanage tourism' in the Netherlands. The study highlights the differential impact of public criticism on orphanage tourism, with a catalysing effect on the trend of informalisation towards increasing prominence of smaller nonspecialist development‐oriented providers in this field. [ABSTRACT FROM AUTHOR]

Abstract Background Within the last decades, genome-editing techniques such as CRISPR/Cas, TALENs, Zinc-Finger Nucleases, Meganucleases, Oligonucleotide-Directed Mutagenesis and base editing have been developed enabling a precise modification of DNA sequences. Such techniques provide options for simple, time-saving and cost-effective applications compared to other breeding techniques and hence genome editing has already been promoted for a wide range of plant species. Although the application of genome-editing induces less unintended modifications (off-targets) in the genome compared to classical mutagenesis techniques, off-target effects are a prominent point of criticism as they are supposed to cause unintended effects, e.g. genomic instability or cell death. To address these aspects, this map aims to answer the following question: What is the available evidence for the range of applications of genome-editing as a new tool for plant trait modification and the potential occurrence of associated off-target effects? This primary question will be considered by two secondary questions: One aims to overview the market-oriented traits being modified by genome-editing in plants and the other explores the occurrence of off-target effects. Methods A literature search in nine bibliographic databases, Google Scholar, and 47 web pages of companies and governmental agencies was conducted using predefined and tested search strings in English language. Articles were screened on title/abstract and full text level for relevance based on pre-defined inclusion criteria. The relevant information of included studies were mapped using a pre-defined data extraction strategy. Besides a descriptive summary of the relevant literature, a spreadsheet containing all extracted data is provided. Results Altogether, 555 relevant articles from journals, company web pages and web pages of governmental agencies were identified containing 1328 studies/applications of genome-editing in model plants and agricultural crops in the period January 1996 to May 2018. Most of the studies were conducted in China followed by the USA. Genome-editing was already applied in 68 different plants. Although most of the studies were basic research, 99 different market-oriented applications were identified in 28 different crops leading to plants with improved food and feed quality, agronomic value like growth characteristics or increased yield, tolerance to biotic and abiotic stress, herbicide tolerance or industrial benefits. 252 studies explored off-target effects. Most of the studies were conducted using CRISPR/Cas. Several studies firstly investigated whether sites in the genome show similarity to the target sequence and secondly analyzed these potential off-target sites by sequencing. In around 3% of the analyzed potential off-target sites, unintended mutations were detected. Only a few studies conducted off-target analyses using unbiased detection methods (e.g. whole genome sequencing). No off-target effects that could be correlated to the genome-editing process were identified in these studies. Conclusions The rapid adoption in plant breeding was demonstrated by a considerable number of market oriented applications (crops and traits) described in publications worldwide. Studies investigating off-target effects are very heterogeneous in their structure and design. Therefore, an in-depth assessment regarding their weight of evidence is mandatory.

CRISPR/Cas enables a targeted modification of DNA sequences. Despite their ease and efficient use, one limitation is the potential occurrence of associated off-target effects. This systematic review aims to answer the following research question: Which factors affect the occurrence of off-target effects caused by the use of CRISPR/Cas in plants? Literature published until March 2019 was considered for this review. Articles were screened for relevance based on pre-defined inclusion criteria. Relevant studies were subject to critical appraisal. All studies included in the systematic review were synthesized in a narrative report, but studies rated as high and medium/high validity were reported separately from studies rated as low and medium/low or unclear validity. In addition, we ran a binary logistic regression analysis to verify five factors that may affect the occurrence of off-target effects: (1) Number of mismatches (2) Position of mismatches (3) GC-content of the targeting sequence (4) Altered nuclease variants (5) Delivery methods. In total, 180 relevant articles were included in this review containing 468 studies therein. Seventy nine percentage of these studies were rated as having high or medium/high validity. Within these studies, 6,416 potential off-target sequences were assessed for the occurrence of off-target effects. Results clearly indicate that an increased number of mismatches between the on-target and potential off-target sequence steeply decreases the likelihood of off-target effects. The observed rate of off-target effects decreased from 59% when there is one mismatch between the on-target and off-target sequences toward 0% when four or more mismatches exist. In addition, mismatch/es located within the first eight nucleotides proximal to the PAM significantly decreased the occurrence of off-target effects. There is no evidence that the GC-content significantly affects off-target effects. The database regarding the impact of the nuclease variant and the delivery method is very poor as the majority of studies applied the standard nuclease SpCas9 and the CRISPR/Cas system was stably delivered in the genome. Hence, a general significant impact of these two factors on the occurrence of off-target effects cannot be proved. This identified evidence gap needs to be filled by systematic studies exploring these individual factors in sufficient numbers.

Background: The Janani Suraksha Yojana (JSY) is the largest ever conditional cash transfer programme worldwide. It primarily aimed to reduce the maternal and child mortality by increasing the facility based delivery in India. Besides, the JSY has resulted in reduction of out-of-pocket expenditure for delivery care and increased antenatal care. Though studies have examined the direct outcome of JSY, limited studies have attempted to understand the unintended effects (indirect) of the programme. The aim of this study is to examine the effect of JSY on contraceptive use, initiation of breast feeding and postnatal check-up in India. Data & Methods: Data from the National Family Health Survey 4, 2015–16 was used in the analyses. A total of 148,746 institutional births in five years preceding the survey were analysed and the analyses were carried out for Low Performing States (LPS) and High Performing States (HPS). Descriptive statistics and the propensity score matching were used to understand the unintended effects of JSY. Results: In India, the use of contraception, early initiation of breastfeeding and postnatal check up was consistently higher among JSY beneficiaries compared to non-JSY beneficiaries. Among JSY beneficiaries, about 45% of the mothers breastfed their child within one hour compared to 42% of the JSY non-beneficiaries. The pattern was almost similar for postnatal check-up. The variations in contraceptive use, breastfeeding practice and postnatal check-up among JSY beneficiaries were higher in LPS states compared to HPS. For instance, in LPS, among JSY beneficiaries, about 58% mothers breastfed their child within one hour of delivery compared to 46% in HPS. Controlling for socio-economic covariates, the JSY beneficiaries in LPS were 12% more likely to use contraception, 8% were more likely to initiate the breast feeding within one hour of child delivery and 6% were more likely to get their postnatal check-up than their counterparts in HPS. Discussion: The unintended effects of JSY were strong and significant in the low performing states. The coverage of JSY should be further extended and the programme needs to be continued.

Unintended effects of genetically modified (GM) crops may pose safety issues. Omics techniques provide researchers with useful tools to assess such unintended effects. Proteomics and metabolomics analyses were performed for three GM maize varieties, 2A-7, CC-2, and 2A-7×CC-2 stacked transgenic maize, and the corresponding non-GM parent Zheng58. Proteomics revealed 120, 271 and 135 maize differentially expressed proteins (DEPs) in the 2A-7/Zheng58, CC-2/Zheng58 and 2A-7×CC-2/Zheng58 comparisons, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most DEPs participated in metabolic pathways and the biosynthesis of secondary metabolite. Metabolomics revealed 179, 135 and 131 differentially accumulated metabolites (DAMs) in the 2A-7/Zheng58, CC-2/Zheng58 and 2A-7×CC-2/Zheng58 comparisons, respectively. Based on KEGG enrichment analysis, most DAMs are involved in the biosynthesis of secondary metabolite and metabolic pathways. According to integrated proteomics and metabolomics analysis, the introduction of exogenous EPSPS did not affect the expression levels of six other enzymes or the abundance of seven metabolites involved in the shikimic acid pathway in CC-2 and 2A-7×CC-2 seeds. Six co-DEPs annotated by integrated proteomics and metabolomics pathway analysis were further analyzed by qRT-PCR. This study successfully employed integrated proteomic and metabolomic technology to assess unintended changes in maize varieties. The results suggest that GM and gene stacking do not cause significantly unintended effects. [ABSTRACT FROM AUTHOR]

This study examines unintended effects of revising Iran's accounting standards. These effects need to be surveyed purposefully and in a planned manner. Providing a comprehensive viewpoint of unintended effects leads to guide and cohere researches, develop more efficient accounting standards, and help decision-makers to decide with broader horizons. Based on theoretical foundations, standards objectives and interviewing with experts, unintended effects are divided into unrealized intended effects, subsequent indirect effects and prior effects. Then the areas of each of these effects collectively include financial reporting, capital markets, contracting, investing, and intellectual capital are identified. The researcher-made questionnaire (consisting of 3 sections and 26 questions) whose validity and reliability were confirmed was prepared based on the theoretical foundations and experts’ opinions. The statistical population of the study included faculty members and PhD students in accounting, auditors, financial managers of listed companies and financial experts. The number of members of the community is unclear, so based on the indicators of the χ² test of the prototype information (82 items) in the PASS software, the sample size is determined 183. The χ² test in SPSS was used as hypotheses testing method because the data was qualitative and in sequential scale. The difference between the observed and expected frequencies across all areas of unrealized intended, subsequent indirect and prior effects was significant, and the accumulations of frequencies were around agree/significant option. Therefore, the existence of unrealized intended effects rejected; the existence of subsequent indirect effects, the primary effects and importance of research in all measured areas were confirmed. [ABSTRACT FROM AUTHOR]

CRISPR/Cas enables a targeted modification of DNA sequences. Despite their ease and efficient use, one limitation is the potential occurrence of associated off-target effects. This systematic review aims to answer the following research question: Which factors affect the occurrence of off-target effects caused by the use of CRISPR/Cas in plants? Literature published until March 2019 was considered for this review. Articles were screened for relevance based on pre-defined inclusion criteria. Relevant studies were subject to critical appraisal. All studies included in the systematic review were synthesized in a narrative report, but studies rated as high and medium/high validity were reported separately from studies rated as low and medium/low or unclear validity. In addition, we ran a binary logistic regression analysis to verify five factors that may affect the occurrence of off-target effects: (1) Number of mismatches (2) Position of mismatches (3) GC-content of the targeting sequence (4) Altered nuclease variants (5) Delivery methods. In total, 180 relevant articles were included in this review containing 468 studies therein. Seventy nine percentage of these studies were rated as having high or medium/high validity. Within these studies, 6,416 potential off-target sequences were assessed for the occurrence of off-target effects. Results clearly indicate that an increased number of mismatches between the on-target and potential off-target sequence steeply decreases the likelihood of off-target effects. The observed rate of off-target effects decreased from 59% when there is one mismatch between the on-target and off-target sequences toward 0% when four or more mismatches exist. In addition, mismatch/es located within the first eight nucleotides proximal to the PAM significantly decreased the occurrence of off-target effects. There is no evidence that the GC-content significantly affects off-target effects. The database regarding the impact of the nuclease variant and the delivery method is very poor as the majority of studies applied the standard nuclease SpCas9 and the CRISPR/Cas system was stably delivered in the genome. Hence, a general significant impact of these two factors on the occurrence of off-target effects cannot be proved. This identified evidence gap needs to be filled by systematic studies exploring these individual factors in sufficient numbers. [ABSTRACT FROM AUTHOR]

American chestnut (Castanea dentata [Marsh.] Borkh.) was once the dominant hardwood species in Eastern North America before an exotic fungal pathogen, Cryphonectria parasitica (Murrill) Barr, functionally eliminated it across its range. One promising approach toward restoring American chestnut to natural forests is development of blight‐tolerant trees using genetic transformation. However, transformation and related processes can result in unexpected and unintended phenotypic changes, potentially altering ecological interactions. To assess unintended tritrophic impacts of transgenic American chestnut on plant–herbivore interactions, gypsy moth (Lymantria dispar L.) caterpillars were fed leaf disks excised from two transgenic events, Darling 54 and Darling 58, and four control American chestnut lines. Leaf disks were previously treated with an LD50 dose of either the species‐specific Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) or the generalist pathogen Bacillus thuringiensis subsp. kurstaki (Btk). Mortality was quantified and compared to water blank controls. Tree genotype had a strong effect on the efficacies of both pathogens. Larval mortality from Btk‐treated foliage from only one transgenic event, Darling 54, differed from its isogenic progenitor, Ellis 1, but was similar to an unrelated wild‐type American chestnut control. LdMNPV efficacy was unaffected by genetic transformation. Results suggest that although genetic modification of trees may affect interactions with other nontarget organisms, this may be due to insertion effects, and variation among different genotypes (whether transgenic or wild‐type) imparts a greater change in response than transgene presence. [ABSTRACT FROM AUTHOR]

This article pioneers new thinking on learning by organizations created by international environmental agreements, especially the boundaries within which learning can take place. It hypothesizes that there are ideological, institutional and technical boundaries to learning, which negatively impact the effectiveness of international environmental programming. This theory is rigorously tested by applying it to a group of new programmes, the forest-focused payment for environmental services programmes, which find their origin in the United Nations Framework Convention on Climate Change. The article systematically researches unintended effects of these programmes and clusters them into four categories. The uncovering of these unintended effects leads to the main research question: do international organizations actually succeed in adapting to these unintended effects? By combining three methods (a structured literature review, a systemic internal programme document analysis and expert interviews), the research finds that organizations struggle to adapt to these unintended effects. Whereas some of the limits to learning can be overcome by enhancing technical capacities, other limits, notably those that are induced by ideological thinking and institutional imperatives, are hard to overcome. [ABSTRACT FROM AUTHOR]

Poplar is an economically important forest tree used for multiple applications, including bioenergy production. Although genetic engineering allows a quick introduction of desirable traits, simultaneously, it may deliver unintended side effects. Herein, we compared the protein composition in leaves of microclonally propagated fast-growing hybrid clone of Populus deltoides × Populus nigra (Populus × euroamericana), genetically modified with a reporter (GUS) and selective (NPTII) traits, and its non-transgenic parental genotype. By two-dimensional gel electrophoresis, we revealed that 5.5% of 330 detected protein spots were differentially accumulated. The vast majority of them showed lower abundance in the transgenic line. These proteins were mainly involved in primary metabolism, energy production, and protein synthesis/homeostasis; notably, none of them was directly linked to neomycin phosphotransferase or β-glucuronidase activities. Some of the differentially accumulated proteins could be associated with stress response caused by Agrobacterium-mediated transformation. Furthermore, the lower abundance of two cytosolic glutamine synthase isoforms and accumulation of bark storage protein A in the transgenic line, plausibly indicated impaired nitrogen metabolism and storage. The insertion of a model genetic construct did not alter the neighboring genetic loci, and neither toxins nor allergens were differentially abundant. In essence, we detected no protein indicating considerable health or environmental hazard in the transgenic hybrid black poplar. [ABSTRACT FROM AUTHOR]

Breeding woody plants is a very time-consuming process, and genetic engineering tools have been used to shorten the juvenile phase. In addition, transgenic trees for commercial cultivation can also be used in classical breeding, but the segregation of transgenes in the progeny of perennial plants, as well as the possible appearance of unintended changes, have been poorly investigated. We studied the inheritance of the uidA gene in the progeny of field-grown transgenic pear trees for 7 years and the physical and physiological parameters of transgenic seeds. A total of 13 transgenic lines were analyzed, and the uidA gene segregated 1:1 in the progeny of 9 lines and 3:1 in the progeny of 4 lines, which is consistent with Mendelian inheritance for one and two transgene loci, respectively. Rare and random deviations from the Mendelian ratio were observed only for lines with one locus. Transgenic seeds’ mass, size, and shape varied slightly, despite significant fluctuations in weather conditions during cultivation. Expression of the uidA gene in the progeny was stable. Our study showed that the transgene inheritance in the progeny of pear trees under field conditions occurs according to Mendelian ratio, does not depend on the environment, and the seed vigor of transgenic seeds does not change.

Low nitrogen availability is one of the main limiting factors for plant growth and development, and high doses of N fertilizers are necessary to achieve high yields in agriculture. However, most N is not used by plants and pollutes the environment. This situation can be improved by enhancing the nitrogen use efficiency (NUE) in plants. NUE is a complex trait driven by multiple interactions between genetic and environmental factors, and its improvement requires a fundamental understanding of the key steps in plant N metabolism—uptake, assimilation, and remobilization. This review summarizes two decades of research into bioengineering modification of N metabolism to increase the biomass accumulation and yield in crops. The expression of structural and regulatory genes was most often altered using overexpression strategies, although RNAi and genome editing techniques were also used. Particular attention was paid to woody plants, which have great economic importance, play a crucial role in the ecosystems and have fundamental differences from herbaceous species. The review also considers the issue of unintended effects of transgenic plants with modified N metabolism, e.g., early flowering—a research topic which is currently receiving little attention. The future prospects of improving NUE in crops, essential for the development of sustainable agriculture, using various approaches and in the context of global climate change, are discussed.

The engineering of plants with enhanced tolerance to abiotic stresses typically involves complex multigene networks and may therefore have a greater potential to introduce unintended effects than the genetic modification for simple monogenic traits. For this reason, it is essential to study the unintended effects in transgenic plants engineered for stress tolerance. We selected drought- and salt-tolerant transgenic wheat overexpressing the transcription factor, GmDREB1, to investigate unintended pleiotropic effects using RNA-seq analysis. We compared the transcriptome alteration of transgenic plants with that of wild-type plants subjected to salt stress as a control. We found that GmDREB1 overexpression had a minimal impact on gene expression under normal conditions. GmDREB1 overexpression resulted in transcriptional reprogramming of the salt response, but many of the genes with differential expression are known to mitigate salt stress and contribute incrementally to the enhanced stress tolerance of transgenic wheat. GmDREB1 overexpression did not activate unintended gene networks with respect to gene expression in the roots of transgenic wheat. This work is important for establishing a method of detecting unintended effects of genetic engineering and the safety of such traits with the development of marketable transgenic crops in the near future.