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International headlines often make mention of side effects of international cooperation, ranging from aid-fuelled corruption to the negative side effects of volunteer tourism. The OECD Development Assistance Committee, an international forum of many of the largest providers of aid, prescribes that evaluators should consider if an intervention has unintended effects. Yet the little that is known suggests that few evaluations of international cooperation projects systematically assess their unintended effects. To address this gap in assessing unintended effects, this study develops an operational typology of 10 types of unintended effects of international cooperation that have emerged in the literature and applies this to all 644 evaluations of the Netherlands’ development cooperation between 2000 and 2020 using structured text mining with manual verification. The results show that approximately 1 in 6 evaluations carefully considered unintended effects and identified 177 different ones. With the exception of 5, these could be classified in 9 of the 10 typologies, indicating that this typology can guide international development cooperation to systematically consider and assess its unintended effects. International development planners, researchers and evaluators are recommended to henceforth make use of and improve this operational typology.

Multigene cotransformation has been widely used in the study of genetic improvement in crops and trees. However, little is known about the unintended effects and causes of multigene cotransformation in poplars. To gain insight into the unintended effects of T-DNA integration during multigene cotransformation in field stands, here, three lines (A1–A3) of Populus × euramericana cv. Neva (PEN) carrying Cry1Ac-Cry3A-BADH genes and three lines (B1–B3) of PEN carrying Cry1Ac-Cry3A-NTHK1 genes were used as research objects, with non-transgenic PEN as the control. Experimental stands were established at three common gardens in three locations and next generation sequencing (NGS) was used to identify the insertion sites of exogenous genes in six transgenic lines. We compared the growth data of the transgenic and control lines for four consecutive years. The results demonstrated that the tree height and diameter at breast height (DBH) of transgenic lines were significantly lower than those of the control, and the adaptability of transgenic lines in different locations varied significantly. The genotype and the experimental environment showed an interaction effect. A total of seven insertion sites were detected in the six transgenic lines, with B3 having a double-site insertion and the other lines having single copies. There are four insertion sites in the gene region and three insertion sites in the intergenic region. Analysis of the bases near the insertion sites showed that AT content was higher than the average chromosome content in four of the seven insertion sites within 1000 bp. Transcriptome analysis suggested that the differential expression of genes related to plant hormone transduction and lignin synthesis might be responsible for the slow development of plant height and DBH in transgenic lines. This study provides an integrated analysis of the unintended effects of transgenic poplar, which will benefit the safety assessment and reasonable application of genetically modified trees.

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.

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.

Tandem mass tag (TMT) quantitative proteomic and flavonoid-targeted metabolomic analyses were applied to evaluate the unintended effects of five herbicide-resistant soybean varieties, in addition to three natural genotypic soybean varieties. A total of 65, 29, 56, 38, and 26 differentially expressed proteins (DEPs) were identified in ZLD6010, FD3003, JY2812, ZLD8001, and ZLD2426, respectively, compared with ZH13. Twenty-four and 16 DEPs were identified in ZLD2426 compared with JD12 and KS1, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that most of the DEPs were involved in ribosome, protein processing in the endoplasmic reticulum, and tropane, piperidine, and pyridine alkaloid biosynthesis. Proteomic analysis of the studied soybean seeds revealed no significant changes in herbicide-resistant soybean varieties compared with natural genotypic soybean varieties. Flavonoid-targeted metabolomics analysis detected and quantified 12 flavonoids. Daidzein, genistein/apigenin, taxifolin, and luteolin contents in the herbicide-resistant soybean variety seeds were significantly greater than those in the natural genotypic soybean variety seeds. Their contents in the seeds of three natural genotypic soybean varieties also significantly differed according to pairwise reciprocal comparisons. The introduction of 3-phosphoshikimate 1-carboxyvinyltransferase (EPSPS) might affect flavonoid accumulation of herbicide-resistant soybean varieties. The genetic background of soybean also influences its flavonoid metabolomic profile.

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.

Like most strategic communication efforts, advertising produces both intended and unintended effects. However, there has been little systematic effort to synthesizing the unintended effects of advertising. This paper attempt to fill the gap in the literature. A thematic review was conducted to review the dimensions, types, and theories concerning the unintended effects of advertising. Variations of unintended effects in valence, levels of analysis, time lapse, content specificity, and audience types were discerned, on the basis of which a typology of nine unintended effects was proposed, including confusion, materialism, idealization, stereotypes, boomerang, violence, creativity, job performance and economic growth. The implications and directions for future research were discussed. It is hoped that the conceptual dimensions and types of unintended effects presented in this paper will serve as an evolving framework for endeavors to enhancing the theory and practice of advertising.

Mobile health (mHealth) interventions can produce both intended and unintended effects. Examining these unintended effects helps create a more complete and objective understanding of mHealth interventions and can reduce potential harm to participants. Existing studies on the unintended effects, which were published several years ago, tend to have either a general focus on health IT or a specific focus on health care providers, thereby excluding other key stakeholders (eg, patients and community health workers). Additionally, these studies did not systematically outline the causes of the unintended effects or strategies for their prevention. To address this gap, this systematic review, guided by the ecological framework, aims to systematically identify the unintended effects of mHealth interventions, create a typology for them, investigate the reasons for their occurrence, describe how they were detected, and propose ways to prevent or lessen them. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was performed to examine the unintended effects of health interventions that use mobile technology. A total of 15 papers were included in the review. An ecological typology of mHealth intervention unintended effects (mHUE) was developed, which includes 26 distinct effects (eg, silencing and boomerang). The majority of these unintended effects (n=20) occur at the individual level and span physical or behavioral (n=7), psychological (n=8), cognitive (n=4), and financial (n=1) domains. Three effects occur at the interpersonal level and another 3 at the community or institutional level. Most of the identified effects (n=22) were negative. Potential causes for these effects include the improper use of mHealth technology, poorly designed interventions, the application of unsuitable intervention mechanisms, or a misalignment between the intended outcomes and the sociocultural context. Strategies and recommendations (eg, considering the context such as cultural norms) were suggested to help prevent or reduce the unintended effects. The unintended effects detailed in the mHUE typology were heterogenous and context-dependent. These effects can influence individuals across different domains and also affect unintended people within the ecological system. As most of the unintended effects are negative, if they are not monitored, mHealth interventions designed to empower participants could paradoxically disempower them (eg, decreasing self-efficacy for disease management, undermining patient control, and engagement). The mHUE typology, together with the proposed recommendations and strategies, can be used as a guide to enhance the planning, design, implementation, and postimplementation evaluation on mHealth interventions. Future research should concentrate on understanding the specific mechanisms behind these unintended effects.

Key message RNAi-based genetically modified maize resistant to Monolepta hieroglyphica (Motschulsky) was demonstrated with negligible transcriptome and metabolome alterations compared to its unmodified equivalent. As one of the most prevalent insect pests afflicting various crops, Monolepta hieroglyphica (Motschulsky) causes severe loss of agricultural and economic productivity for many years in China. In an effort to reduce damages, in this study, an RNA interference (RNAi)-based genetically modified (GM) maize was developed. It was engineered to produce MhSnf7 double-stranded RNAs (dsRNAs), which can suppress the Snf7 gene expression and then lead M. hieroglyphica to death . Field trail analysis confirmed the robustly insecticidal ability of the MhSnf7 GM maize to resist damages by M. hieroglyphica . RNA sequencing analysis identified that only one gene was differentially expressed in the MhSnf7 GM maize compared to non-GM maize, indicating that the transcriptome in MhSnf7 GM maize is principally unaffected by the introduction of the MhSnf7 dsRNA expression vector. Likewise, metabolomics analysis identified that only 8 out of 5787 metabolites were significantly changed. Hence, the integration of transcriptomics and metabolomics demonstrates that there are negligible differences between MhSnf7 GM maize and its unmodified equivalent. This study not only presents a comprehensive assessment of cellular alteration in terms of gene transcription and metabolite abundance in RNAi-based GM maize, but also could be used as a reference for evaluating the unintended effect of GM crops.

Background Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials. Methods Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies. Results Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)). Conclusions Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events.