Добірка наукової літератури з теми "Off-target assessment"

AbstractSix experiments were conducted in 2018 on field sites located in Arkansas, Indiana, Michigan, Nebraska, Ontario, and Wisconsin to evaluate the off-target movement (OTM) of dicamba under field-scale conditions. The highest estimated percentages of dicamba injury in non–dicamba-resistant (DR) soybean were 55%, 44%, 39%, 67%, 15%, and 44% injury for noncovered areas and 55%, 5%, 13%, 42%, 0%, and 41% injury for covered areas during dicamba application in Arkansas, Indiana, Michigan, Nebraska, Ontario, and Wisconsin, respectively. The level of injury generally decreased as the downwind distance increased under covered and noncovered areas at all sites. There was an estimated 10% injury in non-DR soybean at 113, 8, 11, 8, and 8 m; and estimated 1% injury at 293, 28, 71, 15, and 19 m from the edge of treated fields downwind when plants were not covered during dicamba application in Arkansas, Indiana, Michigan, Ontario, and Wisconsin, respectively. Assessment of filter-paper collectors placed from 4 to 137 m downwind from the edge of the sprayed area suggested the dicamba deposition reduced exponentially with distance. The greatest injury to non-DR soybean from dicamba OTM occurred at Nebraska and Arkansas (as far as 250 m). Non-DR soybean injury was greatest adjacent to the dicamba sprayed area, but injury decreased with no injury beyond 20 m downwind or in any other direction from the dicamba sprayed area in Indiana, Michigan, Ontario, and Wisconsin. The presence of soybean injury under covered and noncovered areas during the spray period for primary drift suggests that secondary movement of dicamba was evident at five sites. Additional research is needed to determine the exact forms of secondary movement of dicamba under different environmental conditions.

Abstract The CRISPR-Cas9 genome editing tool is used to study genomic variants and gene knockouts, and can be combined with transcriptomic analyses to measure the effects of such alterations on gene expression. But how can one be sure that differential gene expression is due to a successful intended edit and not to an off-target event, without performing an often resource-demanding genome-wide sequencing of the edited cell or strain? To address this question we developed CRISPRroots: CRISPR–Cas9-mediated edits with accompanying RNA-seq data assessed for on-target and off-target sites. Our method combines Cas9 and guide RNA binding properties, gene expression changes, and sequence variants between edited and non-edited cells to discover potential off-targets. Applied on seven public datasets, CRISPRroots identified critical off-target candidates that were overlooked in all of the corresponding previous studies. CRISPRroots is available via https://rth.dk/resources/crispr.

Assessment for potential adverse effects of plant genome editing logically focuses on the specific characteristics of the derived phenotype and its release environment. Genome-edited crops, depending on the editing objective, can be classified as either indistinguishable from crops developed through conventional plant breeding or as crops which are transgenic. Therefore, existing regulatory regimes and risk assessment procedures accommodate genome-edited crops. The ability for regulators and the public to accept a product focus in the evaluation of genome-edited crops will depend on research which clarifies the precision of the genome-editing process and evaluates unanticipated off-target edits from the process. Interpretation of genome-wide effects of genome editing should adhere to existing frameworks for comparative risk assessment where the nature and degree of effects are considered relative to a baseline of genome-wide mutations as found in crop varieties developed through conventional breeding methods. Research addressing current uncertainties regarding unintended changes from plant genome editing, and adopting procedures that clearly avoid the potential for gene drive initiation, will help to clarify anticipated public and regulatory questions regarding risk of crops derived through genome editing.

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious global health threat. Since no specific therapeutics are available, researchers around the world screened compounds to inhibit various molecular targets of SARS-CoV-2 including its main protease (Mpro) essential for viral replication. Due to the high urgency of these discovery efforts, off-target binding, which is one of the major reasons for drug-induced toxicity and safety-related drug attrition, was neglected. Here, we used molecular docking, toxicity profiling, and multiple molecular dynamics (MD) protocols to assess the selectivity of 33 reported non-covalent inhibitors of SARS-CoV-2 Mpro against eight proteases and 16 anti-targets. The panel of proteases included SARS-CoV Mpro, cathepsin G, caspase-3, ubiquitin carboxy-terminal hydrolase L1 (UCHL1), thrombin, factor Xa, chymase, and prostasin. Several of the assessed compounds presented considerable off-target binding towards the panel of proteases, as well as the selected anti-targets. Our results further suggest a high risk of off-target binding to chymase and cathepsin G. Thus, in future discovery projects, experimental selectivity assessment should be directed toward these proteases. A systematic selectivity assessment of SARS-CoV-2 Mpro inhibitors, as we report it, was not previously conducted.

Abstract A series of Cas9 variants have been developed to improve the editing fidelity or targeting range of CRISPR–Cas9. Here, we employ a high-throughput sequencing approach primer-extension-mediated sequencing to analyze the editing efficiency, specificity and protospacer adjacent motif (PAM) compatibility of a dozen of SpCas9 variants at multiple target sites in depth, and our findings validate the high fidelity or broad editing range of these SpCas9 variants. With regard to the PAM-flexible SpCas9 variants, we detect significantly increased levels of off-target activity and propose a trade-off between targeting range and editing specificity for them, especially for the near-PAM-less SpRY. Moreover, we use a deep learning model to verify the consistency and predictability of SpRY off-target sites. Furthermore, we combine high-fidelity SpCas9 variants with SpRY to generate three new SpCas9 variants with both high fidelity and broad editing range. Finally, we also find that the existing SpCas9 variants are not effective in suppressing genome instability elicited by CRISPR–Cas9 editing, raising an urgent issue to be addressed.

Squid (Loligo opalescens) were surveyed acoustically in an area off the Oregon coast using dual-beam and echo integrator techniques. The method developed is shown to be feasible for in situ estimation of target strength, distribution, and abundance of midwater squids. Average target strength was estimated both while drifting with a squid school and cruising over one. The values derived, −58.6 to −58.7 dB, are much lower than previous estimates, but more realistic in relation to the target strength of fishes. Schools judged to be fish or squid showed little difference in depth or size, but varied significantly in geographic distribution. Density estimates ranged from 9.9 t/km2 in a known spawning area to 0.93 t/km2 in an adjacent area.

Results of the assessment of by-catch in the specialized fishery of target crab species are presented. The studies covered three fishing areas: off Western Kamchatka (Kamchatka-Kuril and West Kamchatka sub- zones) and off the southeastern coast of Kamchatka (Petropavlovsk-Komandorskaya subzone). In addition to the target object, the catches included both non-target species of crabs and representatives of other groups of animals: fish and invertebrates. The by-catch of fish included representatives of several genera, the most common being Pacific cod (Gadus macrocephalus), Irish lords (Hemilepidothus sp.) and snailfishes (Careproctus sp.). Among invertebrate representatives in the by-catch, octopuses (Octopus sp.) most often prevailed by weight in the fishery of red king crab (Paralithodes camtschaticus) off Western Kamchatka and Tanner crab (Chionoecetes bairdi) off Eastern Kamchatka.

Human tissue transglutaminase (TG2) is a calcium-dependent multifunctional enzyme that natively catalyzes the post-translational modification of proteins, namely by the formation of isopeptide bonds between protein- or peptide-bound glutamine and lysine residues. This ubiquitously expressed enzyme plays important roles in cellular differentiation, extracellular matrix stabilization, and apoptosis, to name a few. However, its unregulated activity has been associated with many pathologies such as fibrosis, cancer, neurodegenerative disorders and celiac disease. Most of these disorders are associated with unregulated acyl-transferase activity. As such, the Keillor group has directed its efforts towards the development of TG2 inhibitors. Over the years, the Keillor group has synthesized large libraries of targeted covalent inhibitors against TG2. These compounds have undergone pharmacodynamic testing in order to examine their kinetic parameters of inhibition. Having gained knowledge of their enzyme kinetics, the logical next step was to consider their pharmacokinetic profiles. In the context of this thesis, we considered two important pharmacokinetic properties: membrane permeability and off-target reactivity. Firstly, we aimed to evaluate our inhibitors for their ability to permeate the cell membrane. In efforts to do so, we were able to adapt, optimize, and validate a parallel artificial membrane permeability assay (PAMPA) utilizing hexadecane as our artificial membrane. We were able to test a few of our own inhibitors and found that compounds NC9, VA4 and AA9 possess Log Pe values of -5.26 ± 0.01, -4.66 ± 0.04 and -6.5 ± 0.5 respectively. Secondly, we sought to investigate the susceptibility of our inhibitors to glutathione addition reactions under physiological conditions. We adapted and optimized a colorimetric assay using Ellman’s reagent (DTNB) and found that our inhibitors are minimally reactive with glutathione. The methods developed over the course of this work provide protocols that can be adopted for the characterization of future inhibitors in the Keillor group, along the process of developing TG2 inhibitors into drug candidates.

Clustered regularly interspaced short palindromic repeats (CRISPR) technologies allow for facile genomic modification in a site-specific manner. A key step in this process is the in-silico design of single guide RNAs (sgRNAs) to efficiently and specifically target a site of interest. To this end, it is necessary to enumerate all potential off-target sites within a given genome that could be inadvertently altered by nuclease-mediated cleavage. Off-target sites are quasi-complementary regions of the genome in which the specified sgRNA can bind, even without a perfect complementary nucleotides sequence. This problem is known as off-target sites enumeration and became common after discovery of CRISPR technology. To solve this problem, many in-silico solutions were proposed in the last years but, currently available software for this task are limited by computational efficiency, variant support, genetic annotation, assessment of the functional impact of potential off-target effects at population and individual level, and a user-friendly graphical interface designed to be usable by non-informatician without any programming knowledge. This thesis addresses all these topics by proposing two software to directly answer the off-target enumeration problem and perform all the related analysis. In details, the thesis proposes CRISPRitz, a tool designed and developed to compute fast and exhaustive searches on reference and alternative genome to enumerate all the possible off-target for a user-defined set of sgRNAs with specific thresholds of mismatches (non-complementary bps in RNA-DNA binding) and bulges (bubbles that alters the physical structure of RNA and DNA limiting the binding activity). The thesis also proposes CRISPRme, a tool developed starting from CRISPRitz, which answers the requests of professionals and technicians to implement a comprehensive and easy to use interface to perform off-target enumeration, analysis and assessment, with graphical reports, a graphical interface and the capability of performing real-time query on the resulting data to extract desired targets, with a focus on individual and personalized genome analysis.

Abstract This paper evaluates the potential hazards of food and feed derived from RNAi plants including: adverse changes of plant metabolism; mechanisms and potential for non-target gene silencing in humans and livestock, including gut microbiome; bioinformatics tools for predictionof off-target sequences of interfering RNA; the possible non-specific effects of dsRNA and siRNA in mammals; and the comparison of data requirements for safety assessment of food and feed from RNAi plants and from plants expressing recombinant proteins. It also discusses exposure and RNAi-specific risk assessment.

Abstract This paper evaluates the potential hazards of food and feed derived from RNAi plants including: adverse changes of plant metabolism; mechanisms and potential for non-target gene silencing in humans and livestock, including gut microbiome; bioinformatics tools for predictionof off-target sequences of interfering RNA; the possible non-specific effects of dsRNA and siRNA in mammals; and the comparison of data requirements for safety assessment of food and feed from RNAi plants and from plants expressing recombinant proteins. It also discusses exposure and RNAi-specific risk assessment.

AbstractThe development and regulatory approval of CAR-T cell therapies targeting B-lineage surface antigens (Maude et al. 2018), such as CD19 or CD22, represents a major milestone in cancer immunotherapy. This treatment results in the depletion of malignant and normal B cells and is associated with hypogammaglobulinaemia. These on-target, off-tumour toxicities may result in an increased risk of infection. Careful long-term follow-up assessment of patients receiving CAR-T cell therapy is important. Management of these on-target, off-tumour effects should be well coordinated between treatment and referring centres if the patient returns to local providers following therapy. Aims of this toxicity management:

Schools ordinarily support establishing or increasing target behaviors, for example, increasing the number of letter sounds mastered or the frequency of social initiations; however, supporting the reduction of target behaviors is also an important goal of behavior analytic practice in schools. Although numerous target behaviors may warrant functional assessment and subsequent reduction at the individual level (e.g., aggression, self-injurious behavior), this chapter focuses on describing the implementation of and research outcomes related to reductive interventions designed to help teachers decrease disruptive, inappropriate, off-task, or problem behavior in general education classrooms. Reductive interventions describe strategies that explicitly target reduced levels of a target behavior. These interventions may be implemented to address chronic problem behaviors that may have been unresponsive to other positive interventions. The chapter describes various reductive strategies that may be implemented at a Tier I level, such as time-out, think time, and structured recess.

<em>Abstract</em>.—Florida boasts an abundance of natural and artificial reefs that support a large and diverse recreational fishery off the Gulf of Mexico coast. Recent efforts to mitigate the effects of the <em>Deepwater Horizon </em>oil spill have increased the number of artificial reefs deployed off Florida’s Gulf Coast. Fisheries-dependent data are needed to assess whether artificial reef programs are meeting intended objectives and to understand changes in recreational angler behavior, which may influence catch per unit effort and biomass of landed fish. The objective of this study was to quantify the use of artificial reefs by recreational anglers targeting reef fishes in the Gulf of Mexico off the west coast of Florida. We utilized an existing survey designed to monitor recreational fishing effort by anglers that target reef fishes from private boats. Over a 20-month period, an estimated total of 776,026 (SD ±27,540) angler trips targeted reef fishes off the Gulf Coast of Florida, of which 46% utilized artificial reefs. Approximately two-thirds of all reef angling trips took place nearshore in state-managed waters, and 70% of trips that utilized artificial reefs occurred in this area. Regionally, the highest proportion of angler trips targeting reef-associated species on artificial reefs took place in the panhandle of Florida, where Red Snapper <em>Lutjanus campechanus </em>are most abundant. Seasonally, state and federal fishing regulations also had an apparent influence on fishing effort and artificial reef use by recreational anglers. The method of assessment we present here could be useful for monitoring future trends in recreational fishing effort with respect to artificial reefs.

In this study, we assessed the efficiency and off-target activity of the CRISPR/CAS complex with one of the selected guide RNAs using the CIRCLE-seq technology. The gene encoding the human chemokine receptor CCR5 was used as a target sequence for genome editing. The results of this experiment indicate the correct choice of the guide RNA and efficient work of the CRISPR- CAS ribonucleoprotein complex used. CIRCLE-seq technology has shown high sensitivity compared to bioinformatic methods for predicting off-target activity of CRISPR/CAS complexes. We plan to evaluate the efficiency and off-target activity of CRISPR/CAS ribonucleoprotein complexes with other guide RNAs by slightly adjusting the CIRCLE-seq-technology protocol in order to reduce nonspecific DNA breaks and increase the number of reliable reads.

A full scope Probabilistic Safety Assessment (PSA) was provided as an integral part of the safety case for the UK ABWR Generic Design Assessment (GDA) and this included a Level 3 PSA. The main objectives of the Level 3 PSA for GDA are to provide a demonstration of the compliance, for a single unit UK ABWR, with numerical risk targets defined in the UK Safety Assessment Principles and to support the ALARP assessment. This paper includes: • An overview of the methodology, PSA model development and illustration of some results. • A summary of the key assumptions made during the model development for the GDA phase of the project. Compliance with the numerical risk targets has been investigated through assessments against the individual off site risk from the facility (Target 7), facility dose bands (Target 8) and off site societal risk (Target 9). • Some conclusions of a peer review against the draft ASME/ANS standard for trial use (ASME/ANS RA-S-1.3, Feb 2016 for Level 3 Probabilistic Risk Assessment (PRA)), which was a key aspect of this study.

A fundamental principle of human motor behavior states that the accuracy of targeted movements relates reciprocally to their speed. This is quantified by Fitts’ Law, wherein movement time (MT) and index of difficulty (ID), the log2 ratio of target distance (A) to target height (H) has logarithmic linear relationship; MT = a+b·log2(2A/H) = a+b·ID. The slope, b (seconds/bits), measures targeting performance as the time spent at each difficulty level, expressed as bits of information to be processed by the neuromotor system [1, 2]. Fitts’ paradigm is a common measure of the kinematic performance of the upper limb, but has not been applied to its dynamic performance. Herein, we developed a dynamic speed-accuracy trade-off (DSAT) test of grip force modulation, which can be used both for assessment and training.

Abstract Environmental impact assessment is important when marine renewable energy device is installed. Fishermen concern the effect of device on local fish. To confirm the effect before and after installation of marine renewable energy device, we developed wireless monitoring system using an underwater fish eye camera. The camera system is composed of a dome-shaped fish eye lens, a container, and a float. Two thrusters are attached on the container to change the monitoring directions. In the current research, this system was developed to monitor underwater situation around device remotely and in real time. We tested to monitor a target and fish in a fish case at the site off Kamaishi city. The recorded video showed the target and fish. Effectiveness of this system was shown through the field test for real time monitoring around marine renewable energy device.

Assessment of any significant effects on the local marine environment when considering the installation of a marine renewable energy device is of the utmost importance. In particular, the effect of such device on fish is concerned by local fishermen. To confirm variation of fish before and after installing the device of marine renewable energy, we investigated effective monitoring system using an underwater fish-eye camera. In this paper, visibility of the fish-eye camera was tested off Kamaishi city, Iwate prefecture, Japan, which is a test site of marine renewable energy in Japan. Device of wave power generation is planning to install at this site in the future. We confirmed the visibility of the fish-eye camera using a fish-shaped target by changing the distance between the target and camera. The water depth and photon were simultaneously measured. From the result, the horizontal visibility was discussed, and then we made a plan to observe around wave power generator using this fish-eye camera.

Abstract Classic gas turbine design relies on the definition of a design point, and the subsequent assessment of the design on a range of off-design conditions. On the design point, both component sizing (e.g., in terms of physical dimensions or in terms of map scaling parameters) and a solution to the off-design governing equations are established. With this approach, it is however difficult to capture the contradicting requirements on the full operating envelope. Thus, practical design efforts rely on various multi-point design approaches. This paper introduces a simplified notation of such multi-point approaches via synthesis matching tables. It then summarizes two academic state-of-the-art multi-point design schemes using such tables in a comprehensible fashion. The target audience are students and engineers familiar with the basics of classic cycle design and analysis looking for a practical introduction to such multi-point design approaches. Application examples are given in terms of a simple turbojet and a typical geared turbofan as modeled in state-of-the-art academic cycle design and analysis efforts. The results of the classic design point approach are compared to those of multi-point approaches.

Starting with early 1960's a new approach has been followed by researchers and specialists in developing instructional applications. This new approach was related to the use, as an experiment, of the Natural Language Processing (NLP) in the development of next generation of instructional software. Soon, the experiment has became a reality and a necessity in the context that the quantity of information which had to be processed by students, regardless the domain or discipline, has increased considerably. One of the main goals chased constantly by the researchers and specialists in NLP was related to the improvement of the systems, methods, and techniques used for students' knowledge assessment using NLP facilities. A great opportunity to reach valuable results has arisen once the Intelligent Tutoring Systems (ITS) have been considered into the equation. Taking into consideration the ITS declared purposes to address instructional specific activities such as, teaching, learning, performance assessment and feedback generation/communication/analysis, a merge of the ITS and NLP took place and this merge was in the evident benefit of both, teachers and students. Of course, in all these changes a central role has been played by the progress related to the Information and Communication Technologies (ITC) and mainly by the development of few critical hardware and software components, such as, computers, mobile devices, operating systems for these devices and programming languages. This paper is presenting the author proposal of an automatic system for generating questions and performing the analysis of the students' answers, the system being encapsulated in an ITS using NLP and which is applicable to the Computers Programming and C language discipline. Also, the author will present briefly the algorithm used for the development of the proposed system, with the primary target to detect the incorrect answers based on off-topic/on-topic method.

Assessment of local ocean environment is significant when devices of marine renewable energy are installed at a demonstration site. A concern about how these devices affect the existence of fish is remained among local fishermen. To confirm variation of fish before and after installing the devices of marine renewable energy, we investigated fish using an underwater camera before installation as a main objective of this paper. First, fish-eye video camera was tested to monitor in a fish cage off Kamaishi city, Iwate prefecture, Japan. We aimed to observe the abundance of fish and to specify the species of fish. The fish-eye video camera is composed of a dome-shaped lens, a container, and a digital video equipped into the container. The recorded video showed outlines of fish, consequently it may be possible to know the abundance of fish. However, specifying the species of fish has a difficulty if we use fish-eye camera since the recorded image is unclear enough to identify correctly. In addition, we examined horizontal transparency of fish-eye camera using a fish-shaped target. Before recording by the video camera, vertical transparency was measured using a white plate. Then we recorded the images by varying the water depth and the distance between the camera and target. When the target was close to the camera, it can be displayed clearly, nevertheless the outline of the target was smeared with increasing the distances between them. Our measurement suggested that the horizontal transparency might be relating to the parameters of water depth and vertical transparency. The investigation was conducted under the one condition, thus we need to obtain further data to understand horizontal transparency qualitatively. Next time, we will conduct another test using additional underwater optical video camera, which is attached on the fish-eye video camera. The combination of these two types of video cameras may enable to observe the abundance of fish as well as to specify the species of fish.

This study evaluated, by time-domain simulations, the fatigue lives of several jacket support structures for 4 MW wind turbines distributed throughout an offshore wind farm off Taiwan’s west coast. An in-house RANS-based wind farm analysis tool, WiFa3D, has been developed to determine the effects of the wind turbine wake behaviour on the flow fields through wind farm clusters. To reduce computational cost, WiFa3D employs actuator disk models to simulate the body forces imposed on the flow field by the target wind turbines, where the actuator disk is defined by the swept region of the rotor in space, and a body force distribution representing the aerodynamic characteristics of the rotor is assigned within this virtual disk. Simulations were performed for a range of environmental conditions, which were then combined with preliminary site survey metocean data to produce a long-term statistical environment. The short-term environmental loads on the wind turbine rotors were calculated by an unsteady blade element momentum (BEM) model of the target 4 MW wind turbines. The fatigue assessment of the jacket support structure was then conducted by applying the Rainflow Counting scheme on the hot spot stresses variations, as read-out from Finite Element results, and by employing appropriate SN curves. The fatigue lives of several wind turbine support structures taken at various locations in the wind farm showed significant variations with the preliminary design condition that assumed a single wind turbine without wake disturbance from other units.

Introduction Autism spectrum disorder (ASD), complex neurodevelopmental condition with lifelong impacts, typically identified in early childhood. Despite the fact that 95% of all <5 years of age with developmental disabilities including ASD live in low- and middle-income countries, the prevalence of ASD in many these countries is unknown. Objectives and goals The study aimed to identify the prevalence and clinical characteristics of ASD and its comorbidities among 8-10 y old schoolchildren in Republic of Georgia. Material and Methods The study conducted in four steps: screening, sampling, diagnostic assessment, and quality control of best-estimate diagnosis with target population of 3rd grade students of five main cities (Tbilisi, Kutaisi, Batumi, Zugdidi, Telavi) of Georgia (N=22,553). To determine children at risk for ASD the Autism Spectrum Screening Questionnaire (ASSQ) was used completed by parents and teachers. Parents of children who screened positive were offered comprehensive assessment using standardized diagnostic procedures. Results and Conclusions 16654 (response rate 74%) parents were agreed to participate in the screening stage. Cut-off scores for 99-95 percentiles (top 1-5%) was defined. For the 1168 sampled screen-positive students 704 (60.3%) consented to participate in the diagnostic assessment, and 215 among them (30.5%) completed full assessment. The control group of 23 children (from non in top 10%) were fully assessed for ASD. The prevalence of ASD was estimated to be 1.34% (95%CI=2.15-4.41). From ASD group 77.5% of cases were undiagnosed to have any neurodevelopmental disorder. Comorbidity of Intellectual disability was in 22.5% of children with ASD (IQ<70), and 31% have IQ>111. The study defined need for the use of broader screening in primary healthcare and school settings to identify children with special needs and ensure their adequate services.

Because of the increase in usage of remote sensing tags to track the migration and movements of cetaceans, it has become increasingly important to assess the impact of such techniques on the target species. Between 1988 and 1997, 55 tags (41 satellite telemetry, 14 VHF or acoustic radio transmitter) were attached to 49 North Atlantic right whales (Eubalaena glacialis). All tags had implantable barbs or were fully implanted below the dermis. Right whales are photographically identifiable and the New England Aquarium curates the North Atlantic catalog, which currently numbers 374 individuals. The photo catalog has made it possible for tagged individuals to be tracked after the tag falls off the whale. Photo documentation during and after tagging provides an opportunity to monitor physiological effects from tags and healing responses to tags.

1.1 Macroeconomic summary Economic recovery has consistently outperformed the technical staff’s expectations following a steep decline in activity in the second quarter of 2020. At the same time, total and core inflation rates have fallen and remain at low levels, suggesting that a significant element of the reactivation of Colombia’s economy has been related to recovery in potential GDP. This would support the technical staff’s diagnosis of weak aggregate demand and ample excess capacity. The most recently available data on 2020 growth suggests a contraction in economic activity of 6.8%, lower than estimates from January’s Monetary Policy Report (-7.2%). High-frequency indicators suggest that economic performance was significantly more dynamic than expected in January, despite mobility restrictions and quarantine measures. This has also come amid declines in total and core inflation, the latter of which was below January projections if controlling for certain relative price changes. This suggests that the unexpected strength of recent growth contains elements of demand, and that excess capacity, while significant, could be lower than previously estimated. Nevertheless, uncertainty over the measurement of excess capacity continues to be unusually high and marked both by variations in the way different economic sectors and spending components have been affected by the pandemic, and by uneven price behavior. The size of excess capacity, and in particular the evolution of the pandemic in forthcoming quarters, constitute substantial risks to the macroeconomic forecast presented in this report. Despite the unexpected strength of the recovery, the technical staff continues to project ample excess capacity that is expected to remain on the forecast horizon, alongside core inflation that will likely remain below the target. Domestic demand remains below 2019 levels amid unusually significant uncertainty over the size of excess capacity in the economy. High national unemployment (14.6% for February 2021) reflects a loose labor market, while observed total and core inflation continue to be below 2%. Inflationary pressures from the exchange rate are expected to continue to be low, with relatively little pass-through on inflation. This would be compatible with a negative output gap. Excess productive capacity and the expectation of core inflation below the 3% target on the forecast horizon provide a basis for an expansive monetary policy posture. The technical staff’s assessment of certain shocks and their expected effects on the economy, as well as the presence of several sources of uncertainty and related assumptions about their potential macroeconomic impacts, remain a feature of this report. The coronavirus pandemic, in particular, continues to affect the public health environment, and the reopening of Colombia’s economy remains incomplete. The technical staff’s assessment is that the COVID-19 shock has affected both aggregate demand and supply, but that the impact on demand has been deeper and more persistent. Given this persistence, the central forecast accounts for a gradual tightening of the output gap in the absence of new waves of contagion, and as vaccination campaigns progress. The central forecast continues to include an expected increase of total and core inflation rates in the second quarter of 2021, alongside the lapse of the temporary price relief measures put in place in 2020. Additional COVID-19 outbreaks (of uncertain duration and intensity) represent a significant risk factor that could affect these projections. Additionally, the forecast continues to include an upward trend in sovereign risk premiums, reflected by higher levels of public debt that in the wake of the pandemic are likely to persist on the forecast horizon, even in the context of a fiscal adjustment. At the same time, the projection accounts for the shortterm effects on private domestic demand from a fiscal adjustment along the lines of the one currently being proposed by the national government. This would be compatible with a gradual recovery of private domestic demand in 2022. The size and characteristics of the fiscal adjustment that is ultimately implemented, as well as the corresponding market response, represent another source of forecast uncertainty. Newly available information offers evidence of the potential for significant changes to the macroeconomic scenario, though without altering the general diagnosis described above. The most recent data on inflation, growth, fiscal policy, and international financial conditions suggests a more dynamic economy than previously expected. However, a third wave of the pandemic has delayed the re-opening of Colombia’s economy and brought with it a deceleration in economic activity. Detailed descriptions of these considerations and subsequent changes to the macroeconomic forecast are presented below. The expected annual decline in GDP (-0.3%) in the first quarter of 2021 appears to have been less pronounced than projected in January (-4.8%). Partial closures in January to address a second wave of COVID-19 appear to have had a less significant negative impact on the economy than previously estimated. This is reflected in figures related to mobility, energy demand, industry and retail sales, foreign trade, commercial transactions from selected banks, and the national statistics agency’s (DANE) economic tracking indicator (ISE). Output is now expected to have declined annually in the first quarter by 0.3%. Private consumption likely continued to recover, registering levels somewhat above those from the previous year, while public consumption likely increased significantly. While a recovery in investment in both housing and in other buildings and structures is expected, overall investment levels in this case likely continued to be low, and gross fixed capital formation is expected to continue to show significant annual declines. Imports likely recovered to again outpace exports, though both are expected to register significant annual declines. Economic activity that outpaced projections, an increase in oil prices and other export products, and an expected increase in public spending this year account for the upward revision to the 2021 growth forecast (from 4.6% with a range between 2% and 6% in January, to 6.0% with a range between 3% and 7% in April). As a result, the output gap is expected to be smaller and to tighten more rapidly than projected in the previous report, though it is still expected to remain in negative territory on the forecast horizon. Wide forecast intervals reflect the fact that the future evolution of the COVID-19 pandemic remains a significant source of uncertainty on these projections. The delay in the recovery of economic activity as a result of the resurgence of COVID-19 in the first quarter appears to have been less significant than projected in the January report. The central forecast scenario expects this improved performance to continue in 2021 alongside increased consumer and business confidence. Low real interest rates and an active credit supply would also support this dynamic, and the overall conditions would be expected to spur a recovery in consumption and investment. Increased growth in public spending and public works based on the national government’s spending plan (Plan Financiero del Gobierno) are other factors to consider. Additionally, an expected recovery in global demand and higher projected prices for oil and coffee would further contribute to improved external revenues and would favor investment, in particular in the oil sector. Given the above, the technical staff’s 2021 growth forecast has been revised upward from 4.6% in January (range from 2% to 6%) to 6.0% in April (range from 3% to 7%). These projections account for the potential for the third wave of COVID-19 to have a larger and more persistent effect on the economy than the previous wave, while also supposing that there will not be any additional significant waves of the pandemic and that mobility restrictions will be relaxed as a result. Economic growth in 2022 is expected to be 3%, with a range between 1% and 5%. This figure would be lower than projected in the January report (3.6% with a range between 2% and 6%), due to a higher base of comparison given the upward revision to expected GDP in 2021. This forecast also takes into account the likely effects on private demand of a fiscal adjustment of the size currently being proposed by the national government, and which would come into effect in 2022. Excess in productive capacity is now expected to be lower than estimated in January but continues to be significant and affected by high levels of uncertainty, as reflected in the wide forecast intervals. The possibility of new waves of the virus (of uncertain intensity and duration) represents a significant downward risk to projected GDP growth, and is signaled by the lower limits of the ranges provided in this report. Inflation (1.51%) and inflation excluding food and regulated items (0.94%) declined in March compared to December, continuing below the 3% target. The decline in inflation in this period was below projections, explained in large part by unanticipated increases in the costs of certain foods (3.92%) and regulated items (1.52%). An increase in international food and shipping prices, increased foreign demand for beef, and specific upward pressures on perishable food supplies appear to explain a lower-than-expected deceleration in the consumer price index (CPI) for foods. An unexpected increase in regulated items prices came amid unanticipated increases in international fuel prices, on some utilities rates, and for regulated education prices. The decline in annual inflation excluding food and regulated items between December and March was in line with projections from January, though this included downward pressure from a significant reduction in telecommunications rates due to the imminent entry of a new operator. When controlling for the effects of this relative price change, inflation excluding food and regulated items exceeds levels forecast in the previous report. Within this indicator of core inflation, the CPI for goods (1.05%) accelerated due to a reversion of the effects of the VAT-free day in November, which was largely accounted for in February, and possibly by the transmission of a recent depreciation of the peso on domestic prices for certain items (electric and household appliances). For their part, services prices decelerated and showed the lowest rate of annual growth (0.89%) among the large consumer baskets in the CPI. Within the services basket, the annual change in rental prices continued to decline, while those services that continue to experience the most significant restrictions on returning to normal operations (tourism, cinemas, nightlife, etc.) continued to register significant price declines. As previously mentioned, telephone rates also fell significantly due to increased competition in the market. Total inflation is expected to continue to be affected by ample excesses in productive capacity for the remainder of 2021 and 2022, though less so than projected in January. As a result, convergence to the inflation target is now expected to be somewhat faster than estimated in the previous report, assuming the absence of significant additional outbreaks of COVID-19. The technical staff’s year-end inflation projections for 2021 and 2022 have increased, suggesting figures around 3% due largely to variation in food and regulated items prices. The projection for inflation excluding food and regulated items also increased, but remains below 3%. Price relief measures on indirect taxes implemented in 2020 are expected to lapse in the second quarter of 2021, generating a one-off effect on prices and temporarily affecting inflation excluding food and regulated items. However, indexation to low levels of past inflation, weak demand, and ample excess productive capacity are expected to keep core inflation below the target, near 2.3% at the end of 2021 (previously 2.1%). The reversion in 2021 of the effects of some price relief measures on utility rates from 2020 should lead to an increase in the CPI for regulated items in the second half of this year. Annual price changes are now expected to be higher than estimated in the January report due to an increased expected path for fuel prices and unanticipated increases in regulated education prices. The projection for the CPI for foods has increased compared to the previous report, taking into account certain factors that were not anticipated in January (a less favorable agricultural cycle, increased pressure from international prices, and transport costs). Given the above, year-end annual inflation for 2021 and 2022 is now expected to be 3% and 2.8%, respectively, which would be above projections from January (2.3% and 2,7%). For its part, expected inflation based on analyst surveys suggests year-end inflation in 2021 and 2022 of 2.8% and 3.1%, respectively. There remains significant uncertainty surrounding the inflation forecasts included in this report due to several factors: 1) the evolution of the pandemic; 2) the difficulty in evaluating the size and persistence of excess productive capacity; 3) the timing and manner in which price relief measures will lapse; and 4) the future behavior of food prices. Projected 2021 growth in foreign demand (4.4% to 5.2%) and the supposed average oil price (USD 53 to USD 61 per Brent benchmark barrel) were both revised upward. An increase in long-term international interest rates has been reflected in a depreciation of the peso and could result in relatively tighter external financial conditions for emerging market economies, including Colombia. Average growth among Colombia’s trade partners was greater than expected in the fourth quarter of 2020. This, together with a sizable fiscal stimulus approved in the United States and the onset of a massive global vaccination campaign, largely explains the projected increase in foreign demand growth in 2021. The resilience of the goods market in the face of global crisis and an expected normalization in international trade are additional factors. These considerations and the expected continuation of a gradual reduction of mobility restrictions abroad suggest that Colombia’s trade partners could grow on average by 5.2% in 2021 and around 3.4% in 2022. The improved prospects for global economic growth have led to an increase in current and expected oil prices. Production interruptions due to a heavy winter, reduced inventories, and increased supply restrictions instituted by producing countries have also contributed to the increase. Meanwhile, market forecasts and recent Federal Reserve pronouncements suggest that the benchmark interest rate in the U.S. will remain stable for the next two years. Nevertheless, a significant increase in public spending in the country has fostered expectations for greater growth and inflation, as well as increased uncertainty over the moment in which a normalization of monetary policy might begin. This has been reflected in an increase in long-term interest rates. In this context, emerging market economies in the region, including Colombia, have registered increases in sovereign risk premiums and long-term domestic interest rates, and a depreciation of local currencies against the dollar. Recent outbreaks of COVID-19 in several of these economies; limits on vaccine supply and the slow pace of immunization campaigns in some countries; a significant increase in public debt; and tensions between the United States and China, among other factors, all add to a high level of uncertainty surrounding interest rate spreads, external financing conditions, and the future performance of risk premiums. The impact that this environment could have on the exchange rate and on domestic financing conditions represent risks to the macroeconomic and monetary policy forecasts. Domestic financial conditions continue to favor recovery in economic activity. The transmission of reductions to the policy interest rate on credit rates has been significant. The banking portfolio continues to recover amid circumstances that have affected both the supply and demand for loans, and in which some credit risks have materialized. Preferential and ordinary commercial interest rates have fallen to a similar degree as the benchmark interest rate. As is generally the case, this transmission has come at a slower pace for consumer credit rates, and has been further delayed in the case of mortgage rates. Commercial credit levels stabilized above pre-pandemic levels in March, following an increase resulting from significant liquidity requirements for businesses in the second quarter of 2020. The consumer credit portfolio continued to recover and has now surpassed February 2020 levels, though overall growth in the portfolio remains low. At the same time, portfolio projections and default indicators have increased, and credit establishment earnings have come down. Despite this, credit disbursements continue to recover and solvency indicators remain well above regulatory minimums. 1.2 Monetary policy decision In its meetings in March and April the BDBR left the benchmark interest rate unchanged at 1.75%.