Although geogenic Arsenic (As) contamination is well-recognized in northern Chile, it is not restricted to this part of the country, as the geological conditions favoring As release to the human environment exist across the country as well, although not at the same level, based on comparatively fewer studies in central and southern Chile. The present work provides a critical evaluation of As sources, pathways, and controls with reports and case studies from across the country based on an exhaustive bibliographic review of its reported geogenic sources and processes that affect its occurrence, systematization, and critical revision of this information. Arc magmatism and associated geothermal activities, identified as the primary As sources, are present across the Chilean Andes, except for the Pampean Flat Slab and Patagonian Volcanic Gap. Metal sulfide ore zones, extending from the country’s far north to the south-central part, are the second most important geogenic As source. While natural leaching of As-rich mineral deposits contaminates the water in contact, associated mining, and metallurgical activities result in additional As release into the human environment through mining waste and tailings. Moreover, crustal thickness has been suggested as a principal controlling factor for As release, whose southward decrease has been correlated with lower As values. However, in Chile, these studies have been limited to the Antofagasta Region. Two reviews2 of the articles on As health effects published between 1949 and 2018 in peer-reviewed journals show that the problem is aggravating even in this focused region despite more than half a century of efforts towards mitigation of human exposure to As  have been reported from Chile and Mexico3 updated their earlier review4, with most of the coauthors of the previous work  followed by saline  and thermal water (26 mg/L). They also observed this metalloid's natural presence in some volcanic rocks and sediments in the Arica and Parinacota, and Tarapacá administrative regions, including marine sediments. Moreover, elevated As concentration is reported in saline precipitates of the Atacama Desert (1420 mg/kg14), sinter deposits of El Tatio (21 wt%15) and Puchuldiza  geothermal fields, evaporites of the Altiplano-Puna plateau17, high sulphidation epithermal deposits, viz. El Indio18, river sediments, viz. the Elqui River (55–485 ppm As21).Within the distinct water types present in Chile, Tapia et al.22 reported As occurrence  in thermal waters from 423 geothermal fields, most of them associated with present-day volcanic activity. When mixed with the ground or surface water, these As-rich thermal waters contaminate these water resources23. An example of high As concentration (up to 50 mg/L25) in thermal waters in Chile is from El Tatio Geysers, which is the principal source of As in the Loa River27, a major surface water resource in the Atacama Desert, a continuous strip for nearly 1600 km along the narrow coast of the northern third of Chile, spanning over five administrative regions , from near Arica (18° 24′ S) southward to near La Serena (29° 55′ S)28.A study encompassing 15 Latin American countries by Morales-Simfors et al.29 have studied the link between elevated As concentrations in the Altiplano-Puna region of Chile, consisting of its northernmost regions, with Mio-Pliocene to Quaternary volcanic activity, high crustal thicknesses, and geological structures. These authors hypothesized volcanism as an important As source and the thick continental crust a large As reservoir that can be leached by the thermal fluids upwelling through regional fault systems, leading to As concentration in the fractures. They further proposed that hydrological processes transport dissolved As to lower elevation regions through ground and surface water, where it is diluted in As in the absence of evapoconcentration prevalent in the highlands.Tapia et al.11 attributed decreasing values of As concentration towards southern Chile to dilution because of increased precipitation and the absence of As-rich evaporites, brines, and saline water present in northern Chile30. In another work, Tapia et al.12 attributed this trend to decreased shortening of the Andes in southern Chile, as related lower crustal thickness induces lower crustal contamination, acting as an As-poor provenance for the sediments and surface water. On the contrary, they reported a good correlation between crustal thickness and As concentrations in surface water and fluvial sediments in northern Chile, where crustal thickness in much higher (~ 75 km below the Altiplano region31) than that along the southern Andes (< 40 km31).Moreover, Tapia et al.36, has been chosen to identify the naturally contaminated zones for being one of the most ubiquitous toxic elements present in the near-surface environment and exposed to humans through air, water, soil, and food chain37. On the other hand, groundwater As is selected in particular for the aforementioned project because of its high concentration present in a more toxic form, inorganic trivalent arsenite [As(III)]40.Human exposure to As from geogenic and anthropic sources through water, sediments and soil is a significant health issue in Latin America and Chile see "", and th41 found bottled mineral water from cold springs in central and southern Chile contaminated, with up to 18.97 µg/L As and 3 of 10 popular brands having As concentration above the Chilean legal permissible value of 10 µg/L. This shows how supposedly pure waters are naturally contaminated, underscoring the need for a countrywide in-depth study to identify the As contaminated areas and decipher associated geological conditions. A recent study by Tapia et al.12 is a step forward in this regard.Following decades of geological, geochemical, and epidemiological studies related to As contamination, northern Chile was identified as an As endemic; however, that does not imply that other parts of the country are uncontaminated. For example, Daniele et al.42, which considers two additional steps besides four basic steps in the conventional scientific literature review method, viz. Search , Appraisal , Synthesis (through data extraction and categorization), and Analysis (discuss the results and arrive at conclusions), known as SALSA43. The two additional steps in the modified method of Mengist et al.42 are defining a Protocol , Scopus, Science Direct, Springer, Google Scholar, PubMed, and Research Gate. These databases were searched for the "Topic" that includes "Title" and "Abstract" using the following combinations: "Arsenic" AND "Chile" AND "water", "Arsenic" AND "Chile" AND "soil", and "Arsenic" AND "Chile" AND "sediment". For example, WoS Core Collection provided 261, 70, and 49 results for the combinations above, respectively. Many of the results were common for the aforementioned search combinations. Articles published between 2000 and 2023 were considered in this search. Since water quality standards40 recommendations; prevalence data presented; publications between 2000 and 2023; papers written in English or Spanish . Exclusion criteria: any other metal contamination; only qualitative information; methodology nor presented; methodology for water not as per WHO40 recommendations; publication before 2010. Of the total 284 articles and reports, 69 were excluded for the aforementioned exclusion criteria or repetitive information.The following inclusion and exclusion criteria were used. Inclusion criteria: presence of As in water, soil, and/or sediment; As concentration reported; absolute, average value or range of As concentration presented; analytical method used for water as per WHO24. Data from this report were used in a peer reviewed publication in 201125.Although we have used aforementioned peer reviewed scientific publications for the review work on As data in water, sediments and soil, some government decrees, parliamentary bills, resolutions, reports, or other documents by government agencies, reports by environmental organizations, and news reports in Spanish have been cited while referring to the government initiatives or the lack of it towards mitigation of environmental issues related As or other metal-metalloid contamination of water and soil, e.g., in the context of sacrifice or saturated zones see "". Such d4. That is evident from the signs of As ingestion in the mummies of the Chinchorro people living between Ilo in southern Peru and Antofagasta in northern Chile . Apata et al.48 evaluated whether adverse effects of As on human health, viz. inducing miscarriages, acted as a natural selection pressure that made the Chinchorro population, settled in the Quebrada Camarones , As problem has affected the region since the Precolumbian Era52. However, a significant reduction in exposure followed the installation of an As removal plant in 1970, which provided a unique opportunity to study latency effects of exposure to As, carried out by Smith et al.53 with mortality data up to 40 years after exposure reduction. These authors concluded that lung, bladder, and kidney cancer mortality due to As exposure have very long latencies, with increased risks manifesting 40 years after exposure reduction; and suggested that As in drinking water may involve one of the most prolonged cancer latencies for a human carcinogen.The growing population due to the boom in the mining sector in the mid-twentieth century of the city of Antofagasta Fig.  faced ch1. During the last decade, some of the studies highlighted the importance of the timing (age of the person) of As exposure, which can cause severe health issues with significantly higher risk among those exposed to As early in life56. Another analysis reported a ten-fold increase in the risk of As-associated lung diseases among women exposed to high levels of As in the uterus57. Some other studies found that early-life exposure, even at a relatively low dose, increases the risk of As-induced mortality from pulmonary tuberculosis, respiratory problems, and reduced lung function in adults and children61. Moreover, lifetime and cross-sectional analyses from the Antofagasta Region of Chile  revealed the high risk associated with type 2 diabetes (T2D) hypertension64. Different studies have described As causing lung, bladder, kidney, and laryngeal cancer, particularly in those patients exposed to As since their birth in the Antofagasta Region69. The mortality studies conducted in the same area observed a consistent association with As intake for bladder, laryngeal, and liver cancer among young adults born in Antofagasta, Chile70. Also reported were medical conditions like As methylation, metabolomics, genetic polymorphism, and obesity through drinking water, food chain, and tobacco smoking69. These findings suggest that interventions targeting early-life As exposure and controlling life lifestyle factors could significantly reduce long-term mortality and morbidity. Khan et al.1 have reviewed the effects of early life As exposure on human health, biomarkers, and genetic susceptibility in Latin American countries.Several new scientific studies from As-endemic Antofagasta Region Fig.  in Chile65 found marked increased mortality from many cancers and other diseases between 1950 and 2000 in the Antofagasta Region. Later, Smith et al.53 presented Poisson regression rate ratios (RRs) for lung, bladder, and kidney cancer and acute myocardial infarction mortality for the same region in comparison with the rest of Chile from 2001 to 2010. They found that lung and bladder mortality were greatly elevated , together with kidney cancer mortality . They further compared RRs from the Antofagasta Region with the Valparaiso Region  at the Quintero-Puchuncaví Bay was justified, based on the appeals to patriotic feelings, urging the people to accept "some sacrifices" for the country's progress. On July 17th, 1957, the editorial of the Chilean Newspaper El Mercurio de Valparaíso wrote, "People must approach this problem with patriotism, and they must accept some sacrifices; otherwise, establishing a smelting plant would not be possible in any place in the country. The industrialized nations have accepted these sacrifices. It is the price of progress. Rain is indispensable for agriculture, but when it rains, someone must get wet" (translated from Spanish). The official recognition of this contaminated zone is in terms of the declaration of VIC as a "saturated zone" through a decree78. In his annual message of 21 May of 2012, erstwhile Chilean President Sebastián Piñera referred to this situation by saying that "… the environmental and health tragedies of Ventanas, Huasco, Coronel and Mussels speak better than a thousand words. Chile does not deserve this"79. In a significant move, Chile's state-owned and the world's largest copper producer Codelco ; is much higher than reported median As concentrations in urban soils of Arica , Zinc (Zn), Antimony (Sb), and Iron (Fe) at La Greda were higher than two large urban areas, namely, Venice in Italy88 and Belgrade in Serbia89.Rueda-Holgado et al.95 by environmental activists, researchers and the general public or "saturated zone"78 by the government, there are potential naturally contaminated zones in the country, which are saturated but unrecognized—considering the extent of metallogenic belts across the country and the presence of associated mining and mineral processing industries that accelerates and augments natural As-release and dissemination into human environments.Although VIC is recognized as a "sacrifice zone"97. Moreover, high rates of erosion due to rapid uplift of the arc zones and subsequent transport of the eroded sediments to the downstream basins lead to the presence of As-bearing minerals in arc derived sediments in the aquifer matrix97. The reported As concentrations in various lithologies worldwide suggest a close association with magmatic arcs at convergent continental margins  and collision belts  that inevitably contain arc-derived components105. Accordingly, high As content in arc magmas originates from one or more of the following: (a) the subducting oceanic crust with its sediment cover; (b) the mantle component of the subducting slab; (c) the mantle wedge component overlying the slab; (d) the overlying continental crust through which the arc magma ascends to the surface108.Arc magmatism and associated geothermal activity contribute to As contamination of the aquifers through in situ leaching109 that can be dispersed in the air to eventually settle down or carried in suspension or solution to the downstream basins. Arsenic enriched rhyolitic glass in volcanic ash undergoes hydrolytic dissolution and produce an influx of major  and minor  solutes to groundwater under conducive climatic conditions109.Arc volcanism in the Andes leads to the emission of As-laden volcanic ash up to 10 mg/kg As111 classified geothermal systems along the Liquiñe Ofqui Fault Zone (LOFZ) in south-central Chile into two domains, the first one associated with volcanism  and the other one with a deep circulation of meteoric water .Most of the high-enthalpy Latin American geothermal reservoirs are found at various depths in active volcanic systems between southern Chile and northern Mexico and within the Trans-Mexican volcanic belt. However, there exist geothermal systems not associated with volcanism. For example, Alam et al.112, three belongs to the Chilean Andes, namely, the Central (CVZ), Southern (SVZ), and Austral (AVZ) Volcanic Zones, separated by the Pampean Flat Slab  segment and Patagonian Volcanic Gap , respectively. The absence of volcanism and geothermal activities in PFS is a consequence of the low subduction angle that prevents the formation of an asthenospheric wedge from which magma could be generated in the Earth's mantle112. On the other hand, several workers114 attributed the absence of volcanism in the PVG to a slab window, as without slab, there is no arc magmatism.Of the four Andean volcanic zones115) includes 92 active volcanoes, with the most highly ranked ones belonging to SVZ. According to this ranking, of the 14 volcanoes with the highest associated risk and recent volcanic activities above volcanic explosive index (VEI116) 4, all but Láscar (Antofagasta Region) are in southern Chile. Because of the highly explosive nature (mostly Plinian115) of these volcanoes, pyroclastics emission is vast. Among the ejected tephra, volcanic ash travels intercontinental distances. For example, the eruption of Puyehue-Cordón Caulle not only disrupted the air traffic in Argentina but as far away as Australia and New Zealand117.The most recent list of Chilean volcanoes ranking, based on the specific associated risk, by SERNAGEOMIN  in this plain. Nicolli et al.120 considered volcanic glass dissolution and/or hydrolysis and leaching of silicates minerals hosted in loess one of the three key processes rendering high As concentrations in shallow aquifers. On the other hand, Botto et al. showed adsorptive capability of soil by iron activation122 using two representative samples  of the volcanic ash from Puyehue Cordon Caulle Volcanic Complex (Chile), emitted on June 4, 2011, and deposited in Villa La Angostura ∼ 40 km from the source122.Unlike northern Chile's predominantly mining-based economy and desert climate, southern Chile is characterized by agriculture and agroindustry due to its Mediterranean and temperate climate. Although volcanic ash has been considered suitable for the soil in vineyards and other fruit production because of the nutrient elements 123, Infiernillo and San Ramón-Pocuro fault systems in central Chile124, Liquiñe-Ofqui fault system in southern Chile130. The CVZ of Chile lies between latitude 14° S and 27° S112. The geothermal fields in CVZ (between 14° and 27° S112) at high elevations (> 3000 m above mean sea level: amsl) are structurally controlled by N–S and N–W-trending grabens131, besides volcanic activity. In these geothermal fields, Lower Miocene–Pleistocene ignimbrite deposits and andesitic–rhyolitic volcanics overly Middle Cretaceous-Upper Miocene volcano-sedimentary sequences131. All these lithologies are important As sources with their elevated concentration in volcanic rocks range between 1.0 and 3105 mg/kg (median 7 mg/kg14).Geothermal systems associated with these volcanic centers potentially contaminate the groundwater, where the ascending As-enriched geothermal fluids meet the aquifers. Geothermal activity is controlled mainly by volcanism and regional geologic structures, viz. Toculla-Puchuldiza Fault in northern Chile132, was updated by Risacher and Hauser24 and used by Risacher et al.25 to evaluate the origin of the thermal waters. Pérez133 described most of the southern hot springs between 39 and 42° S in south-central Chile. While Tassi et al.136 and Aguilera et al.138 carried out gas geochemistry of volcanic and hydrothermal fluids in northern Chile, Ray et al.139 studied gas and isotope geochemistry of hydrothermal fluids in southern Chile. Some of the most extensively studied geothermal areas include El Tatio143. Specific studies in other areas are scarce. Mahon and Cusicanqui144 described Puja geothermal field, apart from Puchuldiza, in northern Chile. Sepúlveda et al.146 examined one of the largest active geothermal systems of southern Chile, Puyehue-Cordón Caulle.An inventory of over 150 Chilean hot springs across the country, prepared by HauserWhile the highest reported As concentrations  are from five geothermal fields, namely El Tatio, Alitar, Toro, Negro Francisco, and Puchuldiza, in northern Chile, reported concentrations between 10 and 999 μg/L are for the hot springs evenly distributed in northern and southern Chile Table .Table 1A147. The isotopic data on the geothermal discharges of ETGF indicate an essential role of water–rock interactions141 and mixing between meteoric water, carbon dioxide (CO2) hydrogen sulfide (H2S), and/or hydrocarbon-rich magmatic fluids134 in establishing geochemistry of the hydrothermal fluids. Studies of solid-state partitioning in this geothermal area's sediments have shown that As is mainly associated with carbonates148.In the Antofagasta Region, El Tatio geothermal field (ETGF), known for its geysers located at an elevation of 4300 m amsl, has reported As concentration up to 50 mg/L in the surface discharges30. Close to ETGF, As content in Salado River sediments is ~ 11,000 mg/kg and ~ 700 mg/kg at the Loa river's mouth, where it discharges into the Pacific Ocean . Due to dilution and adsorption of As onto solid materials, the concentration of As in Salado River water decreases downstream to 1.2 mg/L at its confluence with Loa River, and then to ~ 0.1 mg/L at latter's mouth at the Pacific Ocean149. Romero et al.30 used sequential extraction analyses to show that As is mainly associated with Iron and Manganese (Fe–Mn) oxy-hydroxides and residual phases; however, part of the As (about 20%) is readily available, extracted from the exchangeable and carbonate phases. This result is in agreement with the correlation observed between As content in sediments and As concentration in waters in the area148. The extreme arid conditions, high evaporation, and the lack of low-As tributaries that could have diluted the significant As input by Salado tributary contribute to maintaining high As concentration in the Rio Loa water to the mouth. Due to the oxidizing conditions, neutral to alkaline pH, high salinity, and high As concentrations, adsorption of As-species is not favored30. Although the main As source in the Loa River basin is geogenic, smelter emissions and mining wastes and the As-rich effluents from the water treatment plants also contribute to As contamination30.Several authors have identified ETGF as the principal natural As source for the Loa River, the longest (440 km) river of Chile, mainly contributed through its tributary Salado, fed by ETGF waters148 used selected isotopic tracers, including 121Sb and 123Sb to assess contaminant provenance. Thus, ETGF is the source of As and other toxic elements for downstream users across the Antofagasta Region151. Landrum et al.151 also reported that As (∼ 0.45 mmol/L) and Sb (0.021 mmol/L) concentrations at ETGF are the highest reported for natural surface water. The ETGF waters are near neutral Sodium-Chloride (Na-Cl) type with As and Sb primarily in the reduced (III) redox state at the discharge with progressive oxidation downstream. Landrum et al.151 also found that the Fe(III) oxide-hydroxide or ferric (Fe3+) oxyhydroxide associated with the microbial mats and some mineral precipitates accumulate substantial As, identified as arsenate by X-ray absorption spectroscopy analysis (> 10 wt% in the mats). This As is easily mobilized by anion exchange or mild dissolution of hydrous Fe (ferric) oxide The ubiquitous microbial mats represent a significant reservoir of As in this system. Landrum et al.151 reported As concentration in silica sinters up to 274 mmol/kg.To address the problem of determining the relative contribution of contaminants to the Loa River from ETGF and the mines using spatial patterns in trace metal/metalloid concentrations, Wilson152 further identified hydrous ferric oxides as the main As-bearing phase in sinter from this geothermal field, suggesting sorption as the primary mechanism for As scavenging by the solid phases (sinters). Besides, they identified nodular arsenide micro-mineralizations, like Loellingite (FeAs2), during the bulk-scale analysis of the sinter material. Based on the presence of arsenide mineralizations, these authors indicated the development of anoxic environments on the surface of the siliceous sinter, thus suggesting more complex biogeochemistry for As than usually observed for circum-neutral pH brine geothermal environments.Alsina et al.15 reported a rare As borate Cahnite (Ca4B2As2O12∙4H2O) and other unidentified Calcium (Ca)–As–Fe-rich minerals with needle-like and flower-like crystals, detected by both XRD and SEM in the colored sinter samples the sinters from ETGF. Besides, these authors also found other As minerals, viz. Teruggite (Ca4MgAs2B12O28⋅20H2O) and Nobleite (CaB6O10⋅4H2O), documented previously, together with other mineral phases, viz. Halite, Gypsum154. The very soluble As and Boron (B) minerals precipitate by complete evaporation of B and As-enriched waters15. Moreover, these authors highlighted the particularity of the thermal waters and precipitates (sinters) of ETGF, e.g., As and B contents higher than that of Cistern Spring, Champagne Pool, and Reykjanes, and the presence of As and B minerals: Cahnite, Sassolite, Nobleite, and Teruggite.Nicolau et al.15 further observed that the sinter deposits around the group of less diluted thermal springs do not show higher content of accessory minerals , indicating no direct relation between the concentration of these elements in the currently discharging thermal waters and the abundance of Halite, Gypsum, and Cahnite in the sinter deposit. According to these authors, this difference between the water and sinter chemistry could be because some sites do not reach full evaporation states, necessary for this highly soluble minerals’ precipitation. Thus, Sodium (Na), Ca, B, and As largely remain in the fluid phase. They observed reddish coloration of the analyzed sinter samples and attributed it to the occurrence of Ca–As–Fe-rich flower-like crystals between the Silica layers, as they constitute the red porous friable laminations in some sinter samples.Nicolau et al.216. The geothermal activity at PGF is controlled by NW–SE reverse fault and NNE–SSW normal strike-slip fault systems comprising of the Churicollo, Puchuldiza, and Tuja faults123. Sanchez-Yanez et al.16 further provided in situ trace element data, including As , in metal-rich silica sinter samples from the Puchuldiza geothermal field in the Chilean Altiplano. This silica sinter has complete diagenetic sequence, from non-crystalline Opal A to microcrystalline Quartz, wherein As is predominantly enriched in the more amorphous silica phases . Moreover, it contains As-bearing accessory minerals  and Fe-oxyhydroxides that efficiently adsorb As control its incorporation. These authors further reported that no B-bearing minerals were found at Puchuldiza, unlike El Tatio, where Nicolau et al.15 reported As borate Cahnite (Ca4B2As2O12·4H2O) in sinter samples.The Puchuldiza geothermal field (PGF), located in the Tarapacá Region of northern Chile at an elevation of 4200 m amsl, has surface manifestations over an area of ~ 1 km112) is the Andes' most elevated segment155. Although there is an absence of volcanism in PFS, there exist geothermal systems with surface expressions in the form of 17 thermal springs documented by Hauser132 and Risacher and Hauser24. Arsenic concentration in Toro hot spring, located at the northern limit of the PFS at an elevation of approximately 3500 m amsl in Coquimbo Region, is 16.2 mg/L132.The central portion of the Pampean Flat Slab . Thermal waters from 120 hot springs documented by Hauser132, Pérez133, and Risacher and Hauser24 in SVZ geothermal fields, in general, have relatively lower As concentration than CVZ, ranging from 0.003 to 6.127 mg/L with an average of 0.331 mg/L22. These authors associated the lower values of As in the SVZ to the lower crust thickness (30–40 km) and higher precipitation rates, which could dilute As concentrations at the surface.Volcanism and geothermal activities in SVZ, extending the subducting Juan Fernández Ridge to the Chile Rise159). Also, epithermal deposits along the eastern border of northern Chile are known for the presence of As-rich minerals, viz. Enargite (Cu3AsS4) and Tennantite (Cu12As4S13), in copper concentrates . In southern Chile, there are only a few polymetallic deposits exploited in the recent past, e.g., El Toqui mine in the Aysén Region. Other metal deposit types present in this part of the country have not been exploited or studied in detail, viz. Arsenopyrite bearing placer gold deposits in Tierra del Fuego area of the Magallanes Region. In the Coastal Range of south-central Chile, between 38 and 42° S latitudes, there are ore occurrences related with a structurally dismembered Paleozoic ophiolitic complex160. Within this ophiolite suite, there are massive polymetallic sulfides interbedded with metabasites ("greenschists"161), which have been interpreted as volcanic-exhalative depositions formed on the oceanic bottom during the Paleozoic. These ore occurrences are genetically like Japan's Besshi-type deposits, characterized by their spatial relationship with tholeiitic volcanic and volcaniclastic rocks. Moreover, reported placer gold deposits along the beaches in the southernmost Aysén and Magallanes regions162 indicate the gold mineralized zones down South.Major metallogenic belts are confined to northern and central Chile until ~ 35° S Fig. , which m163. Moreover, chemical weathering of the excavated ore bodies, exposed to exogenic forces of weathering and erosion, produce As-contaminated sediments, which are the potential sources of As contamination of the environment and consequent human As exposure163. Mining and metallurgical activities cause proliferation of As contamination to air, sediments, and streams, which might remain contaminated long after the cessation of these activities.Although the distribution of geogenic As contamination around localized ore bodies is generally limited and defined largely by geotectonic setting prevalent at the time of their formation, anthropogenic materials associated with ore mining and processing, viz. tailings and sludge, expand the area of contamination into the hydrosphere, thus affecting surface and groundwater, and pedosphere, thus affecting soil horizon and near-surface ecosystems159), El Indio . Arsenic is mainly related to Tennantite (Cu12As4S13) and Enargite (Cu3AsS4), which diminish the economic value of the concentrate164. Tailing impoundments sampled by SERNAGEOMIN165 show that the highest values of As within solid materials reach up to 60%. In the following paragraphs, we present some specific cases of As contamination associated with smelting plants.Concentrates generated from porphyry copper deposits in Chile present elevated concentrations of As, e.g., Chuquicamata  are As, Lead (Pb), Chromium (Cr), Fe, Cadmium (Cd), Cu, Molybdenum (Mo), and Zinc (Zn).Case 1: Pyrometallurgical processes at the Paipote National Foundry of the National Mining Company (ENAMI), operating since 1951, produce toxic emissions—gases, volatile elements, and microparticles—expelled directly into the atmosphere in the Paipote sector of the Copiapó River Valley167, although absolute values were not reported.Case 2: At VIC see "", studen168. However, by the time this practice was discontinued, up to 9 m thick tailing material deposited along the Chañaral coast for 5 km (N–S) with lateral spread (E–W) varying from 0.4 to 0.88 km by 5 km169. Of 120 grid (250 m × 250 m) sediment samples over 4 km × 3 km grid in Chañaral, Fernández and Tapia170 found As and Cu content exceeding the Canadian standard in 90%, and US and Brazilian standard in 60% of the samples.Case 3: The reported average As concentration in the proximity of Potrerillos smelter in the northern Atacama Region is 730 µg/L and 463 mg/kg in water and sediment, respectively. Mine wastes produced by Potrerillos and El Salvador were discharged directly into the El Salado Rive without any treatment until March 1990, following a court ruling related to this contamination171 reported high As and Sb concentrations in all soils from northern Chile, especially at Calama and Quillagua, in the Loa River Valley. They attributed it to the Salado River's contaminated irrigation waters, originating in the geothermal zone El Tatio  in Holocene (BP 9640 ± 40) lacustrine sediments near the El Indio gold deposit, in which As is mainly related to iron oxides and oxyhydroxides. The available data on As shows its natural presence in rocks , soils and sediments  in Arica and Parinacota, Tarapacá, Atacama, and Coquimbo administrative regions11, as well as in saline precipitates14 and marine sediments173. Arsenic content in the samples of the mud spread throughout the city of Copiapó following the flooding of the Copiapó River in April 2017, and airborne dust of the dried mud was about 5 mg/kg174. In the following paragraphs, we present some studies of As contamination of soil in Puchuncaví and Catemu valleys associated with VIC in Quintero- Puchuncaví area of Valparaíso Region.Based on the analysis of 26 soil samples from three different Chilean administrative regions, De Gregori et al.tio see "". Anothe171, the contaminated soils from Puchuncaví and Catemu valleys have Cu, As, and Sb concentration exceeding the reported critical values for this matrix, while at Catemu Valley, only Cu concentration was higher than this value. Moreover, at Puchuncaví valley, an apparent decrease in the three elements concentrations in soils as a function of the distance from the Ventanas industrial complex reflects the impact produced by Copper smelting in both valleys. While Cu–Sb correlation is significant for all the analyzed soil samples of this study, samples from Puchuncaví and Catemu valleys show more significant Cu–As, Cu–Sb, and Sb–As correlations. Based on this, these authors confirmed that high Cu, As, and Sb concentrations in these soils are coming from the Copper smelter, and the coal-fired thermoelectric power plant.According to the study by De Gregori et al.175 and Sánchez de la Campa et al.176 also reported the Copper smelter at VIC as a source of significant amounts of Cu as well as As, Cd, Pb, Zn, and Titanium (Ti) to the atmosphere in the Puchuncaví Valley. Salmanighabeshi et al.177 arrived at the same conclusion based on a long term (2007–2011) soil monitoring campaign conducted around the industrial area of Puchuncaví-Ventanas involving the measurement of elemental concentration profiles, principal component analysis (PCA) and hierarchical cluster analysis (HCA), and application of several quantitative risk assessment indexes . Based on the distribution of metals in various particle size fractions of the soil from four sites of the Puchuncaví Valley, Parra et al.178 confirmed the emission of As and Cu enriched particulate matter from the Copper smelter. They noticed high Ca concentration in the finer fractions of the contaminated soils containing tenorite and Ca oxide, used to reduce Sulfer dioxide (SO2)emissions from the roasting process of Cu sulfide during the smelting activities. Poblete et al.179 performed spatial interpolation with the data obtained from 466 samples collected through stratified systematic sampling. Using the geostatistical kriging method, it showed concentrations of about 30 mg/kg in VIC vicinity. Moreover, As enrichment and its correlations with other elements helped these authors conclude that abnormal concentrations in both Puchuncaví and Quintero communes can be associated with Ventanas Copper smelter.Ginocchio et al.180 on the other hand studied the effectiveness of lime and compost for in situ immobilization of trace elements in the Cu and As contaminated acidic soils of the Puchuncaví Valley exposed to atmospheric depositions from a Copper smelter by using earthworms as bioindicators of toxicity. They found lime and compost treatments effective in significantly increasing soil pH and decreasing the soluble and exchangeable Zn, exchangeable Cu, and free Cu2+ activity. However, this compost treatment increased soluble Cu and soluble and exchangeable As. Also, the lime application did not affect earthworm reproduction, but compost increased cocoon and juvenile production. There was a spatial variability of soil properties within treatments in the field plots. They concluded that soil organic matter (SOM) was a positive factor for both cocoon and juvenile production, i.e., more SOM increased cocoon or juvenile production. The toxicity (negative) factor was total soil As, while total Cu and total As were well correlated , so it is pretty likely that some of the trends could have been masked. They recommended that the Chilean legislation on threshold concentrations of trace elements in soils should consider SOM content due to its effect on trace element solubility and bioavailability.Neaman et al.181 studied Punchuncaví Valley as a model environment for evaluating the spatial gradient of human health risk, mainly caused by trace elemental pollutants in the soil because of a range of anthropogenic emissions from VIC. These authors used soil elemental profiles in 121 samples from five selected locations representing different degrees of impact from the industrial source for human risk estimation. They found the distance to source dependent cumulative non-carcinogenic hazard indexes above 1 for children (1.5–4.4), ingestion being the most relevant risk pathway. They further confirmed the significance of health risk differences within the study area by statistical analysis, namely, anlaysis of variance (ANOVA) and hierarchical cluster analysis (HCA) of individual hazard index values at the five sampling locations. They found As to be the dominant factor causing unacceptable carcinogenic risk levels for children (< 10−4) at the two sampling locations closer to the industrial complex, whereas the risk was just in the tolerable range (10−6–10−4) for children and adults in the rest of the sampling locations at the valley.Salmani-Ghabeshi et al.182 evaluated potential human health and ecological risks associated with the soils in Puchuncaví and Quintero's townships contaminated by atmospheric deposition of sulfur dioxide and trace elements from the nearby VIC. They determined the spatial distribution of total As, Cu, Pb, and Zn concentrations in soil based on 245 topsoil samples used to generate continuous distribution maps. The background As, Pb, Cu, and Zn concentrations of the soils were 16, 35, 100, and 122 mg/kg, respectively, with 32, 77, and 35% of the study area showing As, Cu, and Pb concentrations, respectively, above the background level. Moreover, the As, Cu, and Pb concentrations were positively correlated, suggesting that their source to be the Ventanas Copper smelter. The carcinogenic risk due to As exposure was above the threshold value of 10−4 for children (1–5 years old) in 27% of the study area.Tapia-Gatica et al.183 assessed Cupressus macrocarpa's usefulness as a biomonitor by studying leaf samples from five selected sites in the Punchuncaví Valley, located between 0.8 and 15 km away from VIC. They found high Cu (93.4–369 mg/kg) and As (7.6–12.7 mg/kg) values near the industrial complex exceed the phytotoxic levels reported in these plants with enrichment factor (EF) > 3000% for Cu and > 1300% for As. Through PCA and HCA, they identified six factors related to the industrial complex, traffic, and geogenic sources, which provided the most significant variance to the component connected to industrial activity, namely Copper smelter, and refinery.Gorena et al.184 studied the chemical composition of rainwater as an environmental pollution factor in the surroundings of VIC with the main objectives of assessing acidification and neutralization factors, measuring elemental pollutant levels, including calculation of enrichment factors and pollution sources assignment, and assessing the risk derived from elemental pollutant loads in rainwater, both for human use and natural ecosystems. Based on the analysis of 47 weekly rainwater samples collected during the winter (May–August) 2010 (24 samples) and 2011 (23 samples) at three sampling location with different degree of impact from the main emission sources, they found the elements emitted by metallurgical activities having significant enrichment values in the rainwater of the studied area through principal component analysis to identify the potential sources. Their risk assessment further showed that As content in rainwater is above the Chilean norms185 and the World health Organization40 guideline value (10 µg/L) for drinking water at some points in the study area around VIC.Cereceda-Balic et al.186 reported 131.2 ± 10.4 ppm of As in the soil in the ChiuChiu village of the Atacama Desert in northern Chile, and attributed it to the presence of volcanoes and geothermal activity by comparing As levels and the growth parameters among plants of the same genus. On the other hand, a study on public playgrounds for children assessed the soil quality in the Biobío Region of south-central Chile in 2018 identified dry weight average As concentrations varying from 18.82 to 23.53 mg/kg at four urban centers . However, based on the international guidelines for soil contamination189, Rodríguez-Oroz et al.190 concluded that there was no health risk for children in the studied playgrounds of the region.Tapia Fernández et al.112, facilitating conditions for geothermal fluids to be enriched in other elements as well. Maity et al.191 underscored the difference in the As concentration in the geothermal fluids at the eastern and western margins of the Pacific Ring of Fire; i.e., up to 75 mg/L As concentrations in the hydrothermal discharges at the western margin  and up to 6.2 mg/L at its eastern margin 192. This difference can be explained in term of crustal thickness in Chile  and their spatial relation with surface topography and amounts of crustal shortening to large and small-scale variations in the isostatic mechanisms compensating the mountain chain and the processes that lead to the Andean orogeny. While associating the main compensation mechanism to thick and buoyant crustal roots in agreement with previous studies195, Tassara and Echaurren31 also attributed mantle thermal roots, elastic flexure, lateral density variations, and dynamic support from the mantle and lower crustal flow for partial compensation of the cordilleran topography. These favorable conditions for the uptake of As and other volatile elements by hydrothermal fluids to transport them to near-surface environments make a strong case for the crustal thickness an important controlling factor for As distribution in Chile. Aguilera et al.196 corroborated this idea by proposing that As could be related to a deep magmatic source characterized by a high content of volatile elements such as As in their work on hydrothermal alteration, fumarolic deposits, and fluids from Lastarria Volcanic Complex in northern Chile. Similarly, Guo et al.197 explained mantle-derived magmas' upwelling and associated high As concentrations at the surface in terms of crustal contamination and the partial melting of rocks in the very thick crust in Tibet. Tapia et al.12 reported a general positive correlation between crustal thickness and As concentrations in surface water and fluvial sediments, which tends to decrease progressively from northern to southern Chile. These authors attributed this trend to decreased shortening of the Andes in southern Chile, as related lower crustal thickness induces lower crustal contamination, acting as an As-poor provenance for the sediments and surface water.Tassara and Echaurren198 accounted basin morphology, prolongation of faults, especially division of the underlying basement into blocks, producing discrete hydrodynamic environments, for the spatial variations in hydrochemical composition, including As speciation. In this basin, these authors found the groundwater extracted from the deep boreholes along the main fault lines oxidizing, alkaline, Sodium-Bicarbonate (Na-HCO3) type with relatively high As concentrations in pentavalent [As(V)] form, up to 241 μg/L. Although some workers have studied structural control for geochemical variation thermal waters and recharge of geothermal waters in Chile , Bangladesh206. To assess hydrogeological control for As concentration in Chile, more in-depth studies are required in the basins where such controls are expected to play a role in As concentration and speciation.Another structural control could be the hydraulic gradient, the lower one providing more residence time for groundwater11 attributed relatively low As in southern Chile to increased dilution due to more precipitation and the absence of As-rich evaporites , saline precipitates14, brines , and saline water  present in dry northern Chile. Moreover, Tapia et al.11 concluded that the high concentrations of As well above the upper continental crust average do not reflect the geochemistry of volcanic or plutonic rocks of the region. Elevated As concentrations in the Atacama Desert's closed basins can be attributed to high evaporation rates due to low precipitation and hyperarid climate since Miocene.Tapia et al.208), followed by saline water and hot springs in the CVZ , saline water in PFS , and hot springs in the SVZ . In brines , dissolved As in the Chilean Altiplano-Puna plateau presents an average of 14,200 µg/L207.In terms of salinity, the highest concentrations of As are found in brines  of the hydrothermal fluids and resulting alteration, rather than being localized, fault controlled. They are the primary As sources in the elevated areas. This control can be observed in terms of the variation of As concentration in some rivers as a function of elevation in Chile. For example, water quality monitoring throughout the Copiapó River and its tributaries show As concentrations below the Chilean guideline for drinking water of 10 µg/L185 in most of the river sections, except for the headwaters section and a downstream sector (Piedra Colgada), where the river is fed by highly mature As-enriched groundwater174. Similarly, Vega et al.210 reported relatively higher As concentrations in the streams and groundwater in the Loa, Elqui, and Lluta river catchments. This could be attributed to the presence of the mineralized zones in the headwaters area, as in Copiapó River's case, geothermal discharges, as in Loa River, fed by its major As contributor Salado River, originating from ETGF, or dissolution of volcanic glass present in volcanic rocks and ashes. This association of As with elevation needs further investigation.The rapid exhumation of the Andean Arc and resulting erosion leaves the active hydrothermal system capless in many segments211, there are scarce reports on coal and hydrocarbon deposits as potential As sources212.Coal deposits and hydrocarbon reservoirs are other two well-known geogenic sources of As across the world , including Latin America (viz. Brazil); however, there is no information currently available on potential As pollution related with either of these energy resources in the country. Although there are studies on As contamination originated from coal-fired (thermoelectric) power plants and petroleum refineries213. Work on As translocation in rice cultivation and its implication for human health by Bastías and Baldarrianand recent work of Moncada et al.215 dealing with the remediation of agricultural soils with long-term As and Cu contamination are efforts towards filling this gap.Also, the role of agricultural activity in accelerating As contamination needs to be investigated, as a significant amount of As could be released from the sediments due to the agriculture activity and contaminate shallow groundwater resources, as in Bengal delta, IndiaArc magmatism and associated geothermal activities are the principal primary As sources, present across the Chilean Andes, except for the Pampean Flat Slab and Patagonian Volcanic Gap. Arsenic from the Andean Cordillera is transported to the lowlands on its either side through exogenic forces like water and wind, leading to As concentration in the sediments deposited in the intermediate basin between the Andes and the Coastal Ranges in Chile towards west or eastward to the Andean foreland basin on the Argentine side. These As-rich sediments are formed either through accelerated erosion of the magmatic arc rocks (primary geogenic source) due to the rapid exhumation of the Andes, or As-rich vitric rhyolitic proportion of the volcanic ash. Arsenic transportation is also possible in solution following the dissolution of volcanic glass locally within the highlands or during the transport of ash by rivers. Geothermal waters rich in As (up to 4500 mg/L) contaminate both groundwater and surface water; viz. Salado River originating from El Tatio Geysers contribute As to the Loa River, the longest one in Chile that drains a major part of the Atacama Desert. The metallogenic belts extending from the country’s far north to the south-central part, and also stretching far south, are the second most important geogenic As source. Natural leaching of As from these mineralized zones contaminates the groundwater and soil horizon in their contact. Associated mining and metallurgical activities further accelerate this process, e.g., air and soil contamination from the smelter emissions. Some of the affected areas in various parts of the country are categorized as “sacrifice” o “saturated” zones. Moreover, a positive correlation between As concentration and crustal thickness, elevation, and evaporation rate envisages them as controlling factors for As distribution, which requires further investigation to understand the mechanism of As dissemination controlled by these factors.


Dairy cows contribute to greenhouse gas emissions from livestock, and reducing methane emissions is vital for the long-term sustainability of the dairy industry. Genetics and breeding strategies can be used to bring about permanent and long-term enteric methane emission reduction from dairy cattle. Here, we assess three definitions for methane emission traits, investigate their genetic parameters, and compare potential implications of including them in a genetic selection program. All three commonly used methane traits  were heritable, and are potential candidates for a selection program. Additionally, all traits were highly correlated with each other, indicating that selection on one trait would lead to an indirect response on the other methane traits. By exploring trait definitions for including methane in selection strategies, this work contributes to potential mitigation strategies for reducing greenhouse gas emissions in dairy cattle using genetics.Genetic selection can be a feasible method to help mitigate enteric methane emissions from dairy cattle, as methane emission-related traits are heritable and genetic gains are persistent and cumulative over time. The objective of this study was to estimate heritability of methane emission phenotypes and the genetic and phenotypic correlations between them in Holstein cattle. We used 1765 individual records of methane emission obtained from 330 Holstein cattle from two Canadian herds. Methane emissions were measured using the GreenFeed system, and three methane traits were analyzed: the amount of daily methane produced (g/d), methane yield (g methane/kg dry matter intake), and methane intensity (g methane/kg milk). Genetic parameters were estimated using univariate and bivariate repeatability animal models. Heritability estimates (±SE) of 0.16 (±0.10), 0.27 (±0.12), and 0.21 (±0.14) were obtained for daily methane production, methane yield, and methane intensity, respectively. A high genetic correlation (rg = 0.94 ± 0.23) between daily methane production and methane intensity indicates that selecting for daily methane production would result in lower methane per unit of milk produced. This study provides preliminary estimates of genetic parameters for methane emission traits, suggesting that there is potential to mitigate methane emission in Holstein cattle through genetic selection. The global population is rapidly increasing, and environmentally sustainable food production is becoming a research priority. The agricultural industry is often targeted for its contribution to climate change due to livestock production. Although dairy cattle represent only a fraction of total greenhouse gas (GHG) emissions, increased awareness of their contribution to the problem has resulted in consumer pressure on the dairy industry to improve its efficiency and sustainability and to investigate ways to mitigate its environmental footprint. Methane is the primary GHG emitted by ruminant livestock, and is generated by the normal feed digestion process; considering that methane is considered to be one of the more potent GHGs, its mitigation is of high priority to the dairy cattle industry.Several systems for measuring direct methane production have become available, including respiration chambers, the automated head-chamber system , and the sulfur hexafluoride SF6) tracer gas system . Studie tracer gPrevious studies have shown that methane emissions from dairy cattle have a heritable component that ranges from 0.12 to 0.45 depending on the trait analyzed and the stage of lactation  ,11,12. AAnimal Care Committee approval was obtained from the University of Guelph  and from the University of Alberta .https://genomedairy.ualberta.ca (accessed on 7 April 2023)), a global initiative investigating the use of selective breeding and novel genomics technologies to improve feed efficiency and reduce methane emissions in dairy cattle. Data from two Canadian research stations located in Alberta and Ontario were used in the analyses. The data collection in these two stations are described below.The data used in this study were collected through the Efficient Dairy Genome Project  at the University of Guelph’s dairy research facility, first lactation cows between 120 and 150 days in milk (DIM) were moved in groups of two to four into a tie-stall area of the barn for methane emission testing. During their time in the tie-stall, animals were fed a total mixed ration (TMR) ad libitum delivered daily at approximately 11:00 h and had ad libitum access to water. The average ingredient composition of the feed was corn silage (30%), haylage (28%), high-moisture corn 26%), supplement (12%), and chopped straw (2%). A detailed composition analysis is available in Seymour et al. . At each%, supple4 emission measurement period, CO2 recovery tests were performed at the start of each group and gas calibration was performed every week during the experimental period. The details of the methane emission measurement methods have been described in our previous study [The Dairy Research and Technology Center (DRTC) is part of the University of Alberta infrastructure. Mixed parity cows between 30 DIM and 250 DIM were housed in a ventilated tie-stall barn with ad libitum access to water and TMR, which was delivered daily at approximately 08:00 h. The average ingredient composition of the feed was barley silage (58%), alfalfa hay (10%), and supplement (31%). Cows were milked twice per day at 03:00 h and 15:00 h. Animals had access to an exercise area (an open dry lot) for 3 h every second day. Methane measurements were collected using the GreenFeed system from 2016 to 2020. Measurements were collected on groups of 10–15 mixed parity lactating cows. Groups were measured over twelve consecutive days at 12-h intervals, providing two measurements per day. The first day measurement was conducted at 01:00 h and 13:00 h, then shifted by one hour every day to cover all 24 h throughout the twelve days of recording. In 2019, this method was adjusted to correspond more closely to the ODRC herd, where measurements were made at three time points per day  for five consecutive days. The GreenFeed system was adjusted so that each cow could receive drops (approximately every 40 s) of the barley grain used to bait the cow to the head compartment. During the entire CHt-test, which assumes unequal variances between the groups, were conducted to test the differences in variances and means between the different measurement time periods, respectively. This was done to evaluate whether there were specific time points at which methane emission peaked or variation in methane outputs corresponding to the time of measurement. Differences were considered significant at 5% probability.Potential differences in methane emission among recording times  were tested for data collected at ODRC using R Version 3.5.0 software [A total of 2469 methane emission records were collected on 422 Holstein cows from August 2016 to March 2020 from the two research herds. Only first lactation cows were analyzed. Records ranged from 26 to 257 DIM from cows who calved between 22 and 33 months of age. Possible outliers were removed using a 1.5 × interquartile range. Cows were required to have at least three methane measurements (days) for analysis, as methane measurements from both herds were collected more than once per cow to assess variability. The pedigree file used for all methane traits in the analysis included 1434 animals, consisting of 892 dams and 253 sires over 25 generations.Various methane emission traits are used in livestock species ,18. Thisμ is the intercept; ith age of cow at calving class ; jth herd-year-season of recording , where season is split in two classes (March–August and September–February) or of the jth herd-year of recording (six classes: MeY); kth days in milk class (three classes); lth animal, distributed as mth animal with records, distributed as nth observation.Variance components were estimated using the Average Information Restricted Maximum Likelihood (AIREML) methodology and a repeatability animal model for MeP, MeY, and MeI. All analyses were performed using the ASReml software Version 4.1 . ConnectA better and less restrictive model for repeated records, such as a random regression model, was not used because of the limitations imposed by the sample size.j and trait k and j and trait k, respectively. Similarly, genetic correlations were estimated as j and trait k and j and trait k, respectively. Lastly, permanent environmental correlations were estimated as j and trait k and j and trait k, respectively.Bivariate models were used to estimate genetic, permanent environment, and phenotypic correlations using the same effects as in the univariate model. Phenotypic correlations were estimated as h2) and repeatability (r) from the univariate models were calculated as follows:The estimates of heritability (Heritability of the average of a different number of methane emission records (from 2 to 5) was obtained following Falconer and MacKay :hn2=h2×nn = 103) with records for the methane traits. The Spearman rank correlations were obtained using the COR.TEST function in R Version 3.5.0 software [Estimated breeding value (EBV) rank correlations between methane traits were used to assess potential re-ranking, considering either all animals or only sires with daughters  for the ODRC herd. Differences in the means between 12:00 h and 16:00 h and between 20:00 h and 8:00 h were not significant . All other differences in means and variances were significant (p < 0.05). The results showed that the highest amount of methane is emitted after feeding, increasing by an average of 35 g/cow from 480 g/cow (8:00 h) to 515 g/cow (12:00 h); fresh feed is delivered approximately an hour before the 12:00 h testing. These results agree with the literature. Hristov et al. [4 measurements were to be reduced due to the amount of effort to make all four measurements in a day, the night measurement at 20:00 would be a good candidate for elimination, as they have the same mean as the 8:00 measurements and the 8:00 measurements, while the 20:00 measurements have the same variance as the measurements at 16:00.F-tests and Welch two-sample v et al. , who usev et al.  observedEstimated variance components, heritability , 0.49 (0.03), and 0.74 (0.02) for MeP, MeY, and MeI, respectively . These rCurrently, the ideal number of days an animal’s methane emission should be measured in order to better capture its genetic merit is unknown , althougHeritability estimates for dry matter intake have been shown to vary throughout lactation ,40,41. TPhenotypic and genetic correlations are presented in Previous reports in the literature concerning correlations between methane traits in dairy cattle are limited. However, Kandel et al.  reportedn = 103) for each methane trait  with phenotyped daughters were much lower, the highest being between MeP and MeI at 0.67. The rank correlations between MeP and MeY and between MeY and MeI were 0.65 and 0.64, respectively, and a large re-ranking of sires was observed. This indicates that sires who may be best for one specific methane trait may not necessarily be the best for the other methane traits. That said, a moderate to high genetic correlation between the methane traits exists, allowing for indirect response to selection.Spearman rank-order correlation coefficients were estimated to determine the degree of re-ranking that may occur due to the use of the ratio traits MeY and MeI, accounting for dry matter intake or milk yield, respectively, or using MeP . ConsideMethane emission is a moderately heritable trait regardless of the expression considered, i.e., methane production, yield, or intensity. The overall rank correlations between estimated breeding values for methane emission traits in this study were high. However, rank correlations for sires with phenotyped daughters were only moderate, indicating substantial sire re-ranking and impact on selection decisions. The methane emission trait of choice depends on the breeding goals of a particular evaluation program. A larger dataset is necessary in order to increase the accuracy of the estimated breeding values for methane emission traits.


Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke. This study was conducted to assess the potential influencing factors on the efficacy and safety of RIVT in recurrent ischemic stroke within 3 months and to explore the strategy of RIVT within 3 months.PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched for cases of RIVT in recurrent ischemic stroke within 3 months up to February 1, 2023. Clinical characteristics were compared and analyzed between the good-outcome and poor-outcome groups and between the symptomatic intracranial hemorrhage (sICH) and non-sICH groups respectively.P > 0.05), but the differences in baseline National Institutes of Health stroke scale (NIHSS) score of the recurrent stroke (P = 0.056) and good outcome after the previous IVT (P = 0.054) nearly reached statistical significance. Comparing the data between the non-sICH group and the sICH group, statistically significant differences were found in terms of the proportion of cardiogenic embolism (P = 0.036), baseline NIHSS score in the recurrent stroke (P = 0.007) and the interval between thrombolysis (P = 0.041), but no significant difference was found by regression analysis.A total of 16 studies including 24 cases of RIVT within 3 months were retrospectively analyzed in the present study. The patients’ ages ranged from 42 to 87 years (median 73.5 years) and the intervals between thrombolysis were from 0.25 to 90 days (median 9.5 days). Comparing the clinical characteristics between the good-outcome group and the poor-outcome group, no statistically significant differences were found (In patients with recurrent ischemic stroke within 3 months, those with a good outcome after the previous IVT and a low baseline NIHSS score in the recurrent stroke may be considered for RIVT, whereas those with a high baseline NIHSS score, a short interval between thrombolysis, and cardiogenic embolism may suffer a higher risk of sICH. Due to sample size and publication bias, more studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.The online version contains supplementary material available at 10.1186/s12883-023-03472-4. Acute ischemic stroke (AIS) is the most common type of stroke. The key to the treatment of AIS is to recanalize the blocked cerebral blood vessels with the least possible delay and improve the symptoms of neurological deficits. At present, the main treatment methods are still intravenous thrombolysis (IVT) and mechanical thrombectomy. However, due to the limitations of medical conditions, not all medical institutions can implement mechanical thrombectomy, so IVT is still the most important treatment for AIS –3.For a long time, a history of AIS within 3 months is regarded as a contraindication for thrombolysis therapy in the AIS treatment guidelines in many countries. The European Stroke Organization (ESO) indicated in their guidelines that there is insufficient evidence to recommend intravenous thrombolysis in patients with a history of AIS within the past 3 months . AmericaThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used for developing this review .Two independent reviewers (Wen SY and Chen FF) performed the search. PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched up to February 1, 2023. Types of articles included but were not limited to case reports, case series, randomized controlled trials, cohort studies, etc. The search strategy was developed according to “recurrent ischemic stroke”, “intravenous thrombolysis” and “within 3 months” and their related text vocabulary and MeSH terms ((“stroke” or “cerebrovascular accident”) and  and (“three months” or “recurrent” or “repeated”)). Studies of RIVT within 3 months of recurrent AIS were screened from the search results, and repeated irrelevant articles were eliminated.All potentially relevant studies were screened for eligibility by two independent reviewers (Chen XT and Zhang Q). These studies met the following inclusion criteria: (1) Recurrent AIS patients were confirmed and diagnosed. (2) IVT was performed both in the index stroke and the recurrent stroke, and the interval between two IVT was no more than 90 days. (3) Containing data for clinical manifestation, treatment, and outcome of the patient was addressed. Studies without individual-level data, review articles, commentary, and other irrelevant articles were excluded. The quality of included studies was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Analytical Cross Sectional Studies. And any disagreements were discussed and resolved by a third investigator (Zhou CQ).Two independent reviewers (Wen SY and Chen FF) conducted data collection. Names of the first author, the year of publication, gender and age of patients, involved vessels, TOAST classification, baseline National Institutes of Health stroke scale (NIHSS) score, onset-to-treatment (OTT) time, the interval between thrombolysis, drug administration, modified Rankin scale (mRS) at 90 days were extracted from all included studies. All information was filled out on a pre-structured form.The NIHSS score was used to assess the severity of symptoms, and the mRS score was used to evaluate the prognosis of patients. The main efficacy index is whether the patient finally obtained a good clinical outcome after RIVT, and the main safety index is whether symptomatic intracranial hemorrhage (sICH) occurred and mortality. We defined a good clinical outcome as the mRS score at 90 days ≤ 2 points after IVT, if no mRS was reported in the case, as a decrease in the NIHSS at discharge ≥ 4 points from the baseline NIHSS score.P < 0.05.Statistical analysis was performed using IBM SPSS Statistics 27.0 software. In the efficacy assessment, cases were divided into a good-outcome group and a poor-outcome group based on the clinical outcome after RIVT for comparative analysis. In the safety assessment, cases were divided into an sICH group and a non-sICH group based on the occurrence of sICH after RIVT for comparative analysis. The amount of measurement data is small and does not fit normality and homogeneity of variance, so those data were shown as [the median ], and the Mann-Whitney U test is used for comparison between groups. Enumeration data were shown as [the number of cases (percentage)], and the Fisher’s precision probability test was used for comparison between groups. Logistic regression analysis was used to analyze the possible influencing factors. The difference was considered statistically significant when After screening the search results, 15 studies were included  and 10 females (41.67%), aged 42–87 years, with a median age of 73.5 years, and the median interval between thrombolysis was 9.5 days. In terms of TOAST classification, there were 9 cases (37.50%) of large artery atherosclerotic (LAA), 8 cases (33.33%) of cardiogenic embolism (CE), 5 cases (20.83%) of small artery occlusion (SAO), and 2 cases (8.33%) in which TOAST classification was not reported. The TOAST classification was the same for both the index stroke and the recurrent stroke. In the index stroke, anterior cerebral circulation was involved in 16 cases (66.67%), posterior cerebral circulation was involved in 6 cases (25.00%), and 2 cases (8.33%) did not report the involved artery. In the recurrent stroke, anterior cerebral circulation was involved in 19 cases (79.17%), posterior cerebral circulation was involved in 4 cases (16.67%), and 1 case (4.17%) did not report the involved artery. The baseline NIHSS score of the index stroke was 2–19 points (5 cases did not report) and the baseline NIHSS score of the recurrent stroke was 2–24 points (2 cases did not report). Except for case 23 which used tenecteplase during the RIVT, all other cases used alteplase as the thrombolytic drug. In addition, mechanical thrombectomy was performed together with IVT in case 12 for the recurrent stroke.After the previous IVT, 22 cases (91.70%) obtained good clinical outcomes and 2 cases (8.30%) obtained poor clinical outcomes. After the RIVT, 18 cases (75.00%) obtained good clinical outcomes and 6 cases (25.00%) obtained poor clinical outcomes, of which 2 cases had poor clinical outcomes after both two IVT. There was no case of sICH after the previous IVT. Three cases (12.50%) occurred sICH after the RIVT and case 13 died of pulmonary infection during hospitalization.P > 0.05). The proportion of good outcomes after the previous IVT (P = 0.054) and baseline NIHSS score of the recurrent stroke (P = 0.056) showed borderline significance between the two groups, which suggests that these two factors may have an effect on clinical outcomes after RIVT.Comparing the differences between the good-outcome group and the poor-outcome group under different influencing factors Table , the resP = 0.036), baseline NIHSS score of the recurrent stroke (P = 0.007), and the interval between IVT (P = 0.041). It indicated that a higher risk of sICH in RIVT is associated with CE, high baseline NIHSS score of the recurrent stroke, and short intervals between two IVT. There were no significant differences in gender, age, and involved arteries between the sICH group and the sICH group (P > 0.05).Comparing the differences between the non-sICH group and the sICH group under different influencing factors Table , there wP = 0.133) and the interval between IVT (P = 0.159) did not affect the risk of sICH.The proportion of CE, baseline NIHSS score of the recurrent stroke and the interval between IVT was considered the possible influencing factors for logistic regression analysis. Since the number of non-CE cases in the sICH group was 0, relevant data were excluded. In the logistic regression model Table , the basAll included studies were assessed for quality using the JBI Critical Appraisal Checklist for Analytical Cross Sectional Studies. The information is summarized in Supplementary Table In this study, we retrospectively analyzed the cases of recurrent AIS who were retreated with RIVT within 3 months and grouped them according to whether they obtained good clinical outcomes and whether sICH occurred.In terms of efficacy, the results showed that the differences in outcomes after the previous IVT and baseline NIHSS score of the recurrent stroke between the good and poor outcome group approached borderline statistical significance. This suggests that these two factors may have an impact on the clinical outcome after RIVT. This is also supported by a previous study by Wu et al.  They revIn terms of safety, several studies have explored the feasibility and safety of IVT for recurrent AIS patients with a history of stroke within 3 months, but there are still some controversies. A study by Karlinski et al. showed no significant difference in the incidence of sICH among patients receiving IVT therapy regardless of whether they had a history of stroke within 3 months . HoweverIn terms of the dosage, a low dose of alteplase was used in the RIVT of two patients due to the old age (80 years) and low body weight (50 kg) of the patient in case 1 (0.9 mg/kg in the previous IVT and 0.6 mg/kg in the RIVT) and the large infarct volume of the patient in case 24 . Since mAt present, aside from alteplase, tenecteplase and urokinase are also available for IVT. A recent meta-analysis which included 14 studies involving 3537 patients compared the efficacy and safety of tenecteplase with alteplase in patients with AIS . The resP = 0.054) and in the baseline NIHSS score of the recurrent stroke (P = 0.056) reached borderline significance. In the aspect of safety, the baseline NIHSS score of the recurrent stroke and interval between IVT were associated with sICH in univariate analysis, but logistic regression analysis did not show their effect on the risk of sICH. Therefore, further studies with larger samples are needed to validate these conclusions. Second, if poor clinical outcomes have been shown in the previous IVT, patients may not want to receive RIVT. Some bias may occur in this situation. Third, since RIVT within 3 months for recurrent AIS is currently an off-guideline treatment, some cases may not be reported due to poor prognoses, such as severe neurological deficit symptoms or death. This may lead to some publication bias in the included studies, and the actual incidence of poor outcomes and sICH may be higher.There are some limitations should be mentioned to appropriately interpret the results of the present study. First, the small number of cases included in the present study inevitably leads to some bias in the results. In the aspect of efficacy, the difference between the two groups in the proportion of good clinical outcomes after the index IVT (This study suggests that RIVT may be considered in patients with recurrent AIS within 3 months when the previous IVT obtained a good outcome and the baseline NIHSS score of the recurrent stroke is low. However, a high baseline NIHSS score, a short interval between thrombolysis and cardiogenic embolism may increase the risk of sICH after RIVT. Due to the small sample size and publication bias, future studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.Below is the link to the electronic supplementary material.Supplementary Material 1


To evaluate the association between sympathovagal balance and exercise performance, as measured by the 6-min walk test (6MWT), in women with systemic sclerosis (SSc) without cardiac involvement.This was a cross-sectional study in which 69 women with SSc [median age 51 (40–63 years)] without cardiac involvement underwent the 6MWT. Throughout the 6MWT, heart rate variability (HRV) was assessed using dedicated software.2 ≤ 4%) was observed in 10.1% of participants. Significant correlations were observed between the 6MWD and the following HRV parameters: number of successive normal-to-normal RR interval differences > 50 ms , low-frequency range , high-frequency range , and parasympathetic nervous system index .The median 6-min walking distance (6MWD) was 451 (392–498) meters, and 29 (42%) participants did not achieve 80% of the predicted value for healthy adults. Desaturation during the 6MWT (SpOIn women with SSc, there is an interrelationship of the 6MWD with both vagal withdrawal and sympathetic hyperactivation. This relationship between autonomic imbalance and worse exercise performance might increase cardiovascular risk, even in patients without apparent cardiac involvement. Control of the heart by the autonomic nervous system may be a potential target for treating patients with SSc. ANS dysfunction with reduced heart rate variability (HRV) potentiates endothelial injury and accelerates the development of myocardial fibrosis in SSc patients, although the latter effect may appear early in the disease , which is predominantly a marker of sympathetic nervous system (SNS) activity, and the high-frequency range , which reflects the modulation of PNS efferent activity by ventilation. The LF/HF ratio, which reflects the autonomic balance, was also measured in the frequency domain analysis; a higher LF/HF ratio indicates a predominance of the SNS. LF and HF power were evaluated in normalized units (nu). Finally, the following nonlinear measures were evaluated with a Poincaré plot: standard deviation, measuring the dispersion of points in the plot perpendicular to the line of identity (SD1), which describes the short-term variability (represents parasympathetic modulation); standard deviation, measuring the dispersion of points along the line of identity (SD2), which describes the long-term variability ; the SD2/SD1 ratio; and approximate entropy, which detects changes over time, indicating the complexity of the ANS. Registration and analysis were performed as recommended by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology .P < 0.05.Data were analyzed with SPSS software, version 26. The Shapiro‒Wilk test was applied to verify the hypothesis of normality of the variables. The associations between the clinical variables of the 6MWT and HRV were analyzed using Spearman’s correlation coefficients. The results are expressed as median (interquartile range) or frequency (percentage). Differences were considered significant when Among the 83 women who were evaluated for inclusion in the study, five were excluded due to heart disease, four due to uncontrolled hypertension, three due to diabetes mellitus, and two due to inability to perform the 6MWT. The median age and time since diagnosis were 50 (39–59) and 9.5 4–15) years, respectively. Participants’ lung function parameters were below the predicted values for normal lung function , 14. Non5 years, 2 ≤ 4%) was observed in 7 (10.1%) participants. The 6MWT data and the HRV measurements obtained during the 6MWT are shown in Table The median 6MWD was 451 392–498) meters, and 29 (42%) participants did not achieve 80% of the predicted value. Desaturation during the 6MWT , LF , HF , and PNS index . No significant correlation was found between delta SpO2 (pre- and post-6MWT) and HRV parameters.The interrelationships between the 6MWT and HRV parameters are shown in Fig. People with SSc may present with subclinical involvement of the cardiovascular system, which can have a significant impact on functional capacity . In thisPatients with SSc have difficulty performing activities that require physical effort. In this regard, it is important to note that vasculopathy causes inadequate blood flow to the cardiopulmonary system, which, together with musculoskeletal limitations, results in exercise intolerance and other exercise limitations . Transth8, so monitoring cardiac involvement is essential in the management of these patients. We observed a direct relationship between LF—which is a marker of sympathetic hypertonia—and 6MWD. In line with our results, Di Paolo et al. [2peak) in SSc patients without pulmonary hypertension who underwent cardiopulmonary exercise testing and monitoring with a 24-hour Holter monitor. Those authors showed that the LF/HF ratio was the only independent predictor of VO2peak, explaining 25% of its variability. Using 24-h Holter monitoring in women with SSc, Poliwczak et al. [Although the overall long-term prognosis of patients with SSc has improved in recent years, the proportion of deaths from heart disease has not changed significantlyo et al.  observedAn increase in vagal activity exerts a protective effect against ischemia and decreases HR and BP . In the 2 using fingertip pulse oximetry may have impacted the correlational analysis, as the preferred method for monitoring SpO2 in patients with SSc involves the use of forehead pulse oximetry because the presence of Raynaud’s phenomenon makes finger and earlobe pulse oximetry readings unreliable [The study has limitations. First, it was performed in a relatively small population, although the sample was homogeneous, and this is a rare condition. Second, a control group would have allowed direct comparisons between the measured variables, although the discrepancies are enormous between SSc patients and healthy controls. Indeed, the absence of a control group was minimized by the severity of SSc, which was highlighted by the patients’ low test results compared to the predicted values for the healthy population. In this sense, our patients had low lung-function values compared with the predicted values for healthy individuals (which is a characteristic of SSc) , and almreliable . DespiteIn conclusion, in women with SSc, there is an interrelationship of 6MWD with both vagal withdrawal and sympathetic hyperactivation. This relationship between autonomic imbalance and reduced exercise performance can increase cardiovascular risk, even in patients who were assessed by transthoracic echocardiography and found to be without cardiac involvement. Thus, drug- and nondrug treatments that reduce sympathetic hypertonia and prevent parasympathetic withdrawal should be considered to counteract autonomic dysfunction in SSc.


Anaplasma ovis is known to infect small ruminants globally and causing significant economic losses to livestock owners, however prevalence of Anaplasma ovis has been least investigated from Pakistan despite having a huge sheep population.Majority of Pakistani population lives in rural areas and raising animals, especially the small ruminants, is their primary source of income. Anaplasma ovis in the blood samples of sheep (n = 239) that were collected from District Dera Ghazi Khan in Pakistan.The present study was conducted from June 2021 till December 2021 to report the PCR based prevalence of msp4 gene of Anaplasma ovis. Represented partial msp4 gene sequences were confirmed by Sanger sequencing and deposited to GenBank (OP620757-59). None of the studied epidemiological factors  showed an association (P > 0.05) with the Anaplasma ovis infection in enrolled sheep. Analysis of the amplified partial mSP4 sequence of Anaplasma ovis revealed that this gene is highly conserved as all three sequences were identical and phylogenetically resembled with the msp4 sequences amplified from small ruminants in China, Kenya, and Germany, Turkey, Portugal, Tunisia and India. In conclusion, for the first time, we are reporting a moderate prevalence of Anaplasma ovis prevalence in Pakistani sheep and this data will help in developing the integrated control policies against this newly reported tick-borne disease that is infecting our sheep breeds.Out of 239 samples, 30 (12.5%) amplified a 347 bp fragment specific for the  Diseases, including metabolic, infectious and vector bone, are a major constraint to small ruminants and livestock industry as diseases impose financial risks to the livestock owners due to morbidity and mortality of their animals , 2. EctoAnaplasma (A.) ovis, an intra erythrocytic gram negative rickettsial bacterium, that belongs to the genus Anaplasma, family Anaplasmataceae that infect sheep, goats and some wild ruminants causing anaplasmosis , Kajli (N = 44), Latti (N = 14), and Baluchi (N = 10). Following the informed consent from the owners, around 3–5 ml of blood sample was collected by pricking the Jugular vein of each sheep with a disposable syringe into a tube containing 0.5 M EDTA as an anticoagulant. This blood was later on used for the DNA extraction. In order to find out the epidemiological factors that are associated with A. ovis infect in enrolled sheep, a questionnaire was filled on the sampling site. Data regarding sex, age, herd size, composition of herd, and dogs present in herd was collected.Randomly selected herds in Dera Ghazi Khan District were targeted to collect 239 blood samples from apparently healthy sheep during June 2021 till December 2021. Enrolled sheep belonged to four breeds: Mundri  and 0.5 mM of each primer. Reaction conditions comprised of an initial denaturation at 95°C for 5 min, 30 cycles of denaturation for 30 s at 94°C, annealing for 30 s at 62°C and extension for 30 s at 72°C and a final elongation for 5 min at 72°C  were sent to First Base Sequencing Service  for purification and DNA sequencing. The resultant partial msp4 sequences from A. ovis isolates were deposited at GenBank under the accession numbers OP620757- OP620759. Anaplasma ovis sequences (having 96–100% similarity to the ones generated in present investigation) were download from the GenBank database (https://www.ncbi.nlm.nih.gov/) and all sequences were trimmed to 309 bp to be used in phylogeny. Maximum Likelihood method was applied in MEGA version 11 for evolutionary analysis . Association between A. ovis occurrence and various risk factors was assessed through the Fisher's exact test (for 2 × 2 tables). Tajima's D Fu and Li's D values were estimated with DnaSP v5  was used for data analysis. DnaSP v5 .msp4 gene of A. ovis in 30 out of 239 (12.5%) collected sheep blood samples during present molecular survey. When prevalence of A. ovis was compared between enrolled sheep breed, one way ANOVA results revealed that the bacterium prevalence was not restricted to a particular sheep breed  with the A. ovis infection in sheep  gene sequences generated during this study (OP620757–OP620759) with those previously deposited GenBank from various parts of the World having sequence homology of 96% or more  were not found associated with the prevalence of fections , 28. It fections , 27.A. ovis in sheep blood samples that were collected from Dera Ghazi Khan in Punjab (Pakistan). None of the enrolled sheep breed was specifically susceptible to A. ovis. Data generated in this study will pave the way for the prophylactic detection and control of ovine anaplasmosis in Pakistan. We recommend that similar and large scale studies must be conducted in all those areas of Pakistan that are unexplored for the incidence and prevalence of A. ovis. This will significantly help in control of tis bacterium and will improve the output of livestock sector in Pakistan.In conclusion, we are reporting a moderate prevalence of OP620757-59.The data presented in the study are deposited in the GenBank, accession numbers The animal study was reviewed and approved by Ethical Committee of Institute of Pure and Applied Biology, Bahauddin Zakariya University Multan (Pakistan). Written informed consent was obtained from the owners for the participation of their animals in this study.FI and AdK designed and supervised the study. MN, MA, and ATar collected blood samples from sheep and noted epidemiological data. MN, MS, AsK, ATaq, and SA extracted DNA from blood samples and carried out PCR assays. IA-E, AS, and AA performed or assisted with the statistical analysis, sequence alignment, and phylogenetic study. MN, AS, AA, and FI wrote the text and edited and finalized the article. All authors approved the final version of the article.