Roosevelt (2014) and others have noted the anthropic terra preta (dark earth) soils of the Amazon as another pedogenic marker of widespread human modification of Earth’s natural ecosystems. Archaeological evidence for such ancient landscape modifications is also mounting, increasing the pressure on those who claim that prehistoric peoples had only limited effects on the Earth’s surface. Beginning

500–1000 years ago, the effects of Selleck MK 1775 European exploration, economic expansion, and globalization also resulted in the rapid spread of a distinctive group of domesticated animals (dogs, horses, cattle, sheep, goats, pigs, chickens, etc.) and plants (wheat, corn, potatoes, AT13387 order rice, etc.), creating a global faunal and floral horizon that will be unmistakable

to future scientists as markers of the Anthropocene (Lightfoot et al., 2014). This was not a one-way Eurocentric phenomena, moreover, as the spread of domesticates moved from the Old World to the New World and vice versa. These cultural contacts also spread deadly infectious diseases that had disastrous consequences for human populations and cultures. Such disease epidemics caused millions of deaths and dramatic cultural changes worldwide, all in a period of four to five centuries. Today, the consequences of this “Columbian exchange” are clearly evident in archaeological records worldwide and will continue to be visible to future archaeologists and geoscientists. If it is decided that the Holocene should continue to be recognized, such global changes could also be used as a boundary marker between the end of the Holocene and the beginning of the Anthropocene. What the papers in this

special issue illustrate is that specific thresholds, tipping points, or developmental indicators used to define the start of the Anthropocene are often directly influenced by the research agenda of the author. This is not a case of self-reflexivity, but a consequence of the inherent challenges of defining “human domination.” Foley et al. (2014) proposed to define the beginning Methamphetamine of the Anthropocene at AD 1780, but to coin a new term and unofficial geological period, the Palaeoanthropocene, marking a more nebulous time interval before the Industrial Revolution when humans transformed local and regional environments with effects that varied across time and space. As a transitional time period, the Palaeoanthropocene would not compete as a geologic epoch, but cover the ancient impacts of humans prior to when “the burning of fossil fuels produced a huge crescendo in anthropogenic effects” ( Foley et al., 2014). This idea may have merit as a compromise, if the only thing at stake is the composition of our geologic timescales. One of the most compelling parts of the Anthropocene debate is the attention it has generated among the media and public.

Pectinase is an enzyme able to degrade pectic substances by hydrolyzing the ester bond between galacturonic acid and methanol or by cleaving the glycosidic bonds of specific

polymers [22]. Indeed, Jin et al [17] used pectinase to hydrolyze ginsenosides and found that compound K is more readily absorbed from HGE compared to non-HGE in human individuals. Compound K has received increasing attention because various pharmacologic actions including anticancer [25], anti-inflammation [26], and antidiabetes [27] were shown to be mediated by this compound. Using pectinase-hydrolyzed ginseng extract, Ramesh et al [28] found an improved antioxidant status and minimized occurrence of oxidative stress-related disorders in aged rats. Moreover, Yuan et al [29] and [30] reported that pectinase-processed ginseng radix had antidiabetic and hypolipidemic effects in high selleck fat diet-fed ICR mice. Taken together, pectinase seems to be an effective tool to transform ginsenosides into deglycosylated ginsenosides, thereby enhancing the bioavailability and functionality of ginseng. Our data demonstrate that 8 wk of HGE supplementation causes a significant reduction in FPG (p = 0.017)

and PPG60min (p = 0.01) in IFG individuals. Such reductions may be due to one or a combination of different mechanisms, including intestinal glucose absorption [31] and [32], insulin secretion from pancreatic β-cells Trichostatin A supplier [33], or peripheral glucose utilization [34]. After the supplementation of HGE, noticeable but not significant difference was found in the glucose level at an earlier time point (PPG30min, p = 0.059) during OGTT. This result suggests that HGE slows the absorption of glucose in the intestinal lumen. Also, our findings of significant decreases in FPG and PPG60min suggest one additional possibility, in which HGE improves glucose intolerance through increasing

the insulin action on the target tissues responsible for glucose uptake. Moreover, FPI (p = 0.063) and PPI60min (p = 0.077) showed a tendency to improve in the HGE group compared to the placebo group. In supporting this possibility, ginsenosides CK and Rg1 have been reported to enhance insulin-mediated glucose uptake in 3T3-L1 adipocytes, which is related to the increased ID-8 GLUT4 translocation [27] and [35]. Similarly, administration of HGE improves glucose homeostasis and insulin resistance state (or glucose and lipid parameters) in high fat diet-fed mice via activation of AMP-dependent protein kinase in muscle tissue [29] and [30]. In this study, however, there was no significant difference in HOMA-β, suggesting no effect on insulin secretion. In contrast to our results, studies reveal that ginseng significantly stimulates insulin release from pancreatic β-cells [36] and [37]. These discrepancies could be due to the differences in designs (human studies vs. animal studies) and materials (hydrolyzed ginseng vs. nonhydrolyzed ginseng) used in the studies.

Pectinase is an enzyme able to degrade pectic substances by hydrolyzing the ester bond between galacturonic acid and methanol or by cleaving the glycosidic bonds of specific

polymers [22]. Indeed, Jin et al [17] used pectinase to hydrolyze ginsenosides and found that compound K is more readily absorbed from HGE compared to non-HGE in human individuals. Compound K has received increasing attention because various pharmacologic actions including anticancer [25], anti-inflammation [26], and antidiabetes [27] were shown to be mediated by this compound. Using pectinase-hydrolyzed ginseng extract, Ramesh et al [28] found an improved antioxidant status and minimized occurrence of oxidative stress-related disorders in aged rats. Moreover, Yuan et al [29] and [30] reported that pectinase-processed ginseng radix had antidiabetic and hypolipidemic effects in high Osimertinib cost fat diet-fed ICR mice. Taken together, pectinase seems to be an effective tool to transform ginsenosides into deglycosylated ginsenosides, thereby enhancing the bioavailability and functionality of ginseng. Our data demonstrate that 8 wk of HGE supplementation causes a significant reduction in FPG (p = 0.017)

and PPG60min (p = 0.01) in IFG individuals. Such reductions may be due to one or a combination of different mechanisms, including intestinal glucose absorption [31] and [32], insulin secretion from pancreatic β-cells SB203580 concentration [33], or peripheral glucose utilization [34]. After the supplementation of HGE, noticeable but not significant difference was found in the glucose level at an earlier time point (PPG30min, p = 0.059) during OGTT. This result suggests that HGE slows the absorption of glucose in the intestinal lumen. Also, our findings of significant decreases in FPG and PPG60min suggest one additional possibility, in which HGE improves glucose intolerance through increasing

the insulin action on the target tissues responsible for glucose uptake. Moreover, FPI (p = 0.063) and PPI60min (p = 0.077) showed a tendency to improve in the HGE group compared to the placebo group. In supporting this possibility, ginsenosides CK and Rg1 have been reported to enhance insulin-mediated glucose uptake in 3T3-L1 adipocytes, which is related to the increased GBA3 GLUT4 translocation [27] and [35]. Similarly, administration of HGE improves glucose homeostasis and insulin resistance state (or glucose and lipid parameters) in high fat diet-fed mice via activation of AMP-dependent protein kinase in muscle tissue [29] and [30]. In this study, however, there was no significant difference in HOMA-β, suggesting no effect on insulin secretion. In contrast to our results, studies reveal that ginseng significantly stimulates insulin release from pancreatic β-cells [36] and [37]. These discrepancies could be due to the differences in designs (human studies vs. animal studies) and materials (hydrolyzed ginseng vs. nonhydrolyzed ginseng) used in the studies.

These results alongside with those previously obtained by other authors suggest that this group of natural compounds might be promising for future antiviral

drug design. This study was supported by CNPq/MCT/Brazil (grant number 470235/2009-8). J.W. Bertol, C.M.O. Simões, F.C. Braga, R.M. Pádua and C.R.M. Barardi are grateful to CNPq for their research fellowships, as well as C. Rigotto thanks to CAPES/MEC/Brazil for her postdoc fellowship. “
“Herpes click here Simplex Virus types 1 and 2 (HSV-1 and HSV-2) are human neurotropic viruses usually associated with infections of the skin and mucosae of different locations, most commonly the oral and genital regions. Although infections are often subclinical, HSV can cause mild to severe diseases, especially in neonates and immunocompromised individuals. Currently, there is no cure for find more the persistent infection, and prolonged therapy with the available antiherpes drugs has induced the emergence of drug-resistant virus strains.

Moreover, HSV has been described as a risk factor for HIV infection (Roizman et al., 2007). This scenario has triggered the search for new antiherpetic agents, especially those with mechanisms of action different from that of nucleoside analogs, the major class of antiviral agents used for the management of HSV infections. Besides, a treatment based on the combination of different antiviral agents can be considered a promising approach to increase antiviral selectivity while simultaneously enabling the reduction of the Glutamate dehydrogenase active concentrations of the drugs (Chou, 2006). Many synthetic or naturally occurring sulfated polysaccharides from different species of marine algae, bacteria, fungi, and animals have been previously shown to have antiviral activity against human and animal viruses (Ghosh et al., 2009). In the case of fungi, cell wall polysaccharides have been chemically modified to increase their solubility and enhance their biological activities (Liu et al., 2010), including their antiviral action (Zhang et al., 2004). The pharmacological effects of Agaricus brasiliensis,

a Basidiomycete fungus native to the Brazilian Atlantic forest region, have been mainly related to the presence of polysaccharides and protein–polysaccharide complexes ( Firenzuoli et al., 2008). Concerning its previous antiviral evaluation, Sorimachi et al. (2001) showed that the ethanolic fractions of A. brasiliensis mycelium and fruiting bodies inhibited HSV, poliovirus, and Western equine encephalitis virus replication. The inhibition of HSV-1 and herpes bovine virus by an aqueous extract of A. brasiliensis fruiting bodies was also demonstrated by Bruggemann et al. (2006). Additionally, both aqueous and ethanolic fruiting bodies extracts and an isolated polysaccharide from this species displayed antiviral activity against poliovirus 1, as reported by Faccin et al. (2007).

The selection of hemiplegic volunteers was based on the same criteria and included the presence of hemiplegia secondary to cerebrovascular disease, with impairment of one of the cerebral hemispheres (determined by computed tomography), with muscle hypertonia on the affected side and sufficient cognitive level to understand verbal commands and perform the voluntary respiratory movements requested. Volunteers unable to perform the required movements, those with muscle hypotonia or in the acute stroke phase, subjects with

emotional liability that would affect movement performance and individuals with facial paralysis were excluded from the study. Patients with hemiplegia were distributed into two groups: patients with right-side hemiplegia and patients

with left-side hemiplegia. All patients were at more than 24 months post-stroke. Lung function tests, diaphragmatic excursion, volumetric measurement, maximal find more check details inspiratory pressure and quantification of motor function were evaluated in this order. Spirometry (Vitalograph 2010 spirometer) was performed in compliance with ATS/ERS (2005). The following parameters were assessed during the test: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), mean forced expiratory flow between 25 and 75% of the FVC maneuver (FEF25–75%), peak expiratory flow (PEF) and maximal voluntary ventilation (MVV). The first two parameters are expressed in liters per second (l/s) and the last three in liters per minute (l/min). A previously calibrated spirometer

was used in the evaluations. Assessment of spirometry was performed with patients in the sitting position. Assessment of diaphragmatic excursion on the cranial-caudal Flavopiridol (Alvocidib) axis was performed using ultrasound in M mode (format that views the movement in a window of time) using the LOGIQTM 100 Pro (Siemens) model C36 and convex transducer (FOV: 68X, ROC: 50 mm), with variable frequency between 3.5 and 5.0 MHz depending on the depth of the structure for best image visualization. For this assessment, the volunteer remained in the supine position, with a ten-degree inclination of the upper part of the body. The movement of each hemidiaphragm was measured in centimeters on the cranial-caudal axis, starting with the condition of functional residual capacity until reaching total lung capacity. Inspiratory capacity was measured simultaneously on an analog ventilometer (Wright–Ferraris), using a mouthpiece and nose clip. To obtain the image, the transducer was positioned on the abdominal wall just below the ribs between the mid axillary line and the mammillary line, forming a 45-degree angle between the transducer and the surface of the abdominal wall in the cephalic direction (Cohen et al., 1994a and Houston et al., 1994), as shown in Fig.

, 2008 and Timms and Moss, 1984).

Another indication of an upcoming shift in this region can be found in the increasing dominance of floating macrophytes at the expense of the submerged selleck chemical macrophytes (Scheffer et al., 2003 and Zhao et al., 2012b). Floating macrophytes are able to better cope with lower light conditions than submerged macrophytes because they grow at the water surface. When light conditions deteriorate close to the shifting point, floating macrophytes will therefore predominate submerged macrophytes (Scheffer et al., 2003). While macrophytes disappeared, the total primary production of Taihu increased more than twofold from 1960 (5.46 t · km− 2 yr− 1) to 1990 (11.66 t · km− 2 yr− 1) owing to the increasing phytoplankton biomass that bloomed due to the excessive nutrient input (Li et al., 2010). The first algal blooms occurred in 1987 in Meiliang

selleck screening library Bay (Fig. 5, 1980s). Subsequently, algal blooms dominated by non-N2 fixing cyanobacteria (Microcystis) increased in coverage and frequency, and appeared earlier in the season ( Chen et al., 2003b, Duan et al., 2009 and Paerl et al., 2011b). The presence of mainly non-N2 fixing cyanobacteria indicates that external and internally-supplied nitrogen are sufficient to maintain proliferation over N2-fixers ( Paerl et al., 2011b). The early blooms in the northern bays and western shores occurred right where enrichment was

most severe and easterly winds drove algae to form thick scums ( Chen et al., 2003b and Li Thymidine kinase et al., 2011a). At that time, high concentrations of suspended solids in the lake centre due to wind action ( Fig. 8) might have prevented algal growth by light limitation ( Li et al., 2011a and Sun et al., 2010). Despite this mechanism, blooms also emerged in the lake centre from 2002 onwards ( Duan et al., 2009). Finally, in 2007 the problems with drinking water became so severe that it was not possible to ignore the blooms anymore ( Qin et al., 2010). The effects of excessive nutrient loads go beyond the shift in primary producers alone and appear also higher in the food web. As the biomass of primary producers and zooplankton grew over time, the biomass of higher trophic levels shrank and several species disappeared (Guan et al., 2011 and Li et al., 2010). There are indications that in the presence of Microcystis, the zooplankton shifted their diet to the detritus-bacteria pathway rather than grazing on living phytoplankton ( de Kluijver et al., 2012). A macroinvertebrate survey in 2007 by Cai et al. (2012) showed that small individuals (e.g. Tubificidae) appear in large numbers in the algal blooming zone ( Fig. 5, 2007). The appearance of mainly small macroinvertebrate species might be related to the absence of refuges to prevent predation (e.g. macrophytes) ( Cai et al.

But inevitably with the creation of settler, mission, and managerial CHIR-99021 solubility dmso colonies in their territories, transformations took place in indigenous political economies that led to modifications in their continued relations with the environment as they became incorporated into the modern world system. Second, the advent of European colonialism produced unprecedented environmental impacts in most areas of the world, which may have led to significant declines in biomass and diversity in some regions (Richards,

2003). We argue that the early modern world system differed from previous kinds of human–ecosystem relationships in the scale and intensity of environmental modifications that took place. The founding of settler colonies, DAPT molecular weight mission agrarian systems, plantations, fur trade outposts, and fishing and whaling factories had significant consequences for maritime and terrestrial ecosystems in temperate and tropical islands and continents around

the world. Third, in considering the environmental transformations that took place with European colonialism, it is crucial to undertake detailed studies of specific regions to understand fully the impacts that these changes had on indigenous populations and local ecosystems. The changes that unfolded with colonialism were not just the result of European agency and the establishment of diverse kinds of colonial enterprises, but also took place through complicated articulations Fenbendazole between natural processes (e.g., dispersal of weeds), decisions made by various indigenous and/or culturally diverse actors, and colonial policies regarding indigenous practices (e.g., burning restrictions, cessation of hunting and gathering, etc.). How these diverse factors played out varied greatly in local contexts in the Americas, Oceania, India, Africa, and Asia. We believe our case study from one colonial province (Alta and Baja California) encapsulates many of the current issues involving the Anthropocene. Most scholars would argue that the Anthropocene did not

begin until quite late, after AD 1850 in Alta California with the Gold Rush, statehood, and massive immigration. But we argue there is substantial evidence to argue for a much longer chronology beginning with the creation of anthropogenic landscapes by native peoples over centuries or millennia. This was followed rather abruptly by the establishment of managerial and mission colonies into the Californias in the 1600s to the early 1800s. The founding of a string of Jesuit, Franciscan, and Dominican missions and a Russian fur trade outpost transformed indigenously created landscapes, modified marine and estuarine ecosystems with the extermination of keystone species, and introduced new agrarian practices and the rapid spread of weeds and livestock that changed terrestrial habitats.

Pectinase is an enzyme able to degrade pectic substances by hydrolyzing the ester bond between galacturonic acid and methanol or by cleaving the glycosidic bonds of specific

polymers [22]. Indeed, Jin et al [17] used pectinase to hydrolyze ginsenosides and found that compound K is more readily absorbed from HGE compared to non-HGE in human individuals. Compound K has received increasing attention because various pharmacologic actions including anticancer [25], anti-inflammation [26], and antidiabetes [27] were shown to be mediated by this compound. Using pectinase-hydrolyzed ginseng extract, Ramesh et al [28] found an improved antioxidant status and minimized occurrence of oxidative stress-related disorders in aged rats. Moreover, Yuan et al [29] and [30] reported that pectinase-processed ginseng radix had antidiabetic and hypolipidemic effects in high Anti-diabetic Compound Library cell assay fat diet-fed ICR mice. Taken together, pectinase seems to be an effective tool to transform ginsenosides into deglycosylated ginsenosides, thereby enhancing the bioavailability and functionality of ginseng. Our data demonstrate that 8 wk of HGE supplementation causes a significant reduction in FPG (p = 0.017)

and PPG60min (p = 0.01) in IFG individuals. Such reductions may be due to one or a combination of different mechanisms, including intestinal glucose absorption [31] and [32], insulin secretion from pancreatic β-cells learn more [33], or peripheral glucose utilization [34]. After the supplementation of HGE, noticeable but not significant difference was found in the glucose level at an earlier time point (PPG30min, p = 0.059) during OGTT. This result suggests that HGE slows the absorption of glucose in the intestinal lumen. Also, our findings of significant decreases in FPG and PPG60min suggest one additional possibility, in which HGE improves glucose intolerance through increasing

the insulin action on the target tissues responsible for glucose uptake. Moreover, FPI (p = 0.063) and PPI60min (p = 0.077) showed a tendency to improve in the HGE group compared to the placebo group. In supporting this possibility, ginsenosides CK and Rg1 have been reported to enhance insulin-mediated glucose uptake in 3T3-L1 adipocytes, which is related to the increased PJ34 HCl GLUT4 translocation [27] and [35]. Similarly, administration of HGE improves glucose homeostasis and insulin resistance state (or glucose and lipid parameters) in high fat diet-fed mice via activation of AMP-dependent protein kinase in muscle tissue [29] and [30]. In this study, however, there was no significant difference in HOMA-β, suggesting no effect on insulin secretion. In contrast to our results, studies reveal that ginseng significantly stimulates insulin release from pancreatic β-cells [36] and [37]. These discrepancies could be due to the differences in designs (human studies vs. animal studies) and materials (hydrolyzed ginseng vs. nonhydrolyzed ginseng) used in the studies.

The Kinh were mainly involved in administration, tourism, and education and settled in the district’s capital, while Crizotinib chemical structure most of the other ethnic groups practiced different types of subsistence agriculture mostly in the form of shifting

cultivation (Tugault-Lafleur, 2007). Apart from the shifting cultivation, ethnic minorities also used to cultivate opium and collect forest products for their survival (Michaud and Turner, 2000, Sowerwine, 2004b and Turner, 2012), which could have contributed to past forest clearance. Today, the ethnic groups cultivate water rice on permanent terraced paddy fields; maize and other crops on upland fields (Leisz et al., 2004 and Turner, 2011). Terraced paddy fields were first introduced by the Hmong and Yao who migrated from southern China to northern Vietnam during the late 19th and early

20th centuries (Michaud, 1997). Additionally, many households cultivate cardamom (Amomum aromaticum) under forest cover as a substitute cash crop, after the ban on opium in 1992 ( Tugault-Lafleur and Turner, 2009 and Turner, 2011). Because of its scenic landscape and presence of five ethnic groups with their traditional way of living, Sa Pa is considered as one of the most attractive tourism areas in Vietnam. The Hoang Lien Mountains GW-572016 price comprise probably the last remnants of native forest of the northern Vietnamese highlands. It became one of the first areas recognized as a ‘special use forest’ in Vietnam, and it was converted into the Hoang Lien National Park (HLNP) in July 2002 following the Prime Minister’s Decision 90/2002/QD-TTg to protect biodiversity by preserving the subtropical and temperate forest ecosystems (Le, 2004 and Jadin et al., 2013). Already under the French Regime (1887–1940), Sa Pa district was a well-known holiday and relaxation resort (Michaud and Turner, 2006). Northern Vietnam suffered a lot under http://www.selleck.co.jp/products/Paclitaxel(Taxol).html the first Indochina war (1945–1954). The town sunk into oblivion, as a large part of the population of Sa Pa town fled

away from the hostilities. In the early 1960s, in the framework of the New Economic Zones Policy, migration schemes were designed by the new socialist regime that stimulated the Vietnamese Kinh from the lowlands to populate the northern Vietnamese Highlands (Hardy, 2005). The decision of the national government to open Sa Pa district for international tourism in 1993 had a large impact on daily life in Sa Pa town and its surrounding communities. The number of domestic and international visitors increased exponentially from 16,100 in 1995 to 405,000 in 2009 (GSO, 1995 and GSO, 2010) (Fig. 1). Tourism is now the most important economic activity in the area, and it generated 58% of Sa Pa district’s GDP in 2010 (GSO, 2010). The poverty rate in Sa Pa district decreased gradually from 36% in 2000 to 21% in 2009 (GSO, 2000 and GSO, 2010).

, 2006, Reineking et al., 2010 and Müller et al., 2013). The resulting small average fire size (9 ha, Valese et al., 2011a) is due to a combination of favourable factors such as the relatively mild fire weather conditions compared to other regions (Brang

et al., 2006), the small-scale variability in plant species composition and flammability (Pezzatti et al., 2009), and effectiveness of fire suppression (Conedera et al., 2004b). However, in the last decades periodic seasons of large fires have been occurring in the Alps (Beghin et al., 2010, Moser et al., 2010, Cesti, 2011, Ascoli et al., 2013a and Vacchiano et al., 2014a), especially in coincidence with periods displaying an exceptional number of days with strong, warm and dry foehn winds, and extreme heat waves (Wohlgemuth et al., 2010 and Cesti, 2011).

When looking at the latest evolution Compound C solubility dmso of such large fires in the Alps, analogies with the drivers of the successive fire generations, as described by Castellnou and Miralles (2009), Ulixertinib cell line become evident (Fig. 3, Table 1). Several studies show how land abandonment has been increasing vegetation fuel build-up and forest connectivity with an enhancing effect on the occurrence of large and intense fires (Piussi and Farrell, 2000, Conedera et al., 2004b, Höchtl et al., 2005, Cesti, 2011 and Ascoli et al., 2013a). A new generation of large fires in the Alps is apparent in Fig. 5: despite the general trend in decreasing fire area over decades mainly as a consequence of fire suppression, periodical seasons such as from 1973 to 1982 in Ticino and from 1983 to 1992 in Piemonte sub-regions, displayed uncharacteristic large fires when compared to historical records. In particular, examples of fires of the first and second generations sensu Castellnou and Miralles (2009) Farnesyltransferase can be found in north-western Italy (Piemonte Region) in the winter

of 1989–90, when the overall burnt areas was 52,372 ha ( Cesti and Cerise, 1992), corresponding to 6% of the entire forested area in the Region. More recently, exceptional large summer fires occurred during the heat-wave in August 2003, which has been identified as one of the clearest indicators of ongoing climate change ( Schär et al., 2004). On 13th August 2003 the “Leuk fire” spread as a crown fire over 310 ha of Scots pine and spruce forests, resulting in the largest stand replacing fire that had occurred in the Swiss central Alpine region of the Valais in the last 100 years ( Moser et al., 2010 and Wohlgemuth et al., 2010). In the following week, there were simultaneous large fires in beech forests throughout the south-western Alps, which had rarely been observed before ( Ascoli et al., 2013a). These events represent a new generation of fires when compared to the historical fire regime, mainly characterized by winter fires ( Conedera et al., 2004a, Pezzatti et al., 2009, Zumbrunnen et al., 2010 and Valese et al.