The degree of human involvement in late Quaternary continental ex

The degree of human involvement in late Quaternary continental extinctions will continue to be debated, but humans clearly played some role over many thousands of years. We view the current

extinction event as having multiple causes, with humans playing an increasingly significant role through time. Ultimately, the spread of highly intelligent, behaviorally adaptable, and technologically sophisticated humans out of Africa and around the world set the stage for the greatest loss of vertebrate species diversity in the Cenozoic Era. As Koch and Barnosky (2006:241) argued: “…it is time to move beyond casting the Pleistocene extinction debate as a simple dichotomy of climate GABA drugs versus humans. Human impacts were essential to precipitate the event, just as climate shifts were critical in shaping the expression and impact of the extinction in space and time. So far, the Anthropocene has been defined, primarily, by significant and measurable increases in anthropogenic greenhouse gas emissions http://www.selleckchem.com/products/gdc-0068.html from ice cores and other geologic features (Crutzen and Steffen, 2003, Ruddiman, 2003, Ruddiman, 2013 and Steffen et al., 2007). Considering the acceleration

of extinctions over the past 50,000 years, in which humans have played an increasingly important role over time, we are left with a number of compelling and difficult questions concerning how the Anthropocene should be defined: whether or not extinctions should contribute to this definition, and how much humans contributed to the earlier phases of the current mass extinction event.

We agree with Grayson (2007) and Lorenzen et al. (2011) that better chronological and contextual resolution is needed to help resolve some of these questions, including a species by species approach to understanding their specific demographic histories. On a global level, such a systematic program of coordinated interdisciplinary research would contribute significantly to the definition of the Anthropocene, as well as an understanding of anthropogenic Fossariinae extinction processes in the past, present, and future. We are grateful for the thoughtful comments of Torben Rick and two anonymous reviewers on earlier drafts of this paper, as well as the editorial assistance of Anne Chin, Timothy Horscraft, and the editorial staff of Anthropocene. This paper was first presented at the 2013 Society for American Archaeology meetings in Honolulu. We are also indebted to the many scholars who have contributed to the ongoing debate about the causes of Late Pleistocene and Holocene extinctions around the world. “
“Anthropogenic soils in general and anthropogenic soil horizons in particular are recalcitrant repositories of artefacts and properties that testify to the dominance of human activities. Hence, such soils are considered appropriate to play the role of golden spikes for the Anthropocene (Certini and Scalenghe, 2011:1273).

7; profiles a–b and i–j) They are equipped with dams at 20 km fr

7; profiles a–b and i–j). They are equipped with dams at 20 km from the outlet for Nitta

River, and at 16 and 12 km from the outlet for the Ota river. Only the finest – and most contaminated – material is exported from PF-01367338 price their reservoirs, as suggested by the very high 134+137Cs activities measured in sediment collected just downstream of the dams (Fig. 7; profiles a–b and i–j). Those reservoirs stored very large quantities of contaminated sediment, as illustrated by the contamination profile documented in sediment accumulated behind Yokokawa dam (Fig. 8). Identification of a 10-cm sediment layer strongly enriched in 134+137Cs (308,000 Bq kg−1) and overlaid by a more recent and less contaminated layer (120,000 Bq kg−1) shows that Fukushima accident produced a distinct geological record that will be useful for

sediment dating and estimation of stocks of contaminated material in this region of Japan during the next years and decades. The succession of typhoons and snowmelt events during the 20 months that LBH589 supplier followed FDNPP accident led to the rapid and massive dispersion of contaminated sediment along coastal rivers draining the catchments located in the main radioactive pollution plume. In this unique post-accidental context, the absence of continuous river monitoring has necessitated the combination of indirect approaches (mapping and tracing based on radioisotopic ratios, connectivity assessment) to provide this first overall picture of early sediment dispersion in Fukushima coastal catchments. These results obtained on riverbed sediment should be compared to the measurements Isoconazole conducted on suspended sediment that are being collected since December 2012. The combination of those measurements with discharge and suspended sediment concentration data will also allow calculating exports of contaminated sediment to the Pacific Ocean. Our

results showing the rapid dispersion of contaminated sediment from inland mountain ranges along the coastal river network should also be compared to the ones obtained with the conventional fingerprinting technique based on the geochemical signatures of contrasted lithologies. Fukushima coastal catchments investigated by this study are indeed constituted of contrasted sources (volcanic, plutonic and metamorphic sources in upper parts vs. sedimentary sources in the coastal plains). This unique combination of surveys and techniques will provide very important insights into the dispersion of particle-borne contamination in mountainous catchments that are particularly crucial in this post-accidental context, but that will also be applicable in other catchments of the world where other particle-borne contaminants are problematic.

Our results shown in Fig  2 and Table 2 demonstrate that LPS as e

Our results shown in Fig. 2 and Table 2 demonstrate that LPS as expected was extremely potent to induce a very significant gene expression of E-selectin, VCAM-1, IL-6, IL-8, CXCL-6 and CD69 at all times analyzed, while a significant increase in gene expression for MMP-10 was detected only at 6 and 24 h. The gene expression of ANG-2 LPS-induced was not detected at any time

point. Considering the jararhagin treated HUVECs INK 128 research buy we can observe that no gene expression was detected at the time point of 3 h, while significant increase was observed at 6 h for the genes coding for E-selectin, VCAM-1, IL-8, CD69, ANG-2 and MMP-10. After 24 h, jararhagin induced a significant up-regulation of gene expression of E-selectin, VCAM-1,

CD69 and ANG-2. Comparing the relative concentration of mRNA for those genes, obtained between LPS and jararhagin treatment (Table 2) we can observe very high Bleomycin mw levels of some genes expressed by LPS. This result suggest that the signaling pathways activated by these two samples are completely different and jararhagin would not activate toll like receptors as LPS, but other receptors as integrins present on HUVEC cell surface, which may induce lower activation signals. In order to identify a positive correlation between mRNA translation and protein production induced by jararhagin, the protein expression of PECAM-1, E-selectin and VCAM-1 was investigated on endothelial cell surface by flow cytometry. As shown in Fig. 3, PECAM-1 expression on HUVECs incubated with PBS, jararhagin or LPS for 1, 2 or 6 h was very similar between the groups, confirming the constitutive molecule expression. Interestingly PECAM-1 expression was significantly lower on HUVECs treated for 24 h with jararhagin, indicating that the expression of this molecule is decreasing probably due the apoptosis process. The adhesion molecule E-selectin (Fig. 4) was significantly up-regulated in HUVECs stimulated with LPS at 3 and 6 h, while jararhagin did not induce changes in this molecule expression at any time analyzed when compared with the PBS group. A similar effect 4-Aminobutyrate aminotransferase was observed with VCAM-1 (Fig. 5). LPS increased the VCAM-1 expression

on HUVECs at 6 and 24 h after treatment, while jararhagin did not induce any expression as also observed for the PBS incubation. As the protein E-selectin was not detected on the HUVEC surface, we analyzed if it could be shed by the action of jararhagin and then released as its soluble form in the cell supernatant, by ELISA. No difference on the soluble form of E-selectin was observed in the supernatants of HUVECs treated with jararhagin (Fig. 6B). The IL-8 secretion was also analyzed on the cell culture supernatants. Our results demonstrate that jararhagin treatment did not induce this cytokine secretion by HUVECs, as showed in Fig. 6A, while the HUVECs incubated with 1 ng/mL of LPS released significant amounts of this cytokine.

We are grateful to Atlas South Sea Pearl Ltd for providing us wit

We are grateful to Atlas South Sea Pearl Ltd for providing us with pearl oysters and a seeding technician for this experiment. “
“Phytoplankton accounts for less than 1% of the photosynthetic biomass on Earth, yet is estimated to contribute half of the world’s net primary production (Field et al., 1998). A substantial fraction of the global carbon flux is controlled by the prokaryotic fraction of the plankton (Binaschi et al., 2001), the so-called bacterioplankton, Akt inhibitor which consist of different heterotrophic taxa with varying ecological strategies (Giovannoni, 2005). Studies based on culture-independent 16S ribosomal RNA gene sequence (16S rDNA)

analysis and transcriptome-based approaches provided insights into the dynamics and functional interactions within such communities (Gilbert et al., 2008). However, several questions remain unanswered, e.g. how a multitude of eukaryotic and prokaryotic planktonic species coexist in a seemingly homogenous habitat with limited resources (Glöckner, 2011). In previous studies,

we used a comprehensive multi-‘omic’ approach to investigate the bacterioplankton’s response to a diatom-dominated spring phytoplankton bloom off the coast of the island Helgoland in the year 2009 (Klindworth Vorinostat price et al., 2014 and Teeling et al., 2012). We observed a tight succession of distinct blooming bacterial clades. Flavobacteria (genera Ulvibacter, Formosa, and Polaribacter) and Gammaproteobacteria (genus Reinekea and SAR92 clade species) acted as major polymer degrader while Alphaproteobacteria (SAR11 clade and Rhodobacteraceae) appeared to hardly benefit from abound algae substrates. The combined analysis of metagenomes, metatranscriptomic and metaproteomes from different time points throughout the succession uncovered differences in the gene repertoires and expression Protein tyrosine phosphatase profiles of distinct clades. The metatranscriptome reported in this study was generated as part of the same sampling campaign but addressing the winter

time before the spring phytoplankton bloom. Prior to appearance of the algae bloom surface water was collected on 11.02.2009 from the long-term ecological research site ‘Kabeltonne’ off the coast of the island Helgoland in the German Bight of the North Sea (54°11.18′N, 7°54.00′E) as described previously (Teeling et al., 2012). RNA extraction was performed without mRNA enrichment and the cleaned total RNA sample was subsequently used for cDNA synthesis as reported by Klindworth et al. (Klindworth et al., 2014). Roche’s 454 pyrosequencing was carried out at LGC Genomics (LGC Genomics GmbH, Berlin, Germany) using the FLX Titanium chemistry (Roche/454 Life Sciences, Branford, CT, USA) according to the manufacturers protocols. The sequencing statistics are summarized in Table 1. Extraction of expressed 16S rDNA fragments from metatranscriptome and their subsequent taxonomic assignments were done with the SILVA pipeline (Quast et al., 2013), which uses the SINA aligner (Pruesse et al., 2012).

O espectro de anormalidades neurológicas que ocorrem na doença he

O espectro de anormalidades neurológicas que ocorrem na doença hepática pode variar desde sutis alterações na concentração

e atenção até deficiências graves que conduzem à morte15 and 20. Inconsistências nos critérios diagnósticos e de métodos entre estudos têm contribuído para as grandes variações referidas na prevalência de disfunção cognitiva em pacientes com doença hepática4. Estas inconsistências dificultam a Ku-0059436 mw realização de estimativas precisas da prevalência e incidência desse quadro21 and 22. No maior estudo realizado até esta data (n = 165) esta disfunção foi observada em 62,4% dos pacientes21. Mas em 2 outros estudos sobre este problema de pesquisa encontrou-se uma prevalência de encefalopatia hepática mínima de 48%, usando-se como critério a pontuação para encefalopatia hepática através da Wechsler adult intelligence scale-performance 17 e avaliação por espectroscopia cerebral 4. Os 2 valores não Epacadostat order foram compatíveis com o valor estimado no presente estudo, através do MEEM, porém, os critérios de avaliação foram diferentes. Os pacientes com doença mais grave (Child C) apresentam maiores déficits cognitivos, como se observou no presente estudo, o que é compatível com

a literatura, onde se supõe que os pacientes com doença mais grave apresentam maior comprometimento em testes de memória 4 and 19. O uso de testes cognitivos também permite a identificação de padrões específicos de comprometimento cognitivo em pacientes com doença hepática 23. McCrea et al. observaram disfunção relativamente seletiva da atenção 5-Fluoracil order e habilidades motoras em um grupo

de cirróticos, na ausência de qualquer anormalidade da memória, linguagem ou habilidades visuais-espaciais 23. É preciso destacar que o maior declínio no desempenho do teste com o aumento da idade provavelmente relaciona-se também ao déficit cognitivo associado ao envelhecimento. Além do fator idade, há também uma relação bem estabelecida na literatura da associação entre alcoolismo crônico, por si só independente da hepatopatia concomitante, e disfunção cognitiva 24 and 25. O comprometimento cognitivo observado em pacientes com alcoolismo sem doença hepática demonstrável cursa frequentemente com déficit de funções executivas, de planejamento, resolução de problemas e memória 24, enquanto os pacientes com a doença neurodegenerativa de Wenicke-Korsakoff geralmente exibem principalmente prejuízos na memória 26. Apesar do grande número de estudos em pacientes com alcoolismo, têm sido relativamente poucos os trabalhos que averiguaram especificamente a contribuição da doença hepática no espectro de alterações cognitivas observadas nos alcoolistas 15.

This work was sponsored by Consejo Nacional de Ciencia y Tecnolog

This work was sponsored by Consejo Nacional de Ciencia y Tecnología, México (CONACYT) No. 111941 and Genzyme Corp (now Sanofi). “
“The authorship for the article in Archives of Medical Research 44 (2013) 21-26 should read as follows: Mohamed Kamel Sabry, Mohamed Nazmy Farres, Nermine Abdelnour Melek, Naglaa Ahmed Arafa, and Annie Arek

Ohanessian. We apologize for any confusion or inconvenience this may have caused. “
“1. Kan Saito Division of Pediatric Dentistry, Department Selleck Sotrastaurin of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry The influence of Sox21 as a novel ameloblast marker on tooth germ differentiation” 2. Hiroyuki Nakamura Nakamura Orthodontic and Pediatric Dental Office Orthopedic treatment using bone-anchored maxillary protraction (BAMP)” 3. Noriko Niizato Department of Pediatric Dentistry, Hiroshima University Graduate School of Biomedical and Health Sciences The dental caries condition of abused children in temporary shelters in Hiroshima” 4. Satoko Oikawa Division of Pediatric Dentistry, find more Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry Regulation of dental epithelial cell proliferation and differentiation by laminin” 5. Yuko Nakamura

Department of Pediatric Dentistry, School of Life Dentistry, Nippon Dental University Three-dimensional reconstruction of root malformation in mice by cyclophosphamide 1. Noriko Niizato Department of Pediatric Dentistry, Hiroshima University Graduate School of Biomedical and Health Sciences The Oral Health Condition of Abused Selleckchem Cobimetinib Children in Temporary Shelters in Japan The Japanese Journal of Pediatric Dentistry; 50 (3) 237–242, 2012 2. Masamichi Ide Department of Pediatric Dentistry,Tsurumi University School of Dental Medicine “Longitudinal Dental Management of Hypophosophatemic Ricketes: Case Report The Japanese Journal of Pediatric Dentistry; 50 (4) 313–319, 2012 3. Aya Yamada Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry Epithelial-mesenchymal interaction reduces inhibitory effects of fluoride on proliferation

and enamel matrix expression in dental epithelial cells Pediatric Dental Journal; 22 (1) 55–63, 2012 4. Maiko Bori Department of Pediatric Dentistry, Kyushu Dental University Influence of childhood type II diabetes on bone formation in the growth period Pediatric Dental Journal; 22 (2) 125–139, 2012 5. Hiroshi Sekiguchi Department of Pediatric Dentistry, Tokyo Dental College Missense mutation of EDA1 gene in Japanese family with X-linked anhidrotic ectodermal dysplasia Pediatric Dental Journal; 22 (2) 188–192, 2012 1. Chiaki Yamada-Ito Department of Pediatric Dentistry, Field of Developmental Medicine Course for Health Science, Kagoshima University Graduate School of Medical and Dental Sciences Smoothness of molar movement during gum chewing in children with primary dentition” 2.

Indeed, the reality of scientific publication shows that the qual

Indeed, the reality of scientific publication shows that the quality of both the “Materials and Methods” section and the “Results” section ranges from very poor to reasonably useful. As the experimental results should serve as a valid basis for the acceptance of hypotheses, or for the creation of new hypotheses that need to be accepted, again, both the materials and the methods applied, and the data generated, must be reported accurately

in ways that do not allow misinterpretation. Even more, enzymology data should be reported in standardized way to link protein (structure) to enzyme function datasets and to make them machine-readable for the creation of protein-function databases. Apweiler et al., 2005 and Apweiler et al., 2010 pointed out the ABT-199 CP-868596 importance of standards when protein-function data are reported in journals (see also Tipton et al., 2014). A framework of criteria that determines a minimum

of data reported will help to ensure that data generated can be located by researchers and computers alike, an important pre-requisite for successful in silico analysis and representation of metabolic systems. In recent years scientists from diverse fields in computational and experimental biology have been developing minimum information standards for improving the data quality in publications and databases. The Minimum Information for Biological and Biomedical Investigations (MIBBI) project has devoted great efforts to coordinating the development of data standards and to avoiding redundancy and incompatibility. MIBBI is intended to be a one-stop-shop for minimum-information new checklists;

it currently provides links to 39 registered checklists in the portal section and assistance for the creation of new, non-redundant guidelines in the foundry section ( Taylor et al., 2008). In the best case, authors can access MIBBI to find the most appropriate set of minimum information guidelines when writing their papers. Examination of the publication guidelines of the major biochemistry journals confirms the emerging interest of their editors in high-quality data reporting, as a growing number of these journals have adopted community-based guidelines for data standards. However, the checklist groups need to take into account the constant changes in technology and methodology, as well as modifications of laboratory standard practices that lead to the need for continual revision and periodic updating of their lists. The advantages of data reporting standards appear to be obvious; potential problems with the standardization of enzyme data in terms of good publication practice are so far unknown. This is a typical question when rules and recommendations are proposed, on account of suspicions that it may restrict scientific freedom and potentially put researchers in a straitjacket, as previously mentioned.

g De Fruyt et al , 2009, Hrebícková et al , 2002 and McCrae et a

g. De Fruyt et al., 2009, Hrebícková et al., 2002 and McCrae et al., 2005). This has led to them being empirically related to a cornucopia of concepts as well as used in mediation and moderation models of current behaviours, helping to define relationships and explain outcomes. In adolescence, personality Ibrutinib solubility dmso may even be a key mediator of individual differences in the course and treatment responses of youth with mental disorders that emerge at this period in development (Costello, Copeland, & Angold, 2011). However, on closer inspection, problems remain with personality measurement in adolescents. In comparison to adult research, studies with adolescents have found more cross loadings, and items that

do not load sufficiently on any factor. Dasatinib price Additionally, the studies demonstrate that items from the Neuroticism and Conscientiousness scales perform better, whereas Extraversion, Agreeableness and Openness items have less reliability (e.g. Parker and Stumpf, 1998 and Sneed et al., 2002). The problems with factor replicability may be due to developmental changes that take place during this time; personality traits are still in flux throughout adolescence (McCrae et al., 2002) and the structure and coherence of the five factors vary at different ages (Soto, John, Gosling, & Potter, 2008). Therefore it is important to

determine if the precision of personality measurement can be maximised for use in behavioural and clinical studies in this age range. Item response theory (IRT) can be used to improve the measurement ID-8 of adolescent personality. The application of IRT allows scale psychometric properties to be revealed with greater precision than other multivariate methodologies; analysing item level information can provide insights into measurement reliability and enables a thorough evaluation of the internal construct validity. IRT provides information by checking the validity of the items and delineating poor performing indicators. It does this by estimating each individual item’s discrimination on the latent trait (the

a parameter) and difficulty within a population (the b parameter) ( Embretson & Reise, 2000). An item’s discrimination reflects how the probability of endorsing an item changes as the level of the underlying trait increases. Thus, highly discriminating items more strongly represent the latent trait. The item’s difficulty corresponds to the likelihood of an individual endorsing it given their level of the latent trait. An item is considered easy if most people endorse it and the difficulty rises as the likelihood of endorsing it decreases. Therefore some items may be easy to endorse even at relatively low levels of the latent trait. IRT also provides estimates of each scale and item’s total information function through total and item information curves (TICs and IICs).

Other limitations of supraglottic airways in a chemical event is

Other limitations of supraglottic airways in a chemical event is the difficulties in performing suction, it does not prevent aspirations, and high-pressure ventilation which is important in preventing acute lung injury is not possible [30]. Several observations should be highlighted: 1. In the present study, the excretions of the cuirass-ventilated animals were frothy white, similar to that seen after deep suctioning. In the Control and Mask groups,

secretions were clear, saliva-like in appearance. In a study testing the use of Biphasic Cuirass Ventilation in OP-exposed cats, the device enabled clearance of bronchial secretions, saving the need for active suctioning of the airways [31]. The use of bag-valve mask ventilation requires further support against airway constriction combined with selleck compound the vast secretions following OP poisoning. Active suction of these secretions is an important supportive measure [7]. The current study demonstrates the efficacy of the cuirass device in severe respiratory distress induced by paraoxon exposure in a pig model. The minimal antidotal treatment applied here was sufficient

to ensure 24 h survival if the cuirass technique was implemented. Without this cuirass ventilation Selleck AG-14699 high mortality rate was seen. We conclude that the MRTX, a noninvasive, easy-to-operate Biphasic Cuirass Ventilation device might be advantageous on-scene in an OP mass casualty event. This finding should be validated in further investigations. “
“Ticagrelor (AZD6140; brand names Brilique™ and Brilinta™, AstraZeneca) is an orally available, direct acting, competitive and reversible P2Y12

receptor antagonist, which has therapeutic utility as an oral antiplatelet agent for treatment of acute coronary syndrome and potentially other conditions [42]. The risk of ischemic events is high after acute coronary syndrome and so inhibition of platelet aggregation is a major strategy for preventing Vildagliptin ischemia in these patients (Yusuf et al., 2001). Platelet aggregation is a complex process involving many factors, but a major mediator of aggregation is the release of adenosine-5′-diphosphate (ADP) from activated platelets leading to sustained activation of the P2Y12 receptor (Gershlick 2000; Shrör 1995). The P2Y12 receptor antagonist activity was demonstrated by Ticagrelor (100 mg b.i.d.) inhibiting platelet aggregation by greater than 90% at 4, 12 and 24 hours, in humans (Tantry et al., 2007). The P2Y12 receptor is expressed by platelets, brain, vascular smooth muscle cells, dendritic cells and other blood cells [15] and [27] and is the molecular target of various antiplatelet drugs such as Ticagrelor and the irreversible P2Y12 antagonists Clopidogrel and Prasugrel (Clopidogrel package insert; Prasugrel package insert).

Thus, while the densities observed in the SPSG remain below those

Thus, while the densities observed in the SPSG remain below those find more reported for the NPSG, they are within the same range of magnitude. The fate of plastic pollution in the marine environment is poorly understood. In this study, the count of plastic particles in the size class between 1 mm and 2.79 mm is greater than the combined three smaller size classes from 0.355 mm to 0.999 mm. This is in contrast to the proportions reported for the NPSG by Moore et al. (2001), who observed more items in the small fraction than in the large fraction (1–2.79 mm). The differences between the NPSG and the SPSG are particularly pronounced in the category of fragments. Whether this is due to more advanced degradation

of microplastics in the NPSG or due to other reasons is not known at present. Photodegraded and oxidized plastic becomes brittle, then fractured by wave mechanics into ever smaller particles (Andrady, 1990), and therefore a greater abundance of smaller particles would be expected if the sea surface were the last stop for plastic pollution. When waves are high, a smaller fraction of plastic remains close

to the surface and is collected by the trawl. It is possible that turbulence on the sea surface, Selleckchem Vorinostat generated by wind and waves, drives the smaller microplastic particles below the 15 cm depth of our sampling equipment (Kukulka et al., 2012). Possibly, the increased ratio of surface area to volume as particles become smaller because the proportional increase of fouling organisms leads to a decrease in the buoyancy of particles Ureohydrolase (see also discussion

in Hidalgo-Ruz et al., 2012). Beach deposition or ingestion by marine organisms may also account for the fate of microplastics. The relatively small number of microplastics <1 mm in our data set warrants further study. Most plastic particles (large and small) accumulating in the SPSG likely have their origin in the countries around the South Pacific Ocean (Lebreton et al., 2012). Large amounts of plastic debris enters the ocean along the coasts of South America (Thiel et al., 2011). Even though a large proportion of this plastic pollution probably becomes deposited on nearby shores, a considerable fraction may escape shore deposition and finally accumulate in the SPSG. While coastal sources of plastic debris around the South Pacific arguably might be fewer than in the North Pacific and North Atlantic, the abundance of microplastics in the SPSG are of similar magnitude as in the oceanic gyres of the northern hemisphere. This result is in contrast to the model estimates by Lebreton et al. (2012) who considered geographic variations in plastic sources. They predicted substantially lower amounts of plastic particles in the SPSG compared to the North Pacific or North Atlantic subtropical gyres. Possibly, they underestimated the sources of plastics around the South Pacific.