Journal articles on the topic 'VARA-model'

Quantifying differences in joint loading for coxa vara and coxa valga is important for understanding what constitutes a pathological deformity. Prior free-body analyses for varus and valgus femora suggest that the loading direction in single-leg stance becomes more vertical for coxa valga and more horizontal for coxa vara. The objectives of this study were: 1) to apply a density-based load estimation technique to varus and valgus femora; 2) to infer potential differences in femoral loading for varus and valgus femora from the density; and 3) to compare the results with previous studies of femoral loading for single-leg stance. Representative valgus, normal, and varus femora from male cadavers were scanned in the plane of the femoral neck using computed tomography. A two-dimensional finite element model, including the density data from the CT scans, was constructed for each femur. A density-based bone load estimation method was used to determine the dominant loading pattern, and an average load direction was calculated. The average load direction varied consistently from more vertical for coxa valga to more horizontal for coxa vara. The results indicate that the differences in loading directions reduce the risk of epiphyseal slip or neck fracture in coxa vara and increase the tendency for subluxation or dislocation in coxa valga. Agreement between relative load angles from the density-based load estimation and free-body analyses confirms that internal femoral density is adapted to applied loads regardless of external femoral geometry.

Abstract The critical roles of retinoic acid (RA), a metabolite of vitamin A (VA), in both tolerogenic and immunogenic immune responses have been documented. However, how VA affects the development of autoimmunity is still unclear. Here we demonstrate that pharmacological doses of VA had adverse effects on the development of autoimmune lupus in the MRL/lpr mouse model. We administered, orally, RA (6 mg/kg body weight/day) or retinyl palmitate combined with 10% RA (VARA, a total of 6.6 mg/kg/day) to the mice starting from 6 weeks of age. At this age, the mice do not exhibit overt signs of lupus. However, the immunogenic environment preceding disease onset has been established that is evidenced by an increase of total IgM/IgG in the plasma and expansion of lymphocytes and dendritic cells in secondary lymphoid organs. After 8 weeks of RA or VARA treatment, significantly higher pathological scores in kidney, lung, and brain were observed, which were correlated with a marked increase in B-cell responses. In addition, although the number of T cells in the mesenteric lymph node decreased with RA that led to reduced tissue weight, the proportions of T-cell subsets did not change. Importantly, neither RA nor VARA affected regulatory T cells in these mice. Altogether, our results suggest that under the immunogenic environment in autoimmune lupus, VA can generate more severe disease rather than inducing tolerance. Thus, administration of VA in lupus treatment should be approached with caution.

AbstractThe present work addresses the urgent demand for methods of quantifying the uncertainties inherent in the current procedures for avalanche hazard assessment. A Monte Carlo approach to hazard mapping is proposed for this purpose. This statistical sampling-analysis method allows us to evaluate the probability distributions of the relevant variables for avalanche hazard assessment –– essentially runout distance and impact pressure-once the release variables and the model parameters are expressed in terms of suitable probability distributions. In this way it is possible to explicitly account for uncertainties both in the input-data definition of the dynamic models and in the mapping results. The overall methodology is presented in detail and applied to a real-world avalanche mapping problem. The one-dimensional version of the VARA models is used for avalanche dynamics simulations.

O presente artigo pretende descrever o fenômeno interacional das prestações de contas não harmônicas no cenário da Vara de Família. A partir do aporte teórico da Análise da Conversa Etnometodológica, a análise de dados de fala-eminteração nesse contexto vai nos possibilitar discutir o papel da representante da instituição nesse tipo de atividade (SARANGI, 2001). Os dados foram gerados no Fórum de uma cidade de interior no Sudeste brasileiro e compõem um corpus de cerca de 200 minutos de gravações em áudio, que foram transcritas de acordo com o modelo Jefferson de transcrição (LODER, 2008).PALAVRAS-CHAVE: Fala de conflito. Prestações de contas. Episódios de conflito. Análise da conversa. Estudo de caso.ABSTRACT This article aims to describe the interactional phenomenon of nonharmonic accounts in Family Court setting. From the theoretical framework of Conversation Analysis, the analysis of talk-in-interaction data in this context will allow us to discuss the role of the professional who acts in name of the institution in this activity-type (Sarangi, 2001). The corpus was generated in Courtroom in a town in southeastern Brazil and comprise a whole of about 200 minutes of audio recordings, which were transcribed according to Jeffersonian model of transcription (Loder, 2008).KEYWORDS: Conflict talk. Accounts. Conflict episodes. Conversation Analysis. Case study.

This study proposes a procedural analysis on the implementation of ludic linguistics to analyze gaming language with wordplays, the core of focus in ludic linguistics, as the point of departure. To formulate the procedural analysis, theories of language play by Crystal ideology of influence and ludonarrative model by Aarseth, wordplay in gaming context by Paul, intended meaning level by Stiles, wordplay transmission by Winter-Froemel, game interface types by Stonehouse and indexical storytelling by Fernández-Vara were applied as the theoretical foundation. To provide a vivid application of the proposed procedural analysis, wordplays appearing on game assets from Konami’s Metal Gear Solid, Metal Gear Solid 2: Sons of Liberty, and Metal Gear Solid 3: Snake Eater were taken as examples of analysis. The five steps procedure is able to show how wordplays in gaming context are designed as mechanical cues to help gamers complete the games and as narrative cues to help them comprehend the story. Further, this proposed procedure is able to indicate that the mechanical and narrative cues have particular ideology of influence, which affects gamers in reacting and responding to particular problems presented by the games. The result of this study discloses future research on the roles of wordplays in gaming context, signifying the importance of ludic linguistics as a bridge between language studies and game studies. Keywords: Wordplay; Gaming Language; Ludic Linguistics; Game Dtudies; Metal Gear Solid

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4—PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4−/− (N = 44) mice of both sexes were injected with rhPRG4 and gait alterations were studied at post-injection day 3 and 6, before joints were harvested for immunohistochemistry for caspase-3 activation. Increased stance and propulsion was shown at 3 days post-injection in male mice. There were significantly fewer caspase-3-positive chondrocytes in tibiofemoral cartilage from rhPRG4-injected mice. The mitochondrial gene Mt-tn, and myosin heavy (Myh7) and light chains (Myl2 and Myl3), known to play a cytoskeletal stabilizing role, were significantly upregulated in both sexes (RNA-Seq) following IA rhPRG4. Chondrocyte mitochondrial dyscrasias attributable to the arthrosis in CACP may be mitigated by IA rhPRG4. In a supporting in vitro crystal microbalance experiment, molecular fouling by albumin did not block the surface activity of rhPRG4.

Purpose We aimed to investigate the association between SHBG and the homeostatic model assessment of insulin resistance (HOMA-Ir) in men and women in a prospective observational study. Methods The Vara-Skövde cohort is a random population of 2816 participants living in southwestern Sweden, aged 30–74. It was recruited between 2002 and 2005, and followed up in 2012–2014. After excluding participants on insulin therapy or hormone replacement therapy, 1193 individuals (649 men, 544 women) were included in the present study. Fasting blood samples were collected at both visits and stored in biobank. All participants were physically examined by a trained nurse. SHBG was measured with immunoassay technique. Linear regressions were computed to investigate the association between SHBG and HOMA-Ir both in cross-sectional and longitudinal analyses, adjusting for confounding factors. Results The mean follow-up time was 9.7 ± 1.4 years. Concentrations of SHBG were significantly inversely associated with log transformed HOMA-Ir in all groups with estimated standardized slopes (95% CI): men: −0.20 (−0.3;−0.1), premenopausal women: −0.26 (−0.4;−0.2), postmenopausal women: −0.13 (−0.3;−0.0) at visit 1. At visit 2 the results were similar. When comparing the groups, a statistically significant difference was found between men and post-menopausal women (0.12 (0.0;0.2) P value = 0.04). In the fully adjusted model, SHBG at visit 1 was also associated with HOMA-Ir at visit 2, and the estimated slopes were −0.16 (−0.2;−0.1), −0.16 (−0.3;−0.1) and −0.07 (−0.2;0.0) for men, premenopausal and postmenopausal women, respectively. Main conclusion Levels of SHBG predicted the development of insulin resistance in both men and women, regardless of menopausal state.

Objective.C677T and A1298C polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with increased cardiovascular (CV) events in non-rheumatoid arthritis (RA) populations. We investigated potential associations of MTHFR polymorphisms and use of methotrexate (MTX) with time-to-CV event in data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry.Methods.VARA participants were genotyped for MTHFR polymorphisms. Variables included demographic information, baseline comorbidities, RA duration, autoantibody status, and disease activity. Patients’ comorbidities and outcome variables were defined using International Classification of Diseases-9 and Current Procedural Terminology codes. The combined CV event outcome included myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass graft surgery, and stroke. Cox proportional hazards regression was used to model the time-to-CV event.Results.Data were available for 1047 subjects. Post-enrollment CV events occurred in 97 patients (9.26%). Although there was a trend toward reduced risk of CV events, MTHFR polymorphisms were not significantly associated with time-to-CV event. Time-to-CV event was associated with prior stroke (HR 2.01, 95% CI 1.03–3.90), prior MI (HR 1.70, 95% CI 1.06–2.71), hyperlipidemia (HR 1.57, 95% CI 1.01–2.43), and increased modified Charlson-Deyo index (HR 1.23, 95% CI 1.13–1.34). MTX use (HR 0.66, 95% CI 0.44–0.99) and increasing education (HR 0.87, 95% CI 0.80–0.95) were associated with a lower risk for CV events.Conclusion.Although MTHFR polymorphisms were previously associated with CV events in non-RA populations, we found only a trend toward decreased association with CV events in RA. Traditional risk factors conferred substantial CV risk, while MTX use and increasing years of education were protective.

ResuméStudiens syfte är att undersöka hur yrkesverksamma i fritidshem beskriver sitt arbete, sin trivsel, de inkluderande arbetssätt som används och samverkan. Detta görs med teoretisk utgångspunkt i förklaringsmodellen formuleringsarenan, transformerings- och medieringsarenan, och realiseringsarenan med fokus på vad fritidshemmets uppdrag blir i pedagogisk praktik. Data samlades in genom enkäter med yrkesverksamma (N=63) i fritidshem från olika orter i Sverige. Studiens resultat påvisar att de har ett varierat arbete, att de trivs, att de erbjuder inkludering och att de, med få undantag, sätter in stödinsatser. Mindre än hälften av dem beskriver att de erbjuds handledning och rådgivning från specialpedagog eller annan profession med specialpedagogiska kunskaper, samt att de samverkar med elevhälsa. Fritidshemmets resurser beskrivs i viss mån som otillräckliga och stödinsatserna kan många gånger anses vara för få. Förslag till vidare forskning diskuteras. AbstractSchool-age educare teachers’ work, well-being, inclusive education strategies and collaboration: a survey The aim of this study is to investigate how professionals in School-age educare (SAEC) describe their work environment, well-being, collaboration and the education strategies used. This is done by means of a theoretical understanding model including a formulation arena, a transformation and mediation arena and a realisation arena where the focus is on the realisation arena. Empirical data was collected through surveys with professionals (N=63) in SAEC working in different Swedish cities. The result of the study shows that they have a multifaceted work, that they are content/happy, that they provide inclusive education and support measures. Less than half of those surveyed describe that they receive adequate supervision and advice from a special needs educator or other profession with special needs education knowledge and that they collaborate with the School health services. The resources of the SAEC are to some extent perceived as insufficient and the support measures are often too limited. Suggestions for further research are discussed.

Purpose The purpose of this paper is to identify strengths and weaknesses in the communication of performance measures and propose guidelines for the visualization of performance measures supporting continuous improvement (CI) in manufacturing small and medium-sized enterprises (SMEs). The goal is to help manufacturing SMEs improve their communication of performance measures, thereby improving performance, and strengthening the company. Design/methodology/approach This paper draws on both theoretical and empirical research. It begins with a literature review of theoretical guidelines for the visualization of performance measures. This theoretical information is then supplemented with a case study and a survey, both carried out at the Vara plant, a manufacturing SME with well-developed communication of performance measures. The case study involved all organizational levels in the company and focused on identifying strengths and weaknesses in visual communication of performance measures supporting CI. The information acquired from the literature survey and the case study was then used as the basis for a survey of the employees in one department as regards their perception, understanding and opinion of visual communication of performance measures. The analysis of the results led to the development of guidelines and a substantive proposal improving visualization of performance measures in this specific company, and in manufacturing SMEs in general. Findings A model for the visualization of performance measures supporting CI in the company was carried out. The guidelines proposed for all such visualizations are as follows: keep the visualization as simple as possible without compromising understanding, use symbols and colors consistently, use simple words and do not include too much information in the visualization. The study also shows that it is important to support a written visualization with an oral presentation to explain the results. Originality/value The originality of this paper lies in its focus on the visualization of performance measures in manufacturing SMEs and the guidelines and proposals developed.

SammanfattningTexten behandlar hur elever på svensk grundskolenivå i årskurs 1–8, med hjälp av olika lässtrategier, kan skaffa sig förmåga att djupläsa texter för att nå förståelse av både läsningen och det lästa. Den teoretiska och metodologiska basen hänvisar till den amerikanska läsforskning som har bedrivits av Judith A. Langer med ett stort forskarteam vid Albany University, USA. Djupläsningsmetoder förklaras och diskuteras. Artikeln diskuterar Langers “envisionment-building” begrepp och presenterar ett empiriskt material taget från en undersökning av lässtrategier hos elever i åldrarna 7–13. I Sverige har teorin operationaliserats av författaren i fortsättningsforskning i skolor. Den didaktiska läsutvecklingen från svenska skolor beskrivs. Resultat och diskussion handlar om hur barn och ungdomar kan skapa djup förståelse av text. De autentiska fasbaserade frågorna som används både muntligt och skriftligt vid djupläsning gör att innehållet blir grundligt diskuterat i samtal med lärare och kamrater. Omläsning visar sig vara viktigt. Genomförda textsamtal resulterar i ett mycket fördjupat läsande för eleverna. Motivationshöjande är att eleverna får agera socialt genom textsamtal vid tolkningen och att det ständigt sker en återkoppling från lärarens och kamraternas sida. Motivationen kan även öka om eleverna lyckas med alltmer utmanande texter. Djupläsning med fas¬baserade frågor är en effektiv lässtrategi för att skapa förutsättningar för djupläsning, som i sin tur ger förutsättning för bästa möjliga förståelse av läsningen såväl som det lästa. Läsmarkeringar under läsningens gång gör att läsningen blir långsammare och mer grundlig. Läsandets förutsättning, villkor och process kan sammanfattas i en modell skapad utifrån operationaliseringsprocessen.Nyckelord: djupläsning, textsamtal, lässtrategier, didaktik, läsmotivationClose reading and reading strategiesAbstractThe text discusses how Swedish pupils in primary and secondary school, aged 7–13, with the aid of different reading strategies, can improve their ability to close-read texts in order to gain a better understanding not only of the text but also of the reading process. The study is theoretically and methodologically anchored in the reading research of Judith A. Langer, University of Albany, USA. The study adapts and develops Langer’s concept of envisionment building. The empirical material includes a study of the reading strategies of Swedish pupils aged 7–13. In Sweden, these findings have been operationalized by the author as part of her continuing research in schools. The results and discussion address how children can acquire a deep understanding of texts. The authentic, stance-based questions, which are used both when students read aloud and silently, ensure that the content is properly discussed in text talks with teachers and other pupils. Re-reading is important. The text talks result in a close reading of the texts. The social interaction that is part of text interpretation, as well as the feedback students receive from one another and from their teacher, boost motivation. Motivation can also increase if the students succeed with more challenging texts. Close reading with stance-based questions is a very effective reading strategy, which enables the students to understand the text and the reading process. Taking notes while reading makes the reading slower and more thorough. The conditions, terms and process of reading are summed up in a model that describes what happens.Keywords: close reading, text talks, reading strategies, didactics, motivation for reading

<p>A model for long-term analysis of the influence of timber production on lichens for reindeer grazing (Cladina, Alectoria, Bryoria spp and others) in Sweden is presented. The annual production of and demand for lichens are estimated and compared. Production of these lichens is presumed to set the upper limit for the reindeer population. Reindeer graze on both ground and tree lichens, which both must be accessible in sufficient amounts and at the right times of the year if reindeer husbandry is to succeed without supplementary feeding. The model is based mainly on existing data, and uses are estimations from the National Forest Survey and the Hugin system for calculation of longterm potential cut (Bengtsson, 1981). Geographically the study is limited to Vasterbotten and Norrbotten, the northernmost counties in Sweden, where most reindeer husbandry in Sweden is located, and where reindeer grazing takes place over almost the whole area. The calculations cover a period of one hundred years from 1980, and are based on a timber production programme which relies more on &laquo;multiple use&raquo; than the current Swedish forest policy (Bengtsson, 1986). The annual production of ground lichens is calculated by multiplying the area covered with ground lichens by their increment as estimated from their rate of biomass increase, which in turn depends on site factors and age of the stand. The estimation of the area is based on data from the National Forest Survey. Sample plots with ground lichens are assumed to maintain lichens during the whole hundred year period. Areas with stands that have been thinned within ten years and stands younger than 20 years are excluded due to logging residues from thinnings and packed snow. Some of the remaining area cannot practically be utilized for reindeer grazing. Representatives of three communities of reindeer herders classified 212 plots from the National Forest Survey with ground lichens and assessed that 3/4 of the plots can be utilized. The reduction was because of location (near buildings, roads, railroads, and recreation facilities), or because the area with lichens was too small and isolat&eacute;d. Demand for ground lichens is calculated as the daily demand for ground lichens by the reindeer multiplied by the number of days every year that reindeer depend on this forage. Figures used are based upon estimations from persons with great experience of reindeer farming. The annual production of tree lichens consists of two parts, i.e., tree lichens within reach of the reindeer, and tree lichens which become accessible after falling down from the trees onto the snow. Forest stands dominated by conifers and older than one hundred years are assumed to bear tree lichens. This area is also reduced to 75 per cent for reasons of practical accessibility. Annual production of lichens in reach of the reindeer is then estimated as the area multiplied by the increment rate of the biomass. One quarter of the annually fallen tree lichens is assumed to be available as fodder during late winter/early spring. The demand for tree lichens is principally estimated in the same way as for ground lichens, but the number of days per years is lower because tree lichens are mainly considered to be fodder in distress periods. Two sources of uncertainty are present in the results, namely the influence of factors not included in the models, and the influence of uncertainty in factors included in the models. The models used to estimate production and demand obviously imply simplifactions of true relations. These simplifications are mainly due to a basic lack of knowledge, one example being that variation, i.e. in volume per hectare, might very well influence the production of lichens, but is not taken into consideration in the models. One example of uncertainty in data used is the increment rate of lichen fodder. Another example is the estimation of biomass of lichens, here based upon investigations (Eriksson, unpubl.) with other purposes than to provide data about grazing availability in the large geographic regions used in this study. The possibilities for drawing reliable conclusions will increase when better estimations of input data and relationship are available. The geographic division into four regions is a result of the design of the National Forest Survey. However, great differences may be present within these geographic areas, each containing a number of communities of reindeer herders. Thus, results are not applicable to single communities of reindeer herders. The study illustrates a method of revealing how lichen fodder for reindeer will develop in relation to timber production. The results of the calculations, however, are too uncertain to allow reliable conclusions to be drawn. Nonetheless, the results indicate that in some areas there is already a shortage of lichen fodder for the number of reindeer assumed in this study. The calculations hint that production will decrease in the future. These indications should motivate more research in this topic. If the results of this study are accurate and if forestry develops according to the assumptions, the owners of the reindeer will have to continue or increase the supplementary feeding and/or reduce the number of reindeer significantly. They will also have to utilize all of the areas that are possible to graze, even if some of them today are considered to be of marginal value for reindeer grazing. Another way to improve the balance of production and demand is to adjust forest management on areas with lichens to a greater extent than has been done in the timber production alternative analysed in this study.</p><p>Virkesproduktionens inverkan p&aring; renskotselns lavbete - En metodstudie.</p><p>Abstract in Swedish / Sammanfattning: En modell for l&aring;ngsiktig analys av virkesproduktionens inverkan p&aring; renskotselns lavbete(Cladina, Alectoria, Bryoria spp mfl) i Sverige presenteras. Modellen ber&aring;knar &aring;rlig produktion och behov av lavbete, ef^ersom tillg&aring;ngen p&aring; dessa lavar bedoms begr&aring;nsa renpopulationen. B&aring;de tr&aring;d- och marklavar betas av renarn&pound;| och m&aring;ste finnas tillg&aring;ngliga i tillr&aring;cklig m&aring;ngd och vid r&aring;tt tidpunkt under &aring;ret om renskotseln skall klara sig utan stodutfordring. Modellen bygger huvudsakligen p&aring; redan existerande data. Skattningarna av areal gors med data fr&aring;n riksskogstaxeringen och fr&aring;n ber&aring;kningar med Hugin-systemet for l&aring;ngsiktiga analyser av avverkningsmojlighe-terna (Bengtsson, 1981). Studien begr&aring;nsas geografiskt till Norr- och V&aring;sterbottens l&aring;n. Ber&aring;kningarna gors for en hun^ra&aring;rsperiod med start 1980, och bygger p&aring; ett virkesproduktionsprogram i A VB-85 som syftar till mera m&aring;ngbruk an dagens skogspolitik (Bengtsson, 1986). Den &aring;rliga produktionen av marklav skattas som produkten av m&aring;ngden marklav per hektar, dess till-v&aring;xtprocerit och arealen med marklav. M&aring;ngden marklav per hektar beror av st&aring;ndortsforh&aring;llanden och bes-t&aring;nds&aring;ldern. Skattningen av arealen baseras p&aring; uppgifter fr&aring;n riksskogstaxeringen. Provytor med marklav antas vara layb&aring;rande under hela prognosperioden. Provytor d&aring;r best&aring;nds&aring;ldern &aring;r l&aring;gre &aring;n 20 &aring;r, samt provytor som i awerkningsber&aring;kningen rojts eller gallrats under senaste tio&aring;rsperiod r&aring;knas dock bort. Orsaken &aring;r att snopacknirig och kvarl&aring;mnade stammar och ris forsv&aring;rar eller omojliggor for renen att komma &aring;t laven. Hela den &aring;terst&aring;ende arealen kan dock inte nytt jas for planerad renskotsel. Representanter for tre samebyar bedomd)e 212 av riksskogstaxeringens provytor med marklav med avseende p&aring; om de kan nytt jas for planerad renskotsel. Resultatet blev att 3/4 av provytorna ans&aring;gs kunna utnyttjas. Provytor r&aring;knades bort p&aring; grund av bel&aring;genlhet n&aring;ra byggnader, v&aring;gar, j&aring;rnv&aring;gar och friluftsanl&aring;ggningar, eller pga att arealen med marklav var for liten och isolerad for att kunna utnyttjas. Behovet av marklav ber&aring;knas som produkten av det genomsnittliga dygnsbehovet for en ren, antalet renar samt det ailital dagar per &aring;r som renarna bedoms ha behov av detta foder. De tv&aring; senare uppgifterna grundas p&aring; uppskattningar av personer med stor erfarenhet av renskotsel. Den &aring;rliga produktionen av tr&aring;dlavar best&aring;r dels av lavtillv&aring;xten i det betningsbara hojdintervallet, dels av tr&aring;dlav som faller ner p&aring; snon. Barrdominerade best&aring;nd aldre &aring;n hundra &aring;r antas vara tr&aring;dlavb&aring;rande, men &aring;ven denna areal reduceras med h&aring;nsyn till praktisk tillg&aring;nglighet. &Aring;rlig produktion av tr&aring;dlav inom r&aring;ckh&aring;ll for renen skattas som produkt av m&aring;ngden tr&aring;dlav, dess tillv&aring;xtprocent och arealen. Av den tr&aring;dlav som &aring;rli-gen faller n)er p&aring; marken antas en fj&aring;rdedel vara tillg&aring;nglig under v&aring;rvintern. Efterfr&aring;gan p&aring; tr&aring;dlav ber&aring;knas p&aring; i princip samma s&aring;tt som efterfr&aring;gan p&aring; marklav, men antal betningsda-gar per &aring;r &aring;k l&aring;gre eftersom tr&aring;dlav huvudsakligen &aring;r ett visserligen hogkvalitativt och l&aring;ttillg&aring;ngligt, men dock nodfoder. Resultaten &aring;r os&aring;kra av tv&aring; huvudorsaker. Dels pga inverkan av faktorer som inte ing&aring;r i modellen, dels os&aring;kerhetejn i de faktorer som ing&aring;r i modellen. Modellen inneh&aring;ller uppenbart forenklingar av verkliga samband. Dessa forenklingar beror huvudsakligen p&aring; viss brist p&aring; grunddata. Mojligheterna att dra s&aring;kre slutsatser kommer att oka i takt med b&aring;ttre kunskap om utnyttjade samband och uppgifter. Den geografiska indelningen i l&aring;nsdelar beror p&aring; utformningen av riksskogstaxeringen. Forh&aring;llandena kan givetvis variera inom dessa l&aring;nsdelar, som var och en best&aring;r av ett flertal samebyar. Resultaten f&aring;r s&aring;ledes inte till&aring;mpas p&aring; enskilda samebyar. Studien visar p&aring; en metod for att belysa hur renskotselns lavbete kommer att utvecklas i relation till virkes-produktionen. Resultaten &aring;r dock allt for os&aring;kra for att man skall kunna dra n&aring;gra s&aring;kra slutsatser. Resultaten antyder emellertid att for vissa omr&aring;den finns redan i dag en brist p&aring; lavbete for den renpopulation som kalkylerats med i denna studie. Ber&aring;kningarna antyder att produktionen av lavbete kommer att minska i framtiden, vilket bor motivera mer forskning inom omr&aring;det. Om resultaten i denna studie &aring;r riktiga och om det virkesproducerande skogsbruket utvecklas enligt exemplet, m&aring;ste ren&aring;garna forts&aring;tta med eller utoka stodutfodringen och/eller minska antalet renar betydligt. De tvingas ocks&aring; utnyttja alla betningsbara omr&aring;den, &aring;ven s&aring;dana som for n&aring;rvarande anses vara marginella. Ett annat s&aring;tt att forb&aring;ttra balansen &aring;r att modifiera det virkesproducerande skogsbruket p&aring; arealer med lavbete i storre utstr&aring;ckning &aring;n vad som gors i det alternativ som analyseras h&aring;r.</p><p>Puuntuotannon vaikutus j&auml;k&auml;l&auml;laitumiin.</p><p>Abstract in Finnish / Yhteenveto: Artikkelissa esitet&aring;&aring;n pitk&aring;naikav&aring;lin analyysimalli puuntuotannon vaikutuksista ruotsin j&aring;k&aring;l&aring;-laitumille (Cladina, Alectoria, Bryoria spp. ym.). Koska j&aring;k&aring;lien saantia pidet&aring;&aring;n porojenlukum&aring;&aring;r&aring;&aring; rajoittava, laskee malli j&aring;k&aring;l&aring;laidunten vuotuisen tuoton ja tarpeen. Porot laiduntavat sek&aring; puussa ett&aring; maassa kasvavia j&aring;k&aring;li&aring;, ja nit&aring; molempia on oltava saatavilla, sek&aring; tarvittava m&aring;&aring;r&aring;, ett&aring; oikeaan aikaan vuodesta, jos poronhoito aikoo selviyty&aring; ilman tukiruokintaa. Malli rakentuu p&aring;&aring;siassa jo aikaisemmin hankittuihin tietoihin. Pinta-ala arviot tehd&aring;&aring;n valtakunnanmets&aring;narvioinnin tietojen, ja hakkuumahdollisuuksien pitk&aring;naikav&aring;lin analysoimiseksi perustetun Hugin-systeemin laskelmien avulla (Bengtsson, 1981). Maantieteellisesti tutkielma rajoittuu Norrbotte-nin ja V&aring;sterbottenin l&aring;&aring;neihin. Laskelmat tehd&aring;&aring;n sadanvuoden aikav&aring;lille alkaen 1980, perustuen yhteen AVB-85:en puuntuotantoohjelmaan, joka t&aring;ht&aring;&aring; t&aring;m&aring;np&aring;iv&aring;ist&aring; laajempaan metsien moninaisk&aring;yttoon (Bengtsson, 1986). Vuotuinen maassa kasvavien j&aring;k&aring;lien tuotanto arvioidaan j&aring;k&aring;lien hehtaarim&aring;&aring;rien, sen kasvuprosentin ja pinta-alan tulona. J&aring;k&aring;lien m&aring;&aring;r&aring; hehtaaria kohti on riippuvainen kasvupaikan ja metsikon i&aring;st&aring;. Pinta-ala arviot perustuvat valtakunnanmets&aring;narvioinnin tietoihin. J&aring;k&aring;l&aring;&aring; kasvavien koealojen odotetaan pit&aring;v&aring;n j&aring;k&aring;-l&aring;kasvustonsa koko prognoosiajan. Koealat, joissa metsikon ik&aring; on alle 20 vuotta, sek&aring; koealat, jotka hak-kuulaskelmissa on perattu tai harvennettu viimeisen kymmenen vuoden aikana, on j&aring;tetty huomioimatta. Syyn&aring; t&aring;h&aring;n on lumenpakkaantuminen, sek&aring; j&aring;ljelle j&aring;tetyt rungot ja oksat, jotka vaikeuttavat tai tekev&aring;t po-rojen j&aring;k&aring;l&aring;n saannin mahdottomaksi. Vuotuinen puussa kasvavien j&aring;k&aring;lien tuotanto koostuu, osittain poron ulottuvilla olevasta, ja osittain lu&not;melle putoavasta jak&aring;l&aring;st&aring;. Yli sata vuotta vanhojen havupuuvaltaisten metsikkojen oletetaan tuottavan puussa kasvavia j&aring;k&aring;li&aring;, mutta myos t&aring;m&aring; pinta-ala pienenee k&aring;yt&aring;nnon syist&aring;. Vuotuinen poronulottuvilla puussa kasvavien j&aring;k&aring;li&aring; tuotanto arvioidaan j&aring;k&aring;l&aring;n m&aring;&aring;r&aring;n, sen kasvuprosentin ja pinta-alan tulona. Yksi nelj&aring;nnesosa siit&aring; vuosittain lumelle tippuvasta j&aring;k&aring;l&aring;m&aring;&aring;r&aring;st&aring; oletetaan olevan saatavilla kev&aring;ttalvella. Puussa kasvavien j&aring;k&aring;lien kysynt&aring; lasketaan periaatteessa samalla tavoin kuin maassa kasvavien j&aring;k&aring;lien ky-synt&aring;, paitsi ett&aring; vuorokausien m&aring;&aring;r&aring; vuodessa on pienempi, koska puussa kasvavavien j&aring;k&aring;lien katsotaan p&aring;-&aring;asiassa olevan h&aring;t&aring;ravintoa. Tulokset ovat ep&aring;varmoja kahdesta p&aring;&aring;syyst&aring;. Osittain niiden tekijoiden vuoksi, jotka eiv&aring;t sis&aring;lly malliin, osittain niiden tekijoiden ep&aring;tarkkuudesta, jotka sis&aring;ltyv&aring;t malliin. Malli sis&aring;lt&aring;&aring; selvi&aring; todellisten yhteyksien yksinkertaistamisia. N&aring;m&aring; yksinkertaistamiset johtuvat p&aring;&aring;asiassa perustietojen puutteesta. Esimerkkin&aring; voidaan mainita, ett&aring; mets&aring;n tila muuttuu paljolti prognoosikauden aikana. T&aring;t&aring; vaihtelua esimerkiksi puus-tossa ei kuitenkaan mallissa huomioida. Esimerkki niiden tekijoiden ep&aring;tarkkuudesta, jotka sis&aring;ltyv&aring;t malliin, on j&aring;k&aring;l&aring;laidunten kasvuprosentti. Toinen esimerkki on j&aring;k&aring;l&aring;m&aring;&aring;rien arviot, jotka t&aring;ss&aring; perustuvat tutkielmiin (Eriksson, julkaisematon), joilla on ollut toinen tarkoitusper&aring; kuin t&aring;ss&aring; tutkimuksessa k&aring;sitelt&aring;vien l&aring;&aring;ninosien laiduntamahdollisuuksien arvioiminen. Mahdollisuudet varmojen johtop&aring;&aring;tosten tekoon lis&aring;&aring;ntyv&aring;t yhdess&aring; parempien perustietojen myot&aring; k&aring;ytetyist&aring; yhteyksist&aring; ja tiedoista. Maantieteellinen jako l&aring;&aring;ninosiin johtuu valtakunnanmets&aring;narvioinin rakenteesta. Olosuhteet voivat tie-tysti vaihdella n&aring;iden l&aring;&aring;ninosien sis&aring;ll&aring;, joista jokainen sis&aring;lt&aring;&aring; useamman paliskunnan. Tuloksia ei siis saa tulkita paliskunta kohtaisesti. Tutkielma esitt&aring;&aring; tavan valoittaa kuinka porohoidon j&aring;k&aring;l&aring;laitumet kehittyv&aring;t suhteessa puuntuotantoon. Tulokset ovat kuitenkin liian ep&aring;varmoja, jotta niist&aring; voitaisiin vet&aring;&aring; varmoja loppup&aring;&aring;telmi&aring;. Tulokset viittaavat kuitenkin, ett&aring; tietyill&aring; alueilla on jo talla hetkell&aring; pula j&aring;k&aring;l&aring;laitumista niill&aring; porom&aring;&aring;rill&aring;, joilla tassa tutkielmassa on laskettu. Laskelmat viittaavat, ett&aring; tuotanto v&aring;henee tulevaisuudessa, mink&aring; pit&aring;isi motivoida laajempaa tutkimukseen t&aring;ll&aring; alueella. Jos tulokset t&aring;ss&aring; tutkimuksessa ovat oikeat ja jos puuntuotannollinen mets&aring;talous kehittyy esimerkin mu-kaisesti, pit&aring;&aring; poronomistajien jatkaa tai lis&aring;t&aring; tukiruokintaa ja/tai v&aring;hent&aring;&aring; porojen lukum&aring;&aring;r&aring;&aring; huomatta-vasti. He joutuvat my os hyodynt&aring;m&aring;&aring;n kaikki laiduntamiskelpoiset alueet, my os sellaiset jotka t&aring;ll&aring; hetkell&aring; ovat v&aring;hemm&aring;n t&aring;rkeit&aring;. Toinen tapa par ant aa tasapainoa on sopeuttaa j&aring;k&aring;l&aring;alueiden puuntuotannollinen mets&aring;talous suuremmassa m&aring;&aring;rin kuin t&aring;ss&aring; analysoitavassa vaihtoehdossa tehd&aring;&aring;n.</p>

Abstract MLN0128 (TAK-228, INK128) is an investigational new drug (IND) that is currently being evaluated in clinical trials and has showed promising efficacies in patients with solid cancer. MLN0128 is one of the second generation of inhibitors for mammalian target of rapamycin (mTORi), which suppresses the dysregulated cell survival signaling activities in cancer cells by specifically inhibiting both mTORC1 and mTORC2 in PI3K/mTOR pathway. MLN0128 was reported inhibiting acute myeloid leukemia (AML) stem cells and progenitors [Zeng et al, Oncotarget, 2016]. However, it is yet to be clarified whether MLN0128 can improve survival time in leukemia patients. Here, we report data from the investigation of the impact of MLN0128 on leukemia survival in mice. We tested MLN0128 in a published mouse model which simultaneously produces experimental mice with genotypes that are associated with pediatric leukemia, including myeloproliferative neoplasm (MPN) and juvenile myelomonocytic leukemia (JMML), and adult chronic myelomonocytic leukemia (CMML) [Vara et al, Blood Adv.2020]. Specifically, mice with deletion of Phosphatase and tensin homolog gene (Pten) and loss-of-heterozygosity of Neurofibromin 1 (Nf1) (Pten Δ/ΔNf1 LOH) develop JMML, mice with Pten deletion and Nf1 heterozygosity (Pten Δ/ΔNf1 Δ/wt) develop pediatric MPN, both of which cause juvenile death; mice with a single copy of Pten deletion and Nf1 LOH (Pten Δ/wtNf1 LOH) develop CMML in adulthood. We previously reported that all of those diseased mice shared a feature with elevated activities in PI3K/MAPK/mTOR pathways. We first collected nucleated cells from bone marrow (BM) of the diseased mice and tested the inhibition of MLN0128 on colony formation of hematopoietic progenitors (CFU-GM) at a concentration range of 1-1000nM. Our data demonstrated that MLN028 significantly inhibited the CFU-GM colony formation of BM cells from mice with all three diseased genotypes, in a dose-dependent fashion. Importantly, the IC50 for CFU-GM was less than 100nM, which is in the concentration range of MLN0128 in the blood from patients who orally received MLN0128 at dosage range of 4-12mg/day [Ghobrial et al AJH 2016]. We then investigated the impact of MLN0128 on life span in diseased mice. We administrated MLN0128 in gavage at dosages of 0.5-1μg/g body weight, starting at an age of postnatal day 17-18 (PND17-18), 3-5 times a week, repeated for 5 weeks followed by a pause in 6 th week every course. Our data showed that MLN0128 significantly reduced the spleen sizes in treated mice with all diseased genotypes comparing to those treated with vehicle. The survival time was significantly prolonged in MLN0128-treated mice with genotypes of MNP (n=7 vs 3, median 150 vs 102 days) and CMML (n=7 vs 6, median 100 vs 56 days), comparing with the mice treated by vehicle. Unfortunately, we did not observe a survival improvement in treated JMML mice, but substantially swollen kidneys were found in the dead JMML mice, which was likely due to tumor-lysis syndrome because JMML mice carried a significantly worse leukemic burden. In conclusion, our data demonstrate that MLN0128 can significantly inhibit colony formation of BM cells from mice with genotypes of JMML, MPN, and CMML; and MLN0128 can significantly expand survival time of mice with genotypes of MPN and CMML, which has never been reported in previous studies that were related to mTORi in pediatric leukemia. Our data suggest that MLN0128 may be a potential target therapy for pediatric MPN and CMML with a benefit of prolonging survival. Further investigation is ongoing to evaluate the potential of MLN0128 in improving survival of JMML mice after minimizing the tumor-lysis syndrome by tipping down MLN0128 dosage. Disclosures Bertaina: Cellevolve Bio: Membership on an entity's Board of Directors or advisory committees; Neovii: Membership on an entity's Board of Directors or advisory committees; AdicetBio: Membership on an entity's Board of Directors or advisory committees.

El objetivo fue diseñar propuestas de mejora para un servicio de mantenimiento y reparación de vehículos que posee la concesión de una marca internacional de automóviles. La metodología consideró principalmente los aportes del modelo chileno de gestión de excelencia, una norma para el tratamiento de los reclamos, una metodología de diagnóstico de gestión, las dimensiones del modelo Servperf y la técnica de análisis de factores. Los principales resultados permitieron conocer el nivel de calidad del servicio, identificación de una dimensión de calidad subyacente, catorce prácticas de gestión y el diseño de un mecanismo de control y seguimiento fundamentado en la teoría del cuadro de mando integral. Las principales conclusiones indican que integrando los aportes de la literatura de gestión de calidad se pueden diseñar propuestas de mejora en los ámbitos estratégico, personal, análisis de datos, métodos y tecnología. 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Amat, «Del dominio del control financiero a una perspectiva cualitativa del control de gestión,» Revista Facultad de Ciencias Económicas: Investigación y Reflexión., vol. 24, nº 1, pp. 5-11, 2016. [30]F. Ganga, L. Ramos, A. Leal y K. Pérez, «Administración estratégica: Aplicación del cuadro de mando integral (CMI) a una organización no gubernamental,»2015. [En línea]. Disponible en: http://www.redalyc.org/articulo.oa?id=28037734012. [31]P. Niven, Balanced Scorecard Evolution: A Dynamic Approach to Strategy Execution, USA: Wiley, 2014. [32]F. Doguett, Calidad y Satisfacción en el Servicio a Clientes de la Industria Automotriz: Análisis de Principales Factores que Afectan la Evaluación de los Clientes, Chile: Tesis de Grado, 2012. [33]F. Vázquez, E. Harzheim, S. Terrasa y S. 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Abstract Background Many genetic variants have been reported from sequencing projects due to decreasing experimental costs. Compared to the current typical paradigm, read mapping incorporating existing variants can improve the performance of subsequent analysis. This method is supposed to map sequencing reads efficiently to a graphical index with a reference genome and known variation to increase alignment quality and variant calling accuracy. However, storing and indexing various types of variation require costly RAM space. Methods Aligning reads to a graph model-based index including the whole set of variants is ultimately an NP-hard problem in theory. Here, we propose a variation-aware read alignment algorithm (VARA), which generates the alignment between read and multiple genomic sequences simultaneously utilizing the schema of the Landau-Vishkin algorithm. VARA dynamically extracts regional variants to construct a pseudo tree-based structure on-the-fly for seed extension without loading the whole genome variation into memory space. Results We developed the novel high-throughput sequencing read aligner deBGA-VARA by integrating VARA into deBGA. The deBGA-VARA is benchmarked both on simulated reads and the NA12878 sequencing dataset. The experimental results demonstrate that read alignment incorporating genetic variation knowledge can achieve high sensitivity and accuracy. Conclusions Due to its efficiency, VARA provides a promising solution for further improvement of variant calling while maintaining small memory footprints. The deBGA-VARA is available at: https://github.com/hitbc/deBGA-VARA.

Syftet med artikeln är att lyfta fram om, och i sådant fall på vilka sätt, en specifik strukturell modell kan utgöra stöd när elever utforskar matematiska strukturer i ekvationer. Artikeln bygger på en empirisk forskningsstudie där elever utforskade matematiska strukturer med stöd av modellen, vilken är avsedd att visualisera strukturer. Lärare och forskare arbetade i en kollaborativ och intervenerande studie i iterativa processer. Sammantaget 149 elever från grundskolans årskurser 3, 8 och 9 deltog i filmade forskningslektioner utifrån forskningsansatsen learning study. Lektionerna designades med inspiration från ramverket lärandeverksamhet och eleverna utmanades i ett teoretiskt arbete. Analysen utfördes utifrån tematisk ansats och två kvalitativt skilda kärnteman identifierades: Formulär respektive Lärandemodell. I analysen framträdde att undervisningen behöver vara tillräckligt utmanande för att eleverna ska finna modellen meningsfull. Undervisningen behöver möjliggöra för eleverna att urskilja relationer mellan alla tal i en ekvation, där relationerna kan beskrivas som en del-helhetsstruktur. A model to support exploring equations The aim of the article is to highlight whether, and if so in what ways, a selected model can constitute support when students explore mathematical structures in equations. The article is based on an empirical research study where students explored mathematical structures with support by the model, which is intended to visualize structures. Teachers and researchers worked in a collaborative and interventional study in iterative processes. A total of 149 students from compulsory school grades 3, 8 and 9 participated in video recorded research lessons based on the research approach learning study. The lessons were designed with inspiration from the framework of learning activity and the students were challenged in a theoretical work. The analysis was performed on the basis of a thematic approach and two qualitatively different core themes were identified: Template respectively Learning model. In the analysis, it emerged that the teaching has to be challenging enough for the students to find the model meaningful. The teaching needs to enable students to discern relationships between all numbers in an equation, where the relationships can be described as a part-whole structure.

INTRODUCTION The causes of high blood pressure are complex and based on an interaction between multiple biological factors and behaviours. Insulin resistance and inflammation are commonly acknowledged mechanisms in the development of CVD, while insulin resistance and relative body weight correspondingly predict the development of high blood pressure. HYPOTHESIS We aimed to compare insulin resistance, relative body weight, and inflammation in the association with SBP. METHODS In 2001-2005 a random sample of residents aged 30-74 years in the municipalities of Vara and Skövde, South-western Sweden, were invited to a survey of cardiovascular risk factors. In all 1811 participants in Vara (participation rate 81%) and 1005 participants in Skövde (70%) were enrolled. Subjects with a known history of hypertension were excluded for the current study. Specially trained nurses saw all subjects in the morning after a 10 hours over night fast, and venous blood samples were taken. A physical examination included body height and body weight (light cloths and no shoes), blood pressure was measured twice in a supine position after a 5 minutes rest (arm in heart level). The mean of the 2 measurements was used for statistical analyses. Hs-CRP and plasma insulin were analysed, and BMI and HOMA-index were calculated using standard algorithms. The log form of HOMA-ir was used in statistical analyses. Associations were explored in males and females separately using multivariate linear regression. RESULTS In all 2538 subjects, 1266 men (50%) and 1272 women (50%) without known hypertension were included. BMI and HOMA-ir were both significantly associated with SBP in both males and females, while hs-CRP was associated with SBP in women only. These factors were accordingly entered into a multivariate linear regression model also including age. In men HOMA-ir [regression coefficient, (95% confidence interval), and p-value] [5.4 (2.5-8.4), p<0.001], was significantly associated with SBP, while BMI [0.2 (-0.3-0.5), p=0.087], and CRP was not [0.02 (-0.1-0.1), p=0.138]. In women all three mechanisms came out significantly; HOMA-ir [5.4 (2.2-8.6), p<0.001], BMI [0.4 (0.2-0.5), p<0.001], and CRP [0.2 (0.02-0.4), p=0.031]. There were statistically significant interaction terms between gender and CRP (p=0.037), and gender and HOMA-ir (P=0.045), respectively, while no corresponding interaction was found for BMI. CONCLUSIONS Our study confirms a strong impact of insulin resistance and relative body weight on blood pressure levels in both men and women. However, a significant association between hs-CRP and systolic blood pressure in women was not seen in men. Gender differences in insulin resistance and inflammation were statistically confirmed by interaction terms. These findings have implications for future research and for development of clinical practice.

Abstract Background Schmid-type metaphyseal chondrodysplasia (MCDS) is an autosomal dominant disorder caused by COL10A1 mutations, which is characterized by short stature, waddling gait, coxa vara and bowing of the long bones. However, descriptions of the expressivity of MCDS are rare. Methods Two probands and available family members affected with MCDS were subjected to clinical and radiological examination. Genomic DNA of all affected individuals was subjected to whole-exome sequencing, and candidate mutations were verified by Sanger sequencing in all available family members and in 250 healthy donors. A spatial model of the type X collagen (α1) C-terminal noncollagenous (NC1) domain was further constructed. Results We found that the phenotype of affected family members exhibited incomplete dominance. Mutation analysis indicated that there were two novel heterozygous missense mutations, [c.1765 T > A (p.Phe589Ile)] and [c.1846A > G (p.Lys616Glu)] in the COL10A1 gene in family 1 and 2, respectively. The two novel substitution sites were highly conserved and the mutations were predicted to be deleterious by in silico analysis. Furthermore, protein modeling revealed that the two substitutions were located in the NC1 domain of collagen X (α1), which potentially impacted the trimerization of collagen X (α1) and combination with molecules in the pericellular matrix. Conclusion Two novel mutations were identified in the present study, which will facilitate diagnosis of MCDS and further expand the spectrum of the COL10A1 mutations associated with MCDS patients. In addition, our research revealed the phenomenon of incomplete dominance in MCDS.

ABSTRACTToxR is a major virulence gene regulator inVibrio cholerae. Although constitutively expressed under many laboratory conditions, our previous work demonstrated that the level of ToxR increases significantly when cells are grown in the presence of the 4 amino acids asparagine, arginine, glutamate, and serine (NRES). We show here that the increase in ToxR production in response to NRES requires the Var/Csr global regulatory circuit. The VarS/VarA two-component system controls the amount of active CsrA, a small RNA-binding protein involved in the regulation of a wide range of cellular processes. Our data show that avarAmutant, which is expected to overproduce active CsrA, had elevated levels of ToxR in the absence of the NRES stimulus. Conversely, specific amino acid substitutions in CsrA were associated with defects in ToxR production in response to NRES. These data indicate that CsrA is a positive regulator of ToxR levels. Unlike previously described effects of CsrA on virulence gene regulation, the effects of CsrA on ToxR were not mediated through quorum sensing and HapR. CsrA is likely essential inV. cholerae, since a complete deletion ofcsrAwas not possible; however, point mutations in CsrA were tolerated well. The CsrA Arg6His mutant had wild-type growthin vitrobut was severely attenuated in the infant mouse model ofV. choleraeinfection, showing that CsrA is critical for pathogenesis. This study has broad implications for our understanding of howV. choleraeintegrates its response to environmental cues with the regulation of important virulence genes.IMPORTANCEIn order to colonize the human host,Vibrio choleraemust sense and respond to environmental signals to ensure appropriate expression of genes required for pathogenesis. Uncovering howV. choleraesenses its environment and activates its virulence gene repertoire is critical for our understanding of howV. choleraetransitions from its natural aquatic habitat to the human host. Here we demonstrate a previously unknown link between the global regulator CsrA and the majorV. choleraevirulence gene regulator ToxR. The role of CsrA in the cell is to receive input from the environment and coordinate an appropriate cellular response. By linking environmental sensing to the ToxR regulon, CsrA effectively acts as a switch that controls pathogenesis in response to specific signals. We demonstrate that CsrA is critical for virulence in the infant mouse model ofV. choleraeinfection, consistent with its role as anin vivoregulator of virulence gene expression.