Health consultation : Sub-Slab Gas and Air Sampling Data Alcoa – Davenport Works CERCLIS No. IAD005270160 Riverdale, Scott County, Iowa (2005)

The U.S. Environmental Protection Agency (EPA), the Alcoa – Davenport Works Facility (Alcoa), and concerned citizens and community leaders of Riverdale, Iowa requested the Iowa Department of Public Health (IDPH) Hazardous Waste Site Health Assessment Program to evaluate the health impacts of exposures to volatile organic vapors detected within residences located immediately to the west of the Alcoa property. This health consultation addresses inhalation exposure to individuals that may have occupied the currently vacant residences in which the air sampling was completed.

Insulin dysfunction and allostic load in bipolar disorder

Bipolar disorder (BD) is associated with substantial morbidity, as well as premature mortality. Available evidence indicates that 'stress-sensitive' chronic medical disorders, such as cardiovascular disease, obesity and Type 2 diabetes mellitus, are critical mediators and/or moderators of BD. Changes in physiologic systems implicated in allostasis have been proposed to impact brain structures and neurocognition, as well as medical comorbidity in this population. For example, abnormalities in insulin physiology, for example, insulin resistance, hyperinsulinemia and central insulinopenia, are implicated as effectors of allostatic load in BD. Insulin's critical role in CNS physiological (e.g., neurotrophism and synaptic plasticity) and pathophysiological (e.g., neurocognitive deficits, pro-apoptosis and amyloid deposition) processes is amply documented. This article introduces the concept that insulin is a mediator of allostatic load in the BD and possibly a therapeutic target.

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder:a meta-analysis of randomized controlled trials

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of ≥6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5,364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review.

Abstract BACKGROUND: The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder. METHODS: A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed, with the combination of the words 'aripiprazole' and 'bipolar'. RESULTS: The search returned 184 articles and was last updated on 15 April 2009. An additional search included repositories of clinical trials and previous systematic reviews specifically in order to trace unpublished trials. There were seven placebo-controlled randomised controlled trials (RCTs), six with comparator studies and one with add-on studies. They assessed the usefulness of aripiprazole in acute mania, acute bipolar depression and during the maintenance phase in comparison to placebo, lithium or haloperidol. CONCLUSION: Aripiprazole appears effective for the treatment and prophylaxis against mania. The data on bipolar depression are so far negative, however there is a need for further study at lower dosages. The most frequent adverse effects are extrapyramidal signs and symptoms, especially akathisia, without any significant weight gain, hyperprolactinaemia or laboratory test changes.

Class effect of pharmacotherapy in bipolar disorder: fact or misbelieff?

BACKGROUND: Anecdotal reports suggests that most clinicians treat medications as belonging to a class with regard to all therapeutic indications; this means that the whole 'class' of drugs is considered to possesses a specific therapeutic action. The present article explores the possible existence of a true 'class effect' for agents available for the treatment of bipolar disorder. METHODS: We reviewed the available treatment data from randomized controlled trials (RCTs) and explored 16 'agent class'/'treatment issue' cases for bipolar disorder. Four classes of agents were examined: first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs), antiepileptics and antidepressants, with respect to their efficacy on four treatment issues of bipolar disorder (BD) (acute mania, acute bipolar depression, maintenance against mania, maintenance against depression). RESULTS: From the 16 'agent class'/' treatment issue' cases, only 3 possible class effects were detected, and they all concerned acute mania and antipsychotics. Four effect cases have not been adequately studied (FGAs against acute bipolar depression and in maintenance protection from depression, and antidepressants against acute mania and protection from mania) and they all concern treatment cases with a high risk of switching to the opposite pole, thus research in these areas is poor. There is no 'class effect' at all concerning antiepileptics. CONCLUSIONS: The available data suggest that a 'class effect' is the exception rather than the rule in the treatment of BD. However, the possible presence of a 'class effect' concept discourages clinicians from continued scientific training and reading. Focused educational intervention might be necessary to change this attitude.

07033-013 Dry Run Creek Sub-watershed Final Report

This watershed project will provide technical and financial assistance to improve surface and groundwater quality. This will be accomplished by installing an alternative tile outlet for 3 agricultural drainage wells (ADWs) and providing incentives to implement nutrient and pest management.

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression. Comment in The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlEfficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis--results to be interpreted with caution.

Staging Bipolar Disorder.

The purpose of this study was to analyze the evidence supporting a staging model for bipolar disorder. The authors conducted an extensive Medline and Pubmed search of the published literature using a variety of search terms (staging, bipolar disorder, early intervention) to find relevant articles, which were reviewed in detail. Only recently specific proposals have been made to apply clinical staging to bipolar disorder. The staging model in bipolar disorder suggests a progression from prodromal (at-risk) to more severe and refractory presentations (Stage IV). A staging model implies a longitudinal appraisal of different aspects: clinical variables, such as number of episodes and subsyndromal symptoms, functional and cognitive impairment, comorbidity, biomarkers, and neuroanatomical changes. Staging models are based on the fact that response to treatment is generally better when it is introduced early in the course of the illness. It assumes that earlier stages have better prognosis and require simpler therapeutic regimens. Staging may assist in bipolar disorder treatment planning and prognosis, and emphasize the importance of early intervention. Further research is required in this exciting and novel area.

Stage managing bipolar disorder.

OBJECTIVES: Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches. METHODS: We provide a narrative review of the relevant information. RESULTS: In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness. CONCLUSIONS: The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible.

Persistence of cognitive impairment and its negative impact on psychosocial functioning in lithium-treated, euthymic bipolar patients: a 6-year follow-up study.

BACKGROUND: Previous cross-sectional studies report that cognitive impairment is associated with poor psychosocial functioning in euthymic bipolar patients. There is a lack of long-term studies to determine the course of cognitive impairment and its impact on functional outcome. Method A total of 54 subjects were assessed at baseline and 6 years later; 28 had DSM-IV TR bipolar I or II disorder (recruited, at baseline, from a Lithium Clinic Program) and 26 were healthy matched controls. They were all assessed with a cognitive battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory) twice over a 6-year follow-up period. All patients were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young mania rating scale score lower than 6) for at least 3 months before both evaluations. At the end of follow-up, psychosocial functioning was also evaluated by means of the Functioning Assessment Short Test. RESULTS: Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain, in the inhibition domain, in the processing speed domain, and in the verbal memory domain (p<0.04). Among the clinical factors, only longer illness duration was significantly related to slow processing (p=0.01), whereas strong relationships were observed between impoverished cognition along time and poorer psychosocial functioning (p<0.05). CONCLUSIONS: Executive functioning, inhibition, processing speed and verbal memory were impaired in euthymic bipolar out-patients. Although cognitive deficits remained stable on average throughout the follow-up, they had enduring negative effects on psychosocial adaptation of patients.

Simulating maize yield in sub‑tropical conditions of southern Brazil using Glam model

The objective of this work was to evaluate the feasibility of simulating maize yield in a sub‑tropical region of southern Brazil using the general large area model (Glam). A 16‑year time series of daily weather data were used. The model was adjusted and tested as an alternative for simulating maize yield at small and large spatial scales. Simulated and observed grain yields were highly correlated (r above 0.8; p<0.01) at large scales (greater than 100,000 km²), with variable and mostly lower correlations (r from 0.65 to 0.87; p<0.1) at small spatial scales (lower than 10,000 km²). Large area models can contribute to monitoring or forecasting regional patterns of variability in maize production in the region, providing a basis for agricultural decision making, and Glam‑Maize is one of the alternatives.

Longer term clinical and virological outcome of sub-Saharan African participants on antiretroviral treatment in the Swiss HIV Cohort Study.

OBJECTIVES: Persons from sub-Saharan Africa (SSA) are increasingly enrolled in the Swiss HIV Cohort Study (SHCS). Cohorts from other European countries showed higher rates of viral failure among their SSA participants. We analyzed long-term outcomes of SSA versus North Western European participants. DESIGN: We analyzed data of the SHCS, a nation-wide prospective cohort study of HIV-infected adults at 7 sites in Switzerland. METHODS: SSA and North Western European participants were included if their first treatment combination consisted of at least 3 antiretroviral drugs (cART), if they had at least 1 follow-up visit, did not report active injecting drug use, and did not start cART with CD4 counts >200 cells per microliter during pregnancy. Early viral response, CD4 cell recovery, viral failure, adherence, discontinuation from SHCS, new AIDS-defining events, and survival were analyzed using linear regression and Cox proportional hazard models. RESULTS: The proportion of participants from SSA within the SHCS increased from 2.6% (<1995) to 20.8% (2005-2009). Of 4656 included participants, 808 (17.4%) were from SSA. Early viral response (6 months) and rate of viral failure in an intent-to-stay-on-cART approach were similar. However, SSA participants had a higher risk of viral failure on cART (adjusted hazard ratio: 2.03, 95% confidence interval: 1.50 to 2.75). Self-reported adherence was inferior for SSA. There was no increase of AIDS-defining events or mortality in SSA participants. CONCLUSIONS: Increased attention must be given to factors negatively influencing adherence to cART in participants from SSA to guarantee equal longer-term results on cART.

Growth mechanisms and timing of emplacement of a vertically layered mafic intrusion in the feeder zone of an ocean island volcano (Fuerteventura, Canary islands)

Résumé pour le grand public L'île de Fuerteventura (Canaries) offre l'occasion rare d'observer les racines d'un volcan océanique édifié il y a 25 à 30 millions d'années et complètement érodé. On y voit de nombreux petits plutons de forme et composition variées, témoignant d'autant d'épisodes de l'activité magmatique. L'un de ces plutons, appelé PX1, présente une structure inhabituelle formée d'une alternance de bandes verticales d'épaisseur métrique à hectométrique de roches sombres de composition pyroxénilique ou gabbroïque. Les pyroxénites résultent clairement de l'accumulation de cristaux de pyroxènes et non de la simple solidification d'un magma? Se pose dès lors la question de la nature du processus qui a conduit à l'accumulation verticale de niveaux concentrés en pyroxènes. En effet, les litages pyroxénitiques classiques sont subhorizontaux, car ils résultent de l'accumulation gravitaire des cristaux séparés du magma dont ils cristalli¬sent par sédimentation. Cette étude vise à identifier et comprendre les mécanismes qui ont engendré ce Iitage minéralogique vertical et l'im¬portant volume de ces faciès cumulatifs. Nous nous sommes également intéressés aux conditions de pression et de température régnant au moment de la mise en place du pluton, ainsi qu'à sa durée de vie et à sa vitesse de refroidis¬sement. Enfin une approche géochimique nous a permis de préciser la nature de la source mantellique des magmas liés à cette activité magmatique. PX1 est en réalité un complexe filonien formé à des conditions de pression et de température de 1-2 kbar et 1050- 1100°C; sa construction a nécessité au moins 150 km3 de magma. L'alternance d'horizons gabbroïques et pyroxéniti¬ques représente des injections successives de magma sous la forme de filons verticaux, mis en place dans un contexte régional en extension. L'étude des orientations des minéraux dans ces faciès révèle que les horizons gabbroïques enregistrent l'extension régionale, alors que les pyroxénites sont générées par une compaction au sein du pluton. Ceci suggère que le régime des contraintes, qui était extensif lors de l'initiation de la mise en place de PX1, est pério¬diquement devenu compressif au sein même du pluton. Cette compression serait liée à des cycles de mise en place où la vitesse de croissance du pluton dépassait celle de l'extension régionale. La différenciation observée au sein de chaque horizon, depuis des pyroxénites riches en olivine jusqu'à des pyroxé¬nites à plagioclase interstitiel et des gabbros, ainsi que la composition géochimique des minéraux qui les constituent suggèrent que chaque filon vertical s'est mis en place à partir d'un magma de composition identique, puis a évolué indépendamment des autres en fonction du régime thermique et du régime des contraintes local. Lorsque le magma en train de cristalliser s'est trouvé en compression, le liquide résiduel a été séparé des cristaux déjà formés et extrait du système, laissant derrière lui une accumulation de cristaux dont la nature et les proportions dépendaient du stade de cristallisation atteint par le magma au moment de l'extraction. Ainsi, les niveaux de pyroxénites à olivine (premier minéral à cristalliser) ont été formés lorsque le magma correspondant était encore peu cristallisé; à l'inverse, les py¬roxénites riches en plagioclase (minéral plus tardif dans la séquence de cristallisation) et certains gabbros à caractère cumulatif résultent d'une compression tardive dans le processus de cristallisation du filon concerné. Les liquides résiduels extraits des niveaux pyroxénitiques sont rarement observés dans PX1, certaines poches et filonets de com¬position anorthositique pourraient en être les témoins. L'essentiel de ces liquides a probablement gagné des niveaux supérieurs du pluton, voire la surface du volcan. L'origine du régime compressif périodique affectant les filons en voie de cristallisation est attribuée aux injections suivantes de magma au sein du pluton, qui se sont succédées à un rythme plus rapide que la vitesse de consolidation des filons. Des datations U/Pb de haute précision sur des cristaux de zircon et de baddeleyite ainsi que40Ar/39Ar sur des cris¬taux d'amphibole révèlent une initiation de la mise en place de PX1 il y a 22.1 ± 0,7 Ma; celle-ci a duré quelque 0,48 ± 0,22 à 0,52 ± 0,29 Ma. Ce laps de temps est compatible avec celui nécessaire à la cristallisation des filons individuels, qui va de moins d'une année lors de l'initiation du magmatisme à 5 ans lors du maximum d'activité de PX1. La présence de cristaux résorbés enregistrant une cristallisation complexe suggère l'existence d'une chambre mag¬matique convective sous-jacente à PX1 et périodiquement rechargée. Les compositions isotopiques des roches étu¬diées révèlent une source mantellique profonde de type point chaud avec une contribution du manteau lithosphéri- que métasomatisé présent sous les îles Canaries. Résumé L'intrusion mafique Miocène PX1 fait partie du soubassement superficiel (0.15-0.2 GPa, 1100 °Q d'un volcan d'île océanique. La particularité de ce pluton est l'existence d'alternances d'unités de gabbros et de pyroxénites qui met¬tent en évidence un litage magmatique vertical (NNE-SSW). Les horizons gabbroiques et pyroxénitiques sont constitués d'unités de différenciation métriques qui suggèrent tine mise en place par injections périodiques de filons verticaux de magma formant un complexe filonien. Chaque filon vertical a subi une différenciation parallèle à un front de solidification sub-vertical parallèle aux bords du filon. Les pyroxénites résultent du fractionnement et de l'accumulation d'olivine ± clinopyroxene ± plagioclase à partir d'un magma basaltique faiblement alcalin et sont interprétées comme étant des imités de différenciation tronquées dont le liquide interstitiel a été extrait par compaction. L'orientation préférentielle des clinopyroxènes dans ces pyroxe- nites (obtenues par analyse EBSD et micro-tomographique) révèle une composante de cisaillement simple dans la genèse de ces roches, ce qui confirme cette interprétation. La compaction des pyroxénites est probablement causée par a mise en place de filons de magma suivants. Le liquide interstitiel expulsé est probablement par ces derniers. Les clinopyroxènes des gabbros, montrent une composante de cisaillement pure suggérant qu'ils sont affectés par une déformation syn-magmatique parallèle aux zones de cisaillement NNE-SSW observées autour de PX1 et liées au contexte tectonique Miocène d'extension régionale. Ceci suggère que les gabbros sont liés à des taux de mise en place faibles à la fin de cycles d'activité magmatique et sont peu ou pas affectés par la compaction. L'initiation et la géométrie de PX1 sont donc contrôlées par le contexte tectonique régional d'extension alors que les taux et les volumes de magma dépendent de facteurs liés à la source. Des taux d'injection élevés résultent probable¬ment en une croissance du pluton supérieure à la place crée par cette extension. Dans ce cas de figure, la propagation des nouveaux dykes et l'inaptitude du magma à circuler à travers les anciens dykes cristallisés pourrait causer une augmentation de la pression non-lithostatique sur ces derniers, exprimée par un cisaillement simple et l'expulsion du liquide interstitiel qu'ils contiennent (documenté par les zones de collecte anorthositiques). Les compositions en éléments majeurs et traces des gabbros et pyroxenites de PX1 sont globalement homogènes et dépendent de la nature cumulative des échantillons. Cependant, de petites variations des concentrations en éléments traces ainsi que les teneurs en éléments traces des bordures de clinopyroxenes suggèrent que ces derniers ont subi un processus de rééquilibrage et de cristallisation in situ. L'homogénéité des compositions chimiques des échantillons, ainsi que la présence de grains de clinopyroxene résorbés suggère que le complexe filonien PX1 s'est mis en place au dessus d'une chambre magmatique périodiquement rechargée dans laquelle la convection est efficace. Chaque filon est donc issu d'un même magma, mais a subi une différenciation par cristallisation in situ (jusqu'à 70% de fraction¬nement) indépendamment des autres. Dans ces filons cristallisés, les minéraux cumulatifs subissent un rééquilibrage partiel avec les liquide interstitiel avant que ce dernier ne soit expulsé lors de la compaction (mettant ainsi un terme à la différenciation). Ce modèle de mise en place signifie qu'un minimum de 150Km3 de magma est nécessaire à la genèse de PX1, une partie de ce volume ayant été émis par le 'Central Volcanic Complex' de Fuerteventura. Les rapports isotopiques radiogéniques mesurés révèlent la contribution de trois pôles mantelliques dans la genèse du magma formant PX1. Le mélange de ces pôles HIMU, DMM et EM1 refléterai l'interaction du point chaud Cana¬rien avec un manteau lithosphérique hétérogène métasomatisé. Les petites variations de ces rapports et des teneurs en éléments traces au sein des faciès pourrait refléter des taux de fusion partielle variable de la source, résultant en un échantillonnage variable du manteau lithosphérique métasomatisé lors de son interaction avec le point chaud. Des datations U/Pb de haute précision (TIMS) sur des cristaux de zircon et de baddeleyite extraits de gabbros de PX1 révèlent que l'initiation de la cristallisation du magma a eu lieu il y a 22.10±0.07 Ma et que l'activité magmatique a duré un minimum de 0.48 à 0.52 Ma. Des âges 40Ar/39Ar obtenus sur amphibole sont de 21.9 ± 0.6 à 21.8 ± 0.3 Ma, identiques aux âges U/Pb. La combinaison de ces méthodes de datations, suggère que le temps maximum nécessaire à PX1 pour se refroidir en dessous de la température de fermeture de l'amphibole est de 0.8Ma. Ceci signifie que la durée de vie de PX1 est de 520 000 à 800 000 ans. La coexistence de cristaux de baddeleyite et de zircon dans un gabbro est attribuée à son interaction avec un fluide riche en C02 relâché par les carbonatites encaissantes lors du métamorphisme de contact généré par la mise en place de PX1 environ 160 000 ans après le début de sa mise en place. Les durées de vie obtenue sont en accord avec le modèle de mise en place suggérant une durée de cristallisation poux chaque filon allant de 1 an à 5 ans. Abstract The Miocene PX1 gabbro-pyroxenite intrusion (Fuerteventura, Canary Islands), is interpreted as the shallow-level feeder-zone (0.15-0.2 GPa and 1100-1120°C), to an ocean island volcano. The particularity of PX1 is that it displays a NNE-SSW trending vertical magmatic banding expressed by alternating gabbro and pyroxeriite sequences. The gabbro and pyroxenite sequences consist of metre-thick differentiation units, which suggest emplacement by pe¬riodic injection of magma pulses as vertical dykes that amalgamated, similarly to a sub-volcanic sheeted dyke com¬plex. Individual dykes underwent internal differentiation following a solidification front (favoured by a significant lateral/horizontal thermal gradient) parallel to the dyke edges. Pyroxenitic layers result from the fractionation and accumulation of clinopyroxene ± olivine ± plagioclase crystals from a mildly alkaline basaltic liquid and are interpre¬ted as truncated differentiation sequences, from which residual melts were extracted by compaction. Clinopyroxene mineral orientation in pyroxenites (evidenced by EBSD and micro X-ray tomography analysis) display a marked pure shear component, supporting this interpretation. Compaction and squeezing of the crystal mush is ascribed to the incoming and inflating magma pulses. The resulting expelled interstitial liquid was likely collected and erupted along with the magma flowing through the newly injected dykes. Gabbro sequences represent crystallised coalesced magma batches, emplaced at lower rates at the end of eruptive cycles, and underwent minor melt extraction as evi¬denced by clinopyroxene orientations that record a simple shear component suggesting syn-magmatic deformation parallel to observed NNF.-SSW trending shear-zones induced by the regional tensional Miocene stress-field. The initiation and geometry of PX1 is controlled by the regional extensional tectonic regime whereas rates and vo¬lumes of magma depend on source-related factors. High injection rates are likely to induce intrusion growth rates larger than could be accommodated by the regional extension. In this case, dyke tip geometry and the inability of magma to circulate through previously emplaced and crystallised dykes could result in an increase of non-lithostatic pressure on previously emplaced mushy dyke walls; generating strong pure-shear compaction and interstitial melt expulsion within the feeder-zone as recorded by the cumulitic pyroxenite bands and anorthositic collection zones. The whole-rock major and trace-element chemistry of PX1 gabbros and pyroxenites is globally homogeneous and controlled by the cumulate nature of the samples (i.e. on the modal proportions of olivine, pyroxene, plagioclase and oxides). However, small variations of whole-rock trace-element contents as well as trace-element contents of clinopyroxene rims suggest that in-situ re-equilibration and crystallisation has occurred. Additionally, the global homogeneity and presence of complex zoning of rare resorbed clinopyroxene crystals suggest that the PX1 feeder- zone overlies a periodically replenished and efficiently mixed magma chamber. Each individual dyke of magma thus originated from a compositionally constant mildly alkaline magma and differentiated independently from the others reaching up to 70% fractionation. Following dyke arrest these are affected by interaction with the trapped interstitial liquid prior to its compaction-linked expulsion (thus stopping the differentiation process). This emplacement model implies that minimum amount of approximately 150 km3 of magma is needed to generate PX1, part of it having been erupted through the overlying Central Volcanic Complex of Fuerteventura. The radiogenic isotope ratios of PX1 samples reveal the contribution on three end-members during magma genesis. This mixing of the H1MU, EMI and DMM end-members could reflect the interaction of the deep-seated Canarian mantle plume with a heterogeneous metasomatic and sepentininsed lithospheric mantle. Additionally, the observed trace-element and isotopic variations within the same fades groups could reflect varying degrees of partial melting of the source region, thus tapping more or less large areas of the metasomatised lithospheric mantle during interac¬tion with the plume. High precision ID-TIMS U/Pb zircon and baddeleyite ages from the PX1 gabbro samples, indicate initiation of magma crystallisation at 22.10 ± 0.07 Ma. The magmatic activity lasted a minimum of 0.48 to 0.52 Ma. 40Ar/39Ar amphibole ages are of 21.9 ± 0.6 to 21.8 ± 0.3, identical within errors to the U/Pb ages. The combination of the 40Ar/39Ar and U/Pb datasets imply that the maximum amount of time PX1 took to cool below amphibole Tc is 0.8 Ma, suggesting PX1 lifetime of 520 000 to 800 000 years. On top of this, the coexistence of baddeleyite and zircon in a single sample is ascribed to the interaction of PX1 with C02-rich carbonatite-derived fluids released from the host-rock carbonatites during contact metamorphism 160 000 years after PX1 initiation. These ages are in agreement with the emplacement model, implying a crystallisation time of less than 1 to 5 years for individual dykes.