Simplicial gauge theory on spacetime

We define a discrete gauge-invariant Yang-Mills-Higgs action on spacetime simplicial meshes. The formulation is a generalization of classical lattice gauge theory, and we prove consistency of the action in the sense of approximation theory. In addition, we perform numerical tests of convergence towards exact continuum results for several choices of gauge fields in pure gauge theory.Comment: 18 pages, 2 figure

The influence of groundwater abstraction on interpreting climate controls and extreme recharge events from well hydrographs in semi-arid South Africa

There is a scarcity of long-term groundwater hydrographs from sub-Saharan Africa to investigate groundwater sustainability, processes and controls. This paper presents an analysis of 21 hydrographs from semi-arid South Africa. Hydrographs from 1980 to 2000 were converted to standardised groundwater level indices and rationalised into four types (C1–C4) using hierarchical cluster analysis. Mean hydrographs for each type were cross-correlated with standardised precipitation and streamflow indices. Relationships with the El Niño–Southern Oscillation (ENSO) were also investigated. The four hydrograph types show a transition of autocorrelation over increasing timescales and increasingly subdued responses to rainfall. Type C1 strongly relates to rainfall, responding in most years, whereas C4 notably responds to only a single extreme event in 2000 and has limited relationship with rainfall. Types C2, C3 and C4 have stronger statistical relationships with standardised streamflow than standardised rainfall. C3 and C4 changes are significantly (p < 0.05) correlated to the mean wet season ENSO anomaly, indicating a tendency for substantial or minimal recharge to occur during extreme negative and positive ENSO years, respectively. The range of different hydrograph types, sometimes within only a few kilometres of each other, appears to be a result of abstraction interference and cannot be confidently attributed to variations in climate or hydrogeological setting. It is possible that high groundwater abstraction near C3/C4 sites masks frequent small-scale recharge events observed at C1/C2 sites, resulting in extreme events associated with negative ENSO years being more visible in the time series

Effects of Antiepileptic Drugs on GABA Responses and on Reduction of GABA Responses by PTZ and DMCM on Mouse Neurons in Cell Culture

The mechanisms of action of antiepileptic drugs effective against generalized absence seizures (antiabsence AEDs) remain uncertain. Antiabsence AEDs are generally effective against seizures induced in experimental animals by pentylenÉtÉtrazol (PTZ) and methyl-6,7-dimethoxy-4-ethyl-Β-carboline-3-carboxylate (DMCM), drugs which reduce GABAergic inhibition. Thus, antiabsence AEDs have been suggested to enhance GABAergic inhibition. We studied the effects of several AEDs on GABA responses recorded from mouse spinal cord neurons grown in primary dissociated cell culture. Four antiabsence AEDs were included: ethosuximide (ESM), dimethadione (DMO), sodium valproate (VPA), and diazepam (DZP). Two experimental AEDs, CGS 9896 and ZK 91296, with anticonvulsant action against PTZ- or DMCM-induced seizures were also included. Possible effects of the antiabsence and experimental AEDS on PTZ- and DMCM-induced inhibition of GABA responses were also evaluated. PTZ and DMCM revers-ibly reduced GABA responses in a concentration-dependent manner. PTZ complÉtÉly inhibited GABA responses at 10 mM (IC 50 of 1.1 mM), whereas DMCM-induced inhibition of GABA responses reached a plateau level of 39% of control values at 1 p.M (IC 50 of 33 nM). ESM (1,200 ΜM), DMO (6 mM), VPA (200 u.M), CGS 9896 (2 ΜM), and ZK 98% (2 Μ M ) did not alter GABA responses. DZP enhanced GABA responses in a concentration-dependent manner. The inhibition of GABA responses produced by PTZ 1 mM was unaltered by ESM (600 Μ M ), DMO (6 mM), CGS 9896 (1 Μ M), or ZK 9896 (1 ΜM)- Coapplication of VPA (200 ΜM) and PTZ (1 mM) slightly enhanced the PTZ effect. DZP (> 10 nM), however, reversed the PTZ-induced reduction of GABA responses. The DMCM (250 nM) inhibition of GABA-responses was unaltered by ESM (600 Μ.M), DMO (2 mM), or VPA (200 ΜM). CGS 9896 (2 Μ M ) and ZK 91296 (2 ΜM), however, antagonized the DMCM effect. DZP (> 10 nM) significantly reversed the DMCM-induced inhibition of GABA responses. The lack of effect of VPA, ESM, and DMO on postsynaptic GABA responses suggests that direct enhancement of postsynaptic GABA action is not a common mechanism of action of antiabsence AEDs. The AEDs DZP, CGS 98%, and ZK 912% all reversed DMCM, but not PTZ, reduction of GABA responses, suggesting that these AEDs blocked DMCM seizures by acting at benzodiazepine receptors. However, since only DZP enhanced GABA responses, it is unclear how CGS 98% and ZK 912% blocked PTZ seizures. Key Words: Anticonvulsants–GABA–Neuron culture–Cell culture–Spinal cord neurons–Convulsants. RESUMEN Los mecanismos de accidn de las medicaciones antiepilÉpticas eficaces contra los ataques generalizados de ausencia (AEDs antiausencia) permanecen inciertos. Los AEDs antiausencia son, generalmente, eficaces contra ataques experimentales inducidos por el pentilentetrazol (PTZ) y el metil-6,7-dimetoxy-4-etil-Pcarbolina-3-carboxilato (DMCM) en animates, medicaciones que reducen la inhibiciÓn GABAÉrgica. Hemos estudiado los efectos de varios AEDs sobre respuestas-GABA registradas en las neuronas de la mÉdula espinal de ratones que habian crecido en cultivos de cÉlulas primarieas disociadas. Cuatro AEDs antiausencia fueron incluidos: etoxusimida (ESM), dimetadiona (DMO), valproato sÓdico (VPA) y diazepan (DZP). TambtÉn se incluyeron dos AEDs experimentales, CGS 9896 y ZK 912%, con acciÓn anticonvulsiva contra los ataques inducidos por PTZ o DMCM. TambiÓn se valoraron los posibles efectos de los AEDs antiausencia y experimentales sobre el PTZ y la inhibiciÓn de las respuestas-GABA inducidas por el DMCM. El PTZ y el DMCM redujeron las respuestas-GABA de modo reversible y dependiendo de sus concentraciones. El PTZ inhibiÓ cmpleta-mente las respuestas-GABA a 10 mM (IC 50 de 1.1 mM) mientras que la inhibitiÓn de las respuestas GABA inducida por el DMCM alcanzÓ un nivel estable del 39% de los valores control con 1 Μ. M (IC 50 de 33 mM). La ESM (1200 Μ.M), la DMO (6 mM), el VPA (200 Μ M ), el CGS 98% (2 Μ M) y el ZK 98% (2 Μ M) no alteraron las respuestas-GABA. El DZP aumentÓ las respuestas GABA de una manera concentraciÓn-dependiente. La inhibition de las respuestas-GABA producidas por el PTZ (1 mM), no se altero con las ESM (600 Μ M), la DMO (6 mM), el CGS 98% (1 Μ M) o el ZK 98% (1 Μ .M). La co-aplicacion de VPA (200 Μ M) y el PTZ (1 mM) aument6 ligeramente los efectos del PTZ. Sin embargo el DZP (10 nM) revirtiÓ significativamente la inhibition de las respuestas GABA inducidas por el DMCM. La falta de efectos de CPA, ESM y DMO sobre las respuestas GABA post-sinÁpticas sugiere que el incremento de la acciÓn GABA post-sinÁptica no es un mecanismo comÚn de actuatiÓn de las AEDs antiausencia. Todas las AEDs DZP, CGS 98% y ZK 912% revirtieron la reduction de las respuestas GABA producidas por el DMCM pero no las inducidas por el PTZ lo que sugiere que estos AEDs bloquean los ataques DMCM actuando sobre los receptores de la benzodiazepina. Sin embargo, puesto que el incremento de las respuestas GABA sÓlÓ se produce por el DZP, permanece todavia sin aclarar el por quÉ el CGS 98% y el ZK 912% bloquean los ataques producidos por el PTZ. ZUSAMMENFASSUNG Der Wirkmechansimus von Antiepileptika gegen generalisierte Absencen ist unklar. Antiabsencemittel sind generell wirkungs-voll gegen PTZ- und Methyl-6,7-Dimethoxy-4-Äthyl-P-Carbolin-Β-Carboxylat (DMCM) induzierte tierexperimentelle AnfÄlle, also von Medikamenten, die die GABA-erge Inhibition reduzieren. Es wurde vermutet, daß Antiabsencemittel die GABA-erge Inhibition verstÄrken. Wir untersuchten die Wirkung von verschiedenen Antiepileptika auf GABA-Antworten in spinalen MÄuseneuronen, die in Zellkulturen gew-achsen waren. Es wurden 4 Absencemittel untersucht: Ethosux-imid (ESM), Dimethadion (DMD), Sodium Valproat (VPA) und Diazepam (DZP). ZusÄtzlich wurden 2 experimentelle Antiepileptika, CGS 98% und ZK 912%, die gegen PTZ0 oder DMCM-induzierte AnfÄlle wirkungsvoll sind, eingeschlossen. Mogliche Wirkungen der Antiabsence- und experimentellen Antiepileptika auf PTZ- und DMCM-induzierte Hemmung der GABA-Antworten wurden ebenfalls ausgewertet. PTZ und DMCM zeigten eine konzentrationsabhÄngige reversible Reduktion der GABA-Antworten. PTZ zeigte eine komplette Hemmung der GABA-Antworten bei 10 mM (IC 50 1,1 mM), DMCM-Hemmung der GABA-Antworten zeigte ein Plateau von 39% der Kontroll-werte bei 1 uJtf (ICJO von 33 mAfl. ESM (1200 uJtf), DMD (6 mM), VPA (200 Μ M), CGS 98% (2 Μ M) und ZK 98% (2 Μ M) anderten nicht die GABA-Antworten. DZP verstarkte die GABA-Antworten konzentrationsabhangig. Die durch PTZ (1 mM) hervorgerufene Hemmung der GABA-Antworten war bei ESM (600 Μ M), DMD (6 mM), CGS 98% (1 mAO und ZK 3836 (1 mM) unverÄndert. ZusÄtliche Anwendung von VPA (200 mM) und PTZ (1 mM) verstÄrkten geringfÜgig den PTZ-Effekt. DZP (10 nM) kehrte die durch PTZ hervorgerufene Reduktion der GABA-Antworten um. Die durch DMCM (250 nM) hervorgerufene Hemmung der GABA-Antworten war durch ESM (600 Μ .M), DMD (2 mM) und VPA (200 Μ M ) unbeeinflusst. CGS 98% (2 Μ M) und ZK 912% (2 Μ M ) antagonisierten die DMCM-Wirkung. DZP (>10 nM) kehrte die durch DMCM-induzierte Hemmung der GABA-Antworten um. Das Fehlen einer Wirkung von VPA. ESM und DMD auf die postsynaptischen GABA-Antworten legen nahe, daß eine direkte VerstÄrkung der postsynaptischen GABA-Aktion kein gemeinsamer Mechanis-mus der Antiabsencemittel darstellt. Die Antiepileptika DZP, CGS 98% und ZK 912% kehrten die DMCM-Wirkung auf die GABA-Antworten um, jedoch nicht die von PTZ, was vermuten lapt, daß diese Antiepileptika die DMCM-AnfÄlle Über die Wirkung an den Benzodiazipin-Rezeptoren verhinderte. Da jedoch nur DZP GABA-Antworten verstarkte, ist unklar, in welcher Weise CGS 98% und ZK 912% die PTZ-AnfaUe ver-hinderten.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65188/1/j.1528-1157.1989.tb05275.x.pd

No Sun-like dynamo on the active star ζ Andromedae from starspot asymmetry

This is the author accepted manuscript. The final version is available from Nature Publishing Group via the DOI in this record.Sunspots are cool areas caused by strong surface magnetic fields inhibiting convection. Moreover, strong magnetic fields can alter the average atmospheric structure , degrading our ability to measure stellar masses and ages. Stars more active than the Sun have more and stronger dark spots than in the solar case, including on the rotational pole itself. Doppler imaging, which has so far produced the most detailed images of surface structures on other stars than the Sun, cannot always distinguish the hemisphere in which the starspots are located, especially in the equatorial region and if the data quality is not optimal . This leads to problems in investigating the north-south distribution of starspot active latitudes (those latitudes with more spot activity), which are crucial constraints of dynamo theory. Polar spots, inferred only from Doppler tomography, could plausibly be observational artifacts, casting some doubt on their very existence. Here we report imaging of the old, magnetically-active star ζ Andromedae using long-baseline infrared interferometry. In our data, a dark polar spot is seen in each of two epochs, while lower-latitude spot structures in both hemispheres do not persist between observations revealing global starspot asymmetries. The north-south symmetry of active latitudes observed on the Sun is absent on ζ And, which hosts global spot patterns that cannot be produced by solar-type dynamos.National Science Foundation (NSF)Hungarian Academy of Science

Observed controls on resilience of groundwater to climate variability in sub-Saharan Africa

Groundwater in sub-Saharan Africa supports livelihoods and poverty alleviation, maintains vital ecosystems, and strongly influences terrestrial water and energy budgets. Yet the hydrological processes that govern groundwater recharge and sustainability—and their sensitivity to climatic variability—are poorly constrained. Given the absence of firm observational constraints, it remains to be seen whether model-based projections of decreased water resources in dry parts of the region are justified. Here we show, through analysis of multidecadal groundwater hydrographs across sub-Saharan Africa, that levels of aridity dictate the predominant recharge processes, whereas local hydrogeology influences the type and sensitivity of precipitation–recharge relationships. Recharge in some humid locations varies by as little as five per cent (by coefficient of variation) across a wide range of annual precipitation values. Other regions, by contrast, show roughly linear precipitation–recharge relationships, with precipitation thresholds (of roughly ten millimetres or less per day) governing the initiation of recharge. These thresholds tend to rise as aridity increases, and recharge in drylands is more episodic and increasingly dominated by focused recharge through losses from ephemeral overland flows. Extreme annual recharge is commonly associated with intense rainfall and flooding events, themselves often driven by large-scale climate controls. Intense precipitation, even during years of lower overall precipitation, produces some of the largest years of recharge in some dry subtropical locations. Our results therefore challenge the ‘high certainty’ consensus regarding decreasing water resources in such regions of sub-Saharan Africa. The potential resilience of groundwater to climate variability in many areas that is revealed by these precipitation–recharge relationships is essential for informing reliable predictions of climate-change impacts and adaptation strategies

Lower Miocene Stratigraphy along the Panama Canal and Its Bearing on the Central American Peninsula

Before the formation of the Central American Isthmus, there was a Central American Peninsula. Here we show that southern Central America existed as a peninsula as early as 19 Ma, based on new lithostratigraphic, biostratigraphic and strontium chemostratigraphic analyses of the formations exposed along the Gaillard Cut of the Panama Canal. Land mammals found in the Miocene Cucaracha Formation have similar body sizes to conspecific taxa in North America, indicating that there existed a terrestrial connection with North America that allowed gene flow between populations during this time. How long did this peninsula last? The answer hinges on the outcome of a stratigraphic dispute: To wit, is the terrestrial Cucaracha Formation older or younger than the marine La Boca Formation? Previous stratigraphic studies of the Panama Canal Basin have suggested that the Cucaracha Formation lies stratigraphically between the shallow-marine Culebra Formation and the shallow-to-upper-bathyal La Boca Formation, the latter containing the Emperador Limestone. If the La Boca Formation is younger than the Cucaracha Formation, as many think, then the peninsula was short-lived (1–2 m.y.), having been submerged in part by the transgression represented by the overlying La Boca Formation. On the other hand, our data support the view that the La Boca Formation is older than the Cucaracha Formation. Strontium dating shows that the La Boca Formation is older (23.07 to 20.62 Ma) than both the Culebra (19.83–19.12 Ma) and Cucaracha (Hemingfordian to Barstovian North American Land Mammal Ages; 19–14 Ma) formations. The Emperador Limestone is also older (21.24–20.99 Ma) than the Culebra and Cucaracha formations. What has been called the “La Boca Formation” (with the Emperador Limestone), is re-interpreted here as being the lower part of the Culebra Formation. Our new data sets demonstrate that the main axis of the volcanic arc in southern Central America more than likely existed as a peninsula connected to northern Central America and North America for much of the Miocene, which has profound implications for our understanding of the tectonic, climatic, oceanographic and biogeographic history related to the formation of the Isthmus of Panama

The El Nino event of 2015-2016: climate anomalies and their impact on groundwater resources in East and Southern Africa

The impact of climate variability on groundwater storage has received limited attention despite widespread dependence on groundwater as a resource for drinking water, agriculture and industry. Here, we assess the climate anomalies that occurred over Southern Africa (SA) and East Africa, south of the Equator (EASE), during the major El Niño event of 2015–2016, and their associated impacts on groundwater storage, across scales, through analysis of in situ groundwater piezometry and Gravity Recovery and Climate Experiment (GRACE) satellite data. At the continental scale, the El Niño of 2015–2016 was associated with a pronounced dipole of opposing rainfall anomalies over EASE and Southern Africa, north–south of ∼12∘ S, a characteristic pattern of the El Niño–Southern Oscillation (ENSO). Over Southern Africa the most intense drought event in the historical record occurred, based on an analysis of the cross-scale areal intensity of surface water balance anomalies (as represented by the standardised precipitation evapotranspiration index – SPEI), with an estimated return period of at least 200 years and a best estimate of 260 years. Climate risks are changing, and we estimate that anthropogenic warming only (ignoring changes to other climate variables, e.g. precipitation) has approximately doubled the risk of such an extreme SPEI drought event. These surface water balance deficits suppressed groundwater recharge, leading to a substantial groundwater storage decline indicated by both GRACE satellite and piezometric data in the Limpopo basin. Conversely, over EASE during the 2015–2016 El Niño event, anomalously wet conditions were observed with an estimated return period of ∼10 years, likely moderated by the absence of a strongly positive Indian Ocean zonal mode phase. The strong but not extreme rainy season increased groundwater storage, as shown by satellite GRACE data and rising groundwater levels observed at a site in central Tanzania. We note substantial uncertainties in separating groundwater from total water storage in GRACE data and show that consistency between GRACE and piezometric estimates of groundwater storage is apparent when spatial averaging scales are comparable. These results have implications for sustainable and climate-resilient groundwater resource management, including the potential for adaptive strategies, such as managed aquifer recharge during episodic recharge events

Novel computed tomographic chest metrics to detect pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Early diagnosis of pulmonary hypertension (PH) can potentially improve survival and quality of life. Detecting PH using echocardiography is often insensitive in subjects with lung fibrosis or hyperinflation. Right heart catheterization (RHC) for the diagnosis of PH adds risk and expense due to its invasive nature. Pre-defined measurements utilizing computed tomography (CT) of the chest may be an alternative non-invasive method of detecting PH.</p> <p>Methods</p> <p>This study retrospectively reviewed 101 acutely hospitalized inpatients with heterogeneous diagnoses, who consecutively underwent CT chest and RHC during the same admission. Two separate teams, each consisting of a radiologist and pulmonologist, blinded to clinical and RHC data, individually reviewed the chest CT's.</p> <p>Results</p> <p>Multiple regression analyses controlling for age, sex, ascending aortic diameter, body surface area, thoracic diameter and pulmonary wedge pressure showed that a main pulmonary artery (PA) diameter ≥29 mm (odds ratio (OR) = 4.8), right descending PA diameter ≥19 mm (OR = 7.0), true right descending PA diameter ≥ 16 mm (OR = 4.1), true left descending PA diameter ≥ 21 mm (OR = 15.5), right ventricular (RV) free wall ≥ 6 mm (OR = 30.5), RV wall/left ventricular (LV) wall ratio ≥0.32 (OR = 8.8), RV/LV lumen ratio ≥1.28 (OR = 28.8), main PA/ascending aorta ratio ≥0.84 (OR = 6.0) and main PA/descending aorta ratio ≥ 1.29 (OR = 5.7) were significant predictors of PH in this population of hospitalized patients.</p> <p>Conclusion</p> <p>This combination of easily measured CT-based metrics may, upon confirmatory studies, aid in the non-invasive detection of PH and hence in the determination of RHC candidacy in acutely hospitalized patients.</p

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation

Chemoradiation is now used more commonly for gastric cancer following publication of the US Intergroup trial results that demonstrate an advantage to adjuvant postoperative chemoradiotherapy. However, there remain concerns regarding the toxicity of this treatment, the optimal chemotherapy regimen and the optimal method of radiotherapy delivery. In this prospective study, we evaluated the toxicity and feasibility of an alternative chemoradiation regimen to that used in the Intergroup trial. A total of 26 patients with adenocarcinoma of the stomach were treated with 3D-conformal radiation therapy to a dose of 45 Gy in 25 fractions with concurrent continuous infusional 5-fluorouracil (5-FU). The majority of patients received epirubicin, cisplatin and 5-FU (ECF) as the systemic component given before and after concurrent chemoradiation. The overall rates of observed grade 3 and 4 toxicities were 38 and 15%, respectively. GIT grade 3 toxicity was observed in 19% of patients, while haematologic grade 3 and 4 toxicities were observed in 23%. Our results suggest that this adjuvant regimen can be delivered safely and with acceptable toxicity. This regimen forms the basis of several new studies being developed for postoperative adjuvant therapy of gastric cancer