Repeating adrenal vein sampling when neither aldosterone/cortisol ratio exceeds peripheral yields a high incidence of aldosterone-producing adenoma

Objectives:In primary aldosteronism, adrenal vein sampling (AVS) suggests unilateral aldosterone-producing adenoma (APA) when the aldosterone/cortisol (A/F) ratio is less than or equal to peripheral on one side and at least two times peripheral on the other. When A/F ratios are lower bilaterally than peripheral despite adequate samples (adrenal venous cortisol 3 times peripheral), we recommend repeat AVS. This study aimed to determine the frequency of this occurrence and outcomes in such cases.Methods:We performed a retrospective observational study of all cases of primary aldosteronism undergoing initial AVS over a 34-year period.Results:Initial AVS in 1397 patients returned satisfactory and discriminatory results in 1066 (76.3%) but 37 patients (2.6%) had adequate samples but bilateral A/F ratios no higher than peripheral. Of the 22 of these 37 who agreed to repeat AVS, 10 demonstrated unilateral aldosterone production, and eight of these had unilateral adrenalectomy disclosing APAs and resulting in cure (3) or improvement (5) in hypertension. Eight had bilateral aldosterone production. Four studies were inconclusive. Patients with initial unsatisfactory AVS because of bilaterally low A/F ratios had significantly (P=0.023) more unilateral disease [10 of 18 satisfactory repeat studies (55.6%) vs. 326 of 1066 satisfactory initial studies (30.6%)] and a significantly higher (67.6 vs. 49.9%, P=0.034) percentage of males.Conclusion:As the incidence of APAs was high in a subgroup with low A/F bilaterally on initial AVS, these patients should be offered repeat AVS. This might reflect both a greater dependence of aldosterone production on adrenocorticotrophic hormone (ACTH) in APAs and the pulsatile nature of ACTH secretion

Isomerization dynamics of a buckled nanobeam

We analyze the dynamics of a model of a nanobeam under compression. The model is a two mode truncation of the Euler-Bernoulli beam equation subject to compressive stress. We consider parameter regimes where the first mode is unstable and the second mode can be either stable or unstable, and the remaining modes (neglected) are always stable. Material parameters used correspond to silicon. The two mode model Hamiltonian is the sum of a (diagonal) kinetic energy term and a potential energy term. The form of the potential energy function suggests an analogy with isomerisation reactions in chemistry. We therefore study the dynamics of the buckled beam using the conceptual framework established for the theory of isomerisation reactions. When the second mode is stable the potential energy surface has an index one saddle and when the second mode is unstable the potential energy surface has an index two saddle and two index one saddles. Symmetry of the system allows us to construct a phase space dividing surface between the two "isomers" (buckled states). The energy range is sufficiently wide that we can treat the effects of the index one and index two saddles in a unified fashion. We have computed reactive fluxes, mean gap times and reactant phase space volumes for three stress values at several different energies. In all cases the phase space volume swept out by isomerizing trajectories is considerably less than the reactant density of states, proving that the dynamics is highly nonergodic. The associated gap time distributions consist of one or more `pulses' of trajectories. Computation of the reactive flux correlation function shows no sign of a plateau region; rather, the flux exhibits oscillatory decay, indicating that, for the 2-mode model in the physical regime considered, a rate constant for isomerization does not exist.Comment: 42 pages, 6 figure

Ambiguous figures and the content of experience

Representationalism is the position that the phenomenal character of an experience is either identical with, or supervenes on, the content of that experience. Many representationalists hold that the relevant content of experience is nonconceptual. I propose a counterexample to this form of representationalism that arises from the phenomenon of Gestalt switching, which occurs when viewing ambiguous figures. First, I argue that one does not need to appeal to the conceptual content of experience or to judgements to account for Gestalt switching. I then argue that experiences of certain ambiguous figures are problematic because they have different phenomenal characters but that no difference in the nonconceptual content of these experiences can be identified. I consider three solutions to this problem that have been proposed by both philosophers and psychologists and conclude that none can account for all the ambiguous figures that pose the problem. I conclude that the onus is on representationalists to specify the relevant difference in content or to abandon their position

Effects of prenatal exercise on fetal heart rate, umbilical and uterine blood flow: a systematic review and meta-analysis

Objective To perform a systematic review and meta-analysis examining the influence of acute and chronic prenatal exercise on fetal heart rate (FHR) and umbilical and uterine blood flow metrics. Design Systematic review with random-effects meta-analysis and meta-regression. Data sources Online databases were searched up to 6 January 2017. Study eligibility criteria Studies of all designs were included (except case studies) if published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [eg, dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcomes (FHR, beats per minute (bpm); uterine and umbilical blood flow metrics (systolic:diastolic (S/D) ratio; Pulsatility Index (PI); Resistance Index (RI); blood flow, mL/min; and blood velocity, cm/s)). Results ‘Very low’ to ‘moderate’ quality evidence from 91 unique studies (n=4641 women) were included. Overall, FHR increased during (mean difference (MD)=6.35bpm; 95% CI 2.30 to 10.41, I2=95%, p=0.002) and following acute exercise (MD=4.05; 95% CI 2.98 to 5.12, I2=83%, p\u3c0.00001). The incidence of fetal bradycardia was low at rest and unchanged with acute exercise. There were no significant changes in umbilical or uterine S/D, PI, RI, blood flow or blood velocity during or following acute exercise sessions. Chronic exercise decreased resting FHR and the umbilical artery S/D, PI and RI at rest. Conclusion Acute and chronic prenatal exercise do not adversely impact FHR or uteroplacental blood flow metrics

Characterization of the acidic cold seep emplaced jarositic Golden Deposit, NWT, Canada, as an analogue for jarosite deposition on Mars

Surficial deposits of the OH-bearing iron sulfate mineral jarosite have been observed in several places on Mars, such as Meridiani Planum and Mawrth Vallis. The specific depositional conditions and mechanisms are not known, but by comparing martian sites to analogous locations on Earth, the conditions of formation and, thus, the martian depositional paleoenvironments may be postulated. Located in a cold semi-arid desert ~100 km east of Norman Wells, Northwest Territories, Canada, the Golden Deposit (GD) is visible from the air as a brilliant golden-yellow patch of unvegetated soil, approximately 140 m x 50 m. The GD is underlain by permafrost and consists of yellow sediment, which is precipitating from seeps of acidic, iron-bearing groundwater. On the surface, the GD appears as a patchwork of raised polygons, with acidic waters flowing from seeps in troughs between polygonal islands. Although UV-Vis-NIR spectral analysis detects only jarosite, mineralogy, as determined by X-Ray Diffraction and Inductively Coupled Plasma Emission Spectrometry, is predominantly natrojarosite and jarosite, with hydronium jarosite, goethite, quartz, clays, and small amounts of hematite. Water pH varies significantly over short distances depending on proximity to acid seeps, from 2.3 directly above seeps, to 5.7 several m downstream from seeps within the deposit, and up to 6.5 in ponds proximal to the deposit. Visual observations of microbial filament communities and phospholipid fatty acid analyses confirm that the GD is capable of supporting life for at least part of the year. Jarositic-bearing sediments extend beneath vegetation up to 70 m out from the deposit and are mixed with plant debris and minerals presumably weathered from bedrock and glacial till. This site is of particular interest because mineralogy (natrojarosite, jarosite, hematite, and goethite) and environmental conditions (permafrost and arid conditions) at the time of deposition are conceivably analogous to jarosite deposits on Mars. Most terrestrial analogues for Mars jarosites have been identified in temperate environments, where evaporation rates are very high and jarosites form along with other sulfates due to rapid evaporation (e.g. Rio Tinto, Spain; Western Australian acidic saline lake deposits). The GD is a rare example of an analogue site where jarosite precipitates under dominant freezing processes similar to those which could have prevailed on early Mars. Thus, the GD offers a new perspective on jarosite deposition by the upwelling of acidic waters through permafrost at Meridiani Planum and Mawrth Vallis, Mars. The GD also demonstrates that martian deposits may show considerably more chemical and mineral variability than indicated by the current remote sensing data sets

Putative mixotrophic nitrifying-denitrifying Gammaproteobacteria implicated in nitrogen cycling within the ammonia/oxygen transition zone of an oil sands pit Lake

Syncrude Canada Ltd.Anthropogenically-impacted environments offer the opportunity to discover novel microbial species and metabolisms, which may be undetectable in natural systems. Here, a combined metagenomic and geochemical study in Base Mine Lake, Alberta, Canada, which is the only oil sands end pit lake to date, revealed that nitrification was performed by members from Nitrosomonadaceae, Chloroflexi and unclassified Gammaproteobacteria “MBAE14.” While Nitrosomonadaceae and Chloroflexi groups were relatively abundant in the upper oxygenated zones, MBAE14 dominated the hypoxic hypolimnetic zones (approximately 30% of total microbial communities); MBAE14 was not detected in the underlying anoxic tailings. Replication rate analyses indicate that MBAE14 grew in metalimnetic and hypolimnetic water cap regions, most actively at the metalimnetic, ammonia/oxygen transition zone consistent with it putatively conducting nitrification. Detailed genomic analyses of MBAE14 evidenced both ammonia oxidation and denitrification into dinitrogen capabilities. However, the absence of known CO2-fixation genes suggests a heterotrophic denitrifying metabolism. Functional marker genes of ammonia oxidation (amo and hao) in the MBAE14 genome are homologous with those conserved in autotrophic nitrifiers, but not with those of known heterotrophic nitrifiers. We propose that this novel MBAE14 inhabits the specific ammonia-rich, oxygen and labile organic matter-limited conditions occurring in Base Mine Lake which selectively favors mixotrophic coupled nitrifier denitrification metabolism. Our results highlight the opportunities to better constrain biogeochemical cycles from the application of metagenomics to engineered systems associated with extractive resource sectors

Microcanonical rates, gap times, and phase space dividing surfaces

The general approach to classical unimolecular reaction rates due to Thiele is revisited in light of recent advances in the phase space formulation of transition state theory for multidimensional systems. We analyze in detail the gap time distribution and associated reactant lifetime distribution for the isomerization reaction HCN $\rightleftharpoons$ CNH. Both algebraic (power law) and exponential decay regimes have been identified. Statistical estimates of the isomerization rate are compared with the numerically determined decay rate. Examination of the decay properties of subsensembles of trajectories that exit the HCN well through either of 2 available symmetry related product channels shows that the complete trajectory ensemble effectively attains the full symmetry of the system phase space on a short timescale $t \lesssim 0.5$ ps, after which the product branching ratio is 1:1, the "statistical" value. At intermediate times, this statistical product ratio is accompanied by nonexponential (nonstatistical) decay. We point out close parallels between the dynamical behavior inferred from the gap time distribution for HCN and nonstatistical behavior recently identified in reactions of some organic molecules.Comment: 44 pages, 9 figure