Baseline morning cortisol level as a predictor of pituitary-adrenal reserve: a comparison across three assays

The short ACTH stimulation test (250 μg) is the dynamic test most frequently used to assess adrenal function. It is possible that a single basal cortisol could be used to predict the dynamic response, but research has been hampered by the use of different assays and thresholds. OBJECTIVE: To propose a morning baseline cortisol criterion of three of the most commonly used modern cortisol immunoassays - Advia Centaur (Siemens), Architect (Abbott) and the Roche Modular System (Roche) - that could predict adrenal sufficiency. DESIGN: Observational, retrospective cross-sectional study at two centres. PATIENTS AND MEASUREMENTS: Retrospective analysis of the results of 1019 Short Synacthen tests (SSTs) with the Advia Centaur, 449 SSTs with the Architect and 2050 SSTs with the Roche Modular System assay. Serum cortisol levels were measured prior to injection of 250 μg Synacthen and after 30 min. Overall, we were able to collate data from a total of 3518 SSTs in 3571 patients. RESULTS: Using receiver-operator curve analysis, baseline cortisol levels for predicting passing the SST with 100% specificity were 358 nmol/l for Siemens, 336 nmol/l for Abbott and 506 nmol/l for Roche. Utilizing these criteria, 589, 158 and 578 SSTs, respectively, for Siemens, Abbott and Roche immunoassays could have been avoided. CONCLUSIONS: We have defined assay-specific morning cortisol levels that are able to predict the integrity of the hypothalamo-pituitary-adrenal axis. We propose that this represents a valid tool for the initial assessment of adrenal function and has the potential to obviate the need for dynamic testing in a significant number of patients

Separation of river network–scale nitrogen removal among the main channel and two transient storage compartments

Transient storage (TS) zones are important areas of dissolved inorganic nitrogen (DIN) processing in rivers. We assessed sensitivities regarding the relative impact that the main channel (MC), surface TS (STS), and hyporheic TS (HTS) have on network denitrification using a model applied to the Ipswich River in Massachusetts, United States. STS and HTS connectivity and size were parameterized using the results of in situ solute tracer studies in first‐ through fifth‐order reaches. DIN removal was simulated in all compartments for every river grid cell using reactivity derived from Lotic Intersite Nitrogen Experiment (LINX2) studies, hydraulic characteristics, and simulated discharge. Model results suggest that although MC‐to‐STS connectivity is greater than MC‐to‐HTS connectivity at the reach scale, at basin scales, there is a high probability of water entering the HTS at some point along its flow path through the river network. Assuming our best empirical estimates of hydraulic parameters and reactivity, the MC, HTS, and STS removed approximately 38%, 21%, and 14% of total DIN inputs during a typical base flow period, respectively. There is considerable uncertainty in many of the parameters, particularly the estimates of reaction rates in the different compartments. Using sensitivity analyses, we found that the size of TS is more important for DIN removal processes than its connectivity with the MC when reactivity is low to moderate, whereas TS connectivity is more important when reaction rates are rapid. Our work suggests a network perspective is needed to understand how connectivity, residence times, and reactivity interact to influence DIN processing in hierarchical river systems

Eddy-mediated transport of warm Circumpolar Deep Water across the Antarctic Shelf Break

The Antarctic Slope Front (ASF) modulates ventilation of the abyssal ocean via the export of dense Antarctic Bottom Water (AABW) and constrains shoreward transport of warm Circumpolar Deep Water (CDW) toward marine-terminating glaciers. Along certain stretches of the continental shelf, particularly where AABW is exported, density surfaces connect the shelf waters to the middepth Circumpolar Deep Water offshore, offering a pathway for mesoscale eddies to transport CDW directly onto the continental shelf. Using an eddy-resolving process model of the ASF, the authors show that mesoscale eddies can supply a dynamically significant transport of heat and mass across the continental shelf break. The shoreward transport of surface waters is purely wind driven, while the shoreward CDW transport is entirely due to mesoscale eddy transfer. The CDW flux is sensitive to all aspects of the model's surface forcing and geometry, suggesting that shoreward eddy heat transport may be localized to favorable sections of the continental slope

Correspondence of Change of Structure of Water with the Change of Apparent Volumes of Ions in Solution

Careful measurements were made of the diffraction curves of dilute aqueous solutions of LiCl, NaCl, KCl, NH4Cl, MgCl2, Co (C2H3O2) CoCl2, KClO3, and AICl3. In view of the inadequacy of the free ion theory to explain the nature of the change of apparent volume of ions in solutions, any evidence of any kind of correlation with that change is important. The x-ray diffraction of water was used to determine the magnitude of the alteration of water structure by the presence of ions. It is found that when the change of apparent molal ionic volume with concentration is more rapid, the alteration in the water structure is greater. The correlation is strong enough to make quite certain that the change of water structure is an important factor in the apparent volume change of the ions. With KClO3 the apparent molal volume of the ions decreases with concentration, which is in the opposite sense. If the water structure is important, as claimed, then this structure must decrease in density with concentration of the ions. The x-ray diffraction of KClO3 indicates that the alteration in water structure is certainly very different than in the cases of the other ions, and to this extent is confirmatory

Benthic assemblages of the Anton Dohrn seamount (NE Atlantic): defining deep-sea biotopes to support habitat mapping and management efforts with a focus on vulnerable marine ecosystems

In 2009 the NW and SE flanks of Anton Dohrn Seamount were surveyed using multibeam echosounder and video ground-truthing to characterise megabenthic biological assemblages (biotopes) and assess those which clearly adhere to the definition of Vulnerable Marine Ecosystems, for use in habitat mapping. A combination of multivariate analysis of still imagery and video ground-truthing defined 13 comprehensive descriptions of biotopes that function as mapping units in an applied context. The data reveals that the NW and SE sides of Anton Dohrn Seamount (ADS) are topographically complex and harbour diverse biological assemblages, some of which agree with current definitions of ‘listed’ habitats of conservation concern. Ten of these biotopes could easily be considered Vulnerable Marine Ecosystems; three coral gardens, four cold-water coral reefs, two xenophyophore communities and one sponge dominated community, with remaining biotopes requiring more detailed assessment. Coral gardens were only found on positive geomorphic features, namely parasitic cones and radial ridges, found both sides of the seamount over a depth of 1311–1740 m. Two cold-water coral reefs (equivalent to summit reef) were mapped on the NW side of the seamount; Lophelia pertusa reef associated with the cliff top mounds at a depth of 747–791 m and Solenosmilia variabilis reef on a radial ridge at a depth of 1318-1351 m. Xenophyophore communities were mapped from both sides of the seamount at a depth of 1099–1770 m and were either associated with geomorphic features or were in close proximity (< 100 m) to them. The sponge dominated community was found on the steep escarpment either side of the seamount over at a depth of 854-1345 m. Multivariate diversity revealed the xenophyophore biotopes to be the least diverse, and a hard substratum biotope characterised by serpulids and the sessile holothurian, Psolus squamatus, as the most diverse

Loss of p16Ink4a Function Rescues Cellular Senescence Induced by Telomere Dysfunction

p16Ink4a is a tumor suppressor and a marker for cellular senescence. Previous studies have shown that p16Ink4a plays an important role in the response to DNA damage signals caused by telomere dysfunction. In this study, we crossed Wrn−/− and p16Ink4a−/− mice to knock out the p16Ink4a function in a Wrn null background. Growth curves showed that loss of p16Ink4a could rescue the growth barriers that are observed in Wrn−/− mouse embryonic fibroblasts (MEFs). By challenging the MEFs with the global genotoxin doxorubicin, we showed that loss of p16Ink4a did not dramatically affect the global DNA damage response of Wrn−/− MEFs induced by doxorubicin. However, in response to telomere dysfunction initiated by the telomere damaging protein TRF2ΔBΔM, loss of p16Ink4a could partially overcome the DNA damage response by disabling p16Ink4a up-regulation and reducing the accumulation of γ-H2AX that is observed in Wrn−/− MEFs. Furthermore, in response to TRF2ΔBΔM overexpression, Wrn−/− MEFs senesced within several passages. In contrast, p16Ink4a−/− and p16Ink4a−/−Wrn−/− MEFs could continuously grow and lose expression of the exogenous TRF2ΔBΔM in their late passages. In summary, our data suggest that in the context of telomere dysfunction, loss of p16Ink4a function could prevent cells from senescence. These results shed light on the anti-aging strategy through regulation of p16Ink4a expression

Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials

Large randomized controlled trials (RCTs) in preterm infants offer unique opportunities for mechanistic evaluation of the risk factors leading to serious diseases, as well as the actions of interventions designed to prevent them. Necrotizing enterocolitis (NEC) a serious inflammatory gut condition and late-onset sepsis (LOS) are common feeding and nutrition-related problems that may cause death or serious long-term morbidity and are key outcomes in two current UK National Institutes for Health Research (NIHR) trials. Speed of increasing milk feeds trial (SIFT) randomized preterm infants to different rates of increases in milk feeds with a primary outcome of survival without disability at 2 years corrected age. Enteral lactoferrin in neonates (ELFIN) randomizes infants to supplemental enteral lactoferrin or placebo with a primary outcome of LOS. This is a protocol for the mechanisms affecting the gut of preterm infants in enteral feeding trials (MAGPIE) study and is funded by the UK NIHR Efficacy and Mechanistic Evaluation programme. MAGPIE will recruit ~480 preterm infants who were enrolled in SIFT or ELFIN. Participation in MAGPIE does not change the main trial protocols and uses non-invasive sampling of stool and urine, along with any residual resected gut tissue if infants required surgery. Trial interventions may involve effects on gut microbes, metabolites (e.g., short-chain fatty acids), and aspects of host immune function. Current hypotheses suggest that NEC and/or LOS are due to a dysregulated immune system in the context of gut dysbiosis, but mechanisms have not been systematically studied within large RCTs. Microbiomic analysis will use next-generation sequencing, and metabolites will be assessed by mass spectrometry to detect volatile organic and other compounds produced by microbes or the host. We will explore differences between disease cases and controls, as well as exploring the actions of trial interventions. Impacts of this research are multiple: translation of knowledge of mechanisms promoting gut health may explain outcomes or suggest alternate strategies to improve health. Results may identify new non-invasive diagnostic or monitoring techniques, preventative or treatment strategies for NEC or LOS, or provide data useful for risk stratification in future studies. Mechanistic evaluation might be especially informative where there are not clear effects on the primary outcome (ISRCTN 12554594)