Chemical trends in the Galactic halo from APOGEE data

Indexación: Web of Science; Scopus.The galaxy formation process in the A cold dark matter scenario can be constrained from the analysis of stars in the Milky Way's halo system. We examine the variation of chemical abundances in distant halo stars observed by the Apache Point Observatory Galactic Evolution Experiment ( APOGEE), as a function of distance from the Galactic Centre ( r) and iron abundance ([M/H]), in the range 5 less than or similar to r less than or similar to 30 kpc and - 2.5 15 kpc and [M/H] > - 1.1 (larger in the case of O, Mg, and S) with respect to the nearest halo stars. This result confirms previous claims for low-alpha stars found at larger distances. Chemical differences in elements with other nucleosynthetic origins (Ni, K, Na, and Al) are also detected. C and N do not provide reliable information about the interstellar medium from which stars formed because our sample comprises red giant branch and asymptotic giant branch stars and can experience mixing of material to their surfaces.https://academic.oup.com/mnras/article-lookup/doi/10.1093/mnras/stw286

Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models

Melanomas are highly lethal skin tumours that are frequently treated by surgical resection. However, the efficacy of such procedures is often limited by tumour recurrence and metastasis. Caveolin-1 (CAV1) has been attributed roles as a tumour suppressor, although in late-stage tumours, its presence is associated with enhanced metastasis. The expression of this protein in human melanoma development and particularly how the presence of CAV1 affects metastasis after surgery has not been defined. CAV1 expression in human melanocytes and melanomas increases with disease progression and is highest in metastatic melanomas. The effect of increased CAV1 expression can then be evaluated using B16F10 murine melanoma cells injected into syngenic immunocompetent C57BL/6 mice or human A375 melanoma cells injected into immunodeficient B6Rag1−/− mice. Augmented CAV1 expression suppresses tumour formation upon a subcutaneous injection, but enhances lung metastasis of cells injected into the tail vein in both models. A procedure was initially developed using B16F10 melanoma cells in C57BL/6 mice to mimic better the situation in patients undergoing surgery. Subcutaneous tumours of a defined size were removed surgically and local tumour recurrence and lung metastasis were evaluated after another 14 days. In this postsurgery setting, CAV1 presence in B16F10 melanomas favoured metastasis to the lung, although tumour suppression at the initial site was still evident. Similar results were obtained when evaluating A375 cells in B6Rag1−/− mice. These results implicate CAV1 expression in melanomas as a marker of poor prognosis for patients undergoing surgery as CAV1 expression promotes experimental lung metastasis in two different preclinical models

Is there an association between cutaneous leishmaniasis and skin cancer? A systematic review

Background: Cutaneous leishmaniasis is a prevalent communicable disease in low- and middle-income countries, where non-communicable diseases like skin cancer are on the rise. However, the study of multi-morbidity or co-morbidity between communicable and non-communicable diseases is limited, and even null for some tropical or neglected diseases. Nevertheless, looking at these conditions together instead of as isolated entities in places where these illnesses exist, could show new prevention and treatment paths. We aimed to summarize and critically appraise the epidemiological evidence on the association between cutaneous leishmaniasis and skin cancer. Methods: Following the PRISMA guidelines, we conducted a systematic review using five search engines (Embase, Medline, Global Health, Scopus and Web of Science). We sought observational studies in which the outcome was skin cancer whilst the exposure was cutaneous leishmaniasis; these conditions should have had laboratory or pathology confirmation. Results: No epidemiological investigations have studied the association between cutaneous leishmaniasis and skin cancer. Most of the evidence about the association of interest is still based on case reports and other clinical observations rather than strong epidemiological observational studies. Conclusions: Research is much needed to verify the repeatedly clinical observation that cutaneous leishmaniasis may be a risk factor for skin cancer. This evidence could inform and guide early diagnosis or prevention of skin cancer in survivors of cutaneous leishmaniasis or where cutaneous leishmaniasis is still highly prevalent. Registration: PROSPERO ID CRD42018111230; registered on 16/10/18

A Methodology for Detecting Field Potentials from the External Ear Canal: NEER and EVestG

An algorithm called the neural event extraction routine (NEER) and a method called Electrovestibulography (EVestG) for extracting field potentials (FPs) from artefact rich and noisy ear canal recordings is presented. Averaged FP waveforms can be used to aid detection of acoustic and or vestibular pathologies. FPs were recorded in the external ear canal proximal to the ear drum. These FPs were extracted using an algorithm called NEER. NEER utilises a modified complex Morlet wavelet analysis of phase change across multiple scales and a template matching (matched filter) methodology to detect FPs buried in noise and biological and environmental artefacts. Initial simulation with simulated FPs shows NEER detects FPs down to −30 dB SNR (power) but only 13–23% of those at SNR’s <−6 dB. This was deemed applicable to longer duration recordings wherein averaging could be applied as many FPs are present. NEER was applied to detect both spontaneous and whole body tilt evoked FPs. By subtracting the averaged tilt FP response from the averaged spontaneous FP response it is believed this difference is more representative of the vestibular response. Significant difference (p < 0.05) between up and down whole body (supine and sitting) movements was achieved. Pathologic and physiologic evidence in support of a vestibular and acoustic origin is also presented

Methods for Analysis of Matrix Metalloproteinase Regulation of Neutrophil-Endothelial Cell Adhesion

Recent evidence indicates novel role for matrix metalloproteinases (MMPs), in particular gelatinase A (MMP-2), in the regulation of vascular biology that are unrelated to their well-known proteolytic breakdown of matrix proteins. We have previously reported that MMP-2 can modulate vascular reactivity by cleavage of the Gly32-Leu33 bound in big endothelin-1 (ET-1) yielding a novel vasoactive peptide ET-1[1-32]. These studies were conducted to investigate whether gelatinolytic MMPs could affect neutrophil-endothelial cell attachment. ET-1[1-32] produced by MMP-2 up-regulated CD11b/CD18 expression on human neutrophils, thereby promoted their adhesion to cultured endothelial cells. ET-1[1-32] evoked release of gelatinase B (MMP-9), which in turn cleaved big ET-1 to yield ET-1[1-32], thus revealing a self-amplifying loop for ET-1[1-32] generation. ET-1[1-32] was rather resistant to cleavage by neutrophil proteases and further metabolism of ET-1[1-32] was not a prerequisite for its biological actions on neutrophils. The neutrophil responses to ET-1[1-32] were mediated via activation of ET(A)receptors through activation of the Ras/Raf-1/MEK/ERK signaling pathway. These results suggest a novel role for gelatinase A and B in the regulation of neutrophil functions and their interactions with endothelial cells. Here we describe the methods in detail as they relate to our previously published work

Deconstructing Weight Management Interventions for Young Adults: Looking Inside the Black Box of the EARLY Consortium Trials.

ObjectiveThe goal of the present study was to deconstruct the 17 treatment arms used in the Early Adult Reduction of weight through LifestYle (EARLY) weight management trials.MethodsIntervention materials were coded to reflect behavioral domains and behavior change techniques (BCTs) within those domains planned for each treatment arm. The analytical hierarchy process was employed to determine an emphasis profile of domains in each intervention.ResultsThe intervention arms used BCTs from all of the 16 domains, with an average of 29.3 BCTs per intervention arm. All 12 of the interventions included BCTs from the six domains of Goals and Planning, Feedback and Monitoring, Social Support, Shaping Knowledge, Natural Consequences, and Comparison of Outcomes; 11 of the 12 interventions shared 15 BCTs in common across those six domains.ConclusionsWeight management interventions are complex. The shared set of BCTs used in the EARLY trials may represent a core intervention that could be studied to determine the required emphases of BCTs and whether additional BCTs add to or detract from efficacy. Deconstructing interventions will aid in reproducibility and understanding of active ingredients

Early growth patterns and cardiometabolic function at the age of 5 in a multiethnic birth cohort: the ABCD study

<p>Abstract</p> <p>Background</p> <p>The relation between fetal growth retardation and cardiovascular and metabolic diseases in later life has been demonstrated in many studies. However, debate exists around the potential independent role of postnatal growth acceleration. Furthermore, it is unknown whether a potential effect of growth acceleration on cardiovascular and metabolic function is confined to certain timeframes.</p> <p>The present study assesses the (predictive) role of prenatal and postnatal growth on 5 components of cardiovascular and metabolic function in children aged 5. The potential association of timing of postnatal growth acceleration with these outcomes will be explored.</p> <p>Methods and design</p> <p>Prospective multiethnic community-based cohort study of 8266 pregnancies (Amsterdam Born Children and their Development, ABCD study). Up till now, anthropometry of 5104 children from the original cohort was followed during the first 5 years of life, with additional information about birth weight, pregnancy duration, and various potential confounding variables.</p> <p>At age 5, various components of cardiovascular and metabolic function are being measured. Outcome variables are body size, body composition and fat distribution, insulin sensitivity, lipid profile, blood pressure and autonomic regulation of cardiovascular function.</p> <p>Discussion</p> <p>This study will be one of the first population-based prospective cohort studies to address the association between measures of both prenatal and postnatal growth and various components of cardiovascular and metabolic function. Specific attention is paid to the timing of acceleration in growth and its potential association with the outcome variables. Importantly, the longitudinal design of this study gives us the opportunity to gain more insight into growth trajectories associated with adverse outcomes in later life. If identified as an independent risk factor, this provides further basis for the hypothesis that accelerated growth during the first years of life is a modifiable factor for the prevention of cardiovascular and metabolic disorders in later life. Moreover, identification of specific vulnerable periods during development may reveal suitable timeframes for early interventions.</p

The circadian rhythm of corticosteroid-binding globulin has little impact on cortisol exposure after hydrocortisone dosing

CONTEXT: Optimisation of hydrocortisone replacement therapy is important to prevent under- and over dosing. Hydrocortisone pharmacokinetics is complex as circulating cortisol is protein bound mainly to corticosteroid-binding globulin (CBG) that has a circadian rhythm. OBJECTIVE: A detailed analysis of the CBG circadian rhythm and its impact on cortisol exposure after hydrocortisone administration. DESIGN AND METHODS: CBG was measured over 24 h in 14 healthy individuals and, employing a modelling and simulation approach using a semi-mechanistic hydrocortisone pharmacokinetic model, we evaluated the impact on cortisol exposure (area under concentration-time curve and maximum concentration of total cortisol) of hydrocortisone administration at different clock times and of the changing CBG concentrations. RESULTS: The circadian rhythm of CBG was well described with two cosine terms added to the baseline of CBG: baseline CBG was 21.8 μg/mL and inter-individual variability 11.9%; the amplitude for the 24 h and 12 h cosine functions were relatively small (24 h: 5.53%, 12 h: 2.87%) and highest and lowest CBG were measured at 18:00 and 02:00, respectively. In simulations, the lowest cortisol exposure was observed after administration of hydrocortisone at 23:00-02:00, whereas the highest was observed at 15:00-18:00. The differences between the highest and lowest exposure were minor (≤12.2%), also regarding the free cortisol concentration and free fraction (≤11.7%). CONCLUSIONS: CBG has a circadian rhythm but the difference in cortisol exposure is ≤12.2% between times of highest and lowest CBG concentrations; therefore hydrocortisone dose adjustment based on time of dosing to adjust for the CBG concentrations is unlikely to be of clinical benefit

Phenomenological Consequences of sub-leading Terms in See-Saw Formulas

Several aspects of next-to-leading (NLO) order corrections to see-saw formulas are discussed and phenomenologically relevant situations are identified. We generalize the formalism to calculate the NLO terms developed for the type I see-saw to variants like the inverse, double or linear see-saw, i.e., to cases in which more than two mass scales are present. In the standard type I case with very heavy fermion singlets the sub-leading terms are negligible. However, effects in the percent regime are possible when sub-matrices of the complete neutral fermion mass matrix obey a moderate hierarchy, e.g. weak scale and TeV scale. Examples are cancellations of large terms leading to small neutrino masses, or inverse see-saw scenarios. We furthermore identify situations in which no NLO corrections to certain observables arise, namely for mu-tau symmetry and cases with a vanishing neutrino mass. Finally, we emphasize that the unavoidable unitarity violation in see-saw scenarios with extra fermions can be calculated with the formalism in a straightforward manner.Comment: 22 pages, matches published versio