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Domestic value chains (DVCs) led by retailers within the global South often overlap with global value chains (GVCs) as well as domestic arm's length markets. DVCs incorporate some private governance, but we know little about the role of public governance. Based on analysis of Kenyan fresh fruit and vegetables, we ask: How is the power (or ability) of lead firms to govern producers being reshaped by the increased complexity of polycentric trade in the Kenyan horticultural sector? We reveal constraints to lead firms' ability to directly exercise bargaining power; and shifts towards institutional power in a context of polycentric trade. [ABSTRACT FROM AUTHOR]

Background: Inborn errors of metabolism comprise a set of more than 2000 known disorders which can result in significant morbidity and may be rapidly fatal. Diagnosing these disorders at birth and treating immediately, however, may often result in a normal to near-normal life for the affected infant. Thus, newborn screening (NBS) has saved or improved the lives of countless individuals since its inception in the 1960s. Content: This review covers NBS, from its early beginnings up to the current day practice. We follow the evolution of NBS, as well as describe the need and how disorders are added to NBS programs, the testing and how its performance is monitored, and the follow-up to the testing. We also briefly touch on NBS outside the United States. Summary: Newborn screening in the United States is a major public health success story and it continues to grow and evolve to cover more disorders and utilize new technological advances. [ABSTRACT FROM AUTHOR]

This article, published in the British Journal of Dermatology, discusses the findings of a study on psoriasis, a chronic skin inflammatory disease. The researchers used single-cell transcriptomic analysis to examine the cell subsets and interactions in the epidermis of psoriasis patients. They found altered differentiation trajectories and dynamic changes in epidermal cell states in psoriasis, as well as the presence of a unique plasmacytoid dendritic cell population. The study also revealed physical immune cell-keratinocyte interactions in psoriatic epidermis. The findings suggest potential roles for epidermal plasmacytoid dendritic cells in exacerbating skin inflammation in psoriasis. [Extracted from the article]

Using MUSE data, we investigate the radial gradients of stellar population properties (namely age, [M/H], and the abundance ratio of α elements [α/Fe]) for a sample of nine dwarf early-type (dE) galaxies with log(M ⋆/M⊙) ∼ 9.0 and an infall time onto the Virgo cluster of 2–3 Gyr ago. We followed a similar approach as in Bidaran et al. to derive their stellar population properties and star formation histories (SFHs) through fitting observed spectral indices and full spectral fitting, respectively. We find that these nine dE galaxies have truncated [Mg/Fe] versus [Fe/H] profiles than equally massive Virgo dE galaxies with longer past infall times. Short profiles of three dE galaxies are the result of their intense star formation which has been quenched long before their accretion onto the Virgo cluster, possibly as a result of their group environment. In the remaining six dE galaxies, profiles mainly trace a recent episode of star burst within 0.4 R e which results in higher light-weighted [α/Fe] values. The latter SFH peak can be due to ram pressure exerted by the Virgo cluster at the time of the accretion of the dE galaxies. Also, we show that younger, more metal-rich, and less α-enhanced stellar populations dominate their inner regions (i.e. < 0.4 R e) resulting in mainly flat ∇age, negative ∇[M/H], and positive ∇[α/Fe]. We find that with increasing log(σRe) of dE galaxies, ∇age and ∇[α/Fe] flatten, and the latter correlation persists even after including early-type galaxies up to log(σRe ∼ 2.5), possibly due to the more extended star formation activity in the inner regions of dEs, as opposed to more massive early-type galaxies. [ABSTRACT FROM AUTHOR]

Using a sample of >200 clusters, each with typically 100–200 spectroscopically confirmed cluster members, we search for a signal of alignment between the position angle (PA) of the Brightest Cluster Galaxy (BCG) and the distribution of cluster members on the sky about the cluster centre out to projected distances of 3  R 200. The deep spectroscopy, combined with corrections for spectroscopic incompleteness, makes our sample ideal to determine alignment signal strengths. We also use an SDSS based skeleton of the filamentary large-scale structure (LSS), and measure BCG alignment with the location of the LSS skeleton segments on the sky out to projected distances of 10  R 200. The alignment signal is measured using three separate statistical measures; Rao's spacing test (U), Kuiper's V parameter (V), and the Binomial probability test (P). The significance of the BCG alignment signal with both cluster members and LSS segments is extremely high (1 in a million chance or less to be drawn randomly from a uniform distribution). We investigate a wide set of parameters that may influence the strength of the alignment signal. Clusters with more elliptical-shaped BCGs show stronger alignment with both their cluster members and LSS segments. Also, selecting clusters with closely connected filaments, or using a luminosity-weighted LSS skeleton, increases the alignment signal significantly. Alignment strength decreases with increasing projected distance. Combined, these results provide strong evidence for the growth of clusters and their BCGs by preferential feeding along the direction of the filaments in which they are embedded. [ABSTRACT FROM AUTHOR]

We measure the [α/Fe] abundances for 183 quiescent galaxies at z  = 0.60−0.75 with stellar masses ranging 10.4 ≤ log10(M */ M ⊙) ≤ 11.6 selected from the Large Early Galaxy Astrophysics Census survey. We estimate [α/Fe] from the ratio of the spectral indices Mgb (λ ∼ 5177 Å) and Fe4383, compared to predictions of simple stellar population models. We find that 91 per cent of quiescents in our sample have supersolar [α/Fe], with an average value of [α/Fe] = +0.24 ± 0.01. We find no significant correlation between [α/Fe] and stellar metallicity, mass, velocity dispersion, and average formation time. Galaxies that formed the bulk of their stellar mass on time-scales shorter than 1 Gyr follow the same [α/Fe] distribution as those which formed on longer time-scales. In comparison to local early-type galaxies and to stacked spectra of quiescent galaxies at z  = 0.38 and z  = 0.07, we find that the average [α/Fe] has not changed between z  = 0.75 and the present time. Our work shows that the vast majority of massive quiescent galaxies at z ∼ 0.7 are α-enhanced, and that no detectable evolution of the average [α/Fe] has taken place over the last ∼6.5 Gyr. [ABSTRACT FROM AUTHOR]

We analyse the quenched fractions, gas content, and star formation histories of ∼1200 satellite galaxies with M * ≥ 5 × 106 M⊙ around 198 Milky Way- (MW) and Andromeda-like (M31) hosts in TNG50, the highest-resolution simulation of IllustrisTNG. Satellite quenched fractions are larger for smaller masses, for smaller distances to their host galaxy, and in the more massive M31-like compared to MW-like hosts. As satellites cross their host's virial radius, their gas content drops: Most satellites within 300 kpc lack detectable gas reservoirs at z = 0, unless they are massive like the Magellanic Clouds and M32. Nevertheless, their stellar assembly exhibits a large degree of diversity. On average, the cumulative star formation histories are more extended for brighter, more massive satellites with a later infall, and for those in less massive hosts. Based on these relationships, we can even infer infall periods for observed MW and M31 dwarfs, e.g. 0–4 Gyr ago for the Magellanic Clouds and Leo I, and 4–8 and 0–2 Gyr ago for M32 and IC 10, respectively. Ram pressure stripping (in combination with tidal stripping) deprives TNG50 satellites of their gas reservoirs and ultimately quenches their star formation, even though only a few per cent of the present-day satellites around the 198 TNG50 MW/M31-like hosts appear as jellyfish. The typical time since quenching for currently quenched TNG50 satellites is |$6.9\substack{+2.5\\-3.3}$| Gyr ago. The TNG50 results are consistent with the quenched fractions and stellar assembly of observed MW and M31 satellites, however, satellites of the SAGA survey with M * ∼ 108–109 M⊙ exhibit lower quenched fractions than TNG50 and other, observed analogues. [ABSTRACT FROM AUTHOR]

We derived stellar ages and metallicities [Z/H] for ∼70 passive early-type galaxies (ETGs) selected from VANDELS survey over the redshift range 1.0 < z < 1.4 and stellar mass range 10 < log(M */M⊙) < 11.6. We find significant systematics in their estimates depending on models and wavelength ranges considered. Using the full-spectrum fitting technique, we find that both [Z/H] and age increase with mass as for local ETGs. Age and metallicity sensitive spectral indices independently confirm these trends. According to EMILES models, for 67 per cent of the galaxies we find [Z/H] > 0.0, a percentage which rises to ∼90 per cent for log(M */M⊙) > 11 where the mean metallicity is [Z/H] = 0.17 ± 0.1. A comparison with homogeneous measurements at similar and lower redshift does not show any metallicity evolution over the redshift range 0.0 < z < 1.4. The derived star formation (SF) histories show that the stellar mass fraction formed at early epoch increases with the mass of the galaxy. Galaxies with log(M */M⊙) > 11.0 host stellar populations with [Z/H] > 0.05, formed over short time-scales (Δ t 50 < 1 Gyr) at early epochs (t form < 2 Gyr), implying high star formation rates (SFR > 100 M⊙ yr−1) in high-mass density regions (log(Σ1kpc) > 10 M⊙/kpc2). This sharp picture tends to blur at lower masses: log(M */M⊙) ∼ 10.6 galaxies can host either old stars with [Z/H] < 0.0 or younger stars with [Z/H] > 0.0, depending on the duration (Δ t 50) of the SF. The relations between galaxy mass, age, and metallicities are therefore largely set up ab initio as part of the galaxy formation process. Mass, SFR, and SF time-scale all contribute to shape up the stellar mass–metallicity relation with the mass that modulates metals retention. [ABSTRACT FROM AUTHOR]

We explore the stellar mass density and colour profiles of 118 low redshift, massive, central galaxies, selected to have assembled 90 per cent of their stellar mass 6 Gyr ago, finding evidence of the minor merger activity expected to be the driver behind the size growth of quiescent galaxies. We use imaging data in the g, r, i, z, y bands from the Subaru Hyper Suprime-Cam survey and perform SED fitting to construct spatially well-resolved radial profiles in colour and stellar mass surface density. Our visual morphological classification reveals that ∼42 per cent of our sample displays tidal features, similar to previous studies, ∼43 per cent of the remaining sample displays a diffuse stellar halo, and only ∼14 per cent displays no features, down to a limiting μ r -band ∼ 28 mag arcsec−2. We find good agreement between the stacked colour profiles of our sample to those derived from previous studies and an expected smooth, declining stellar mass surface density profile in the central regions (< 3 R e). However, we also see a flattening of the profile (Σ* ∼ 107.5 M⊙ kpc−2) in the outskirts (up to 10 R e), which is revealed by our method of specifically targeting tidal/accretion features. We find similar levels of tidal features and behaviour in the stellar mass surface density profiles in a younger comparison sample, however, a lack of diffuse haloes. We also apply stacking techniques similar to those in previous studies, finding such procedures wash out tidal features and thereby produce smooth declining profiles. The stellar material in the outskirts contributes on average ∼1010 M⊙ or a few per cent of the total stellar mass and has similar colours to SDSS satellites of similar stellar mass. [ABSTRACT FROM AUTHOR]

Using MUSE spectra, we investigate how pre-processing and accretion on to a galaxy cluster affect the integrated stellar population properties of dwarf early-type galaxies (dEs). We analyse a sample of nine dEs with stellar masses of |$\rm \sim 10^9 \, M_\odot$|⁠ , which were accreted (∼ 2–3 Gyr ago) on to the Virgo cluster as members of a massive galaxy group. We derive their stellar population properties, namely age, metallicity ([M/H]), and the abundance ratio of α elements ([α/Fe]), by fitting observed spectral indices with a robust, iterative procedure, and infer their star formation history (SFH) by means of full spectral fitting. We find that these nine dEs are more metal-poor (at the 2–3σ level) and significantly more α-enhanced than dEs in the Virgo and Coma clusters with similar stellar mass, clustercentric distance, and infall time. Moreover, for six dEs, we find evidence for a recent episode of star formation during or right after the time of accretion on to Virgo. We interpret the high [α/Fe] of our sample of dEs as the result of the previous exposure of these galaxies to an environment hostile to star formation, and/or the putative short burst of star formation they underwent after infall into Virgo. Our results suggest that the stellar population properties of low-mass galaxies may be the result of the combined effect of pre-processing in galaxy groups and environmental processes (such as ram-pressure triggering star formation) acting during the early phases of accretion on to a cluster. [ABSTRACT FROM AUTHOR]

Aim: To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM). Method: We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration < 10 years and without decreased estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m2) or macrovascular complications. Thirty-four age-matched healthy subjects [M/F 13/21; age 53.5 (50.0-57.7) years; eGFR 107.5 (97.0-119.7) mL/ min1.73 m2] served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers. Results: Albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g (5.6-17.2) with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy. Serum parathyroid hormone, fibroblast growth factor 23, and sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (P < 0.001), hemoglobin 1A1c (P = 0.036), and systolic (P = 0.021) and diastolic blood pressure (DBP) (P = 0.001) and negatively correlated with 25-hydroxyvitamin D (P = 0.046). In multivariate analysis, age, DBP, ACR, and serum Klotho were independent positive predictors of CAVI. Conclusion: In the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP and ACR are modifiable risk factors of vascular stiffness in T2DM, thus warranting optimal assessment. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is an immune‐mediated inflammatory skin disease, in which an interplay between infiltrating immune cells and keratinocytes sustains chronic skin inflammation. Interleukin (IL)‐17A is a key inflammatory cytokine in psoriasis and its main cellular targets are keratinocytes. Objectives: To explore the role of miR‐378a in psoriasis. Methods: Keratinocytes obtained from psoriatic skin and healthy epidermis were separated by magnetic sorting, and the expression of miR‐378a was analysed by quantitative polymerase chain reaction. The regulation and function of miR‐378a was studied using primary human keratinocytes. The expression of miR‐378a was modulated by synthetic mimics, and nuclear factor kappa B (NF‐κB) activity and transcriptomic changes were studied. Synthetic miR‐378a was delivered to mouse skin in conjunction with induction of psoriasiform skin inflammation by imiquimod. Results: We show that miR‐378a is induced by IL‐17A in keratinocytes through NF‐κB, C/EBP‐β and IκBζ and that it is overexpressed in psoriatic epidermis. In cultured keratinocytes, ectopic expression of miR‐378a resulted in the nuclear translocation of p65 and enhanced NF‐κB‐driven promoter activity even in the absence of inflammatory stimuli. Moreover, miR‐378a potentiated the effect of IL‐17A on NF‐κB nuclear translocation and downstream activation of the NF‐κB pathway. Finally, injection of miR‐378a into mouse skin augmented psoriasis‐like skin inflammation with increased epidermal proliferation and induction of inflammatory mediators. Mechanistically, miR‐378a acts as a suppressor of NFKBIA/IκBζ, an important negative regulator of the NF‐κB pathway in keratinocytes. Conclusions: Collectively, our findings identify miR‐378a as an amplifier of IL‐17A‐induced NF‐κB signalling in keratinocytes and suggest that increased miR‐378a levels contribute to the amplification of IL‐17A‐driven skin inflammation in psoriasis. [ABSTRACT FROM AUTHOR]

This article focuses on small- and medium-sized enterprises (SMEs) in Kenya's leather sector. It explores how public governance impacts SMEs' technological capabilities and access to global value chains (GVCs). By public governance, we mean all government regulations and interventions set in place to shape the organization of value chains. Drawing on interview data, the article compares Kenya's leather handbag and footwear manufacturers. On the one hand, handbag SMEs have succeeded in upgrading and entering GVCs through a combination of foreign knowledge and partnership with local universities. Despite meeting with public governance barriers, this process has enabled the transfer of technological capabilities from foreign-owned firms to a number of emerging SMEs owned by Kenyan nationals. On the other hand, leather footwear production was developed during the 1970s by large firms under state support. As protectionist measures were lifted in the 1990s, firms shut down and producers moved into the informal economy, replicating outdated capabilities in a context of price-driven competition, thereby limiting upgrading and participation in GVCs. The article concludes by comparing these findings with the experience of Kenya's apparel manufacturers and highlighting the critical need for GVC research to account for the role of public governance in shaping firms' technological capabilities and access to global markets. [ABSTRACT FROM AUTHOR]

This article analyses how the private governance of global value chains (GVCs) varies across multiple end-markets. This is explored through a two-stage mixed-methods analysis of Kenya's participation in leather value chains serving Europe, China, India and the COMESA region. We first draw on transaction-level customs data to analyse private governance in terms of the stability of buyer–supplier interactions and presence of intermediaries. We then interrogate these results through supplier interviews. Our article highlights the combined role of product specifications and trust in shaping private governance, and heterogeneity of GVCs across the global North and South, as well as within the South. It further questions commonly held assumptions that lower quality products (generally characterising Southern end-markets) are necessarily governed by market-based coordination mechanisms. We therefore challenge links established in the GVC literature between product standards and private governance. [ABSTRACT FROM AUTHOR]

We study the abundance of satellite galaxies around 198 Milky Way- (MW) and M31-like hosts in TNG50, the final installment in the IllustrisTNG suite of cosmological magnetohydrodynamical simulations. MW/M31-like analogues are defined as discy galaxies with stellar masses of |$M_* = 10^{10.5 - 11.2}~\rm {M}_\odot$| in relative isolation at z = 0. By defining satellites as galaxies with |$M_* \ge 5\times 10^{6}~\rm {M}_\odot$| within |$300~\rm {kpc}$| (3D) of their host, we find a remarkable level of diversity and host-to-host scatter across individual host galaxies. The median TNG50 MW/M31-like galaxy hosts a total of |$5^{+6}_{-3}$| satellites with |$M_* \ge 8 \times 10^6~\rm {M}_\odot$|⁠ , reaching up to |$M_* \sim 10^{8.5^{+0.9}_{-1.1}}~\rm {M}_\odot$|⁠. Even at a fixed host halo mass of |$10^{12}~\rm {M}_\odot$|⁠ , the total number of satellites ranges between 0 and 11. The abundance of subhaloes with |$M_\rm {dyn} \ge 5 \times 10^7~\rm {M}_\odot$| is larger by a factor of more than 10. The number of all satellites (subhaloes) ever accreted is larger by a factor of 4–5 (3–5) than those surviving to z = 0. Hosts with larger galaxy stellar mass, brighter K -band luminosity, more recent halo assembly, and – most significantly – larger total halo mass typically have a larger number of surviving satellites. The satellite abundances around TNG50 MW/M31-like galaxies are consistent with those of mass-matched hosts from observational surveys (e.g. SAGA) and previous simulations (e.g. Latte). While the observed MW satellite system falls within the TNG50 scatter across all stellar masses considered, M31 is slightly more satellite-rich than our 1σ scatter but well consistent with the high-mass end of the TNG50 sample. We find a handful of systems with both a Large and a Small Magellanic Cloud-like satellite. There is no missing satellites problem according to TNG50. [ABSTRACT FROM AUTHOR]

We investigate how cosmic web environment impacts the average properties of central galaxies in the Sloan Digital Sky Survey (SDSS). We analyse how the average specific star formation rate, stellar age, metallicity, and element abundance ratio [α/Fe] of SDSS central galaxies depend on distance from the cosmic web nodes, walls, and filaments identified by the Discrete Persistent Structures Extractor (DisPerSE). In our approach we control for galaxy stellar mass and local density differentiated between field and group environment. Our results confirm the known trend whereby galaxies exhibit lower specific star formation rates with decreasing distance to the cosmic web features. Furthermore, we show that centrals closer to either nodes, walls, or filaments are on average older, metal richer, and α-enhanced compared to their equal mass counterparts at larger distances. The identified property gradients appear to have the same amplitude for central galaxies in the field as for those in groups. Our findings support a cosmic web quenching that stems from nurture effects, such as ram pressure stripping and strangulation, and/or nature effects linked to the intrinsic properties of the cosmic web. [ABSTRACT FROM AUTHOR]

Using new, homogeneous, long-slit spectroscopy in the wavelength range from ∼0.35 to |$\sim 1 \, \mu$| m, we study radial gradients of optical and near-infrared (NIR) initial mass function (IMF)-sensitive features along the major axis of the bulge of M31, out to a galactocentric distance of ∼200 arcsec (∼800 pc). Based on state-of-the-art stellar population synthesis models with varying Na abundance ratio, we fit a number of spectral indices, from different chemical species (including TiO's, Ca, and Na indices), to constrain the low-mass (≲0.5 M⊙) end slope (i.e. the fraction of low-mass stars) of the stellar IMF, as a function of galactocentric distance. Outside a radial distance of ∼10 arcsec, we infer an IMF similar to a Milky Way-like distribution, while at small galactocentric distances, an IMF radial gradient is detected, with a mildly bottom-heavy IMF in the few inner arcsec. We are able to fit Na features (both NaD and |$\rm Na\,{\small I}8190$|⁠), without requiring extremely high Na abundance ratios. |$\rm [Na/Fe]$| is ∼0.4 dex for most of the bulge, rising up to ∼0.6 dex in the innermost radial bins. Our results imply an overall, luminosity-weighted, IMF and mass-to-light ratio for the M31 bulge, consistent with those for a Milky Way-like distribution, in contrast to results obtained, in general, for most massive early-type galaxies. [ABSTRACT FROM AUTHOR]

Objective: The association between chronic autoimmune thyroiditis (CAT) a nd differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when scre ening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ult rasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT. Design and methods: A retrospective longitudinal cohort study was designed. For th e study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enro lled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD-; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and dev elopment of DTC during follow-up. Results: During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD - group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-n eedle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases. Conclusions: In our series of CAT patients, the appearance of new thyroid-n odules was frequent, but none of them were found to be malignant. The presence of CAT appears to be a ssociated with a negligible risk of developing clinically overt DTC. [ABSTRACT FROM AUTHOR]

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Morquio syndrome type A, also known as MPS IVA, is a rare autosomal recessive disorder caused by deficiency of N -acetylgalactosamine-6-sulfatase, a lysosomal hydrolase critical in the degradation of keratan sulfate (KS) and chondroitin sulfate (CS). The CS that accumulates in MPS IVA patients has a disease-specific nonreducing end (NRE) terminating with N -acetyl-D-galactosamine 6-sulfate, which can be specifically quantified after enzymatic depolymerization of CS polysaccharide chains. The abundance of N -acetyl-D-galactosamine 6-sulfate over other possible NRE structures is diagnostic for MPS IVA. Here, we describe an assay for the liberation and measurement of N -acetyl-D-galactosamine 6-sulfate and explore its application to MPS IVA patient samples in pilot studies examining disease detection, effects of age and treatment with enzyme-replacement therapy. This assay complements the existing urinary KS assay by quantifying CS-derived substrates, which represent a distinct biochemical aspect of MPS IVA. A more complete understanding of the disease could help to more definitively detect disease across age ranges and more completely measure the pharmacodynamic efficacy of therapies. Larger studies will be needed to clarify the potential value of this CS-derived substrate to manage disease in MPS IVA patients. [ABSTRACT FROM AUTHOR]

Background Doppler ultrasound (DU) monitoring early after arteriovenous fistula (AVF) creation allows the identification of low blood flow (Qa) requiring prompt revision, but it is costly (needs skilled operators and technical instruments) and is not available in all dialysis units. Therefore alternative first-line methods to measure Qa would be welcomed. We reasoned that once an AVF is created, an increment in central venous oxygen saturation (ScvO2) is predictable and proportional to Qa. Methods Accordingly, in patients receiving dialysis through a central venous catheter (CVC) in whom an AVF was created, we measured, by means of blood gas analysis, the ScvO2 increment before and after manual compression of the arteriovenous shunt and verified its correlation with DU-measured Qa. Results We sampled blood gas in 18 patients with CVC and AVF before and after 30 s manual compression of the AVF. ScvO2 averaged 70.5 ± 3% before and 65.2 ± 3% after AVF closure, with an average drop of 5.1 ± 3% (range 1–12). AVF Qa, which was measured within 24 h by means of DU, averaged 635 ± 349 mL/min (range 50–1300) and was strictly and positively correlated with ΔScvO2 (r = 0.954, P < 0.0001). Conclusions Therefore we suggest that in patients with CVC and a newly created AVF, it is possible to monitor AVF Qa without DU by simply measuring blood gas and ΔScvO2. This technique is simple, cheap, repeatable, non-invasive and operator independent and represents a new useful screening test to detect delayed AVF access maturation deserving prompt DU measurement and surgical revision. It helps to quickly identify patients in urgent need of DU verification and possible surgical revision. Regrettably, it is applicable only in patients with CVC. [ABSTRACT FROM AUTHOR]

We present modelling of the geophysical data from the Newcastle area, west of Dublin, Ireland within the framework of the IRETHERM project. IRETHERM's overarching objective was to facilitate a more thorough strategic understanding of Ireland's geothermal energy potential through integrated modelling of new and existing geophysical, geochemical and geological data. The Newcastle area, one of the target localities, is situated at the southern margin of the Dublin Basin, close to the largest conurbation on the island of Ireland in the City of Dublin and surrounds. As part of IRETHERM, magnetotelluric (MT) soundings were carried out in the highly urbanized Dublin suburb in 2011 and 2012, and a description of MT data acquisition, processing methods, multidimensional geoelectrical models and porosity modelling with other geophysical data are presented. The MT time-series were heavily noise-contaminated and distorted due to electromagnetic noise from nearby industry and Dublin City tram/railway systems. Time-series processing was performed using several modern robust codes to obtain reasonably reliable and interpretable MT impedance and geomagnetic transfer function 'tipper' estimates at most of the survey locations. The most 'quiet' 3-hr subsets of data during the night time, when the DC 'LUAS' tram system was not operating, were used in multisite and multivariate processing. The final 2-D models underwent examination using a stability technique, and the final two 2-D profiles, with reliability estimations expressed through conductance and resistivity, were derived. In the final stage of this study, 3-D modelling of all MT data in the Newcastle area was also undertaken. Comparison of the MT models and their interpretation with existing seismic profiles in the area reveals that the Blackrock–Newcastle Fault (BNF) zone is visible in the models as a conductive feature down to depths of 4 km. The investigated area below Newcastle can be divided into two domains of different depths, formed as depth zones. The first zone, from the surface down to 1–2 km, is dominated by NE–SW oriented conductors connected with shallow faults or folds probably filled with less saline waters. The conductors are also crossing the surface trace of the BNF. The second depth domain can be identified from depths of 2–4 km, where structures are oriented along the BNF and the observed conductivity is lower. The deeper conductive layers are interpreted as geothermal-fluid-bearing rocks. Porosity and permeability estimations from the lithological borehole logs indicate the geothermal potential of the bedrock, to deliver warm water to the surface. The fluid permeability estimation, based on Archie's law for porous structures and synthetic studies of fractured zones, suggests a permeability in the range 100 mD–100 D in the study area, which is prospective for geothermal energy exploitation. [ABSTRACT FROM AUTHOR]

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest. [ABSTRACT FROM AUTHOR]

Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made. [ABSTRACT FROM AUTHOR]

Presents a general model of organizational problem-solving. Relationships between problem complexity, decentralization of tasks and problem-solving efficiency; Requirements of organizational problem-solving; Possible trade-offs between decomposition patterns and search efficiency involved in different organizational architectures.

Motivation UMI-4C, a technique that combines chromosome conformation capture (4C) and unique molecular identifiers (UMI), is widely used to profile and quantitatively compare targeted chromosomal contact profiles. The analysis of UMI-4C experiments presents several computational challenges, including the removal of the PCR duplication bias and the identification of differential chromatin contacts. Results We have developed UMI4Cats (UMI-4C Analysis Turned Simple), an R package that facilitates processing, analyzing and visualizing of data obtained by UMI-4C experiments. Availability and implementation UMI4Cats is implemented as an R package supported on Linux, MacOS and MS Windows. UMI4Cats is available from Bioconductor (https://www.bioconductor.org/packages/release/bioc/html/UMI4Cats.html) and GitHub (https://github.com/Pasquali-lab/UMI4Cats). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Using new long-slit spectroscopy obtained with X-Shooter at ESO-VLT, we study, for the first time, radial gradients of optical and near-infrared initial mass function (IMF)-sensitive features in a representative sample of galaxies at the very high mass end of the galaxy population. The sample consists of seven early-type galaxies (ETGs) at z ∼ 0.05, with central velocity dispersion in the range 300 ≲ σ ≲ 350 km s−1. Using state-of-the-art stellar population synthesis models, we fit a number of spectral indices, from different chemical species (including TiO and Na indices), to constrain the IMF slope (i.e. the fraction of low-mass stars), as a function of galactocentric distance, over a radial range out to ∼4 kpc. ETGs in our sample show a significant correlation of IMF slope and surface mass density. The bottom-heavy population (i.e. an excess of low-mass stars in the IMF) is confined to central galaxy regions with surface mass density above |$\rm \sim 10^{10}\, M_\odot \, kpc^{-2}$|⁠ , or, alternatively, within a characteristic radius of ∼2 kpc. Radial distance, in physical units, and surface mass density are the best correlators to IMF variations, with respect to other dynamical (e.g. velocity dispersion) and stellar population (e.g. metallicity) properties. Our results for the most massive galaxies suggest that there is no single parameter that fully explains variations in the stellar IMF, but IMF radial profiles at z ∼ 0 rather result from the complex formation and mass accretion history of galaxy inner and outer regions. [ABSTRACT FROM AUTHOR]

We constrain the stellar population properties of a sample of 52 massive galaxies – with stellar mass log (M s/M⊙) ≳ 10.5 – over the redshift range 0.5 < z < 2 by use of observer-frame optical and near-infrared slitless spectra from Hubble Space Telescope 's ACS and WFC3 grisms. The deep exposures (∼100 ks) allow us to target individual spectra of massive galaxies to F160W = 22.5 AB. Our spectral fitting approach uses a set of six base models adapted to the redshift and spectral resolution of each observation, and fits the weights of the base models, including potential dust attenuation, via a Markov Chain Monte Carlo method. Our sample comprises a mixed distribution of quiescent (19) and star-forming galaxies (33). We quantify the width of the age distribution (Δ t) that is found to dominate the variance of the retrieved parameters according to principal component analysis. The population parameters follow the expected trend towards older ages with increasing mass, and Δ t appears to weakly anticorrelate with stellar mass, suggesting a more efficient star formation at the massive end. As expected, the redshift dependence of the relative stellar age (measured in units of the age of the Universe at the source) in the quiescent sample rejects the hypothesis of a single burst (aka monolithic collapse). Radial colour gradients within each galaxy are also explored, finding a wider scatter in the star-forming subsample, but no conclusive trend with respect to the population parameters. [ABSTRACT FROM AUTHOR]

Thyroid hormones (FT3, FT4) and thyroid-stimulating hormone (TSH) were evaluated in a population of 672 well-characterized Italian subjects (age range: 52-113 years), including an unprecedented number of centenarians, semi-supercentenarians, as well as centenarian's offspring and age-matched elderly (CENT, 105+, CENTOFF, and CTRL, respectively). The results show that FT3 level and FT3/FT4 ratio decrease while FT4 and TSH increase in an age-dependent manner. In CENT/105+, higher FT4 level, and lower FT3/FT4 ratio are associated with an impaired functional status and an increased mortality. A cluster analysis identified three clusters of CENT/105+ based on their FT3, FT4, and TSH levels. Cluster 3, characterized by lower FT3 and TSH and higher FT4, shows the worst health status and the shortest survival. Thus, the age-related changes of thyroid hormones extend to the most advanced age, and CENT/105+ are highly heterogeneous regarding thyroid function. This heterogeneity is related to different health, functional and cognitive status, as well as with survival/mortality in CENT/105+. Finally, we investigated a remarkable number of CENT/105+ showing a thyroid profile suggestive of non-thyroidal illness syndrome (NTIS) (excluded from the previous analysis). NTIS CENT/105+ are characterized by a worse functional and cognitive status and an increased mortality with respect to CENT/105+ without NTIS. [ABSTRACT FROM AUTHOR]

The advent of new 'omics' techniques determined a massive boost in the measurement of the whole spectra of molecules within cells, favoring promising new radiobiological studies at low doses. The main aim of this work was to assess the radiation-induced perturbations of miRNA profiles and their temporal dynamics. Human Umbilical Vein Endothelial Cells were irradiated with low doses of γ-rays. At different time points post-irradiation, cells were harvested and miRNAs isolated. A full mapping of the miRNA sequences via Next-Generation-Sequencing analysis was performed followed by bioinformatic analyses. Pathway enrichment analyses on the differentially expressed miRNAs focused both on the averaged effects of different doses over the 24-h experiment and on the altered temporal dynamics of the miRNA profiles. These complementary analyses provided a picture of the dose- and time-dependent miRNAs responses, allowing to better explore the candidate biomarkers linked to radiation exposures and their corresponding pathways and functions. [ABSTRACT FROM AUTHOR]

We investigate how environment affects satellite galaxies using their location within the projected phase space of their host haloes from the Wang et al.'s group catalogue. Using the Yonsei Zoom-in Cluster Simulations, we derive zones of constant mean infall time |$\overline{T}_{\rm inf}$| in projected phase space, and catalogue in which zone each observed galaxy falls. Within each zone, we compute the mean observed galaxy properties including specific star formation rate, luminosity-weighted age, stellar metallicity, and [α/Fe] abundance ratio. By comparing galaxies in different zones, we inspect how shifting the mean infall time from recent infallers (⁠|$\overline{T}_{\rm inf}~\lt$|  3 Gyr) to ancient infallers (⁠|$\overline{T}_{\rm {inf}}\gt$|  5 Gyr) impacts galaxy properties at fixed stellar and halo mass. Ancient infallers are more quenched, and the impact of environmental quenching is visible down to low host masses (≤group masses). Meanwhile, the quenching of recent infallers is weakly dependent on host mass, indicating they have yet to respond strongly to their current environment. [α/Fe] and especially metallicity are less dependent on host mass, but show a dependence on |$\overline{T}_{\rm {inf}}$|⁠. We discuss these results in the context of longer exposure times for ancient infallers to environmental effects, which grow more efficient in hosts with a deeper potential well and a denser intracluster medium. We also compare our satellites with a control field sample, and find that even the most recent infallers (⁠|$\overline{T}_{\rm {inf}}~\lt ~2$| Gyr) are more quenched than field galaxies, in particular for cluster mass hosts. This supports the role of pre-processing and/or faster quenching in satellites. [ABSTRACT FROM AUTHOR]

We tested the implementation of different initial mass functions (IMFs) in our model for the chemical evolution of ellipticals, with the aim of reproducing the observed relations of [Fe/H] and [Mg/Fe] abundances with galaxy mass in a sample of early-type galaxies selected from the SPIDER-SDSS catalogue. Abundances in the catalogue were derived from averaged spectra, obtained by stacking individual spectra according to central velocity dispersion, as a proxy of galaxy mass. We tested IMFs already used in a previous work, as well as two new models, based on low-mass tapered ('bimodal') IMFs, where the IMF becomes either (1) bottom-heavy in more massive galaxies, or (2) is time-dependent, switching from top-heavy to bottom-heavy in the course of galactic evolution. We found that observations could only be reproduced by models assuming either a constant, Salpeter IMF, or a time-dependent distribution, as other IMFs failed. We further tested the models by calculating their M/L ratios. We conclude that a constant, time-independent bottom-heavy IMF does not reproduce the data, especially the increase of the [α/Fe] ratio with galactic stellar mass, whereas a variable IMF, switching from top to bottom-heavy, can match observations. For the latter models, the IMF switch always occurs at the earliest possible considered time, i.e. t switch = 0.1 Gyr. [ABSTRACT FROM AUTHOR]

Polyphagous phytophagous organisms that shelter in man-made objects have a higher chance of becoming invasive fast-spreading pests, going undetected during phytosanitary checks and travelling with any type of goods. However, if the same organisms are also a household nuisance, they could be used in crowdsourcing surveys aimed at their early detection and to track their spread in real time. By participating in these surveys, people can be educated on the destructive potential of invasive species and on sustainable management options. However, in order to obtain good-quality data, useful to plant protection stakeholders, a one-to-one approach with people is crucial. The case study is the Italian invasion of Halyomorpha halys, among the most dangerous global crop-threatening pests. A 4-year survey that combined active search and a crowdsourcing approach made the tracking of its spread and investigation of its spatiotemporal dynamics possible, showing the functionality of coordinated multiactor approach in data collection. [ABSTRACT FROM AUTHOR]

Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase). Further, in recent years the close link between bone and inflammation has been better appreciated and a wide range of chronic inflammatory states (from rheumatoid arthritis to ageing) are being explored to discover the biochemical changes that ultimately lead to bone loss and OP. Also, it has been acknowledged that the concept of the bone–vascular axis may explain, for example, the relationship between bone metabolism and vessel wall diseases like atherosclerosis and arteriosclerosis, with potential involvement of a number of cytokines and metabolic pathways. A very important discovery in bone physiology is the bone marrow (BM) niche, the functional unit where stem cells interact, exchanging signals that impact on their fate as bone-forming cells or immune-competent haematopoietic elements. This new element of bone physiology has been recognized to be dysfunctional in diabetes (so-called diabetic mobilopathy), with possible clinical implications. In our opinion, ROD, the metabolic bone disease of renal patients, will in the future probably be identified as a cause of BM niche dysfunction. An integrated view of bone, which includes the BM niche, now seems necessary in order to understand the complex clinical entity of chronic kidney disease–mineral and bone disorders and its cardiovascular burden. Bone is thus becoming a recurrently considered paradigm for different inter-organ communications that needs to be considered in patients with complex diseases. [ABSTRACT FROM AUTHOR]

Within the variety of objects populating stellar clusters, blue straggler stars (BSSs) are among the most puzzling ones. BSSs are commonly found in globular clusters, but they are also known to populate open clusters of the Milky Way. Two main theoretical scenarios (collisions and mass transfer) have been suggested to explain their formation, although finding observational evidence in support of either scenario represents a challenging task. Among the APOGEE observations of the old open cluster M67, we found eight BSS candidates known from the literature and two known evolved BSSs. We carried out a chemical analysis of three BSS candidates and of the two evolved BSSs out of the sample and found that the BSS candidates have surface abundances similar to those of stars on the main-sequence turn-off of M67. Especially the absence of any anomaly in their carbon abundances seems to support a collisional formation scenario for these stars. Furthermore, we note that the abundances of the evolved BSSs S1040 and S1237 are consistent with the abundances of the red clump stars of M67. In particular, they show a depletion in carbon by ∼0.25 dex, which could be either interpreted as the signature of mass transfer or as the product of stellar evolutionary processes. Finally, we summarize the properties of the individual BSSs observed by APOGEE, as derived from their APOGEE spectra and/or from information available in the literature. [ABSTRACT FROM AUTHOR]

In this paper, we present a new derivation of the shape and evolution of the integrated galaxy-wide initial mass function (IGIMF), incorporating explicitly the effects of cosmic rays (CRs) as regulators of the chemical and thermal state of the gas in the dense cores of molecular clouds. We predict the shape of the IGIMF as a function of star formation rate and CR density and show that it can be significantly different with respect to local estimates. In particular, we focus on the physical conditions corresponding to IGIMF shapes that are simultaneously shallower at high-mass end and steeper at the low-mass end than those of a Kroupa IMF. These solutions can explain both the levels of α-enrichment and the excess of low-mass stars as a function of stellar mass, observed for local spheroidal galaxies. As a preliminary test of our scenario, we use idealized star formation histories to estimate the mean IMF shape for galaxies of different $$z$$  = 0 stellar mass. We show that the fraction of low-mass stars as a function of galaxy stellar mass predicted by these mean IMFs agrees with the values derived from high-resolution spectroscopic surveys. [ABSTRACT FROM AUTHOR]

Background: Classic galactosemia is an inherited disorder of galactose metabolism caused by the impaired activity of galactose-1-phosphate uridyltransferase (GALT). Untreated galactosemia is life-threatening; however, early dietary intervention prevents mortality and reduces morbidity associated with this disease. The diagnosis of galactosemia includes the measurement of GALT activity in red blood cells (RBC) and GALT gene analysis. In this study, we evaluate GALT activity in different genotypes using the results of combined biochemical and molecular testing in 927 samples. Methods: GALT activity in RBC was measured by LC-MS/MS. The analysis of the GALT gene was performed by targeted gene analysis and/or full gene sequencing. Samples were assigned based on the presence of pathogenic (G) or Duarte 2 (D) variants, or their absence (Neg), to G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes. Finite mixture models were applied to investigate distributions of GALT activities in these genotypes. The reference ranges were determined using the central 95% of values of GALT activities. Results: The ranges of GALT activity in G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes are 0.0 to 0.7 μmol·h-1 gHb-1, 3.1 to 7.8 μmol·h-1 gHb-1, 6.5 to 16.2 μmol·h-1 gHb-1, 6.4 to 16.5 μmol·h-1 gHb-1, 12.0 to 24.0 μmol·h-1 gHb-1, and 19.4 to 33.4 μmol·h-1 gHb-1, respectively. Conclusions: The GALT activity ranges established in this study are in agreement with the expected impact of the genotype on the enzymatic activity. Molecular findings should be interpreted in view of biochemical results to confirm genotype--phenotype correlation. [ABSTRACT FROM AUTHOR]

One of the main theories for explaining the formation of spiral arms in galaxies is the stationary density wave theory. This theory predicts the existence of an age gradient across the arms. We use the stellar cluster catalogues of the galaxies NGC 1566, M51a, and NGC 628 from the Legacy ExtraGalactic UV Survey (LEGUS) program. In order to test for the possible existence of an age sequence across the spiral arms, we quantified the azimuthal offset between star clusters of different ages in our target galaxies. We found that NGC 1566, a grand-design spiral galaxy with bisymmetric arms and a strong bar, shows a significant age gradient across the spiral arms that appear to be consistent with the prediction of the stationary density wave theory. In contrast, M51a with its two well-defined spiral arms and a weaker bar does not show an age gradient across the arms. In addition, a comparison with non-LEGUS star cluster catalogues for M51a yields similar results. We believe that the spiral structure of M51a is not the result of a stationary density wave with a fixed pattern speed. Instead, tidal interactions could be the dominant mechanism for the formation of spiral arms. We also found no offset in the azimuthal distribution of star clusters with different ages across the weak spiral arms of NGC 628. [ABSTRACT FROM AUTHOR]

Investigating the chemical homogeneity of stars born from the same molecular cloud at virtually the same time is very important for our understanding of the chemical enrichment of the interstellar medium and with it the chemical evolution of the Galaxy. One major cause of inhomogeneities in the abundances of open clusters is stellar evolution of the cluster members. In this work, we investigate variations in the surface chemical composition of member stars of the old open cluster M67 as a possible consequence of atomic diffusion effects taking place during the main-sequence phase. The abundances used are obtained from high-resolution UVES/FLAMES spectra within the framework of the Gaia-ESO Survey. We find that the surface abundances of stars on the main sequence decrease with increasing mass reaching a minimum at the turn-off. After deepening of the convective envelope in subgiant branch stars, the initial surface abundances are restored. We found the measured abundances to be consistent with the predictions of stellar evolutionary models for a cluster with the age and metallicity of M67. Our findings indicate that atomic diffusion poses a non-negligible constraint on the achievable precision of chemical tagging methods. [ABSTRACT FROM AUTHOR]

In this paper, we investigate whether the stellar initial mass function (IMF) of early-type galaxies depends on their host environment. To this purpose, we have selected a sample of early-type galaxies from the SPIDER catalogue, characterized their environment through the group catalogue of Wang et al., and used their optical Sloan Digital Sky Survey (SDSS) spectra to constrain the IMF slope, through the analysis of IMF-sensitive spectral indices. To reach a high enough signal-to-noise ratio, we have stacked spectra in velocity dispersion (σ0) bins, on top of separating the sample by galaxy hierarchy and host halo mass, as proxies for galaxy environment. In order to constrain the IMF, we have compared observed line strengths and predictions of MIUSCAT/EMILES synthetic stellar population models, with varying age, metallicity, and 'bimodal' (low-mass tapered) IMF slope (Γb). Consistent with previous studies, we find that Γb increases with σ0, becoming bottom-heavy (i.e. an excess of low-mass stars with respect to the Milky Way like IMF) at high σ0. We find that this result is robust against the set of isochrones used in the stellar populationmodels, as well as the way the effect of elemental abundance ratios is taken into account.We thus conclude that it is possible to use currently state-of-the-art stellar population models and intermediate resolution spectra to consistently probe IMF variations. For the first time, we show that there is no dependence of Γb on environment or galaxy hierarchy, as measured within the 3 arcsec SDSS fibre, thus leaving the IMF as an intrinsic galaxy property, possibly set already at high redshift. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants--rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes. [ABSTRACT FROM AUTHOR]

Galactinol synthase (GolS) is a key enzyme in the biosynthetic pathway of raffinose family oligosaccharides (RFOs), which play roles in carbon storage, signal transduction, and osmoprotection. The present work assessed the evolutionary history of GolS genes across the Rosaceae using several bioinformatic tools. Apple (Malus × domestica) GolS genes were transcriptionally characterized during bud dormancy, in parallel with galactinol and raffinose measurements. Additionally, MdGolS2, a candidate to regulate seasonal galactinol and RFO content during apple bud dormancy, was functionally characterized in Arabidopsis. Evolutionary analyses revealed that whole genome duplications have driven GolS gene evolution and diversification in Rosaceae speciation. The strong purifying selection identified in duplicated GolS genes suggests that differential gene expression might define gene function better than protein structure. Interestingly, MdGolS2 was differentially expressed during bud dormancy, concomitantly with the highest galactinol and raffinose levels. One of the intrinsic adaptive features of bud dormancy is limited availability of free water; therefore, we generated transgenic Arabidopsis plants expressing MdGolS2. They showed higher galactinol and raffinose contents and increased tolerance to water deficit. Our results suggest that MdGolS2 is the major GolS responsible for RFO accumulation during apple dormancy, and these carbohydrates help to protect dormant buds against limited water supply. [ABSTRACT FROM AUTHOR]

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic-pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity. [ABSTRACT FROM AUTHOR]

Background: Specific factors underlying successful surgical sperm retrieval rates (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in adult patients with Klinefelter syndrome (KS) have not been completely clarified.Objective and Rationale: The aim of this review was to meta-analyse the currently available data from subjects with KS regarding SRRs as the primary outcome. In addition, when available, PRs and live birth rates (LBRs) after the ICSI technique were also investigated as secondary outcomes.Search Methods: An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR for conventional-TESE (cTESE) or micro-TESE (mTESE) and its specific determinants without any arbitrary restriction were included.Outcomes: Out of 139 studies, 37 trials were included in the study, enrolling a total of 1248 patients with a mean age of 30.9 ± 5.6 years. The majority of the studies (n = 18) applied mTESE, 13 applied cTESE and in one case testicular sperm aspiration (TESA) was used. Additionally, four studies used a mixed approach and in one study, the method applied for sperm retrieval was not specified. Overall, a SRR per TESE cycle of 44[39;48]% was detected. Similar results were observed when mTESE was compared to cTESE (SRR 43[35;50]% vs 45[38;52]% for cTESE vs micro-TESE, respectively; Q = 0.20, P = 0.65). Meta-regression analysis showed that none of the parameters tested, including age, testis volume and FSH, LH and testosterone (T) levels at enrollment, affected the final SRR. Similarly, no difference was observed when a bilateral procedure was compared to a unilateral approach. No sufficient data were available to evaluate the effect of previous T treatment on SRR. Information on fertility outcome after ICSI was available for 29 studies. Overall a total of 218 biochemical pregnancies after 410 ICSI cycles were observed (PR = 43[36;50]%). Similar results were observed when LBR was analyzed (LBR = 43[34;53]%). Similar to what was observed for SRR, no influence of KS age, mean testis volume, LH, FSH or total T levels on either PR and LBR was observed. No sufficient data were available to test the effect of the women's age or other female fertility problems on PR and LBR. Finally, no difference in PR or LBR was observed when the use of fresh sperm was compared to the utilization of cryopreserved sperm.Wider Implications: The present data suggest that performing TESE/micro-TESE in subjects with KS results in SRRs of close to 50%, and then PRs and LBRs of close to 50%, with the results being independent of any clinical or biochemical parameters tested. [ABSTRACT FROM AUTHOR]