ABSTRACT
We present new Hubble Space Telescope Wide-Field Camera 3/infrared medium-band photometry of the compact elliptical galaxy M32, chemically resolving its thermally pulsating asymptotic giant ...branch stars. We find 2829 M-type stars and 57 C stars. The carbon stars are likely contaminants from M31. If carbon stars are present in M32 they are so in very low numbers. The uncorrected C/M ratio is 0.020 ± 0.003; this drops to less than 0.007 after taking into account contamination from M31. As the mean metallicity of M32 is just below solar, this low ratio of C to M stars is unlikely due to a metallicity ceiling for the formation of carbon stars. Instead, the age of the asymptotic giant branch (AGB) population is likely to be the primary factor. The ratio of AGB to red giant branch stars in M32 is similar to that of the inner disc of M31 which contain stars that formed 1.5–4 Gyr ago. If the M32 population is at the older end of this age then its lack of C-stars may be consistent with a narrow mass range for carbon star formation predicted by some stellar evolution models. Applying our chemical classifications to the dusty variable stars identified with Spitzer, we find that the x-AGB candidates identified with Spitzer are predominately M-type stars. This substantially increases the lower limit to the cumulative dust-production rate in M32 to > 1.20 × 10−5${\rm M}_{\odot } \, {\rm yr}^{-1}$.
► Cancer cachexia is a syndrome whose result in marked reduction of total fat mass. ► In such state inflammatory mediators may unbalance adipose tissue homeostases. ► Gene products are crucial for ...lipid storage in adipose tissue during cancer cachexia. ► Interaction between NF-κB and PPARγ seems to be disrupted during cancer cachexia.
Cancer cachexia is a multifaceted syndrome whose aetiology is extremely complex and is directly related to poor patient prognosis and survival. Changes in lipid metabolism in cancer cachexia result in marked reduction of total fat mass, increased lipolysis, total oxidation of fatty acids, hyperlipidaemia, hypertriglyceridaemia, and hypercholesterolaemia. These changes are believed to be induced by inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and other factors.
Attention has recently been drawn to the current theory that cachexia is a chronic inflammatory state, mainly caused by the host’s reaction to the tumour. Changes in expression of numerous inflammatory mediators, notably in white adipose tissue (WAT), may trigger several changes in WAT homeostasis. The inhibition of adipocyte differentiation by PPARγ is paralleled by the appearance of smaller adipocytes, which may partially account for the inhibitory effect of PPARγ on inflammatory gene expression. Furthermore, inflammatory modulation and/or inhibition seems to be dependent on the IKK/NF-κB pathway, suggesting that a possible interaction between NF-κB and PPARγ is required to modulate WAT inflammation induced by cancer cachexia.
In this article, current literature on the possible mechanisms of NF-κB and PPARγ regulation of WAT cells during cancer cachexia are discussed. This review aims to assess the role of a possible interaction between NF-κB and PPARγ in the setting of cancer cachexia as well as its significant role as a potential modulator of chronic inflammation that could be explored therapeutically.
ABSTRACT The Infrared Spectrograph on the Spitzer Space Telescope observed 184 carbon stars in the Magellanic Clouds. This sample reveals that the dust-production rate (DPR) from carbon stars ...generally increases with the pulsation period of the star. The composition of the dust grains follows two condensation sequences, with more SiC condensing before amorphous carbon in metal-rich stars, and the order reversed in metal-poor stars. MgS dust condenses in optically thicker dust shells, and its condensation is delayed in more metal-poor stars. Metal-poor carbon stars also tend to have stronger absorption from C2H2 at 7.5 m. The relation between DPR and pulsation period shows significant apparent scatter, which results from the initial mass of the star, with more massive stars occupying a sequence parallel to lower-mass stars, but shifted to longer periods. Accounting for differences in the mass distribution between the carbon stars observed in the Small and Large Magellanic Clouds reveals a hint of a subtle decrease in the DPR at lower metallicities, but it is not statistically significant. The most deeply embedded carbon stars have lower variability amplitudes and show SiC in absorption. In some cases they have bluer colors at shorter wavelengths, suggesting that the central star is becoming visible. These deeply embedded stars may be evolving off of the asymptotic giant branch and/or they may have non-spherical dust geometries.
To contain the COVID-19 pandemic, India imposed a national lockdown at the end of March 2020, a decision that resulted in a massive reverse migration as many workers across economic sectors returned ...to their home regions. Migrants provide the foundations of the agricultural workforce in the ‘breadbasket’ states of Punjab and Haryana in Northwest India.There are mounting concerns that near and potentially longer-term reductions in labor availability may jeopardize agricultural production and consequently national food security. The timing of rice transplanting at the beginning of the summer monsoon season has a cascading influence on productivity of the entire rice-wheat cropping system. To assess the potential for COVID-related reductions in the agriculture workforce to disrupt production of the dominant rice-wheat cropping pattern in these states, we use a spatial ex ante modelling framework to evaluate four scenarios representing a range of plausible labor constraints on the timing of rice transplanting. Averaged over both states, results suggest that rice productivity losses under all delay scenarios would be low as compare to those for wheat, with total system productivity loss estimates ranging from 9%, to 21%, equivalent to economic losses of USD $674 m to $1.48 billion. Late rice transplanting and harvesting can also aggravate winter air pollution with concomitant health risks. Technological options such as direct seeded rice, staggered nursery transplanting, and crop diversification away from rice can help address these challenges but require new approaches to policy and incentives for change.
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•An ex-ante analysis was done using geospatial tools on potential effect of labour shortage on rice-wheat system.•Food grain production loss due to labor shortage can be 23% from current levels of production.•Residue burning will exacerbate air pollution in winter and could coincide with an anticipated COVID resurgence in the fall.•India needs new strategies to use available technological and management innovations to address emerging constraints.
Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been ...proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked genetic markers. To assess stratification empirically, we analyzed data from 11 case-control and case-cohort association studies. We did not detect statistically significant evidence for stratification but did observe that assessments based on a few dozen markers lack power to rule out moderate levels of stratification that could cause false positive associations in studies designed to detect modest genetic risk factors. After increasing the number of markers and samples in a case-cohort study (the design most immune to stratification), we found that stratification was in fact present. Our results suggest that modest amounts of stratification can exist even in well designed studies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
This systematic review update summarizes the current evidence on the use of natalizumab for induction of remission in Crohn's disease (CD).
Objectives
To determine the efficacy and safety ...of natalizumab for induction of remission in CD.
Search methods
We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Trials Register, and clinicaltrials.gov from inception to 10 May 2018.
Selection criteria
We included randomized controlled trials (RCTs) comparing natalizumab to a placebo or control therapy for induction of remission in CD.
Data collection and analysis
Two authors independently screened studies, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was failure to enter clinical remission. Secondary outcomes included clinical response, mean change in Crohn's Disease Activity Index (CDAI), adverse events (AEs), withdrawal due to AEs and serious AEs. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Data were pooled for meta‐analysis when the interventions, patient groups and outcomes were sufficiently similar (determined by consensus). We used GRADE to assess the overall quality of the evidence.
Main results
A total of five RCTs (1771 participants) were included. Four studies (1692 participants) compared one, two or three infusions of natalizumab (300 mg or 3 mg/kg or 6mg/kg) to placebo. One study (79 participants) compared three infusions of natalizumab (300 mg) and infliximab (5 mg/kg) to infliximab and placebo. Four studies were rated as low risk of bias. One study was rated as unclear risk of bias for selective reporting.
One, two and three infusions of natalizumab were superior to placebo for induction of remission and clinical response. Infusions were administered at weeks zero, four and eight. After one infusion, 76% (849/1117) of natalizumab participants failed to enter remission at 4 weeks compared to 83% (411/494) of placebo participants (RR 0.91, 95% CI 0.86 to 0.96, 3 studies, GRADE high quality). At 4 weeks, the RR for clinical response was 0.78 (95% CI 0.66 to 0.92, 3 studies, 1611 participants, GRADE moderate quality). After two infusions, after 8 weeks, 66% (693/1049) of natalizumab participants failed to enter remission compared to 77% (382/494) of placebo participants (RR 0.85, 95% CI 0.76 to 0.95; 3 studies, GRADE moderate quality). At 8 weeks, the RR for clinical response was 0.73 (95% CI 0.58 to 0.91, 3 studies, 1543 participants, GRADE low quality). After three infusions, at 12 weeks, 61% (596/983) of natalizumab participants failed to enter remission compared to 73% (313/431) of placebo participants (RR 0.85, 95% CI 0.78 to 0.92, 2 studies, GRADE high quality). At 12 weeks, the RR for clinical response was 0.76 (95% CI 0.67 to 0.86, 2 studies, 1414 participants, GRADE high quality). One study (507 participants) reported on change in CADI from baseline. Natalizumab participants had a larger drop in mean CDAI scores than placebo participants at 4, 8 and 12 weeks.
The rates of AEs, withdrawals due to AEs and serious AEs were similar across groups at 4, 8 and 12 weeks. After one infusion, 74% (50/68) of natalizumab participants experienced an AE compared to 81% (51/63) of placebo participants (RR 0.91, 95% CI 0.75 to 1.09, GRADE moderate quality). Withdrawal due to an AE occurred in 1% (1/68) of natalizumab participants and 3% of placebo participants (RR 0.46, 95% CI 0.04 to 4.98, GRADE low quality). SAEs occurred in 10% (7/68) of natalizumab participants compared to 11% (7/63) of placebo participants (RR 0.93, 95% CI 0.34 to 2.49, GRADE low quality). After two infusions, 86% (57/66) of natalizumab participants experienced an AE compared to 81% (51/63) of placebo participants (RR 1.07, 95% CI 0.92 to 1.24, GRADE moderate quality). Withdrawal due to an AE occurred in 3% (2/66) natalizumab participants compared to 3% (2/63) placebo participants (RR 0.95, 95% CI 0.14 to 6.57, GRADE low quality). SAEs occurred in 9% (6/66) of natalizumab participants and 11% (7/63) of placebo participants (RR 0.82, 95% CI 0.29 to 2.30, GRADE low quality). After three infusions, 86% (848/984) of natalizumab participants experienced an AE compared to 83% (359/431) placebo participants (RR 1.03, 95% CI 0.98 to 1.08, GRADE high quality). Withdrawals due to AEs occurred in 8% (82/984) of natalizumab participants compared to 10% (45/431) of placebo participants (RR 0.86, 95% CI 0.59 to 1.26, GRADE moderate quality). SAEs occurred in 7% (65/983) of natalizumab participants and 8% (36/431) of placebo participants (RR 0.76. 95% CI 0.37 to 1.56, GRADE low quality). Adverse events included headache, nausea, nasopharyngitis, abdominal pain, fatigue, vomiting, and exacerbation of CD.
The study comparing combination therapy with natalizumab and infliximab to infliximab and placebo demonstrated similar remission rates at 10 weeks. Sixty‐four per cent (33/52) of participants assigned to natalizumab and infliximab failed to achieve remission compared to 70% (19/27) assigned to placebo and infliximab (RR 0.90, 95% CI 0.65 to 1.24, GRADE moderate quality). The rates of AEs (moderate quality evidence), withdrawals due to AEs (low quality evidence) and serious AEs (low quality evidence) were similar across groups at 10 weeks. Adverse events included headache, exacerbation of CD, nausea, and nasopharyngitis.
Natalizumab is associated with the development of progressive multifocal leukoencephalopathy (PML) resulting in some patient deaths. There are currently no tests which can reliably predict those at risk of developing PML.
Authors' conclusions
High quality data suggest that natalizumab is effective for induction of clinical remission and response in some patients with moderately to severely active CD. However, none of the included studies had the power to detect rare but serious adverse events such as PML. Due to the association with PML, and the availability of alternative agents that are not associated with PML, natalizumab is not likely to be used in patients who fail currently available medical therapy. The use of natalizumab in select patients (e.g. patients allergic to different biologics) needs to be carefully considered against the potential risk of developing PML. Futher studies of natalizumab are not likely to be done.
•Various nutrient management strategies were evaluated under NT and CT based wheat production.•SSNM based on Nutrient expert® increased yield and economic profitability than state recommended and ...farmers’ practice of nutrient management.•SSNM and NT system had lower GWP than CT system and farmer's fertilization practice, respectively.
In the high-yielding wheat production systems in Northwest (NW) Indo-Gangetic Plains of India, intensive tillage operations and blanket fertilizer recommendations have led to high production costs, decreased nutrient use efficiency, lower profits and significant environmental externalities. No-tillage (NT) has been increasingly adopted in this region to reduce costs and increase input use efficiency. But, optimal nutrient management practices for NT based wheat production are still poorly understood. Opportunities exist to further enhance the yield, profitability, and resource use efficiency of NT wheat through site-specific nutrient management (SSNM).
On-farm trials were conducted in seven districts of Haryana, India for two consecutive years (2010–11 and 2011–12) to evaluate three different approaches to SSNM based on recommendations from the Nutrient Expert® (NE) decision support system in NT and conventional tillage (CT) based wheat production systems. Performance of NE based recommendations was evaluated against current state recommendations and farmers’ practices for nutrient management. Three SSNM treatments based on NE based recommendation were (1) ‘NE80:20’ with 80% N applied at planting and 20% at second irrigation (2) ‘NE33:33:33’ with N split as 33% basal, 33% at Crown Root Initiation (CRI) and 33% at second irrigation; and (3) ‘NE80:GS’ with N split as 80% basal and further application of N based on optical sensor (Green Seeker™)-guided recommendations. Yield, nutrient use efficiency and economic profitability were determined following standard agronomic and economic measurements and calculations. Cool Farm Tool (CFT), an empirical model to estimate greenhouse gases (GHGs) from agriculture production, was used to estimate GHG emissions under different treatments.
Wheat grain and biomass yield were higher under NT in 2010–11 but no difference was observed in 2011–12. The three NE-based nutrient management strategies increased yield, nutrient use efficiency as well as net return as compared to state recommendation and farmers’ fertilization practice. Global warming potential (GWP) of wheat production was also lower with NT system as compared to CT system and NE-based nutrient managements as compared to farmers’ fertilization practice. State recommended nutrient management had similar GWP as NE-based nutrient managements except NE80:GS in which GWP was the lowest. Results suggest that no-tillage system along with site-specific approaches for nutrient management can increase yield, nutrient use efficiency and profitability while decreasing GHG from wheat production in NW India.
The Magellanic Clouds are uniquely placed to study the stellar contribution to dust emission. Individual stars can be resolved in these systems even in the mid-infrared, and they are close enough to ...allow detection of infrared excess caused by dust. We have searched the Spitzer Space Telescope data archive for all Infrared Spectrograph (IRS) staring-mode observations of the Small Magellanic Cloud (SMC) and found that 209 Infrared Array Camera (IRAC) point sources within the footprint of the Surveying the Agents of Galaxy Evolution in the Small Magellanic Cloud (SAGE-SMC) Spitzer Legacy programme were targeted, within a total of 311 staring-mode observations. We classify these point sources using a decision tree method of object classification, based on infrared spectral features, continuum and spectral energy distribution shape, bolometric luminosity, cluster membership and variability information. We find 58 asymptotic giant branch (AGB) stars, 51 young stellar objects, 4 post-AGB objects, 22 red supergiants, 27 stars (of which 23 are dusty OB stars), 24 planetary nebulae (PNe), 10 Wolf–Rayet stars, 3 H ii regions, 3 R Coronae Borealis stars, 1 Blue Supergiant and 6 other objects, including 2 foreground AGB stars. We use these classifications to evaluate the success of photometric classification methods reported in the literature.
We present optical spectroscopy of galaxies in clusters detected through the Sunyaev-Zel'dovich (SZ) effect with the South Pole Telescope (SPT). We report our own measurements of 61 spectroscopic ...cluster redshifts, and 48 velocity dispersions each calculated with more than 15 member galaxies. This catalog also includes 19 dispersions of SPT-observed clusters previously reported in the literature. The majority of the clusters in this paper are SPT-discovered; of these, most have been previously reported in other SPT cluster catalogs, and five are reported here as SPT discoveries for the first time. By performing a resampling analysis of galaxy velocities, we find that unbiased velocity dispersions can be obtained from a relatively small number of member galaxies (lap30), but with increased systematic scatter. We use this analysis to determine statistical confidence intervals that include the effect of membership selection.We fit scaling relations between the observed cluster velocity dispersions and mass estimates from SZ and X-ray observables. In both cases, the results are consistent with the scaling relation between velocity dispersion and mass expected from dark-matter simulations. We measure a ~30% log-normal scatter in dispersion at fixed mass, and a ~10% offset in the normalization of the dispersion-mass relation when compared to the expectation from simulations, which is within the expected level of systematic uncertainty.
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