The landforms of northern Gale crater on Mars expose thick sequences of sedimentary rocks. Based on images obtained by the Curiosity rover, we interpret these outcrops as evidence for past fluvial, ...deltaic, and lacustrine environments. Degradation of the crater wall and rim probably supplied these sediments, which advanced inward from the wall, infilling both the crater and an internal lake basin to a thickness of at least 75 meters. This intracrater lake system probably existed intermittently for thousands to millions of years, implying a relatively wet climate that supplied moisture to the crater rim and transported sediment via streams into the lake basin. The deposits in Gale crater were then exhumed, probably by wind-driven erosion, creating Aeolis Mons (Mount Sharp).
Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from ...matched inflamed and non-inflamed colonic mucosa 50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.
Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (ERG) has prognostic value in prostate cancer is unclear.
Among men with ...prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random-effects models to estimate associations between rearrangement status and outcomes.
The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.78-1.26 or lethal disease (HR, 0.93; 95% CI, 0.61-1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2:ERG was associated with stage at diagnosis risk ratio (RR)(≥T3 vs. T2), 1.23; 95% CI, 1.16-1.30) but not with biochemical recurrence (RR, 1.00; 95% CI, 0.86-1.17) or lethal disease (RR, 0.99; 95% CI, 0.47-2.09).
These results suggest that TMPRSS2:ERG, or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy.
This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy.
What allows a planet to be both within a potentially habitable zone and sustain habitability over long geologic time? With the advent of exoplanetary astronomy and the ongoing discovery of ...terrestrial-type planets around other stars, our own solar system becomes a key testing ground for ideas about what factors control planetary evolution. Mars provides the solar systems longest record of the interplay of the physical and chemical processes relevant to habitability on an accessible rocky planet with an atmosphere and hydrosphere. Here we review current understanding and update the timeline of key processes in early Mars history. We then draw on knowledge of exoplanets and the other solar system terrestrial planets to identify six broad questions of high importance to the development and sustaining of habitability (unprioritized): (1) Is small planetary size fatal? (2) How do magnetic fields influence atmospheric evolution? (3) To what extent does starting composition dictate subsequent evolution, including redox processes and the availability of water and organics? (4) Does early impact bombardment have a net deleterious or beneficial influence? (5) How do planetary climates respond to stellar evolution, e.g., sustaining early liquid water in spite of a faint young Sun? (6) How important are the timescales of climate forcing and their dynamical drivers? Finally, we suggest crucial types of Mars measurements (unprioritized) to address these questions: (1) in situ petrology at multiple units/sites; (2) continued quantification of volatile reservoirs and new isotopic measurements of H, C, N, O, S, Cl, and noble gases in rocks that sample multiple stratigraphic sections; (3) radiometric age dating of units in stratigraphic sections and from key volcanic and impact units; (4) higher-resolution measurements of heat flux, subsurface structure, and magnetic field anomalies coupled with absolute age dating. Understanding the evolution of early Mars will feed forward to understanding the factors driving the divergent evolutionary paths of the Earth, Venus, and thousands of small rocky extra solar planets yet to be discovered.
Background
Probiotic supplementation to mothers and/or their term‐born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics ...for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants.
Methods
This sub‐study was an a priori secondary outcome of the ProPrems multi‐center, double‐blind, placebo‐controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens.
Results
There was no difference in eczema incidence between the probiotic and placebo groups (3530% of 118 infants vs 3727% of 137 infants, respectively, absolute difference 2.65%, 95% CI −8.45 to 13.75). Similarly, the incidence of atopic eczema (65% of 118 vs 32% of 137), food allergy (43% of 124 vs 21% of 154), wheeze (3931% of 127 vs 4529% of 154), and atopic sensitization (1413% of 106 vs 1311% of 123) were similar between the probiotic and placebo groups.
Conclusion
This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed.
We evaluated the effect of postnatal probiotic supplementation on the development of allergic diseases and atopic sensitization in very preterm infants. We found no difference in the incidence of allergic diseases or atopic sensitization between the probiotic and placebo groups. Although current guidelines recommend probiotics for prevention of allergic diseases in high‐risk infants, our findings demonstrate that there is insufficient evidence to determine whether the guideline recommendations are applicable to very preterm infants.
ABSTRACT
We report the results of long-term reverberation mapping campaigns of the nearby active galactic nuclei (AGNs) NGC 4151, spanning from 1994 to 2022, based on archived observations of the ...FAST Spectrograph Publicly Archived Programs and our new observations with the 2.3 m telescope at the Wyoming Infrared Observatory. We reduce and calibrate all the spectra in a consistent way, and derive light curves of the broad H β line and 5100 Å continuum. Continuum light curves are also constructed using public archival photometric data to increase sampling cadences. We subtract the host galaxy contamination using Hubble Space Telescope imaging to correct fluxes of the calibrated light curves. Utilizing the long-term archival photometric data, we complete the absolute flux-calibration of the AGN continuum. We find that the H β time delays are correlated with the 5100 Å luminosities as $\tau _{\rm H\beta }\propto L_{5100}^{0.46\pm 0.16}$. This is remarkably consistent with Bentz et al. (2013)’s global size–luminosity relationship of AGNs. Moreover, the data sets for five of the seasons allow us to obtain the velocity-resolved delays of the H β line, showing diverse structures (outflows, inflows, and discs). Combining our results with previous independent measurements, we find the measured dynamics of the H β broad-line region (BLR) are possibly related to the long-term trend of the luminosity. There is also a possible additional ∼1.86 yr time lag between the variation in BLR radius and luminosity. These results suggest that dynamical changes in the BLR may be driven by the effects of radiation pressure.
Urbanisation is occurring globally, leading to dramatic environmental changes that are altering the ecology and evolution of species. In particular, the expansion of human infrastructure and the loss ...and fragmentation of natural habitats in cities is predicted to increase genetic drift and reduce gene flow by reducing the size and connectivity of populations. Alternatively, the 'urban facilitation model' suggests that some species will have greater gene flow into and within cities leading to higher diversity and lower differentiation in urban populations. These alternative hypotheses have not been contrasted across multiple cities. Here, we used the genomic data from the GLobal Urban Evolution project (GLUE), to study the effects of urbanisation on non-adaptive evolutionary processes of white clover (Trifolium repens) at a global scale. We found that white clover populations presented high genetic diversity and no evidence of reduced N
linked to urbanisation. On the contrary, we found that urban populations were less likely to experience a recent decrease in effective population size than rural ones. In addition, we found little genetic structure among populations both globally and between urban and rural populations, which showed extensive gene flow between habitats. Interestingly, white clover displayed overall higher gene flow within urban areas than within rural habitats. Our study provides the largest comprehensive test of the demographic effects of urbanisation. Our results contrast with the common perception that heavily altered and fragmented urban environments will reduce the effective population size and genetic diversity of populations and contribute to their isolation.
CONTEXT Elderly patients with major depression are at high
risk for recurrence, increased mortality, and chronic disability. OBJECTIVE To determine the efficacy of maintenance nortriptyline
...hydrochloride and interpersonal psychotherapy (IPT) in preventing
recurrence of major depressive episodes in patients older than 59 years. DESIGN A 2×2 randomized, double-blind,
placebo-controlled clinical trial, stratified by therapist. SETTING University-based psychiatric research clinic. PATIENTS Of a total of 187 patients with recurrent nonpsychotic
unipolar major depression (average age, 67 years; one third aged ≥70
years) recruited through clinical referral and media announcements, 107
were fully recovered after open acute and treatment continuation with
nortriptyline and IPT. These patients were randomly assigned to 1 of 4
maintenance therapy conditions. INTERVENTIONS Monthly medication clinic with nortriptyline
hydrochloride (80-120 ng/mL steady-state levels)
(n=24); medication clinic with placebo
(n=29); monthly maintenance IPT with placebo
(n=21); and monthly maintenance IPT with nortriptyline
(n=22). MAIN OUTCOME MEASURE Recurrence of major depressive episode. RESULTS The time to recurrence of a major depressive episode for
all 3 active treatments was significantly better than for placebo.
Recurrence rates over 3 years were as follows: nortriptyline and IPT,
20% (95% confidence interval CI, 4%-36%); nortriptyline and
medication clinic visits, 43% (95% CI, 25%-61%); IPT and placebo,
64% (95% CI, 45%-83%); and placebo and medication clinic visits,
90% (95% CI, 79%-100%). Combined treatment with nortriptyline and
IPT was superior to IPT and placebo and showed a trend to superior
efficacy over nortriptyline monotherapy (Wald
χ2=3.56; P=.06).
Subjects aged 70 years and older had a higher and more rapid rate of
recurrence than those aged 60 to 69 years. CONCLUSION In geriatric patients with recurrent major depression,
maintenance treatment with nortriptyline or IPT is superior to placebo
in preventing or delaying recurrence. Combined treatment using both
appears to be the optimal clinical strategy in preserving
recovery.
Current European Commission (EC) surveillance regulations require discriminatory testing of all transmissible spongiform encephalopathy (TSE)-positive small ruminant (SR) samples in order to classify ...them as bovine spongiform encephalopathy (BSE) or non-BSE. This requires a range of tests, including characterization by bioassay in mouse models. Since 2005, naturally occurring BSE has been identified in two goats. It has also been demonstrated that more than one distinct TSE strain can coinfect a single animal in natural field situations. This study assesses the ability of the statutory methods as listed in the regulation to identify BSE in a blinded series of brain samples, in which ovine BSE and distinct isolates of scrapie are mixed at various ratios ranging from 99% to 1%. Additionally, these current statutory tests were compared with a new in vitro discriminatory method, which uses serial protein misfolding cyclic amplification (sPMCA). Western blotting consistently detected 50% BSE within a mixture, but at higher dilutions it had variable success. The enzyme-linked immunosorbent assay (ELISA) method consistently detected BSE only when it was present as 99% of the mixture, with variable success at higher dilutions. Bioassay and sPMCA reported BSE in all samples where it was present, down to 1%. sPMCA also consistently detected the presence of BSE in mixtures at 0.1%. While bioassay is the only validated method that allows comprehensive phenotypic characterization of an unknown TSE isolate, the sPMCA assay appears to offer a fast and cost-effective alternative for the screening of unknown isolates when the purpose of the investigation was solely to determine the presence or absence of BSE.
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