Search

We present a novel technique called "photometric IGM tomography" to map the intergalactic medium (IGM) at $z\simeq4.9$ in the COSMOS field. It utilizes deep narrow-band (NB) imaging to photometrically detect faint Ly$\alpha$ forest transmission in background galaxies across the Subaru/Hyper-Suprime Cam (HSC)'s $1.8\rm\,sq.\,deg$ field of view and locate Ly$\alpha$ emitters (LAEs) in the same cosmic volume. Using ultra-deep HSC images and Bayesian spectral energy distribution fitting, we measure the Ly$\alpha$ forest transmission at $z\simeq4.9$ along a large number ($140$) of background galaxies selected from the DEIMOS10k spectroscopic catalogue at $4.98, Comment: 27 pages, 21 figures, accepted by MNRAS, full tables available as online supplementary material

We present new observations of sixteen bright ($r=19-21$) gravitationally lensed galaxies at $z\simeq 1-3$ selected from the CASSOWARY survey. Included in our sample is the $z=1.42$ galaxy CSWA-141, one of the brightest known reionization-era analogs at high redshift (g=20.5), with a large sSFR (31.2 Gyr$^{-1}$) and an [OIII]+H$\beta$ equivalent width (EW$_{\rm{[OIII]+H\beta}}$=730~\r{A}) that is nearly identical to the average value expected at $z\simeq 7-8$. In this paper, we investigate the rest-frame UV nebular line emission in our sample with the goal of understanding the factors that regulate strong CIII] emission. Whereas most of the sources in our sample show weak UV line emission, we find elevated CIII] in the spectrum of CSWA-141 (EW$_{\rm{CIII]}}$=4.6$\pm1.9$~\r{A}) together with detections of other prominent emission lines (OIII], Si III], Fe II$^\star$, Mg II). We compare the rest-optical line properties of high redshift galaxies with strong and weak CIII] emission, and find that systems with the strongest UV line emission tend to have young stellar populations and nebular gas that is moderately metal-poor and highly ionized, consistent with trends seen at low and high redshift. The brightness of CSWA-141 enables detailed investigation of the extreme emission line galaxies which become common at $z>6$. We find that gas traced by the CIII] doublet likely probes higher densities than that traced by [OII] and [SII]. Characterisation of the spectrally resolved Mg II emission line and several low ionization absorption lines suggests neutral gas around the young stars is likely optically thin, potentially facilitating the escape of ionizing radiation., Comment: 20 pages, 9 figures, Accepted for publication in MNRAS

Dental staining is a common concern for tobacco users. However, little is known about which components of tobacco are responsible for the staining and whether nicotine may be implicated. This is of increasing relevance with the popularity of novel products such as heated-tobacco products and electronic cigarettes (E-cigarettes).This systematic review aimed to establish the evidence base for the effect if any, of the various tobacco and nicotine products in causing staining of dental hard tissues and materials.This systematic review was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. There were four structured population intervention comparison outcomesquestions. A search was conducted up to December 2021 in three databases: MEDLINE, EMBASE, and Web of Science, and manual searching of relevant sources was also completed. Two researchers individually reviewed the titles then abstracts and finally full articles. A reporting quality appraisal was conducted appropriately to the study methodology.Of the 815 records titles identified, 56 full-text articles were assessed for eligibility, of which 27 were included for analysis. The included studies were mainly laboratory studies of varying reporting quality. There was evidence from 18 studies that tobacco exposure caused staining of dental hard tissues (pooled results from three studies- enamel/dentine; mean difference [MD]: 16.22; 95% confidence interval[12.11, 20.32; ITobacco smoking causes dental staining. There was limited evidence that E-cigarettes and HTPs did cause dental staining that was less intense than that caused by traditional tobacco products.

Septoplasty and inferior turbinate reduction is a common operation performed by ear, nose and throat surgeons for obstructive nasal symptoms. We present a case of complete unilateral scarring of the Eustachian tube orifice, a previously unreported complication, following septoplasty and inferior turbinate reduction for nasal obstruction. It is important to consider this differential diagnosis in patients presenting with unilateral middle ear effusion postoperatively.

Hematite is a classical photoanode material for photoelectrochemical water splitting due to its stability, performance, and low cost. However, the effect of particle size is still a question due to the charge transfer to the electrodes. In this work, we addressed this subject by the fabrication of a photoelectrode with hematite nanoparticles embedded in close contact with the electrode substrate. The nanoparticles were synthesized by a solvothermal method and colloidal stabilization with charged hydroxide molecules, and we were able to further use them to prepare electrodes for water photo-oxidation. Hematite nanoparticles were embedded within electrospun tin-doped indium oxide nanofibers. The fibrous layer acted as a current collector scaffold for the nanoparticles, supporting the effective transport of charge carriers. This method allows better contact of the nanoparticles with the substrate, and also, the fibrous scaffold increases the optical density of the photoelectrode. Electrodes based on nanofibers with embedded nanoparticles display significantly enhanced photoelectrochemical performance compared to their flat nanoparticle-based layer counterparts. This nanofiber architecture increases the photocurrent density and photon-to-current internal conversion efficiency by factors of 2 and 10, respectively.

Lake Tanganyika ranks among the most valuable modern analogs for understanding depositional processes of carbonaceous sediments in ancient tropical rifts. Prior research on Lake Tanganyika has emphasized the importance of bottom-water anoxia, depositional processes (hemipelagic settling versus gravity flows), and large-scale (100s of meters) lake level change on the quality of sedimentary organic matter content. Here, facies analysis and numerous organic geochemical tools (elemental, carbon isotope, and programmed pyrolysis) were applied to a radiocarbon-dated core from southern Lake Tanganyika to investigate the accumulation of carbonaceous sediments in a deepwater slope environment influenced by high-frequency climatic fluctuations accompanied by only minor (10s of meters) lake level changes. Considerable variability in lithofacies and geochemistry characterizes the ∼ 1030-year-long core record, chiefly driven by climate-mediated changes to the lake's upwelling system. Laminated diatom oozes and sapropels with mean total organic carbon (TOC) concentrations and hydrogen indices of 6.9 wt.% and 385 mg hydrocarbon/g TOC, respectively, characterize sediments deposited during periods of strong upwelling and variable water levels. Silty sediments deposited via gravity-flow processes were likewise rich in organic matter, likely due to preservation-enhancing bottom-water anoxia. Dilution by reworked tephra was the chief constraint on organic enrichment at the study site. Data from this study reveal that oscillations in atmospheric and limnological processes in the absence of major shoreline movements can result in geochemically diverse deepwater slope sediments, which have implications for improving depositional models of petroliferous continental rift basins.

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers.

IntroductionCommunity health workers are essential to frontline health outreach throughout low- and middle-income countries, including programming for early childhood immunization. The World Health Organization estimates a projected shortage of 18 million health workers by 2030. Understanding how community health workers are engaged for successful early childhood vaccination among countries who showed success in immunization coverage would support evidence-based policy guidance across contexts. To that end, we identified factors of community health worker programs that contributed to improved vaccination coverage in Nepal, Senegal, and Zambia.MethodsWe conducted interviews and focus group discussions at the national, regional, district, health facility, and community levels of the health systems of Nepal, Senegal, and Zambia, and used thematic analysis to investigate contributing factors of community health worker programming that supported early childhood immunization within each country and across contexts. We developed a model that could be used for assessment and adaptation based on lessons learned.FindingsAcross all countries, implementation of vaccination programming relied principally on the 1) organization, 2) motivation, and 3) trust of community health workers. Organization was accomplished by expanding cadres of community health workers to carry out their roles and responsibilities related to vaccination. Motivation of community health workers was supported by intrinsic and extrinsic incentives. Trust was expressed by communities due to community health worker respect and value placed on work.ConclusionImprovements in immunization coverage followed successful community health worker programs, facilitated by diversification of cadres, roles and responsibilities, motivation, and trust. With the continued projection of health worker shortages, especially in low-income countries, community health workers bridged the equity gap in access to vaccination services by enabling wider reach to minority populations and populations in hard-to-reach areas. Although improvements in vaccination programming were seen in all three countries - including government - commitment to addressing human resource deficits, training and renumeration; workload, low and inconsistent compensation, inconsistency in training duration and scope, and supervision are still major challenges to immunization programming. Vaccination and health decision-makers should consider organization, motivation, and trust of community health workers to improve the implementation of immunization programming.

Purpose: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. Experimental design: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/− salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. Results: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1–2), 25% nausea (grade 1–2), and 20% fatigue (grade 1–2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). Conclusion: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

Incorporating species distributions into conservation planning has traditionally involved long-term representations of habitat use where temporal variation is averaged to reveal habitats that are most suitable across time. Advances in remote sensing and analytical tools have allowed for the integration of dynamic processes into species distribution modeling. Our objective was to develop a spatiotemporal model of breeding habitat use for a federally threatened shorebird (piping plover, Charadrius melodus). Piping plovers are an ideal candidate species for dynamic habitat models because they depend on habitat created and maintained by variable hydrological processes and disturbance. We integrated a 20-year (2000–2019) nesting dataset with volunteer-collected sightings (eBird) using point process modeling. Our analysis incorporated spatiotemporal autocorrelation, differential observation processes within data streams, and dynamic environmental covariates. We evaluated the transferability of this model in space and time and the contribution of the eBird dataset. eBird data provided more complete spatial coverage in our study system than nest monitoring data. Patterns of observed breeding density depended on both dynamic (e.g., surface water levels) and long-term (e.g., proximity to permanent wetland basins) environmental processes. Our study provides a framework for quantifying dynamic spatiotemporal patterns of breeding density. This assessment can be iteratively updated with additional data to improve conservation and management efforts, because reducing temporal variability to average patterns of use may cause a loss in precision for such actions.

Lithium and hydrogen are volatile elements which diffuse rapidly in crystals and melt, making them powerful geochemical tools to reconstruct geological processes that take place on short time scales, such as syn- and post-eruptive degassing. Although the dynamics of hydrogen are fairly well understood to better constrain such processes, the assessment of Li behaviour within the magma reservoir relevant for ascent-related degassing still lacks detailed evaluation. Here, the first in situ Li concentrations and isotopic compositions (using SIMS analysis) of rhyolitic quartz-hosted, naturally glassy and crystallised melt inclusions (MIs) and groundmass glass (Mesa Falls Tuff, Yellowstone) are used to reconstruct Li elemental and isotopic evolution in the magma reservoir. Lithium concentrations in quartz-hosted glassy MIs (10–61 ppm) from a fallout deposit overlap with their groundmass glass (32–46 ppm) and their host quartz (8–15 ppm). Crystallised MIs from a later erupted flow pumice clast sample have higher Li concentrations (8–190 ppm) compared to the groundmass glass (32–51 ppm) and their host quartz (15–24 ppm). Lithium content in quartz from the early erupted sample is relatively homogenous, whereas it is up to a factor of two higher and heterogeneous in the later erupted sample, with a simultaneous increase in Li versus a decrease in H towards crystal rims. The δ7Li difference (expressed as Δ7LiMI–glass) between MIs (−8.0‰ to + 12.3‰) and groundmass glass (+9.0‰ to + 20.5‰) of two pyroclastic deposits reaches up to 29‰. Glassy MIs are internally heterogeneous in δ7Li and Li abundance. The cores of the glassy MIs record the δ7Li of the least modified melt during entrapment and the data distribution can be modelled by equilibrium fractionation between the melt and vapour phase during early open-system degassing in the magma reservoir. Late degassing during eruption triggers Li–H diffusional exchange between quartz and melt, as the degassing of H2O and the accompanying pressure change trigger H diffusion out of the host quartz and the MIs, which is charge balanced by inward Li diffusion. This results in the modification of Li contents in quartz and δ7Li values in the rims of the glassy MIs. Crystallised MIs reflect the loss of H2O from the MIs and the resulting enrichment of Li during the crystallisation. Additionally, the variations of δ7Li in the groundmass glass can be explained through modelling by kinetic fractionation between the melt and vapour during late stage open-system degassing linked with magma ascent. ISSN:0016-7037 ISSN:1872-9533

Lithium is an economically important element that is increasingly extracted from brines accumulated in continental basins. While a number of studies have identified silicic magmatic rocks as the ultimate source of dissolved brine lithium, the processes by which Li is mobilized remain poorly constrained. Here we focus on the potential of low-temperature, post-eruptive processes to remove Li from volcanic glass and generate Li-rich fluids. The rhyolitic glasses in this study (from the Yellowstone-Snake River Plain volcanic province in western North America) have interacted with meteoric water emplacement as revealed by textures and a variety of geochemical and isotopic signatures. Indices of glass hydration correlate with Li concentrations, suggesting Li is lost to the water during the water-rock interaction. We estimate the original Li content upon deposition and the magnitude of Li depletion both by direct in situ glass measurements and by applying a partition-coefficient approach to plagioclase Li contents. Across our whole sample set (19 eruptive units spanning ca. 10 m.y.), Li losses average 8.9 ppm, with a maximum loss of 37.5 ppm. This allows estimation of the dense rock equivalent of silicic volcanic lithologies required to potentially source a brine deposit. Our data indicate that surficial processes occurring post-eruption may provide sufficient Li to form economic deposits. We found no relationship between deposit age and Li loss, i.e., hydration does not appear to be an ongoing process. Rather, it occurs primarily while the deposit is cooling shortly after eruption, with δ18O and δD in our case study suggesting a temperature window of 40° to 70°C.

Emerging cancers are sculpted by neo-Darwinian selection for superior growth and survival but minimal immunogenicity; consequently, metastatic cancers often evolve common genetic and epigenetic signatures to elude immune surveillance. Immune subversion by metastatic tumours can be achieved through several mechanisms; one of the most frequently observed involves the loss of expression or mutation of genes composing the MHC-I antigen presentation machinery (APM) that yields tumours invisible to Cytotoxic T lymphocytes, the key component of the adaptive cellular immune response. Fascinating ethnographic and experimental findings indicate that cannabinoids inhibit the growth and progression of several categories of cancer; however, the mechanisms underlying these observations remain clouded in uncertainty. Here, we screened a library of cannabinoid compounds and found molecular selectivity amongst specific cannabinoids, where related molecules such as Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol can reverse the metastatic immune escape phenotype in vitro by inducing MHC-I cell surface expression in a wide variety of metastatic tumours that subsequently sensitizing tumours to T lymphocyte recognition. Remarkably, H3K27Ac ChIPseq analysis established that cannabigerol and gamma interferon induce overlapping epigenetic signatures and key gene pathways in metastatic tumours related to cellular senescence, as well as APM genes involved in revealing metastatic tumours to the adaptive immune response. Overall, the data suggest that specific cannabinoids may have utility in cancer immunotherapy regimens by overcoming immune escape and augmenting cancer immune surveillance in metastatic disease. Finally, the fundamental discovery of the ability of cannabinoids to alter epigenetic programs may help elucidate many of the pleiotropic medicinal effects of cannabinoids on human physiology.