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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

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder arising from biallelic non-functional survival motor neuron 1 (SMN1) genes with variable copies of partially functional SMN2 gene. Intrathecal onasemnogene abeparvovec administration, at fixed, low doses, may enable treatment of heavier patients ineligible for weight-based intravenous dosing. Objective: STRONG (NCT03381729) assessed the safety/tolerability and efficacy of intrathecal onasemnogene abeparvovec for sitting, nonambulatory SMA patients. Methods: Sitting, nonambulatory SMA patients (biallelic SMN1 loss, three SMN2 copies, aged 6–

The DepEd Computerization Program (DCP) is a nationwide initiative to provide public elementary schools with computers and other ICT equipment to enhance the teaching and learning process. However, the effectiveness of this program and its impact on the computer literacy level of school personnel have yet to be fully explored. This study attempted to fill this gap by examining the perceptions of the school personnel of public elementary schools in the Bohol Division of the Department of Education about the DCP implementation and its relation to their computer literacy level and the problems they encountered in using the ICT equipment in the school year 2020–2021. The study also investigated the influence of the school personnel's profile on their computer literacy level and the problems they encountered. Results revealed that the DepEd Computerization Program (DCP) is highly effective, and the computer literacy of school personnel is very satisfactory. There is a significant relationship between the effectiveness of DCP and the problems encountered by school personnel. The computer literacy of school personnel is also significantly related to their years of teaching, specialized training attended, and age. The problems encountered by school personnel are significantly related to their age, gender, years of teaching, specialized training attended, IPCRF rating and DCP packages received. The study concludes that the implementation of DCP and the computer literacy of school personnel are congruent based on the data gathered, despite the problems encountered.

Background: Human gut microbiome has complex relationships with the host, contributing to metabolism, immunity, and carcinogenesis. Methods: Summary-level data for gut microbiota and metabolites were obtained from MiBioGen, FINRISK and human metabolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively. Results: Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (β = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gammaproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06×10−8), Enterobacteriaceae (β = 0.023, P = 1.29×10−5). Conclusions: We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colorectal cancer risk. Impact: This study highlights the need of future complementary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.

This Article provides recommendations both for improving the accuracy of applications of the Sherman Act and Clayton Act to mergers and acquisitions (M&A)s and for creating morally-desirable (M&A) policies. It defines the specific-anticompetitive-intent and lessening-competition tests of illegality that current U.S. antitrust law applies to (M&A)s; explains why neither classical economic markets nor antitrust markets can be defined non-arbitrarily, and why it is therefore inaccurate and unconstitutional to use market-oriented approaches to analyzing the illegality of (M&A)s under current U.S. antitrust law; outlines appropriate non-market-oriented protocols for determining the illegality of (M&A)s under the Sherman and Clayton Acts—whether the (M or A) was motivated by specific anticompetitive intent or would tend to lessen competition; delineates the liberal conception of justice and various egalitarian conceptions of the moral good and argues that in the U.S. those moral norms should be used to evaluate antitrust policies; outlines the protocol that is economically efficient to use to predict the economic efficiency of particular (M or A)s or particular (M&A) policies; and considers the relevance of the economic efficiency and competitive impact of any (M or A) or any (M&A)-focused antitrust policy for its moral desirability.

The Metal Earth project integrates geophysics, geology, geochemistry, and geochronology to improve the understanding of metal endowment in Precambrian terranes. Magnetics (airborne), gravity, magnetotellurics, and reflection seismic methods are the primary geophysical tools employed. Data were collected along 13 transects in the initial phase of the project. All geophysical tools are crucial for understanding the structure of the shallow, middle, and deeper crust and identifying pathways along which the constituents of critical minerals might have migrated from a source to a deposit. The magnetic data are used predominantly to help map the geology away from the transects, and the gravity data are useful for extending the near-surface geology to depths up to 8 km. The magnetotelluric data show the upper Archean crust to about 10 km as highly resistive, except for some conductive subvertical zones that correspond to major deformation zones, many of which are known to be metalliferous. This suggests that these conductive zones could have been hydrothermal fluid pathways feeding the mineral deposits. These zones can be traced to larger horizontal conductive zones in the midcrust. The seismic reflection data are consistent with and complement this: the upper crust is primarily nonreflective; however, the midcrust shows many horizontal reflectors, usually with a consistent dip to the north. Processing crooked-line seismic data is problematic, and techniques have been developed to improve the imaging, including multifocusing, 3D processing, full-waveform inversion, and cross-dip moveout methods. Passive seismic data have also been collected. Ambient-noise surface-wave tomography can be used to infer broad zones of similar seismic velocity between major reflectors, while receiver function analysis has been used to identify deeper structures such as horizontal features at or below the Moho and a dipping structure evident to about 70 km depth.

Writing in 2022 we are at a global crisis point, as our use of the planet’s finite resources outstrips supply. Our current lifestyles continue to perpetuate this problem by encouraging excessive and wasteful models of consumption. One of the most detrimental industries for this is the clothing industry. Our fashion cycle is now programmed to be ‘ultra-fast’, encouraging excessive consumption of garments causing myriad environmental issues. This article argues that there are developing models of both manufacture and consumption, which can satiate this need for ‘fast’ fashion whilst being part of the wider sustainable fashion conversation. Rather than understanding the short-term life cycle of clothing as inherently unsustainable, this can be reframed as matching a garment’s use phase to the longevity of the material it is made from. This article uses a material culture approach to explore original 1960s paper garments, alongside a critical analysis of the sustainability of their manufacture and disposal from a green chemical perspective. Using the combined knowledge and experience of its authors, from historians and sustainable fashion designers to green chemists and biochemical engineers, this article demonstrates how such garments could inspire new models of sustainable fashion production and consumption. We argue that the current paradigm of slow fashion as the only antidote to fast fashion must be challenged. Instead, the fashion and textile sector must consider a range of solutions to the environmental burden of fast fashion that are human-centred and sympathetic to all consumer demographics and needs.

Although highly desirable, the nature of wood-cellulose in its native state has remained difficult to comprehend. Contrary to the traditional acceptance of wood-cellulose being crystalline, in 2016, the authors’ research found that the cellulose was not crystalline. Here, additional evidence is presented that further supports the non-crystalline model. One of the key pieces of evidence was obtained by 64% H2SO4 hydrolysis of tension- and opposite-aspen woods (TW and OW, respectively). The TW (G-layer rich) yielded significant amount of CNCs (TW-CNCs, 20.7%), the OW yielded a much lower amount (OW-CNCs, 5.4%). Although a higher yield of TW-CNCs was expected due to the presence crystalline cellulose in the G-layer, the lower yield of the OW-CNCs was a surprise because, assuming absence of G-layer, based on the authors’ earlier findings no CNCs were expected to be generated. To explain this anomaly, anatomical examination of the woods using stains was carried out which showed that some OW fibers also contained the crystalline G-layer and therefore, provided an explanation as to why the OW-CNCs were produced. The results clearly showed that the acid hydrolysis did not destroy the crystalline cellulose and therefore, in the case of a normal (G-layer free) wood which, as previously reported had not generated CNCs, the cellulose must have been non-crystalline. An additional indication of the wood’s S2 cellulose being not crystalline was the absence of the 93 cm−1 Raman band in the low frequency spectrum of the TW S2 layer. Further evidence was obtained by comparing low frequency Raman spectra of TW-CNCs, TW-holopulp, and aspen-holopulp as well as the mixture-samples of crystalline cellulose and xylan at the concentration levels of their occurrence in these holopulps. Overall, these findings provided further support to the contention that the native wood-cellulose is non-crystalline.

Fibrosis is characterized by inappropriately persistent myofibroblast accumulation and excessive extracellular matrix deposition with the disruption of tissue architecture and organ dysfunction. Regulated death of reparative mesenchymal cells is critical for normal wound repair, but profibrotic signaling promotes myofibroblast resistance to apoptotic stimuli. A complex interplay between immune cells and structural cells underlies lung fibrogenesis. However, there is a paucity of knowledge on how these cell populations interact to orchestrate physiologic and pathologic repair of the injured lung. In this context, gasdermin-D (GsdmD) is a cytoplasmic protein that is activated following cleavage by inflammatory caspases and induces regulated cell death by forming pores in cell membranes. This study was undertaken to evaluate the impact of human (Thp-1) monocyte-derived extracellular vesicles and GsdmD on human lung fibroblast death. Our data show that active GsdmD delivered by monocyte-derived extracellular vesicles induces caspase-independent fibroblast and myofibroblast death. This cell death was partly mediated by GsdmD-independent induction of cellular inhibitor of apoptosis 2 (cIAP-2) in the recipient fibroblast population. Our findings, to our knowledge, define a novel paradigm by which inflammatory monocytes may orchestrate the death of mesenchymal cells in physiologic wound healing, illustrating the potential to leverage this mechanism to eliminate mesenchymal cells and facilitate the resolution of fibrotic repair.

AimsThis study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure.MethodsA total of 59 participants with symptomatic Kellgren-Lawrence grade 2 knee OA were randomly allocated to TAE or a sham procedure. The intervention group underwent TAE of one or more genicular arteries. The control group received a blinded sham procedure. The primary outcome was knee pain at 12 months according to the Knee injury and Osteoarthritis Outcome Score (KOOS) pain scale. Secondary outcomes included self-reported function and quality of life (KOOS, EuroQol five-dimension five-level questionnaire (EQ-5D-5L)), self-reported Global Change, six-minute walk test, 30-second chair stand test, and adverse events. Subgroup analyses compared participants who received complete embolization of all genicular arteries (as distinct from embolization of some arteries) (n = 17) with the control group (n = 29) for KOOS and Global Change scores at 12 months. Continuous variables were analyzed with quantile regression, adjusting for baseline scores. Dichotomized variables were analyzed with chi-squared tests.ResultsOverall, 58 participants provided questionnaire data at 12 months. No significant differences were found for the primary and secondary outcomes, with both groups improving following the procedure. At 12 months, KOOS pain scores improved by 41.3% and 29.4% in the intervention and control groups, respectively. No adverse events occurred. Subgroup analysis indicated that the complete embolization group had significantly better KOOS Sports and Recreation, KOOS Quality of Life, and Global Change scores than the control group; 76.5% of participants who received complete embolization reporting being moderately or much better compared to 37.9% of the control group.ConclusionTAE might produce benefits above placebo, but only when complete embolization of all genicular arteries is performed. Further comparative studies are required before definitive conclusions regarding the effectiveness of TAE can be made.Level of evidence: ICite this article: Bone Jt Open 2023;4(3):158–167.

Background To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. Methods Swedish-born individuals (1972–1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). Results We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. Conclusions The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

Background In 2020, pembrolizumab was approved as a therapy for triple-negative breast cancer (TNBC) with the companion diagnostic DAKO 22C3 programmed death ligand-1 (PD-L1) immunohistochemistry assay. The study aimed to determine the landscape of PD-L1 expression as detected by the DAKO 22C3 PD-L1 assay in breast cancer subtypes and compare the clinicopathologic and genomic characteristics of PD-L1 positive and negative TNBC. Methods PD-L1 expression using the DAKO 22C3 antibody was scored using a combined positive score (CPS) and positive status was defined as CPS ≥10. Comprehensive genomic profiling was performed using the FoundationOne CDx assay. Results Of the 396 BC patients stained with DAKO 22C3, the majority were HR+/HER2− and TNBC (42% and 36%, respectively). Median PD-L1 expression and frequency of CPS ≥10 was highest in TNBC cases (median: 7.5, 50% CPS ≥10) and lowest in the HR+/HER2− group (median: 1.0, 15.5% CPS ≥10) (P Conclusions The subtypes of breast cancer have distinct patterns of PD-L1 expression, supporting that further research of immunotherapies may include specific evaluation of optimum cutoffs for non-TNBC patients. In TNBC, PD-L1 positivity is not associated with other clinicopathologic or genomic features and should be integrated into future studies of immunotherapy efficacy.

Background: Breast cancer brain metastasis (BCBM) represents an area of unmet clinical need. We previously demonstrated the genomic differences between primary BC and BCBM. In this study we examined the genomic differences between BCBM by BC subtypes and the potential actionable targets that might be taken forward for each subtype in clinical trials. Material and Methods: A total of 761 BCBMs were analyzed by comprehensive genomic profiling (CGP) for alterations in up to 395 genes (Foundation Medicine, USA). The samples were classified by immunohistochemistry (IHC) of the BCBM to ER+ (ER+/HER2-, ER+/HER2+), ER-/HER2+ and ER-/HER2-. Homologous recombination deficiency (HRD-gLOH; cutoff 16%), tumour mutational burden (TMB; cutoff 10 mutations/Mb), microsatellite instability (MSI) and PD-L1 prevalence and expression by IHC using the VENTANA SP142 assay (Immune Cell Score [IC] cutoff 1%) were also investigated. Results: For all BC subtypes the most enriched gene alterations in BCBM (>20% prevalence) were: TP53, MYC and PIK3CA. ESR1 and ERBB2 were more prevalent in ER+ and HER2+ tumours respectively, with ESR1 alterations significantly enriched in ER+/HER2- BCBMs (p< 0.0001). Frequently altered genes by BCBM subtype were: ER+/HER2-: CDH1 (8%) and BRCA2 (7%); ER+/HER2+: PIK3C2B (11%), MDM4 (11%), TBX3 (9%) and AKT2 (8%); ER-/HER2+: LYN (9%). Significantly enriched genes (p< 0.01) by BCBM subtype were: HER2+: CDK12 (15%); ER-/HER2-: BRCA1 (14%), CCND3 (9%), VEGFA, JAK2 (8% each) and the immune checkpoint inhibition (ICPI) biomarkers PDCD1LG2 (PDL2), CD274 (PDL1) (7% each). HRD-gLOH was high in ER+/HER2-: (43%) and ER-/HER2-: (70%). TMB and MSI were present in 10%-21% and 1-3% of BCBM respectively, whereas PDL1 protein expression by subtypes was: ER+/HER2- 23%, ER+/HER2+ 27%, ER-/HER2+ 57% , ER-/HER2- 48%. Table 1 summarizes the proportion of BCBMs with actionable alterations and selected clinical trials in BCBM. Conclusion: Clinically-relevant genomic alterations were identified across all BCBM subtypes. High HRD-gLOH, TMB and MSI were observed across all the BCBMs subtypes whereas PDL1/PDL2 alterations were a distinctive feature of ER-/HER2- BCBM. These data highlight the need to assess the genomic landscape of BCBM to enable rational treatment decisions with targeted agents, as well as to enable enrichment of relevant populations within clinical trials. Table 1. Selected studies with targeted therapy and/or immunotherapy in breast cancer brain metastases. The percentage (%) of actionable alterations by ER and HER2 status is summarized. ND: Not Detectable. Citation Format: Athina Giannoudis, Ethan Sokol, Shakti Ramkissoon, Talvinder Bhogal, Jeff Ross, Kimberly McGregor, Evangelia Razis, Rupert Bartsch, Richard S. Huang, Carlo Palmieri. Targetable alterations and genomic signatures within breast cancer brain metastases: Data from comprehensive genomic profiling of 761 breast cancer brain metastases [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-10.

What is this summary about? This is a summary of an article about a study called “P-REALITY X” that was published in the medical journal npj Breast Cancer in October 2022. “P-REALITY X” stands for Palbociclib REAl-world first-LIne comparaTive effectiveness studY eXtended. This study used information from a database to look at whether adding a second treatment (palbociclib) to an aromatase inhibitor (AI) helped people with a certain type of breast cancer to live longer. The type of breast cancer is metastatic hormone receptor-positive/human epidermal growth factor-negative breast cancer, also called HR-positive (or HR+)/HER2-negative (or HER2–) breast cancer. The study used information from the Flatiron Database. This database contains unidentified health care information collected from people seen by doctors in the USA. Only data from people who did not participate in a clinical trial were used. When people are treated outside of a clinical trial, this is called the real-world setting, or routine clinical practice. In clinical trials, people lived longer without their disease worsening if they were treated with palbociclib plus an AI versus being treated with an AI only. Based on the results of clinical trials, treatment with palbociclib plus an AI is already approved and recommended for people with HR+/HER2– breast cancer. This study looked at whether people lived longer if they were treated with palbociclib plus an AI versus being treated with an AI only in routine clinical practice as well. What were the results? This study showed that, in routine clinical practice, people treated with the medicine palbociclib plus an AI lived longer than people treated with only an AI. What do the results mean? These results support the continued use of palbociclib plus an AI as the standard first medicine to be given to people with metastatic HR+/HER2– breast cancer. Clinical Trial Registration: NCT05361655 ( ClinicalTrials.gov )

We wanted to look at the way opioid pain drugs are provided to mothers after the birth of their children and see what doctors tell mothers about the pain drugs. We interviewed doctors and asked which opioid pain drug they would choose, what made them prescribe the drug, the thoughts about giving mothers the drug and what they told the mothers about the drug. We then looked at all the responses to look for patterns in how doctors gave pain drugs to mothers. Our team interviewed 38 doctors. Some key points were seen; first is that the choice of opioid pain drug, dose and number of pills prescribed was different from doctor to doctor; second is that whether the baby was delivered vaginally or by cesarean was the main factor upon which doctors based their decisions for giving opioid pain drugs. Whether a mother was taking medications that help with addiction, the doctor’s assessment of the mother’s pain and the doctor’s thoughts on the mother’s risk of opioid addiction were also considered. All doctors would give opioid pain drugs to breastfeeding mothers. Finally, some doctors talked to mothers about using other medications for pain, but not about the overuse of opioid pain drugs. At our two hospital centers in Pennsylvania, the 38 doctors gave opioid pain drugs to mothers in 38 different ways. Doctors said that opioids are necessary after cesarean, but not after vaginal birth, unless there is a problem. A mother’s history and social situation inform decision making. Doctors talk to mothers about short-term pain, but not about the overuse of opioid pain drugs.

Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3. Patients and Methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of a 28-day cycle. Tumor response was assessed every two cycles. Results: Forty patients were assigned to subprotocol Z1B; 4 patients had outside assays identifying the CCND1, 2, or 3 amplification and were not confirmed centrally; 3 were ineligible and 2 were not treated (1 untreated patient was also ineligible), leaving 32 evaluable patients for this analysis. There were no partial responses; 12 patients (37.5%) had stable disease as best response. There were seven deaths on study, all during cycle 1 and attributable to disease progression. Median progression-free survival was 1.8 months. The most common toxicities were leukopenia (n = 21, 55%) and neutropenia (n = 19, 50%); neutropenia was the most common grade 3/4 event (n = 12, 32%). Conclusions: Palbociclib was not effective at treating nonbreast solid tumors with a CCND1, 2, or 3 amplification in this cohort. These data do not support further investigation of single-agent palbociclib in tumors with CCND1, 2, or 3 amplification.

The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC.Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations (EpCAMHCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Background Research and innovation are essential for effective healthcare service delivery, leading to improvements in patient health and wellbeing. National policy dictates that research delivery is embedded into daily practice of United Kingdom (UK) healthcare professionals, including pharmacists. There is a limited understanding of critical care pharmacist research activities, experiences and interests. It is, therefore, important to describe current practice including barriers and facilitators to enable increased engagement. Objectives To describe UK critical care pharmacist research activity, experiences, interests and barriers to better engagement. Method An electronic survey was developed, piloted and distributed (June to October 2021) to all critical care pharmacists via UK professional organisations. Key findings The survey was completed by 126 pharmacists, providing a 54% response rate. Few pharmacists reported research capability (postgraduate qualification with a research component, 31% (39/126)) and opportunity (dedicated research time, 28.6% (36/126)), only 12.7% (16/126) have both these influencers. Those that did, produced significantly more research outputs (median 4 (0,9) versus 0 (0,1), P = 0.023) and undertook grant funding applications (X2 (1, n = 126) = 25.8, P < 0.001), compared to those without. The most frequently reported barrier to research was the time (opportunity), (71.4%, 90/126). Few pharmacists reported having a research mentor (13.3%, 16/120). Most pharmacists reported an interest in collaborating on research projects across a broad range of areas. Conclusions Critical care pharmacists are motivated to participate in the evaluation continuum including research, although most report capability and opportunity barriers to delivery. We suggest policy recommendations to address limitations and increase pharmacist research involvement.

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

Our understanding of lipid biogeochemistry of the ocean’s interior is still in its infancy. Here we focus on early lipid transformation and the formation of lipid degradation products in the NE Atlantic Ocean (49.0°N, 16.5°W). We employed high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), a method that allows observation and elemental composition assignment of thousands of lipids in a single sample. Using these data, we infer molecular-level changes that occur during lipid transformation in the oceanic water column to shed new light on early lipid transformation processes and the formation of lipid decomposition intermediates, here termed CHO compounds (i.e., lipid-derived species that contain carbon, hydrogen and oxygen in their molecular formula). We considered the distribution of molecular rings and/or double bonds (DBE), H/C and O/C ratios, molecular diversity based on the number of mass spectral signals for monoisotopic species, and carbon number in CHO molecules. Data are elaborated for the four ocean zones, the epipelagic, mesopelagic, bathypelagic and abyssal. The highest molecular diversity characterizes CHO compounds associated with the epipelagic zone, which is explained by numerous and diverse planktonic communities inhabiting the epipelagic and by the effects of both biotic and abiotic processes on lipid transformation. Lipid transformations include crosslinking (condensation), partial degradation or fragmentation, double bond reduction, oxidation, hydrogenation, dehydrogenation and cyclization. Crosslinking likely results in a unimodal distribution of carbon number of CHO compounds, in contrast to cell lipids (referred to as Reported lipids based on the Lipid Maps Database), which have a bimodal distribution of carbon number. CHO compounds that appear to be formed by fragmentation (decrease of the number of C atoms) and ring/double bond reduction were more stable to further transformation and remained longer in the water column, i.e., these compounds were transferred deeper into the water column. Low unsaturation and fast transport to depth promotes CHO compound preservation in the water column. Dehydrogenation leads to increased desaturation (average DBE up to 21.3), condensation, and cyclization, resulting in high molecular weight compounds with a high degree of unsaturation. Our data demonstrate that lipids with cyclic structures are more refractory than those with acyclic structures. The formation of aromatic structures is not a significant process during early lipid transformation in the oceanic water column.

We described trends and disparities in utilization of systemic chemotherapy in metastatic hepato-pancreato-biliary (HPB) cancers.We queried the National Cancer Database for metastatic HPB cancers [hepatocellular carcinoma (HCC), biliary tract cancers (BTC), pancreatic adenocarcinoma (PDAC)]. We used multivariable analysis to examine the factors associated with utilization of systemic chemotherapy. We utilized marginal structural logistic models to estimate the effect of health insurance, facility type, or facility volume on utilization of systemic chemotherapy.We identified 162,283 patients with metastatic HPB cancers: 23,923 (14.7%) had HCC, 26,766 (16.5%) had BTC, and 111,594 (68.8%) had PDAC. A total of 37.2% patients with HCC, 55.6% with BTC, and 56.4% with PDAC received chemotherapy. Age ≥70 years and Charlson-Deyo score ≥2 were associated with lower likelihood of receiving chemotherapy across all cancers. Patients with private health insurance had higher receipt of chemotherapy. Receiving treatment at academic facilities had no effect on the receipt of chemotherapy. Treatment of patients with HCC or PDAC at high-volume facilities resulted in higher receipt of chemotherapy.A significant proportion of patients with metastatic HPB cancers do not receive systemic chemotherapy. Several disparities in administration of chemotherapy for metastatic HPB cancers exist.