An Analysis of ALMA Deep Fields and the Perceived Dearth of High-z Galaxies

Deep, pencil-beam surveys from ALMA at 1.1-1.3mm have uncovered an apparent absence of high-redshift dusty galaxies, with existing redshift distributions peaking around $z\sim1.5-2.5$. This has led to a perceived dearth of dusty systems at $z>4$, and the conclusion, according to some models, that the early Universe was relatively dust-poor. In this paper, we extend the backward evolution galaxy model described by Casey et al. (2018) to the ALMA regime (in depth and area) and determine that the measured number counts and redshift distributions from ALMA deep field surveys are fully consistent with constraints of the infrared luminosity function (IRLF) at $z<2.5$ determined by single-dish submillimeter and millimeter surveys conducted on much larger angular scales ($\sim1-10$deg$^{2}$). We find that measured 1.1-1.3mm number counts are most constraining for the measurement of the faint-end slope of the IRLF at $z4$. Recent studies have suggested that UV-selected galaxies at $z>4$ may be particularly dust-poor, but we find their millimeter-wave emission cannot rule out consistency with the Calzetti dust attenuation law even by assuming relatively typical, cold-dust ($T_{\rm dust}\approx30\,$K) SEDs. Our models suggest that the design of ALMA deep fields requires substantial revision to constrain the prevalence of $z>4$ early Universe obscured starbursts. The most promising avenue for detection and characterization of such early dusty galaxies will come from future ALMA 2mm blank field surveys covering a few hundred arcmin$^{2}$ and the combination of existing and future dual-purpose 3mm datasets.Comment: 21 pages, 12 figures, accepted for publication in Ap

The Brightest Galaxies in the Dark Ages: Galaxies' Dust Continuum Emission During the Reionization Era

Though half of cosmic starlight is absorbed by dust and reradiated at long wavelengths (3$\mu$m-3mm), constraints on the infrared through millimeter galaxy luminosity function (the `IRLF') are poor in comparison to the rest-frame ultraviolet and optical galaxy luminosity function, particularly at z>2.5. Here we present a backward evolution model for interpreting number counts, redshift distributions, and cross-band flux density correlations in the infrared and submillimeter sky, from 70$\mu$m-2mm, using a model for the IRLF out to the epoch of reionization. Mock submillimeter maps are generated by injecting sources according to the prescribed IRLF and flux densities drawn from model spectral energy distributions that mirror the distribution of SEDs observed in $0<z<5$ dusty star-forming galaxies (DSFGs). We explore two extreme hypothetical case-studies: a dust-poor early Universe model, where DSFGs contribute negligibly ($<$10%) to the integrated star-formation rate density at $z>4$, and an alternate dust-rich early Universe model, where DSFGs dominate $\sim$90% of $z>4$ star-formation. We find that current submm/mm datasets do not clearly rule out either of these extreme models. We suggest that future surveys at 2mm will be crucial to measuring the IRLF beyond $z\sim4$. The model framework developed in this paper serves as a unique tool for the interpretation of multiwavelength IR/submm extragalactic datasets and will enable more refined constraints on the IRLF than can be made from direct measurements of individual galaxies' integrated dust emission.Comment: 34 pages, 16 figures, accepted for publication in Ap

In vitro and in vivo activities of linezolid alone and combined with vancomycin and imipenem against Staphylococcus aureus with reduced susceptibility to glycopeptides

The objective of this study was to evaluate the in vitro and in vivo efficacies of linezolid (35 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), linezolid+imipenem, linezolid+vancomycin and vancomycin+imipenem against two clinical Staphylococcus aureus isolates with reduced susceptibility to glycopeptides using time–kill curves and the murine peritonitis model. Time–kill curves were performed over 24 h. For the murine peritonitis model, peritonitis was induced by the intraperitoneal inoculation of 108 CFU/ml of each bacterial strain. Four hours later (0 h), the mice were randomly assigned to a control group or to therapeutic groups receiving subcutaneous treatment for 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. The time–kill curves showed that the addition of linezolid to imipenem yielded synergistic results after 24 h. The addition of linezolid decreased vancomycin activity. In the animal model, vancomycin and linezolid monotherapies produced comparable bacterial decreases in mice infected with each strain but linezolid achieved higher rates of blood sterilisation. Linezolid tested either in monotherapy or in combination showed similar efficacy against both strains in terms of bacterial killing, number of negative blood cultures and survival. Linezolid and vancomycin were moderately bactericidal and similar in efficacy against glycopeptide-intermediate or -resistant S. aureus. Linezolid combinations, as effective as linezolid tested alone, could be considered as alternative options for the treatment of glycopeptide-intermediate S. aureus (GISA) infections

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527

Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving

GATA2 is required for lymphatic vessel valve development and maintenance.

Heterozygous germline mutations in the zinc finger transcription factor GATA2 have recently been shown to underlie a range of clinical phenotypes, including Emberger syndrome, a disorder characterized by lymphedema and predisposition to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). Despite well-defined roles in hematopoiesis, the functions of GATA2 in the lymphatic vasculature and the mechanisms by which GATA2 mutations result in lymphedema have not been characterized. Here, we have provided a molecular explanation for lymphedema predisposition in a subset of patients with germline GATA2 mutations. Specifically, we demonstrated that Emberger-associated GATA2 missense mutations result in complete loss of GATA2 function, with respect to the capacity to regulate the transcription of genes that are important for lymphatic vessel valve development. We identified a putative enhancer element upstream of the key lymphatic transcriptional regulator PROX1 that is bound by GATA2, and the transcription factors FOXC2 and NFATC1. Emberger GATA2 missense mutants had a profoundly reduced capacity to bind this element. Conditional Gata2 deletion in mice revealed that GATA2 is required for both development and maintenance of lymphovenous and lymphatic vessel valves. Together, our data unveil essential roles for GATA2 in the lymphatic vasculature and explain why a select catalogue of human GATA2 mutations results in lymphedema

Banff 2022 liver group meeting report: monitoring long term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participantsincluded hepatologists, surgeons, pathologists, immunologists and histocompatibility specialists.Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimisation and long-term structural changes.Potential revision of the rejection classification scheme to better accommodate and communicate lateT cell-mediated rejection patterns and related structural changes, such as nodular regenerativehyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression tomatch the heterogeneity of patient settings will be central to improving long-term patient survival.Such personalised therapeutics are in turn contingent on better understanding and monitoring ofallograft status within a rational decision-making approach, likely to be facilitated in implementationwith emerging decision support tools. Proposed revisions to rejection classification emerging fromthe meeting include incorporation of interface hepatitis and fibrosis staging. These will be opened toonline testing, modified accordingly and subject to consensus discussion leading up to the next Banffconference

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes