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The objectives of this article are to present a case of type II cryoglobulinemic vasculitis, explain why mucosa-associated lymphoid tissue (MALT) lymphoma is an unusual cause of type II cryoglobulins and to discuss the aetiology, epidemiology, pathophysiology and treatment of cryoglobulinemic vasculitis. A 67-year-old woman presented with 4 months of weight loss, intermittent epistaxis and a purpuric skin rash. Prior to presentation, she was found to have an elevated rheumatoid factor. Further investigation revealed an acute kidney injury and elevated type II cryoglobulins suspicious for cryoglobulinemic vasculitis, which was confirmed by kidney biopsy. Additional workup for the weight loss included biopsy of newly found splenomegaly. Pathology revealed MALT lymphoma, a rare cause of type II cryoglobulinemic vasculitis. Successful medical therapy required treating the underlying malignancy with rituximab and high-dose steroids. After initial resolution of symptoms with this regimen, the patient’s vasculitis worsened, which was thought to be secondary to undertreatment of the lymphoma. Bendamustine was added to further treat the lymphoma, after which the patient recovered and was able to discharge without recurrence of symptoms at 6 months.

The goal for the next generation of terrestrial reference frames (TRF) is to achieve a 1mm and 0.1mm/yr accurate frame realization through the combination of reference station solutions by multi-technique geodetic observatories (GOs), quality benchmarks which are motivated by the user needs from commercial and scientific disciplines that rely on high precision positioning and spatial referencing. A potentially significant source of error in TRF realizations is the inter-system ties between the instruments at multi-technique stations, usually independently measured through ground-based local surveys. In this work, a successful endeavor to satisfy the tie accuracy goals while exceeding the 200m GGOS baseline guidelines is detailed for the McDonald Geodetic Observatory (MGO), located in the Davis Mountains, Texas, USA.MGO consists of a VLBI Geodetic Observing System (VGOS), infrastructure in place for a Space Geodesy Satellite Laser Ranging (SGSLR) telescope, and several GNSS stations spanning a 900m baseline and a 120m elevation change. The results of the local ties between the GNSS stations across the near-kilometer baseline, as measured between their antenna reference points, show sub-mm precision and 1mm accuracy. These results are validated through day to day repeatability across several metrology surveys conducted in 2021 and sub-mm consistency in direct comparisons with baselines derived from GPS monthly averaged solutions. This presentation will report these results, highlighting the novel designs and techniques employed in the procedure, processing, and error-budget analysis. We present framework for assessment of sensitivities of future TRF realizations to ingesting ties of this quality, and present preliminary results., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile cilia in unicellular eukaryotes. We demonstrate that in zebrafish, cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Human patients and zebrafish with CFAP20 mutations both exhibit retinal dystrophy. Hence, CFAP20 functions within a structural/functional hub centered on the inner junction that is shared between motile and non-motile cilia, and is distinct from other ciliopathy-associated domains or macromolecular complexes. Our findings suggest an uncharacterised pathomechanism for retinal dystrophy, and potentially for motile and non-motile ciliopathies in general.

Mammaliicoccus sciuri (previously Staphylococcus sciuri ) is a frequent colonizer of mammals. We report the draft genomes of a methicillin-resistant strain (2254A) isolated from an armadillo and a methicillin-susceptible strain (6942A) from a cow. Genomes were sequenced using long-read Nanopore sequencing.

Background Assessing the long term effects of many surgical interventions tested in pragmatic RCTs may require extended periods of participant follow-up to assess effectiveness and use patient-reported outcomes that require large sample sizes. Consequently the RCTs are often perceived as being expensive and time-consuming, particularly if the results show the test intervention is not effective. Adaptive, and particularly group sequential, designs have great potential to improve the efficiency and cost of testing new and existing surgical interventions. As a means to assess the potential utility of group sequential designs, we re-analyse data from a number of recent high-profile RCTs and assess whether using such a design would have caused the trial to stop early. Methods Many pragmatic RCTs monitor participants at a number of occasions (e.g. at 6, 12 and 24 months after surgery) during follow-up as a means to assess recovery and also to keep participants engaged with the trial process. Conventionally one of the outcomes is selected as the primary (final) outcome, for clinical reasons, with others designated as either early or late outcomes. In such settings, novel group sequential designs that use data from not only the final outcome but also from early outcomes at interim analyses can be used to inform stopping decisions. We describe data from seven recent surgical RCTs (WAT, DRAFFT, WOLLF, FASHION, CSAW, FIXDT, TOPKAT), and outline possible group sequential designs that could plausibly have been proposed at the design stage. We then simulate how these group sequential designs could have proceeded, by using the observed data and dates to replicate how information could have accumulated and decisions been made for each RCT. Results The results of the simulated group sequential designs showed that for two of the RCTs it was highly likely that they would have stopped for futility at interim analyses, potentially saving considerable time (15 and 23 months) and costs and avoiding patients being exposed to interventions that were either ineffective or no better than standard care. We discuss the characteristics of RCTs that are important in order to use the methodology we describe, particularly the value of early outcomes and the window of opportunity when early stopping decisions can be made and how it is related to the length of recruitment period and follow-up. Conclusions The results for five of the RCTs tested showed that group sequential designs using early outcome data would have been feasible and likely to provide designs that were at least as efficient, and possibly more efficient, than the original fixed sample size designs. In general, the amount of information provided by the early outcomes was surprisingly large, due to the strength of correlations with the primary outcome. This suggests that the methods described here are likely to provide benefits more generally across the range of surgical trials and more widely in other application areas where trial designs, outcomes and follow-up patterns are structured and behave similarly.

Background In the setting of the COVID-19 pandemic, residency programs implemented videoconferencing “virtual” interviews for the 2020 to 2021 match cycle. There is limited published information on virtual ophthalmology residency interviews. Objective The study aimed (1) to assess applicant, selection committee member, and resident opinions of technical quality, communication quality, and ability to assess applicant or program “fit” during virtual interviews; (2) to determine which interview format—in-person or virtual—each party would prefer in the future; and (3) to survey which residency resources applicants found helpful. Design Surveys were sent to applicants, selection committee members, and residents to assess the above objectives for the 2020 to 2021 match cycle virtual interviews at the Moran Eye Center, University of Utah. Setting This study was conducted in a single residency program interview season from 2020 to 2021. Participants Forty applicants, eight committee members, and seven residents who participated in the virtual interview process were surveyed. Intervention or Exposure Prior to interviews, various avenues were implemented to connect with applicants. A videoconferencing software was utilized for interviews. Applicants and selection committee members met in one-on-one or small group interviews. Residents communicated with applicants in a large group setting between interviews. Main Outcome and Measure The study aims to survey the participants as stated in the objectives. There was no planned outcome for this quality improvement study. Results Survey response rate was 98.2% (54/55). All parties rated the technical components as good or very good. Applicants and selection committee members rated communication as overall good or very good, although residents thought communication was very poor. A total of 92.3% applicants, 75% selection committee members, and 0% residents were reported that they were able to appropriately assess fit of the program with the applicant. However, 46.3% respondents preferred in-person interviews in the future. Popular applicant resources were resident-produced videos (82.1%), conversations with residents (46.2%), and a gift bag (43.6%). Conclusion and Relevance Overall, the technical components of the interview were successful. Small, structured group interactions led to better communication and assessment of fit. There were variable opinions regarding future interview format preference between in-person, virtual, or choice. Amid the COVID-19 pandemic, connecting with applicants via various means can optimize the match process.

NKX3.1 is a multifaceted protein with roles in prostate development and protection from oxidative stress. Acting as a pioneer factor, NKX3.1 interacts with chromatin at enhancers to help integrate androgen regulated signalling. In prostate cancer, NKX3.1 activity is frequently reduced through a combination of mutational and post-translational events. Owing to its specificity for prostate tissue, NKX3.1 has found use as an immunohistochemical marker in routine histopathology practice.