The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance

Funding: We acknowledge support from the US National Institutes of Health (http://www.nih.gov/) (grant 2R01GM078536 to DES), European Commission (http://ec.europa.eu/index_en.htm) (grant PCIG9-GA-2011-291798 to DES) and UK Biotechnology and Biological Sciences Research Council (http://www.bbsrc.ac.uk/) (grants BB/L000113/1 to DES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

On a Conjecture of Rapoport and Zink

In their book Rapoport and Zink constructed rigid analytic period spaces $F^{wa}$ for Fontaine's filtered isocrystals, and period morphisms from PEL moduli spaces of $p$-divisible groups to some of these period spaces. They conjectured the existence of an \'etale bijective morphism $F^a \to F^{wa}$ of rigid analytic spaces and of a universal local system of $Q_p$-vector spaces on $F^a$. For Hodge-Tate weights $n-1$ and $n$ we construct in this article an intrinsic Berkovich open subspace $F^0$ of $F^{wa}$ and the universal local system on $F^0$. We conjecture that the rigid-analytic space associated with $F^0$ is the maximal possible $F^a$, and that $F^0$ is connected. We give evidence for these conjectures and we show that for those period spaces possessing PEL period morphisms, $F^0$ equals the image of the period morphism. Then our local system is the rational Tate module of the universal $p$-divisible group and enjoys additional functoriality properties. We show that only in exceptional cases $F^0$ equals all of $F^{wa}$ and when the Shimura group is $GL_n$ we determine all these cases.Comment: v2: 48 pages; many new results added, v3: final version that will appear in Inventiones Mathematica

Outcomes of Heavy Silicone Oil (Densiron) compared to Silicone Oil in primary rhegmatogenous retinal detachment:a multivariable regression model

PURPOSE: To measure the visual outcomes, proliferative vitreoretinopathy (PVR) and retinectomy rates following primary rhegmatogenous retinal detachment (RRD) repair, comparing silicone oil (SO) and heavy SO (Densiron). METHODS: Retrospective, continuous comparative study from January 2017 to May 2021 of all primary RRD. Multivariable linear (logMAR gain) and binary-logistic (PVR-C and retinectomy rate) regression models to compare tamponade were performed. Covariates included age, gender, ocular co-morbidities, high myopia, macula-status, giant-retinal-tear (GRT), pre-op vision, PVR-C, oil type, perfluorocarbon-use, combined scleral buckle/vitrectomy, combined phaco-vitrectomy, 360-degrees-endolaser and oil duration. Cases with trauma or less than six-month follow-up were excluded. RESULTS: A total of 259 primary RD were analysed. There were 179 SO patients and 80 Densiron patients that had six-month primary re-detachment in 18 (10.1%) and 8 (10.0%) respectively (p = 1.000). No difference in logMAR gain was detected between tamponade choice on multivariable linear regression. Subsequent glaucoma surgery was 5 (2.8%) and 4 (5.0%) for SO and Densiron patients respectively (p = 0.464). On multivariate binary-logistic regression we found no difference in development of PVR-C between oil tamponades. However, SO had significantly higher subsequent retinectomy rate compared to Densiron (odds ratio 15.3, 95% CI 1.9–125.5, p = 0.011). Duration of oil tamponade was not linked to differences in logMAR gain, PVR-C formation or increased retinectomy rate. CONCLUSIONS: We report no difference in primary anatomical success, number of further RRD surgeries, subsequent glaucoma surgery, visual outcomes, PVR-C between both tamponades on multivariable models. Densiron oil was found to be more retinectomy sparing relative to SO

Effect of deprivation and ethnicity on primary macula-on retinal detachment repair success rate and clinical outcomes:A study of 568 patients

Purpose Socio-economic deprivation and ethnic variation have been frequently linked to poorer health outcomes. We collected a large series of primary macula-on rhegmatogenous retinal detachment (RRD) cases and analysed the effect of socio-economic deprivation and ethnicity on both six-month retinal re-detachment rate and visual outcomes. Materials and methods Retrospective consecutive case series of 568 patients attending Birmingham and Midlands Eye Centre from January 2017–2020. Multiple Indices of Deprivation (IMD) deciles were used for deprivation status and split to two groups: IMD-A (Decile 1–5) and IMD-B (Decile 6–10). The two largest subgroups of ethnicities were compared, White and South Asians (SA). Results We report an overall retinal re-detachment rate of 8.5%. IMD-A re-detached significantly more than IMD-B (11.2% vs 6.0% respectively, p = 0.034). No statistical significance was found between White and SA re-detachment rate (9.1% and 5.6% respectively, p = 0.604). SA median age significantly lower at 49 years (IQR: 37–61) compared to White patients at 57 years (IQR: 50–65) (p = Conclusion We demonstrated an increased retinal re-detachment rate in our more deprived patients according to IMD and a younger cohort of SA compared to White ethnicity. Further prospective studies are required to demonstrate the link between socio-economic deprivation and surgical success

Generalization of Conditioned Contextual Anxiety and the Modulatory Effects of Anxiety Sensitivity

Anxiety patients overgeneralize fear responses, possibly because they cannot distinguish between cues never been associated with a threat (i.e., safe) and threat-associated cues. However, as contexts and not cues are discussed as the relevant triggers for prolonged anxiety responses characterizing many anxiety disorders, we speculated that it is rather overgeneralization of contextual anxiety, which constitutes a risk factor for anxiety disorders. To this end, we investigated generalization of conditioned contextual anxiety and explored modulatory effects of anxiety sensitivity, a risk factor for anxiety disorders. Fifty-five participants underwent context conditioning in a virtual reality paradigm. On Day 1 (acquisition), participants received unpredictable mildly painful electric stimuli (unconditioned stimulus, US) in one virtual office (anxiety context, CTX+), but never in a

The Particle Spectrum of Heterotic Compactifications

Techniques are presented for computing the cohomology of stable, holomorphic vector bundles over elliptically fibered Calabi-Yau threefolds. These cohomology groups explicitly determine the spectrum of the low energy, four-dimensional theory. Generic points in vector bundle moduli space manifest an identical spectrum. However, it is shown that on subsets of moduli space of co-dimension one or higher, the spectrum can abruptly jump to many different values. Both analytic and numerical data illustrating this phenomenon are presented. This result opens the possibility of tunneling or phase transitions between different particle spectra in the same heterotic compactification. In the course of this discussion, a classification of SU(5) GUT theories within a specific context is presented.Comment: 77 pages, 3 figure

Week 48 outcomes from the BRAAVE 2020 study: a randomised switch to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in African American adults with HIV

Background: Black Americans are disproportionately impacted by HIV. The BRAAVE 2020 study, evaluated the safety and efficacy of switching to the guidelines- recommended single- tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) in Black adults through week (W) 48. Method: Adults with HIV self- identifying as Black or African American and virologically suppressed on 2 NRTIs plus a 3rd agent were randomised (2:1) to switch to open- label B/F/TAF once daily or stay on their baseline regimen (SBR). Prior virologic failure was allowed except failure on an INSTI. Prior resistance to NNRTIs, PIs and/or NRTIs was permitted except K65R/E/N, ≥3 thymidine analog mutations or T69- insertions. Primary INSTI- resistance was excluded. SBR participants switched to B/F/TAF at W24. Efficacy was assessed at W24 (Primary endpoint, noninferiority margin 6%) and at W48 as the proportion with HIV- 1 RNA ≥50 c/mL by FDA Snapshot and by changes in CD4 count. Safety was assessed by adverse events (AE) and lab results. Results: 495 were randomised and treated (B/F/TAF n = 330, SBR n = 165): 32% cis women, 2% transgender women, median age 49 years (range 18– 79) and 10% had pre- existing M184V/I mutation. At W24, 1% (2/328) on B/F/TAF vs 2% (3/165) on SBR had HIV- 1 RNA ≥50 c/mL (difference - 1.2%; 95% CI - 4.8% to 0.9%) demonstrating non-inferiority of B/F/TAF; 2 with pre- existing primary INSTI resistance were excluded from analysis. 163 assigned to SBR completed W24 and switched to B/F/TAF (SBR to B/F/TAF). At W48 1% (3/328) originally randomised to B/F/TAF and 0 SBR to B/F/TAF had HIV- 1 RNA ≥50 c/mL. Baseline NRTI resistance did not affect the efficacy of B/F/TAF. No treatment emergent resistance was detected. Median (IQR) weight increased 0.9 kg (- 1.5, 4.1) and 0.6 kg (- 1.0, 3.1) for B/F/TAF and SBR to B/F/TAF groups, respectively. Study drug- related AEs occurred in 10% of participants while on B/F/TAF; most were grade 1. Conclusion: Switching to B/F/TAF was highly effective for Black adults regardless of baseline regimen or pre- existing NRTI resistance and was associated with few treatment re-lated AEs or discontinuations

Psychomotor control in a virtual laparoscopic surgery training environment: gaze control parameters differentiate novices from experts

Background: Surgical simulation is increasingly used to facilitate the adoption of technical skills during surgical training. This study sought to determine if gaze control parameters could differentiate between the visual control of experienced and novice operators performing an eye-hand coordination task on a virtual reality laparoscopic surgical simulator (LAP Mentor™). Typically adopted hand movement metrics reflect only one half of the eye-hand coordination relationship; therefore, little is known about how hand movements are guided and controlled by vision. Methods: A total of 14 right-handed surgeons were categorised as being either experienced (having led more than 70 laparoscopic procedures) or novice (having performed fewer than 10 procedures) operators. The eight experienced and six novice surgeons completed the eye-hand coordination task from the LAP Mentor basic skills package while wearing a gaze registration system. A variety of performance, movement, and gaze parameters were recorded and compared between groups. Results: The experienced surgeons completed the task significantly more quickly than the novices, but only the economy of movement of the left tool differentiated skill level from the LAP Mentor parameters. Gaze analyses revealed that experienced surgeons spent significantly more time fixating the target locations than novices, who split their time between focusing on the targets and tracking the tools. Conclusion: The findings of the study provide support for the utility of assessing strategic gaze behaviour to better understand the way in which surgeons utilise visual information to plan and control tool movements in a virtual reality laparoscopic environment. It is hoped that by better understanding the limitations of the psychomotor system, effective gaze training programs may be developed. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 01 Dec 201

Conscious monitoring and control (reinvestment) in surgical performance under pressure.

Research on intraoperative stressors has focused on external factors without considering individual differences in the ability to cope with stress. One individual difference that is implicated in adverse effects of stress on performance is "reinvestment," the propensity for conscious monitoring and control of movements. The aim of this study was to examine the impact of reinvestment on laparoscopic performance under time pressure

Perceptual impairment and psychomotor control in virtual laparoscopic surgery

Background: It is recognised that one of the major difficulties in performing laparoscopic surgery is the translation of two-dimensional video image information to a three-dimensional working area. However, research has tended to ignore the gaze and eye-hand coordination strategies employed by laparoscopic surgeons as they attempt to overcome these perceptual constraints. This study sought to examine if measures related to tool movements, gaze strategy, and eye-hand coordination (the quiet eye) differentiate between experienced and novice operators performing a two-handed manoeuvres task on a virtual reality laparoscopic surgical simulator (LAP Mentor™). Methods: Twenty-five right-handed surgeons were categorised as being either experienced (having led more than 60 laparoscopic procedures) or novice (having performed fewer than 10 procedures) operators. The 10 experienced and 15 novice surgeons completed the "two-hand manoeuvres" task from the LAP Mentor basic skills learning environment while wearing a gaze registration system. Performance, movement, gaze, and eye-hand coordination parameters were recorded and compared between groups. Results: The experienced surgeons completed the task significantly more quickly than the novices, used significantly fewer movements, and displayed shorter tool paths. Gaze analyses revealed that experienced surgeons spent significantly more time fixating the target locations than novices, who split their time between focusing on the targets and tracking the tools. A more detailed analysis of a difficult subcomponent of the task revealed that experienced operators used a significantly longer aiming fixation (the quiet eye period) to guide precision grasping movements and hence needed fewer grasp attempts. Conclusion: The findings of the study provide further support for the utility of examining strategic gaze behaviour and eye-hand coordination measures to help further our understanding of how experienced surgeons attempt to overcome the perceptual difficulties inherent in the laparoscopic environment. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201