Learned holographic light transport: Invited

Computer-generated holography algorithms often fall short in matching simulations with results from a physical holographic display.Our work addresses this mismatch by learning the holographic light transport in holographic displays. Using a camera and a holographic display, we capture the image reconstructions of optimized holograms that rely on ideal simulations to generate a dataset. Inspired by the ideal simulations, we learn a complex-valued convolution kernel that can propagate given holograms to captured photographs in our dataset. Our method can dramatically improve simulation accuracy and image quality in holographic displays while paving the way for physically informed learning approaches

Optimizing vision and visuals: lectures on cameras, displays and perception

The evolution of the internet is underway, where immersive virtual 3D environments (commonly known as metaverse or telelife) will replace flat 2D interfaces. Crucial ingredients in this transformation are next-generation displays and cameras representing genuinely 3D visuals while meeting the human visual system's perceptual requirements. This course will provide a fast-paced introduction to optimization methods for next-generation interfaces geared towards immersive virtual 3D environments. Firstly, we will introduce lensless cameras for high dimensional compressive sensing (e.g., single exposure capture to a video or one-shot 3D). Our audience will learn to process images from a lensless camera at the end. Secondly, we introduce holographic displays as a potential candidate for next-generation displays. By the end of this course, you will learn to create your 3D images that can be viewed using a standard holographic display. Lastly, we will introduce perceptual guidance that could be an integral part of the optimization routines of displays and cameras. Our audience will gather experience in integrating perception to display and camera optimizations. This course targets a wide range of audiences, from domain experts to newcomers. To do so, examples from this course will be based on our in-house toolkit to be replicable for future use. The course material will provide example codes and a broad survey with crucial information on cameras, displays and perception

Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency.

IntroductionHereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.AimThe aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.MethodsSubjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL−1) received 25 IU kg−1 pdFX as on‐demand treatment or short‐term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end‐of‐study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.ResultsSixteen enrolled subjects (six aged 12–17 years; 10 aged 18–58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half‐life were 2.00 (2.12; 1.79–2.37) IU dL−1 per IU kg−1 and 29.4 (28.6; 25.8–33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.ConclusionThese results demonstrate that a dose of 25 IU kg−1 pdFX is safe and efficacious for on‐demand treatment and short‐term prophylaxis in subjects with moderate or severe hereditary FX deficiency

Plasma-derived factor X concentrate compassionate use for hereditary factor X deficiency: Long-term safety and efficacy in a retrospective data-collection study.

Background: Coagadex is a high-purity plasma-derived factor X concentrate (pdFX) developed to treat hereditary factor X deficiency (FXD). Objective: Evaluate the efficacy and safety of pdFX administered to patients with hereditary FXD. Methods: This was an open-label, multicenter, retrospective analysis of patients receiving pdFX for compassionate use. Efficacy end points included treatments administered, the number and treatment of bleeds, and investigator assessments. Adverse drug reactions (ADRs) were monitored. Results: Fifteen patients were included: seven received routine prophylaxis, seven received on-demand treatment, and one alternated. Most were aged ≥12 years (n = 13) and had severe hereditary FXD (n = 12). The median follow-up time was 19.2 months (range, 3.5-48.8). The number of infusions per patient per month was higher for the routine prophylaxis group (median [range], 5.4 [1.4-10.1]) than for the on-demand group (0.8 [0.1-2.3]), as was the dose per infusion (27.9 [21.9-53.6] IU/kg vs 20.0 [13.6-27.7] IU/kg). Patients experienced 88 bleeds (34 minor, 7 major, 47 unclassified). The monthly bleed rate per patient was 0.04 in the routine prophylaxis group (based on 17 bleeds in four patients) and 0.8 in the on-demand group (based on 71 bleeds in eight patients). pdFX was used to treat 79 bleeds and was rated effective in all instances. In an overall assessment, investigators rated pdFX as excellent for 14 patients (93.3%) and good for 1 patient (6.3%). No ADRs or safety concerns were reported. Conclusions: This analysis supports the use of pdFX as a safe, effective treatment for hereditary FXD. Routine prophylaxis with pdFX may reduce bleed frequency

Perceptually guided computer-generated holography

Computer-Generated Holography (CGH) promises to deliver genuine, high-quality visuals at any depth. We argue that combining CGH and perceptually guided graphics can soon lead to practical holographic display systems that deliver perceptually realistic images. We propose a new CGH method called metameric varifocal holograms. Our CGH method generates images only at a user’s focus plane while displayed images are statistically correct and indistinguishable from actual targets across peripheral vision (metamers). Thus, a user observing our holograms is set to perceive a high quality visual at their gaze location. At the same time, the integrity of the image follows a statistically correct trend in the remaining peripheral parts. We demonstrate our differentiable CGH optimization pipeline on modern GPUs, and we support our findings with a display prototype. Our method will pave the way towards realistic visuals free from classical CGH problems, such as speckle noise or poor visual quality

Diagnosis, therapeutic advances, and key recommendations for the management of factor X deficiency.

Factor X deficiency is a rare coagulation disorder that can be hereditary or acquired. The typology and severity of the associated bleeding symptoms are highly heterogeneous, adding to the difficulties of diagnosis and management. Evidence-based guidelines and reviews on factor X deficiency are generally limited to publications covering a range of rare bleeding disorders. Here we provide a comprehensive review of the literature on factor X deficiency, focusing on the hereditary form, and discuss the evolution in disease management and the evidence associated with available treatment options. Current recommendations advise clinicians to use single-factor replacement therapy for hereditary disease rather than multifactor therapies such as fresh frozen plasma, cryoprecipitate, and prothrombin complex concentrates. Consensus in treatment guidelines is still urgently needed to ensure optimal management of patients with factor X deficiency across the spectrum of disease severity

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Background: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. Methods: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA\uae, Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. Results: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean&nbsp;\ub1&nbsp;standard deviation (SD) increase in MCF was 5.8&nbsp;\ub1&nbsp;2.5&nbsp;mm one hour after the first HFC infusion (mean&nbsp;\ub1&nbsp;SD dose, 61.88&nbsp;\ub1&nbsp;11.73&nbsp;mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80&nbsp;mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. Conclusions: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia

Common themes and challenges in hemophilia care: a multinational perspective

This is an Accepted Manuscript of an article published by Taylor & Francis in Hematology on 3 Aug 2018, available online: https://doi.org/10.1080/10245332.2018.150522

Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery

Essentials Recombinant von Willebrand factor (rVWF) is effective in von Willebrand disease (VWD). A phase 3 study of rVWF, with/without recombinant factor VIII (rFVIII) before surgery in VWD. Overall rVWF's efficacy was rated excellent/good; rVWF was administered alone in most patients. rVWF was well-tolerated and hemostasis was achieved in patients with severe VWD undergoing surgery. Summary: Background Recombinant von Willebrand factor (rVWF) has demonstrated efficacy for on-demand treatment of bleeding in severe von Willebrand disease (VWD), warranting evaluation in the surgical setting. Objectives This study (NCT02283268) evaluated the hemostatic efficacy/safety profile of rVWF, with/without recombinant factor VIII (rFVIII), in patients with severe VWD undergoing surgery. Patients/Methods Patients received rVWF 40\u201360\ua0IU\ua0kg 121, VWF ristocetin cofactor activity was measured 12\u201324\ua0h before surgery. If endogenous FVIII activity (FVIII:C) target levels were achieved 3\ua0h before surgery, rVWF was administered alone 1\ua0h before surgery; rVWF was co-administered with rFVIII if target endogenous FVIII levels were not achieved. rVWF was infused postoperatively to maintain target trough levels. Overall and intraoperative hemostatic efficacy, the pharmacodynamics of rVWF administration and the incidence of adverse events (AEs) were assessed. Results All patients treated with rVWF for major (n\ua0=\ua010), minor (n\ua0=\ua04) and oral (n\ua0=\ua01) surgery had overall and intraoperative hemostatic efficacy ratings of excellent (73.3% and 86.7%) or good (26.7% and 13.3%). Most rVWF infusions (89.4%) were administered alone, resulting in hemostatically effective levels of endogenous FVIII within 6\ua0h, which were sustained for 72\u201396\ua0h; 70% (n\ua0=\ua07/10) of major surgeries\ua0were performed without rFVIII co-administration. Six patients reported 12 treatment-emergent AEs. Two\ua0patients each had one serious AE: diverticulitis (not treatment related) and deep vein thrombosis (sponsor-assessed as possibly treatment related). No severe allergic reactions or inhibitory antibodies were reported. Conclusions These data support the efficacy and safety profile of rVWF in patients with severe VWD undergoing elective surgery