Solution of Physics-based Bayesian Inverse Problems with Deep Generative Priors

Inverse problems are notoriously difficult to solve because they can have no solutions, multiple solutions, or have solutions that vary significantly in response to small perturbations in measurements. Bayesian inference, which poses an inverse problem as a stochastic inference problem, addresses these difficulties and provides quantitative estimates of the inferred field and the associated uncertainty. However, it is difficult to employ when inferring vectors of large dimensions, and/or when prior information is available through previously acquired samples. In this paper, we describe how deep generative adversarial networks can be used to represent the prior distribution in Bayesian inference and overcome these challenges. We apply these ideas to inverse problems that are diverse in terms of the governing physical principles, sources of prior knowledge, type of measurement, and the extent of available information about measurement noise. In each case we apply the proposed approach to infer the most likely solution and quantitative estimates of uncertainty.Comment: Paper: 18 pages, 5 figures. Supplementary: 9 pages, 6 Figures, 2 Table

Clinical and endoscopic features of pill-induced esophagitis

Background: Medication can cause an injury in the esophagus by local and systemic effect, leading to esophagitis. Many such medications have been identified as a cause of pill-induced esophagitis. This study was performed to evaluate the clinical and endoscopic findings of pill-induced esophagitis.Methods: This was retrospective observational study, conducted among patients diagnosed endoscopically with pill-induced esophagitis at Ansh gastroenterology clinic, Ahmedabad, India, from April 2017 to March 2021. The data of these patients were recorded in pre-designed case record form by evaluating their past medical records.Results: Total 90 patients were diagnosed with pill-induced esophagitis. Retrosternal chest pain (68.9%), odynophagia (41.1%), dysphagia (25.6%), and epigastric pain (14.4%) were common clinical findings. The major culprit medications were antibiotics, and NSAIDs (non-steroidal anti-inflammatory drugs). Common esophageal endoscopic findings were ulcer (84.4%), erosion (17.8%), and active ulcer bleeding (12.2%). Kissing ulcers were observed in the majority (46.7%) of cases. The majority of ulcer and erosion were located in middle third of the esophagus. All the patients were recovered within 6 to 10 days after treatment with PPIs (proton pump inhibitors) and/or antacids, and withdrawal of the causative medication.Conclusions: Pill-induced esophagitis commonly manifests as retrosternal chest pain, odynophagia and dysphagia, and endoscopy reveals kissing ulcer and erosion in the majority of cases. The condition can be treated with PPIs and/or antacids, and withdrawal of the offending medication.

Use of dorsalis pedis artery flap in coverage of distal lower leg defects

Soft tissue defect in the distal one third of leg have always posed a challenge for reconstructive surgeons. Such wounds are difficult to manage due the tenuous blood supply, limited subcutaneous cover over the tendons and bones. The aim of our study is to investigate the outcome of Dorsalis pedis artery flap for the coverage of such defects. In the present study, we share our clinical experience with the use of dorsalis pedis artery flap for the coverage of defect in the distal one third leg. This is a series of 4 cases where dorsalis pedis artery flap was used to cover lower one third defect. One case had focal squamous cell carcinoma due to long standing post burns contracture in distal one third of leg anteriorly. Other 3 cases had chronic non healing ulcer in the malleolar region. Patient outcome was assessed according to patients’ age distribution, duration of surgery, hospital stay, and post-operative complications. All 4 patients had excellent outcome with no major donor site complications, infection, and graft loss. Donor site was closed with split thickness skin graft. One patient developed a minor raw area over the dorsum of foot which healed secondarily. Although a potential risk in applying this flap is insufficient venous drainage, no problems with blood inflow or outflow were encountered in the present case series. The flaps survived, and the patient had good postoperative outcome. Hence dorsalis pedis flap can be used for the coverage of the distal foot as a good option

Medial plantar artery flap: a versatile workhorse flap for foot reconstruction, our experience

Soft tissue defect in the foot is commonly seen as it is more prone to trophic ulcers since it is the main weight bearing area of the body. Reconstruction of the weight bearing area of the foot requires the provision of a stable, supple, durable and preferably sensate skin coverage. Following Sir Gilli’s principle of replacing like with like, medial plantar artery flap provides an anatomically similar, glabrous skin for coverage on the plantar surface. In the present study, we share our clinical experience with the use of medial plantar artery flap for coverage of soft tissue defect over sole of foot. At our institution, a total of 10 patients presented with soft tissue defect of the sole, underwent medial plantar artery flap coverage. All the 10 patients were diagnosed cases of type 2 DM. patient outcome was assessed according to patients’ age distribution, duration of surgery, hospital stay, and post operative complications. Out of all the 10 patients, 5 were male and 5 were female. All the flaps healed uneventfully without major complications like partial flap necrosis. Donor site was covered with split thickness skin graft. There was suture site dehience in 2 cases which healed with secondary healing. Medial plantar artery flap has been described as an optimal reconstructive option for this type of soft tissue defect.

Brain-localized CD4 and CD8 T cells perform correlated random walks and not Levy walks [version 2; peer review: 1 approved, 2 approved with reservations]

Background. For survival of the organism, T cells must efficiently control pathogens invading different peripheral tissues. Whether or not such control is achieved by utilizing different movement strategies in different tissues remains poorly understood. Liver-localized CD8 T cells perform correlated random walks  --- a type of a Brownian walk -- in liver sinusoids but in some condition these T cells may also perform Levy flights -- rapid and large displacements by floating with the blood flow. CD8 T cells in lymph nodes or skin also undergo Brownian walks. A recent study suggested that brain-localized CD8 T cells, specific to Toxoplasma gondii, perform generalized Levy walks -- a walk type in which T cells alternate pausing and displacing long distances --- which may indicate that brain is a unique organ where T cells exhibit movement strategies different from other tissues. Methods.  We quantified movement patterns of brain-localized Plasmodium berghei-specific CD4 and CD8 T cells by using well-established statistical and computational methods. Results.  We found that T cells change their movement pattern with time since infection and that CD4 T cells move faster and turn less than CD8 T cells. Importantly, both CD4 and CD8 T cells move in the brain by correlated random walks without long displacements challenging previous observations. We have also re-analyzed the movement data of brain-localized CD8 T cells in T. gondii-infected mice and found no evidence of Levy walks. We hypothesize that the previous conclusion of Levy walks of T. gondii-specific CD8 T cells in the brain was reached due to missing time-frames in the data that create an impression of large movement lengths between assumed-to-be-sequential movements.  Conclusion. Our results suggests that movement strategies of CD8 T cells are largely similar between LNs, liver, and the brain and consistent with correlated random walks and not Levy walks

The Event Horizon Telescope Image of the Quasar NRAO 530

We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5−7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of ∼20 μas, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of ∼5%-8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 μas along a position angle ∼ −28°. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin

A Universal Power-law Prescription for Variability from Synthetic Images of Black Hole Accretion Flows

We present a framework for characterizing the spatiotemporal power spectrum of the variability expected from the horizon-scale emission structure around supermassive black holes, and we apply this framework to a library of general relativistic magnetohydrodynamic (GRMHD) simulations and associated general relativistic ray-traced images relevant for Event Horizon Telescope (EHT) observations of Sgr A*. We find that the variability power spectrum is generically a red-noise process in both the temporal and spatial dimensions, with the peak in power occurring on the longest timescales and largest spatial scales. When both the time-averaged source structure and the spatially integrated light-curve variability are removed, the residual power spectrum exhibits a universal broken power-law behavior. On small spatial frequencies, the residual power spectrum rises as the square of the spatial frequency and is proportional to the variance in the centroid of emission. Beyond some peak in variability power, the residual power spectrum falls as that of the time-averaged source structure, which is similar across simulations; this behavior can be naturally explained if the variability arises from a multiplicative random field that has a steeper high-frequency power-law index than that of the time-averaged source structure. We briefly explore the ability of power spectral variability studies to constrain physical parameters relevant for the GRMHD simulations, which can be scaled to provide predictions for black holes in a range of systems in the optically thin regime. We present specific expectations for the behavior of the M87* and Sgr A* accretion flows as observed by the EHT

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation