A Bayesian Nonparametric Conditional Two-sample Test with an Application to Local Causal Discovery

For a continuous random variable $Z$, testing conditional independence $X \perp\!\!\!\perp Y |Z$ is known to be a particularly hard problem. It constitutes a key ingredient of many constraint-based causal discovery algorithms. These algorithms are often applied to datasets containing binary variables, which indicate the 'context' of the observations, e.g. a control or treatment group within an experiment. In these settings, conditional independence testing with $X$ or $Y$ binary (and the other continuous) is paramount to the performance of the causal discovery algorithm. To our knowledge no nonparametric 'mixed' conditional independence test currently exists, and in practice tests that assume all variables to be continuous are used instead. In this paper we aim to fill this gap, as we combine elements of Holmes et al. (2015) and Teymur and Filippi (2020) to propose a novel Bayesian nonparametric conditional two-sample test. Applied to the Local Causal Discovery algorithm, we investigate its performance on both synthetic and real-world data, and compare with state-of-the-art conditional independence tests

Correcting for Selection Bias and Missing Response in Regression using Privileged Information

When estimating a regression model, we might have data where some labels are missing, or our data might be biased by a selection mechanism. When the response or selection mechanism is ignorable (i.e., independent of the response variable given the features) one can use off-the-shelf regression methods; in the nonignorable case one typically has to adjust for bias. We observe that privileged data (i.e. data that is only available during training) might render a nonignorable selection mechanism ignorable, and we refer to this scenario as Privilegedly Missing at Random (PMAR). We propose a novel imputation-based regression method, named repeated regression, that is suitable for PMAR. We also consider an importance weighted regression method, and a doubly robust combination of the two. The proposed methods are easy to implement with most popular out-of-the-box regression algorithms. We empirically assess the performance of the proposed methods with extensive simulated experiments and on a synthetically augmented real-world dataset. We conclude that repeated regression can appropriately correct for bias, and can have considerable advantage over weighted regression, especially when extrapolating to regions of the feature space where response is never observed

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used

Trunk muscle activation and low back loading in lifting in the absence of load knowledge

People who know the actual mass of an object to be lifted normally prepare themselves before attempting a lift to control the movement and to minimize low back loading. In this study, the trunk muscular reactions and low back torque were investigated in the situation in which the individual did not know the actual mass but only had some idea of the range within which the mass lay. Nine males lifted boxes weighing 6.5 or 16.5 kg under the condition in which they knew the actual mass before attempting a lift (the 'known' condition) and the condition in which they only had the information that the mass would be within the range of 6.5 - 16.5 kg (the 'unknown' condition). The ground reaction forces and body movements were measured in the trials and, from these, the L5/S1 torques were calculated. The activation of back and abdominal muscles was also measured. For the 6.5 kg weight, a higher (16%) back muscle activation in grasping the box and a higher (10%) peak L5/S1 torque in actual lifting were observed in the 'unknown' compared with the 'known' weight condition. For the 16.5 kg weight, the back muscle activation was lower (10%) during grasping, and higher (10%) during lifting in the 'unknown' compared with the 'known' weight condition. Knowledge of the load had no effect on the activation of the abdominal muscles. It was concluded that in the so-called 'unknown' conditions, the risks of low back injury were increased in comparison with the conditions where the actual weight was known in advance

Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass

Objectives Cardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6). Materials and methods The role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model. Results In the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB). Conclusion CPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflammatory response to cardiac surgery may be manipulated to improve clinical outcomes

Indications, complications, and outcomes of cardiac surgery after heart transplantation: results from the cash study

[Abstract] Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports. Methods: We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate. Results: Data were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively. Conclusion: Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma : results of 2 european organization for research and treatment of cancer randomized trials with Mitomycin C and Doxorubicin comparing early versus delayed instillations and short-term versus long-term treatment

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