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

Characterizing functional modules in the human thalamus: coactivation-based parcellation and systems-level functional decoding

The human thalamus relays sensory signals to the cortex and facilitates brain-wide communication. The thalamus is also more directly involved in sensorimotor and various cognitive functions but a full characterization of its functional repertoire, particularly in regard to its internal anatomical structure, is still outstanding. As a putative hub in the human connectome, the thalamus might reveal its functional profile only in conjunction with interconnected brain areas. We therefore developed a novel systems-level Bayesian reverse inference decoding that complements the traditional neuroinformatics approach towards a network account of thalamic function. The systems-level decoding considers the functional repertoire (i.e., the terms associated with a brain region) of all regions showing co-activations with a predefined seed region in a brain-wide fashion. Here, we used task-constrained meta-analytic connectivity-based parcellation (MACM-CBP) to identify thalamic subregions as seed regions and applied the systems-level decoding to these subregions in conjunction with functionally connected cortical regions. Our results confirm thalamic structure–function relationships known from animal and clinical studies and revealed further associations with language, memory, and locomotion that have not been detailed in the cognitive neuroscience literature before. The systems-level decoding further uncovered large systems engaged in autobiographical memory and nociception. We propose this novel decoding approach as a useful tool to detect previously unknown structure–function relationships at the brain network level, and to build viable starting points for future studies.Peer Reviewe

Characterization and Use of Bacteriocin-Containing Microbial Fermentates for Control of Listeria Monocytogenes in RTE Meat Applications

Bacteriocins produced by lactic acid bacteria (LAB) are able to inhibit the growth of Listeria monocytogenes, and because of their GRAS (generally recognized as safe) status, they have become subjects of interest for use as additives in foods as an antimicrobial.Bacteriocins work by different modes of action (MOA). By screening bacteriocins based on mode of action against Listeria monocytogenes, a multiple MOA bacteriocin cocktail can be created for use as a "hurdle" technology to inhibit the growth of Listeria, as well as prevent the outgrowth of spontaneously-resistant listerial strains.We developed a series of Listeria strains resistant to three different MOA and screened animal-sourced samples for bacteriocins displaying a unique fourth MOA. From this procedure, two unique bacteriocin-producing bacteria were isolated and identified using 16s PCR. Cell-free supernatant (CFS) containing bacteriocin from one of these isolates, Streptococcus spp. 323 was purified using ammonium sulfate precipitation, C18 sep-pack elution, and elution from reverse-phase HPLC with an acetonitrile gradient. Purified sample was submitted to the Oklahoma State University Core Facility for analysis by mass spectrometry.Certain bacteriocin-producing cultures have been implicated as opportunistic pathogens and thus merits analysis of these strains for virulence factors prior to application of CFS in foods. Streptococcal and enterococcal strains were analyzed for hemolysin and gelatinase production, with only one strain producing hemolysin and four displaying gelatinase production. Results assisted in the development of a bacteriocin cocktail utilizing 3 MOA for use in hotdog applications.Frankfurters were formulated with different antimicrobial treatments (bacteriocin cocktail applications, NovaGard, Durafresh 2016) and underwent a series of shelf-life studies. Studies showed antimicrobials tested had a significant decrease in L. monocytogenes from control hotdog batches. Most notably, the use of bacteriocin cocktails within the meat matrix provided a nearly 7-log reduction 16 weeks after inoculation with L. monocytogenes.Given the results of this study, the use of multiple MOA bacteriocin cocktails significantly reduce L. monocytogenes in hotdogs and can be used as an effective antimicrobial intervention in foods.Food Scienc

Ventricular constraint in dilated cardiomyopathy: A new, compliant textile mesh exerts prophylactic and therapeutic properties

BackgroundDilated cardiomyopathy is associated with a progressive decrease in cardiac function, leading to end-stage heart failure. We aimed to stop this process by mechanically constraining the heart with a new, compliant textile mesh.MethodsIn 16 male Munich minipigs (50 ± 7 kg), dilated cardiomyopathy with congestive heart failure was induced through 4 weeks of rapid ventricular pacing (220 beats/min). In the early-mesh group (n = 8), a polyvinylidene fluoride mesh was positioned around both ventricles before pacing was started. In the other group (n = 8), experimental dilated cardiomyopathy through rapid pacing was induced (no mesh). After mesh grafting, rapid pacing was continued (late mesh).ResultsRapid pacing in the no-mesh group (control group) significantly decreased both systolic (cardiac output, peak systolic pressure, and the derivative of pressure increase [dP/dtmax]) and diastolic (minimum rate of pressure rise [dP/dtmin] and left ventricular end-diastolic pressure) variables, whereas these variables remained almost unchanged in the early-mesh group. In the late-mesh group the passive-elastic constraint not only prevented further deterioration but even exerted reverse remodeling to some extent (dP/dtmax and left ventricular end-diastolic pressure, P < .05).ConclusionsVentricular constraint with the new mesh seems to be a prophylactic and therapeutic option in cardiac insufficiency caused by ventricular dilation. This passive-elastic cardioplasty induced reverse remodeling of dilated hearts and significantly improved diastolic and systolic ventricular function

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

Who is seeking help for psychological distress associated with the COVID-19 pandemic?

Background: The COVID-19 pandemic and accompanying restrictions are associated with substantial psychological distress. However, it is unclear how this increased strain translates into help-seeking behavior. Here, we aim to characterize those individuals who seek help for COVID-19 related psychological distress, and examine which factors are associated with their levels of distress in order to better characterize vulnerable groups. Methods: We report data from 1269 help-seeking participants subscribing to a stepped-care program targeted at mental health problems due to the COVID-19 pandemic. Sample characteristics were compared to population data, and linear regression analyses were used to examine which risk factors and stressors were associated with current symptom levels. Results: Seeking for help for COVID-19 related psychological distress was characterized by female gender, younger age, and better education compared to the general population. The majority reported mental health problems already before the pandemic. 74.5% of this help-seeking sample also exceeded clinical thresholds for depression, anxiety, or somatization. Higher individual symptom levels were associated with higher overall levels of pandemic stress, younger age, and pre-existing mental health problems, but were buffered by functional emotion regulation strategies. Conclusions: Results suggest a considerable increase in demand for mental-healthcare in the pandemic aftermath. Comparisons with the general population indicate diverging patterns in help-seeking behavior: while some individuals seek help themselves, others should be addressed directly. Individuals that are young, have pre-existing mental health problems and experience a high level of pandemic stress are particularly at-risk for considerable symptom load. Mental-healthcare providers should use these results to prepare for the significant increase in demand during the broader aftermath of the COVID-19 pandemic as well as allocate limited resources more effectively.Peer Reviewe

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

Muscle invasive bladder cancer treated by transurethral resection, followed by external beam radiation and interstitial iridium-192

Purpose: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. Methods and Materials: From May 1989 until September 1995. 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of .58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. Results: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 31 was experienced by only one patient. Conclusions: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare

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