Shedding Light on Cardiac Excitation: In Vitro and In Silico Analysis of Native Ca2+ Channel Activation in Guinea Pig Cardiomyocytes using Organic Photovoltaic Devices.

OBJECTIVE: This study aims to explore the potential of organic electrolytic photocapacitors (OEPCs), an innovative photovoltaic device, in mediating the activation of native voltage-gated Cav1.2 channels (ICa,L) in Guinea pig ventricular cardiomyocytes. METHODS: Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated ICa,L activation, integrating the channel's kinetic properties into a multicompartment cell model to take intracellular ion concentrations into account. A multidomain model was additionally incorporated to evaluate effects of OEPC-mediated stimulation. The final model combines external stimulation, multicompartmental cell simulation, and a patch-clamp amplifier equivalent circuit to assess the impact on achievable intracellular voltage changes. RESULTS: Light pulses activated ICa,L, with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca2+ channel blocker, nifedipine. Light-triggered ICa,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation. CONCLUSION: OEPC-mediated activation of ICa,L demonstrates their potential for nongenetic optical modulation of cellular physiology potentially paving the way for the development of innovative therapies in cardiovascular health. The integrated model proves the light-mediated activation of ICa,L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices. SIGNIFICANCE: Treating cardiac conduction disorders by minimal-invasive means without genetic modifications could advance therapeutic approaches increasing patients' quality of life compared with conventional methods employing electronic devices.

A Novel Approach for Single Step Analyte Fractionation of Raw Milk Prior to Antbiotica Residue Trace Analysis as an Alternative to QuEchERS Based Extraction.

BACKGROUND: Antibiotic residues in milk are a well-known hazard in the dairy food chain. Detection methods for these residues, such as non-specific microbiological inhibitor tests or group-specific receptor tests, respectively, are relatively inexpensive, easy to use and widely applied to ensure food safety. In contrast, specific detection by liquid chromatography tandem mass spectrometry (LC-MS/MS) - although a critical, complimentary method to confirm the results of non-specific testing-is relatively costly, time consuming and laborious. Furthermore, sample processing before LC-MS/MS analysis requires unique preparation procedures for different groups of antibiotic compounds. OBJECTIVE: To simplify and speed up specific antibiotic residue detection, a low-cost, passive and single-step method to fractionate analytes in raw milk was developed. METHODS: Untreated raw milk was fractionated into its water and fat/protein phases using a FraMiTrACR® AB fractionation unit. The water fraction was then analyzed by LC-MS/MS. The analyte fractionation method was evaluated against a QuEChERS based method for sample preparation. RESULTS: Our method allows qualitative and quantitative detection of substances from the Penicillin, Cephalosporin, Macrolide, Lincosamide, Sulfonamide, Tetracycline and Fluoroquinolone groups of antibiotics. Detection limits are below the legally prescribed maximum residue levels, allowing reliable, specific and rapid validation of a positive result in non-specific microbiological inhibitor tests. CONCLUSION: Analyte fractionation by FraMiTrACR® AB is a faster alternative to QuEChERS based sample preparation for the detection of antibiotic substances in milk. HIGHLIGHT: This method describes a low-cost, environmentally friendly, passive and single-step milk analyte fractionation. As an alternative to QuEChERS based preparation, this fractionation method simplifies and speeds up the process for specific antibiotic residue detection.

TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16).

BACKGROUND: TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional doxorubicin liposomal formulations in preclinical models. This phase I first-in-human study aimed to define the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary activity of TLD-1 in patients with advanced solid tumors. PATIENTS AND METHODS: We recruited patients with advanced solid tumors who failed standard therapy and received up to 3 prior lines of palliative systemic chemotherapy. TLD-1 was administered intravenously every 3 weeks up to a maximum of 9 cycles (6 for patients with prior anthracyclines) from a starting dose of 10 mg/m2, according to an accelerated titration design followed by a modified continual reassessment method. RESULTS: 30 patients were enrolled between November 2018 and May 2021. No dose-limiting toxicities (DLT) were observed. Maximum administered dose of TLD-1 was 45 mg/m2, RP2D was defined at 40 mg/m2. Most frequent treatment-related adverse events (TRAE) of any grade included palmar-plantar erythrodysesthesia (PPE) (50% of patients), oral mucositis (50%), fatigue (30%) and skin rash (26.7%). Most common G3 TRAE included PPE in 4 patients (13.3%) and oral mucositis in 2 (6.7%). Overall objective response rate was 10% in the whole population and 23.1% among 13 patients with breast cancer; median time-to-treatment failure was 2.7 months. TLD-1 exhibit linear pharmacokinetics, with a median terminal half-life of 95 h. CONCLUSIONS: The new liposomal doxorubicin formulation TLD-1 showed a favourable safety profile and antitumor activity, particularly in breast cancer. RP2D was defined at 40 mg/m2 administered every 3 weeks. (NCT03387917).

[Use of milk haptoglobin concentration as an indicator in animal health monitoring of dairy cows]. / Nutzung der Haptoglobinkonzentration in Milch als Indikator für das Tiergesundheitsmonitoring bei Milchkühen.

OBJECTIVE: The aim of the present study was to investigate relationships between elevated haptoglobin concentrations in milk and clinical as well as laboratory parameters in early lactating dairy cows. Furthermore, cut-off values should be identified for the differentiation of healthy and affected animals. MATERIAL AND METHODS: 1462 dairy cows between 5.-65. days in milk were examined on 68 Bavarian farms. Milk and blood samples were taken once a week for a 7-week period per farm and body-condition-scoring, backfat thickness measurement and Metricheck examination, to evaluate uterine health, were performed. Milk samples were analysed for milk fat, milk protein, lactose, urea, ß-hydroxybutyrate and non-esterified fatty acids (indirect measurement, based on IR spectra), cell count, and milk haptoglobin. Blood samples were analysed for creatinine, aspartate aminotransferase, gamma-glutamyl transferase, glutamate dehydrogenase, total protein, albumin, creatine kinase, ß-hydroxybutyrate, non-esterified fatty acids, and blood haptoglobin.Cluster analyses were performed to determine cut-off values for haptoglobin. RESULTS: Besides milk haptoglobin (µg/ml) and blood haptoglobin (µg/ml), cell count (cells/ml milk), milk fat (%), milk protein (%), non-esterified fatty acids in blood (mmol/l), lactation number, days in milk, breed, season, and milk yield (kg) were included as significant input variables (p<0.005) in the cluster analyses. Cluster analysis, using k-means resp. k-prototypes algorithms, resulted in 5 (clusters 1-5 M1) resp. 4 different clusters (clusters 0-3 M2 and 0-3 B).A cut-off value of 0.5 µg/ml haptoglobin in milk was determined for the differentiation of healthy and affected animals. CONCLUSION AND CLINICAL RELEVANCE: As milk is an easily available substrate, routine determination of haptoglobin in milk might be a suitable parameter for animal health monitoring. Using the detected cut-off value, apparently healthy animals with subclinical inflammatory diseases can be identified more quickly.

Machine and Deep Learning Dominate Recent Innovations in Sensors, Signals and Imaging Informatics.

OBJECTIVES: This review presents research papers highlighting notable developments and trends in sensors, signals, and imaging informatics (SSII) in 2022. METHOD: We performed a bibliographic search in PubMed combining Medical Subject Heading (MeSH) terms and keywords to create particular queries for sensors, signals, and imaging informatics. Only papers published in journals containing greater than three articles in the search query were considered. Using a three-point Likert scale (1 = not include, 2 = perhaps include, 3 = include), we reviewed the titles and abstracts of all database results. Only articles that scored three times Likert scale 3, or two times Likert scale 3, and one time Likert scale 2 were considered for full paper review. On this pre-selection, only papers with a total of at least eight points of the three section co-editors were considered for external review. Based on the external reviewers, we selected the top two papers representing significant research in SSII. RESULTS: Among the 469 returned papers published in 2022 in the various areas of SSII, 90, 31, and 348 papers for sensors, signals, and imaging informatics, and then, the full review process selected the two best papers. From the 469 papers, the section co-editors identified 29 candidate papers with at least 8 Likert points in total, of which 9 were nominated as the best contributions after a full paper assessment. Five external reviewers evaluated the nominated papers, and the two highest-scoring papers were selected based on the overall scores of all external reviewers. A consensus of the International Medical Informatics Association (IMIA) Yearbook editorial board finally approved the nominated papers. Machine and deep learning-based techniques continue to be the dominant theme in this field. CONCLUSIONS: Sensors, signals, and imaging informatics is a dynamic field of intensive research with increasing practical applications to support medical decision-making on a personalized basis.

Effectiveness of a web-based self-help tool to reduce problem gambling: A randomized controlled trial.

Background and Aims: Problem gambling constitutes a public health concern associated with psychopathological comorbidity, substance use, and financial difficulties. Most individuals with gambling problems avoid counseling services due to perceived stigma and their preference for self-reliance. Treatment accessibility could be improved through web-based interventions. Methods: We recruited 360 individuals with gambling problems and randomized them to a web-based intervention (n = 185) or an active control group consisting of a self-help manual for problem gambling (n = 175). The primary outcome was the number of days of gambling in the last 30 days. Secondary outcomes included money spent in the last 30 days, time gambling in the last 7 days, gambling-related problems, consumption of alcohol and cigarettes, and psychopathological comorbidity measured at posttreatment and 6-month follow-up. Results: The primary outcome decreased significantly for both groups, with no significant difference between the groups. There were significant group × time interactions according to the Gambling Symptom Assessment Scale (F = 8.83, p <0 .001), the Problem Gambling Severity Index (F = 3.54, p = 0.030), for cigarettes smoked in the last 7 days (F = 26.68, p < 0.001), the Patient Health Questionnaire-9 (F = 19.41, p <0 .001), and the Generalized Anxiety Disorder-7 (F = 41.09, p <0 .001) favoring the intervention group. We experienced an overall high dropout rate (76%). Conclusions: Win Back Control seems to be an effective low-threshold treatment option for individuals with gambling problems that might otherwise be unapproachable for outpatient treatment services. Nevertheless, the high dropout rate should be considered when interpreting the study results, as they may have introduced a degree of variability.

A system theory based digital model for predicting the cumulative fluid balance course in intensive care patients.

Background: Surgical interventions can cause severe fluid imbalances in patients undergoing cardiac surgery, affecting length of hospital stay and survival. Therefore, appropriate management of daily fluid goals is a key element of postoperative intensive care in these patients. Because fluid balance is influenced by a complex interplay of patient-, surgery- and intensive care unit (ICU)-specific factors, fluid prediction is difficult and often inaccurate. Methods: A novel system theory based digital model for cumulative fluid balance (CFB) prediction is presented using recorded patient fluid data as the sole parameter source by applying the concept of a transfer function. Using a retrospective dataset of n = 618 cardiac intensive care patients, patient-individual models were created and evaluated. RMSE analyses and error calculations were performed for reasonable combinations of model estimation periods and clinically relevant prediction horizons for CFB. Results: Our models have shown that a clinically relevant time horizon for CFB prediction with the combination of 48 h estimation time and 8-16 h prediction time achieves high accuracy. With an 8-h prediction time, nearly 50% of CFB predictions are within ±0.5 L, and 77% are still within the clinically acceptable range of ±1.0 L. Conclusion: Our study has provided a promising proof of principle and may form the basis for further efforts in the development of computational models for fluid prediction that do not require large datasets for training and validation, as is the case with machine learning or AI-based models. The adaptive transfer function approach allows estimation of CFB course on a dynamically changing patient fluid balance system by simulating the response to the current fluid management regime, providing a useful digital tool for clinicians in daily intensive care.

Efficacy of a novel online integrated treatment for problem gambling and tobacco smoking: Results of a randomized controlled trial.

Background and aims: Problem gambling and tobacco use are highly comorbid among adults. However, there are few treatment frameworks that target both gambling and tobacco use simultaneously (i.e., an integrated approach), while also being accessible and evidence-based. The aim of this two-arm open label RCT was to examine the efficacy of an integrated online treatment for problem gambling and tobacco use. Methods: A sample of 209 participants (Mage = 37.66, SD = 13.81; 62.2% female) from North America were randomized into one of two treatment conditions (integrated [n = 91] or gambling only [n = 118]) that lasted for eight weeks and consisted of seven online modules. Participants completed assessments at baseline, after treatment completion, and at 24-week follow-up. Results: While a priori planned generalized linear mixed models showed no condition differences on primary (gambling days, money spent, time spent) and secondary outcomes, both conditions did appear to significantly reduce problem gambling and smoking behaviours over time. Post hoc analyses showed that reductions in smoking and gambling craving were correlated with reductions in days spent gambling, as well as with gambling disorder symptoms. Relatively high (versus low) nicotine replacement therapy use was associated with greater reductions in gambling behaviours in the integrated treatment condition. Discussion and conclusions: While our open label RCT does not support a clear benefit of integrated treatment, findings suggest that changes in smoking and gambling were correlated over time, regardless of treatment condition, suggesting that more research on mechanisms of smoking outcomes in the context of gambling treatment may be relevant.

K2S Challenge: From Undersampled K-Space to Automatic Segmentation.

Magnetic Resonance Imaging (MRI) offers strong soft tissue contrast but suffers from long acquisition times and requires tedious annotation from radiologists. Traditionally, these challenges have been addressed separately with reconstruction and image analysis algorithms. To see if performance could be improved by treating both as end-to-end, we hosted the K2S challenge, in which challenge participants segmented knee bones and cartilage from 8× undersampled k-space. We curated the 300-patient K2S dataset of multicoil raw k-space and radiologist quality-checked segmentations. 87 teams registered for the challenge and there were 12 submissions, varying in methodologies from serial reconstruction and segmentation to end-to-end networks to another that eschewed a reconstruction algorithm altogether. Four teams produced strong submissions, with the winner having a weighted Dice Similarity Coefficient of 0.910 ± 0.021 across knee bones and cartilage. Interestingly, there was no correlation between reconstruction and segmentation metrics. Further analysis showed the top four submissions were suitable for downstream biomarker analysis, largely preserving cartilage thicknesses and key bone shape features with respect to ground truth. K2S thus showed the value in considering reconstruction and image analysis as end-to-end tasks, as this leaves room for optimization while more realistically reflecting the long-term use case of tools being developed by the MR community.

Best Research Papers in the Field of Sensors, Signals, and Imaging Informatics 2021.

OBJECTIVES: In this synopsis, we identify and highlight research papers representing noteworthy developments in signals, sensors, and imaging informatics in 2021. METHODS: A broad literature search was conducted on PubMed and Scopus databases. We combined Medical Subject Heading (MeSH) terms and keywords to construct particular queries for sensors, signals, and imaging informatics. Except for the sensor section, we only consider papers that have been published in journals providing at least three articles in the query response. Using a three-point Likert scale (1=not include, 2=maybe include, and 3=include), we reviewed the titles and abstracts of all database returns. Only those papers which reached two times three points were further considered for full paper review using the same Likert scale. Again, we only considered works with two times three points and provided these for external reviews. Based on the external reviews, we selected three best papers, as it happens that the three highest ranked papers represent works from all three parts of this section: sensors, signals, and imaging informatics. RESULTS: The search for papers was executed in January 2022. After removing duplicates and conference proceedings, the query returned a set of 88, 376, and 871 papers for sensors, signals, and imaging informatics, respectively. For signals and images, we filtered out journals that had less than three papers in the query results, reducing the number of papers to 215 and 512, respectively. From this total of 815 papers, the section co-editors identified 35 candidate papers with two times three Likert points, from which nine candidate best papers were nominated after full paper assessment. At least three external reviewers then rated the remaining papers and the three best-ranked papers were selected using the composite rating of all external reviewers. By accident, these three papers represent each of the three fields of sensor, signal, and imaging informatics. They were approved by consensus of the International Medical Informatics Association (IMIA) Yearbook editorial board. Deep and machine learning techniques are still a dominant topic as well as concepts beyond the state-of-the-art. CONCLUSIONS: Sensors, signals, and imaging informatics is a dynamic field of intense research. Current research focuses on creating and processing heterogeneous sensor data towards meaningful decision support in clinical settings.

Predicting prediction: A systematic workflow to analyze factors affecting the classification performance in genomic biomarker discovery.

High throughput technologies in genomics enable the analysis of small alterations in gene expression levels. Patterns of such deviations are an important starting point for the discovery and verification of new biomarker candidates. Identifying such patterns is a challenging task that requires sophisticated machine learning approaches. Currently, there are a variety of classification models, and a common approach is to compare the performance and select the best one for a given classification problem. Since the association between the features of a data set and the performance of a particular classification method is still not fully understood, the main contribution of this work is to provide a new methodology for predicting the prediction results of different classifiers in the field of biomarker discovery. We propose here a three-steps computational workflow that includes an analysis of the data set characteristics, the calculation of the classification accuracy and, finally, the prediction of the resulting classification error. The experiments were carried out on synthetic and microarray datasets. Using this method, we showed that the predictability strongly depends on the discriminatory ability of the features, e.g., sets of genes, in two or multi-class datasets. If a dataset has a certain discriminatory ability, this method enables prediction of the classification performance before applying a learning model. Thus, our results contribute to a better understanding of the relationship between dataset characteristics and the corresponding performance of a machine learning method, and suggest the optimal classification method for a given dataset based on its discriminatory ability.

The world's first digital cell twin in cancer electrophysiology: a digital revolution in cancer research?

BACKGROUND: The introduction of functional in-silico models, in addition to in-vivo tumor models, opens up new and unlimited possibilities in cancer research and drug development. The world's first digital twin of the A549 cell's electrophysiology in the human lung adenocarcinoma, unveiled in 2021, enables the investigation and evaluation of new research hypotheses about modulating the function of ion channels in the cell membrane, which are important for better understanding cancer development and progression, as well as for developing new drugs and predicting treatments. MAIN BODY: The developed A549 in-silico model allows virtual simulations of the cell's rhythmic oscillation of the membrane potential, which can trigger the transition between cell cycle phases. It is able to predict the promotion or interruption of cell cycle progression provoked by targeted activation and inactivation of ion channels, resulting in abnormal hyper- or depolarization of the membrane potential, a potential key signal for the known cancer hallmarks. For example, model simulations of blockade of transient receptor potential cation channels (TRPC6), which are highly expressed during S-G2/M transition, result in a strong hyperpolarization of the cell's membrane potential that can suppress or bypass the depolarization required for the S-G2/M transition, allowing for possible cell cycle arrest and inhibition of mitosis. All simulated research hypotheses could be verified by experimental studies. SHORT CONCLUSION: Functional, non-phenomenological digital twins, ranging from single cells to cell-cell interactions to 3D tissue models, open new avenues for modern cancer research through "dry lab" approaches that optimally complement established in-vivo and in-vitro methods.

Supercurrent diode effect and magnetochiral anisotropy in few-layer NbSe2.

Nonreciprocal transport refers to charge transfer processes that are sensitive to the bias polarity. Until recently, nonreciprocal transport was studied only in dissipative systems, where the nonreciprocal quantity is the resistance. Recent experiments have, however, demonstrated nonreciprocal supercurrent leading to the observation of a supercurrent diode effect in Rashba superconductors. Here we report on a supercurrent diode effect in NbSe2 constrictions obtained by patterning NbSe2 flakes with both even and odd layer number. The observed rectification is a consequence of the valley-Zeeman spin-orbit interaction. We demonstrate a rectification efficiency as large as 60%, considerably larger than the efficiency of devices based on Rashba superconductors. In agreement with recent theory for superconducting transition metal dichalcogenides, we show that the effect is driven by the out-of-plane component of the magnetic field. Remarkably, we find that the effect becomes field-asymmetric in the presence of an additional in-plane field component transverse to the current direction. Supercurrent diodes offer a further degree of freedom in designing superconducting quantum electronics with the high degree of integrability offered by van der Waals materials.

Examining differential responses to the Take Care of Me trial: A latent class and moderation analysis.

Given prevalent alcohol misuse-emotional comorbidities among young adults, we developed an internet-based integrated treatment called Take Care of Me. Although the treatment had an impact on several secondary outcomes, effects were not observed for the primary outcome. Therefore, the goal of the current study was to examine heterogeneity in treatment responses. The initial RCT randomized participants to either a treatment or psychoeducational control condition. We conducted an exploratory latent class analysis to distinguish individuals based on pre-treatment risk and then used moderated regressions to examine differential treatment responses based on class membership. We found evidence for three distinct groups. Most participants fell in the "low severity" group (n = 123), followed by the "moderate severity" group (n = 57) who had a higher likelihood of endorsing a previous mental health diagnosis and treatment and higher symptom severity than the low group. The "high severity" group (n = 42) endorsed a family history of alcoholism, and the highest symptom severity and executive dysfunction. Moderated regressions revealed significant class differences in treatment responses. In the treatment condition, high severity (relative to low) participants reported higher alcohol consumption and hazardous drinking and lower quality of life at follow-up, whereas moderate severity (relative to low) individuals had lower alcohol consumption at follow-up, and lower hazardous drinking at end-of-treatment. No class differences were found for participants in the control group. Higher risk individuals in the treatment condition had poorer responses to the program. Tailoring interventions to severity may be important to examine in future research.

A Systematic Review of the Transthoracic Impedance during Cardiac Defibrillation.

For cardiac defibrillator testing and design purposes, the range and limits of the human TTI is of high interest. Potential influencing factors regarding the electronic configurations, the electrode/tissue interface and patient characteristics were identified and analyzed. A literature survey based on 71 selected articles was used to review and assess human TTI and the influencing factors found. The human TTI extended from 12 to 212 Ω in the literature selected. Excluding outliers and pediatric measurements, the mean TTI recordings ranged from 51 to 112 Ω with an average TTI of 76.7 Ω under normal distribution. The wide range of human impedance can be attributed to 12 different influencing factors, including shock waveforms and protocols, coupling devices, electrode size and pressure, electrode position, patient age, gender, body dimensions, respiration and lung volume, blood hemoglobin saturation and different pathologies. The coupling device, electrode size and electrode pressure have the greatest influence on TTI.

Cannabis Use in Adults Who Screen Positive for Attention Deficit/Hyperactivity Disorder: CANreduce 2.0 Randomized Controlled Trial Subgroup Analysis.

BACKGROUND: Prevalence rates for lifetime cannabis use and cannabis use disorder are much higher in people with attention deficit/hyperactivity disorder than in those without. CANreduce 2.0 is an intervention that is generally effective at reducing cannabis use in cannabis misusers. This self-guided web-based intervention (6-week duration) consists of modules grounded in motivational interviewing and cognitive behavioral therapy. OBJECTIVE: We aimed to evaluate whether the CANreduce 2.0 intervention affects cannabis use patterns and symptom severity in adults who screen positive for attention deficit/hyperactivity disorder more than in those who do not. METHODS: We performed a secondary analysis of data from a previous study with the inclusion criterion of cannabis use at least once weekly over the last 30 days. Adults with and without attention deficit/hyperactivity disorder (based on the Adult Attention deficit/hyperactivity disorder Self-Report screener) who were enrolled to the active intervention arms of CANreduce 2.0 were compared regarding the number of days cannabis was used in the preceding 30 days, the cannabis use disorder identification test score (CUDIT) and the severity of dependence scale score (SDS) at baseline and the 3-month follow-up. Secondary outcomes were Generalized Anxiety Disorder score, Center for Epidemiological Studies Depression scale score, retention, intervention adherence, and safety. RESULTS: Both adults with (n=94) and without (n=273) positive attention-deficit/hyperactivity disorder screening reported significantly reduced frequency (reduction in consumption days: with: mean 11.53, SD 9.28, P<.001; without: mean 8.53, SD 9.4, P<.001) and severity of cannabis use (SDS: with: mean 3.57, SD 3.65, P<.001; without: mean 2.47, SD 3.39, P<.001; CUDIT: with: mean 6.38, SD 5.96, P<.001; without: mean 5.33, SD 6.05, P<.001), as well as anxiety (with: mean 4.31, SD 4.71, P<.001; without: mean 1.84, SD 4.22, P<.001) and depression (with: mean 10.25, SD 10.54; without: mean 4.39, SD 10.22, P<.001). Those who screened positive for attention deficit/hyperactivity disorder also reported significantly decreased attention deficit/hyperactivity disorder scores (mean 4.65, SD 4.44, P<.001). There were no significant differences in change in use (P=.08), dependence (P=.95), use disorder (P=.85), attention deficit/hyperactivity disorder status (P=.84), depression (P=.84), or anxiety (P=.26) between baseline and final follow-up, dependent on positive attention-deficit/hyperactivity disorder screening. Attention deficit/hyperactivity disorder symptom severity at baseline was not associated with reduced cannabis use frequency or severity but was linked to greater reductions in depression (Spearman ρ=.33) and anxiety (Spearman ρ=.28). Individuals with positive attention deficit/hyperactivity disorder screening were significantly less likely to fill out the consumption diary (P=.02), but the association between continuous attention deficit/hyperactivity disorder symptom severity and retention (Spearman ρ=-0.10, P=.13) was nonsignificant. There also was no significant intergroup difference in the number of completed modules (with: mean 2.10, SD 2.33; without: mean 2.36, SD 2.36, P=.34), and there was no association with attention deficit/hyperactivity disorder symptom severity (Spearman ρ=-0.09; P=.43). The same was true for the rate of adverse effects (P=.33). CONCLUSIONS: Cannabis users screening positive for attention deficit/hyperactivity disorder may benefit from CANreduce 2.0 to decrease the frequency and severity of cannabis dependence and attenuate symptoms of depression and attention deficit/hyperactivity disorder-related symptoms. This web-based program's advantages include its accessibility for remote users and a personalized counselling option that may contribute to increased adherence and motivation to change among program users. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 11086185; http://www.isrctn.com/ISRCTN11086185.

Comparing a mindfulness- and CBT-based guided self-help Internet- and mobile-based intervention against a waiting list control condition as treatment for adults with frequent cannabis use: a randomized controlled trial of CANreduce 3.0.

BACKGROUND: Though Internet- and mobile-based interventions (IMIs) and mindfulness-based interventions (generally delivered in-situ) appear effective for people with substance use disorders, IMIs incorporating mindfulness are largely missing, including those targeting frequent cannabis use. METHODS: This paper details the protocol for a three-arm randomized controlled trial comparing a mindfulness-based self-help IMI (arm 1) and cognitive-behavioral therapy (CBT)-based self-help IMI (arm 2) versus being on a waiting list (arm 3) in their effectiveness reducing cannabis use in frequent cannabis users. Predictors of retention, adherence and treatment outcomes will be identified and similarities between the two active intervention arms explored. Both active interventions last six weeks and consist of eight modules designed to reduce cannabis use and common mental health symptoms. With a targeted sample size of n = 210 per treatment arm, data will be collected at baseline immediately before program use is initiated; at six weeks, immediately after program completion; and at three and six months post baseline assessment to assess the retention of any gains achieved during treatment. The primary outcome will be number of days of cannabis use over the preceding 30 days. Secondary outcomes will include further measures of cannabis use and use of other substances, changes in mental health symptoms and mindfulness, client satisfaction, intervention retention and adherence, and adverse effects. Data analysis will follow ITT principles and primarily employ (generalized) linear mixed models. DISCUSSION: This RCT will provide important insights into the effectiveness of an IMI integrating mindfulness to reduce cannabis use in frequent cannabis users. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Registry: ISRCTN14971662 ; date of registration: 09/09/2021.

Sampling Possible Reconstructions of Undersampled Acquisitions in MR Imaging With a Deep Learned Prior.

Undersampling the k-space during MR acquisitions saves time, however results in an ill-posed inversion problem, leading to an infinite set of images as possible solutions. Traditionally, this is tackled as a reconstruction problem by searching for a single "best" image out of this solution set according to some chosen regularization or prior. This approach, however, misses the possibility of other solutions and hence ignores the uncertainty in the inversion process. In this paper, we propose a method that instead returns multiple images which are possible under the acquisition model and the chosen prior to capture the uncertainty in the inversion process. To this end, we introduce a low dimensional latent space and model the posterior distribution of the latent vectors given the acquisition data in k-space, from which we can sample in the latent space and obtain the corresponding images. We use a variational autoencoder for the latent model and the Metropolis adjusted Langevin algorithm for the sampling. We evaluate our method on two datasets; with images from the Human Connectome Project and in-house measured multi-coil images. We compare to five alternative methods. Results indicate that the proposed method produces images that match the measured k-space data better than the alternatives, while showing realistic structural variability. Furthermore, in contrast to the compared methods, the proposed method yields higher uncertainty in the undersampled phase encoding direction, as expected.