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Abstract Software that employs screening prioritization through active learning (AL) has accelerated the screening process significantly by ranking an unordered set of records by their predicted relevance. However, failing to find a relevant paper might alter the findings of a systematic review, highlighting the importance of identifying elusive papers. The time to discovery (TD) measures how many records are needed to be screened to find a relevant paper, making it a helpful tool for detecting such papers. The main aim of this project was to investigate how the choice of the model and prior knowledge influence the TD values of the hard-to-find relevant papers and their rank orders. A simulation study was conducted, mimicking the screening process on a dataset containing titles, abstracts, and labels used for an already published systematic review. The results demonstrated that AL model choice, and mostly the choice of the feature extractor but not the choice of prior knowledge, significantly influenced the TD values and the rank order of the elusive relevant papers. Future research should examine the characteristics of elusive relevant papers to discover why they might take a long time to be found.

There is increasing interest in examining the development of frontal EEG power in relation to self-regulation in early childhood. However, the majority of previous studies solely focuses on the brain’s alpha rhythm and little is known about the differences between young boys and girls. The aim of the current study was therefore to gain more insight into the neural mechanisms involved in the emergence of self-regulation. The sample consisted of 442 children and data were collected at approximately 5 months, 10 months, and around 3 years of age. Latent growth curve models indicated that,while the neurobiological foundations of self-regulation are established during infancy,it is the maturation of the frontal alpha rhythm that contributes to variations in both observed and parent-reported self-regulation. In addition, it appears that boys might have a greater reliance on external regulation than girls during early childhood, as evident by higher scores of girls on both measures of self-regulation. More insight into the role of external regulators in brain maturation can help to implement interventions aimed at establishing bottom-up self-regulatory skills early in life, in order to provide the necessary foundations for the emergence of top-down self-regulatory skills in the preschool period.

During infancy and toddlerhood, parents show large individual differences in the extent to which they are able to tailor their parenting behaviors to their children's swiftly changing developmental needs. The first aim of our study was, therefore, to distinguish parenting profiles at three time points during infancy and toddlerhood (i.e., 5, 10, and 36 months) based on mothers' supportive presence, structure and limit-setting, and quality of instruction, as well as to examine the stability of profile structure and profile membership across time. The second aim was to examine how profile membership and profile transitions at each time point are associated with relevant parental, contextual, and child-specific factors. Data from 244 Dutch mother-child dyads were collected at three waves: when children were approximately 5 months (n = 203), 10 months (n = 181), and 3 years of age (n = 178). We found three types of parenting profiles at each wave: a competent profile, a sufficient profile, and a maladaptive profile. Only the competent parenting profile was found to have a stable structure across all three waves. In general, profile membership was least stable for the maladaptive profile. Results also showed that maternal agreeableness and a higher educational level increased the likelihood to exhibit a more competent parenting profile. Our findings advance our understanding of how parenting profiles might change due to children's swiftly changing needs and inform efforts to tailor parenting interventions to individual parents.

Integrating behavioral and neurophysiological measures has created new and advanced ways to understand the development of self-regulation. Electroencephalography (EEG) has been used to examine how self-regulatory processes are related to frontal alpha power during infancy and early childhood. However, findings across previous studies have been inconsistent. To address this issue, the current meta-analysis synthesized all prior literature examining associations between individual differences in self-regulation and frontal EEG alpha power (baseline and/or task). In total, 23 studies consisting of 1275 participants between 1 month and 6 years of age were included, which yielded 149 effect sizes. Findings of the three-level meta-analytic model demonstrated a non-significant overall association between self-regulation and frontal alpha power. Yet, significant moderating effects were found for self-regulation construct (emotion regulation, effortful control, executive function), self-regulation measurement (behavioral task, computer assessment, lab observation, questionnaire), and children's mean age. Self-regulation was only significantly correlated with frontal alpha power when studies focused on the executive functioning construct. Moreover, the use of behavioral tasks or questionnaires and a higher mean age of the children resulted in small but significant effect size estimates. Higher frontal alpha power values were related to higher order top-down mechanisms of self-regulation, indicating that these mechanisms might become stronger when the frontal cortex is sufficiently developed. The findings of the current meta-analysis highlight the importance of longitudinal analyses and multimethod approaches in future work to reach a more comprehensive understanding of the role of frontal EEG alpha activity in the etiology of individual differences in early self-regulation.

Abstract Background Distant relapse of breast cancer complicates management of the disease and accounts for 90% of breast cancer‐related deaths. Monocyte chemoattractant protein‐1 (MCP‐1) has critical roles in breast cancer progression and is widely accepted as a pro‐metastatic chemokine. Methods This study explored MCP‐1 expression in the primary tumour of 251 breast cancer patients. A simplified ‘histoscore’ was used to determine if each tumour had high or low expression of MCP‐1. Patient breast cancers were retrospectively staged based on available patient data. p

Abstract Cytomegalovirus (CMV) is known to alter circulating effector memory or re-expressing CD45RA+ (TemRA) T-cell numbers, but whether Epstein–Barr virus (EBV) does the same or this is amplified during a CMV and EBV co-infection is unclear. Immune cell numbers in blood of children and young, middle-aged, and senior adults (n = 336) were determined with flow cytometry, and additional multivariate linear regression, intra-group correlation, and cluster analyses were performed. Compared to non-infected controls, CMV-seropositive individuals from all age groups had more immune cell variance, and CMV+ EBV− senior adults had more late-differentiated CD4+ and CD8+ TemRA and CD4+ effector memory T-cells. EBV-seropositive children and young adults had a more equal immune cell composition than non-infected controls, and CMV− EBV+ senior adults had more intermediate/late-differentiated CD4+ TemRA and effector memory T-cells than non-infected controls. CMV and EBV co-infected young and middle-aged adults with an elevated BMI and anti-CMV antibody levels had a similar immune cell composition as senior adults, and CMV+ EBV+ middle-aged adults had more late-differentiated CD8+ TemRA, effector memory, and HLA-DR+ CD38− T-cells than CMV+ EBV− controls. This study identified changes in T-cell numbers in CMV- or EBV-seropositive individuals and that some CMV and EBV co-infected young and middle-aged adults had an aging-related T-cell phenotype.

PurposeLamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved.MethodsClinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated.ResultsMicrodeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated.ConclusionsThis study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.

IntroductionThis study examines the performance of active learning-aided systematic reviews using a deep learning-based model compared to traditional machine learning approaches, and explores the potential benefits of model-switching strategies.MethodsComprising four parts, the study: 1) analyzes the performance and stability of active learning-aided systematic review; 2) implements a convolutional neural network classifier; 3) compares classifier and feature extractor performance; and 4) investigates the impact of model-switching strategies on review performance.ResultsLighter models perform well in early simulation stages, while other models show increased performance in later stages. Model-switching strategies generally improve performance compared to using the default classification model alone.DiscussionThe study's findings support the use of model-switching strategies in active learning-based systematic review workflows. It is advised to begin the review with a light model, such as Naïve Bayes or logistic regression, and switch to a heavier classification model based on a heuristic rule when needed.

Background An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11–18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13–0.25), maintenance OCS use (OR 0.75, 95% CI 0.61–0.92) and dose (mean −3.93 mg·day−1, 95% CI −5.24–2.62 mg·day−1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

Objectives The primary aim was to gain insight into the growth of the aortic root in children and young adults with Marfan syndrome (MFS). Furthermore, we aimed to identify a clinical profile of patients with MFS who require an aortic root replacement at a young age with specific interest in age, sex, height and fibrillin-1 (FBN1) genotype.Methods Aortic root dimensions of 97 patients with MFS between 0 year and 20 years and 30 controls were serially assessed with echocardiography. Trends were analysed using a linear mixed-effect model. Additionally, including only patients with MFS, we allowed trends to differ by sex, aortic root replacement and type of FBN1 mutation.Results Average aortic root dilatation in patients with MFS became more pronounced after the age of 8 years. In the MFS cohort, male patients had a significantly greater aortic root diameter than female patients, which was in close relationship with patient height. There was no difference in aortic root growth between children with dominant negative (DN) or haploinsufficient FBN1 mutations. However, DN-FBN1 variants resulting in loss of cysteine content were associated with a more severe phenotype. Eleven children needed an aortic root replacement. Compared with patients with MFS without aortic root surgery, these children had a significantly larger aortic root diameter from an early age.Conclusions This study provides clinically useful longitudinal growth charts on aortic root growth in children and young adults with MFS. Children requiring prophylactic aortic root replacement during childhood can be identified at a young age. Our growth charts can help clinicians in decision making with regard to follow-up and prophylactic therapy. Loss of cysteine content in the FBN1 protein was associated with larger aortic root dimensions.

A fracture-related infection (FRI) is a serious complication that can occur after surgical fixation of bone fractures. Affected patients may encounter delayed healing and functional limitations. Although it is well established that Staphylococcus aureus (S. aureus) is the main causative pathogen of an FRI, the pathophysiology of an S. aureus-induced FRI is not well characterised over time. Therefore, an experimental study in mice comparing S. aureus-inoculated and non-inoculated groups was performed that particularly focused on staphylococcal abscess communities (SACs) and host cellular response. C57Bl/6N female mice received a double osteotomy of the femur, which was stabilised using a titanium 6-hole MouseFix locking plate and four screws. Animals were either S. aureus-inoculated or non-inoculated and euthanised between 1 and 28 d post-surgery. Histopathological evaluation showed normal bone healing for non-inoculated mice, whereas inoculated mice had no fracture consolidation and severe osteolysis. Within the bone marrow of inoculated mice, SACs were observed from 7 d, which increased in size and number over time. A fibrin pseudocapsule enclosed the SACs, which were surrounded by many Ly6G+ neutrophils with some Ly6C+ monocytes and F4/80+ macrophages, the majority of which were viable. The abscesses were encapsulated by fibrin(ogen), collagen and myofibroblasts, with regulatory T cells and M2 macrophages at the periphery. Only bone marrow monocytes and neutrophils of inoculated mice displayed functional suppression of T cells, indicative of myeloid-derived suppressor cells. The present study revealed that an FRI in mice is persistent over time and associated with osteolysis, SAC formation and an immunosuppressive environment.

S. aureus infection of bone is difficult to eradicate due to its ability to colonize the osteocyte-lacuno-canalicular network (OLCN), rendering it resistant to standard-of-care (SOC) antibiotics. To overcome this, we proposed two bone-targeted bisphosphonate-conjugated antibiotics (BCA): bisphosphonate-conjugated sitafloxacin (BCS) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS). Initial studies demonstrated that the BCA kills S. aureus in vitro. Here we demonstrate the in vivo efficacy of BCS and HBCS versus bisphosphonate, sitafloxacin, and vancomycin in mice with implant-associated osteomyelitis. Longitudinal bioluminescent imaging (BLI) confirmed the hypothesized “target and release”-type kinetics of BCS and HBCS. Micro-CT of the infected tibiae demonstrated that HBCS significantly inhibited peri-implant osteolysis versus placebo and free sitafloxacin (p < 0.05), which was not seen with the corresponding non-antibiotic-conjugated bisphosphonate control. TRAP-stained histology confirmed that HBCS significantly reduced peri-implant osteoclast numbers versus placebo and free sitafloxacin controls (p < 0.05). To confirm S. aureus killing, we compared the morphology of S. aureus autolysis within in vitro biofilm and infected tibiae via transmission electron microscopy (TEM). Live bacteria in vitro and in vivo presented as dense cocci ~1 μm in diameter. In vitro evidence of autolysis presented remnant cell walls of dead bacteria or “ghosts” and degenerating (non-dense) bacteria. These features of autolyzed bacteria were also present among the colonizing S. aureus within OLCN of infected tibiae from placebo-, vancomycin-, and sitafloxacin-treated mice, similar to placebo. However, most of the bacteria within OLCN of infected tibiae from BCA-treated mice were less dense and contained small vacuoles and holes >100 nm. Histomorphometry of the bacteria within the OLCN demonstrated that BCA significantly increased their diameter versus placebo and free antibiotic controls (p < 0.05). As these abnormal features are consistent with antibiotic-induced vacuolization, bacterial swelling, and necrotic phenotype, we interpret these findings to be the initial evidence of BCA-induced killing of S. aureus within the OLCN of infected bone. Collectively, these results support the bone targeting strategy of BCA to overcome the biodistribution limits of SOC antibiotics and warrant future studies to confirm the novel TEM phenotypes of bacteria within OLCN of S. aureus-infected bone of animals treated with BCS and HBCS.

BackgroundIncreasingly popular mobile health (mHealth) programs have been proposed to promote better utilization of maternal, newborn and child health services. However, women who lack access to a mobile phone are often left out of both mHealth programs and research. In this study, we determine whether household mobile phone ownership is an independent predictor of utilization of maternal and newborn health services in Timor-Leste.MethodsThe study included 581 women aged 15-49 years with a child under the age of two years from the districts of Manufahi and Ainaro in Timor-Leste. Participants were interviewed via a structured survey of knowledge, practices, and coverage of maternal and child health services, with additional questions related to ownership and utilization of mobile phones. Mobile phone ownership was the exposure variable, and the dependent variables included having at least four antenatal care visits, skilled birth attendance, health facility delivery, a postnatal checkup within 24 h, and a neonatal checkup within 24 h for their youngest child. Logistic regression models were applied to assess for associations.ResultsSixty-seven percent of women reported having at least one mobile phone in the family. Women who had a mobile phone were significantly more likely to be of higher socioeconomic status and to utilize maternal and newborn health services. However, after adjusting socioeconomic factors, household mobile phone ownership was not independently associated with any of the dependent variables.ConclusionEvaluations of the effects of mHealth programs on health in a population need to consider the likelihood of socioeconomic differentials indicated by mobile phone ownership.

Abstract Background Immense improvements in sequencing technologies enable producing large amounts of high throughput and cost effective next-generation sequencing (NGS) data. This data needs to be processed efficiently for further downstream analyses. Computing systems need this large amounts of data closer to the processor (with low latency) for fast and efficient processing. However, existing workflows depend heavily on disk storage and access, to process this data incurs huge disk I/O overheads. Previously, due to the cost, volatility and other physical constraints of DRAM memory, it was not feasible to place large amounts of working data sets in memory. However, recent developments in storage-class memory and non-volatile memory technologies have enabled computing systems to place huge data in memory to process it directly from memory to avoid disk I/O bottlenecks. To exploit the benefits of such memory systems efficiently, proper formatted data placement in memory and its high throughput access is necessary by avoiding (de)-serialization and copy overheads in between processes. For this purpose, we use the newly developed Apache Arrow, a cross-language development framework that provides language-independent columnar in-memory data format for efficient in-memory big data analytics. This allows genomics applications developed in different programming languages to communicate in-memory without having to access disk storage and avoiding (de)-serialization and copy overheads. Implementation We integrate Apache Arrow in-memory based Sequence Alignment/Map (SAM) format and its shared memory objects store library in widely used genomics high throughput data processing applications like BWA-MEM, Picard and GATK to allow in-memory communication between these applications. In addition, this also allows us to exploit the cache locality of tabular data and parallel processing capabilities through shared memory objects. Results Our implementation shows that adopting in-memory SAM representation in genomics high throughput data processing applications results in better system resource utilization, low number of memory accesses due to high cache locality exploitation and parallel scalability due to shared memory objects. Our implementation focuses on the GATK best practices recommended workflows for germline analysis on whole genome sequencing (WGS) and whole exome sequencing (WES) data sets. We compare a number of existing in-memory data placing and sharing techniques like ramDisk and Unix pipes to show how columnar in-memory data representation outperforms both. We achieve a speedup of 4.85x and 4.76x for WGS and WES data, respectively, in overall execution time of variant calling workflows. Similarly, a speedup of 1.45x and 1.27x for these data sets, respectively, is achieved, as compared to the second fastest workflow. In some individual tools, particularly in sorting, duplicates removal and base quality score recalibration the speedup is even more promising. Availability The code and scripts used in our experiments are available in both container and repository form at: https://github.com/abs-tudelft/ArrowSAM .

High-level feature maps of Convolutional Neural Networks are computed by reusing their corresponding low-level feature maps, which brings into full play feature reuse to improve the computational efficiency. This form of feature reuse is referred to as feature reuse between convolutional layers. The second type of feature reuse is referred to as feature reuse within the convolution, where the channels of the output feature maps of the convolution are computed by reusing the same channels of the input feature maps, which results in an approximation of the channels of the output feature maps. To compute them accurately, we need specialized input feature maps for every channel of the output feature maps. In this paper, we first discuss the approximation problem introduced by full feature reuse within the convolution and then propose a new feature reuse scheme called Reducing Approximation of channels by Reducing Feature reuse (REAF). The paper also shows that group convolution is a special case of our REAF scheme and we analyze the advantage of REAF compared to such group convolution. Moreover, we develop the REAF+ scheme and integrate it with group convolution-based models. Compared with baselines, experiments on image classification demonstrate the effectiveness of our REAF and REAF+ schemes. Under the given computational complexity budget, the Top-1 accuracy of REAF-ResNet50 and REAF+-MobileNetV2 on ImageNet will increase by 0.37% and 0.69% respectively. The code and pre-trained models will be publicly available.

Systems for computer based assessment as well as learning management systems offer a number of innovative closed question types, which are used more and more in higher education. These closed questions are used in computer based summative exams, in diagnostic tests, and in computer based activating learning material. Guidelines focusing on the design of closed questions were formulated. The use of these guidelines was evaluated in fifteen case studies in higher education. The conclusion is drawn that guidelines are useful, but should be applied in a broad approach that is best to be supported by educational technologists.

Loss-of-function mutations in the recycling endosomal (Na+,K+)/H+ exchanger gene SLC9A6/NHE6 result in overacidification and dysfunction of endosomal-lysosomal compartments, and cause a neurodevelopmental and degenerative form of X-linked intellectual disability called Christianson Syndrome (CS). However, knowledge of the disease heterogeneity of CS is limited. Here, we describe the clinical features and underlying molecular and cellular mechanisms associated with a CS patient carrying a de novo missense variant (p.Gly218Arg; G218R) of a conserved residue in its ion translocation domain that results in a potential gain-of-function. The patient manifested several core symptoms typical of CS, including pronounced cognitive impairment, mutism, epilepsy, ataxia and microcephaly; however, deterioration of motor function often observed after the first decade of life in CS children with total loss of SLC9A6/NHE6 function was not evident. In transfected non-neuronal cells, complex glycosylation and half-life of the G218R were significantly decreased compared to the wild-type transporter. This correlated with elevated ubiquitination and partial proteasomal-mediated proteolysis of G218R. However, a major fraction was delivered to the plasma membrane and endocytic pathways. Compared to wild-type, G218R-containing endosomes were atypically alkaline and showed impaired uptake of recycling endosomal cargo. Moreover, instead of accumulating in recycling endosomes, G218R was redirected to multivesicular bodies/late endosomes and ejected extracellularly in exosomes rather than progressing to lysosomes for degradation. Attenuated acidification and trafficking of G218R-containing endosomes were also observed in transfected hippocampal neurons, and correlated with diminished dendritic branching and density of mature mushroom-shaped spines and increased appearance of filopodia-like protrusions. Collectively, these findings expand our understanding of the genetic diversity of CS and further elucidate a critical role for SLC9A6/NHE6 in fine-tuning recycling endosomal pH and cargo trafficking, processes crucial for the maintenance of neuronal polarity and mature synaptic structures.

Abstract Selenium deficiency during pregnancy can impair fetal development and predispose offspring to thyroid dysfunction. Given that key selenoproteins are highly expressed in the kidney and that poor thyroid health can lead to kidney disease, it is likely that kidney function may be impaired in offspring of selenium‐deficient mothers. This study utilized a mouse model of maternal selenium deficiency to investigate kidney protein glycation, mitochondrial adaptations, and urinary excretion in offspring. Female C57BL/6 mice were fed control (>190 µg selenium/kg) or low selenium (

Self-regulation is the ability to monitor and modulate emotions, behaviour, and cognition in order to adapt to changing circumstances. Developing adequate self-regulation is associated with better social coping and higher educational achievement later in life; poor self-regulation has been linked to a variety of detrimental developmental outcomes. Here, we focus on the development of neurocognitive processes essential for self-regulation. We outline a conceptual framework emphasizing that this is inherently an integrated, dynamic process involving interactions between brain maturation, child characteristics (genetic makeup, temperament, and pre‐ and perinatal factors) and environmental factors (family characteristics, parents and siblings, peers, and broader societal influences including media development). We introduce the Consortium of Individual Development (CID), which combines a series of integrated large-scale, multi-modal, longitudinal studies to take essential steps towards the ultimate goal of understanding and supporting this process.

Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells. Subsequently, it was shown that SAC-exposed human CD11blow/− myeloid cells or SAC-exposed murine CD11b+ Gr-1+ cells were immunosuppressive mainly by reducing absolute CD4+ and CD8α+ T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an S. aureus bone infection also strongly reduced CD4+ and CD8α+ T cell numbers. Using protein biomarker analysis and an immunoassay, we detected in SAC–bone marrow co-cultures high levels of GM-CSF, IL-6, VEGF, IL-1β, TNFα, IL-10, and TGF-β. Furthermore, SAC-exposed neutrophils expressed Arg-1 and SAC-exposed monocytes expressed Arg-1 and iNOS, as shown via immunofluorescent stains. Overall, this study showed that SACs cause MDSC expansion from bone marrow cells and identified possible mediators to target as an additional strategy for treating chronic S. aureus infections.

Mixtures of sodium bentonite and crushed rock are being examined as components of the engineered barrier system in a geologic repository of high-level nuclear waste. Laboratory experiments were performed to determine the thermal and unsaturated hydraulic properties of bentonite/crushed diorite mixtures. Water-retention curves were conventionally obtained from pressure cell and evaporation experiments. In addition, transient data from heating and gas injection experiments on laboratory columns were analyzed using inverse modeling techniques. Measured pressures, temperatures, and drained-water volumes were jointly inverted to estimate absolute permeability, thermal conductivity, specific heat, and capillary strength parameters. Simultaneous matching of all available data specifically the gas breakthrough at the top of the column proved difficult, pointing towards aspects of the experimental design and the conceptual model that need to be refined. The analysis of sensitivity coefficients and the correlation structure of the parameters revealed the importance of accurately capturing coupled thermal hydrological processes within the column as well as the details of the experimental apparatus, such as heat losses and storage of water and gas in the measuring burette. The parameters estimated using different experimental and analytical procedures were consistent with one another, providing backfill material properties useful for the simulation of gas- and heat-generating nuclear waste repositories.