Predicting the impact and duration of persistent and mobile organic compounds in groundwater systems using a contaminant mass discharge approach.

This study investigated methods for predicting the duration and impact on groundwater quality from persistent and mobile organic compounds (PMOCs) at a drinking water well field affected by multiple contaminant sources. The fungicide metabolite N,N-dimethylsulfamide (DMS), which frequently occurs above the Danish groundwater quality criterion (0.1 µg/L), was used as an example. By combining contaminant mass discharge (CMD) estimations, modeling, and groundwater dating, a number of important discoveries were made. The current center of contaminant mass was located near the source area. The CMD at the well field was predicted to peak in 2040, and an effect from the investigated sources on groundwater quality could be expected until the end of the 21st century. A discrepancy in the current CMD at the well field and the estimated arrival time from the studied source area suggested an additional pesticide source, which has not yet been thoroughly investigated. The presence of the unknown source was supported by model simulations, producing an improved mass balance after inclusion of a contaminant source closer to the well field. The approach applied here was capable of predicting the duration and impact of DMS contamination at a well field at catchment scale. It furthermore shows potential for identification and quantification of the contribution from individual sources, and is also applicable for other PMOCs. Predicting the duration of the release and impact of contaminant sources on abstraction wells is highly valuable for water resources management and authorities responsible for contaminant risk assessment, remediation, and long-term planning at water utilities.

Long-term leaching through clayey till of N,N-dimethylsulfamide, a Persistent and Mobile Organic Compound (PMOC).

Environmental pollution with Persistent and Mobile Organic Compounds (PMOC) from anthropogenic activities is an increasing cause for concern. These compounds are readily leached to groundwater aquifers and are likely to resist degradation, putting pressure on groundwater resources. Pesticides can form PMOCs upon degradation in the environment. The PMOC N,N-dimethylsulfamide (DMS) was the most frequently detected pesticide metabolite in Danish drinking water wells in 2020, although the pesticidal use of the last parent compound (tolylfluanid) ended in 2007. This study aimed to improve the understanding of the leaching of the PMOC DMS from clayey tills by combining a review of compound properties, sources and use, comprehensive field observations and numerical flow and solute transport modeling. The modeling explored the mechanisms of DMS retention during vertical transport in clayey till and the fingerprint in the underlying aquifer. The results were supported by detailed field observations at an agricultural site with strawberry production. Porewater samples were collected from clayey till to a depth of 12 m bgs by a custom designed installation method of suction cups. Groundwater sampling (249 samples) was designed to provide vertical concentration profiles at various distances from the presumed sources. The review of properties showed that the parent compounds and intermediates degrade quickly in topsoil, releasing the highly persistent and mobile DMS. We tested the effect of fractures on transport with different hydraulic apertures and a scenario without fractures by numerical modeling. The results showed that the presence of fractures can smooth the breakthrough curve below the clayey till, leading to faster breakthrough, lower maximum concentration, and several decades of prolonged leaching in simulations with the largest aperture (20 µm). The fracture-matrix interaction is a possible explanation for the observed delay of leaching from clayey till. The vertical concentration profiles in groundwater were used for identifying the sources at the field site and testing source strengths. Assigning one point source (200 µg/L) and two diffuse sources (40-50 µg/L) to the model produced vertical concentration profiles that compared well with observed field data in clayey till and the aquifer. All results were integrated into a conceptual model for the environmental fate of PMOCs in soil and groundwater. The findings of this study imply that the presence of fractures in clayey till should be considered in conceptual site models, since they can substantially prolong the leaching of PMOCs to groundwater. The integration of comprehensive field investigations and numerical modeling is key to understand the fate of PMOCs in complex field systems with different source types. Together with widespread occurrences of PMOCs in groundwater systems, the results highlight the need for improved approval procedures for pesticides and biocides which considers their persistent and mobile metabolites.

Phase IIa Clinical Biomarker Trial of Dietary Arginine Restriction and Aspirin in Colorectal Cancer Patients.

After potentially curative treatment, colorectal cancer (CRC) patients remain at high risk for recurrence, second primary CRC, and high-risk adenomas. In combination with existing data, our previous findings provide a rationale for reducing tissue polyamines as tertiary prevention in non-metastatic CRC patients. The goal of this study was to demonstrate rectal tissue polyamine reduction in optimally treated stage I-III CRC patients after intervention with daily oral aspirin + dietary arginine restriction. A single-institution phase IIa clinical trial was conducted. Patients were treated with aspirin 325 mg/day and an individualized dietary regimen designed to reduce arginine intake by ≥30% over a 12-week study period. Dietary intake, endoscopy with rectal biopsies, and phlebotomy were performed pre- and post-intervention. The primary endpoint was to demonstrate ≥50% decrease in rectal tissue putrescine levels from baseline as a measure of polyamine reduction in the target tissue. Twenty eligible patients completed the study. After study intervention, mean dietary arginine intake decreased from 3.7 g/day ± 1.3 SD to 2.6 g/day ± 1.2 SD (29.7% decrease, p < 0.02 by Sign test). Mean plasma arginine levels decreased from 46.0 ng/mL ± 31.5 SD at baseline to 35 ng/mL ± 21.7 SD (p < 0.001). Rectal tissue putrescine levels were 0.90 nMol/mg-protein pre-intervention and 0.99 nMol/mg-protein post-intervention (p < 0.64, NS). No significant differences were observed for the other tissue polyamines investigated: spermidine (p < 0.13), spermine (p < 0.21), spermidine:spermine ratio (p < 0.71). Among CRC survivors, treatment with daily oral aspirin and an individualized dietary arginine restriction intervention resulted in lower calculated dietary arginine intake and plasma arginine levels but did not affect rectal tissue polyamine levels.

Effective treatment of highest instability in a subacute fragility fracture of the pelvis (FFP IV) using a cement augmented transsacral screw only.

The highest instability in fragility fractures of the pelvis (FFP) is noted in presence of H-, U-type sacral fractures. Suggested surgical treatment options include uni- or bilateral sacroiliac or transsacral screw fixation at different levels or in combination, as well as lumbopelvic and bilateral triangular lumbopelvic stabilization. However, distinct treatment recommendations for this subset of injuries are scarce. We present a case sustaining rapid FFP crescendo instability following initial conservative treatment of a FFP type II injury resulting in a U-type spinopelvic dissociation. Fixation using one percutaneous cement augmented transsacral S1 screw resulted in perpetual clinical improvements in pain and mobility in presence of radiologic fracture consolidation.

The nucleus pulposus microenvironment in the intervertebral disc: the fountain of youth?

The intervertebral disc (IVD) is a complex tissue, and its degeneration remains a problem for patients, without significant improvement in treatment strategies. This mostly age-related disease predominantly affects the nucleus pulposus (NP), the central region of the IVD. The NP tissue, and especially its microenvironment, exhibit changes that may be involved at the outset or affect the progression of IVD pathology. The NP tissue microenvironment is unique and can be defined by a variety of specific factors and components characteristic of its physiology and function. NP progenitor cell interactions with their surrounding microenvironment may be a key factor for the regulation of cellular metabolism, phenotype, and stemness. Recently, celltransplantation approaches have been investigated for the treatment of degenerative disc disease, highlighting the need to better understand if and how transplanted cells can give rise to healthy NP tissue. Hence, understanding all the components of the NP microenvironment seems to be critical to better gauge the success and outcomes of approaches for tissue engineering and future clinical applications. Knowledge about the components of the NP microenvironment, how NP progenitor cells interact with them, and how changes in their surroundings can alter their function is summarised. Recent discoveries in NP tissue engineering linked to the microenvironment are also reviewed, meaning how crosstalk within the microenvironment can be adjusted to promote NP regeneration. Associated clinical problems are also considered, connecting bench-to-bedside in the context of IVD degeneration.

Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips.

In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.

Anterior column reconstruction of the thoracolumbar spine with a new modular PEEK vertebral body replacement device: retrospective clinical and radiologic cohort analysis of 48 cases with 1.7-years follow-up.

PURPOSE: To evaluate whether a new PEEK vertebral body replacement can maintain the sagittal alignment as an anterior column reconstruction device in thoracic and lumbar spinal defects due to trauma or tumor. METHODS: Retrospective review of 48 patients who underwent a corpectomy between T5 and L5 due to trauma or tumor and were stabilized with the new PEEK vertebral body replacement, between 2013 and 2017. We excluded patients who underwent a corpectomy for infection or degenerative disease and patients without complete follow-up in our institution. The primary outcome was the bi-segmental kyphotic angle (BKA). Secondary outcomes were the assessment of pedicle screw loosening, cage height, and subsidence or tilting of the cage. The clinical outcomes were assessed through the COMI-Score, EuroQol-5D, and Karnofsky indexes. Bony fusion and complications were registered. RESULTS: After the surgery BKA decreased by 12.1° (p < 0.001). At the end of the follow-up, we observed a mean loss of reduction of 1.6° (p = 0.002). This was accompanied by an increase in subsidence of 2.1 mm (p < 0.001) and mean tilting of the cage of 1.4° (p = 0.003). The height of the cage and other parameters did not experience any changes. Clinically, the COMI-Score (p = 0.02) and the EuroQol-5D Index (p = 0.012) showed significant improvement, same as Karnofsky-Index (p = 0.015) at final follow-up. The fusion rate according to Bridwell was 92.1%. The 2% late complications were related to implant malpositioning. CONCLUSION: The new PEEK expandable vertebral body replacement is effective and safe in thoracic and lumbar anterior column reconstruction in tumor and trauma diseases.

A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index.

Obesity is associated with risk of colorectal adenoma (CRA) and colorectal cancer. The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6Ser235/S6Ser235 ratio in polyps. We hypothesized that metformin would affect colorectal tissue S6Ser235 among obese patients with recent history of CRA. A phase IIa clinical biomarker trial was conducted via the U.S. National Cancer Institute-Chemoprevention Consortium. Nondiabetic, obese subjects (BMI ≥30) ages 35 to 80 with recent history of CRA were included. Subjects received 12 weeks of oral metformin 1,000 mg twice every day. Rectal mucosa biopsies were obtained at baseline and end-of-treatment (EOT) endoscopy. Tissue S6Ser235 and Ki-67 immunostaining were analyzed in a blinded fashion using Histo score (Hscore) analysis. Among 32 eligible subjects, the mean baseline BMI was 34.9. Comparing EOT to baseline tissue S6Ser235 by IHC, no significant differences were observed. Mean (SD) Hscore at baseline was 1.1 (0.57) and 1.1 (0.51) at EOT; median Hscore change was 0.034 (P = 0.77). Similarly, Ki-67 levels were unaffected by the intervention. The adverse events were consistent with metformin's known side-effect profile. Among obese patients with CRA, 12 weeks of oral metformin does not reduce rectal mucosa pS6 or Ki-67 levels. Further research is needed to determine what effects metformin has on the target tissue of origin as metformin continues to be pursued as a colorectal cancer chemopreventive agent.

Multitechnique Determination of Halogens in Soil after Selective Volatilization Using Microwave-Induced Combustion.

A method for digestion of soils with high inorganic matter content (ranging from 50 to 92%) by microwave-induced combustion (MIC) is proposed for the first time for further halogens (F, Cl, Br, and I) determination by ion chromatography (IC) and also by inductively coupled plasma mass spectrometry (ICP-MS). Microcrystalline cellulose (100-500 mg), used as a combustion aid, was mixed with sample and water or NH4OH solutions (10-100 mmol L-1) were investigated for analytes absorption. The use of cellulose (400 mg) was mandatory to volatilize the halogens from soils with high inorganic matter. It was possible to use diluted absorbing solutions (up to 100 mmol L-1 NH4OH) for halogens retention, providing limits of quantification in the range of 0.06 (I) to 60 (Cl) µg g-1. Accuracy was evaluated using certified reference materials (CRMs), spiked samples, and pyrohydrolysis method. Recoveries for halogens after spiked samples were in the range of 94 to 103% and the results after digestion of CRMs by MIC were in agreement better than 95% to certified values. Blanks were low, relative standard deviation was below 8% for all soils and no statistical difference was observed for results by pyrohydrolysis and MIC methods showing the feasibility of the proposed method for further halogens determination in soil samples.

[Resection at symptomatic cam impingement. Use of a minimally invasive antero-lateral approach]. / Offene Offsetkorrektur bei symptomatischem Cam-Impingement. Therapie über einen minimalinvasiven anterolateralen Zugang.

BACKGROUND: Surgical treatment of femoroacetabular impingement (FAI) is nowadays achieved by either open surgical hip dislocation or hip arthroscopy. However, drawbacks of both procedures include the invasiveness of the open procedure and a high learning curve to successfully perform arthroscopic treatment. In our institution, we established a minimally invasive, arthroscopically assisted, antero-lateral approach for the correction of cam type FAI. OBJECTIVES: The goal of the study was to describe the surgical technique and highlight the short-term clinical outcome in a consecutive series of patients operated between 2011 and 2014 in our institution. MATERIALS AND METHODS: In total, 77 patients were included in this study. The patients were allocated to two groups (Toennis = 0: Group I; Toennis 1 and 2: Group II). Clinical and radiographic follow up was obtained at 6 and 12 weeks postoperatively. Clinical outcome was assessed using the Hip-Outcome-Score. RESULTS: The mean age of patients in Group I was 25 (16-48) years and in Group II 38 (17-50) years respectively. Internal rotation (IR) in 90° flexion increased by 11 degrees from pre- to postoperatively in Group I (p < 0.001) and by 14° in Group II (p < 0.001). The Hip Outcome Score revealed the ability to perform sports with reduced pain at three months follow up. Subjectively, all patients benefitted in terms of pain and hip function in both groups (p < 0.001). There were no complications with long-term morbidity during the perioperative course. CONCLUSION: Arthroscopically assisted cam resection using a minimally invasive anterolateral approach is a safe technique for the treatment of FAI. At short term follow up, nearly all operated patients seem to benefit in terms of pain and hip function. The influence of progression of osteoarthritis still has to be shown.

Grb10 is involved in BCR-ABL-positive leukemia in mice.

The SH2-containing adaptor protein Grb10 was first identified in a yeast screen as a new binding partner for BCR-ABL and associates with BCR-ABL in a tyrosine-dependent manner. However, its function in BCR-ABL-mediated leukemogenesis in vivo is still unknown. Here we describe an important role of Grb10 in BCR-ABL-induced leukemia by using a versatile system for efficient oncogene expression and simultaneous Grb10 knockdown from a single vector. Primary bone marrow (BM) cells coexpressing Grb10-miR/BCR-ABL showed a significant decrease in colony formation and cell cycle progression. Transplantation of Grb10miR/BCR-ABL- or control-miR/BCR-ABL- transduced BM leads to a CML/B-ALL-like phenotype with significantly delayed disease onset and progression resulting in prolonged overall survival in Grb10-miR-transplanted mice. Methylcellulose experiments exhibit additive effects of imatinib treatment and Grb10 knockdown. Cell cycle analysis suggests an anti-proliferative effect of Grb10 knockdown in BCR-ABL(+) primary BM cells. However, Grb10 abrogation was not capable of completely abolishing the BCR-ABL-induced disease. Our findings were confirmed in the human BCR-ABL(+) cell line K562, where we demonstrate reduced viability, cell cycle progression and induction of apoptosis by stable Grb10 microRNA expression. Taken together, our results suggest that Grb10 knockdown in vivo leads to impaired proliferation, longer survival and reduced colony formation, suggesting an important role of Grb10 in BCR-ABL-mediated leukemogenesis.

Measurement bias detection through Bayesian factor analysis.

Measurement bias has been defined as a violation of measurement invariance. Potential violators-variables that possibly violate measurement invariance-can be investigated through restricted factor analysis (RFA). The purpose of the present paper is to investigate a Bayesian approach to estimate RFA models with interaction effects, in order to detect uniform and nonuniform measurement bias. Because modeling nonuniform bias requires an interaction term, it is more complicated than modeling uniform bias. The Bayesian approach seems especially suited for such complex models. In a simulation study we vary the type of bias (uniform, nonuniform), the type of violator (observed continuous, observed dichotomous, latent continuous), and the correlation between the trait and the violator (0.0, 0.5). For each condition, 100 sets of data are generated and analyzed. We examine the accuracy of the parameter estimates and the performance of two bias detection procedures, based on the DIC fit statistic, in Bayesian RFA. Results show that the accuracy of the estimated parameters is satisfactory. Bias detection rates are high in all conditions with an observed violator, and still satisfactory in all other conditions.

Does Radar Technology Support the Diagnosis of Pneumothorax? PneumoScan-A Diagnostic Point-of-Care Tool.

Background. A nonrecognized pneumothorax (PTX) may become a life-threatening tension PTX. A reliable point-of-care diagnostic tool could help in reduce this risk. For this purpose, we investigated the feasibility of the use of the PneumoScan, an innovative device based on micropower impulse radar (MIR). Patients and Methods. addition to a standard diagnostic protocol including clinical examination, chest X-ray (CXR), and computed tomography (CT), 24 consecutive patients with chest trauma underwent PneumoScan testing in the shock trauma room to exclude a PTX. Results. The application of the PneumoScan was simple, quick, and reliable without functional disorder. Clinical examination and CXR each revealed one and PneumoScan three out of altogether four PTXs (sensitivity 75%, specificity 100%, positive predictive value 100%, and negative predictive value 95%). The undetected PTX did not require intervention. Conclusion. The PneumoScan as a point-of-care device offers additional diagnostic value in patient management following chest trauma. Further studies with more patients have to be performed to evaluate the diagnostic accuracy of the device.

What is the incidence of intracranial bleeding in patients with mild traumatic brain injury? A retrospective study in 3088 Canadian CT head rule patients.

OBJECTIVE: Only limited data exists in terms of the incidence of intracranial bleeding (ICB) in patients with mild traumatic brain injury (MTBI). METHODS: We retrospectively identified 3088 patients (mean age 41 range (7-99) years) presenting with isolated MTBI and GCS 14-15 at our Emergency Department who had undergone cranial CT (CCT) between 2002 and 2011. Indication for CCT was according to the "Canadian CT head rules." Patients with ICB were either submitted for neurosurgical treatment or kept under surveillance for at least 24 hours. Pearson's correlation coefficient was used to correlate the incidence of ICB with age, gender, or intake of coumarins, platelet aggregation inhibitors, or heparins. RESULTS: 149 patients (4.8%) had ICB on CCT. No patient with ICB died or deteriorated neurologically. The incidence of ICB increased with age and intake of anticoagulants without clinically relevant correlation (R = 0.11; P < 0.001; R = -0.06; P < 0.001). CONCLUSION: Our data show an incidence of 4.8% for ICB after MTBI. However, neurological deterioration after MTBI seems to be rare, and the need for neurosurgical intervention is only required in selected cases. The general need for CCT in patients after MTBI is therefore questionable, and clinical surveillance may be sufficient when CCT is not available.

Can handheld micropower impulse radar technology be used to detect pneumothorax? Initial experience in a European trauma centre.

BACKGROUND: Pneumothoraces are a common injury pattern in emergency medicine. Rapid and safe identification can reduce morbidity and mortality. A new handheld, battery powered device, the Pneumoscan (CE 561036, PneumoSonics Inc., Cleveland, OH, USA), using micropower impulse radar (MIR) technology, has recently been introduced in Europe for the rapid and reliable detection of PTX. However, this technology has not yet been tested in trauma patients. This is the first quality control evaluation to report on emergency room performance of a new device used in the trauma setting. MATERIAL AND METHODS: This study was performed at a Level I trauma centre in Switzerland. All patients with thoracic trauma and undergoing chest X-ray and CT-scan were eligible for the study. Readings were performed before the chest X-ray and CT scan. The patients had eight lung fields tested (four on each side). All readings with the Pneumoscan were performed by two junior residents in our department who had previously received an instructional tutorial of 15min. The qualitative MIR results were blinded, and stored on the device. We then compared the results of the MIR to those of the clinical examination, chest X-ray and CT-scan. RESULTS: 50 patients were included, with a mean age of 46 (SD 17) years. Seven patients presented with PTX diagnosed by CT; six of these were detected by Pneumoscan, leading to an overall sensitivity of 85.7 (95% confidence interval 42.1-99.6)%. Only two of seven PTX were found during clinical examination and on chest X-ray (sensitivity 28.6 (95% CI 3.7-71.0)%). Of the remaining 43 of 50 patients without PTX, one false-positive PTX was found by the Pneumoscan, resulting in a specificity of 97.7 (95% CI 87.7-99.9)%. DISCUSSION: The Pneumoscan is an easy to use handheld technology with reliable results. In this series, the sensitivity to detect a PTX by the Pneumoscan was higher than by clinical examination and chest X-ray. Further studies with higher case numbers and a prospective study design are needed to confirm our findings.

Quantitative T2 mapping of the patella at 3.0T is sensitive to early cartilage degeneration, but also to loading of the knee.

OBJECTIVE: The aim of the study was to explore the sensitivity and robustness of T2 mapping in the detection and quantification of early degenerative cartilage changes at the patella. MATERIALS AND METHODS: Forty-two patients (22 women, 20 men) with a mean age of 30.3 years and a symptomatic cartilage defect of ICRS grade ≤2 were examined using a 3T MRI with an 8-channel knee coil. The cartilage lesion was graded based on high-resolution PD TSE and 3D isotropic TrueFISP images. T2 maps were calculated from a standard MESE-sequence, performed at the beginning and at the end of the scan (40min in-between). Depending on the defect size, a region-of-interest (ROI) analysis was performed on 1-3 consecutive slices. Mean T2 values for the deep, superficial, and global layer as well as the zonal variation were compared among defect grades (ANOVA, post hoc Duncan-test) and over time (Student's t-test). RESULTS: T2-measurements directly correlated with the extent of cartilage defect (ICRS grade) at all layers and at both time-points. However, correlations were closer for the second measurement at the end of the scan. In this unloaded state, differences in T2-values became more pronounced and were significant even between cartilage of normal appearance adjacent to the defect and healthy cartilage of control patients (both ICRS grade 0). In contrast, there were no such differences among grades in the zonal variation at any time. CONCLUSION: T2 mapping might be a sensitive method for the detection of early cartilage degeneration at the patella in the unloaded joint.

Coherent heavy quasiparticles in a CePt5 surface alloy.

We report on the results of a high-resolution angle-resolved photoemission study on the ordered surface alloy CePt(5). The temperature dependence of the spectra show the formation of the coherent low-energy heavy-fermion band near the Fermi level. These experimental data are supported by a multiband model calculation in the framework of the dynamical mean-field theory.