The duality of UiO-67-Pt MOFs: connecting treatment conditions and encapsulated Pt species by operando XAS.

An X-ray absorption spectroscopy study of the UiO-67 Pt functionalized metal organic frameworks (MOFs) demonstrates that under appropriate conditions, at least two types of catalytically active sites can be formed in the cavities of the MOF: isolated Pt-complexes and Pt nanoparticles (Pt-NPs). Both pre-made linker synthesis (PMLS) and post-synthesis functionalization (PSF) methods were adopted. XAS was used to monitor the temperature-dependent behaviour of UiO-67-Pt while heating from RT to 623 K, in different gas feeds (pure He, 3% H2/He and 10% H2/He). We collected static in situ Pt LIII XANES and EXAFS spectra at room temperature (RT) before and after the thermal treatment, as well as spectra acquired under operando conditions upon heating. Under 10% H2/He thermal treatment, we unambiguously detected Pt-NP formation which has been followed by a parametric EXAFS analysis of the data collected during temperature programmed H2-reduction (TPR), using the Einstein model to predict the temperature dependence of the Debye-Waller factors. Conversely, in pure He flow, the only significant change observed during TPR is the progressive decrease of the Pt-Cl single scattering contribution, leading to the conclusion that the Pt grafted to the bpydc-linkers remains naked. Advanced EXAFS/TEM analysis allowed us to quantify the fraction of Pt in the form of Pt-NPs, values that have been quantitatively confirmed by linear combination analysis of the XANES spectra. In situ XANES/EXAFS study was supported by ex situ XRPD and BET analyses, confirming the framework stability and testifying a loss of the internal volume after TPR due to the formation of Pt-NPs insides the MOF pores, more relevant in the sample where smaller Pt-NPs were formed.

Tuning Pt and Cu sites population inside functionalized UiO-67 MOF by controlling activation conditions.

The exceptional thermal and chemical stability of the UiO-66, -67 and -68 classes of isostructural MOFs [J. Am. Chem. Soc., 2008, 130, 13850] makes them ideal materials for functionalization purposes aimed at introducing active centres for potential application in heterogeneous catalysis. We previously demonstrated that a small fraction (up to 10%) of the linkers in the UiO-67 MOF can be replaced by bipyridine-dicarboxylate (bpydc) moieties exhibiting metal-chelating ability and enabling the grafting of Pt(ii) and Pt(iv) ions in the MOF framework [Chem. Mater., 2015, 27, 1042] upon interaction with PtCl2 or PtCl4 precursors. Herein we extend this functionalization approach in two directions. First, we show that by controlling the activation of the UiO-67-Pt we can move from a material hosting isolated Pt(ii) sites anchored to the MOF framework with Pt(ii) exhibiting two coordination vacancies (potentially interesting for C-H bond activation) to the formation of very small Pt nanoparticles hosted inside the MOF cavities (potentially interesting for hydrogenation reactions). The second direction consists of the extension of the approach to the insertion of Cu(ii), obtained via interaction with CuCl2, and exhibiting interesting redox properties. All materials have been characterized by in situ X-ray absorption spectroscopy at the Pt L3- and Cu K-edges.

Pitfalls in metal-organic framework crystallography: towards more accurate crystal structures.

Single crystal X-ray diffraction (SC-XRD) is the principal method for determining the crystal structures of metal-organic frameworks (MOFs). This tutorial deals with the handling of MOF crystals and analysis of crystallographic data obtained from single-crystal X-ray diffraction, focusing on two features that are particularly important in MOF crystallography and have a large impact on the quality and reliability of the final crystal structures: (1) the treatment of pore-occupying entities (both in the physical crystals and in the crystallographic model) and (2) crystallographic twinning. Proper handling of samples and data will reduce the need for using solvent masking software (e.g. SQUEEZE) to obtain acceptable crystal structures. If SC-XRD is to retain its position as the definitive method of MOF structure determination, these issues must be addressed when a new MOF structure is determined and reported. The issues addressed in this review is also valid for other porous, crystalline solids such as porous organic cages, metal-organic polyhedra, covalent organic frameworks and zeotype materials.

Differentiation of Metastatic and Non-Metastatic Mesenteric Lymph Nodes by Strain Elastography in Surgical Specimens.

PURPOSE: To investigate if strain elastography could differentiate between metastatic and non-metastatic mesenteric lymph nodes ex-vivo. MATERIALS AND METHODS: 90 mesenteric lymph nodes were examined shortly after resection from 25 patients including 17 patients with colorectal cancer and 8 patients with Crohn's disease. Ultrasound-based strain elastography was performed with a linear probe. Tissue hardness in lymph nodes was assessed using visual scales and measuring the strain ratio. B-mode characteristics were also recorded. Pathological diagnosis with grading of fibrosis served as the reference standard. RESULTS: 20 lymph nodes were metastatic and 70 lymph nodes were non-metastatic. The strain ratios of metastatic and non-metastatic lymph nodes were significantly different (1.83 vs. 1.42, p = 0.021). The VAS scale (0 - 100) for tissue hardness gave higher mean values for metastatic than non-metastatic nodes, but the difference was not significant (65.5 vs. 55.0, p = 0.055). There was no difference between lymph nodes in Crohn's and non-metastatic cancer specimens. The metastatic lymph nodes were significantly more fibrotic than the non-metastatic lymph nodes by the ordinal fibrosis score (0 - 3). In an ROC analysis, quantitative strain imaging was not superior to the measurement of the short-axis diameter of lymph nodes in differentiating metastatic from non-metastatic mesenteric lymph nodes ex-vivo. CONCLUSION: Strain elastography is correlated to fibrosis in lymph nodes and a significant difference was observed on a group level using the strain ratio. Due to measurement overlap, individual mesenteric lymph nodes could not be identified accurately as metastatic or not in this ex-vivo model by strain imaging alone.

Endorectal ultrasonography, strain elastography and MRI differentiation of rectal adenomas and adenocarcinomas.

AIM: Strain elastography is a method for recording tissue hardness. Strain in different areas may be compared using strain ratio (SR). The aims of this study were to validate a previously proposed SR cut-off value of 1.25 for differentiating adenocarcinomas from adenomas and to compare the performance of endorectal ultrasonography (ERUS), strain elastography and MRI in the same patients. METHOD: A prospective evaluation of 120 consecutive patients with rectal neoplasia, using a predetermined elastography strain ratio cut-off value, was performed to differentiate adenomas from adenocarcinomas. ERUS and MRI were performed according to standard routine at Haukeland University Hospital, defining T0 as adenomas and T1-T4 as adenocarcinomas. Subsequent histopathology was used as the reference standard. RESULTS: Histopathological evaluation revealed 21 adenomas and 99 adenocarcinomas. Sensitivity, specificity and accuracy (with 95% CI) were as follows: ERUS: 0.96 (0.90-0.99), 0.62 (0.40-0.80) and 0.90 (0.83-0.94); elastography SR: 0.96 (0.90-0.99), 0.86 (0.66-0.96) and 0.94 (0.88-0.97); and MRI: 0.99 (0.94-1.00), 0.07 (0.00-0.31) and 0.87 (0.80-0.93). CONCLUSION: This study confirms that the elastography SR assessment accurately differentiates sessile adenomas from adenocarcinomas. SR assessment has a superior ability to differentiate adenomas and adenocarcinomas when compared with ERUS and MRI. MRI examination seems unable to recognize adenomas and should be interpreted with care when early-stage rectal neoplasia is suspected.

Combined endorectal ultrasonography and strain elastography for the staging of early rectal cancer.

AIM: Strain elastography is a novel approach to rectal tumour evaluation. The primary aim of this study was to correlate elastography to pT stages of rectal tumours and to assess the ability of the method to differentiate rectal adenomas (pT0) from early rectal cancer (pT1-2). Secondary aims were to compare elastography with endorectal ultrasonography (ERUS) and to propose a combined strain elastography and ERUS staging algorithm. METHOD: In all, 120 consecutive patients with a suspected rectal tumour were examined in this staging study. Patients receiving surgery without neoadjuvant radiotherapy were included (n = 59). All patients were examined with ERUS and elastography. Treatment decisions were made by multidisciplinary team (MDT) assessment, without considering the strain elastography examination. RESULTS: Histopathology identified 21 adenomas, 13 pT1, 9 pT2, 15 pT3 and one pT4. Mean elastography strain ratios were predictive of T stage (P = 0.01). Differentiation of adenomas from early rectal cancer (pT1-2) had sensitivity, specificity and accuracy of 0.82, 0.86 and 0.84 for elastography and 0.82, 0.62 and 0.72 for ERUS. A combined staging algorithm was developed to identify tumours eligible for local resection. Based on MDT evaluation 32% of tumours later identified as pT0 or pT1 were treated with total mesorectal excision, even though a local excision might have sufficed. Combined ERUS and elastography evaluation would have significantly reduced this number to 9% (P = 0.008). CONCLUSION: Elastography may improve the staging of adenomas and early rectal cancer compared with ERUS alone. Combined ERUS and elastography assessment is likely to further improve the selection of patients for local resection.

Strain assessment in surgically resected inflammatory and neoplastic bowel lesions.

PURPOSE: To investigate whether ultrasound-based strain imaging can discriminate between colorectal adenocarcinomas and stenotic Crohn's lesions in newly resected surgical specimens. MATERIALS AND METHODS: Resected surgical specimens from 27 patients electively operated for colorectal tumors or stenotic lesions from Crohn's disease were prospectively examined with ultrasonography using a Hitachi HV 900 US scanner with real-time elastography (RTE). Three different methods were applied to assess tissue strain: A four-level categorical visual classification, a continuous visual analog scale (VAS, 0 - 100) and a strain ratio (SR) measurement between the lesion and surrounding reference tissue. The imaged sections were marked and subsequently examined by a pathologist. Results from RTE were evaluated according to diagnosis, degree of fibrosis, inflammatory parameters, tumor stage and grade. RESULTS: 16 sections from Crohn's lesions, 18 sections from adenocarcinomas and 4 sections from adenomas were examined. Both adenocarcinomas and Crohn's lesions were found to be harder than the surrounding tissue, but they could not be discriminated from each other by any of the strain imaging evaluation methods. All adenocarcinomas had significantly higher strain ratios than adenomas. The categorical classification differentiated poorly between Crohn's lesions, adenocarcinomas and adenomas. Categorical evaluation and VAS score showed fair interobserver agreement. SR measurements provided semi-quantitative strain data and added improved information about elasticity properties, despite substantial intra-observer variation. CONCLUSION: Sonoelastography with SR measurements and visual evaluation of strain differences could not differentiate stenotic Crohn's lesions from adenocarcinomas in resected bowel specimens. A small number of adenomas were found to be significantly softer than adenocarcinomas using the same evaluation methods. The tumor stage or grade did not have a significant impact on the elastography results.

Gastrointestinal wall thickness measured with transabdominal ultrasonography and its relationship to demographic factors in healthy subjects.

PURPOSE: To describe the gastrointestinal (GI) wall thickness and the thickness of individual wall layers in healthy subjects using ultrasound and to determine whether demographic factors, the ultrasound transducer frequency, or a fasting state influences these measurements. MATERIALS AND METHODS: After overnight fasting, the GI wall thickness and wall layers were measured in several regions with transabdominal, high-frequency ultrasound. 122 healthy subjects aged 23 - 79 were included. All measurements were performed with both 8 and 12-MHz transducers except for the rectum measurement (4 MHz). 23 patients were given a 300 Kcal test meal and re-examined after 30 minutes. RESULTS: Wall thickness measurements of the GI tract with transabdominal ultrasonography are dependent on transducer frequency (p < 0.001), weight (p < 0.001) and age (p < 0.018). The thickness of individual wall layers in the ileum and the sigmoid colon was found to be dependent on both age (p = 0.007) and weight (p < 0.001). The mean wall thickness from the jejunum to the sigmoid colon ranged from 0.9 to 1.2 mm with standard deviations (SD) of 0.3 mm or less. The mean (SD) was 2.9 (0.8) mm in the gastric antrum, 1.6 (0.3) mm in the duodenum, and 2.1 (0.5) mm in the rectum. The gastric antrum was thinner and the ileum and sigmoid colon were thicker after the test meal (p < 0.05). CONCLUSION: GI wall thickness depends on weight and age. Provided adequate measurement, an abnormal GI wall should be suspected if the thickness exceeds 2 mm except for in the gastric antrum, duodenum and rectum. Reference values for wall thickness can be used regardless of fasting state or probe frequency except for in the gastric antrum.

A randomized trial on elderly laypersons' CPR performance in a realistic cardiac arrest simulation.

BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is important for survival after cardiac arrest. We hypothesized that elderly laypersons would perform CPR poorer in a realistic cardiac arrest simulation, compared to a traditional test. METHODS: Sixty-four lay rescuers aged 50-75 were randomized to realistic or traditional test, both with ten minutes of telephone assisted CPR. Realistic simulation started suddenly without warning, leaving the test subject alone in a confined and noisy apartment. Traditional test was conducted in a spacious and calm classroom with a researcher present. CPR performance was recorded with a manikin with human like chest properties. Heart rate and self-reported exhaustion were registered. RESULTS: CPR quality was not different in the two groups: compression depth, 43 mm ± 7 versus 43 ± 4, P = 0.72; compressions rate, 97 min(-1) ± 11 versus 93 ± 15, P = 0.26; ventilation rate, 2.4 min(-1) ± 1.7 versus 2.8 ± 1.1, P = 0.35; and hands-off time 273 s ± 50 versus 270 ± 66, P = 0.82; in realistic (n = 31) and traditional (n = 33) groups, respectively. No fatigue was evident in the repeated measures analysis of variance. Work load was not different between the groups; attained percentage of age predicted maximum heart rate, 73% ± 9 and 76 ± 11, P = 0.37, reported exhaustion 43 ± 21 (scale: 0 to 100) and 37 ± 19, P = 0.24. CONCLUSIONS: Elderly lay people are capable of performing chest compressions with acceptable quality for ten minutes in a realistic cardiac arrest simulation. Ventilation quality and hands-off time were not adequate in either group.

Real-Time Elastography: Strain Ratio Measurements Are Influenced by the Position of the Reference Area.

PURPOSE: Real-time elastography (RTE) is an ultrasound-based method for the visualization of relative strain distribution in soft tissues. Strain ratio is a semi-quantitative measurement of strain differences between two user-defined areas in an elastogram. The aim of this study was to evaluate the impact of the size and location of a reference area when measuring the strain ratio of focal lesions in a tissue-mimicking phantom and in normal liver tissue. We also investigated whether the strain ratio was affected by changing the scanner parameter: elasticity dynamic range (E-dyn). MATERIALS AND METHODS: Two investigators individually collected data by scanning 4 spherical inclusions with different elasticity in a phantom in which the elastic modulus was known in both the lesions and the background. Subsequently, a liver scan was performed in-vivo using the same scanning protocol. Five different setups with changes in reference area position or size were tested. All eight levels of the scanner setting Edyn were recorded for each setup and the strain ratio was measured in 3 different representative elastograms for each recording situation. RESULTS: The four inclusions had significantly different mean strain ratio levels (p < 0.01) when compared to the surrounding material. Changing the position of the reference area to a deeper position influenced the strain ratio measurements significantly for all phantom lesions and in the liver. Changing the size of the reference area, while keeping the center depth unchanged, did not influence the mean strain ratio levels significantly. The strain ratio was independent of the E-dyn parameter setting. The intraand interobserver reliability was high when measuring the strain ratio with a free-hand technique. CONCLUSION: Strain ratio provides reproducible measurements of inclusions representing different elastic contrasts using a free-hand technique in vitro. Changes in the distance of the reference areas to the ultrasound probe, representing the stress source, seem to have a significant impact on strain ratio measurements.

Endorectal elastography in the evaluation of rectal tumours.

AIM: Real-time elastography visualizes tissue compliance using an ultrasound platform. Elastography has been used, particularly in the breast, to characterize indeterminate lesions on B-mode imaging as either benign or malignant. The primary aim of this study was to assess the feasibility of routine endorectal elastography to evaluate rectal neoplasia. The secondary aim was to correlate elastography data with histopathological end-points. METHOD: Sixty-nine patients referred to the outpatient clinic of the Department of Colorectal Surgery at Haukeland University Hospital for the evaluation of rectal tumours were included in this prospective cohort study. All patients underwent digital rectal examination, rigid rectoscopy with biopsy, endorectal ultrasonography and endorectal elastography. In each case a strain ratio was calculated, comparing the tumour tissue with adjacent reference tissue that appeared normal on ultrasound scanning. RESULTS: Histopathologically there were 23 adenomas and 45 adenocarcinomas. One patient died before surgical treatment. Adequate elastography images were obtained in 66/69 (96%) patients. Optimal discrimination of malignant and benign lesions was obtained using a strain ratio cut-off value of 1.25 (sensitivity, 0.93; specificity, 0.96; and accuracy, 0.94). CONCLUSION: Endorectal elastography can be performed as an integral part of the clinical evaluation of rectal tumours and has good patient compliance. The method is a promising modality for the discrimination between adenocarcinoma and adenoma of the rectum.

Sensation evoked by esophageal distension in functional chest pain patients depends on mechanical stress rather than on ischemia.

BACKGROUND: Functional chest pain is commonly reproduced by bag distension in the esophageal body. It is unknown whether such pain is primarily associated with mechanical stress and strain (force-deformation) or with changes in mucosal perfusion. METHODS: Fourteen patients (6M, 8F, average age 55.9 years) underwent ramp bag distension before and after injection of 20 mg butylscopolamine bromide (BS) using a novel bag catheter incorporating endosonography and laser Doppler perfusion monitoring. Healthy subjects served as controls. Mucosal perfusion was evaluated and stress and strain were computed and related to the sensation. KEY RESULTS: The symptom score increased with bag volume (P < 0.001). Volume as a function of pressure was higher in patients than in controls (P < 0.001), both before and during BS. The stress-strain relationship was exponential and indicated a stiffer esophageal wall in patients especially before BS (P < 0.01). The stress-strain curves indicate increased muscle tone in the functional chest pain patients. The perfusion decreased with increasing symptom score from visual analog scale 1-7 during BS. The decrease was on average 18.9% in patients and 19.7% in controls (P = ns). Multiple regression analysis from distensions during BS showed that the discomfort/pain sensations depended on stress and strain (P < 0.001) and with stress as the largest contributor. Perfusion did not contribute. CONCLUSIONS & INFERENCES: Pain evoked by bag distension in patients with functional chest pain is stress-dependent rather than dependent on mucosal perfusion. Furthermore, the esophagus of the patients was characterized by more pronounced muscle tone during the distensions.

Searching a role for endoscopic ultrasonography in Barrett's esophageus and other acid-related or gastrointestinal motility disorders.

Endoscopic ultrasonography (EUS) can image the GI-wall in detail. Substaging of T1-tumours (e.g. in Barrett's esophageus) is possible with EUS which may have clinical significance regarding therapeutic options. Abnormal motility occurs in several gastrointestinal (GI) diseases and EUS can be used in biomechanical and motility studies. Three-dimensional EUS, elastography and strain rate imaging are new techniques which are promising in imaging the GI-tract and in the examination of gut motility.

A multimodal laser Doppler and endosonographic distension device for studying mechanosensation and mucosal blood flow in the oesophagus.

We describe the development of a multimodal device combining bag distension, manometry, high frequency intraluminal ultrasound, laser Doppler flowmetry and symptom registration. Bench tests showed that the different modalities did not influence each other. During bag distension we obtained high quality images of the oesophageal wall for computing biomechanical parameters, and laser Doppler signals showing variation in mucosal perfusion. We conclude that the principle of measurement is sound and that the device can provide a basis for further studies.

Mechanosensory properties in the human gastric antrum evaluated using B-mode ultrasonography during volume-controlled antral distension.

The aims of this study were to evaluate gastric antral mechanical behavior and distension-induced sensorimotor responses in the human gastric antrum using transabdominal ultrasound scanning. Ten healthy volunteers underwent volume-controlled ramp inflation of a bag located in the antrum with volumes up to 125 ml. The active and passive circumferential tensions and stresses were calculated from measurements of pressure, diameter, and wall thickness before and during the administration of the anticholinergic drug butylscopolamine. The bag distensions elicited contractions in the antrum and sensory responses below the pain threshold. Butylscopolamine abolished the contractions and significantly reduced the sensory response. The length-tension diagram known from in vitro studies of smooth muscle strips could be reproduced as tension-volume diagrams in the human gastric antrum. The number of induced contractions and the contraction pressure amplitude (afterload) showed a parabolic behavior as function of the distension volume (preload), with maximum approximately at 70 ml. At the sensation threshold, the luminal circumference showed the lowest variation coefficient (13-25%), whereas the variation coefficient was more than 100% for the pressure, tensions, and stresses. We conclude that the muscle length-tension diagram and typical preload-afterload curves ad modem the Frank-Starling cardiac law can be obtained in the human gastric antrum. The sensory responses were most closely associated with the luminal circumference, indicating that the sensation during antral distension depends on deformation rather than on tension.

Comparison of homeopathy, placebo and antibiotic treatment of clinical mastitis in dairy cows - methodological issues and results from a randomized-clinical trial.

Based on the widespread use of homeopathy in treatment of animal disease and the poor documentation of its possible effects and consequences, a clinical trial was carried out in order to evaluate the efficacy of homeopathy in treatment of clinical mastitis in dairy cows and a design for clinical studies on homeopathic treatment, taking into account the guidelines for randomized-clinical trials (RCT) as well as the basic principles of homeopathy. A three-armed, stratified, semi-crossover design comparing homeopathy, placebo and a standardized antibiotic treatment was used. Fifty-seven dairy cows were included. Evaluation was made by two score scales, with score I measuring acute symptoms and score II measuring chronic symptoms, and by recording the frequencies of responders to treatment based on four different responder definitions. Significant reductions in mastitis signs were observed in all treatment groups. Homeopathic treatment was not statistically different from either placebo or antibiotic treatment at day 7 (P = 0.56, P = 0.09) or at day 28 (P = 0.07, P = 0.35). The antibiotic treatment was significantly better than placebo measured by the reduction in score I (P < 0.01). Two-thirds of the cases both in the homeopathy and placebo groups responded clinically within 7 days. The outcome measured by frequencies of responders at day 28 was poor in all treatment groups. Evidence of efficacy of homeopathic treatment beyond placebo was not found in this study, but the design can be useful in subsequent larger trials on individualized homeopathic treatment.

Endoscopic augmentation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease: multicenter study of the Gatekeeper Reflux Repair System.

BACKGROUND AND STUDY AIMS: The safety and effectiveness of the Gatekeeper Reflux Repair System (Medtronic Europe, Tolochenaz, Switzerland) in the treatment of gastroesophageal reflux disease (GERD) was evaluated. This new, reversible treatment modality involves the endoscopic introduction of expandable polyacrylonitrile-based hydrogel prostheses into the esophageal submucosa to augment the lower esophageal sphincter (LES). PATIENTS AND METHODS: For this study, data from two prospective, nonrandomized European multicenter trials were pooled. Sixty-nine GERD patients with heartburn and regurgitation and abnormal esophageal acid exposure (24-h pH < 4.0 for > 4 % of the total time) who had responded to proton-pump inhibitor (PPI) therapy were recruited, and 68 were treated with up to six prostheses placed at the gastroesophageal junction. Patients underwent esophageal manometry, endoscopy, 24-h pH-metry, and symptom scoring at intake and 1, 3, and 6 months after the procedure. RESULTS: A total of 77 procedures were performed in 67 patients, and a total of 270 prostheses were placed (mean 4.3 per procedure). At 1 and 6 months, 80.4 % and 70.4 % of the prostheses were retained, respectively. At 6 months, 24-h pH-metry outcomes with pH < 4.0 for > 4.0 % of the time decreased from 9.1 % to 6.1 % (n = 45; P < 0.05). Median LES pressure increased significantly from 8.8 mmHg at baseline to 13.8 mmHg at 6 months (n = 42, P < 0.01). Median GERD heartburn-related quality-of-life scores improved significantly from 24.0 to 5.0 (n = 53, P < 0.01) in patients no longer receiving PPI therapy. Two serious adverse events (3.0 %) occurred. Both patients recovered uneventfully. Prostheses were endoscopically removed from one patient without any adverse events. CONCLUSIONS: The Gatekeeper Reflux Repair System is a safe endoscopic treatment modality that significantly improves GERD symptoms and has objective effects on acid reflux.