Platinum Group Metal-Doped Tungsten Phosphates for Selective C-H Activation of Lower Alkanes

Platinum group metal (PGM)-based catalysts are known to be highly active in the total combustion of lower hydrocarbons. However, through an alternative catalyst design reported in this paper by isolating PGM-based active sites in a tungsten phosphate matrix, we present a class of catalysts for selective oxidation of n-butane, propane, and propylene that do not contain Mo or V as redox-active elements. Two different catalyst concepts have been pursued. Concept A: isolating Ru-based active sites in a tungsten phosphate matrix coming upon as ReO3-type structure. Concept B: dilution of PGM-based active sites through the synthesis of X-ray amorphous Ru tungsten phosphates supported on SiO2. Using a high-throughput screening approach, model catalysts over a wide compositional range were evaluated for C3 and C4 partial oxidation. Bulk crystalline and supported XRD amorphous phases with similar Ru/W/P compositions showed comparable performance. Hence, for these materials, composition is more crucial than the degree of crystallinity. Further studies for optimization on second-generation supported systems revealed even better results. High selectivity for n-butane oxidation to maleic anhydride and propane oxidation to an acrolein/acrylic acid has been achieved

Treatment response evaluation with (18)F-FDG PET/CT and (18)F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

AIM The aim of this study was to assess the combined use of the radiotracers (18)F-FDG and (18)F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). PATIENTS AND METHODS Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with (18)F-FDG and (18)F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). RESULTS An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, (18)F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, (18)F-FDG PET/CT-based treatment response revealed CR in 14 patients ((18)F-FDG PET/CT CR), PR in 11 patients ((18)F-FDG PET/CT PR) and progressive disease in four patients ((18)F-FDG PET/CT PD). In terms of (18)F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, (18)F-NaF PET/CT depicted 56 of the 129 (18)F-FDG positive lesions (43 %). Follow-up (18)F-NaF PET/CT showed persistence of 81.5 % of the baseline (18)F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to (18)F-FDG negative. Treatment response according to (18)F-NaF PET/CT revealed CR in one patient ((18)F-NaF PET/CT CR), PR in five patients ((18)F-NaF PET/CT PR), SD in 12 patients ((18)F-NaF PET/CT SD), and PD in seven patients ((18)F-NaF PET/CT PD). Dynamic (18)F-FDG and (18)F-NaF PET/CT studies showed that SUVaverage, SUVmax, as well as the kinetic parameters K1, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p < 0.001). CONCLUSION F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of (18)F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, (18)F-NaF PET/CT does not seem to add significantly to (18)F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy

Quantitative techniques in 18FDG PET scanning in oncology

The clinical applications of 18F-fluoro-2-deoxyglucose (18FDG) positron emission tomography (PET) in oncology are becoming established. While simple static scanning techniques are used for the majority of routine clinical examinations, increasing use of PET in clinical trials to monitor treatment response with 18FDG and novel tracers reflecting different pharmacodynamic end points, often necessitates a more complex and quantitative analysis of radiopharmaceutical kinetics. A wide range of PET analysis techniques exist, ranging from simple visual analysis and semiquantitative methods to full dynamic studies with kinetic analysis. These methods are discussed, focusing particularly on the available methodologies that can be utilised in clinical trials

The pyramidalis-anterior pubic ligament-adductor longus complex (PLAC) and its role with adductor injuries: a new anatomical concept.

PURPOSE: Adductor longus injuries are complex. The conflict between views in the recent literature and various nineteenth-century anatomy books regarding symphyseal and perisymphyseal anatomy can lead to difficulties in MRI interpretation and treatment decisions. The aim of the study is to systematically investigate the pyramidalis muscle and its anatomical connections with adductor longus and rectus abdominis, to elucidate injury patterns occurring with adductor avulsions. METHODS: A layered dissection of the soft tissues of the anterior symphyseal area was performed on seven fresh-frozen male cadavers. The dimensions of the pyramidalis muscle were measured and anatomical connections with adductor longus, rectus abdominis and aponeuroses examined. RESULTS: The pyramidalis is the only abdominal muscle anterior to the pubic bone and was found bilaterally in all specimens. It arises from the pubic crest and anterior pubic ligament and attaches to the linea alba on the medial border. The proximal adductor longus attaches to the pubic crest and anterior pubic ligament. The anterior pubic ligament is also a fascial anchor point connecting the lower anterior abdominal aponeurosis and fascia lata. The rectus abdominis, however, is not attached to the adductor longus; its lateral tendon attaches to the cranial border of the pubis; and its slender internal tendon attaches inferiorly to the symphysis with fascia lata and gracilis. CONCLUSION: The study demonstrates a strong direct connection between the pyramidalis muscle and adductor longus tendon via the anterior pubic ligament, and it introduces the new anatomical concept of the pyramidalis-anterior pubic ligament-adductor longus complex (PLAC). Knowledge of these anatomical relationships should be employed to aid in image interpretation and treatment planning with proximal adductor avulsions. In particular, MRI imaging should be employed for all proximal adductor longus avulsions to assess the integrity of the PLAC

Proximal adductor avulsions are rarely isolated but usually involve injury to the PLAC and pectineus: Descriptive MRI findings in 145 athletes

Purpose The purpose of the study is to review the MRI findings in a cohort of athletes who sustained acute traumatic avulsions of the adductor longus fibrocartilaginous entheses, and to investigate related injuries namely the pyramidalis- anterior pubic ligament - adductor longus complex (PLAC). Associated muscle and soft tissue injuries were also assessed. Methods The MRIs were reviewed for a partial or complete avulsion of the adductor longus fibrocartilage, as well as continuity or separation of the adductor longus from the pyramidalis. The presence of a concurrent partial pectineus tear was noted. Demographic data was analysed. Linear and logistic regression was used to examine associations between injuries. Results The mean age was 32.5 (SD 10.9). The pyramidalis was absent in 3 of 145 patients. 85 of 145 athletes were professional and 52 competed in the football Premier League. 132 had complete avulsions and 13 partial. The adductor longus was in continuity with pyramidalis in 55 athletes, partially separated in seven and completely in 81 athletes. 48 athletes with a PLAC injury had a partial pectineus avulsion. Six types of PLAC injuries patterns were identified. Associated rectus abdominis injuries were rare and only occurred in five patients (3.5%). Conclusion The proximal adductor longus forms part of the PLAC and is rarely an isolated injury. The term PLAC injury is more appropriate term. MRI imaging should assess all the anatomical components of the PLAC post-injury, allowing recognition of the differentpatterns of injury

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study

Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study

OBJECTIVETo determine if circulating concentrations of vitamin D are causally associated with risk of cancer.DESIGNMendelian randomisation study.SETTINGLarge genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAMEON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).PARTICIPANTS70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.EXPOSURESFour single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multipolymorphism score for circulating 25-hydroxyvitamin D (25(OH) D) concentrations.MAIN OUTCOMES MEASURESThe primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.RESULTSThere was little evidence that the multi-polymorphism score of 25(OH) D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH) D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH) D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.CONCLUSIONSThere is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention

Reproducibility of quantitative F-18-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography

Positron emission tomography (PET) using F-18-3'-deoxy-3'-fluorothymidine ([F-18]FLT) allows noninvasive monitoring of tumour proliferation. For serial imaging in individual patients, good reproducibility is essential. The purpose of the present study was to evaluate the reproducibility of quantitative [F-18]FLT measurements. Nine patients with non-small-cell lung cancer (NSCLC) and six with head-and-neck cancer (HNC) underwent [F-18]FLT PET twice within 7 days prior to therapy. The maximum pixel value (SUVmax) and a threshold defined volume (SUV41%) were defined for all delineated lesions. The plasma to tumour transfer constant (K-i) was estimated using both Patlak graphical analysis and nonlinear regression (NLR). NLR was also used to estimate k(3), which, at least in theory, selectively reflects thymidine kinase 1 activity. The level of agreement between test and retest values was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. All primary tumours and > 90% of clinically suspected locoregional metastases could be delineated. In total, 24 lesions were defined. NLR-derived K-i, Patlak-derived K-i, SUV41% and SUVmax showed excellent reproducibility with ICCs of 0.92, 0.95, 0.98 and 0.93, and SDs of 16%, 12%, 7% and 11%, respectively. Reproducibility was poor for k(3) with an ICC of 0.43 and SD of 38%. Quantitative [F-18]FLT measurements are reproducible in both NSCLC and HNC patients. When monitoring response in individual patients, changes of more than 15% in SUV41%, 20-25% in SUVmax and Patlak-derived K-i, and 32% in NLR3k-derived K-i are likely to represent treatment effect