The Embedded Local Monitor Board upgrade proposals

The Embedded Local Monitor Board (ELMB) is a microcontroller based plug-in module usingthe CANopen communication protocol. It has been widely used in LHC systems and experimentsfor slow-control and monitoring purposes, providing multiple, galvanically isolated analog inputs,and multiple digital inputs and outputs. While the module showed excellent performance in thepast 15 years, a new design is deemed necessary due to the obsolescence of some components ofthe existing ELMB and the higher radiation tolerance required for the planned HL-LHC upgrade.Three development paths, one fully backward compatible and two conceptually different solutionswith different levels of radiation tolerance are presented

Termination of prehospital resuscitative efforts: a study of documentation on ethical considerations at the scene

Abstract Background Discussions on ethical aspects of life-and-death decisions within the hospital are often made in plenary. The prehospital physician, however, may be faced with ethical dilemmas in life-and-death decisions when time-critical decisions to initiate or refrain from resuscitative efforts need to be taken without the possibility to discuss matters with colleagues. Little is known whether these considerations regarding ethical issues in crucial life-and-death decisions are documented prehospitally. This is a review of the ethical considerations documented in the prehospital medical records of patients in a Danish prehospital setting for whom the decision to resuscitate or not was made at the scene. Methods The study is based on discharge summaries of all patients subjected to crucial life-and-death decisions by the Mobile Emergency Care Unit in Odense in the years 2010 to 2014. The medical records with possible documentation of ethical issues were independently reviewed by two philosophers in order to identify explicit ethical or philosophical considerations pertaining to the decision to resuscitate or not. Results In total, 1275 patients were either declared dead at the scene without exhibiting layman’s reliable signs of death or admitted to hospital following resuscitation. In a total of 62 patients, 85 specific ethical issues related to resuscitation were documented. The expressions of the ethical considerations were generally vague or unclear and almost exclusively concerned the interests of the patient and not the relatives. In the vast majority of cases where an ethical content was identified, the ethical considerations led to a decision to terminate treatment. Conclusions A strengthened practice of documenting ethical considerations in prehospital life-and-death decision-making in the patient’s medical records is required. We suggest that a template be implemented in the prehospital medical records describing the basis for any ethical decisions. This template should contain information regarding the persons involved in the deliberations and notes on ethical considerations. The documentation should include considerations concerning the patient’s end-of-life wishes, the estimations of the quality of life before and after the incident, and a summary of other ethical concerns taken into account, such as the integrity of the patient and frame of mind of relatives

25-hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-hydroxylated vitamin D analogue

INTRODUCTION: The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues where 1alpha-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1alpha-hydroxylase in breast cancer and to investigate whether a non-1alpha-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated. METHODS: The expression of 1alpha-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 mum essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells. RESULTS: 1alpha-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1alpha-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1alpha-hydroxylase, 1 +/- 0.07 versus 0.7 +/- 0.05, respectively (p < 0.001); 24-hydroxylase, 1 +/- 0.08 verus 2.1 +/- 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 +/- 0.09 and 1.4 +/- 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1alpha-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3. CONCLUSION: These results demonstrate nearly normal expression levels of 1alpha-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1alpha-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1alpha-hydroxylase is expressed

Positron emission tomography/computed tomography for optimized colon cancer staging and follow up

OBJECTIVES: Optimal management of colon cancer (CC) requires detailed assessment of extent of disease. This study prospectively investigates the diagnostic accuracy of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) for staging and detection of recurrence in primary CC. MATERIAL AND METHODS: PET/CT for preoperative staging was performed in 66 prospectively included patients with primary CC. Diagnostic accuracy for PET/CT and CT was analyzed. In addition to routine follow up, 42 stages I–III CC patients had postoperative PET/CT examinations every 6 months for 2 years. Serological levels of tissue inhibitor of metalloproteinase-1 (TIMP-1), carcinoembryonic antigen, and liberated domain I of urokinase plasminogen activator receptor were analyzed. RESULTS: Accuracy for tumor, nodal, and metastases staging by PET/CT were 82% (95% confidence interval [CI]: 70; 91), 66% (CI: 51; 78), and 89% (CI: 79; 96); for CT the accuracy was 77% (CI: 64; 87), 60% (CI: 46; 73), and 69% (CI: 57; 80). Cumulative relapse incidences for stages I–III CC at 6, 12, 18, and 24 months were 7.1% (CI: 0; 15); 14.3% (CI: 4; 25); 19% (CI: 7; 31), and 21.4% (CI: 9; 34). PET/CT diagnosed all relapses detected during the first 2 years. High preoperative TIMP-1 levels were associated with significant hazards toward risk of recurrence and shorter overall survival. CONCLUSIONS: This study indicates PET/CT as a valuable tool for staging and follow up in CC. TIMP-1 provided prognostic information potentially useful in selection of patients for intensive follow up