Control Software for Reconfigurable Coprocessors

On-line data processing at the ATLAS general purpose particle detector, which is currently under construction at Geneva, generates demands on computing power that are difficult to satisfy with commodity CPU-based computers. One of the most demanding applications is the recognition of particle tracks that originate from B-quark decays. However, this and many others applications can benefit from parallel execution on field programmable gate arrays (FPGA). After the demonstration of accelerated track recognition with big FPGA-based custom computers, the development of FPGA based coprocessors started in the late 1990's. Applications of FPGA coprocessors are usually partitioned between the host and the tightly coupled coprocessor. The objective of the research that I present in this thesis was the development of software that mediates to applications the access to FPGA coprocessors. I used a software process based on iterative prototyping to cope with the expected changing requirements. Also, I used a strict bottom-up design to create classes that model devices on the coprocessors. Using these low-level classes, I developed tools which were used for bootstrapping, debugging, and firmware update of the coprocessors during their development and maintenance. Measurements show that the software overhead introduced by object-oriented programming and software layering is small. The software-support for six different coprocessors was partitioned into corresponding independent packages, which reuse a set of packages that provide common and basic functions. The steady evolution and use of the software during more than four years shows that the software is maintainable, adaptable, and usable

Rapid Downregulation of H3K4me3 Binding to Immunoregulatory Genes in Altered Gravity in Primary Human M1 Macrophages

The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this process they finally act as immunoeffector cells, and are essential for tissue regeneration and remodeling. Recently, we demonstrated in the human Jurkat T cell line that genes are differentially regulated in cluster structures under altered gravity. In order to study an in vivo near system of immunologically relevant human cells under physically real microgravity, we performed parabolic flight experiments with primary human M1 macrophages under highly standardized conditions and performed chromatin immunoprecipitation DNA sequencing (ChIP-Seq) for whole-genome epigenetic detection of the DNA-binding loci of the main transcription complex RNA polymerase II and the transcription-associated epigenetic chromatin modification H3K4me3. We identified an overall downregulation of H3K4me3 binding loci in altered gravity, which were unequally distributed inter- and intrachromosomally throughout the genome. Three-quarters of all affected loci were located on the p arm of the chromosomes chr5, chr6, chr9, and chr19. The genomic distribution of the downregulated H3K4me3 loci corresponds to a substantial extent to immunoregulatory genes. In microgravity, analysis of RNA polymerase II binding showed increased binding to multiple loci at coding sequences but decreased binding to central noncoding regions. Detection of altered DNA binding of RNA polymerase II provided direct evidence that gravity changes can lead to altered transcription. Based on this study, we hypothesize that the rapid transcriptional response to changing gravitational forces is specifically encoded in the epigenetic organization of chromatin

Comparing restrictive versus liberal oxygen strategies for trauma patients-the TRAUMOX2 trial:protocol for a randomised clinical trial

INTRODUCTION: Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma. METHODS AND ANALYSIS: TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial. Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO(2) of 94%. The liberal group receives 12–15 L O(2)/min or FiO(2)=0.6–1.0. The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome). With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group. ETHICS AND DISSEMINATION: TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBERS: EudraCT 2021-000556-19; NCT05146700

Perioperative cardiac arrest in the operating room environment: A review of the literature

INTRODUCTION: Cardiac arrest in the operating room (OR) environment is a rare but potentially catastrophic event with mortality rates of more than 50%. Contributing factors are known, and the event is generally rapidly recognized, as patients are usually under full monitoring. The nature of the cardiac arrest in the OR is different to other environments as it is not only related to the patient's conditions but likewise to the anaesthetic and the surgical procedure. The aim of this article is to review recent literature on cardiac arrest in the immediate perioperative environment with a focus on incidence, causes and treatment. EVIDENCE ACQUISITION: Retrospective analysis of literature published in PubMed. EVIDENCE SYNTHESIS: Several recent retrospective registry studies have investigated the incidence of perioperative cardiac arrest; in non-cardiac surgery patients, the incidence is reported to range from 0.2 to 1.1 per 10,000 adults and from 1.4 to 4.6 per 10,000 children. CONCLUSIONS: Successful management of cardiac arrest during surgery and beyond requires not only individual technical skills and a well-organized team response, but also an institutional safety culture embedded in everyday practice through continuous education, training and multidisciplinary cooperation. Evidence based guidelines and standardized treatment algorithms addressing the particularities of peri-operative cardiac arrest would be helpful to facilitate training. Existing guidelines are not comprehensive enough to cover specific aspects in depth; for the future, more detailed and more explicit guidelines are required

Case report of Tako-Tsubo cardiomyopathy associated with repetitive anaesthesia in a female patient with Tako-Tsubo cardiomyopathy

Background: Tako-Tsubo cardiomyopathy (TTC) is a rare disorder with high relevance for anaesthesia. It is an acute cardiac syndrome characterized by an acute onset of reversible left ventricular dysfunction associated with emotional and physical stress. This is the only case published of a patient having five severe Tako-Tsubo incidents in five consecutive general anaesthesia procedures within one year. Case presentation: A 61 years old female patient (height 1.65 m; weight 70 kg) presented with a haemorrhagic pituitary adenoma with compression of the optic chiasm and was scheduled for transnasal endoscopic tumour resection. We report a case series with five consecutive anaesthesia procedures in the same patient for neurosurgery. This case series is remarkable since the severe symptoms occurred during every anaesthesia procedure. The female patient was resuscitated two times including therapeutic hypothermia, but fortunately no neurological or cognitive deficit was detectable. Conclusions: TTC may initially present in the perioperative period with pulmonary oedema, electrocardiographic (ECG) changes, elevation of cardiac enzymes, and cardiogenic shock or cardiac arrest. Since the risk of recurrence is considered to be low in TTC, this case report is of high interest. In each procedure similar clinical signs were found which resulted in severe haemodynamic derangements in every manifestation and cardiac arrest in two of the manifestations. Despite cardiopulmonary resuscitation twice, the patient survived without any neurological deficiency