Identifying oncogenic drivers associated with increased risk of late distant recurrence in postmenopausal, estrogen receptor-positive, HER2-negative early breast cancer: results from the BIG 1-98 study.

BACKGROUND: In postmenopausal, estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer, the risk for distant recurrence can extend beyond 5 years of adjuvant endocrine therapy. This study aims to identify genomic driver alterations associated with late distant recurrence. PATIENTS AND METHODS: Next generation sequencing was used to characterize driver alterations in primary tumors from a subset of 764 postmenopausal estrogen receptor-positive/HER2-negative patients from the BIG 1-98 randomized trial. Late distant recurrence events were defined as ≥5 years from time of randomization). The association of driver alterations with distant recurrence-free interval in early and late time periods was assessed using Cox regression models. Multivariable analyses were carried out to adjust for clinicopathological factors. Weighted analysis methods were used in order to correct for over-sampling of distant recurrences. RESULTS: A total of 538 of 764 (70%) samples were successfully sequenced including 88 (63%) early and 52 (37%) late distant recurrence events after a median follow up of 8.1 years. In univariable analysis for late distant recurrence, PIK3CA mutations (58.8%) were significantly associated with reduced risk [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.20-0.82, P = 0.012], whereas amplifications on chromosome 8p11 (10.9%) (HR 4.79, 95% CI 2.30-9.97, P < 0.001) and BRCA2 mutations (2.3%) (HR 5.39, 95% CI 1.51-19.29, P = 0.010) were significantly associated with an increased risk. In multivariable analysis, only amplifications on 8p11 (P = 0.002) and BRCA2 mutations (P = 0.013) remained significant predictors. CONCLUSIONS: In estrogen receptor-positive/HER2-negative postmenopausal early breast cancer, PIK3CA mutations were associated with reduced risk of late distant recurrence, whereas amplifications on 8p11 and BRCA2 mutations were associated with increased risk of late distant recurrence. The characterization of oncogenic driver alterations may aid in refining treatment choices in the late disease setting, and help identify potential drug targets for testing in future trials.

Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score ≥ 4) and mortality. RESULTS: Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24) mL and were 71 (IQR, 61-76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. CONCLUSION: Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.

EsPRit: ethics committee proposals for Long Term Medical Data Registries in rapidly evolving research fields - a future-proof best practice approach.

BACKGROUND: Long-term data collection is a challenging task in the domain of medical research. Many effects in medicine require long periods of time to become traceable e.g. the development of secondary malignancies based on a given radiotherapeutic treatment of the primary disease. Nevertheless, long-term studies often suffer from an initial lack of available information, thus disallowing a standardized approach for their approval by the ethics committee. This is due to several factors, such as the lack of existing case report forms or an explorative research approach in which data elements may change over time. In connection with current medical research and the ongoing digitalization in medicine, Long Term Medical Data Registries (MDR-LT) have become an important means of collecting and analyzing study data. As with any clinical study, ethical aspects must be taken into account when setting up such registries. This work addresses the problem of creating a valid, high-quality ethics committee proposal for medical registries by suggesting groups of tasks (building blocks), information sources and appropriate methods for collecting and analyzing the information, as well as a process model to compile an ethics committee proposal (EsPRit). METHODS: To derive the building blocks and associated methods software and requirements engineering approaches were utilized. Furthermore, a process-oriented approach was chosen, as information required in the creating process of ethics committee proposals remain unknown in the beginning of planning an MDR-LT. Here, we derived the needed steps from medical product certification. This was done as the medical product certification itself also communicates a process-oriented approach rather than merely focusing on content. A proposal was created for validation and inspection of applicability by using the proposed building blocks. The proposed best practice was tested and refined within SEMPER (Secondary Malignoma - Prospective Evaluation of the Radiotherapeutics dose distribution as the cause for induction) as a case study. RESULTS: The proposed building blocks cover the topics of "Context Analysis", "Requirements Analysis", "Requirements Validation", "Electronic Case Report (eCRF) Design" and "Overall Concept Creation". Additional methods are attached with regards to each topic. The goals of each block can be met by applying those methods. The proposed methods are proven methods as applied in e.g. existing Medical Data Registry projects, as well as in software or requirements engineering. CONCLUSION: Several building blocks and attached methods could be identified in the creation of a generic ethics committee proposal. Hence, an Ethics Committee can make informed decisions on the suggested study via said blocks, using the suggested methods such as "Defining Clinical Questions" within the Context Analysis. The study creators have to confirm that they adhere to the proposed procedure within the ethic proposal statement. Additional existing Medical Data Registry projects can be compared to EsPRit for conformity to the proposed procedure. This allows for the identification of gaps, which can lead to amendments requested by the ethics committee.

Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors.

BACKGROUND: This phase I dose-escalation study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics (PDs), and preliminary antitumor activity of BGT226, a potent, oral dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin inhibitor. PATIENTS AND METHODS: Fifty-seven patients with advanced solid tumors received BGT226 2.5-125 mg/day three times weekly (TIW). Dose escalation was guided by an adaptive Bayesian logistic regression model with overdose control. Assessments included response per RECIST, [18F]-fluorodeoxyglucose uptake, and phosphorylated-S6 in skin and paired tumor samples. RESULTS: Three patients (125 mg cohort) had dose-limiting toxic effects (grade 3 nausea/vomiting, diarrhea). BGT226-related adverse events included nausea (68%), diarrhea (61%), vomiting (49%), and fatigue (19%). BGT226 demonstrated rapid absorption, variable systemic exposure, and a median half-life of 6-9 h. Seventeen patients (30%) had stable disease (SD) as best response. Nine patients had SD for ≥16 weeks. Thirty patients (53%) achieved stable metabolic disease as assessed by [18F]-fluorodeoxyglucose-positron emission tomography; however, no correlation between metabolic response and tumor shrinkage according to computed tomography was observed. PD changes suggested PI3K pathway inhibition but were inconsistent. CONCLUSIONS: The MTD of BGT226 was 125 mg/day TIW, and the clinically recommended dose was 100 mg/day TIW. Limited preliminary antitumor activity and inconsistent target inhibition were observed, potentially due to low systemic exposure.

Clinical Information Systems Research in the Pandemic Year 2020.

OBJECTIVE: In this synopsis, we give an overview of recent research and propose a selection of best papers published in 2020 in the field of Clinical Information Systems (CIS). METHOD: As CIS section editors, we annually apply a systematic process to retrieve articles for the International Medical Informatics Association Yearbook of Medical Informatics. For seven years now, we use the same query to find relevant publications in the CIS field. Each year we retrieve more than 2,400 papers which we categorize in a multi-pass review to distill a preselection of 15 candidate papers. External reviewers and yearbook editors then assess the selected candidate papers. Based on the review results, the IMIA Yearbook editorial board chooses up to four best publications for the section at a selection meeting. To get an overview of the content of the retrieved articles, we use text mining and term co-occurrence mapping techniques. RESULTS: We carried out the query in mid-January 2021 and retrieved a deduplicated result set of 2,787 articles from 1,135 different journals. We nominated 15 papers as candidates and finally selected four of them as the best papers in the CIS section. As in the previous years, the content analysis of the articles revealed the broad spectrum of topics covered by CIS research. Thus, this year we could observe a significant impact of COVID-19 on CIS research. CONCLUSIONS: The trends in CIS research, as seen in recent years, continue to be observable. What was very visible was the impact of the Corona Virus Disease 2019 (COVID-19) pandemic, which has affected not only our lives but also CIS.

Effects of ensiling cereal grains (barley, wheat, triticale and rye) on total and pre-caecal digestibility of proximate nutrients and amino acids in pigs.

Inclemency of weather frequently causes critical water contents in cereal grains above 15%. Ensiling in pre-mature condition may be an alternative to other techniques of preservation. Aim of this study was to compare apparent total tract digestibility (D(t) ; barley, wheat, triticale, rye) of proximate nutrients and pre-caecal digestibility (D(pc); barley, wheat) of amino acids (AA), respectively, from cereal grains in ensiled and almost dry condition. Moistly harvested cereal grains (67-73% dry matter) were milled through a 4-mm sieve and ensiled with lactic acid bacteria (LAB, 3 × 10(5) colony forming units/g Lactobacillus plantarum DSMZ 8862 and 8866). To investigate D(t), two trials were conducted with six Mini-Lewe pigs and four German Landrace pigs, respectively. D(pc) of AA was determined using four German Landrace pigs with ileo-rectal anastomosis. D(t) of proximate nutrients did not differ between cereal grains and their silages, except for ether extract, which was more digestible in ensiled than dry wheat, triticale and rye (p < 0.05). Lysine content was lower in ensiled than dry barley and wheat. In barley, ensiling was accompanied by reduced D(pc) of lysine and histidine (p < 0.05). In wheat, ensiling increased D(pc) of lysine, methionine, threonine and leucin (p < 0.05). Ensiling of pre-mature cereal grains with LAB can serve as a reasonable storage alternative. However, as limited data are yet available, further research is required to understand completely the impact of ensiling on nutritional value as indicated, for example, by the lysine content and the D(pc) of certain AA.

Trends in Clinical Information Systems Research in 2019.

OBJECTIVE: To give an overview of recent research and to propose a selection of best papers published in 2019 in the field of Clinical Information Systems (CIS). METHOD: Each year, we apply a systematic process to retrieve articles for the CIS section of the IMIA Yearbook of Medical Informatics. For six years now, we use the same query to find relevant publications in the CIS field. Each year we retrieve more than 2,000 papers. As CIS section editors, we categorize the retrieved articles in a multi-pass review to distill a pre-selection of 15 candidate best papers. Then, Yearbook editors and external reviewers assess the selected candidate best papers. Based on the review results, the IMIA Yearbook Editorial Committee chooses the best papers during the selection meeting. We used text mining, and term co-occurrence mapping techniques to get an overview of the content of the retrieved articles. RESULTS: We carried out the query in mid-January 2020 and retrieved a de-duplicated result set of 2,407 articles from 1,023 different journals. This year, we nominated 14 papers as candidate best papers, and three of them were finally selected as best papers in the CIS section. As in previous years, the content analysis of the articles revealed the broad spectrum of topics covered by CIS research. CONCLUSIONS: We could observe ongoing trends, as seen in the last years. Patient benefit research is in the focus of many research activities, and trans-institutional aggregation of data remains a relevant field of work. Powerful machine-learning-based approaches, that use readily available data now often outperform human-based procedures. However, the ethical perspective of this development often comes too short in the considerations. We thus assume that ethical aspects will and should deliver much food for thought for future CIS research.

A 69-kD protein that associates reversibly with the Sm core domain of several spliceosomal snRNP species.

The biogenesis of the spliceosomal small nuclear ribonucleoproteins (snRNPs) U1, U2, U4, and U5 involves: (a) migration of the snRNA molecules from the nucleus to the cytoplasm; (b) assembly of a group of common proteins (Sm proteins) and their binding to a region on the snRNAs called the Sm-binding site; and (c) translocation of the RNP back to the nucleus. A first prerequisite for understanding the assembly pathway and nuclear transport of the snRNPs in more detail is the knowledge of all the snRNP proteins that play essential roles in these processes. We have recently observed a previously undetected 69-kD protein in 12S U1 snRNPs isolated from HeLa nuclear extracts under non-denaturing conditions that is clearly distinct from the U1-70K protein. The following evidence indicates that the 69-kD protein is a common, rather than a U1-specific, protein, possibly associating with the snRNP core particles by protein-protein interaction. (a) Antibodies raised against the 69-kD protein, which did not cross-react with any of the Sm proteins B'-G, precipitated not only U1 snRNPs, but also the other spliceosomal snRNPs U2, U4/U6 and U5, albeit to a lower extent. (b) U1, U2, and U5 core RNP particles reconstituted in vitro contain the 69-kD protein. (c) Xenopus laevis oocytes contain an immunologically related homologue of the human 69-kD protein. When U1 snRNA as well as a mutant U1 snRNA, that can bind the Sm core proteins but lacks the capacity to bind the U1-specific proteins 70K, A, and C, were injected into Xenopus oocytes to allow assembly in vivo, they were recognized by antibodies specific against the 69-kD protein in the ooplasm and in the nucleus. The 69-kD protein is under-represented, if present at all, in purified 17S U2 and in 25S [U4/U6.U5] tri-snRNPs, isolated from HeLa nuclear extracts. Our results are consistent with the working hypothesis that this protein may either play a role in the cytoplasmic assembly of the core domain of the snRNPs and/or in the nuclear transport of the snRNPs. After transport of the snRNPs into the nucleus, it may dissociate from the particles as for example in the case of the 17S U2 or the 25S [U4/U6.U5] tri-snRNP, which bind more than 10 different snRNP specific proteins each in the nucleus.

Clinical Information Systems as the Backbone of a Complex Information Logistics Process: Findings from the Clinical Information Systems Perspective for 2016.

Objective: To summarize recent research and to propose a selection of best papers published in 2016 in the field of Clinical Information Systems (CIS). Method: The query used to retrieve the articles for the CIS section of the 2016 edition of the IMIA Yearbook of Medical Informatics was reused. It again aimed at identifying relevant publications in the field of CIS from PubMed and Web of Science and comprised search terms from the Medical Subject Headings (MeSH) catalog as well as additional free text search terms. The retrieved articles were categorized in a multi-pass review carried out by the two section editors. The final selection of candidate papers was then peer-reviewed by Yearbook editors and external reviewers. Based on the review results, the best papers were then chosen at the selection meeting with the IMIA Yearbook editorial board. Text mining, term co-occurrence mapping, and topic modelling techniques were used to get an overview on the content of the retrieved articles. Results: The query was carried out in mid-January 2017, yielding a consolidated result set of 2,190 articles published in 921 different journals. Out of them, 14 papers were nominated as candidate best papers and three of them were finally selected as the best papers of the CIS field. The content analysis of the articles revealed the broad spectrum of topics covered by CIS research. Conclusions: The CIS field is multi-dimensional and complex. It is hard to draw a well-defined outline between CIS and other domains or other sections of the IMIA Yearbook. The trends observed in the previous years are progressing. Clinical information systems are more than just sociotechnical systems for data collection, processing, exchange, presentation, and archiving. They are the backbone of a complex, trans-institutional information logistics process.

Evaluation Considerations for Secondary Uses of Clinical Data: Principles for an Evidence-based Approach to Policy and Implementation of Secondary Analysis.

Objectives: To set the scientific context and then suggest principles for an evidence-based approach to secondary uses of clinical data, covering both evaluation of the secondary uses of data and evaluation of health systems and services based upon secondary uses of data. Method: Working Group review of selected literature and policy approaches. Results: We present important considerations in the evaluation of secondary uses of clinical data from the angles of governance and trust, theory, semantics, and policy. We make the case for a multi-level and multi-factorial approach to the evaluation of secondary uses of clinical data and describe a methodological framework for best practice. We emphasise the importance of evaluating the governance of secondary uses of health data in maintaining trust, which is essential for such uses. We also offer examples of the re-use of routine health data to demonstrate how it can support evaluation of clinical performance and optimize health IT system design. Conclusions: Great expectations are resting upon "Big Data" and innovative analytics. However, to build and maintain public trust, improve data reliability, and assure the validity of analytic inferences, there must be independent and transparent evaluation. A mature and evidence-based approach needs not merely data science, but must be guided by the broader concerns of applied health informatics.

New Problems - New Solutions: A Never Ending Story. Findings from the Clinical Information Systems Perspective for 2015.

OBJECTIVE: To summarize recent research and to propose a selection of best papers published in 2015 in the field of Clinical Information Systems (CIS). METHOD: The query which had been used last year to retrieve articles for the CIS section of the IMIA Yearbook of Medical Informatics 2015 was refined. It again aimed at identifying relevant publications in the field of CIS and comprised search terms from the Medical Subject Headings (MeSH) catalog as well as additional free text search terms from PubMed and Web of Science. The retrieved articles were categorized in a multi-pass review carried out separately by the two section editors. The final selection of 15 candidate papers was then peer-reviewed by Yearbook editors and external reviewers. Based on the review results the four best papers were then selected at the best papers selection meeting with the IMIA Yearbook editorial board. To get an overview on the content of the retrieved articles we applied text mining and term co-occurrence mapping techniques. RESULTS: The query was carried out in mid-January 2016, yielding a combined result set of 1851 articles which were published in 790 different journals. The most relevant terms from abstracts and titles of these articles were assigned to six different clusters. A majority of articles dealt with two thematic blocks, problems and solutions in the CIS field. The majority of the 2016 CIS candidate papers and all four best papers could be assigned to these two thematic blocks. CONCLUSIONS: We identified two main tracks among the CIS candidate and best papers as well as in CIS research activities in general: problems and solutions. A never ending cycle of continuous improvement.

SPIRIT: Systematic Planning of Intelligent Reuse of Integrated Clinical Routine Data. A Conceptual Best-practice Framework and Procedure Model.

BACKGROUND: Secondary use of clinical routine data is receiving an increasing amount of attention in biomedicine and healthcare. However, building and analysing integrated clinical routine data repositories are nontrivial, challenging tasks. As in most evolving fields, recognized standards, well-proven methodological frameworks, or accurately described best-practice approaches for the systematic planning of solutions for secondary use of routine medical record data are missing. OBJECTIVE: We propose a conceptual best-practice framework and procedure model for the systematic planning of intelligent reuse of integrated clinical routine data (SPIRIT). METHODS: SPIRIT was developed based on a broad literature overview and further refined in two case studies with different kinds of clinical routine data, including process-oriented nursing data from a large hospital group and high-volume multimodal clinical data from a neurologic intensive care unit. RESULTS: SPIRIT aims at tailoring secondary use solutions to specific needs of single departments without losing sight of the institution as a whole. It provides a general conceptual best-practice framework consisting of three parts: First, a secondary use strategy for the whole organization is determined. Second, comprehensive analyses are conducted from two different viewpoints to define the requirements regarding a clinical routine data reuse solution at the system level from the data perspective (BOTTOM UP) and at the strategic level from the future users perspective (TOP DOWN). An obligatory clinical context analysis (IN BETWEEN) facilitates refinement, combination, and integration of the different requirements. The third part of SPIRIT is dedicated to implementation, which comprises design and realization of clinical data integration and management as well as data analysis solutions. CONCLUSIONS: The SPIRIT framework is intended to be used to systematically plan the intelligent reuse of clinical routine data for multiple purposes, which often was not intended when the primary clinical documentation systems were implemented. SPIRIT helps to overcome this gap. It can be applied in healthcare institutions of any size or specialization and allows a stepwise setup and evolution of holistic clinical routine data reuse solutions.

Molecular cloning and subcellular localisation of the snRNP-associated protein 69KD, a structural homologue of the proto-oncoproteins TLS and EWS with RNA and DNA-binding properties.

We recently isolated and characterised a 69 kDa protein (69KD) found associated with spliceosomal small nuclear ribonucleoproteins (snRNPs). Here, we report the molecular cloning of a cDNA encoding this protein, its nucleic acid binding properties and its subcellular localisation. Sequence analysis of the 69KD cDNA revealed: (1) that 69KD shares structural similarity with the human RNA binding proteins TLS and EWS (95% and 65% identity, respectively), the products of two genes frequently targeted by tumour-specific chromosomal translocations; (2) that 69KD contains a consensus RNA binding domain (CS-RBD) and three Arg/Gly-rich RNA binding motifs, structural features typical of many RNA binding proteins, in particular of hnRNP proteins; and (3) that 69KD contains a single putative Cys2/Cys2 zinc finger domain, a characteristic of many DNA-binding proteins. Consistent with its possession of these motifs, 69KD display a general nucleic acid binding activity, with a strong preference for guanyl and uridyl-rich RNA sequences, as well as for single-stranded and double-stranded DNA. The functional significance of this affinity for nucleic acids remains unclear. However, based on the established association of 69KD with the Sm core domain of snRNPs in vivo, these motifs might help mediate 69KD binding to snRNPs or be involved in some, as yet, unknown aspect of RNA metabolism. Consistent with both possibilities, 69KD is detected within typical snRNP containing subnuclear structures referred to as speckles, and is also more widely distributed throughout the nucleoplasm, as observed for many hnRNP proteins.

Direct binding of small nuclear ribonucleoprotein G to the Sm site of small nuclear RNA. Ultraviolet light cross-linking of protein G to the AAU stretch within the Sm site (AAUUUGUGG) of U1 small nuclear ribonucleoprotein reconstituted in vitro.

The major small nuclear ribonucleoproteins (snRNPs) U1, U2, U5 and U4/U6 participate in the splicing of pre-mRNA. U1, U2, U4 and U5 RNAs share a highly conserved sequence motif PuA(U)nGPu, termed the Sm site, which is normally flanked by two hairpin loops. The Sm site provides the major binding site for the group of common proteins, B', B, D1, D2, D3, E, F and G, which are shared by the spliceosomal snRNPs. We have investigated the ability of common snRNP proteins to recognize the Sm site of snRNA by using ultraviolet light-induced RNA-protein cross-linking within U1 snRNP particles. The U1 snRNP particles, reconstituted in vitro, contained U1 snRNA labelled with 32P. Cross-linking of protein to this U1 snRNA occurred only in the presence of the single-stranded stretch of snRNA that makes up the conserved Sm site. Characterization of the cross-linked protein by one and two-dimensional gel electrophoresis indicated that snRNP protein G had become cross-linked to the U1 snRNA. This was confirmed by specific immunoprecipitation of the cross-linked RNA-protein complex with an anti-G antiserum. The cross-link was located on the U1 snRNA by fingerprint analysis with RNases T1 and A; this demonstrated that the protein G has been cross-linked to the AAU stretch within the 5'-terminal half of the Sm site (AAUUUGUGG). These results suggest that the snRNP protein G may be involved in the direct recognition of the Sm site.

Job Profiles of Biomedical Informatics Graduates. Results of a Graduate Survey.

BACKGROUND: Biomedical informatics programs exist in many countries. Some analyses of the skills needed and of recommendations for curricular content for such programs have been published. However, not much is known of the job profiles and job careers of their graduates. OBJECTIVES: To analyse the job profiles and job careers of 175 graduates of the biomedical informatics bachelor and master program of the Tyrolean university UMIT. METHODS: Survey of all biomedical informatics students who graduated from UMIT between 2001 and 2013. RESULTS: Information is available for 170 graduates. Eight percent of graduates are male. Of all bachelor graduates, 86% started a master program. Of all master graduates, 36% started a PhD. The job profiles are quite diverse: at the time of the survey, 35% of all master graduates worked in the health IT industry, 24% at research institutions, 9% in hospitals, 9% as medical doctors, 17% as informaticians outside the health care sector, and 6% in other areas. Overall, 68% of the graduates are working as biomedical informaticians. The results of the survey indicate a good job situation for the graduates. CONCLUSIONS: The job opportunities for biomedical informaticians who graduated with a bachelor or master degree from UMIT seem to be quite good. The majority of graduates are working as biomedical informaticians. A larger number of comparable surveys of graduates from other biomedical informatics programs would help to enhance our knowledge about careers in biomedical informatics.

Findings from the Clinical Information Systems Perspective.

OBJECTIVE: To summarize recent research and to propose a selection of best papers published in 2014 in the field of Clinical Information Systems (CIS). METHOD: A query with search terms from the Medical Subject Headings (MeSH) catalog as well as additional free text search terms was designed to identify relevant publications in the field of clinical information systems from PubMed and Web of Science®. The retrieved articles were then categorized in a multi-pass review carried out separately by the section editors. The final selection of 15 candidate papers was then peerreviewed by Yearbook editors and external reviewers. Based on the review results the four best papers were then selected at the best papers selection meeting with the IMIA Yearbook editorial board. RESULTS: The query was carried out in mid-January 2015, yielding a combined result set of 1525 articles which were published in 722 different journals. Among these articles two main thematic sections were identified: i) Interoperability from a syntactical and semantic point of view as well as from a longterm preservation and organizational/legal point of view and ii) secondary use of existing health data in all its shades. Here, patient safety was a major scope of application. CONCLUSIONS: CIS have become mature over the last years. The focus has now moved beyond data acquisition for just supporting the local care workflows. Actual research efforts in the CIS domain comprise the breakdown of information silos, the reduction of barriers between different systems of different care providers and secondary use of accumulated health data for multiple purposes.

A Nursing Intelligence System to Support Secondary Use of Nursing Routine Data.

BACKGROUND: Nursing care is facing exponential growth of information from nursing documentation. This amount of electronically available data collected routinely opens up new opportunities for secondary use. OBJECTIVES: To present a case study of a nursing intelligence system for reusing routinely collected nursing documentation data for multiple purposes, including quality management of nursing care. METHODS: The SPIRIT framework for systematically planning the reuse of clinical routine data was leveraged to design a nursing intelligence system which then was implemented using open source tools in a large university hospital group following the spiral model of software engineering. RESULTS: The nursing intelligence system is in routine use now and updated regularly, and includes over 40 million data sets. It allows the outcome and quality analysis of data related to the nursing process. CONCLUSIONS: Following a systematic approach for planning and designing a solution for reusing routine care data appeared to be successful. The resulting nursing intelligence system is useful in practice now, but remains malleable for future changes.

Three-dimensional location of ribosomal protein BL2 from Bacillus stearothermophilus, a key component of the peptidyl transferase center.

Protein BL2 from Bacillus stearothermophilus has been localized by immunoelectron microscopy on the interface side of the 50 S subunit, beneath the angle formed between the central protuberance and the L1 protuberance. The immuno-electron microscopic data suggest that the interface region of the 50 S particle is not as flat as most of the proposed three-dimensional models suggest, but instead there is a significant concavity. Since several studies demonstrated that BL2 is implicated in peptidyl transferase activity or at least located close to the peptidyl transferase center, the location of protein BL2 also provides information as to the location of this important functional domain.

Effect of large volume replacement with balanced electrolyte solutions on extravascular lung water in surgical patients with sepsis syndrome.

We investigated the effect of large volume replacement with balanced electrolyte solutions on extravascular lung water (EVLW) in 16 adult surgical patients with sepsis syndrome. Patients entered the study within the 24 h period following surgical interventions for acute necrotizing pancreatitis, intra-abdominal abscesses, and/or peritonitis. Sequential measurements (n = 108) were made at intervals of 6-12 h over a 48 h period. There were no significant differences between initial and final values of thermal-dye EVLW (5.0 +/- 1.1 vs. 5.7 +/- 1.1 ml/kg), plasma colloid osmotic pressure (COP, 13.3 +/- 2.5 vs. 13.2 +/- 2.9 mmHg), pulmonary artery wedge pressure (PAWP, 9.2 +/- 3.0 vs. 10.8 +/- 3.0 mmHg), and COP-PAWP gradient (4.0 +/- 3.5 vs. 2.4 +/- 3.9 mmHg). All results expressed as (mean +/- SD). The EVLW did not correlate with plasma COP, PAWP, or COP-PAWP gradient. We conclude that large volume replacement with balanced electrolyte solutions with the secondary decrease in plasma COP and COP-PAWP gradient do not necessarily contribute to a substantial increase in EVLW. This study fails to show any causal relationship between decrease in plasma COP or COP-PAWP gradient and oedema formation in the lung.

Facial injuries in skiing. A retrospective study of 549 cases.

In the last 2 decades, reports of skiing injuries have shown an increasing number of skiers with severe trauma. This article provides an account of a retrospective study of 549 patients with 1155 facial injuries sustained while skiing who received treatment at the Department of Oral and Maxillofacial Surgery at the University Hospital in Innsbruck, Austria between 1991 and 1996. The study was based on a questionnaire answered by the patients and on case report forms. Most of the patients were male (65.2%) and were aged between 3 and 81 years (average 28.4 years). A simple fall while skiing was the main type of accident (45.9%), followed by collisions with other people (23.5%). Injuries were classified into 1 of 3 groups: (i) lesions of the soft tissue (32.2% of all injuries); (ii) dentoalveolar traumas (24.3%); and (iii) fractures of facial bones (43.5%). Lacerations and haematomas were the most frequent lesions in patients with injuries to the soft tissues. The group of patients with dentoalveolar trauma mainly presented with fractures of tooth crowns. Fractures involving the mandible and the zygomatic bone were predominant in patients in the third group. Concomitant injuries mainly included injuries to the brain and skull fractures. Treatment was ambulatory, or by admission and surgery. We did not observe an increase in the number of skiing accidents causing facial injury in the last 5 years. Facial injuries represented 4% of all skiing injuries, a lower proportion than in other sports.