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High throughput sequencing technologies have facilitated an outburst in biological knowledge over the past decades and thus enables improvements in personalized medicine. In order to support (international) medical research with the combination of genomic and clinical patient data, a standardization and harmonization of these data sources is highly desirable. To support this increasing importance of genomic data, we have created semantic mapping from raw genomic data to both FHIR (Fast Healthcare Interoperability Resources) and OMOP (Observational Medical Outcomes Partnership) CDM (Common Data Model) and analyzed the data coverage of both models. For this, we calculated the mapping score for different data categories and the relative data coverage in both FHIR and OMOP CDM. Our results show, that the patients genomic data can be mapped to OMOP CDM directly from VCF (Variant Call Format) file with a coverage of slightly over 50%. However, using FHIR as intermediate representation does not lead to further information loss as the already stored data in FHIR can be further transformed into OMOP CDM format with almost 100% success. Our findings are in favor of extending OMOP CDM with patient genomic data using ETL to enable the researchers to apply different analysis methods including machine learning algorithms on genomic data.

High throughput sequencing technologies have facilitated an outburst in biological knowledge over the past decades and thus enables improvements in personalized medicine. In order to support (international) medical research with the combination of genomic and clinical patient data, a standardization and harmonization of these data sources is highly desirable. To support this increasing importance of genomic data, we have created semantic mapping from raw genomic data to both FHIR (Fast Healthcare Interoperability Resources) and OMOP (Observational Medical Outcomes Partnership) CDM (Common Data Model) and analyzed the data coverage of both models. For this, we calculated the mapping score for different data categories and the relative data coverage in both FHIR and OMOP CDM. Our results show, that the patients genomic data can be mapped to OMOP CDM directly from VCF (Variant Call Format) file with a coverage of slightly over 50%. However, using FHIR as intermediate representation does not lead to further information loss as the already stored data in FHIR can be further transformed into OMOP CDM format with almost 100% success. Our findings are in favor of extending OMOP CDM with patient genomic data using ETL to enable the researchers to apply different analysis methods including machine learning algorithms on genomic data.

The MIRACUM consortium is developing a Clinical Trials Recruitment Support System to support the data-driven recruitment of patients for clinical trials. The design of the prototype includes both open source solutions (OMOP CDM, Atlas) and open standards for interoperability (FHIR). The aim of the prototype is to create a patient screening list of potential participants for a clinical study. The paper shows the modular structure and functionality of the prototype building the foundation for the practical implementation of the CTRSS and, at the same time, demonstrating the use of open source solutions and standards for the development of clinical support systems.

BACKGROUND Clinical trial registries increase transparency in medical research by making information and results of planned, ongoing, and completed studies publicly available. However, the registration of clinical trials remains a time-consuming manual task complicated by the fact that the same studies often need to be registered in different registries with different data entry requirements and interfaces. OBJECTIVE This study investigates how Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) may be used as a standardized format for exchanging and storing clinical trial records. METHODS We designed and prototypically implemented an open-source central trial registry containing records from university hospitals, which are automatically exported and updated by local study management systems. RESULTS We provided an architecture and implementation of a multisite clinical trials registry based on HL7 FHIR as a data storage and exchange format. CONCLUSIONS The results show that FHIR resources establish a harmonized view of study information from heterogeneous sources by enabling automated data exchange between trial centers and central study registries.

Background Clinical trial registries increase transparency in medical research by making information and results of planned, ongoing, and completed studies publicly available. However, the registration of clinical trials remains a time-consuming manual task complicated by the fact that the same studies often need to be registered in different registries with different data entry requirements and interfaces. Objective This study investigates how Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) may be used as a standardized format for exchanging and storing clinical trial records. Methods We designed and prototypically implemented an open-source central trial registry containing records from university hospitals, which are automatically exported and updated by local study management systems. Results We provided an architecture and implementation of a multisite clinical trials registry based on HL7 FHIR as a data storage and exchange format. Conclusions The results show that FHIR resources establish a harmonized view of study information from heterogeneous sources by enabling automated data exchange between trial centers and central study registries.

Background Lack of a national neonatal screening protocol in Iran, displaces routine hearing screening at elementary school entry. Early diagnosis of hearing loss (HL) leads to early intervention and improvement of developmental skills in children. The current research aimed to determine diagnostic age and causes of HL in male students at school entry to evaluate this hearing screening performance and its efficacy as a guideline for deciding early diagnosis. Methods This cross sectional study included 2277 male students aged 6–7 years from elementary school boys in Mashhad, Iran from 2010 to 2011. We evaluated subjects’ medical archives, interviewed with their parents and hygiene teacher and took physical examination, demographic information, birth and HL history for data gathering. Audiologic assessment consisted of otoscopy, tympanometry and audiometry. Results 36 (1.58%) of students had hearing impairment. Prevalence of HL in urban schools was significantly higher than rural ones ( P = 0.02). Making diagnosis by physician was significantly more than by parents ( P P = 0.001). The common age of diagnosis was at elementary school entry ( P Discussion Screening protocol at elementary school entry suggested late diagnosis and poor outcome in Iran. National screening is necessary in newborns, elementary school entry and when suspect to HL. The parents, teachers and population should have much greater awareness of HL diagnosis. In present study, chicken pox may lead to HL, therefore routine vaccination is recommended.

Einleitung: Datenintegration und -aufbereitung zur Sekundärnutzung in der medizinischen Forschung gewinnt aufgrund steigendender Patientenzahlen zunehmend an Bedeutung. Das vom Bundesministerium für Bildung und Forschung im Rahmen der Medizininformatik-Initiative geförderte Konsortium[zum vollständigen Text gelangen Sie über die oben angegebene URL], 64. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS)

Understanding the prevalence of structured data elements within clinical trial eligibility criteria is a crucial step for prioritizing integration efforts to supported automated patient recruitment into clinical trials based on electronic health record data. In this work, we extract data elements from 50 clinical trials using a collaborative, crowd-sourced, and iterative method. A total of 1.120 criteria were analyzed, and 204 unique data elements were extracted. The most prevalent elements were diagnosis code, procedure code, and medication code, occurring in 414 (37 %), 112 (10 %), and 91 (8 %) of eligibility criteria respectively. The results of this study may aid in optimizing data integration and documentation efforts in the EHR to support clinical trial eligibility determination.

Background: The aim of the present study was to evaluate the characteristics and accuracy of cerebrospinal fluid (CSF) parameters for neonatal meningitis, by comparing CSF data in newborns and in infants ≤2 months of age, with or without meningitis. Methods: This case–control study was performed on 120 newborns and infants ≤2 months old. 60 patients with meningitis were considered as the case group and 60 ill patients without meningitis were defined as the control group. Each of the two groups was divided into 0–1 months and 1–2 months old. CSF characteristics were compared in newborns in the case and control groups; in infants ≤2 months old in the case and control groups; and in healthy newborns and healthy infants ≤2 months old. Results: The mortality rate was 16.7% in the case group. The differences of CSF parameters in the case and control groups were mostly not significant, except for CSF glucose only in term newborns

Background: Neonatal jaundice is a common cause of sensorneural hearing loss in children. Objectives: We aimed to detect the neurotoxic effects of pathologic hyperbilirubinemia on brain stem and auditory tract by auditory brain stem evoked response (ABR) which could predict early effects of hyperbilirubinemia. Patients and Methods: This case-control study was performed on newborns with pathologic hyperbilirubinemia. The inclusion criteria were healthy term and near term (35 - 37 weeks) newborns with pathologic hyperbilirubinemia with serum bilirubin values of ≥ 7 mg/dL, ≥ 10 mg/dL and ≥14 mg/dL at the first, second and third-day of life, respectively, and with bilirubin concentration ≥ 18 mg/dL at over 72 hours of life. The exclusion criteria included family history and diseases causing sensorineural hearing loss, use of auto-toxic medications within the preceding five days, convulsion, congenital craniofacial anomalies, birth trauma, preterm newborns < 35 weeks old, birth weight < 1500 g, asphyxia, and mechanical ventilations for five days or more. A total of 48 newborns with hyperbilirubinemia met the enrolment criteria as the case group and 49 healthy newborns as the control group, who were hospitalized in a university educational hospital (22 Bahaman), in a north-eastern city of Iran, Mashhad. ABR was performed on both groups. The evaluated variable factors were latency time, inter peak intervals time, and loss of waves. Results: The mean latencies of waves I, III and V of ABR were significantly higher in the pathologic hyperbilirubinemia group compared with the controls (P < 0.001). In addition, the mean interpeak intervals (IPI) of waves I-III, I-V and III-V of ABR were significantly higher in the pathologic hyperbilirubinemia group compared with the controls (P < 0.001). For example, the mean latencies time of wave I was significantly higher in right ear of the case group than in controls (2.16 ± 0.26 vs. 1.77 ± 0.15 milliseconds, respectively) (P < 0.001). Conclusions: Pathologic hyperbilirubinemia causes acute disorder on brain stem function; therefore, early diagnosis of neonatal jaundice for prevention of bilirubin neurotoxic effects is essential. As national neonatal hearing screening in not yet established in Iran, we recommend performing ABR for screening of bilirubin neurotoxicity in all cases with hyperbilirubinemia.

The aim of the present study was to evaluate the characteristics and accuracy of cerebrospinal fluid (CSF) parameters for neonatal meningitis, by comparing CSF data in newborns and in infants ≤ 2 months of age, with or without meningitis.This case-control study was performed on 120 newborns and infants ≤ 2 months old. 60 patients with meningitis were considered as the case group and 60 ill patients without meningitis were defined as the control group. Each of the two groups was divided into 0-1 months and 1-2 months old. CSF characteristics were compared in newborns in the case and control groups; in infants ≤ 2 months old in the case and control groups; and in healthy newborns and healthy infants ≤ 2 months old.The mortality rate was 16.7% in the case group. The differences of CSF parameters in the case and control groups were mostly not significant, except for CSF glucose only in term newborns7 days old (P= 0.04), and white cell count (WBC) only in 0-7-day-old term and preterm neonates (P= 0.04 and P= 0.01, respectively). Polymorphonuclear leukocyte (PMNL) level in the case group was significantly higher than in the control group (P= 0.02). CSF characteristics in healthy newborns were nearly the same as in healthy infants ≤ 2 months old. Prevalence of positive CSF culture was 31.7% in the case group. The most common pathogen was Neisseria meningitidis in the two age groups. The concomitant positive blood culture in the case group was 26.3%.In the case of meningitis with negative CSF culture and Gram stain, diagnosis can be made on CSF parameters, clinical and laboratory findings and suspicion of meningitis. Therefore, a clinical prediction rule to classify risk for bacterial meningitis on evaluation of CSF parameters in any region should be established. More regional trials are needed to enhance the probability of diagnosis according to CSF parameters.

To evaluate the in vitro effects of chichorium intybus on bilirubin levels.In this study the bilirubin levels in the serum of thirty neonates staying in the NICU and suffering from clinical jaundice was determined three times: first without any alterations, second after adding chichorium intybus extract and third after adding the same amount of distilled water. The results were compared using SPSS statistical software.Of the patients evaluated 76.7% were male and 23.3% were female. The average age was 7.35 days. The mean difference observed in unconjugated bilirubin levels in the specimens containing chichorium intybus extract was 3.84 +/- 2.38 mg/dl and in the ones containing distilled water was 2.85 +/- 2.00 mg/dl. The mean difference observed in conjugated bilirubin levels was 0.29 +/- 0.32 mg/dl in specimens containing distilled water and 0.35 +/- 0.26 in the ones containing chichorium intybus. In none of the cases the results were found to be significant.In this study chichorium intybus was found to have no significant in vitro effect on the bilirubin level reported by the laboratory. The in vivo effects of this herbal medicine must be evaluated more closely.

Integration of circuits on semiconductor devices with resulting increase in pin counts is driving the need for improvements in packaging for functionality and reliability. One solution to this demand is the Flip- Chip concept in Ultra Large Scale Integration (ULSI) applications [1]. The flip-chip technology is based on the direct attach principle of die to substrate interconnection.. The absence of bondwires clearly enables packages to become more slim and compact, and also provides higher pin counts and higher-speeds [2]. However, due to its construction, with inherent hidden structures the Flip-Chip technology presents a challenge for non-destructive Failure Analysis (F/A). The scanning acoustic microscope (SAM) has recently emerged as a valuable evaluation tool for this purpose [3]. C-mode scanning acoustic microscope (C-SAM), has the ability to demonstrate non-destructive package analysis while imaging the internal features of this package. Ultrasonic waves are very sensitive, particularly when they encounter density variations at surfaces, e.g. variations such as voids or delaminations similar to air gaps. These two anomalies are common to flip-chips. The primary issue with this package technology is the non-uniformity of the die attach through solder ball joints and epoxy underfill. The ball joints also present defects as open contacts, voids or cracks. In our acoustic microscopy study packages with known defects are considered. It includes C-SCAN analysis giving top views at a particular package interface and a B-SCAN analysis that provides cross-sectional views at a desired point of interest. The cross-section analysis capability gives confidence to the failure analyst in obtaining information from a failing area without physically sectioning the sample and destroying its electrical integrity. Our results presented here prove that appropriate selection of acoustic scanning modes and frequency parameters leads to good reliable correlation between the physical defects in the devices and the information given by the acoustic microscope.

Es wird eine Vorschrift mitgeteilt, die sich dafur eignet mit guter Ausbeute das spezifisch in einer Methylgruppe 14C- oder 13C-markierte 4-(3-Methyl-2-butenyl)tryptophan (6) zu synthetisieren. Weiter wird beschrieben, wie man die E- und Z-isomeren Nitrile 11E bzw. l l Z und daraus die ihnen entsprechenden Aldehyde 12E bzw. 1 2 2 sowie die Alkohole 8E bzw. 8Z darstellt. Durch „Umkehrung” der Wittigreaktion unter Verwendung des Phosphoniumsalzes 15 und Brenztraubensaureester kommt man zu den Estern 4Ea und 4Za und von diesen zu den entsprechenden Alkoholen. Ebenfalls aus 15 und 1,3-Diacetoxyaceton erhalt man die Dihydroxyverbindung 18. - Ein besonderer Vorteil bei diesen Synthesen ist die Verwendung der Tosylgruppe am Indolstickstoff. - Einige Zwischenprodukte konnen mit guten Ausbeuten nur unter Hochdruck gewonnen werden. Biosynthesis of Ergot Alkaloids, V1). - New Synthetic Approaches for Possible Intermediates in Ergot Alkaloid Biosynthesis A procedure is given for the facile synthesis of 4-(3-methyl-2-butenyl)tryptophan (6), which can be specifically labelled with 14C or 13C in one of the methyl groups. Furthermore, the preparation of the isomeric nitriles 11E and l l Z is described, and a method given for their transformation into the corresponding aldehydes 12E and 1 2 2 and alcohols 8 E and 8 2 . „Inverted” Wittig reaction using the phosphonium salt 15 and ethyl pyruvate affords the isomeric esters 4Ea and 4Za, which furnish the alcohols 8E and 8 Z on reduction. Reaction of 1,3-diacetoxyacetone with 15 leads to the dihydroxy compound 18. - A special advantage of these syntheses is the use of the tosyl group at the nitrogen of the indole nucleus. - Some of the intermediates could be obtained in good yields only under high pressure.

Publisher Summary This chapter presents a comparison of the sensitivities of PEP/LVET, d2z/dt2, 1/(PEP)2, and HI in response to drug interventions that either enhance or depress myocardial contractility. The two sets of experiments were conducted three years apart. In both cases, there was much learning in the experimental procedures and techniques so that later experiments in each set reflected the learning experience that was manifested by better records and more consistent data; however, the results shown represent the pooling of all data in each set. While additional experiments are needed to evaluate the sensitivities to smaller amounts of the inotropic agents, the striking differences between impedance derived indices of contraction and the clinically accepted PEP/LVET clearly indicate the greater sensitivity of the impedance indices. As the impedance derived indices have the units of acceleration, they would appear to be more directly related to the pumping ability of the heart than are the systolic time intervals.