Evaluation of Pelvic Floor Muscles in Pregnancy and Postpartum With Non-Invasive Magnetomyography.

Objective: To record and characterize features of levator ani muscles (LAM) activity in pregnancy and postpartum using non-invasive and novel Magnetomyography (MMG) technique with amplitude and spectral parameters. Methods: Nulliparous women with uncomplicated pregnancies participated in the MMG data collection during rest and voluntary LAM contractions (Kegels) with modulated intensity in third trimester and approximately 2 months postpartum (PP). Simultaneous surface electromyography was recorded to document the recruitment of accessory muscles. Moderate strength Kegel (MK) MMG trials were analyzed. Amplitude and spectral parameters including root-mean square (RMS) amplitude, power spectrum density (PSD) and normalized PSD (rPSD) in three frequency bands (low, middle, high) were computed on MK epochs. Statistical comparisons between pregnancy and postpartum were calculated. Results: MMG recordings were measured from 10 pregnant women. Results showed decreased RMS and power between third trimester and postpartum, trending towards significance. rPSD values in the low frequency band decreased significantly (p = 0.028) from third trimester to postpartum, while significant increase was observed in the middle frequency band (p = 0.018). Conclusions: This study shows that MMG as non-invasive tool has the ability to detect and characterize changes of LAM activity with amplitude and spectral parameters during pregnancy and postpartum.

Coupling Analysis of Fetal and Maternal Heart Rates via Transfer Entropy Using Magnetocardiography.

Recent studies have shown that occasional short term coupling between fetal and maternal cardiac systems occurs. Fetal magnetocardiography (fMCG) is a non-invasive technique that records the magnetic fields associated with the electrical activity of the fetal heart through sensors placed over the maternal abdomen. The fMCG allows accurate estimation of fetal heart rates (fHR) due to its high signal-to-noise ratio (SNR) and temporal resolution. In this study, we analyzed couplingbetween fHR and maternal heart rates (mHR) using Transfer Entropy (TE). TE determines coupling between two variables by quantifying the information transferred between them in both directions. In this work, we used 74 fMCG recordings to compute TE in both directions over 1-minute disjoint time windows (TW). We examined the effect of fetal movement (FM) as a factor of influence on the TE analysis. We identified 21 subjects with FM during the recording and separated them into two gestational age (GA) groups (GA1<32 and GA2≥32 weeks). Next, TE values were compared between TWs containing non- FM with TWs containing FM using Wilcoxon Signed-Rank test. In addition, we compared TE calculations for non-FM segments obtained from the 74 subjects using Rank-Sum test in the two GA groups. Our results showed that TE values from TWs containing FM are not significantly different than those computed for TWs of non-FM. In both directions, we found that TE values obtained from the 74 subjects did not show any significant difference between GA1 and GA2 which is consistent with previous studies. Our study suggests that FM does not affect the TE computations.

Selection of Reference Channels Based on Mutual Information for Frequency-Dependent Subtraction Method Applied to Fetal Biomagnetic Signals.

OBJECTIVE: We propose a method that uses minimal redundancy and maximal relevance (mRMR) based on mutual information as criteria to automatically select references for the frequency-dependent subtraction (SUBTR) method to attenuate maternal (mMCG) and fetal (fMCG) magnetocardiograms of fetal magnetoencephalography recordings. METHODS: mRMR is calculated between all channels and mMCG/fMCG target channels and the most promising sensors are used as references to perform SUBTR. We measured the performance of SUBTR at removing interferences in two steps for different number of references in 38 real datasets. The evaluation was based on the MCG amplitude reduction. We compared the performance of the mRMR approach with random selection of references. RESULTS: Significant differences in interference removal were found when a distinct number of references were chosen by mRMR compared to random selection. CONCLUSION: mRMR provides an effective tool to automatically select a set of featured references. SIGNIFICANCE: Although we show the utility of the mRMR method to biomagnetic signals, the approach can easily be adapted to sensor array data from other applications.

Cardiac time intervals derived by magnetocardiography in fetuses exposed to pregnancy hypertension syndromes.

OBJECTIVE: To test the hypothesis that fetuses exposed to maternal preeclampsia or chronic hypertension have deranged development of cardiac time intervals. STUDY DESIGN: Pregnancies were divided into three groups: Intrauterine Growth Restricted (IUGR), Hypertensive, and Normal. Each group's mean fetal cardiac time intervals (P, PR, QRS and RR) derived by magnetocardiography were calculated using an analysis of covariance model's regression-adjusted estimates for a gestational age of 35 weeks. RESULTS: We reviewed 141 recordings from 21 IUGR, 46 Hypertensive and 74 Normal patients. The IUGR, Hypertensive and Normal groups, respectively, had adjusted mean intervals in milliseconds of 66.4, 66.8 and 76.2 for P (P=0.001), 95.9, 101.6 and 109.6 for PR (P=0.002), 77.2, 78.7 and 78.7 for QRS (P=0.81) and 429.8, 429.2 and 428.5 for RR (P=0.97). CONCLUSION: P and PR intervals are abbreviated in normotrophic fetuses exposed to maternal hypertension, suggesting shortened atrioventricular conduction times.

Is bisphosphonate-related osteonecrosis of the jaw an infection? A histological and microbiological ten-year summary.

The role of infection in the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is poorly understood. Large-scale epidemiological descriptions of the histology and microbiology of BRONJ are not found in the literature. Herein, we present a systematic review of BRONJ histology and microbiology (including demographics, immunocompromised associations, clinical signs and symptoms, disease severity, antibiotic and surgical treatments, and recovery status) validating that infection should still be considered a prime component in the multifactorial disease.

Mammaglobin B (SCGB2A1) is a novel tumour antigen highly differentially expressed in all major histological types of ovarian cancer: implications for ovarian cancer immunotherapy.

BACKGROUND: We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b (SCGB2A1), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen. METHODS: We profiled 70 ovarian carcinomas including 24 serous (OSPC), 15 clear-cell (CC), 24 endometrioid (EAC) and 7 poorly differentiated tumours, and 14 normal human ovarian surface epithelial (HOSE) control cell lines using the Human HG-U133 Plus 2.0 chip (Affymetrix). Quantitative real-time PCR and immunohistochemistry staining techniques were used to validate microarray data at RNA and protein levels for SCGB2A1. Full-length human-recombinant SCGB2A1 was used to pulse monocyte-derived dendritic cells (DCs) to stimulate autologous SCGB2A1-specific cytotoxic T-lymphocyte (CTL) responses against chemo-naive and chemo-resistant autologous ovarian tumours. RESULTS: Gene expression profiling identified SCGB2A1 as a top differentially expressed gene in all histological ovarian cancer types tested. The CD8+ CTL populations generated against SCGB2A1 were able to consistently induce lysis of autologous primary (chemo-naive) and metastatic/recurrent (chemo-resistant) target tumour cells expressing SCGB2A1, whereas autologous HLA-identical noncancerous cells were not lysed. Cytotoxicity against autologous tumour cells was significantly inhibited by anti-HLA-class I (W6/32) monoclonal antibody. Intracellular cytokine expression measured by flow cytometry showed a striking type 1 cytokine profile (i.e., high IFN-γ secretion) in SCGB2A1-specific CTLs. CONCLUSION: SCGB2A1 is a top differentially expressed gene in all major histological types of ovarian cancers and may represent a novel and attractive target for the immunotherapy of patients harbouring recurrent disease resistant to chemotherapy.

Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer.

BACKGROUND: Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients. METHODS: SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR, immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied. RESULTS: SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by RT-PCR=162 vs 2.21; P=0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (mug ml(-1)) had a median (95% CIs) of 6.0 (4.0-8.9) in normal healthy females and 6.0 (4.2-8.1) in patients with benign disease (P=0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2-56.2), significantly higher than those in the healthy group (P=0.0005) and benign group (P=0.0006). Receiver operating characteristics (ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837 (P=0.0024). CONCLUSION: SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy.

Contribution of de novo point mutations to the overall mutational burden in mitochondrial DNA of adult rats.

This study analyzed the incidence of point mutations in mitochondrial DNA of brain and muscle tissues from young (6-month) and old (24-month) male F344 rats. Coding sequence mutations in subunit 5 of the NADH dehydrogenase gene were detected after high-fidelity PCR amplification and cloning by denaturing gradient gel electrophoresis (DGGE) assay followed by sequencing of detected mutants. In total, almost a thousand individual clones were analyzed both in brain and muscle samples. On average, mtDNA from brain tissue showed a 66% increase with age in mutation frequencies (2.3+/-1.9 vs. 3.8+/-4.5 x 10(-4) mutations/bp, mean+/-SD), which failed to reach statistical significance (p=0.45). Muscle tissues yielded substantially fewer mutants with average mutant frequencies for both young and old rats almost 10 times lower than the corresponding values in the brain tissue (0.3+/-0.4 and 0.5+/-0.6 x 10(-4), respectively). The difference in mutation accumulation between muscle and brain was highly significant in both the younger group (Chi-squared=9.7, p < or = 0.01) and in older animals (Chi-squared=10.9, p < or = 0.001). Molecular analysis of the mutated sequences revealed that almost half were identical sequences recurring in different samples and tissues. Our findings indicate that the process of mutation accumulation in mitochondria begins in the germ-line and/or during earlier stages of life, contributing up to half of the total mutational burden, whereas de novo spontaneous formation of point mutations in adulthood is far less than was anticipated.

Enhancing communications and connectivity in Africa: the multilateral initiative on malaria (MIM) model.

The U.S. National Library of Medicine, working in concert with the Multilateral Initiative on Malaria (MIM), has developed and implemented a unique organizational and technical strategy to connect malaria research sites to the Internet for purposes of facilitating North-South scientific communications and access to electronic information resources on the Web. The model employs microwave and VSAT technologies, and shares bandwidth and costs among participating malaria research sites and their respective research funders in Mali, Kenya, Ghana, Tanzania and other sub-Saharan locations affiliated with MIM. The concept of institutional partnership is an essential element of this information technology capacity building effort, which may find applicability in other developing regions of the world with similar communications and research networking needs and capabilities.

Public library consumer health information pilot project: results of a National Library of Medicine evaluation.

In October 1998, the National Library of Medicine (NLM) launched a pilot project to learn about the role of public libraries in providing health information to the public and to generate information that would assist NLM and the National Network of Libraries of Medicine (NN/LM) in learning how best to work with public libraries in the future. Three regional medical libraries (RMLs), eight resource libraries, and forty-one public libraries or library systems from nine states and the District of Columbia were selected for participation. The pilot project included an evaluation component that was carried out in parallel with project implementation. The evaluation ran through September 1999. The results of the evaluation indicated that participating public librarians were enthusiastic about the training and information materials provided as part of the project and that many public libraries used the materials and conducted their own outreach to local communities and groups. Most libraries applied the modest funds to purchase additional Internet-accessible computers and/or upgrade their health-reference materials. However, few of the participating public libraries had health information centers (although health information was perceived as a top-ten or top-five topic of interest to patrons). Also, the project generated only minimal usage of NLM's consumer health database, known as MEDLINEplus, from the premises of the monitored libraries (patron usage from home or office locations was not tracked). The evaluation results suggested a balanced follow-up by NLM and the NN/LM, with a few carefully selected national activities, complemented by a package of targeted activities that, as of January 2000, are being planned, developed, or implemented. The results also highlighted the importance of building an evaluation component into projects like this one from the outset, to assure that objectives were met and that evaluative information was available on a timely basis, as was the case here.

Evaluating Internet end-to-end performance: overview of test methodology and results.

OBJECTIVE: An evaluation of Internet end-to-end performance was conducted for the purpose of better understanding the overall performance of Internet pathways typical of those used to access information in National Library of Medicine (NLM) databases and, by extension, other Internet-based biomedical information resources. DESIGN: The evaluation used a three-level test strategy: 1) user testing to collect empirical data on internet performance as perceived by users when accessing NLM Web-based databases, 2) technical testing to analyze the Internet paths between the NLM and the user's desktop computer terminal, and 3) technical testing between the NLM and the World Wide Web ("Web") server computer at the user's institution to help characterize the relative performance of Internet pathways. MEASUREMENTS: Time to download the front pages of NLM Web sites and conduct standardized searches of NLM databases, data transmission capacity between NLM and remote locations (known as the bulk transfer capacity [BTC]), "ping" round-trip time as an indication of the latency of the network pathways, and the network routing of the data transmissions (number and sequencing of hops). RESULTS: Based on 347 user tests spread over 16 locations, the median time per location to download the main NLM home page ranged from 2 to 59 seconds, and 1 to 24 seconds for the other NLM Web sites tested. The median time to conduct standardized searches and get search results ranged from 2 to 14 seconds for PubMed and 4 to 18 seconds for Internet Grateful Med. The overall problem rate was about 1 percent; that is, on the average, users experienced a problem once every 100 test measurements. The user terminal tests at five locations and Web host tests at 13 locations provided profiles of BTC, RTT, and network routing for both dial-up and fixed Internet connections. CONCLUSION: The evaluation framework provided a profile of typical Internet performance and insights into network performance and time-of-day/day-of-week variability. This profile should serve as a frame of reference to help identify and diagnose connectivity problems and should contribute to the evolving concept of Internet quality of service.

G7: a framework for international cooperation in medical informatics.

The world's major economic powers, the G7, have initiated a collaborative International research and demonstration program to exploit the benefits of information and communications technology for society. The Global Healthcare Applications Project (GHAP) is investigating a variety of informatics applications in disease specific domains, telemedicine, and multilingual textual and image database systems. This paper summarizes the nine GHAP sub-projects undertaken to date, with emphasis on those in which the U.S. is a participant. The growing use of smart card technology, especially in Europe, is adding new impetus for similar medical and health experiments in the U.S. A pilot project now underway in several Western states is described.

Transitioning to the Internet: results of a National Library of Medicine user survey.

In late 1995, several months prior to the introduction of Internet Grateful Med, the National Library of Medicine (NLM) conducted a customer survey as part of its efforts to make a transition from Grateful Med to new forms of electronic information access and retrieval. A questionnaire survey was mailed to a sample of 2,500 online users randomly selected from domestic users (excluding fixed-fee users) who searched NLM databases during the second quarter of 1995. The final response rate was nearly 83% of eligible respondents. About 70% of NLM customers responding already had access to the Internet, and of those, more than 90% had access to the World Wide Web. However, only 26% of customers with Internet access were using the Internet to access NLM databases. Health care providers account for about 46% of NLM customers but, as a group, search NLM databases relatively infrequently even though they have higher-end equipment. Librarians and information professionals represent about one-fifth of NLM customers and are by far the most intensive users, but tend to have lower-end equipment. Overall, the survey results provide a strong basis for the transition to Internet-based delivery of NLM online database services, including Internet Grateful Med and the NLM family of World Wide Web sites. However, Internet access is uneven, especially in rural areas and at hospitals. This reinforces the need for continuing special outreach efforts directed at improving access for rural and hospital-based users and rural libraries, upgrading computer equipment for medical librarians, and training health care providers in more effective use of Internet-based biomedical information resources.

Use of MEDLINE by physicians for clinical problem solving.

OBJECTIVE: To understand the ways in which computer-mediated searching of the biomedical literature affects patient care and other professional activities. Undertaken to determine the ways in which on-line access to the biomedical literature via the National Library of Medicine's MEDLINE database "makes a difference" in what physicians do when confronted with a medical problem requiring new or additional information. DESIGN: An adaptation of the Critical Incident Technique used to gather detailed reports of MEDLINE search results that were especially helpful (or not helpful) in carrying out the individual's professional activities. The individual physician was the source of the patient care incident reports. One thousand one hundred fifty-eight reports were systematically analyzed from three different perspectives: (1) why the information was sought; (2) the effect of having (or not having) the needed information on professional decisions and actions; and (3) the outcome of the search. PARTICIPANTS AND SETTING: Telephone interviews were carried out with a purposive sample of 552 physicians, scientists, and other professionals working in a variety of clinical care and other settings. Of these, 65% were direct users of MEDLINE throughout the United States, and 35% had MEDLINE searches conducted for them either at a major health sciences center or in community hospitals. RESULTS: Three comprehensive and detailed inventories that describe the motivation for the searches, how search results affected the actions and decisions of the individual who initiated the search, and how they affected the outcome of the situation that motivated the search. CONCLUSIONS: MEDLINE searches are being carried out by and for physicians to meet a wide diversity of clinical information needs. Physicians report that in situations involving individual patients, rapid access to the biomedical literature via MEDLINE is at times critical to sound patient care and favorably influences patient outcomes.

Evaluating the impact of MEDLINE using the Critical Incident Technique.

An adaptation of the Critical Incident Technique for the evaluation of an online information system is described. 552 users of the National Library of Medicine's MEDLINE database, interviewed by telephone and responding to a highly structured set of open-ended questions, reported 1,158 incidents in which the results of a MEDLINE search was especially helpful (or not helpful) in carrying out professional activities. Systematic analysis of these "critical incidents" produced three comprehensive and detailed views of the purposes and outcomes of MEDLINE searches: (1) why information is sought from MEDLINE; (2) the impact of MEDLINE-derived information on medical decision-making; and (3) the ultimate outcome of having (or not having) the desired information on medical situations prompting a MEDLINE search. Results revealed that MEDLINE is used to satisfy a diversity of medical needs concerning patient care, the progress of biomedical research, the quality of education received by health professionals in training, the safety and effectiveness of health care institutions, the operation of the system of third-party reimbursement, for legal decisions, and for the knowledge of the public.

Bibliographic retrieval: a survey of individual users of MEDLINE.

The National Library of Medicine (NLM) has been providing online access to the MEDLINE database for nearly 20 years. In recent years, there has been a shift in the composition of the user population. Nearly half the online access codes are now held by individuals who conduct their own searches of the database. The NLM has conducted a survey to identify the demographic features of this end-user population, their reasons for searching the database, their methods of access, and their satisfaction with MEDLINE as available on the NLM system.