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The expansion of the Universe is understood to have accelerated during twoepochs: in its very first moments during a period of Inflation and much morerecently, at $z < 1$, when Dark Energy is hypothesized to drive cosmicacceleration. The undiscovered mechanisms behind these two epochs representsome of the most important open problems in fundamental physics. The largecosmological volume at $2 < z < 5$, together with the ability to efficientlytarget high-$z$ galaxies with known techniques, enables large gains in thestudy of Inflation and Dark Energy. A future spectroscopic survey can test theGaussianity of the initial conditions up to a factor of ~50 better than ourcurrent bounds, crossing the crucial theoretical threshold of$\sigma(f_{NL}^{\rm local})$ of order unity that separates single field andmulti-field models. Simultaneously, it can measure the fraction of Dark Energyat the percent level up to $z = 5$, thus serving as an unprecedented test ofthe standard model and opening up a tremendous discovery space.

Upcoming imaging surveys, such as LSST, will provide an unprecedented view ofthe Universe, but with limited resolution along the line-of-sight. Common waysto increase resolution in the third dimension, and reduce misclassifications,include observing a wider wavelength range and/or combining the broad-bandimaging with higher spectral resolution data. The challenge with theseapproaches is matching the depth of these ancillary data with the originalimaging survey. However, while a full 3D map is required for some science,there are many situations where only the statistical distribution of objects(dN/dz) in the line-of-sight direction is needed. In such situations, there isno need to measure the fluxes of individual objects in all of the surveys.Rather a stacking procedure can be used to perform an `ensemble photo-z'. Weshow how a shallow, higher spectral resolution survey can be used to measuredN/dz for stacks of galaxies which coincide in a deeper, lower resolutionsurvey. The galaxies in the deeper survey do not even need to appearindividually in the shallow survey. We give a toy model example to illustratetradeoffs and considerations for applying this method. This approach will allowdeep imaging surveys to leverage the high resolution of spectroscopic andnarrow/medium band surveys underway, even when the latter do not have the samereach to high redshift.

Acoustic waves travelling through the early Universe imprint a characteristic scale in the clustering of galaxies, QSOs and intergalactic gas. This scale can be used as a standard ruler to map the expansion history of the Universe, a technique known as baryon acoustic oscillations (BAO). BAO offer a high-precision, low-systematics means of constraining our cosmological model. The statistical power of BAO measurements can be improved if the 'smearing' of the acoustic feature by non-linear structure formation is undone in a process known as reconstruction. In this paper, we use low-order Lagrangian perturbation theory to study the ability of 21-cm experiments to perform reconstruction and how augmenting these surveys with galaxy redshift surveys at relatively low number densities can improve performance. We find that the critical number density which must be achieved in order to benefit 21-cm surveys is set by the linear theory power spectrum near its peak, and corresponds to densities achievable by upcoming surveys of emission line galaxies such as eBOSS and DESI. As part of this work, we analyse reconstruction within the framework of Lagrangian perturbation theory with local Lagrangian bias, redshift-space distortions, k-dependent noise and anisotropic filtering schemes.

One of the most striking properties of galaxies is the bimodality in their star formation rates. A major puzzle is why any given galaxy is star forming or quiescent, and a wide range of physical mechanisms have been proposed as solutions. We consider how observations, such as might be available in upcoming large galaxy surveys, might distinguish different galaxy quenching scenarios. To do this, we combine an N-body simulation and multiple prescriptions from the literature to create several quiescent galaxy mock catalogues. Each prescription uses a different set of galaxy properties (such as history, environment, centrality) to assign individual simulation galaxies as quiescent. We find how and how much the resulting quiescent galaxy distributions differ from each other, both intrinsically and observationally. In addition to tracing observational consequences of different quenching mechanisms, our results indicate which sorts of quenching models might be most readily disentangled by upcoming observations and which combinations of observational quantities might provide the most discriminatory power. Our observational measures are auto, cross, and marked correlation functions, projected density distributions, and group multiplicity functions, which rely upon galaxy positions, stellar masses and of course quiescence. Although degeneracies between models are present for individual observations, using multiple observations in concert allows us to distinguish between all 10 models we consider. In addition to identifying intrinsic and observational consequences of quiescence prescriptions and testing these quiescence models against each other and observations, these methods can also be used to validate colours (or other history and environment dependent properties) in simulated mock catalogues. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

One of the most striking properties of galaxies is the bimodality in their star formation rates. A major puzzle is why any given galaxy is star forming or quiescent, and a wide range of physical mechanisms have been proposed as solutions. We consider how observations, such as might be available in upcoming large galaxy surveys, might distinguish different galaxy quenching scenarios. To do this, we combine an N-body simulation and multiple prescriptions from the literature to create several quiescent galaxy mock catalogues. Each prescription uses a different set of galaxy properties (such as history, environment, centrality) to assign individual simulation galaxies as quiescent. We find how and how much the resulting quiescent galaxy distributions differ from each other, both intrinsically and observationally. In addition to tracing observational consequences of different quenching mechanisms, our results indicate which sorts of quenching models might be most readily disentangled by upcoming observations and which combinations of observational quantities might provide the most discriminatory power. Our observational measures are auto, cross, and marked correlation functions, projected density distributions, and group multiplicity functions, which rely upon galaxy positions, stellar masses and of course quiescence. Although degeneracies between models are present for individual observations, using multiple observations in concert allows us to distinguish between all 10 models we consider. In addition to identifying intrinsic and observational consequences of quiescence prescriptions and testing these quiescence models against each other and observations, these methods can also be used to validate colours (or other history and environment dependent properties) in simulated mock catalogues. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

This Resource Letter provides a guide to the literature on the theory ofanisotropies in the cosmic microwave background. Journal articles, web pages,and books are cited for the following topics: discovery, cosmological origin,early work, recombination, general CMB anisotropy references, primary CMBanisotropies (numerical, analytical work), secondary effects,Sunyaev-Zel'dovich effect(s), lensing, reionization, polarization, gravitywaves, defects, topology, origin of fluctuations, development of fluctuations,inflation and other ties to particle physics, parameter estimation, recentconstraints, web resources, foregrounds, observations and observational issues,and gaussianity.

Background and Objectives: Maternal morbidity and mortality disproportionally affect marginalized populations in both rural and urban settings. While the workforce of family physicians (FPs) who provide maternity care is declining, an enhanced obstetrics (OB) curriculum during residency training can help prepare future FPs to provide competent pregnancy care, particularly in marginalized communities., Methods: We developed an innovative OB curriculum-PROMOTE: Primary care obstetrics and maternal outcomes training enhancement-in an urban underserved residency program in Pennsylvania that directly addressed barriers previously known to impact maternity care practice. We created a clinical competency assessment aligned with Accreditation Council for Graduate Medical Education requirements, and we reviewed resident feedback and logs throughout and upon completion of the track., Results: After 3 years of implementation, 23 of 48 (48%) total residents entered and/or completed PROMOTE, compared to 17 of 45 (38%) total residents who chose the OB track in the 5 years prior to implementation. Postimplementation, 29.6% of total graduates practice inpatient obstetrics, compared to 26.6% prior to implementation. Twice annual competency evaluations were completed for all residents on the track. Our review of resident submitted feedback, logs, and competency assessments suggests that the curriculum has positively impacted their knowledge, skills, and clinical care provision., Conclusions: PROMOTE's curricular innovation enhances obstetrical training by addressing known facilitators and barriers to practicing family medicine obstetrics. PROMOTE was implemented in an existing family medicine residency with an obstetrics track and could be adapted by other residency programs to enhance the future maternity care workforce.

We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model used twenty cross-sectional and 190 longitudinal variables observed in eight time intervals covering 7.5 years prior to the time of prediction. Ensembles of seven base models were created and fine-tuned with ten variables expected to change with study design and outcome definition in order to predict suicide and combined outcome in a prospective cohort. The ensemble models achieved c-statistics of 0.73 on 2-year suicide risk and 0.83 on the combined outcome when predicting on a prospective cohort of [Formula: see text] 4.2 M veterans. The ensembles rely on nonlinear base models trained using a matched retrospective nested case-control (Rcc) study cohort and show good calibration across a diversity of subgroups, including risk strata, age, sex, race, and level of healthcare utilization. In addition, a linear Rcc base model provided a rich set of biological predictors, including indicators of suicide, substance use disorder, mental health diagnoses and treatments, hypoxia and vascular damage, and demographics., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Histopathology images of tumor biopsies present unique challenges for applying machine learning to the diagnosis and treatment of cancer. The pathology slides are high resolution, often exceeding 1GB, have non-uniform dimensions, and often contain multiple tissue slices of varying sizes surrounded by large empty regions. The locations of abnormal or cancerous cells, which may constitute a small portion of any given tissue sample, are not annotated. Cancer image datasets are also extremely imbalanced, with most slides being associated with relatively common cancers. Since deep representations trained on natural photographs are unlikely to be optimal for classifying pathology slide images, which have different spectral ranges and spatial structure, we here describe an approach for learning features and inferring representations of cancer pathology slides based on sparse coding., Results: We show that conventional transfer learning using a state-of-the-art deep learning architecture pre-trained on ImageNet (RESNET) and fine tuned for a binary tumor/no-tumor classification task achieved between 85% and 86% accuracy. However, when all layers up to the last convolutional layer in RESNET are replaced with a single feature map inferred via a sparse coding using a dictionary optimized for sparse reconstruction of unlabeled pathology slides, classification performance improves to over 93%, corresponding to a 54% error reduction., Conclusions: We conclude that a feature dictionary optimized for biomedical imagery may in general support better classification performance than does conventional transfer learning using a dictionary pre-trained on natural images.

This paper explores the application of text mining to the problem of detecting protein functional sites in the biomedical literature, and specifically considers the task of identifying catalytic sites in that literature. We provide strong evidence for the need for text mining techniques that address residue-level protein function annotation through an analysis of two corpora in terms of their coverage of curated data sources. We also explore the viability of building a text-based classifier for identifying protein functional sites, identifying the low coverage of curated data sources and the potential ambiguity of information about protein functional sites as challenges that must be addressed. Nevertheless we produce a simple classifier that achieves a reasonable ∼69% F-score on our full text silver corpus on the first attempt to address this classification task. The work has application in computational prediction of the functional significance of protein sites as well as in curation workflows for databases that capture this information.

Background: We propose a method for automatic extraction of protein-specific residue mentions from the biomedical literature. The method searches text for mentions of amino acids at specific sequence positions and attempts to correctly associate each mention with a protein also named in the text. The methods presented in this work will enable improved protein functional site extraction from articles, ultimately supporting protein function prediction. Our method made use of linguistic patterns for identifying the amino acid residue mentions in text. Further, we applied an automated graph-based method to learn syntactic patterns corresponding to protein-residue pairs mentioned in the text. We finally present an approach to automated construction of relevant training and test data using the distant supervision model., Results: The performance of the method was assessed by extracting protein-residue relations from a new automatically generated test set of sentences containing high confidence examples found using distant supervision. It achieved a F-measure of 0.84 on automatically created silver corpus and 0.79 on a manually annotated gold data set for this task, outperforming previous methods., Conclusions: The primary contributions of this work are to (1) demonstrate the effectiveness of distant supervision for automatic creation of training data for protein-residue relation extraction, substantially reducing the effort and time involved in manual annotation of a data set and (2) show that the graph-based relation extraction approach we used generalizes well to the problem of protein-residue association extraction. This work paves the way towards effective extraction of protein functional residues from the literature.

Background: Classification is difficult for shotgun metagenomics data from environments such as soils, where the diversity of sequences is high and where reference sequences from close relatives may not exist. Approaches based on sequence-similarity scores must deal with the confounding effects that inheritance and functional pressures exert on the relation between scores and phylogenetic distance, while approaches based on sequence alignment and tree-building are typically limited to a small fraction of gene families. We describe an approach based on finding one or more exact matches between a read and a precomputed set of peptide 10-mers., Results: At even the largest phylogenetic distances, thousands of 10-mer peptide exact matches can be found between pairs of bacterial genomes. Genes that share one or more peptide 10-mers typically have high reciprocal BLAST scores. Among a set of 403 representative bacterial genomes, some 20 million 10-mer peptides were found to be shared. We assign each of these peptides as a signature of a particular node in a phylogenetic reference tree based on the RNA polymerase genes. We classify the phylogeny of a genomic fragment (e.g., read) at the most specific node on the reference tree that is consistent with the phylogeny of observed signature peptides it contains. Using both synthetic data from four newly-sequenced soil-bacterium genomes and ten real soil metagenomics data sets, we demonstrate a sensitivity and specificity comparable to that of the MEGAN metagenomics analysis package using BLASTX against the NR database. Phylogenetic and functional similarity metrics applied to real metagenomics data indicates a signal-to-noise ratio of approximately 400 for distinguishing among environments. Our method assigns ~6.6 Gbp/hr on a single CPU, compared with 25 kbp/hr for methods based on BLASTX against the NR database., Conclusions: Classification by exact matching against a precomputed list of signature peptides provides comparable results to existing techniques for reads longer than about 300 bp and does not degrade severely with shorter reads. Orders of magnitude faster than existing methods, the approach is suitable now for inclusion in analysis pipelines and appears to be extensible in several different directions.

We present an approach that integrates protein structure analysis and text mining for protein functional site prediction, called LEAP-FS (Literature Enhanced Automated Prediction of Functional Sites). The structure analysis was carried out using Dynamics Perturbation Analysis (DPA), which predicts functional sites at control points where interactions greatly perturb protein vibrations. The text mining extracts mentions of residues in the literature, and predicts that residues mentioned are functionally important. We assessed the significance of each of these methods by analyzing their performance in finding known functional sites (specifically, small-molecule binding sites and catalytic sites) in about 100,000 publicly available protein structures. The DPA predictions recapitulated many of the functional site annotations and preferentially recovered binding sites annotated as biologically relevant vs. those annotated as potentially spurious. The text-based predictions were also substantially supported by the functional site annotations: compared to other residues, residues mentioned in text were roughly six times more likely to be found in a functional site. The overlap of predictions with annotations improved when the text-based and structure-based methods agreed. Our analysis also yielded new high-quality predictions of many functional site residues that were not catalogued in the curated data sources we inspected. We conclude that both DPA and text mining independently provide valuable high-throughput protein functional site predictions, and that integrating the two methods using LEAP-FS further improves the quality of these predictions.

Recent studies have noted extensive inconsistencies in gene start sites among orthologous genes in related microbial genomes. Here we provide the first documented evidence that imposing gene start consistency improves the accuracy of gene start-site prediction. We applied an algorithm using a genome majority vote (GMV) scheme to increase the consistency of gene starts among orthologs. We used a set of validated Escherichia coli genes as a standard to quantify accuracy. Results showed that the GMV algorithm can correct hundreds of gene prediction errors in sets of five or ten genomes while introducing few errors. Using a conservative calculation, we project that GMV would resolve many inconsistencies and errors in publicly available microbial gene maps. Our simple and logical solution provides a notable advance toward accurate gene maps.

Background: Evolutionary divergence in the position of the translational start site among orthologous genes can have significant functional impacts. Divergence can alter the translation rate, degradation rate, subcellular location, and function of the encoded proteins., Results: Existing Genbank gene maps for Burkholderia genomes suggest that extensive divergence has occurred--53% of ortholog sets based on Genbank gene maps had inconsistent gene start sites. However, most of these inconsistencies appear to be gene-calling errors. Evolutionary divergence was the most plausible explanation for only 17% of the ortholog sets. Correcting probable errors in the Genbank gene maps decreased the percentage of ortholog sets with inconsistent starts by 68%, increased the percentage of ortholog sets with extractable upstream intergenic regions by 32%, increased the sequence similarity of intergenic regions and predicted proteins, and increased the number of proteins with identifiable signal peptides., Conclusions: Our findings highlight an emerging problem in comparative genomics: single-digit percent errors in gene predictions can lead to double-digit percentages of inconsistent ortholog sets. The work demonstrates a simple approach to evaluate and improve the quality of gene maps.

Background: We present a fast version of the dynamics perturbation analysis (DPA) algorithm to predict functional sites in protein structures. The original DPA algorithm finds regions in proteins where interactions cause a large change in the protein conformational distribution, as measured using the relative entropy Dx. Such regions are associated with functional sites., Results: The Fast DPA algorithm, which accelerates DPA calculations, is motivated by an empirical observation that Dx in a normal-modes model is highly correlated with an entropic term that only depends on the eigenvalues of the normal modes. The eigenvalues are accurately estimated using first-order perturbation theory, resulting in a N-fold reduction in the overall computational requirements of the algorithm, where N is the number of residues in the protein. The performance of the original and Fast DPA algorithms was compared using protein structures from a standard small-molecule docking test set. For nominal implementations of each algorithm, top-ranked Fast DPA predictions overlapped the true binding site 94% of the time, compared to 87% of the time for original DPA. In addition, per-protein recall statistics (fraction of binding-site residues that are among predicted residues) were slightly better for Fast DPA. On the other hand, per-protein precision statistics (fraction of predicted residues that are among binding-site residues) were slightly better using original DPA. Overall, the performance of Fast DPA in predicting ligand-binding-site residues was comparable to that of the original DPA algorithm., Conclusion: Compared to the original DPA algorithm, the decreased run time with comparable performance makes Fast DPA well-suited for implementation on a web server and for high-throughput analysis.

A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F(o) - F(c))exp(i(phi)c) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule.

Anatomic, histologic and ultrasound studies demonstrate two distinct types of longitudinal veins in the lower extremities. The great saphenous vein is deep to the saphenous fascia. Accessory saphenous veins are superficial to this layer, have thin walls with diminished muscle cells and elastic fibers. Vein characteristics may affect long-term graft patency. This study assesses the incidence of accessory saphenous veins in various patient groups and evaluates issues related to their use as coronary conduits. Ultrasound imaging assessed great and accessory saphenous veins in 476 normal limbs, in 42 patients post-saphenous vein harvesting and in 75 patients undergoing coronary revascularization. Accessory saphenous veins are found in 67% of normal subjects. Intraoperative ultrasound identifies accessory saphenous veins in 54% of limbs, most in the proximal calf where 42% of all accessory vein segments are located. Great saphenous vein segments are more common in males while accessory veins are more common in females. In 54 limbs following saphenectomy, patent great saphenous vein segments are demonstrated in 20%, adjacent to incision sites, indicating use of accessory saphenous veins in these patients. Ultrasound studies at two medical centers document the common occurrence of accessory saphenous veins. Additional studies are required to determine the efficacy of utilizing accessory saphenous vein segments for coronary artery bypass conduits.

A procedure for fitting of ligands to electron-density maps by first fitting a core fragment of the ligand to density and then extending the remainder of the ligand into density is presented. The approach was tested by fitting 9327 ligands over a wide range of resolutions (most are in the range 0.8-4.8 A) from the Protein Data Bank (PDB) into (Fo - Fc)exp(i phi(c)) difference density calculated using entries from the PDB without these ligands. The procedure was able to place 58% of these 9327 ligands within 2 A (r.m.s.d.) of the coordinates of the atoms in the original PDB entry for that ligand. The success of the fitting procedure was relatively insensitive to the size of the ligand in the range 10-100 non-H atoms and was only moderately sensitive to resolution, with the percentage of ligands placed near the coordinates of the original PDB entry for fits in the range 58-73% over all resolution ranges tested.

Background: Limbs with varicose veins are difficult to assess as a source of saphenous vein conduit. Anatomic, histologic, and ultrasound studies demonstrate two types of longitudinal veins in the lower extremities. The great saphenous vein is deep to the saphenous fascia. Accessory saphenous veins are superficial to this layer and have thin walls with diminished muscle cells and elastic fiber. Accessory saphenous veins dilate and form varicosities. Segments of great saphenous veins are often suitable as coronary conduits. No studies have assessed the suitability of saphenous veins as coronary artery conduits in patients with varicose vein disease., Methods: Intraoperative high-resolution ultrasound studies were performed in coronary artery bypass graft procedures to assess lower extremity venous morphology in limbs of 77 patients without known venous disease, in 19 limbs with venous telangiectases, and in 23 limbs with varicose veins., Results: Dilated great saphenous vein segments were identified in 6% of normal limb venous segments compared with 21% of segments in limbs with telangiectases (p = 0.027) and 22% of segments in limbs with varicosities (p = 0.012). The incidence of absent or hypoplastic great saphenous vein segments is increased in limbs with varicosities (35%) compared with normal limbs (21%; p = 0.032). In the calf, at least one great saphenous vein segment suitable for coronary artery bypass grafting is present in 70% of limbs with varicosities and in 89% of limbs with telangiectases., Conclusions: Ultrasound studies document that varicose veins are limited to accessory saphenous veins. Great saphenous vein conduits, identified by ultrasonography, are available in limbs with varicose vein disease.

Background: Saphenous vein is the most common conduit utilized for coronary artery bypass. However, preoperative noninvasive venous studies to evaluate saphenous vein morphology are not commonly performed due to limited logistical support. A prospective, nonrandomized study was developed to assess the utility of intraoperative saphenous vein duplex ultrasound studies in optimizing saphenous vein site selection., Methods: Intraoperative saphenous vein duplex scanning was performed in 58 consecutive patients undergoing coronary artery bypass surgery utilizing two-dimensional ultrasound monitoring equipment. Following anesthetic intubation, studies were performed by one of the surgeons. Most scans were completed in less than 8 minutes., Results: Findings demonstrate at least 1 venous abnormality in 31 of 116 (26.7%) above knee saphenous veins and 59 of 116 (50.9%) below knee veins. In 38 of 58 patients (65.5%), duplex ultrasound scanning proved beneficial in surgical site selection. Most abnormalities are related to major branches and bifurcations except in the lower calf where small lumen caliber is the most common abnormal finding. Additional beneficial findings include identifying abnormal vein course, identifying suitable conduit in reoperative procedures and precise localization of vein segments for endoscopic surgery., Conclusions: Intraoperative saphenous vein duplex scanning is rapidly and easily accomplished with available operating room resources. Study information allows optimal surgical site selection, avoiding unnecessary surgical dissection, time delays, vein wastage and potential for wound complications. Optimizing incision site selection eliminates blind exploration for vein conduit, improves conduit planning, and expedites surgical dissection during endoscopic vein harvest.

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.

Over a 7-year period, follow-up data were available on 163 patients who underwent 209 pacemaker-related operations for initial insertion or revision of previously implanted units. During the follow-up period, 16 pacemaker generator units were remoaved from 16 pacemaker generator units were removed from 12 patients solely because of the development of local skin erosion. This represents a 7.7% incidence of pacemaker generator erosion. Tree units were removed within a 3-month interval following pacemaker implantation and were associated with positive bacterial cultures, theraby indicating an infectious cause. Findings at removal of the remaining 13 pacemaker generators included extensive fibrosis with chronic inflammation, fibroblastic proliferation, and granulation tissue, which was most prominent at the site of insertion of the pacemaker lead into the pacemaker generator unit. Granulation tissue frequently led from this area to the area of skin attenuation and erythema. Inspection of the pacemaker generator units and electrodes demonstrated fluid ingress and tissue ingrowth toward the electrode due to inadequate seal mechanisms. Inadequate seal design of the pacemaker generator and electrode junction leads to tissue ingrowth with fibroblastic proliferatiog chronic inflammation, and eventual pacemaker erosion.

An automated system has been developed for measuring hemodynamic, oxygen transport and tissue utilization functions. Rapid measurement and data analysis of physiologic profiles by paramedical personnel allow prompt evaluation of altered cardiovascular function. Evaluation of physiologic function allows therapeutic interventions to be instituted on a timely basis, appropriately directed toward improvement of the measured cardiovascular abnormalities. Physiologic profile studies were performed on 1016 occasions in 580 patients during a three-year period and form the basis of this report. Although utilized on hospitalized patients, there are implications for use in evaluating and treating all critically ill patients.

Two cases of flow-directed, balloon-tipped catheterizations of the right heart via a persistent left superior vena cava are presented. In both cases, the monitoring catheters assumed similar, atypical configurations on plain chest roentgenograms. Recognition of the characteristic configuration of the course of transvenous catheters through the persistent left superior vena cava allows for plain film diagnosis of this anomaly.

An automatic cardiac output analysis system is described in which indicator dilution studies are performed serially without operator assistance. Indicator dye injection, blood sampling, and monitoring for air entry into the system are performed automatically through a present program sequence. Sampled blood is returned to the subject through a venous cannula resulting in an absence of blood loss. This system may be used in performing cardiac output analyses on a serial basis and in infants and small animals where blood loss is critical.

A modification of the Berggren pulmonary shunt equation was derived for use in estimating the splenic component of portal hypertension. It was used in nine patients, six of whom had sufficient decreases in portal flow and pressure after splenic artery and coronary vein ligation. The average decrease in portal flow was 52%.

Most major intra-abdominal fistulas result from trauma or surgery. Spontaneous fistulas are rare with less than 100 reported cases since 1831. From a review of hospital records, five such spontaneous fistulas were identified among 215 cases of abdominal aortic aneurysm between 1975 and 1983. These cases are presented and supplemented by 73 similar cases collected from a literature review for discussion of the salient features of clinical presentation and management of spontaneous major fistulas. Major intra-abdominal arteriovenous fistulas usually present with a machinery bruit over a pulsatile mass, but may present more subtly with pain and otherwise unexplained hematuria. Because these fistulas lead to refractory heart failure, surgery should be expeditious. Closure should be performed from within the aneurysm with arterial and pulmonary artery pressure monitoring. Care must be taken to prevent pulmonary embolization.

A relatively simple and inexpensive data management system is described with which comprehensive physiologic and cardiovascular profiles are produced. The system is comprised of a desk-top programmable calculator interfaced with an acoustic digitizer input, and an X-Y plotter, with alphanumeric printing output capability. Numerical clinical data such as intracardiac pressures and blood gas values are entered into the calculator via the keyboard, and graphical data such as dye-dilution curves or ventricular contours are digitized with a pen stylus on the acoustic tablet. The data are processed in the calculator and the results charted in familiar and readily interpreted bar-graph format on preprinted charts on the X-Y plotter. The entire system is inexpensive and compact enough to be applicable to small- and medium-size community hospitals.

The automated physiologic profile provides the critical care physician with hemodynamic, oxygen consumption and tissue utilization data at reasonable cost. A paramedical assistant performs all data acquisition, recordings and blood sampling procedures. Data reduction is performed through use of off-the-shelf desk-top calculator equipment and accessories and a standardized graphic display is provided for the physician in charge. The physiologic profile has been utilized in high-risk patients requiring medical and surgical interventions. It is routinely employed in postoperative monitoring of cardiac patients and patients undergoing major surgical procedures with associated cardiovascular decompensation. Diagnosis of cardiac and pulmonary deterioration and promptness of advanced support interventions represent additional areas of effective clinical application.

Estimation of intrapulmonary blood shunt fraction requires accurate evaluation of pulmonary capillary, arterial, and mixed venous oxygen contents. The presence of carboxyhemoglobin, as well as methemoglobin and sulfhemoglobin, may lead to large errors in the calculated intrapulmonary blood shunt fraction. The errors are most pronounced at low values of carboxyhemoglobin and low values of true intrapulmonary shunt fraction.

An instrument has been developed to record contrast dilution curves by a noninvasive technique. Transthoracic roentgen density alterations are recorded by use of a solid state radiation detector array. A small amount of injected nonradioactive, radiopaque contrast material is distrubuted throughout the central circulation. The detector array positioned over the cardiopulmonary silhouette, records changes in density during the passage of the contrast material, and typical indicator dilution curves are transcribed. These curves reflect changes in blood flow distribution, vascular volume, cardiac function, and intrathoracic vascular shunts; and define the hemodynamic status of the circulatory system.

Effective median sternotomy closure requires approximation of the sterum under appropriate tension in an expeditious manner. An instrument has been developed to provide tightening of applied sternal wires, allowing proper tension to be established. After tightening, the twisted wire is automatically trimmed by the instrument. The ease and reproducibility of this wire closure technic has allowed the method to be performed on a routine basis.

An improved subclavian cannulation technique using a 3 milliliter syringe attached to a No. 16 gauge needle and a guide wire is presented. Major complications, such as air embolism, vein laceration and retained catheter fragments, are eliminated by using this method of catheterization.

Measurements of hemodynamic, oxygen transport, and tissue utilization functions were incorporated into a physiologic profile assessment system in order to evaluate patients who are candidates for mechanical support of the failing heart. Circulatory function was assessed in patients with acute myocardial infarction associated with diminished peripheral perfusion and compared to an age-matched, normal patient group. Serial studies performed prior to and during intra-aortic balloon counterpulsation provide a means to assess circulatory status accurately and document the efficacy of therapeutic interventions.

Indocyanine green dye dilution curves with abnormal contours have been recorded in four patients with acute and critical illnesses using standardized recording methods. The abnormal curves are characterized by a high and prolonged concentration of dye occurring after the peak concentration. This altered contour can be detected by use of routine mathematical processing since the derived hemodynamic parameters are affected by the altered contour. A physiologic basis for the altered curve contour is proposed.