ARAX: a graph-based modular reasoning tool for translational biomedicine.

MOTIVATION: With the rapidly growing volume of knowledge and data in biomedical databases, improved methods for knowledge-graph-based computational reasoning are needed in order to answer translational questions. Previous efforts to solve such challenging computational reasoning problems have contributed tools and approaches, but progress has been hindered by the lack of an expressive analysis workflow language for translational reasoning and by the lack of a reasoning engine-supporting that language-that federates semantically integrated knowledge-bases. RESULTS: We introduce ARAX, a new reasoning system for translational biomedicine that provides a web browser user interface and an application programming interface (API). ARAX enables users to encode translational biomedical questions and to integrate knowledge across sources to answer the user's query and facilitate exploration of results. For ARAX, we developed new approaches to query planning, knowledge-gathering, reasoning and result ranking and dynamically integrate knowledge providers for answering biomedical questions. To illustrate ARAX's application and utility in specific disease contexts, we present several use-case examples. AVAILABILITY AND IMPLEMENTATION: The source code and technical documentation for building the ARAX server-side software and its built-in knowledge database are freely available online (https://github.com/RTXteam/RTX). We provide a hosted ARAX service with a web browser interface at arax.rtx.ai and a web API endpoint at arax.rtx.ai/api/arax/v1.3/ui/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RTX-KG2: a system for building a semantically standardized knowledge graph for translational biomedicine.

BACKGROUND: Biomedical translational science is increasingly using computational reasoning on repositories of structured knowledge (such as UMLS, SemMedDB, ChEMBL, Reactome, DrugBank, and SMPDB in order to facilitate discovery of new therapeutic targets and modalities. The NCATS Biomedical Data Translator project is working to federate autonomous reasoning agents and knowledge providers within a distributed system for answering translational questions. Within that project and the broader field, there is a need for a framework that can efficiently and reproducibly build an integrated, standards-compliant, and comprehensive biomedical knowledge graph that can be downloaded in standard serialized form or queried via a public application programming interface (API). RESULTS: To create a knowledge provider system within the Translator project, we have developed RTX-KG2, an open-source software system for building-and hosting a web API for querying-a biomedical knowledge graph that uses an Extract-Transform-Load approach to integrate 70 knowledge sources (including the aforementioned core six sources) into a knowledge graph with provenance information including (where available) citations. The semantic layer and schema for RTX-KG2 follow the standard Biolink model to maximize interoperability. RTX-KG2 is currently being used by multiple Translator reasoning agents, both in its downloadable form and via its SmartAPI-registered interface. Serializations of RTX-KG2 are available for download in both the pre-canonicalized form and in canonicalized form (in which synonyms are merged). The current canonicalized version (KG2.7.3) of RTX-KG2 contains 6.4M nodes and 39.3M edges with a hierarchy of 77 relationship types from Biolink. CONCLUSION: RTX-KG2 is the first knowledge graph that integrates UMLS, SemMedDB, ChEMBL, DrugBank, Reactome, SMPDB, and 64 additional knowledge sources within a knowledge graph that conforms to the Biolink standard for its semantic layer and schema. RTX-KG2 is publicly available for querying via its API at arax.rtx.ai/api/rtxkg2/v1.2/openapi.json . The code to build RTX-KG2 is publicly available at github:RTXteam/RTX-KG2 .

Vehicle emissions of radical precursors and related species observed in the 2009 SHARP campaign.

UNLABELLED: The 2009 Study of Houston Atmospheric Radical Precursors (SHARP) field campaign had several components that yielded information on the primary vehicular emissions of formaldehyde (HCHO) and nitrous acid (HONO), in addition to many other species. Analysis of HONO measurements at the Moody Tower site in Houston, TX, yielded emission ratios of HONO to the vehicle exhaust tracer species NOx and CO of 14 pptv/ppbv and 2.3 pptv/ppbv, somewhat smaller than recently published results from the Galleria site, although evidence is presented that the Moody Tower values should be upper limits to the true ratios of directly emitted HONO, and are consistent with ratios used in current standard emissions models. Several other Moody Tower emission ratios are presented, in particular a value for HCHO/CO of 2.4 pptv/ppbv. Considering only estimates of random errors, this would be significantly lower than a previous value, though the small sample size and possible systematic differences should be taken into account. Emission factors for CO, NOx, and HCHO, as well as various volatile organic compounds (VOCs), were derived from mobile laboratory measurements both in the Washburn Tunnel and in on-road exhaust plume observations. These two sets of results and others reported in the literature all agree well, and are substantially larger than the CO, NOx, and HCHO emission factors derived from the emission ratios reported from the Galleria site. IMPLICATIONS: Emission factors for the species measured in the various components of the 2009 SHARP campaign in Houston, TX, including HCHO, HONO, CO, CO2, nitrogen oxides, and VOCs, are needed to support regional air quality monitoring. Components of the SHARP campaign measured these species in several different ways, each with their own potential for systematic errors and differences in vehicle fleets sampled. Comparisons between data sets suggest that differences in sampling place and time may result in quite different emission factors, while also showing that different vehicle mixes can yield surprisingly similar emission factors.

Short-term variation in near-highway air pollutant gradients on a winter morning.

Quantification of exposure to traffic-related air pollutants near highways is hampered by incomplete knowledge of the scales of temporal variation of pollutant gradients. The goal of this study was to characterize short-term temporal variation of vehicular pollutant gradients within 200-400 m of a major highway (>150 000 vehicles/d). Monitoring was done near Interstate 93 in Somerville (Massachusetts) from 06:00 to 11:00 on 16 January 2008 using a mobile monitoring platform equipped with instruments that measured ultrafine and fine particles (6-1000 nm, particle number concentration (PNC)); particle-phase (>30 nm) [Formula: see text], [Formula: see text], and organic compounds; volatile organic compounds (VOCs); and CO(2), NO, NO(2), and O(3). We observed rapid changes in pollutant gradients due to variations in highway traffic flow rate, wind speed, and surface boundary layer height. Before sunrise and peak traffic flow rates, downwind concentrations of particles, CO(2), NO, and NO(2) were highest within 100-250 m of the highway. After sunrise pollutant levels declined sharply (e.g., PNC and NO were more than halved) and the gradients became less pronounced as wind speed increased and the surface boundary layer rose allowing mixing with cleaner air aloft. The levels of aromatic VOCs and [Formula: see text], [Formula: see text] and organic aerosols were generally low throughout the morning, and their spatial and temporal variations were less pronounced compared to PNC and NO. O(3) levels increased throughout the morning due to mixing with O(3)-enriched air aloft and were generally lowest near the highway reflecting reaction with NO. There was little if any evolution in the size distribution of 6-225 nm particles with distance from the highway. These results suggest that to improve the accuracy of exposure estimates to near-highway pollutants, short-term (e.g., hourly) temporal variations in pollutant gradients must be measured to reflect changes in traffic patterns and local meteorology.

Adaptation of a proton transfer reaction mass spectrometer instrument to employ NO+ as reagent ion for the detection of 1,3-butadiene in the ambient atmosphere.

A proton transfer reaction mass spectrometer (PTR-MS) instrument was adapted to employ NO+ as a chemical reagent ion without any hardware changes by switching the reagent ion source gas from water vapor to dry air. Ionization of dry air within the hollow cathode ion source generates a very intense source of NO+ with only a minor impurity of NO2+. The intensities of the primary NO+ reagent ion and the unwanted impurity NO2+ are controllable and dependent on the operational conditions of the hollow cathode ion source. Ion source tuning parameters are described, which maintain an intense source of NO+ while keeping the impurity NO2+ signal to less than 2% of the total reagent ion intensity. This method is applied to the detection of 1,3-butadiene. NO+ reacts efficiently with 1,3-butadiene via a charge exchange reaction to produce only the molecular ion, which is detected at m/z 54. Detection sensitivities of the order of 45 pptv for a 1-s measurement of 1,3-butadiene are demonstrated. We present the first real-time on-line sub parts per billion measurement of 1,3-butadiene in the ambient atmosphere. The only likely interference is from 1,2-butadiene. Concurrent measurements of benzene are provided and suggest that the vehicular emissions are the predominant source of 1,3-butadiene in a suburban Boston area monitoring location.

Lost surgical specimens.

It is an unfortunate fact that surgical specimens can become lost in the peritoneal cavity. Several reparative actions may be required, including laparotomy. The preferred method to avoid this complication, however, is to prevent it from occurring.

Fresh and cryopreserved ovarian tissue samples from donors with lymphoma transmit the cancer to graft recipients.

Girls and young women who require ovariectomy or cancer therapy may consider having their own eggs, embryos or ovarian tissue stored (cryopreserved) for their own future use. Ovarian tissue is simple to collect and contains large numbers of germ cells. Transplantation of fresh and frozen-thawed ovarian tissue in healthy sheep and mice has resulted in normal live young. Similar techniques may be effective in the human but it is unclear whether ovarian tissue cryopreservation and grafting is suitable for ovaries from individuals with cancer or infections. If cancer cells were present in an ovary at the time of collection and survived cryopreservation and grafting they could establish cancer in the recipient. We therefore performed ovarian cryopreservation and transplantation trials using a mouse lymphoma model. This established that the lymphoma was transmitted by grafts of both fresh and frozen ovarian tissue. The normal healthy recipient mice died 9-43 days after receiving a small piece (1 mm3) of ovarian tissue from a donor with lymphoma. We conclude that ovarian tissue which is collected, cryopreserved and grafted while it contains cancer cells has the potential to spread the cancer to the graft recipient.

Routine use of ureteric catheters at laparoscopic hysterectomy may cause unnecessary complications.

STUDY OBJECTIVE: To test the use of ureteric catheters in preventing ureteric trauma during laparoscopic hysterectomy. DESIGN: Prospective study of 492 consecutive women. SETTING: Pelosi Women's Medical Center, New Jersey, and Cliveden Hill Private Hospital, Melbourne, Australia. PATIENTS: Four hundred ninety-two consecutive women. INTERVENTIONS: Laparoscopic hysterectomy was performed in all women. Because of the reported increased risk of ureteric trauma during laparoscopic hysterectomy, we passed ureteric catheters in 92 such procedures and ceased the practice with the last 400 when further reports suggested lack of increased risk. MEASUREMENTS AND MAIN RESULTS: Oliguria and anuria occurred in 7 of 92 patients having ureteric catheterization. No ureteric trauma occurred in 400 patients without ureteric catheterization. The injury rate in this series was significantly lower than in three other series of abdominal hysterectomy. CONCLUSIONS: As long as surgical techniques incorporate various procedures to avoid ureteric injury, routine ureteric catheterization during laparoscopic hysterectomy is not indicated and may result in unnecessary complications.

Evolutions of an orientation concerning the nature of the male homosexualities.

None of the adults I have treated have had major disturbances in their sexual identity except for the selection of the sex of the person with whom they express their sexual feelings. Only one lives out a role that is ambisexual. All the men I have seen have been able to relate sexually to women with varying degrees of comfort. Six have had sexual intercourse with women and can function physiologically but without a sense of closeness or satisfaction, and five have been able to achieve climax. Some decided not to stay in their marriages, divorced, and adopted an overtly homosexual lifestyle. Some felt increasing ability to relate to women and decided to marry. Still others resolved current conflicts with their gay partners and felt no need for further therapy. All but one were actively employed and functioning well by external observation in demanding jobs requiring postgraduate college education. In terms of the detailed analytic work, there were no sets of insights that resulted in a major sexual partner reorientation. Those who decided to marry did so when they felt more able to resolve their narcissistic needs and make a relationship with a caring tolerant woman. They maintained their homosexual fantasies though the fantasies were more acceptable and less disruptive. It was not always the partner's penis that determined the sexual interest of these men. More often, it was the contour of the male body, the firmness of the musculature, the masculine bodily movements, the very identity and role of the father in the family. I did not see these foci of interest only as displacements from the genitals but rather as primary erotogenic stimuli. It is the seeking of a narcissistic object, the self in the other. This very orientation may be the innate variable. This position is spelled out in some detail by Leavy (1985). To varying degrees, the families of all these men were experienced as being composed of vigorous, active, articulate, determined, aspiring mothers and rather quiet, removed, passive fathers. The reported presence of this general pattern is impressive though the prominence of these characteristics differed from family to family. I have not postulated that these parental-child relations are causative in the boy's development of a homosexual life. However, they may be crucial if the genetic and/or constitutional factors discussed above are also present.(ABSTRACT TRUNCATED AT 400 WORDS)

Endoscopic minilaparotomy.

In a preliminary study the principles of standard gynaecological surgery, new operative laparoscopic techniques and mechanical elevation of the abdominal wall are combined. These early results indicate an advantage to both patient and hospitals from this approach. Further studies are required to verify our impressions that minilaparotomy combined with no insufflation laparoendoscopy will open up the concept of operative laparoscopic surgery to most gynaecologists.

Decreased natural killer cell activity in endometriosis patients: relationship to disease pathogenesis.

A number of reports have measured NK cell activity in patients with endometriosis with varied results. Therefore we have examined the NK activity of PBL from 44 gynecological patients undergoing laparoscopy. This analysis has demonstrated a significant reduction in NK activity only in more severe stages of endometriosis (stages III and IV) relative to patients with milder disease and controls. These data indicate that decreased NK activity is unlikely to be a primary etiological factor in the development of endometriosis but may indicate that decreased NK activity is related to the development of the more frequent and/or larger lesions characteristic of severe endometriosis. These data could indicate potential for immunotherapy of patients with advanced endometriosis by the upregulation of NK activity in vivo.

Gasless laparoscopy--useless or useful?

Carbon dioxide (CO2) pneumoperitoneum for advanced operative laparoscopy has well-documented inherent pathophysiologic risks. Problems are associated with creating and maintaining the pneumoperitoneum, lowering body temperature, infective particles in the insufflation gas, and ensuring hemostasis of port entry sites after intraabdominal pressure is reduced. When the vagina is opened to remove surgical specimens or at the time of hysterectomy, loss of vision occurs. In some patients general anesthesia and CO2 pneumoperitoneum are contraindicated, and in them such problems could be avoided by gasless laparoscopy. Three types of mechanical anterior abdominal wall elevators have been used at the Melbourne Gynoscopy Centre for a variety of laparoscopic procedures, all of which have their advantages and disadvantages.

Evaluation of a unique mechanical client lift: efficiency and perspectives of nursing staff.

This study evaluated the acceptability of a mechanical client lift based on the design employed for helicopter rescue lifts. Twenty-three nursing personnel completed questionnaires which explored their preferences, intentions to use the lift, perceptions of helpfulness, and exertion. Sixteen clients in a long term care setting consented to participate. One hundred manual lifts and 100 belt lifts were observed for comparative time and staff measures. The findings suggest that: 1) nursing staff will prefer the belt lift device for changing incontinent briefs; 2) nursing staff will prefer the belt lift device for toileting; 3) nursing staff will prefer the belt lift device to the currently used lift (in cases where either lift is appropriate) for bed/chair transfer; and, 5) the time required to utilize the belt lift as compared to manual lifting methods will not increase significantly.

Laparoscopically assisted hysterectomy.

OBJECTIVE: To determine the feasibility and effectiveness of laparoscopically assisted hysterectomy. DESIGN: A prospective study of the planned surgical procedure was carried out by two teams, each with two gynaecologists, who were experienced in operative laparoscopy. SETTING: The operations were carried out in a private hospital, where advanced operative laparoscopy equipment was available. PATIENTS: Seventeen patients were selected for the procedure, all of whom required hysterectomy for symptoms of pain or menorrhagia in association with uterine or other pelvic disease. Patients with carcinoma or uterine enlargement beyond 12 cm were excluded. PROCEDURE: Laparoscopically assisted hysterectomy was carried out by means of a video monitor, uterine manipulation by vaginal instrumentation, three or four abdominal punctures of less than 1 cm, and bipolar diathermy to secure vascular pedicles. The uterus was removed from the vagina by cutting vaginal skin and the cardinal ligaments. RESULTS: The operating time was 90-220 min, the blood loss was 30-200 mL, and the hospital stay lasted two to five days and convalescence two to four weeks. No serious complications occurred. CONCLUSIONS: Laparoscopically assisted hysterectomy may be valuable when adnexal or uterine abnormalities are present and vaginal hysterectomy is either contraindicated or more difficult. The procedure requires special equipment and may only be carried out by experienced gynaecological operative laparoscopists. Its acceptance will depend upon reducing the operating time to less than 90 min. It has the advantage of reducing the duration of hospital stay and the duration of convalescence when compared with abdominal hysterectomy.

Pregnancy following intra-fallopian insemination of spermatozoa from a male with obstructive azoospermia.

A pregnancy obtained after intratubal insemination with epididymal spermatozoa recovered from a patient with obstructive azoospermia is reported. The successful outcome of the case emphasizes the beneficial nature of the intra-Fallopian environment.

A comparison of vaginal ultrasonic-guided and laparoscopic retrieval of oocytes for in vitro fertilization.

A retrospective analysis was undertaken to compare the less invasive technique of vaginal ultrasonic-guided oocyte retrieval with the standard laparoscopic technique. We have shown that the outcome of the transvaginal technique with respect to oocytes harvested, fertilization rate, and pregnancy rate is comparable with the laparoscopy technique. We have also shown that 9 clinicians with little previous expertise in ultrasound have been able to incorporate this technique into a busy and successful in vitro fertilization unit.

Referral issues in psychotherapy and psychoanalysis.

The authors consider the complex decisions involved in the initial consultation of a person looking for treatment when this person must be referred to a professional colleague. They explore the way decisions are made in the referral processes and the complex practical and transference-countertransference issues that arise at the outset and whenever second opinions are sought during an ongoing psychotherapy. They present four clinical examples in varying detail to emphasize how readily misunderstandings can develop when even experienced consultants are not sufficiently alert to the complex conscious and unconscious motives and messages being expressed in the exchanges. They make recommendations on how to conceptualize and respond to them.