Field-Based Planetary Protection Operations for Melt Probes: Validation of Clean Access into the Blood Falls, Antarctica, Englacial Ecosystem.

Subglacial environments on Earth offer important analogs to Ocean World targets in our solar system. These unique microbial ecosystems remain understudied due to the challenges of access through thick glacial ice (tens to hundreds of meters). Additionally, sub-ice collections must be conducted in a clean manner to ensure sample integrity for downstream microbiological and geochemical analyses. We describe the field-based cleaning of a melt probe that was used to collect brine samples from within a glacier conduit at Blood Falls, Antarctica, for geomicrobiological studies. We used a thermoelectric melting probe called the IceMole that was designed to be minimally invasive in that the logistical requirements in support of drilling operations were small and the probe could be cleaned, even in a remote field setting, so as to minimize potential contamination. In our study, the exterior bioburden on the IceMole was reduced to levels measured in most clean rooms, and below that of the ice surrounding our sampling target. Potential microbial contaminants were identified during the cleaning process; however, very few were detected in the final englacial sample collected with the IceMole and were present in extremely low abundances (∼0.063% of 16S rRNA gene amplicon sequences). This cleaning protocol can help minimize contamination when working in remote field locations, support microbiological sampling of terrestrial subglacial environments using melting probes, and help inform planetary protection challenges for Ocean World analog mission concepts.

Bat predation and the evolution of frog vocalizations in the neotropics.

Bat predation has probably had an important influence on the evolution of frog vocalizations in the Neotropics. The rate at which fringe-lipped bats capture frogs is significantly higher when the frogs are calling. These bats respond to a wide variety of calls from edible frogs, and, when simultaneously presented with a choice, choose the recorded call of a palatable species over that of a poisonous species and the call of a small species over that of one too large to capture. Thus the selective advantages of loud, rapid mating calls in anurans are balanced by an increased risk of predation.

The 1986 lake nyos gas disaster in cameroon, west Africa.

The sudden, catastrophic release of gas from Lake Nyos on 21 August 1986 caused the deaths of at least 1700 people in the northwest area of Cameroon, West Africa. Chemical, isotopic, geologic, and medical evidence support the hypotheses that (i) the bulk of gas released was carbon dioxide that had been stored in the lake's hypolimnion, (ii) the victims exposed to the gas cloud died of carbon dioxide asphyxiation, (iii) the carbon dioxide was derived from magmatic sources, and (iv) there was no significant, direct volcanic activity involved. The limnological nature of the gas release suggests that hazardous lakes may be identified and monitored and that the danger of future incidents can be reduced.

Comparison of the mutagenicities of malondialdehyde and the side products formed during its chemical synthesis.

Malondialdehyde, a product of polyunsaturated fatty acid metabolism and degradation, has been reported to be mutagenic and carcinogenic. The malondialdehyde used for testing was generated by the acidic hydrolysis of tetraalkoxypropanes. We have studied the production of compounds mutagenic to Salmonella typhimurium strain his D 3052 following the hydrolysis of tetraalkoxypropanes. The major mutagenic compound produced from tetraethoxypropane is beta-ethoxy-acrolein (90 to 100 revertants/mumol) and not malondialdehyde (3 to 5 revertants/mumol). Hydrolysis of tetramethoxypropane produces two compounds, beta-methoxy-acrolein (125 to 160 revertants/mumol) and 3,3-dimethoxypropionaldehyde (105 to 135 revertants/mumol), which are more mutagenic than is malondialdehyde. Using standard conditions for the hydrolysis of tetraethoxypropane, the yield of malondialdehyde is 25%, and the yield of beta-ethoxyacrolein is 13%. Considering the differences in specific mutagenicity, the compound which accounts for the bulk of the mutagenicity of a crude hydrolsate of tetraethoxypropane is not malondialdehyde. The presence of these incomplete hydrolysis products may lead to a substantial overestimation of the actual mutagenicity and carcinogenicity of malondialdehyde.

Age-associated structural alterations in senescent mouse brain DNA.

The maintenance of structural integrity in the DNA of aging mice has been examined with the amin in view of determining whether changes in genome structure constitute the molecular basis of aging. Cell lysate DNA from brains of differently aged mice was subjected to alkaline sucrose gradient sedimentation. The results show that brain DNA from young mice sediments mondispersely while that from senescent mice exhibits polydisperse sedimentation patterns, bainding in four peaks corresponding to number-average molecular weights of 1.4-10(8), 70-10(6), 15-10(6) and 3-10(6). When treated with nuclease S1, it was the 30 month mouse DNA whose sedimentation shifted to the top of the gradient indicating a reduction in its molecular weight as a result of nuclease digestion. The apparent increase in single strand breaks implies that the rate of breakage in old mouse brain DNA is faster than that of repair replication. The conclusion is drawn that senescence could result from an accumulation of defects in the genome.

Controlled release of water-soluble macromolecules from bioerodible hydrogels.

A bioerodible hydrogel based on water-soluble unsaturated polyesters crosslinked through the double bonds and capable of immobilizing water-soluble macromolecules has been developed. As the ester linkages cleave, the entrapped macromolecule is gradually released to the surrounding aqueous environment. In vitro rate of hydrolysis and concommitant macromolecule release can be controlled by constructing unsaturated polyesters containing varying proportions of esters activated by electron-withdrawing substituents vicinal to the ester function and/or by varying crosslink density. Polyesters containing unsaturation either in the polymer backbone or pendant have been prepared. Macromolecule-containing hydrogels have been fabricated as dessicated microspheres that can be resuspended in water and passed through a 22-gauge hypodermic needle.

Screening for genetic aberrations in papillary thyroid cancer by using comparative genomic hybridization.

BACKGROUND: Determination of the genetic composition of papillary thyroid cancers may help explain differences in observed clinical behavior. Comparative genomic hybridization (CGH) is a novel molecular cytogenetic assay that allows simultaneous detection of gains, losses, and amplification of genetic information, making it an ideal screening tool. The aim of this study was to identify genetic aberrations occurring in papillary thyroid cancers by using CGH analysis. METHODS: CGH analysis was performed on 21 individual cases of papillary thyroid cancers. Nonparametric statistical comparisons were performed with the Fisher exact test. RESULTS: Genetic abnormalities were identified by CGH in 10 of 21 cases (48%). A recurrent pattern of aberrations was seen in cases where genetic changes were detected, involving losses at chromosome arms 1p and 9q and chromosomes 17, 19, and 22, and gains at chromosome 4 and chromosome arms 5q, 6q, 9q, and 13q. The loss of chromosome 22 was unique to younger patients (P =.05) and was associated with a higher rate of regional lymphatic metastasis (19% vs 80%, P =.02). CONCLUSIONS: Two genetically unique groups of patients were identified by using CGH analysis. One group had no detectable aberrations; the other had a recurrent pattern of aberrations, localizing to the identical chromosomal loci. This pattern of aberrations suggests that the involved loci may contain genes important in thyroid carcinogenesis. The clinical significance of the presence of copy number changes detected by CGH needs to be determined. In addition, molecular cloning of involved genes in each of the aberrations is warranted.

Information technology outside health care: what does it matter to us?

Non-health-care uses of information technology (IT) provide important lessons for health care informatics that are often overlooked because of the focus on the ways in which health care is different from other domains. Eight examples of IT use outside health care provide a context in which to examine the content and potential relevance of these lessons. Drawn from personal experience, five books, and two interviews, the examples deal with the role of leadership, academia, the private sector, the government, and individuals working in large organizations. The interviews focus on the need to manage technologic change. The lessons shed light on how to manage complexity, create and deploy standards, empower individuals, and overcome the occasional "wrongness" of conventional wisdom. One conclusion is that any health care informatics self-examination should be outward-looking and focus on the role of health care IT in the larger context of the evolving uses of IT in all domains.

Menses induction in rhesus monkeys using a controlled-release vaginal delivery system containing (15S) 15-methyl prostaglandin F2 alpha methyl ester.

Polymeric controlled-release vaginal delivery systems were designed for (15S)15-methyl prostaglandin (PG)F2 alpha methyl ester (carboprost methyl). The drug was incorporated into a highly permeable reservoir membrane that was bound to a relatively nonpermeable support membrane. The rate of drug release was controlled by coating the reservoir membrane with a less permeable rate-controlling membrane. Vaginal devices were prepared with in vitro steady-state release rates from 5 to 180 microgram/hour. The release curves were characterized by an initial, transient rapid release of the drug, followed by a linear zero-order release phase. Pregnancy was terminated in rhesus monkeys following a 24-hour treatment with vaginal devices having release rates of carboprost methyl of 45 microgram/hour or greater. Successful menses induction was associated with peripheral plasma concentrations of (15S)15-methyl PGF2 alpha between 2000 and 3000 pg/ml. Peripheral plasma concentrations of progesterone declined very rapidly to less than 1.0 ng/ml in monkeys in which pregnancy was terminated. These studies demonstrate the feasibility of manufacturing controlled-release vaginal delivery systems containing carboprost methyl for use in early pregnancy termination.

Potato-lactulose breath hydrogen testing as a function of gastric motility in diabetes mellitus.

OBJECTIVE: Scintigraphic determination of gastric emptying is the current standard for the assessment of gastric motility and the diagnosis of diabetic gastroparesis. However, such studies are expensive, inconvenient, and involve exposure to radiation. Because the time course of breath hydrogen (H2) excretion after ingestion of lactulose correlates with upper gastrointestinal transit time, we hypothesized that patients with diabetic gastroparesis would exhibit prolonged breath H2 excretion after ingestion of a test meal containing complex carbohydrate and lactulose compared to subjects without diabetes and subjects with diabetes but without gastroparesis. RESEARCH DESIGN AND METHODS: Ten healthy subjects without diabetes, 10 subjects with diabetes but without gastroparesis (gastric emptying T1/2,T1/2 < 90 minutes), and 10 subjects with diabetes and previously diagnosed gastroparesis (T1/2 > 90 minutes) were admitted for a single 24-hour study. Gastric motility agents were withheld 24 hours prior to the study. Euglycemia was established and maintained overnight in subjects with diabetes with continuous intravenous insulin infusion. At 6:00 AM, all subjects ingested a breakfast containing 100 g of cooked potato starch and 20 g lactulose. Breath H2 excretion was monitored at baseline and every 30 minutes for 12 hours after ingestion of the test meal. RESULTS: Twelve hours after ingestion of the test meal, raw and baseline adjusted breath H2 excretion was significantly elevated in the gastroparesis group compared to the unaffected group with diabetes and the group without diabetes (p < 0.001). The baseline and 12-hour data points were adequate to discriminate between normal and delayed gastric emptying. CONCLUSIONS: We conclude that patients with previously diagnosed gastroparesis exhibit prolonged breath H2 excretion after ingestion of a test meal. This test may prove to be a safe, reliable, and affordable outpatient screening test for diabetic gastroparesis.

Developing actionable dietary guidance messages: dietary fat as a case study.

Although consumers say they are concerned about nutrition and are aware that eating a healthful diet is important for good health, this knowledge does not always translate into healthful diet behaviors or motivate behavior change. In an effort to better understand consumer attitudes about nutrition and to explore alternatives for communicating dietary advice in language that is meaningful and motivates behavior change, the International Food Information Council (IFIC) conducted qualitative research with consumers (using focus groups) and registered dietitians (using telephone interviews) in 1998 and 1999. Results of the research are presented using dietary fat as a case study. Findings from the IFIC research were reported to the Dietary Guidelines Advisory Committee to assist the Committee in developing meaningful and action-oriented dietary advice related to dietary fat for inclusion in the 2000 Dietary Guidelines for Americans that would be motivating and easy for consumers to implement. The recommendation to moderate fat intake in the new dietary guideline, "Choose a diet that is low in saturated fat and cholesterol and moderate in total fat" is consistent with communication recommendations in the IFIC research. Further, the moderate fat message is empowering because it suggests an achievable dietary regimen and reduces guilt and worry about foods. It allows flexibility to enjoy desired foods and promotes using common sense when it comes to diet. Several issues emerged from the IFIC research that apply to general nutrition communications with consumers, whether it be through national nutrition recommendations or in one-on-one counseling situations: to be effective, messages to consumers about nutrition, and specifically dietary fat, must address sources of discomfort about dietary choices; they must engender a sense of empowerment; and they should motivate both by providing clear information that propels toward taking action and appeals to the need to make personal choices.

Development of an estriol-releasing intrauterine device.

Estriol-releasing intrauterine devices were developed for experimental use in animals and humans. The devices consist of a reservior containing the steroid surrounded by a rate-limiting polyurethane membrane. After an initial transient, the drug is released from the device at a constant rate for 1 year or more; devices with a much longer release period can be fabricated readily. A constant release rate is achieved by maintaining solid drug in the reservoir and good physical contact between the drug and the inside wall of the device. The methods used to fabricate the devices are described along with release rate and stability data.

Menses induction and second-trimester pregnancy termination using a polymeric controlled release vaginal delivery system containing (15S)15-methyl PGF2 alpha methyl ester.

A polymeric controlled release vaginal delivery system was developed for 15(S)15-methyl PGF2 alpha methyl ester. This delivery system is a reservoir-type device consisting of laminated membranes that are mounted on an inert holder. The delivery systems were designed to have in vitro steady-state release rates of 50 or 100 micrograms/hr. Included in the study were seven early pregnant (amenorrhea up to 49 days) patients who were treated with 50 micrograms/hr devices and five early pregnant patients who were treated with 100 micrograms/hr devices. Three second-trimester cases received a 50 micrograms/hr device and five received a 100 micrograms/hr device. Five of the seven early first-trimester patients given 50 micrograms/hr devices aborted completely. The plasma levels of PG in those patients were 400-600 pg/ml for up to 6 hours. In the two cases that did not abort completely, the plasma levels of drug dropped sharply after both patients had started to bleed vaginally one hour after administration of the device. All five early pregnant patients treated with 100 micrograms/hr devices aborted completely. None of the three second-trimester cases aborted within 24 hours following administration of the 50 micrograms/hr devices. Three of the five second-trimester patients aborted within 24 hours following treatment with 100 micrograms/hr devices. The plasma levels of drug reached 1-1.5 ng/ml during the first 2-5 hours and then declined, especially after rupture of the membranes. The variation of plasma levels of drug following vaginal administration of the devices in different individuals was considerably less than following vaginal suppositories. Therefore, this device seems to be close to an ideal delivery system for vaginal administration of abortifacients.

PIP: The vaginal delivery system described is a reservoir type device consisting of laminated membranes that are mounted on an inert holder which are designed to have in vitro steady state release rates of 50 or 100 mcg/hour. 7 early pregnant patients were treated with 50 mcg/hour devices and 5 early pregnant patients with 100 mcg/hour devices, 3 2nd trimester cases received a 50 mcg/hour and 5 a 100 mcg/hour device. 5 early 1st trimester patients given 50 mcg/hour devices aborted completely. The plasma levels of progesterone in those patients were 400-600 ng/ml for up to 6 hours. In 2 cases that did not abort completely plasma levels dropped sharply after they started to bleed vaginally 1 hour after administration of the device. All 5 1st trimester patients with 100 mcg/hour devices aborted completely. None of the 3 2nd trimester cases aborted within 24 hours following administration of the 50 mcg/hour devices. 3 2nd trimester patients aborted within 24 hours following treatment with 100 mcg/hour devices. Plasma levels of drug reached 1-1.5 ng/ml during the 1st 2-5 hours and then declined. This device seems to be close to an ideal delivery system since the variation of plasma levels is less than following vaginal suppositories. The major clinical indication in the future will be menses induction and the ideal release rate should be between 50-100 mcg/hour.

An analytical scheme for determining forms of sulphur in oil shales and associated rocks.

An analytical scheme for determining various forms of sulphur in oil shales and associated rocks is presented. Acid-soluble sulphate, sulphur contained in monosulphide and in disulphide minerals, and organically-bound sulphur are all quantitatively recovered as separate fractions. Finely-ground oil-shale samples are treated in an inert atmosphere with 6M hydrochloric acid to dissolve the acid-soluble sulphate minerals and form H(2)S from the decomposition of monosulphide minerals. The acid-soluble sulphate is precipitated as barium sulphate and the H(2)S is collected and weighed as silver sulphide. Disulphide minerals in the solid residue from the acid treatment are reduced by an acidified Cr(II) solution in an inert atmosphere, releasing the sulphide as H(2)S. The H(2)S is collected as silver sulphide. An Eschka fusion oxidizes and solubilizes all sulphur remaining within the Cr(II)-treated residue. This sulphate represents organically-bound sulphur and is collected as barium sulphate. The analytical procedures have been verified by using (57)Fe Mössbauer spectroscopy. Good agreement between the chemical and Mössbauer data substantiated the sequential removal of the forms of sulphur and also demonstrated the ability of Mössbauer spectroscopy to determine the absolute quantities of iron present in specific minerals.

A poor precedent.

The single greatest impediment to the successful leveraging of computer-based patient records (CPRs) is the difficulty of creating and maintaining comparable patient descriptions. Specifically, it will be hard to justify the investment required to deploy CPRs widely if the patient descriptions they store are not comparable across successive releases of controlled health-care vocabularies. Thus, it is necessary to solve the controlled health-care vocabulary update problem for CPRs before the comparability of patient descriptions can be sustained. What may seem to be a narrow technical problem of interest only to maintainers of health-care enterprise systems is, instead, a central problem of medical informatics. Cimino's "Formal descriptions and adaptive mechanisms for changes in controlled medical vocabularies" describes a classification of the changes appearing in the 1994 Edition of the International Classification of Diseases (ICD-9-CM). His paper describes the conversion of differences detected between the 1993 and 1994 releases of ICD-9-CM and a conversion of the elements of the classification into the required formal changes to the Medical Entities Dictionary (MED), part of the CPR in use at Columbia Presbyterian Medical Center. Because the process of detecting differences begins with an empirical analysis of the ASCII representations of the 1993 and 1994 releases of ICD-9-CM, it is impossible for a computer program to infer the intent of the changes that caused the differences; instead, a content expert must infer the intent and then update the MED accordingly. A typical task is to infer whether a change in naming also reflects a change in the meaning named. While Cimino's methods and their execution are exemplary in every respect, they nevertheless constitute a kind of "reverse engineering"-an ad hoc attempt to infer intent from details. Reverse engineering of changes to controlled medical vocabularies is a poor precedent. Such methods should be viewed as necessary short-term expedients only, and all parties concerned should work toward an incremental plan by which the intent of changes to controlled health-care vocabularies can be made both explicit and machine processible. Only then can the comparability of patient descriptions be sustained.

Navigating to knowledge.

One way to fulfill point-of-care knowledge needs is to present caregivers with a visual representation of the available "answers". Using such a representation, caregivers can recognize what they want, rather than have to recall what they need, and then navigate to an appropriate answer. Given selected pieces of information from a computer-based patient record, an interface can anticipate certain knowledge needs by initializing caregiver navigation in a semantic neighborhood of answers likely to be relevant to the patient at hand. These notions draw heavily on two collaborative projects--the U.S. National Library of Medicine Unified Medical Language System and the U.S. National Cancer Institute Knowledge Server. Both of these projects support navigation because they make the structure of medical knowledge explicit in a way that can be exploited by human interfaces.

Metaphrase: an aid to the clinical conceptualization and formalization of patient problems in healthcare enterprises.

Patient descriptors, or "problems," such as "brain metastases of melanoma" are an effective way for caregivers to describe patients. But most problems, e.g., "cubital tunnel syndrome" or "ulnar nerve compression," found in problem lists in an Electronic Medical Record (EMR) are not comparable computationally--in general, a computer cannot determine whether they describe the same or a related problem, or whether the user would have preferred "ulnar nerve compression syndrome." Metaphrase is a scalable, middleware component designed to be accessed from problem-manager applications in EMR systems. In response to caregivers' informal descriptors it suggests potentially equivalent, authoritative, and more formally comparable descriptors. Metaphrase contains a clinical subset of the 1997 UMLS Metathesaurus and some 10,000 "problems" from the Mayo Clinic and Harvard Beth Israel Hospital. Word and term completion, spelling correction, and semantic navigation, all combine to ease the burden of problem conceptualization, entry and formalization.

An evaluation of UMLS as a controlled terminology for the Problem List Toolkit.

We are developing a set of software components--the Problem List Toolkit (PL-Tk)--to support operations on clinical problem labels. An adaptation of the National Library of Medicine's Unified Medical Language System (UMLS) provides general vocabulary services to domain-specific software components. Our initial investigation centers on the inclusion in UMLS of problem labels used in the Beth Israel Deaconess Medical Center's Online Medical Record (OMR). We also explore the semantic typing of problem labels matched in UMLS. We have operationally defined a clinical problem to derive its semantic type from classes of terms representing findings or processes typically requiring diagnostic evaluation or therapeutic management in clinical practice. Of 1262 unique OMR problem labels, 999 terms (79%) have matches in UMLS. 986 of 999 terms (99%) map to the UMLS concept of the corresponding lexical match. 952 of 999 terms (95%) have semantic types that comply with our operational definition of clinical problems. These 952 terms (75%) constitute Version 1.0 of the problem list vocabulary B196. Matching terms with inappropriate semantic types raise issues regarding requirements for PL-Tk, typing of existing UMLS terms, and the adequacy of our operational definition for clinical problems. UMLS provides a large repertoire of pre-coordinated terms that are used as problem labels in a heavily used computer-based patient record system. The semantic type hierarchy provides a framework for the consistent use of clinical concepts in problem lists such that clinical problem labels represent "good" clinical problems.

The role of compositionality in standardized problem list generation.

Compositionality is the ability of a Vocabulary System to record non-atomic strings. In this manuscript we define the types of composition, which can occur. We will then propose methods for both server based and client-based composition. We will differentiate the terms Pre-Coordination, Post-Coordination, and User-Directed Coordination. A simple grammar for the recording of terms with concept level identification will be presented, with examples from the Unified Medical Language System's (UMLS) Metathesaurus. We present an implementation of a Window's NT based client application and a remote Internet Based Vocabulary Server, which makes use of this method of compositionality. Finally we will suggest a research agenda which we believe is necessary to move forward toward a more complete understanding of compositionality. This work has the promise of paving the way toward a robust and complete Problem List Entry Tool.

Biogeochemical evolution of a landfill leachate plume, Norman, Oklahoma.

Leachate from municipal landfills can create groundwater contaminant plumes that may last for decades to centuries. The fate of reactive contaminants in leachate-affected aquifers depends on the sustainability of biogeochemical processes affecting contaminant transport. Temporal variations in the configuration of redox zones downgradient from the Norman Landfill were studied for more than a decade. The leachate plume contained elevated concentrations of nonvolatile dissolved organic carbon (NVDOC) (up to 300 mg/L), methane (16 mg/L), ammonium (650 mg/L as N), iron (23 mg/L), chloride (1030 mg/L), and bicarbonate (4270 mg/L). Chemical and isotopic investigations along a 2D plume transect revealed consumption of solid and aqueous electron acceptors in the aquifer, depleting the natural attenuation capacity. Despite the relative recalcitrance of NVDOC to biodegradation, the center of the plume was depleted in sulfate, which reduces the long-term oxidation capacity of the leachate-affected aquifer. Ammonium and methane were attenuated in the aquifer relative to chloride by different processes: ammonium transport was retarded mainly by physical interaction with aquifer solids, whereas the methane plume was truncated largely by oxidation. Studies near plume boundaries revealed temporal variability in constituent concentrations related in part to hydrologic changes at various time scales. The upper boundary of the plume was a particularly active location where redox reactions responded to recharge events and seasonal water-table fluctuations. Accurately describing the biogeochemical processes that affect the transport of contaminants in this landfill-leachate-affected aquifer required understanding the aquifer's geologic and hydrodynamic framework.