The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project.

BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing for effectiveness in a large cluster randomised trial is required.

Consent for routine neonatal procedures: A study of practices in Irish neonatal units. How do we compare with the gold standard BAPM guidelines?

The Irish National Consent Policy (NCP) proposes that the legal requirement for consent extends to all forms of interventions, investigations and treatment, carried out on or behalf of the Health Service Executive (HSE). This study employs a quantitative descriptive approach to investigate the practices for obtaining consent for an identified group of routine neonatal procedures in neonatal facilities throughout Ireland. The BAPM (British Association of Perinatal Medicine) guidelines were identified as 'gold standard' for the purposes of this study. The results indicated a lack of consistency between participating units pertaining to the modes of consent utilised and notable variances from 'gold standard' guidelines. Unanimity was evident for 3 procedures only (administering BCG, 6-in-1, and donor breast milk to infant). Significant findings related to EEG with video recordings, MRI/CT and gastro intestinal imaging, screening of an infant with suspected substance abuse or retinopathy of prematurity screening (ROP), administration of Vitamin K, and the carrying out of a lumbar puncture.

Sniffing out cancer using the JPL electronic nose: a pilot study of a novel approach to detection and differentiation of brain cancer.

UNLABELLED: A proof-of-concept study was done to determine whether an electronic nose developed for air quality monitoring at the Jet Propulsion Laboratory (JPL) could be used to distinguish between the odors of organ and tumor tissues, with an eye to using such a device as one of several modes in multi-modal imaging and tumor differentiation during surgery. HYPOTHESIS: We hypothesized that the JPL electronic nose (ENose) would be able to distinguish between the odors of various organ and tumor tissues. MATERIALS AND METHODS: The odor signatures, or array response, of two organs, chicken heart and chicken liver, and cultured glioblastoma and melanoma tumor cell lines were recorded using the JPL Electronic Nose. The overall array responses were compared to determine whether they were sufficiently different to allow the organs and cell lines to be identified by their array responses. RESULTS: The ENose was able to distinguish between the two types of organ tissue and between the two types of tumor cell lines. The variation in array response for the organ tissues was 19% and between the two types of cultured cell lines was 22%. CONCLUSION: This study shows that it is possible to use an electronic nose to distinguish between two types of tumor cells and between two types of organ tissue. As we conducted the experiment with a sensor array built for air quality monitoring rather than for medical purposes, it may be possible to select an array that is optimized to distinguish between different types of cells and organ tissues. Further focused studies are needed to investigate the odor signatures of different cells as well as cellular proliferation, growth, differentiation and infiltration.

A comparison of the metabolism of eighteen-carbon 13C-unsaturated fatty acids in healthy women.

Altered use of different dietary fatty acids may contribute to several chronic diseases, including obesity, noninsulin-dependent diabetes mellitus, and cardiovascular disease. However, few comparative data are available to support this link, so the goal of the present study was to compare the metabolism of [(13)C]oleate, [(13)C]alpha-linolenate, [(13)C]elaidate, and [(13)C]linoleate through oxidation and incorporation into plasma lipid fractions and adipose tissue. Each tracer was given as a single oral bolus to six healthy women. Samples were collected over 8 days, and (13)C was analyzed using isotope ratio mass spectrometry. At 9 h postdose, cumulative oxidation was similar for [(13)C]elaidate, [(13)C]oleate, and [(13)C]alpha-linolenate (19 +/- 1%, 20 +/- 4%, and 19 +/- 3% dose, respectively). Significantly lower oxidation of [(13)C]linoleate (12 +/- 4% dose; P < 0.05) was accompanied by its higher incorporation into plasma phospholipids and cholesteryl esters. Abdominal adipose tissue was enriched with [(13)C]alpha-linolenate, [(13)C]elaidate, or [(13)C]linoleate within 6 h. The percentage linoleate in plasma phospholipids correlated positively with [(13)C]linoleate and [(13)C]elaidate oxidation, indicating a potential role of background diet. Conversion of [(13)C]linoleate and [(13)C]alpha-linolenate to longer chain polyunsaturates was a quantitatively minor route of utilization.

Polymer-carbon black composite sensors in an electronic nose for air-quality monitoring.

An electronic nose that uses an array of 32 polymer-carbon black composite sensors has been developed, trained, and tested. By selecting a variety of chemical functionalities in the polymers used to make sensors, it is possible to construct an array capable of identifying and quantifying a broad range of target compounds, such as alcohols and aromatics, and distinguishing isomers and enantiomers (mirror-image isomers). A model of the interaction between target molecules and the polymer-carbon black composite sensors is under development to aid in selecting the array members and to enable identification of compounds with responses not stored in the analysis library.

Occurrence of amyotrophic lateral sclerosis among Gulf War veterans.

BACKGROUND: In response to Gulf War veterans' concerns of high rates of ALS, this investigation sought to determine if Gulf War veterans have an elevated rate of ALS. METHODS: A nationwide epidemiologic case ascertainment study design was used to ascertain all occurrences of ALS for the 10-year period since August 1990 among active duty military and mobilized Reserves, including National Guard, who served during the Gulf War (August 2, 1990, through July 31, 1991). The diagnosis of ALS was confirmed by medical record review. Risk was assessed by the age-adjusted, average, annual 10-year cumulative incidence rate. RESULTS: Among approximately 2.5 million eligible military personnel, 107 confirmed cases of ALS were identified for an overall occurrence of 0.43 per 100,000 persons per year. A significant elevated risk of ALS occurred among all deployed personnel (RR = 1.92; 95% CL = 1.29, 2.84), deployed active duty military (RR = 2.15, 95% CL = 1.38, 3.36), deployed Air Force (RR = 2.68, 95% CL = 1.24, 5.78), and deployed Army (RR = 2.04; 95% CL = 1.10, 3.77) personnel. Elevated, but nonsignificant, risks were observed for deployed Reserves and National Guard (RR = 2.50; 95% CL = 0.88, 7.07), deployed Navy (RR = 1.48, 95% CL = 0.62, 3.57), and deployed Marine Corps (RR = 1.13; 95% CL = 0.27, 4.79) personnel. Overall, the attributable risk associated with deployment was 18% (95% CL = 4.9%, 29.4%). CONCLUSIONS: Military personnel who were deployed to the Gulf Region during the Gulf War period experienced a greater post-war risk of ALS than those who were not deployed to the Gulf.

Molecular modeling of polymer composite-analyte interactions in electronic nose sensors.

We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL electronic nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereoisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings with no hydrogens. The Dreiding 2.21 force field is used for the polymer, solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4-vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic and organic compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites.

Potential role of polyunsaturates in seizure protection achieved with the ketogenic diet.

Epilepsy is a serious neurological disease that responds to two very different treatments involving lipids. Clinically, it responds to a state of ketosis induced by a very high-fat 'ketogenic' diet. Experimentally, in vitro and in vivo models demonstrate that injection or infusion of free (non-esterified) polyunsaturates such as arachidonate and docosahexaenoate also reduces seizure susceptibility. In our experience, rats on a very high-fat ketogenic diet not only have mild-to-moderate ketosis, but also have raised serum free fatty acids. Some polyunsaturates, particularly linoleate and alpha-linolenate, are relatively easily beta-oxidized and are therefore ketogenic. We conclude that raised levels of free plasma polyunsaturates could contribute to the beneficial effect of the ketogenic diet in refractory epilepsy not only by helping sustain ketosis, but also by their own direct (though poorly defined) antiseizure effects.

The Department of Defense Birth Defects Registry: overview of a new surveillance system.

BACKGROUND: The U.S. Department of Defense (DoD) is challenged with monitoring and protecting the health and wellbeing of its service members. The growing number of women on active duty and the diverse hazardous exposures associated with military service make reproductive health issues a special concern of DoD. To address this concern, the DoD Birth Defects Registry was established at the DoD Center for Deployment Health Research located at the Naval Health Research Center, San Diego, California. METHODS: The registry captures comprehensive data on healthcare utilization to calculate the prevalence of birth defects in the children of military beneficiaries. Population-based electronic surveillance is supplemented by active case validation efforts. RESULTS: Since its establishment in 1998, the registry has captured data on more than 90,000 births that occur in military families each year. Detailed analyses, to include linking registry data with military occupational exposure data (e.g., anthrax vaccination), are underway. CONCLUSIONS: The DoD Birth Defects Registry provides important reproductive health information on the geographically dispersed military population. This program is expected to complement civilian public health programs and be especially valuable to military members and their families.

Low power, lightweight vapor sensing using arrays of conducting polymer composite chemically-sensitive resistors.

Arrays of broadly responsive vapor detectors can be used to detect, identify, and quantify vapors and vapor mixtures. One implementation of this strategy involves the use of arrays of chemically-sensitive resistors made from conducting polymer composites. Sorption of an analyte into the polymer composite detector leads to swelling of the film material. The swelling is in turn transduced into a change in electrical resistance because the detector films consist of polymers filled with conducting particles such as carbon black. The differential sorption, and thus differential swelling, of an analyte into each polymer composite in the array produces a unique pattern for each different analyte of interest, Pattern recognition algorithms are then used to analyze the multivariate data arising from the responses of such a detector array. Chiral detector films can provide differential detection of the presence of certain chiral organic vapor analytes. Aspects of the spaceflight qualification and deployment of such a detector array, along with its performance for certain analytes of interest in manned life support applications, are reviewed and summarized in this article.

National Department of Defense Surveillance for Invasive Streptococcus pneumoniae: antibiotic resistance, serotype distribution, and arbitrarily primed polymerase chain reaction analyses.

To provide surveillance among US military personnel and their beneficiaries, 157 invasive Streptococcus pneumoniae clinical isolates were collected systematically from 7 large military hospitals between August 1997 and August 1999. The isolates were studied for antibiotic resistance, and 120 were serotyped and subjected to arbitrarily primed polymerase chain reaction (AP-PCR). Fifty (31.9%) of 157 isolates had intermediate or high-level resistance to penicillin, and 15.9% had multidrug resistance. The most common serotypes were 4, 6B, 9V, 14, 19F, and 23F. Those serotypes associated with penicillin resistance were 6B, 9V, 19A, and 19F. Most invasive disease cases were caused by serotypes included in the currently available 23- and 7-valent pneumococcal vaccines. By use of AP-PCR, 4 DNA groups were correlated with health care site (P< or =.0001). These results are valuable in assessing appropriate use of antibiotics and vaccines against S. pneumoniae in both military personnel and their families.

Handwashing and respiratory illness among young adults in military training.

OBJECTIVES: In response to increasing concerns about respiratory illness in military recruits, a simple handwashing program was developed and evaluated at a large Navy training center. METHODS: Clinical records from 1996 through 1998 were reviewed to determine weekly rates of respiratory illness before and after program implementation (1,089,800 person-weeks reviewed). A supplemental survey was given to a sample of recruits to assess self-reported respiratory illness and compliance with the handwashing program. RESULTS: A 45% reduction in total outpatient visits for respiratory illness was observed after implementation of the handwashing program. No change was noted in hospitalization rates for respiratory illness, which remained low during the observation period. Survey data supported clinical observations, as frequent handwashers self-reported fewer respiratory illness episodes when compared to infrequent handwashers. Surveys also revealed challenges with handwashing compliance. CONCLUSIONS: Implementation of a handwashing program in this population of healthy young adults was associated with a marked reduction in outpatient visits for respiratory illness. Despite its success, maintenance of the handwashing program has been challenging in the time-constrained setting of military training.

Lipid and fatty acid profiles in rats consuming different high-fat ketogenic diets.

High-fat ketogenic diets are used to treat intractable seizures in children, but little is known of the mechanism by which these diets work or whether fats rich in n-3 polyunsaturates might be beneficial. Tissue lipid and fatty acid profiles were determined in rats consuming very high fat (80 weight%), low-carbohydrate ketogenic diets containing either medium-chain triglyceride, flaxseed oil, butter, or an equal combination of these three fat sources. Ketogenic diets containing butter markedly raised liver triglyceride but had no effect on plasma cholesterol. Unlike the other fats, flaxseed oil in the ketogenic diet did not raise brain cholesterol. Brain total and free fatty acid profiles remained similar in all groups, but there was an increase in the proportion of arachidonate in brain total lipids in the medium-chain triglyceride group, while the two groups consuming flaxseed oil had significantly lower arachidonate in brain, liver, and plasma. The very high dietary intake of alpha-linolenate in the flaxseed group did not change docosahexaenoate levels in the brain. Our previous report based on these diets showed that although ketosis is higher in rats consuming a ketogenic diet based on medium-chain triglyceride oil, seizure resistance in the pentylenetetrazol model is not clearly related to the degree of ketosis achieved. In combination with our present data from the same seizure study, it appears that ketogenic diets with widely differing effects on tissue lipids and fatty acid profiles can confer a similar amount of seizure protection.

Pneumococcal vaccine to counter emerging infectious disease threat in the military.

Streptococcus pneumoniae causes severe morbidity and mortality worldwide and poses a significant threat to the health and readiness of U.S. military personnel. Although a vaccine to prevent pneumococcal infections has been available for almost 25 years, its use has been limited. Recently, increasing antibiotic resistance among S. pneumoniae strains has emerged, prompting health care professionals to reevaluate the benefit of administering pneumococcal vaccine. The Naval Health Research Center, in collaboration with professionals from numerous civilian and military organizations, has initiated a rigorous double-blind, placebo-controlled trial investigating the operational value of vaccinating young adults as they enlist in the military.

Specific linoleate deficiency in the rat does not prevent substantial carbon recycling from [(14)C]linoleate into sterols.

Compared with classic essential fatty acid deficiency or the feeding of a fat-free diet, little is known about specific linoleate deficiency in the rat. Carbon recycling into de novo lipogenesis has been reported to be an obligatory feature of linoleate metabolism in the liver, even in extreme linoleate deficiency (LA-D). The present study had two objectives: 1) to report a brief summary of the tissue n-6 polyunsaturated fatty acid (PUFA) profiles in specific LA-D, and 2) to quantify whole body carbon recycling from [(14)C]linoleate in specific LA-D. Rats consumed a linoleate-deficient diet for 12 weeks and then received a bolus of [1-(14)C]linoleate by gavage. In linoleate-deficient rats, the triene/tetraene ratio in several organs increased by 18- to 100-fold. The amount of (14)C appearing in organ sterols (dpm/g) of linoleate-deficient rats was 2- to 10-fold higher than in the controls and equaled 16.3% of the [(14)C]linoleate dose given, compared with 7.4% in the controls. We conclude that a similar amount (about 10%) of the carbon skeleton of linoleate is normally recycled into lipids synthesized de novo, as remains in the whole body pool of n-6 polyunsaturates.

Adult adenovirus infections: loss of orphaned vaccines precipitates military respiratory disease epidemics. For the Adenovirus Surveillance Group.

Adenovirus vaccines have greatly reduced military respiratory disease morbidity since the 1970s. However, in 1995, for economic reasons, the sole manufacturer of these vaccines ceased production. A population-based adenovirus surveillance was established among trainees with acute respiratory illness at 4 US military training centers as the last stores of vaccines were depleted. From October 1996 to June 1998, 1814 (53.1%) of 3413 throat cultures for symptomatic trainees (78% men) yielded adenovirus. Adenovirus types 4, 7, 3, and 21 accounted for 57%, 25%, 9%, and 7% of the isolates, respectively. Unvaccinated trainees were much more likely than vaccinated trainees to be positive for types 4 or 7 (odds ratio [OR] = 28.1; 95% CI, 20.2-39.2). Two training centers experienced epidemics of respiratory disease affecting thousands of trainees when vaccines were not available. Until a new manufacturer is identified, the loss of orphaned adenovirus vaccines will result in thousands of additional preventable adenovirus infections.

Heat shock inhibits phosphorylation of I-kappaBalpha.

Previous studies demonstrated that induction of the heat shock response is associated with inhibition of the proinflammatory transcription factor NF-kappaB by a mechanism involving inhibition of I-kappaBalpha degradation. To provide further insight regarding the interactions of these fundamental cellular responses, the present experiments were designed to elucidate the mechanism(s) by which heat shock inhibits degradation of I-kappaBalpha. In an in vitro model of inflammatory cell signaling, treatment of RAW 264.7 murine macrophages with LPS (100 ng/mL) caused rapid degradation of I-kappaBalpha. Heat shock, 1 h before treatment with LPS, completely inhibited LPS-mediated degradation of I-kappaBalpha. Immunoprecipitation studies demonstrated that heat shock inhibited LPS-mediated ubiquitination of I-kappaBalpha. Western-blot analyses using a phosphorylated I-kappaBalpha-specific antibody demonstrated that heat shock inhibited LPS-mediated phosphorylation of I-kappaBalpha. In contrast, heat shock induced phosphorylation of c-jun. In murine fibroblasts having genetic ablation of the heat shock factor-1 gene, heat shock inhibited tumor necrosis factor-alpha mediated degradation of I-kappaBalpha. We conclude that the mechanism by which heat shock inhibits LPS-mediated degradation of I-kappaBalpha involves specific inhibition of I-kappaBalpha phosphorylation and subsequent I-kappaBalpha ubiquitination. In addition, this mechanism does not involve activation of heat shock factor-1 or the heat shock proteins regulated by heat shock factor-1.