Vibrational Characterization of Radical Ion Adducts between Imidazole and CO2.

We address the molecular level origins of the dramatic difference in the catalytic mechanisms of CO2 activation by the seemingly similar molecules pyridine (Py) and imidazole (Im). This is accomplished by comparing the fundamental interactions of CO2 radical anions with Py and Im in the isolated, gas phase PyCO2- and ImCO2- complexes. These species are prepared by condensation of the neutral compounds onto a (CO2) n- cluster ion beam by entrainment in a supersonic jet ion source. The structures of the anionic complexes are determined by theoretical analysis of their vibrational spectra, obtained by IR photodissociation of weakly bound CO2 molecules in a photofragmentation mass spectrometer. Although the radical PyCO2- system adopts a carbamate-like configuration corresponding to formation of an N-C covalent bond, the ImCO2- species is revealed to be best described as an ion-molecule complex in which an oxygen atom in the CO2- radical anion is H-bonded to the NH group. Species that feature a covalent N-C interaction in ImCO2- are calculated to be locally stable structures, but are much higher in energy than the largely electrostatically bound ion-molecule complex. These results support the suggestion from solution phase electrochemical studies (Bocarsly et al. ACS Catal. 2012, 2, 1684-1692) that the N atoms are not directly involved in the catalytic activation of CO2 by Im.

Multilaboratory particle image velocimetry analysis of the FDA benchmark nozzle model to support validation of computational fluid dynamics simulations.

This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re(throat)) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re(throat)=500) and turbulent flow conditions (Re(throat)≥3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ∼10% at most of the locations. However, for the transitional flow case (Re(throat)=2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ∼60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to ∼15%. The experimental procedure and flow results from this interlaboratory study (available at http://fdacfd.nci.nih.gov) will be useful in validating CFD simulations of the benchmark nozzle model and in performing PIV studies on other medical device models.

Auricular acupuncture as a treatment for pregnant women who have low back and posterior pelvic pain: a pilot study.

OBJECTIVE: The primary aim of this study was to examine whether 1 week of continuous auricular acupuncture could reduce low back and posterior pelvic pain associated with pregnancy. STUDY DESIGN: A randomized controlled trial was conducted on pregnant women who have lower back and posterior pelvic pain. These women were randomly assigned into an acupuncture group, a sham acupuncture group, or a waiting list control group. All participants were monitored for 2 weeks. RESULTS: Baseline and day 7 showed significant group differences in pain (F = 15; P < .0001) and in the disability rating index score (F = 7; P < .0001). The participants in the acupuncture group reported a significant reduction of pain and improvement of functional status as compared with those in the sham acupuncture and control groups. CONCLUSION: One week of continuous auricular acupuncture decreases the pain and disability experienced by women with pregnancy-related low back and posterior pelvic pain.

Pediatric circulatory support: an FDA perspective.

The Department of Health and Human Services, at the direction of Congress, has recently begun to address concerns regarding the development of medical devices designed specifically for the pediatric population, including devices for pediatric mechanical circulatory support, as evidenced by the National Institutes of Health's (NIH) funding of several development contracts. Food and Drug Administration (FDA) approval for marketing of these devices will typically follow either of two regulatory pathways: the Humanitarian Device Exemption (HDE) or the Premarket Application (PMA). An HDE is limited both in the extent of clinical use and economic benefit to the manufacturer, but does not require data derived from a clinical trial for market approval. A PMA allows for use in a larger patient population and offers economic benefit for the manufacturer; it does, however, almost always necessitate data derived from a clinical trial. The HDE and PMA require demonstration of a reasonable assurance of safety. In addition, an HDE requires a demonstration of probable benefit, whereas a PMA requires a demonstration of a reasonable assurance of effectiveness. The evidence that can be used to support an HDE or a PMA approval may include both preclinical and clinical data. Types of preclinical tests needed depend upon the device design and its intended use, because circulatory support devices are all unique.

Low back pain during pregnancy: prevalence, risk factors, and outcomes.

OBJECTIVE: To estimate the severity of the low back pain (LBP) during pregnancy, including prevalence, risk factors, impact on daily living, and health provider management. METHODS: An anonymous survey consisting of 36 questions was distributed to pregnant women participating in various prenatal care clinics and educational classes in New Haven County, Connecticut. A total of 950 surveys was returned from May 2002 through October 2003. At each site, a researcher was available each week to answer questions and gather surveys. RESULTS: Six hundred forty-five (68.5%; 95% confidence interval [CI] 65-72%) respondents reported experiencing LBP during their current pregnancy. The prevalence was not affected by gestational age (P =.56). Low back pain during the current pregnancy was predicted by age (younger women were more likely to develop it; P =.004), history of LBP without pregnancy (P =.002), during menstruation (P =.01), and during a previous pregnancy (P =.002). The majority of respondents reported that LBP during pregnancy caused sleep disturbances (58%; 95% CI 54-62%) and impaired daily living (57%; 95% CI 53-62%). Average pain was moderate in severity. Nearly 30% of respondents stopped performing at least one daily activity because of pain and reported that pain also impaired the performance of other routine tasks. Only 32% (95% CI 28-36%) of the respondents with LBP during pregnancy informed their prenatal care providers of this problem, and only 25% (95% CI 21-28%) of prenatal care providers recommended a treatment. CONCLUSION: Low back pain during pregnancy is a common problem that causes hardship in this population. Further studies are indicated in the areas of prevention and treatment.

Food and Drug Administration's perspectives on pediatric cardiac assist devices.

Dual missions of the Center for Devices and Radiological Health at the Food and Drug Administration (FDA) are 1) promoting public health by promptly reviewing and taking appropriate, timely action regarding the marketing of regulated medical devices while at the same time, and 2) protecting public health by ensuring a reasonable assurance of the safety and effectiveness of medical devices deemed appropriate for human use. In the past, clinicians have used cardiac assist devices intended for adults to treat pediatric heart failure patients. However, because of the larger size of the approved devices, many pediatric patients are underserved by this approach. Currently, several cardiac assist devices intended for use in pediatric patients are being developed. FDA believes that clinical data used to support such safety and probable benefit may be derived from a small focused clinical trial in this target population, and developers may want to consider this approach for approval of the humanitarian device exemption application. Pediatric device development is challenging and early communication with FDA to develop an appropriate regulatory and scientific pathway for device submission is advised and warranted. This early interaction can facilitate the development of a small but necessary trial for these life-sustaining pediatric cardiac assist devices.

HNNC radical and its role in the CH+N2 reaction.

A previously unreported channel in the spin-allowed reaction path for the CH+N2 reaction that involves the HNNC radical is presented. The structures and energetics of the HNNC radical and its isomers HCNN and HNCN and the relevant intermediates and transition states that are involved in the proposed mechanism are obtained at the coupled cluster singles and doubles level of theory with noniterative triples correction (CCSD(T)) using a converging series of basis sets aug-cc-pVDZ, aug-cc-pVTZ, and aug-cc-pVQZ. The aug-cc-pVQZ basis is used for all the final single point energy calculations using the CCSD(T)/aug-cc-pVTZ optimized geometries. We find the HNNC radical to have a heat of formation of DeltafH0 (HNNC)=116.5 kcal mol(-1). An assessment of the quality of computed data of the radical species HNCN and HCNN is presented by comparison with the available experimental data. We find that HNNC can convert to HNCN, the highest barrier in this path being 14.5 kcal mol(-1) above the energy of the CH+N2 reactants. Thus, HNNC can play a role in the high-temperature spin-allowed mechanism for the reaction of CH+N2 proposed by Moskaleva, Xia, and Lin (Chem. Phys. Lett. 2000, 331, 269).

High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.