Specifying Exposure Classification Parameters for Sensitivity Analysis: Family Breast Cancer History

One of the challenges to implementing sensitivity analysis for exposure misclassification is the process of specifying the classification proportions (eg, sensitivity and specificity). The specification of these assignments is guided by three sources of information: estimates from validation studies, expert judgment, and numerical constraints given the data. The purpose of this teaching paper is to describe the process of using validation data and expert judgment to adjust a breast cancer odds ratio for misclassification of family breast cancer history. The parameterization of various point estimates and prior distributions for sensitivity and specificity were guided by external validation data and expert judgment. We used both nonprobabilistic and probabilistic sensitivity analyses to investigate the dependence of the odds ratio estimate on the classification error. With our assumptions, a wider range of odds ratios adjusted for family breast cancer history misclassification resulted than portrayed in the conventional frequentist confidence interval.Children's Cancer Research Fund, Minneapolis, MN, US

Using negative detections to estimate source finder reliability

We describe a simple method to determine the reliability of source finders based on the detection of sources with both positive and negative total flux. Under the assumption that the noise is symmetric and that real sources have positive total flux, negative detections can be used to assign to each positive detection a probability of being real. We discuss this method in the context of upcoming, interferometric HI surveys.Comment: Accepted for publication on the 2012 PASA source finding special issu

Biomolecular imaging and electronic damage using X-ray free-electron lasers

Proposals to determine biomolecular structures from diffraction experiments using femtosecond X-ray free-electron laser (XFEL) pulses involve a conflict between the incident brightness required to achieve diffraction-limited atomic resolution and the electronic and structural damage induced by the illumination. Here we show that previous estimates of the conditions under which biomolecular structures may be obtained in this manner are unduly restrictive, because they are based on a coherent diffraction model that is not appropriate to the proposed interaction conditions. A more detailed imaging model derived from optical coherence theory and quantum electrodynamics is shown to be far more tolerant of electronic damage. The nuclear density is employed as the principal descriptor of molecular structure. The foundations of the approach may also be used to characterize electrodynamical processes by performing scattering experiments on complex molecules of known structure.Comment: 16 pages, 2 figure

Altered paired associative stimulation-induced plasticity in NMDAR encephalitis

Objective: To determine whether neurophysiological mechanisms indicating cortical excitability, long-term potentiation (LTP)-like plasticity, GABAergic and glutamatergic function are altered in patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response. Methods: Neurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 ± 11 years; 30 females) and age/gender-matched healthy controls (n = 27, 28.5 ± 10 years; 25 females) were performed using transcranial magnetic stimulation-derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP-like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging. Results: PAS-induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor-evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS-induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = −0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow-up assessments were available in six patients and demonstrated parallel improvement of PAS-induced plasticity and mRS. Interpretation: Assessment of PAS-induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well-tolerated “electrophysiological biomarker” to monitor therapy response in the future.Clinical Trial Registration: ClinicalTrials.gov: Identifier: NCT0186557

The Effects of Slow Deep Breathing on Measures of Microvascular and Autonomic Function in an Irritable Bowel Syndrome Population

Irritable Bowel Syndrome (IBS) is a functional disorder linked to disruptions in autonomic nervous system regulation, which could impair vascular homeostasis. Studies have shown that slow, deep breathing reduces muscle sympathetic nerve activity and arterial stiffness; however, its effects on autonomic regulation in adults with IBS have not been previously investigated. Moreover, the effects of breathing on microvascular endothelium function are unknown. PURPOSE: To investigate the effects of slow, deep breathing on measures of autonomic function and microvascular endothelial function in adults with IBS. METHODS: Adults (ages 18-65 years) with a formal diagnosis of IBS were enrolled and randomized to 4-week controlled breathing or time-control conditions. The experimental group followed a 20-minute slow, deep breathing video 4 to 6 days per week while the control group maintained their regular activity. To assess autonomic function, heart rate variability (HRV) and exercise heart rate recovery (HRR) were measured at baseline and week 4. The HRV test was accompanied by respiration rate measurements to ensure no significant deviations in respiration occurred between assessments as this could impact HRV. Exercise HRR was assessed 30, 60, and 120 seconds following a Balke treadmill VO2 max test. Laser Doppler flowmetry was assessed at baseline (33°C) and in response to local heating up to 43.5°C while blood pressure was measured throughout for the calculation of cutaneous vascular conductance (CVC). RESULTS: Of the 14 participants enrolled, 12 (n=6 for control and experimental groups) completed the study. At baseline, age (p = 0.47) and body mass index (p=0.14) were similar between groups. Respiration rate was similar between HRV assessments in both groups. In the experimental group, %CVC max significantly increased (p = 0.027) at week 4 while HRR was unchanged. A tendency toward a time by group interaction was observed for HRV low frequency to high frequency (LF/HF) ratio (p = 0.066) with slight reductions in the breathing group and increases in the control group. In the control group, %CVC max and HRR were unaltered, though HRR at 120 seconds tended to improve (p=0.08). CONCLUSIONS: Preliminary results from this ongoing study suggest that microvascular endothelial function can improve with 4 weeks of slow, deep breathing exercises in adults with IBS. These alterations in vascular function were unaccompanied by significant changes in autonomic function though trends were observed in HRV. Results show that slow, deep breathing is a viable alternative to physical exercise for improving microvascular function. Findings also suggest that this intervention could result in improved sympathovagal balance in adults with IBS and potentially other individuals with functional disorders

Effects of radiation damage and inelastic scattering on single-particle imaging of hydrated proteins with an X-ray Free-Electron Laser

We present a computational case study of X-ray single-particle imaging of hydrated proteins on an example of 2-Nitrogenase–Iron protein covered with water layers of various thickness, using a start-to-end simulation platform and experimental parameters of the SPB/SFX instrument at the European X-ray Free-Electron Laser facility. The simulations identify an optimal thickness of the water layer at which the effective resolution for imaging the hydrated sample becomes significantly higher than for the non-hydrated sample. This effect is lost when the water layer becomes too thick. Even though the detailed results presented pertain to the specific sample studied, the trends which we identify should also hold in a general case. We expect these findings will guide future single-particle imaging experiments using hydrated proteins

SDSS J092455.87+021924.9: an Interesting Gravitationally Lensed Quasar from the Sloan Digital Sky Survey

We report the discovery of a new gravitationally lensed quasar from the Sloan Digital Sky Survey, SDSS J092455.87+021924.9 (SDSS J0924+0219). This object was selected from among known SDSS quasars by an algorithm that was designed to select another known SDSS lensed quasar (SDSS 1226-0006A,B). Five separate components, three of which are unresolved, are identified in photometric follow-up observations obtained with the Magellan Consortium's 6.5m Walter Baade telescope at Las Campanas Observatory. Two of the unresolved components (designated A and B) are confirmed to be quasars with z=1.524; the velocity difference is less than 100 km sec^{-1} according to spectra taken with the W. M. Keck Observatory's Keck II telescope on Mauna Kea. A third stellar component, designated C, has the colors of a quasar with redshift similar to components A and B. The maximum separation of the point sources is 1.78". The other two sources, designated G and D, are resolved. Component G appears to be the best candidate for the lensing galaxy. Although component D is near the expected position of the fourth lensed component in a four image lens system, its properties are not consistent with being the image of a quasar at z~1.5. Nevertheless, the identical redshifts of components A and B and the presence of component C strongly suggest that this object is a gravitational lens. Our observations support the idea that a foreground object reddens the fourth lensed component and that another unmodeled effect (such as micro- or milli-lensing) demagnificates it, but we cannot rule out the possibility that SDSS0924+0219 is an example of the relatively rare class of ``three component'' lens systems.Comment: 24 pages, 6 figures, accepted by A

Water Walls Architecture: Massively Redundant And Highly Reliable Life Support For Long Duration Exploration Missions

The Water Wall concept proposes a system for structural elements that provide,thermal, radiation, water, solids and air treatment functions which are placed at the periphery of inflatable or rigid habitats. It also provides novel and potentially game changing mass reduction and reuse options for radiation protection. The approach would allow water recycling, air treatment, thermal control, and solids residuals treatment and recycling to be removed from the usable habitat volume, and placed in the walls by way of a radiation shielding water wall. It would also provide a mechanism to recover and reuse water treatment (solids) residuals to strengthen the habitat shell and a method of deriving radiation shielding from wastes generated on orbit. Water wall treatment elements would be a much-enlarged version of the commercially available hydration bags. Some water bags may have pervaporation membranes facing outward, which would provide the ability to remove H20, C02 and trace organics from the atmosphere and some would have hydrophobic internal membranes which would provide water, and waste recycling and some power generation

Multilfiltration Bed Replacement (MFBR) System for the International Space Station using Aquaporin Membranes and Humidity Condensate Ersatz Wastewater

The Multifiltration Bed system in the International Space Station (ISS) Water Processor Assembly (WPA) needs to be improved by reducing or eliminating the usage rate of expendable media, removing dimethylsilanediol (DMSD), and reducing the overall system mass. The WPA contains two multifiltration beds, each with a mass of approximately 50 kg. Reducing the mass of the WPA is an important part of evolving the ISS system for future exploration missions. The Multifiltration Bed Replacement (MFBR) technology is based on biomimetic membranes, which derive their unique characteristics from aquaporins, or water channel proteins. Aquaporin membranes were commercialized by the company Aquaporin AS. Tests were conducted using the Aquaporin Inside Hollow Fiber Module to determine the maximum water recovery ratio and membrane life. Samples were analyzed for total organic carbon (TOC), DMSD, acetate, ions, and volatiles such as ethanol and acetone. The results indicate that at a 97.498.1 water recovery ratio, the membrane module can reject approximately 50 of the TOC and specific conductance using the simulated ISS MSFC humidity condensate ersatz. Additionally, the life of the membrane was determined to be a minimum of 7103 hours