Efficacy of Whole-Blood Model of Gadolinium-Based Contrast Agent Relaxivity in Predicting Vascular MR Signal Intensity In Vivo.

BACKGROUND: Previous in vitro studies have described sub-linear longitudinal and heightened transverse H2 O relaxivities of gadolinium-based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking. PURPOSE: Validate theory describing blood behavior of R1 and R2 * in an animal model. STUDY TYPE: Prospective, animal. ANIMAL MODEL: Seven swine (54-65 kg). FIELD STRENGTH/SEQUENCE: 1.5 T; time-resolved 3D spoiled gradient-recalled echo (SPGR) and quantitative Look-Locker and multi-echo fast field echo sequences. ASSESSMENT: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time-resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time-varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub-linear R1 and R2 * effects (whole-blood model) and simpler models incorporating linear R1 , with and without R2 * effects. Predicted SIs were compared to measured aortic SI. STATISTICAL TESTS: Linear correlation (coefficient of determination, R2 ) and mean errors were compared across the SI prediction models. RESULTS: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non-linear dependence of R1 and high blood R2 * (regression slopes 0.91-1.04, R2 ≥ 0.91). Simplified models (linear R1 with and without R2 * effects) showed poorer correlation (slopes 0.67-0.85 and 0.54-0.64 respectively, both R2 ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively). DATA CONCLUSION: Incorporating sub-linear R1 and high first-pass R2 * effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Evaluation of 3-dimensional stereotactic surface projection rendering of arterial spin labeling data in a clinical cohort.

BACKGROUND AND PURPOSE: To assess the feasibility of 3-dimensional stereotactic surface projection (3D-SSP) as applied to arterial spin labeling (ASL) in a clinical pilot study. METHODS: A retrospective sample of 10 consecutive patients who underwent ASL as part of a clinically indicated MR examination was collected during this pilot study. Five additional subjects with normal cerebral perfusion served as a control group. Following voxel-wise M0-correction, cerebral blood flow (CBF) quantification, and stereotactic anatomic standardization, voxel-wise CBF from an individual's ASL dataset was extracted to a set of predefined surface pixels (3D-SSP). A normal database was created from averaging the extracted CBF datasets of the control group. Patients' datasets were compared individually with the normal database by calculating a Z-score on a pixel-by-pixel basis and were displayed in 3D-SSP views for visual inspection. Independent, two-expert reader assessment, using a 3-point scale, compared standard quantitative CBF images to the 3D-SSP maps. RESULTS: Patterns and severities of regionally reduced CBF were identified, by both independent readers, in the 3D-SSP maps. Reader assessment demonstrated preference for 3D-SSP over traditionally displayed standard quantitative CBF images in three of four evaluated imaging metrics (p = .026, .031, and .013, respectively); 3D-SSP maps were never found to be inferior to the standard quantitative CBF images. CONCLUSIONS: Three-dimensional SSP maps are feasible in a clinical population and enable quantitative data extraction and localization of perfusion abnormalities by means of stereotactic coordinates in a condensed display. The proposed method is a promising approach for interpreting cerebrovascular pathophysiology.

Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial.

BACKGROUND: HIV subtypes B and C together account for around 60% of HIV-1 cases worldwide. We evaluated the safety and immunogenicity of a subtype B DNA vaccine prime followed by a subtype C viral vector boost. METHODS: Fourteen healthy adults received DNA plasmid encoding HIV-1 subtype B nef/tat/vif and env (n = 11) or placebo (n = 3) intramuscularly (IM) via electroporation (EP) at 0, 1, and 3 months, followed by IM injection of recombinant vesicular stomatitis virus encoding subtype C Env or placebo at 6 and 9 months. Participants were assessed for safety, tolerability of EP, and Env-specific T-cell and antibody responses. RESULTS: EP was generally well tolerated, although some device-related adverse events did occur, and vaccine reactogenicity was mild to moderate. The vaccine stimulated Env-specific CD4 + T-cell responses in greater than 80% of recipients, and CD8 + T-cell responses in 30%. Subtype C Env-specific IgG binding antibodies (bAb) were elicited in all vaccine recipients, and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to vaccine-matched subtype C targets in 80%. Negligible V1/V2 and neutralizing antibody (nAb) responses were detected. CONCLUSIONS: This prime/boost regimen was safe and tolerable, with some device-related events, and immunogenic. Although immunogenicity missed targets for an HIV vaccine, the DNA/rVSV platform may be useful for other applications. CLINICALTRIALS: gov: NCT02654080.

Metabolic activity diffusion imaging (MADI): I. Metabolic, cytometric modeling and simulations.

Evidence mounts that the steady-state cellular water efflux (unidirectional) first-order rate constant (kio [s-1 ]) magnitude reflects the ongoing, cellular metabolic rate of the cytolemmal Na+ , K+ -ATPase (NKA), c MRNKA (pmol [ATP consumed by NKA]/s/cell), perhaps biology's most vital enzyme. Optimal 1 H2 O MR kio determinations require paramagnetic contrast agents (CAs) in model systems. However, results suggest that the homeostatic metabolic kio biomarker magnitude in vivo is often too large to be reached with allowable or possible CA living tissue distributions. Thus, we seek a noninvasive (CA-free) method to determine kio in vivo. Because membrane water permeability has long been considered important in tissue water diffusion, we turn to the well-known diffusion-weighted MRI (DWI) modality. To analyze the diffusion tensor magnitude, we use a parsimoniously primitive model featuring Monte Carlo simulations of water diffusion in virtual ensembles comprising water-filled and -immersed randomly sized/shaped contracted Voronoi cells. We find this requires two additional, cytometric properties: the mean cell volume (V [pL]) and the cell number density (ρ [cells/µL]), important biomarkers in their own right. We call this approach metabolic activity diffusion imaging (MADI). We simulate water molecule displacements and transverse MR signal decays covering the entirety of b-space from pure water (ρ = V = 0; kio undefined; diffusion coefficient, D0 ) to zero diffusion. The MADI model confirms that, in compartmented spaces with semipermeable boundaries, diffusion cannot be described as Gaussian: the nanoscopic D (Dn ) is diffusion time-dependent, a manifestation of the "diffusion dispersion". When the "well-mixed" (steady-state) condition is reached, diffusion becomes limited, mainly by the probabilities of (1) encountering (ρ, V), and (2) permeating (kio ) cytoplasmic membranes, and less so by Dn magnitudes. Importantly, for spaces with large area/volume (A/V; claustrophobia) ratios, this can happen in less than a millisecond. The model matches literature experimental data well, with implications for DWI interpretations.

Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.

We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.

Range and Consistency of Cardiovascular Outcomes Reported by Clinical Trials in Kidney Transplant Recipients: A Systematic Review.

Cardiovascular disease is a major cause of morbidity and mortality in kidney transplant recipients. Trial evidence to improve cardiovascular outcomes is limited by inconsistent reporting of outcomes, which may also lack patient-relevance. This study aimed to assess the range and consistency of cardiovascular outcomes reported by contemporary trials in kidney transplant recipients. Methods: A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of the cardiovascular outcome measures reported were analyzed (the measure definition, metric' and method of aggregation). Measures assessing a similar aspect of cardiovascular disease were categorized into outcomes. Results: From 93 eligible trials involving 27 609 participants, 490 outcome measures were identified. The outcome measures were grouped into 38 outcomes. A cardiovascular composite was the most common outcome reported (40 trials, 43%) followed by cardiovascular mortality (42%) and acute coronary syndrome (31%). Cardiovascular composite was also the most heterogeneous outcome with 77 measures reported followed by cardiovascular mortality (n = 58) and inflammatory biomarkers (n = 51). The most common cardiovascular composite outcome components reported were major cardiovascular events (18 trials), stroke unspecified (11 trials), and myocardial infarction unspecified (10 trials). Conclusions: There is substantial heterogeneity in cardiovascular outcome reporting in kidney transplant trials.

Serious and Fatal Complications after Neonatal Circumcision.

Neonatal circumcision (NNC) is the most frequently performed surgical procedure worldwide and is generally considered safe in Western societies. Deaths attributed to NNC are seldom reported and are mostly explained by lack of adherence to medical standards. We reviewed our emergency department database for circumcision-related emergency admissions. During 2000-2013, 19 previously healthy neonates were admitted for acute complications after circumcision. Four were admitted for bleeding, with hemophilia identified in two cases and von Willebrand disease in one. Eight boys required emergency surgery, three for severe bleeding. Four boys with amputation of the glans underwent immediate surgical reconstruction. One infant was taken to the operating room to remove an obstructing Plastibell ring. Seven boys were admitted to the intensive care unit with severe bleeding or sepsis, three of whom ultimately progressed to hemorrhagic or septic shock. Two of these children died of their complications. We estimate that the annual incidence of severe complications requiring hospitalization after NNC in the Greater Toronto Area was approximately 0.01%, and the incidence of fatalities over the 14-yr review period was approximately 0.0012%. Our results indicate that the risk of serious complications and death as a result of NNC is greater than generally assumed.

Relationship Between Simulated Gadolinium-Based Contrast Agent Injection Profile and Achievable Resolution Metrics in Contrast-Enhanced Magnetic Resonance Angiography.

BACKGROUND: Contrast bolus variation during contrast-enhanced magnetic resonance angiography (CE-MRA) acquisition may lead to vessel blurring. PURPOSE: To combine knowledge of how contrast signal intensity (SI) evolves for different injection strategies with anatomically familiar parametric computer models to measure and visually assess the effects of a wide range of variables on modeled CE-MRA, and in doing so develop contrast rate injection guidelines. STUDY TYPE: Computer modeling. PHANTOM: Digital three-dimensional phantom consisting of orthogonal "aorta," 7 mm diameter "renal arteries" (with 57% and 86% diameter stenoses), and 7 mm diameter "superior mesenteric artery" (with 57% diameter stenosis). FIELD STRENGTH/SEQUENCE: One millimeter in-plane resolution arterial CE-MRA imaging at 3 T. ASSESSMENT: "Background" (time invariant) and "vascular" (time varying) components of the phantom were each Fourier transformed into the spatial frequency domain, the latter modulated by the SI evolution of a contrast bolus of varying "plateau" lengths and "tail" heights. Data are presented as surface plots of stenosis measurement error and blurring vs. a reference-standard injection. STATISTICAL TESTS: Descriptive. RESULTS: Shorter plateau lengths and lower tail heights resulted in increased measured stenosis error and blurring vs. the reference standard. Under a 44-second acquisition, full width half maximum stenosis error of the 86% stenosis with 25% plateau length and 25% tail height is 24% as compared to that from the reference standard. As plateau length and tail height approach 100%, stenosis error and blurring approach a floor defined by the MR acquisition's limitations. DATA CONCLUSION: We propose that to achieve minimal degradation with CE-MRA, one can create a contrast bolus with either 60% plateau and 50% tail height or 80% plateau with any tail. These considerations may well prove to be of practical importance, possibly via manipulating the tail by means of multiphasic contrast injections. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network.

Intracellular protein homeostasis is maintained by a network of chaperones that function to fold proteins into their native conformation. The eukaryotic TRiC chaperonin (TCP1-ring complex, also called CCT for cytosolic chaperonin containing TCP1) facilitates folding of a subset of proteins with folding constraints such as complex topologies. To better understand the mechanism of TRiC folding, we investigated the biogenesis of an obligate TRiC substrate, the reovirus σ3 capsid protein. We discovered that the σ3 protein interacts with a network of chaperones, including TRiC and prefoldin. Using a combination of cryoelectron microscopy, cross-linking mass spectrometry, and biochemical approaches, we establish functions for TRiC and prefoldin in folding σ3 and promoting its assembly into higher-order oligomers. These studies illuminate the molecular dynamics of σ3 folding and establish a biological function for TRiC in virus assembly. In addition, our findings provide structural and functional insight into the mechanism by which TRiC and prefoldin participate in the assembly of protein complexes.

Tunable transition metal complexes as hole transport materials for stable perovskite solar cells.

Transition metal complexes offer cost-effective alternatives as hole-transport materials (HTMs) in perovskite solar cells. However, the devices suffer from low performance. We boost the power conversion efficiency of devices with transition metal complex HTMs from 2% to above 10% through energy level tuning. We further demonstrate the excellent photostability of the device based on the additive-free HTM.

Optimizing Disclosure of HIV Status to a Diverse Population of HIV-Positive Youth at an Urban Pediatric HIV Clinic.

PURPOSE: The purpose of the study was to increase the proportion of youth living with HIV (YLWH) aged ≥11 years who undergo developmentally appropriate disclosure about their HIV status. METHODS: A quality improvement project was initiated at an urban pediatric HIV clinic between July 2018 and March 2020. The primary outcome measure was the proportion of YLWH aged ≥11 years who were disclosed to about their HIV status. The proportion of undisclosed YLWH who had documented nondisclosure status was also assessed as a process measure. Plan-Do-Study-Act (PDSA) cycles for change included monthly clinic staff check-ins to discuss new disclosures, quarterly team meetings to discuss strategies to improve disclosure, and modifying a clinic note template to prompt providers to document disclosure status. Annotated run charts were used to analyze the data. RESULTS: Before the first PDSA cycle, 26/46 (57%) of the target population of YLWH aged ≥11 years had their HIV status disclosed to them, and none of the undisclosed youth had disclosure status documented in their medical record. After 20 months and six PDSA cycles, the proportion of YLWH aged ≥11 years disclosed to about their HIV status increased to 80% and the proportion of undisclosed YLWH with documentation of their disclosure status increased to 100%. CONCLUSIONS: Several interventions integrated throughout the pediatric HIV care process were associated with an increase in the proportion of YLWH with developmentally appropriate HIV disclosure and documentation of disclosure status, an important psychosocial aspect of care in these individuals.

Dimensionality-Controlled Surface Passivation for Enhancing Performance and Stability of Perovskite Solar Cells via Triethylenetetramine Vapor.

Perovskite solar cells (PSCs) have achieved unprecedented progress in terms of enhancement of power conversion efficiency (PCE). Nevertheless, device stability is still an obstacle to the commercialization of this emerging photovoltaic technology. Though strategies such as compositional management and ligand engineering have been reported to tackle this critical issue, these methods often have drawbacks such as compromised device performance. Herein, we propose an approach combining material dimensionality control and interfacial passivation by a post-device treatment via triethylenetetramine (TETA) vapor to enhance both efficiency and stability of Cs0.05FA0.79MA0.16PbI2.5Br0.5-based PSCs. Results of X-ray diffraction and scanning electron microscopy show the formation of low-dimensional perovskites at the interface between the perovskite film and the hole transporting layer after the TETA vapor treatment. Measurements of the energy level alignment and electrochemical properties by ultraviolet photoelectron spectroscopy and impedance spectra confirm the reduced density of trap states and improved interfacial charge transport. Consequently, TETA-based treatment significantly enhances both efficiency (from 17.07 to 18.03%) and stability (PCE retention from 73.4 to 88.9%) of the PSCs under >65% relative humidity for 1000 h compared to the controlled device without TETA treatment. Furthermore, the TETA vapor also shows an advantageous effect of dramatically improving the performance of PSC devices, which initially had poor performance (from 6.8 to 10.5%) through surface defect passivation.

Passivation by pyridine-induced PbI2 in methylammonium lead iodide perovskites.

Defects at discontinuities of the perovskite lattice limit the performance of the perovskite solar cell (PSC). Lead iodide (PbI2) and pyridine have been shown to passivate these defects. We treat methylammonium lead iodide (MAPbI3) films with pyridine solutions to investigate the effects of the two passivators. By comparing confocal fluorescence microscopy (CFM) images at 405 nm excitation and then at 559 nm excitation we demonstrate the pyridine treatment passivates and forms PbI2 crystallites which cause additional passivation.

Strategically Constructed Bilayer Tin (IV) Oxide as Electron Transport Layer Boosts Performance and Reduces Hysteresis in Perovskite Solar Cells.

Nanostructured tin (IV) oxide (SnO2 ) is emerging as an ideal inorganic electron transport layer in n-i-p perovskite devices, due to superior electronic and low-temperature processing properties. However, significant differences in current-voltage performance and hysteresis phenomena arise as a result of the chosen fabrication technique. This indicates enormous scope to optimize the electron transport layer (ETL), however, to date the understanding of the origin of these phenomena is lacking. Reported here is a first comparison of two common SnO2 ETLs with contrasting performance and hysteresis phenomena, with an experimental strategy to combine the beneficial properties in a bilayer ETL architecture. In doing so, this is demonstrated to eliminate room-temperature hysteresis while simultaneously attaining impressive power conversion efficiency (PCE) greater than 20%. This approach highlights a new way to design custom ETLs using functional thin-film coatings of nanomaterials with optimized characteristics for stable, efficient, perovskite solar cells.

Methodologies in Spectral Tuning of DSSC Chromophores through Rational Design and Chemical-Structure Engineering.

The investigation of new photosensitizers for Grätzel-type organic dye-sensitized solar cells (DSSCs) remains a topic of interest for researchers of alternative solar cell materials. Over the past 20 years, considerable and increasing research efforts have been devoted to the design and synthesis of new materials, based on "donor, π-conjugated bridge, acceptor" (D-π-A) organic dye photosensitizers. In this paper, the computational chemistry methods are outlined and the design of organic sensitizers (compounds, dyes) is discussed. With reference to recent literature reports, rational molecular design is demonstrated as an effective process to study structure-property relationships. Examples from established organic dye sensitizer structures, such as TA-St-CA, Carbz-PAHTDDT (S9), and metalloporphyrin (PZn-EDOT), are used as reference structures for an examination of this concept applied to generate systematically modified structural derivatives and hence new photosensitizers (i.e., dyes). Using computer-aided rational design (CARD), the in silico design of new chromophores targeted an improvement in spectral properties via the tuning of electronic structures by substitution of molecular fragments, as evaluated by the calculation of absorption profiles. This mini review provides important rational design strategies for engineering new organic light-absorbing compounds towards improved spectral absorption and related optoelectronic properties of chromophores for photovoltaic applications, including the dye-sensitized solar cell (DSSC).

Long-term outcomes of patients with end-stage kidney disease due to membranoproliferative glomerulonephritis: an ANZDATA registry study.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied. METHODS: All adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression. RESULTS: Of 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p < 0.01). The risk of disease recurrence was significantly higher in patients with MPGN compared to patients with other glomerulonephritidites (18% vs. 5%; p < 0.01). In patients with MPGN who had allograft loss, patients with MPGN recurrence had a significantly shorter time to allograft loss compared to patients with MPGN who had allograft loss due to any other cause (median time to allograft loss 3.2 years vs. 4.4 years, p < 0.01). CONCLUSIONS: Compared with other forms of glomerulonephritis, patients with MPGN experienced comparable rates of survival on dialysis and following kidney transplantation, but significantly higher rates of allograft loss due to disease recurrence.

DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial.

BACKGROUNDRV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or combinations with AIDSVAX B/E (protein).METHODSOne hundred and four HIV-uninfected participants were randomized to 4 treatment groups (T1, T2, T3, and T4) and received intramuscular injections at 0, 1, 3, and 6 months (M): T1 received protein at M0 and M1 and DNA at M3 and M6; T2 received DNA at M0 and M1 and protein at M3 and M6; T3 received DNA at M0, M1, M3, and M6 with protein coadministered at M3 and M6; and T4 received protein and DNA coadministered at each vaccination visit.RESULTSAll regimens were well tolerated. Antibodies binding to gp120 and V1V2 scaffold were observed in 95%-100% of participants in T3 and T4, two weeks after final vaccination at high magnitude. While IgG3 responses were highest in T3, a lower IgA/IgG ratio was observed in T4. Binding antibodies persisted at 12 months in 35%-100% of participants. Antibody-dependent cell-mediated cytotoxicity and tier 1 neutralizing-antibody responses had higher response rates for T3 and T4, respectively. CD4+ T cell responses were detectable in all treatment groups (32%-64%) without appreciable CD8+ T cell responses.CONCLUSIONThe DNA/protein combination regimens induced high-magnitude and long-lasting HIV V1V2-binding antibody responses, and early coadministration of the 2 vaccines led to a more rapid induction of these potentially protective responses.TRIAL REGISTRATIONClinicalTrials.gov NCT02207920.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069511, UM1 AI069470, UM1 AI069534, P30 AI450008, UM1 AI069439, UM1 AI069481, and UM1 AI069496; the National Center for Advancing Translational Sciences, NIH (grant UL1TR001873); and the Bill & Melinda Gates Foundation (grant OPP52845).

Evaluation of four injection profiles for uniform contrast-enhanced signal intensity profiles in MR angiography.

BACKGROUND: Gadolinium concentration variation during acquisition of contrast-enhanced MR angiography (CE-MRA) may lead to artifacts. PURPOSE: To compare signal intensity (SI) profiles of four different contrast agent injection strategies during CE-MRA with the goal of minimizing SI variation during acquisition. STUDY TYPE: Prospective. SUBJECTS: Forty subjects randomized to receive one of four injection profiles of gadobenate dimeglumine (0.1 mmol/kg), either undiluted (0.5 M) or diluted to 40 ml total volume. Tested profiles: 1) nondiluted single-phase ("standard" NS; 1.6 ml/s), 2) diluted single-phase (DS; 1.6 ml/s), 3) diluted biphasic (DB; 9 ml @ 3.3 ml/s, 29 ml @ 1.4 ml/s), 4) patient-tailored protocol using linear prediction (DT). FIELD STRENGTH/SEQUENCE: Time-resolved SI measured at 3T with spoiled gradient echo sequences having analogous parameters to those of CE-MRA. ASSESSMENT: Plateau arrival time, rise time, duration, peak and tail SI, plateau quality (sum of squared residuals; SSR), average SI for each injection type derived were used. STATISTICAL TEST: Two-tailed t-test. RESULTS: Peak SI, arrival, and rise times were not significantly different between groups, excepting peak SI DB slightly > DS (P = 0.042). Duration of NS vs. the diluted groups was significantly shorter (all P < 0.0001), and DS duration was significantly shorter than that of DT and DB (NS 11.4 ± 3.5 vs. DS 22.9 ± 4.3, DB 25.4 ± 2.3, DT 28.3 ± 4.1 sec). Quality (SSR) of the 20-second plateau was significantly better for DS, DB, DT as compared with NS (all P < 0.001). DATA CONCLUSION: Three different strategies to power-inject diluted gadobenate dimeglumine targeting a 20-second plateau produced SI profiles with longer duration, more consistent plateau, and no significant loss in peak SI. Such injection profiles may provide more uniform SI during CE-MRA, potentially reducing blurring artifacts. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1808-1816.

2D-3D Mixed Organic-Inorganic Perovskite Layers for Solar Cells with Enhanced Efficiency and Stability Induced by n-Propylammonium Iodide Additives.

Device instability has become an obstacle for the industrial application of organic-inorganic metal halide perovskite solar cells that has already demonstrated over 23% laboratory power conversion efficiency (PCE). It has been discovered that the sliding of A-site cations in the perovskite compound through and out of the three-dimensional [PbI6]4- crystal frame is one of the main reasons that are responsible for decomposition of the perovskite compound. Herein, we report an effective method to enhance the stability of the FA0.79MA0.16Cs0.05PbI2.5Br0.5 perovskite film through the incorporation of n-propylammonium iodide (PAI). Both density functional theory calculation and the X-ray diffraction patterns have confirmed the formation of two-dimensional (PA)2PbI4 with the Ruddlesden-Popper perovskite as a result of the reaction between PAI and PbI2 in the perovskite film. X-ray photoelectron spectroscopy reveals less -COOH (carboxyl) groups on the surface of the perovskite film containing (PA)2PbI4, which indicates the suppressed penetration of oxygen and moisture into the perovskite material. This is further confirmed by the surface water wettability test of the (PA)2PbI4 film that exhibits excellent hydrophobic property with over 110° contact angle. Ultraviolet photoelectron spectroscopy demonstrates the introduction of PAI additives that resulted in the upshift of the conduction band minimum of the perovskite by 160 meV, leading to a more favorable energy alignment with an adjacent electron transporting material. As a consequence, enhanced 17.23% PCE with suppressed hysteresis was obtained with the 5% PAI additive (molar ratio) in perovskite solar cells that retained nearly 50% of the initial efficiency after 2000 h in air without encapsulation under 45% average relative humidity.