Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.

Comparison of in-laboratory and home diagnosis of sleep apnea using a cordless portable acoustic device.

Background And Objectives: Sleep apnea (SA) is a common, serious, but underdiagnosed condition. There is a need for more accessible and economic means of diagnosing SA in the home. The aim of this study was to test the validity of a cordless acoustic portable device (BresoDx™) for home diagnosis of SA compared with standard polysomnography (PSG).

Association Between Plasma Uric Acid Levels and Cardiorenal Function in Adolescents With Type 1 Diabetes.

Objective: The relationship between plasma uric acid (PUA) and renal and cardiovascular parameters in adolescents with type 1 diabetes (T1D) is not well understood. Our aims in this exploratory analysis were to study the association between PUA and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), blood pressure, endothelial function, and arterial stiffness in T1D adolescents. These associations were also studied in healthy control (HC) subjects.

Early changes in cardiovascular structure and function in adolescents with type 1 diabetes.

Background: Children with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters.

Methods And Results: 199 T1D [14.

Left Ventricular Myocardial and Hemodynamic Response to Exercise in Young Patients after Endovascular Stenting for Aortic Coarctation.

Background: Endovascular stenting has emerged as a treatment option for children with coarctation of the aortic (CoA), but the impact on left ventricular (LV) function has been poorly documented. The aim of this study was to characterize the LV myocardial and hemodynamic response to exercise in young patients who underwent endovascular stenting for CoA during childhood using semisupine bicycle exercise stress echocardiography.

Methods: This was a single-center prospective cross-sectional study including 30 patients with CoA and 30 age- and gender-matched control subjects who underwent semisupine bicycle exercise stress echocardiography.

Estimation of sleep status in sleep apnea patients using a novel head actigraphy technique.

Polysomnography is a comprehensive modality for diagnosing sleep apnea (SA), but it is expensive and not widely available. Several technologies have been developed for portable diagnosis of SA in the home, most of which lack the ability to detect sleep status. Wrist actigraphy (accelerometry) has been adopted to cover this limitation.

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not.

A Practical Guide to Clinical Management of Thoracic Aortic Disease.

Physicians and surgeons faced with patients with thoracic aortic disease (TAD) need to determine the underlying diagnosis to facilitate decisions regarding appropriate investigations as well as which other specialists to involve, when to start medical therapy, when to refer for surgery, and how to plan follow-up and family screening. Increased understanding of conditions predisposing to thoracic aortic aneurysm (TAA) provides the opportunity for more personalized care. However, given advances in the genetics of TAD, clinicians are now faced with an expanded and often confusing list of associated differential diagnoses.

Association between resting-state brain functional connectivity and muscle sympathetic burst incidence.

The insula (IC) and cingulate are key components of the central autonomic network and central nodes of the salience network (SN), a set of spatially distinct but temporally correlated brain regions identified with resting-state (task free) functional MRI (rsMRI). To examine the SN's involvement in sympathetic outflow, we tested the hypothesis that individual differences in intrinsic connectivity of the SN correlate positively with resting postganglionic muscle sympathetic nerve activity (MSNA) burst incidence (BI) in subjects without and with obstructive sleep apnea (OSA). Overnight polysomnography, 5-min rsMRI, and fibular MSNA recording were performed in 36 subjects (mean age 57 yr; 10 women, 26 men).

Factors affecting Fontan length of stay: Results from the Single Ventricle Reconstruction trial.

Background: In the Single Ventricle Reconstruction trial, infants with hypoplastic left heart syndrome (HLHS) who received a right-ventricle-to-pulmonary-artery shunt (RVPAS) versus a modified Blalock-Taussig shunt (MBTS) had lower early postoperative mortality, but more complications at 14 months. We explored the effect of shunt type and other patient, medical, and surgical factors on postoperative length of stay (LOS) after the Fontan operation.

Methods: Fontan postoperative course was ascertained from medical record review.

Optical side scattering radiometry for high resolution, wide dynamic range longitudinal assessment of optical fibers.

Current optical reflectometric techniques used to characterize optical fibers have to trade-off longitudinal range with spatial resolution and therefore struggle to provide simultaneously wide dynamic range (>20dB) and high resolution (<10cm). In this work, we develop and present a technique we refer to as Optical Side Scattering Radiometry (OSSR) capable of resolving discrete and distributed scattering properties of fibers along their length with up to 60dB dynamic range and 5cm spatial resolution. Our setup is first validated on a standard single mode telecoms fiber.

Outcomes of Aortic Valve-Sparing Operations in Marfan Syndrome.

Background: In many cardiac units, aortic valve-sparing operations have become the preferred surgical procedure to treat aortic root aneurysm in patients with Marfan syndrome, based on relatively short-term outcomes.

Objectives: This study examined the long-term outcomes of aortic valve-sparing operations in patients with Marfan syndrome.

Methods: All patients with Marfan syndrome operated on for aortic root aneurysm from 1988 through 2012 were followed prospectively for a median of 10 years.

Impact of Disease Duration on Vascular Surrogates of Early Atherosclerosis in Childhood-Onset Systemic Lupus Erythematosus.

Objective: To determine whether longer disease duration negatively impacts carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and pulse wave velocity (PWV) in a cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare CIMT, FMD, and PWV in patients with childhood-onset SLE with those in healthy children and explore determinants of vascular test results in childhood-onset SLE.

Methods: Cross-sectional analysis was performed in a prospective longitudinal cohort of patients with childhood-onset SLE at the latest followup visit. Clinical and laboratory data were collected for patients with childhood-onset SLE.

Hypervolemia and Sleep Apnea in Kidney Disease.

In end-stage renal disease (ESRD) and heart failure, conditions characterized by fluid overload, both obstructive sleep apnea (OSA) and central sleep apnea (CSA) are highly prevalent. This observation suggests that fluid overload may be a unifying mechanism in the pathogenesis of both OSA and CSA in these conditions. An overnight rostral fluid shift from the legs to the neck and lungs has been shown to contribute to the pathogenesis of OSA and CSA, respectively, in various different patient populations.

Dense WDM transmission at 2 μm enabled by an arrayed waveguide grating.

We show, for the first time, dense WDM (8×20  Gbit/s) transmission at 2 μm enabled by advanced modulation formats (4-ASK Fast-OFDM) and the development of key components, including a new arrayed waveguide grating (AWGr) at 2 μm. The AWGr shows -12.8±1.

Internal Applicants to Pediatric Emergency Medicine Fellowships and Current Use of the National Resident Matching Program Match: A Survey of Fellowship Directors.

Objectives: Applicants to fellowship programs are divided into the following 2 distinct groups: the external versus internal candidate. Internal fellowship candidates did residency at the same institution they are applying to, whereas the external candidate is from another institution. Internal candidates have likely done rotation(s) within the fellowship's division and are known to faculty, whereas the external candidates are evaluated by their applications and interviews alone.

Heart Failure and Sleep Apnea.

Obstructive and central sleep apnea are far more common in heart failure patients than in the general population and their presence might contribute to the progression of heart failure by exposing the heart to intermittent hypoxia, increased preload and afterload, sympathetic nervous system activation, and vascular endothelial dysfunction. There is now substantial evidence that supports a role for fluid overload and nocturnal rostral fluid shift from the legs as unifying mechanisms in the pathogenesis of obstructive and central sleep apnea in heart failure patients, such that the predominant type of sleep apnea is related to the relative distribution of fluid from the leg to the neck and chest. Despite advances in therapies for heart failure, mortality rates remain high.