American Gastroenterological Association Institute Clinical Practice Update—Expert Review: Care of Patients Who Have Achieved a Sustained Virologic Response After Antiviral Therapy for Chronic Hepatitis C Infection

Chronic hepatitis C virus infection is well-recognized as a common blood-borne infection with global public health impact affecting 3 to 5 million persons in the United States and more than 170 million persons worldwide. Chronic hepatitis C virus infection is associated with significant morbidity and mortality due to complications of liver cirrhosis and hepatocellular carcinoma. Current therapies with all-oral direct-acting antiviral agents are associated with high rates of sustained virologic response (SVR), generally exceeding 90%. SVR is associated with a reduced risk of liver cirrhosis, hepatic decompensation, need for liver transplantation, and both liver-related and all-cause mortality. However, a subset of patients who achieve SVR will remain at long-term risk for progression to cirrhosis, liver failure, hepatocellular carcinoma, and liver-related mortality. Limited evidence is available to guide clinicians on which post-SVR patients should be monitored vs discharged, how to monitor and with which tests, how frequently should monitoring occur, and for how long. In this clinical practice update, available evidence and expert opinion are used to generate best practice recommendations on the care of patients with chronic hepatitis C virus who have achieved SVR

Dynamics of the Sharp Edges of Broad Planetary Rings

(Abridged) The following describes a model of a broad planetary ring whose sharp edge is confined by a satellite's m^th Lindblad resonance (LR). This model uses a streamline formalism to calculate the ring's internal forces, namely, ring gravity, pressure, viscosity, as well as a hypothetical drag force. The model calculates the streamlines' forced orbit elements and surface density throughout the perturbed ring. The model is then applied to the outer edge of Saturn's B ring, which is maintained by an m=2 inner LR with the satellite Mimas. Ring models are used to illustrate how a ring's perturbed state depends on the ring's physical properties: surface density, viscosity, dispersion velocity, and the hypothetical drag force. A comparison of models to the observed outer B ring suggests that the ring's surface density there is between 10 and 280 gm/cm^2. The ring's edge also indicates where the viscous torque counterbalances the perturbing satellite's gravitational torque on the ring. But an examination of seemingly conventional viscous B ring models shows that they all fail to balance these torques at the ring's edge. This is due ring self-gravity and the fact that a viscous ring tends to be nearly peri-aligned with the satellite, which reduces the satellite's torque on the ring and makes the ring's edge more difficult to maintain. Nonetheless, the following shows that a torque balance can still be achieved in a viscous B ring, but only in an extreme case where the ratio of the ring's bulk/shear viscosities satisfy ~10^4. However, if the dissipation of the ring's forced motions is instead dominated by a weak drag force, then the satellite can exert a much stronger torque that can counterbalance the ring's viscous torque.Comment: Accepted for publication in the Astrophysical Journal on April 3, 200

Mediating and Moderating Effects of Iron Homeostasis Alterations on Fetal Alcohol-Related Growth and Neurobehavioral Deficits

We have previously demonstrated prenatal alcohol exposure (PAE)-related alterations in maternal and infant iron homeostasis. Given that early iron deficiency and PAE both lead to growth restriction and deficits in recognition memory and processing speed, we hypothesized that PAE-related iron homeostasis alterations may mediate and/or moderate effects of PAE on growth and neurobehavior. We examined this hypothesis in a prenatally recruited, prospective longitudinal birth cohort [87 mother-infant pairs with heavy prenatal alcohol exposure (mean = 7.2 drinks/occasion on 1.4 days/week); 71 controls], with serial growth measures and infant neurobehavioral assessments. PAE was related to growth restriction at 2 weeks and 5 years, and, in infancy, poorer visual recognition memory, slower processing speed, lower complexity of symbolic play, and higher emotionality and shyness on a parental report temperament scale. Lower maternal hemoglobin-to-log(ferritin) ratio, which we have shown to be associated with PAE, appeared to exacerbate PAE-related 2-week head circumference reductions, and elevated maternal ferritin, which we have shown to be associated with PAE, appeared to exacerbate PAE-related visual recognition memory deficits. In causal inference analyses, PAE-related elevations in maternal ferritin and hemoglobin:log(ferritin) appeared to statistically mediate 22.6–82.3% of PAE-related growth restriction. These findings support potential mechanistic roles of iron homeostasis alterations in fetal alcohol spectrum disorders (FASD)

Diversity and Tropism of HIV-1 Rebound Virus Populations in Plasma Level After Treatment Discontinuation

Human immunodeficiency virus–infected people discontinuing therapy experience a rebound in the virus level (hereafter, “rebound virus”) from a persistent reservoir. We examined 10 samples from patients in AIDS Clinical Trials Group study A5068 with rebound virus, using single-genome amplification and Primer ID deep sequencing, to assess env genetic diversity of the virus population. Most rebound-virus populations showed significant diversity. All env examined required high levels of CD4 for entry, consistent with selection of replication in CD4+ T cells. These results indicate that most people discontinuing therapy release a diverse population of virus and that this released virus has entry features of virus selected for replication in CD4+ T cells, rather than in myeloid cells

High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high-risk CTV sizes

Purpose: To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated. Material and methods: Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (\u3c 20 cc), low-bulky (\u3e 20 cc and \u3c 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed. Results: Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (\u3e 40 cc) when using T&O applicator approach. Conclusions: MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator

The population of propellers in Saturn's A Ring

We present an extensive data set of ~150 localized features from Cassini images of Saturn's Ring A, a third of which are demonstrated to be persistent by their appearance in multiple images, and half of which are resolved well enough to reveal a characteristic "propeller" shape. We interpret these features as the signatures of small moonlets embedded within the ring, with diameters between 40 and 500 meters. The lack of significant brightening at high phase angle indicates that they are likely composed primarily of macroscopic particles, rather than dust. With the exception of two features found exterior to the Encke Gap, these objects are concentrated entirely within three narrow (~1000 km) bands in the mid-A Ring that happen to be free from local disturbances from strong density waves. However, other nearby regions are similarly free of major disturbances but contain no propellers. It is unclear whether these bands are due to specific events in which a parent body or bodies broke up into the current moonlets, or whether a larger initial moonlet population has been sculpted into bands by other ring processes.Comment: 31 pages, 10 figures; Accepted at A

Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential