Rebound Time Research Articles

Theta Oscillations Gate the Transmission of Reliable Sequences in the Medial Entorhinal Cortex.

Stability and precision of sequential activity in the entorhinal cortex (EC) is crucial for encoding spatially guided behavior and memory. These sequences are driven by constantly evolving sensory inputs and persist despite a noisy background. In a realistic computational model of a medial EC (MEC) microcircuit, we show that intrinsic neuronal properties and network mechanisms interact with theta oscillations to generate reliable outputs. In our model, sensory inputs activate interneurons near their most excitable phase during each theta cycle. As the inputs change, different interneurons are recruited and postsynaptic stellate cells are released from inhibition. This causes a sequence of rebound spikes. The rebound time scale of stellate cells, because of an h–current, matches that of theta oscillations. This fortuitous similarity of time scales ensures that stellate spikes get relegated to the least excitable phase of theta and the network encodes the external drive but ignores recurrent excitation. In contrast, in the absence of theta, rebound spikes compete with external inputs and disrupt the sequence that follows. Further, the same mechanism where theta modulates the gain of incoming inputs, can be used to select between competing inputs to create transient functionally connected networks. Our results concur with experimental data that show, subduing theta oscillations disrupts the spatial periodicity of grid cell receptive fields. In the bat MEC where grid cell receptive fields persist even in the absence of continuous theta oscillations, we argue that other low frequency fluctuations play the role of theta.

Directionally Guided Droplets on a Modular Bottom-Up Anisotropic Locally Ordered Nickel Nanocone Superhydrophobic Surface.

The anisotropic surface prepared by the top-down etching technology shows unique advantages in terms of functional superhydrophobicity. However, it still has a shackle of the smallest etching size, which largely restricts the development of better superhydrophobicity. Therefore, it is still a huge challenge to realize the stepless size adjustment of an anisotropic surface in order to achieve better functionalization. In this work, a bottom-up approach inspired via the modular segmented preparation technology has been used to successfully build an anisotropic, locally ordered functionalized unique superhydrophobic structure, whose contact and rebound time of water droplets is extremely short. Furthermore, this structure with artfully arranged "tracks", which has a relatively large contact angle value, not only lasts more than 15 consecutive bounce cycles in the same direction, where the droplets after merging still bounce, but also exhibits a significant anisotropic sliding behavior, which is presented in different sliding angles, toward droplets rolling in different directions and has lower adhesion work and better self-cleaning and anti-fouling performance. Besides, some mechanisms such as the reduction-replacement-reduction cycle and repulsion-adhesion-switching have been proposed especially in modular preparation and anisotropic sliding behavior. More importantly, this sorted bottom-up structure has great potential for achieving higher efficiency of functionalized superhydrophobicity and other related applications.

Adiposity rebound and cardiometabolic health in childhood: results from the Generation XXI birth cohort.

We aimed to evaluate the association of adiposity rebound (AR) timing on cardiometabolic health in childhood. Participants were part of the Generation XXI birth cohort, enrolled in 2005/2006 in Porto. All measurements of the child's weight and height performed by health professionals as part of routine healthcare were collected. Individual body mass index (BMI) curves were fitted for 3372 children, using mixed-effects models with smooth spline functions for age and random effects. The AR was categorized into very early (<42 months), early (42-59 months), normal (60-83 months) and late (≥84 months). At age 10 years, cardiometabolic traits were assessed and age- and sex-specific z-scores were generated. Adjusted regression coefficients and 95% confidence intervals [β (95% CI)] were computed. The mean age at AR was 61.9 months (standard deviations 15.7). Compared with children with normal AR, children with very early or early AR had higher z-scores for BMI [β = 0.40 (95% CI: 0.28; 0.53); β = 0.21 (95% CI: 0.12; 0.30)], waist circumference [β = 0.33 (95% CI: 0.23; 0.43); β = 0.18 (95% CI: 0.10; 0.25)], waist-height ratio [β = 0.34 (95% CI: 0.24; 0.44); β = 0.14 (95% CI: 0.07; 0.22)], fat mass index [β = 0.24 (95% CI: 0.15; 0.33); β = 0.14 (95% CI: 0.08; 0.21)], fat-free mass index [β = 0.25 (95% CI: 0.14; 0.35); β = 0.11 (95% CI: 0.03; 0.19)], systolic blood pressure [β = 0.10 (95% CI: 0.01; 0.20); β = 0.08 (95% CI: 0.01; 0.15)], insulin [β = 0.16 (95% CI: 0.04; 0.29); β = 0.10 (95% CI: 0.01; 0.19)], HOMA-IR [β = 0.17 (95% CI: 0.04; 0.29); β = 0.10 (95% CI: 0.03; 0.19)] and C-reactive protein [β = 0.14 (95% CI: 0.02; 0.26); β = 0.10 (95% CI: 0.01; 0.19)]. Children with very early AR also had worse levels of diastolic blood pressure [β = 0.09 (95% CI: 0.02; 0.16)], triglycerides [β = 0.21 (95% CI: 0.08; 0.34)] and high-density lipoprotein cholesterol [β=-0.18 (95% CI: -0.31; -0.04)]. When analysed continuously, each additional month of age at the AR was associated with healthier cardiometabolic traits. The earlier the AR, the worse the cardiometabolic health in late childhood, which was consistently shown across a wide range of outcomes and in the categorical and continuous approach.

Water droplet bouncing on a non-superhydrophobic Si nanospring array.

Self-cleaning surfaces often make use of superhydrophobic coatings that repel water. Here, we report a hydrophobic Si nanospring surface that effectively suppresses wetting by repelling water droplets. The dynamic response of Si nanospring arrays fabricated by glancing-angle deposition is investigated. These hydrophobic arrays of vertically standing nanosprings (about 250 nm high and 60 nm apart) allow the droplets to rebound within a few milliseconds after contact. Amazingly, the morphology of the nanostructures influences the impact dynamics. The rebound time and coefficient of restitution are higher for Si nanosprings than for vertical Si columns. By considering the droplet/nanospring surface as a coupled-spring system, we argue that the restoring force of the nanosprings may be responsible for the water-droplet rebound. The bouncing phenomena studied here are essential in the design of self-cleaning surfaces and are also of fundamental importance for the study of wetting behavior on nanostructures.

Superhydrophobicity and Rapid Rebounding Induced via a Unique Nonfluorinated Aluminum-Based Multiscale Multilayer Nickel "Trampoline" Structure.

The development of a unique multilayer detached superhydrophobic structure inspired by biology with excellent superhydrophobic properties, extremely short rebound time, and low surface free energy has become a challenging issue. In this work, a superhydrophobic coating is prepared on the surface of Al 1060 via a fluorine-free, efficient, economical, and environment-friendly approach. First, a Ni nanocone layer is obtained from a recyclable electrodeposition solution. Then, stearic acid is prepared on the Ni nanocone layer by dip-coating technology, resulting in a special superhydrophobic surface called the "trampoline" structure, which is quite different from the Ni nanocone structure, as the substrate. The contact angle of water is 161.3°, and the sliding angle is 7°. In addition, the superhydrophobic coating with this special structure has had great achievement in adhesion work, resilience performance, porosity, corrosion resistance, and self-cleaning and antifouling performance. So far, very few reports have analyzed the performance of this special structure. To explain the bounce performance induced by this special trampoline structure, a multidimensional superhydrophobic bouncing mechanism was proposed. Furthermore, this work is expected to provide inspiration for future applications of the unique nonfluorinated trampoline structure in superhydrophobic materials.

HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.

Body mass index trajectories and adiposity rebound during the first 6 years in Korean children: Based on the National Health Information Database, 2008-2015.

We analyzed the nationwide longitudinal data to explore body mass index (BMI) growth trajectories and the time of adiposity rebound (AR). Personal data of 84,005 subjects born between 2008 and 2012 were obtained from infant health check-ups which were performed at 5, 11, 21, 33, 45, 57, and 69 months. BMI trajectories of each subject were made according to sex and the timing of AR, which was defined as the lowest BMI occurred. Subjects were divided according to birth weight and AR timing as follows: very low birth weight (VLBW), 0.5 kg ≤ Bwt ≤ 1.5 kg; low birth weight (LBW), 1.5 kg < Bwt ≤ 2.5 kg; non-LBW, 2.5 kg < Bwt ≤ 5.0 kg; very early AR, before 45 months; early AR, at 57 months; and moderate-to-late AR, not until 69 months. Median time point of minimum BMI was 45 months, and the prevalence rates of very early, early, and moderate-to-late AR were 63.0%, 16.6%, and 20.4%, respectively. BMI at the age of 57 months showed a strong correlation with AR timing after controlling for birth weight (P < 0.001). Sugar-sweetened beverage intake at 21 months (P = 0.02) and no-exercise habit at 57 months (P < 0.001) showed correlations with early AR. When VLBW and LBW subjects were analyzed, BMI at 57 months and breastfeeding at 11 months were correlated with rapid weight gain during the first 5 months (both P < 0.001). Based on this first longitudinal study, the majority of children showed AR before 57 months and the degree of obesity at the age of 57 months had a close correlation with early AR or rapid weight gain during infancy.

Numerical analysis of permeability rebound and recovery during coalbed methane extraction: Implications for CO2 injection methods

The coal’s permeability plays a crucial role in coalbed methane (CBM) extraction and coal seam CO2 sequestration. An accurate understanding of permeability rebound and recovery is therefore essential. This study establishes an improved fully coupled gas migration model for CBM extraction. The permeability rebound and recovery times as well as rebound values are proposed to accurately quantify permeability evolution during CBM extraction. The evolution of these three parameters under the influence of different factors are evaluated in detail, such as initial gas pressure, the diffusion coefficient, and the permeability. The results show that the permeability rebound and recovery times increase along with initial gas pressure and the amount over time rises rapidly under high gas pressures. As the initial gas pressure increases, the permeability rebound value decreases. However, initial diffusion coefficient and permeability have a negative trend in permeability rebound, recovery time, and rebound value. These tendencies are particularly large for low initial permeabilities and diffusion coefficients, yet the change in rebound time is smaller than the one in recovery time. Finally, inspired by the relationship between permeability rebound and gas pressure change during CBM extraction, the evolution of coal seam permeability under different CO2 injection method is discussed. A stepwise increasing-pressure CO2 injection method is also proposed, which could effectively increase the volume of CO2 sequestered and reduce project costs. Therefore, our findings shall shed light on improving coal mine safety production and reducing greenhouse gas emission.

Theoretical and numerical studies on the collapse of single‐ and double‐bubble system in water

AbstractThe cavitation bubbles that collapse in the hydraulic machinery can cause damage to the structure and the internal wall. In order to find feasible preventive measures, the mechanism of cavitation bubble collapse needs to be thoroughly studied. However, the influence of the initial radius or the interaction between multi‐bubbles has not been studied in depth. In this paper, the collapse process of single‐ and double‐bubble system is studied by the volume of fluid (VOF) method. Three conditions are considered in this paper, single‐bubble (R0 = 0.3 mm, R0 = 0.4 mm) and double‐bubble system (R0,1 = 0.3 mm and R0,2 = 0.4 mm). The time evolution of pressure, bubble radius, radial velocity, and acceleration during the bubble collapse can be obtained. The bubble collapse time, pressure distribution, and radial velocity of single bubble are verified by theoretical values. It is found that with the increase of bubble initial radius, the collapse, and rebound time is delayed, the maximum pressure of the bubble center increases, the minimum radius of the bubble decreases, the maximum radial velocity increases. In double‐bubble system, during the first rebound of the small bubble, the central pressure, radius and radial velocity of the small bubble fluctuate with time. And the collapse time of each bubble is delayed, the maximum central pressure decreases and the minimum radius of the bubble increases.

The Influence Of Hamstring Muscle-tendon Stiffness On Isolated And Dynamic Velocity Based Parameters

Previous research has demonstrated sex differences in active hamstring muscle-tendon stiffness as well as associations between stiffness and landing biomechanics and architectural tissue properties. Little is known whether active stiffness relates to other measures of muscle function (i.e., maximum voluntary isometric contraction [MVIC], isotonic dynamometry) and performance (i.e., sprinting). PURPOSE: To conduct a pilot study examining the relationship between active hamstring muscle-tendon stiffness and isometric torque production, isotonic velocity development, and sprint velocity. A secondary research interest was to examine the relationship between the isotonic velocity parameters and sprint performance. METHODS: Nine recreationally active and healthy subjects (7 males, 2 females) (24 ± 3 years) completed an MVIC for the hamstrings (30° knee flexion) followed by three 40m sprint trials using an infrared timing gate system (Brower, Draper, UT). At least 48 hours later, subjects completed a measure of hamstring muscle-tendon stiffness (damped oscillatory technique) and an isotonic knee flexion test on a fixed dynamometer (Biodex, Shirley, NY). The isotonic test began at 90° of knee flexion and was eccentric/concentric through a 90° arc of motion with subjects lying prone. Eccentric velocity was set at 180°/s and concentric torque was set at 25% of MVIC. Bivariate correlations were conducted between stiffness, MVIC (normalized to body mass), sprint times, time to peak velocity, rate of velocity development (RVD, 0-100ms), and rebound time (-50°/s to +50°/s). RESULTS: Stiffness (24.3 ± 11.7 Nm/kg) was only significantly related (r= .681, P= .043) to MVIC (1.48 ± 0.23 Nm/kg). Stiffness was not significantly related to rebound time (0.076 ± 0.026s) (r= -.354, P= .350), time to peak velocity (0.214 ± 0.034s) (r= -.285, P= .457), RVD0-100 (1314.64 ± 222.30°/s2) (r= -.336, P= .377), or sprint velocities (5.90 ± 0.56 m/s) (r= .248, P= .521). Rebound time (r= -.535, P= .138) and RVD0-100 (r= -.436, P= .241) were not significantly related to sprint times. CONCLUSIONS: Although only the association between stiffness and normalized MVIC reached statistical significance, the magnitude of the other observed relationships provides impetus for further study with a larger sample size.

Dynamic decay of viral reservoirs in systemic and lymphoid compartments of SIV-infected rhesus macaques on long-term combined antiretroviral therapy

Abstract Material &amp; Method By quantitative real-time/digital PCR, we here longitudinally examined dynamic decay of viral parameters (cell-associated unspliced and multiply spliced viral RNA, episomal 2-LTR circular viral DNA and integrated proviral DNA) in systemic and lymphoid tissues in SIV-infected rhesus macaques on long-term combined antiretroviral therapy (cART, up to 20 months), and evaluated reservoir size and timing of viral rebound after treatment interruption. SIV RNA or DNA copy numbers were normalized and expressed as per 106 cell equivalents. Frequencies and absolute numbers of peripheral CD4+ T cells were analyzed before and after suppressive antiretroviral therapy. Results Our results showed that suppressive ART significantly reduced levels of cell-associated unspliced and multiply spliced SIV RNA/2-LTR DNA to undetectable, yet levels of integrated proviral DNA alone were stably maintained in systemic and lymphoid compartments throughout cART, which correlated with levels of viral replication prior to initiating cART. Following ATI, rapid clonal expansion of cells with integrated provirus were detected, as indicated by undetectable spliced tat/rev RNA and 2-LTR but increased levels of total proviral DNA, which may have contributed to subsequent viral rebound. Cell-associated SIV RNA and DNA levels completely recovered to pre-treatment levels in blood, spleen, lymph node, tonsil and gut-associated lymphoid tissues by 3 months after ATI. Conclusions These findings suggest that discriminating integrated HIV proviral DNA from non-integrated or defective proviruses in tissues are useful biomarkers for monitoring HIV persistence and latency for treatment and cure strategies.

Rebound of HBV DNA after cessation of nucleos/tide analogues in chronic hepatitis B patients with undetectable covalently closed.

Background & AimsNucleos(t)ide analogues (NUCs) effectively suppress serum HBV DNA. Previously, we have identified 21 patients with undetectable covalently closed circular DNA (cccDNA) upon long-term NUC therapy. This study investigated the effect of NUC withdrawal in patients with undetectable cccDNA.MethodsNineteen patients on long term NUCs (median 13.4 years) were recruited: 13 were randomized to discontinue NUCs; 6 to continue taking NUCs. All had undetectable cccDNA at the time of last liver biopsy (median time 2.9 years prior to randomization). Serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), liver biochemistry, and serum HBV RNA were monitored.ResultsAt the time of randomization, all patients had undetectable serum HBV DNA and HBV RNA. Twelve of the 13 patients had HBV DNA rebound to 100 IU/ml within 20 weeks of NUC discontinuation. The thirteenth patient had HBV DNA rebound at week 70. Three patients experienced biochemical flares after re-treatment which subsequently resolved. There was no significant association between the time of HBV DNA rebound and baseline HBsAg, HBcrAg and alanine aminotransferase, duration of treatment, and age at which treatment was stopped (all p >0.05). At the time of HBV DNA rebound, HBV DNA levels correlated with HBcrAg levels (p = 0.003), but not with HBsAg levels (p = 0.262).ConclusionsIn patients with undetectable intrahepatic cccDNA, virologic rebound still occurred after NUC cessation. At the rebound of HBV DNA, the kinetics of HBsAg production were independent of those of viral DNA replication. Additional studies are required to determine the factors that may predict virologic rebound and when NUCs can be discontinued in HBsAg-positive patients with chronic hepatitis B.Lay summaryIt has been shown that following long-term nucleos(t)ide analogue treatment for chronic hepatitis B, some patients have undetectable levels of viral DNA in their livers. We tested the results of withdrawing nucleos(t)ide analogue treatment in these patients and found that viral relapse could occur in patients with undetectable viral DNA. Further research is required to determine whether nucleos(t)ide analogue treatment can be discontinued in specific patients with chronic hepatitis B.

Comparison of Ultrabio HIV DNA PCR and Gag Real-Time PCR Assays for Total Hiv-1 DNA Quantification

Total HIV-1 DNA has been shown to reflect reservoir size in HIV-1 infected individuals and correlate with viral rebound time after therapy interruption. Quantification of total HIV-1 DNA level may be used to study and evaluate reservoir elimination therapies. There is currently no FDA approved HIV- 1 DNA quantification assay available. The performance of a research uses only kit, Ultrabio HIV DNA quantification kit, was compared to a commonly used laboratory qPCR method targeting the gag region (GAG PCR). The limit of detection (LOD) and precision was evaluated with serially diluted 8E5/LAV DNA. LOD of Ultrabio Kit and GAG PCR was determined to be 4 and 25 copies/reaction, respectively. The Ultrabio Kit showed less variation when HIV-1 DNA concentration was lower than 20 copies/reaction. Twentysix HIV-1 infected patients’ PBMCs samples were quantified by both methods and the Ultrabio kit showed higher sensitivity. GAG PCR was unable to detect 2 of the samples while Ultrabio Kit was able to detect all. Both 2 samples had undetectable viral load. The quantified HIV DNA copies/million cells of the 24 detected samples by both methods showed good correlation, r=0.91. The difference was within one log.

HIV-1: towards understanding the nature and quantifying the latent reservoir.

The human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) pandemic constitutes one of the greatest public health issues, since 36.9 million people worldwide were living with HIV in 2017 and 940,000 died from AIDS- related illnesses in the same year. One of the main obstacles in the effort to achieve viral eradication or long-term virologic remission is the existence of the HIV-reservoir. Except for resting memory CD4+ T cells there is a plethora of innate immunity cells including macrophages, dendritic cells, follicular T helper cells and NK cells which are now considered to play a role in viral latency and persistence. Hematopoietic precursor cells and progenitor mast cells, astrocytes, fibrocytes, renal and liver epithelial cells could also contribute to the reservoir, but their role remains controversial. Tissue reservoirs, such as the central nervous system (CNS), lymphoid tissue, adipose tissue and the gut-associated-lymphoid-tissue (GALT) are usually referred to as anatomic sanctuaries, where it is difficult to achieve high concentration and efficacy of antiretroviral agents. Accurate quantification of this reservoir is of the utmost importance and multiple assays have been developed for this purpose. The role of several cell populations in viral latency needs to be clarified by further studies. Furthermore, there is an urgent need for new assays, which will accurately measure the size of the reservoir, which plays a key role in predicting the timing of viral rebound upon cessation of antiretroviral treatment, since the currently available ones either overestimate or underestimate the size and have significant limitations. Keywords: HIV-1; cellular reservoirs; tissue reservoirs; quantification.

Drop impact on hot plates: contact times, lift-off and the lamella rupture.

When a liquid drop impacts on a heated substrate, it can remain deposited, or violently boil in contact, or lift off with or without ever touching the surface. The latter is known as the Leidenfrost effect. The duration and area of the liquid-substrate contact are highly relevant for the heat transfer, as well as other effects such as corrosion. However, most experimental studies rely on side view imaging to determine contact times, and those are often mixed with the time until the drop lifts off from the substrate. Here, we develop and validate a reliable method of contact time determination using high-speed X-ray imaging and total internal reflection imaging. We exemplarily compare contact and lift-off times on flat silicon and sapphire substrates. We show that drops can rebound even without formation of a complete vapor layer, with a wide range of lift-off times. On sapphire, we find a local minimum of lift-off times that is much shorter than expected from capillary rebound in the comparatively low-temperature regime of transition boiling/thermal atomization. We elucidate the underlying mechanism related to spontaneous rupture of the lamella and receding of the contact area.

Dynamic behaviours of water droplets impacting on laser ablated surfaces

In order to reveal the underlying mechanism of surface microstructure-determined wetting states, this paper adopted Volume of Fluid (VOF) method to investigate the dynamic behaviours of water droplets impacting on surfaces with different structures at low and high Weber numbers. The simulation results showed that the high and stable pressure of air pockets is critical for the formation of the superhydrophobicity. A superhydrophobic substrate will result in shorter recoiling time and longer rebound time for water droplet than the hydrophobic substrate. Furthermore, superhydrophobic surface resulted in higher kinetic energy for water droplet than hydrophobic surfaces, which is the underlying mechanism of microstructure-enabled self-cleaning function. High-speed camera tests of laser processed surface microstructures were conducted to validate the observation in dynamic impacting simulation. The results in both high-speed camera testing and VOF simulation proved that water droplet will have a lower adhesion force when impacting superhydrophobic surface than hydrophobic surface.

Predictions of time to HIV viral rebound following ART suspension that incorporate personal biomarkers.

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Suspension of therapy is followed by rebound of viral loads to high, pre-therapy levels. However, there is significant heterogeneity in speed of rebound, with some rebounds occurring within days, weeks, or sometimes years. We present a stochastic mathematical model to gain insight into these post-treatment dynamics, specifically characterizing the dynamics of short term viral rebounds (≤ 60 days). Li et al. (2016) report that the size of the expressed HIV reservoir, i.e., cell-associated HIV RNA levels, and drug regimen correlate with the time between ART suspension and viral rebound to detectable levels. We incorporate this information and viral rebound times to parametrize our model. We then investigate insights offered by our model into the underlying dynamics of the latent reservoir. In particular, we refine previous estimates of viral recrudescence after ART interruption by accounting for heterogeneity in infection rebound dynamics, and determine a recrudescence rate of once every 2-4 days. Our parametrized model can be used to aid in design of clinical trials to study viral dynamics following analytic treatment interruption. We show how to derive informative personalized testing frequencies from our model and offer a proof-of-concept example. Our results represent first steps towards a model that can make predictions on a person living with HIV (PLWH)’s rebound time distribution based on biomarkers, and help identify PLWH with long viral rebound delays.

Modeling HIV Dynamics Under Combination Therapy with Inducers and Antibodies.

A mathematical model is proposed to simulate the "shock-kill" strategy where broadly neutralizing antibodies (bNAbs) are injected with a combination of HIV latency activators to reduce persistent HIV reservoirs. The basic reproductive ratio of virus is computed to extrapolate how the combinational therapy of inducers and antibodies affects the persistence of HIV infection. Numerical simulations demonstrate that a proper combination of inducers and bNAbs can drive the basic reproductive ratio below unity. Interestingly, it is found that a longer dosage interval leads to the higher HIV survival opportunity and a smaller dosage interval is preferred, which is fundamental to design an optimal therapeutic scheme. Further simulations reveal the conditions under which the joint therapy of inducer and antibodies induces a large extension of viral rebound time, which highlights the mechanism of delayed viral rebound from the experiment (Halper-Stromberg et al. in Cell 158:989-999, 2014). Optimal time for cessation of treatment is also analyzed to aid practical applications.

Predictors of Symptom Rebound in Critically Ill Patients With Croup

There are no data to inform the ideal length of in-hospital observation after symptom improvement or to inform the ideal dexamethasone dose in critically ill children with croup. We describe a cohort of critically ill children with croup who rebound (have return of symptom(s) after meeting hospital discharge criteria) and examine the association between the cumulative dexamethasone dose before PICU discharge and both the odds and timing of rebound. In this single-center retrospective cohort study of subjects 6 months to 13 years of age admitted to the PICU with a primary diagnosis of croup, we employed multivariable logistic regression to evaluate the association between cumulative pre-PICU discharge dexamethasone dose and rebound. In the model, we controlled for subject age and sex, insurance, season, and history of prematurity, croup, or intubation. Kaplan-Meier curves were used to compare time to rebound between subjects receiving ≤2 standard (0.6 mg/kg) doses and those receiving >2 standard doses of dexamethasone before PICU discharge. Data were analyzed over 69 months (January 2011-October 2016), and 275 unique subjects met inclusion criteria. The median cumulative dose of dexamethasone in the hospital was 1.57 mg/kg (interquartile range 0.98-2.63). Thirty-seven percent (n = 102) of subjects developed rebound croup symptoms after meeting hospital discharge criteria. The median time to rebound was 13.1 hours (interquartile range 6.1-23.7). There was no association between cumulative pre-PICU discharge dexamethasone dose and the odds (odds ratio = 1.00; 95% confidence interval 0.83-1.19; P = .96) or timing of rebound. A clinically significant number of critically ill patients with croup rebounded. Total pre-PICU discharge dexamethasone dose did not predict either the odds or timing of rebound.

Analytical treatment interruption in chronic HIV-1 infection: time and magnitude of viral rebound in adults with 10 years of undetectable viral load and low HIV-DNA (APACHE study).

Despite the fact that there are individuals who have chronic HIV infection, few studies have investigated ART interruption in this setting. The aim of this study was to evaluate the ability to spontaneously control viral replication during analytical treatment interruption (ATI) in adults with chronic HIV-1 infection, on ART, with suppressed viraemia for >10 years and with a low reservoir. This was a prospective, open-label, single-arm, non-randomized, proof-of-concept study (NCT03198325) of subjects with chronic HIV-1 infection, HIV-RNA <50 copies/mL for ≥10 years, without residual viraemia for ≥5 years, CD4+ >500 cells/mm3, HIV-DNA <100 copies/106 PBMCs and without comorbidities or AIDS-defining diseases. Enrolled patients were strictly monitored. The ART regimen in use at ATI was resumed in the case of confirmed viral rebound (CVR, two consecutive HIV-RNA >50 copies/mL). Results are reported as median (IQR). Nine patients underwent ATI. All participants experienced CVR [4.84 (IQR: 3.47-6.47) HIV-RNA log10 copies/mL] after ATI at a median time of 21 days (range 14-56) and restarted ART. After ART resumption, all the subjects achieved HIV-RNA <50 copies/mL in a median of 88 days (range 15-197). No serious adverse event occurred; one subject experienced acute retroviral syndrome. No significant correlation between baseline factors and time to viral rebound was observed, while the magnitude of viral rebound was significantly associated with pre-ART HIV-1 RNA (Spearman r = 0.786, P = 0.036), nadir CD4+ (Spearman r = -0.800, P = 0.010), baseline CD4+ (Spearman r = -0.667, P = 0.049) and years with undetectable viral load (Spearman r = -0.717, P = 0.030). Despite a long period of HIV viral load suppression and a low viral reservoir, early and consistent viral rebound was observed during ATI in all subjects.