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Summary: Background and Aims: Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss. Methods: We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues. Conclusion: Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one‐third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission. [ABSTRACT FROM AUTHOR]

The rise of life expectancy of the human population is accompanied by the drastic increases of age‐associated diseases, in particular Alzheimer's disease (AD), and underscores the need to understand how aging influences AD development. The Forkhead box O transcription factor 3 (FoxO3) is known to mediate aging and longevity downstream of insulin/insulin‐like growth factor signaling across species. However, its function in the adult brain under physiological and pathological conditions is less understood. Here, we report a region and cell‐type‐specific regulation of FoxO3 in the central nervous system (CNS). We found that FoxO3 protein levels were reduced in the cortex, but not hippocampus, of aged mice. FoxO3 was responsive to insulin/AKT signaling in astrocytes, but not neurons. Using CNS Foxo3‐deficient mice, we reveal that loss of FoxO3 led to cortical astrogliosis and altered lipid metabolism. This is associated with impaired metabolic homoeostasis and β‐amyloid (Aβ) uptake in primary astrocyte cultures. These phenotypes can be reversed by expressing a constitutively active FOXO3 but not a FOXO3 mutant lacking the transactivation domain. Loss of FoxO3 in 5xFAD mice led to exacerbated Aβ pathology and synapse loss and altered local response of astrocytes and microglia in the vicinity of Aβ plaques. Astrocyte‐specific overexpression of FOXO3 displayed opposite effects, suggesting that FoxO3 functions cell autonomously to mediate astrocyte activity and also interacts with microglia to address Aβ pathology. Our studies support a protective role of astroglial FoxO3 against brain aging and AD. [ABSTRACT FROM AUTHOR]

I present an open source code Esh3D that evaluates the quasi‐static elastic displacement and stress fields perturbed by ellipsoidal inclusions, known as the Eshelby solution. The improvement over my previous work includes obtaining solutions in half‐space by numerically canceling the traction to stage a free surface. The discrete numerical domain allows nonplanar surface. I first briefly introduce the ellipsoidal inclusion problem and solution evaluation. Then, I describe the traction cancellation method in forming the half‐space solutions. Next, I emulate a planar fault with a low aspect ratio ellipsoid and compare the half‐space solution against the well‐known Okada solution for flat and topographic surfaces. Finally, I provide comparisons between the full space and half‐space solutions to illustrate the free surface effects on the displacement and stress fields. Plain Language Summary: In a number of geophysical applications, our code presented in Meng et al. (2012, https://doi.org/10.1016/j.cageo.2011.07.008) is adopted. Among those, people sometimes use the code to fit surface deformation/strain data. However, the original code is for full space without considering the free surface. Now I extend the code to cover both the full space and half surface cases. In the last figure, I show that the free surface effect cannot be neglected even at depth of 4 km. Key Points: Esh3D evaluates Eshelby solution for ellipsoidal inclusions in full or half‐spaceHalf space Eshelby solution is obtained seminumerically by traction cancellationThe half‐space solution allows nonplanar surface [ABSTRACT FROM AUTHOR]

Mitochondria play crucial roles in regulating metabolism and longevity. A body of recent evidences reveals that the gut microbiome can also exert significant effects on these activities in the host. Here, by summarizing the currently known mechanisms underlying these regulations, and by comparing mitochondrial fission–fusion dynamics with bacterial interactions such as quorum sensing, we hypothesize that the microbiome impacts the host by communicating with their intracellular relatives, mitochondria. We highlight recent discoveries supporting this model, and these new findings reveal that metabolite molecules derived from bacteria can fine‐tune mitochondrial dynamics in intestinal cells and hence influence host metabolic fitness and longevity. This perspective mode of chemical communication between bacteria and mitochondria may help us understand complex and dynamic environment–microbiome–host interactions regarding their vital impacts on health and diseases. Gut microbiome orchestrates biological processes in the host by communicating with mitochondria, intracellular organelles that originated from bacteria. Reciprocating to environmental challenges, bacteria produce metabolites that can modulate mitochondrial dynamics to adjust intracellular activities. Together, the interplay between microbiome and mitochondria provides new insights into the regulation of host metabolic health and longevity. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancers result in substantial morbidity and mortality to the Australian society each year. The usual investigation for bowel malignancy is optical colonoscopy (OC), with computed tomography colonography (CTC) used as an alternative investigation. The catharsis and colon insufflation associated with these investigations pose a higher risk in the elderly and frail. Risks include perforation, serum electrolyte disturbance and anaesthesia/sedation risks. Minimal preparation computed tomography colonography (MPCTC) eliminates these risks. Aims: To audit the accuracy of a MPCTC programme for the investigation of colonic masses in symptomatic elderly and frail patients. Methods: This paper audits a 6‐year period of MPCTC in an Australian tertiary referral hospital. A total of 145 patients underwent MPCTC during the study period. Results: There were seven true positives, two false positives and two false negatives. Analysis of this population indicates a sensitivity of 0.78 (95% CI 0.51–1.05), specificity of 0.99 (95% CI 0.97–1.01), positive predictive value (PPV) of 0.78 (95% CI 0.51–1.05) and negative predictive value (NPV) of 0.99 (95% CI 0.97–1.01). These findings are concordant with other published studies. Conclusions: This audit confirms that minimal preparation CT colonography is a reasonable alternative to OC and CTC in detecting colorectal cancer in symptomatic elderly and frail patients, without the procedural risks inherent in more invasive investigations. For most patients, MPCTC ruled out significant colorectal carcinoma with a high NPV. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α-synuclein, modifies the association between head injury and Parkinson's disease (PD) risk.Methods: Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case-Control Historical Interviews (SEARCH), 2 independent case-control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury.Results: Consistent with prior reports, relative to medium-length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5-0.9), and long Rep1 with increased risk (pooled OR, 1.4; 95% CI, 0.95-2.2). Overall, head injury was not significantly associated with PD (pooled OR, 1.3; 95% CI, 0.9-1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR, 5.4; 95% CI, 1.5-19; SEARCH OR, 2.3; 95% CI, 0.6-9.2; pooled OR, 3.5; 95% CI 1.4-9.2, p-interaction = 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor (p = 0.03).Interpretation: While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential. [ABSTRACT FROM AUTHOR]

Background and Aim: Fibrotic progression in non-alcoholic fatty liver disease (NAFLD) is associated with impaired hepatic function. The 13C-caffeine breath test (CBT) is a non-invasive, quantitative test of liver function. We sought to determine the utility of the CBT in detecting hepatic fibrosis in NAFLD. Methods: The CBT was applied to 48 patients with NAFLD. CBT results were compared to clinical, biochemical and histological data. Twenty-four healthy subjects served as controls. Results: Patients with simple steatosis had similar CBT values (2.28 ± 0.71 Δ‰ per 100 mg caffeine) to controls (2.31 ± 0.85, P = 1.0). However, CBT was significantly reduced in patients with non-alcoholic steatohepatitis (1.59 ± 0.65, P = 0.005) and cirrhosis (1.00 ± 0.73, P < 0.001). CBT significantly correlated with Brunt's fibrosis score ( r = −0.49, P < 0.001) but not with steatosis ( P = 0.23) or inflammation ( P = 0.08). CBT also correlated with international normalized ratio ( r = −0.61, P < 0.001), albumin ( r = 0.37, P = 0.009), aspartate aminotransferase/alanine aminotransferase ( r = −0.34, P = 0.018) and platelets ( r = 0.31, P = 0.03). On multivariate analysis, age (odds ratio 1.12, 95% confidence interval 1.042-1.203, P = 0.002) and CBT (OR 0.264, 95% CI 0.084-0.822, P = 0.02) were independent predictors of significant fibrosis ( F ≥ 2). CBT yielded an area under the receiver operating characteristic curve of 0.86 for the diagnosis of cirrhosis. Conclusions: The CBT reflects the extent of hepatic fibrosis in NAFLD and represents a non-invasive predictor of fibrosis severity in this condition. [ABSTRACT FROM AUTHOR]

A variational data assimilation algorithm for assimilating land surface temperature (LST) in the Common Land Model (COLM) is implemented using the land surface energy balance as the adjoint physical constraint. In this data assimilation algorithm, the evaporative fraction of soil and canopy is adjusted according to the surface temperature observations. The analysis results from COLM with the LST assimilation algorithm compare well with the field observations from AmeriFlux data at four sites with different land surface conditions. These results indicate that the surface temperature assimilation method is efficient and effective when only one observation for each day is available (e.g., an observation at 1400 local solar time). A sensitivity analysis for the COLM estimation of evapotranspiration (ET) is also carried out, and the impact of the surface temperature data assimilation on the ET estimates is assessed. It is found that except for time periods with a heavy rainfall event, the ET estimates with the surface temperature assimilation once per day during 0800-1600 local solar time compare better with the AmeriFlux ET measurements than do those without the LST data assimilation. This study implies that the data assimilation algorithm for assimilating regional-scale remote sensing LST data into COLM is promising. [ABSTRACT FROM AUTHOR]

Background and Aim: The outcomes of lamivudine-resistant chronic hepatitis B patients treated with long-term adefovir dipivoxil have not been well described. This study aims to characterize the virological and biochemical response and to determine factors that may influence the development of resistance to adefovir. Methods: A retrospective review was conducted on all patients with lamivudine-resistant chronic hepatitis B treated with adefovir for a minimum of 6 months at two tertiary referral centers. Results: Data on 161 patients were analyzed. Seventy-two percent achieved an initial virological response with eventual normalization of alanine aminotransferase in only 67% of patients. Seventeen patients developed adefovir resistance with cumulative resistance rates of 3.2%, 8.8%, and 18% at 12, 24, and 36 months, respectively. Twelve (71%) of these patients had a biochemical breakthrough, with one death from fulminant hepatic failure. The median duration of lamivudine crossover was 1 month in adefovir-resistant patients, compared with 12 months for the remainder of the cohort ( P < 0.01). Longer crossover therapy reduced the adefovir resistance rate, but did not eliminate it. No adefovir resistance is reported in those who were continued on long-term combination lamivudine–adefovir without a period of adefovir monotherapy. Conclusions: Combination lamivudine–adefovir therapy protected against the emergence of adefovir resistance. [ABSTRACT FROM AUTHOR]

The fully integrated GaInP/GaAs heterojunction bipolar transistor, transformer-based top-series quadrature voltage controlled oscillator (QVCO) is demonstrated at 4 GHz. The transformers on the semi-insulating GaAs substrate possess good electrical properties at high frequencies. The QVCO at 4.1 GHz has phase noise of -120 dBc/Hz at 1 MHz offset frequency, output power of 2 dBm and the figure of merit -178 dBc/Hz. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 49: 215–218, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.22067 [ABSTRACT FROM AUTHOR]

In this article, we propose a mapping method in which the system function of filter in z-domain is founded by discrete-time domain techniques as well as by chain-scatte ring matrices of various transmission-lines is derived to fulfill a dualbandpass microwave filter based on equal-length nonuniform coupled lines. A dualband filter with the desired bandwidth and low insertion loss is recognized by cascading bandpass and bandstop filters. The five-order Butterworth bandstop filter, which uses a coupled-serial-shunted lines structure, causes the implantation and correct placement of the bandstop filter. The wide-band bandpass filter is implemented by the five-order Chebyshev Type II band-pass filter, which uses serial lines and shunted stubs lines configuration. The design process is finished by using optimization algorithms to tune the values of characteristic impedances of each transmission-line section. Experimental results significantly agree with the theoretical values. Measurement shows that the 3 dB passband widths are about 20% for the frequency of 2.45 GHz and 10% for the frequency of 5.25 GHz. The insertion loss is about 0.831 dB at the frequency of 2.38 GHz and 1.873 dB at the frequency of 5.216 GHz. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 49: 210–215, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.22075 [ABSTRACT FROM AUTHOR]

Two major techniques for gain improvement of the CMOS low noise amplifier (LNA) and mixer are presented. First, the inductive interstage matching is applied to design a cascode amplifier for increasing the power transfer between the common source (CS) and common gate (CG) stages. Second, a super source follower (SSF) is utilized in a P-type micromixer for increasing the conversion gain of the mixer. A series of investigations are performed for demonstrating the feasibilities of the proposed techniques. The LNA and mixer designs based on the proposed techniques are realized using 0.35 ìm 1P4M CMOS technology. Then their measured results are compared with those of a preliminary design, which fully integrates a conventional cascode amplifier and a P-type micromixer. The gain of the LNA is increased 2.1 dB and the noise figure is maintained at the same value of the preliminary design. On the other hand, the conversion gain of the super source follower (SSF) of the micromixer output is improved about 9.5 dB. Such improvements reveal great potential of the proposed design techniques on the gain enhancement for the LNA and mixer. Then, the measured results of the preliminary design show the return-loss of 25 dB, the isolation of better than 30 dB, and the conversion gain of 4.8 dB in the 2.4 GHz ISM band. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 48: 2067–2070, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21838 [ABSTRACT FROM AUTHOR]

A compact physics-based transit-time model is established for the GaInP/GaAs HBT device. The VBIC model fails to describe the transit-time frequency versus bias (IC, VCE), especially at low- and medium-current regimes. Starting with the HICUM model, we introduce a new time constant to describe the transit-time frequency versus bias (IC, VCE) more precisely. This model has obvious advantages over the VBIC model for showing the relation of ft versus bias (IC, VCE) in the low and medium current regimes for GaInP/GaAs HBT devices. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 48: 780–783, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21474 [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of combined radiation and targeted, intra-arterial (IA) cisplatin infusions (RADPLAT) in patients with advanced squamous cell carcinoma (SCC) of the tonsil. Study design and setting: Prospective study of treatment outcomes and toxicity of patients enrolled on the RADPLAT protocol, with specific analysis of patients with advanced SCC of the tonsil. Results: Thirty patients with advanced tonsil carcinoma (17 T4, 12 T3, 1 T2) were enrolled, and 24 of 30 patients completed at least 3 IA cisplatin infusions and a minimum of 63 Gy or radiation therapy (minimum therapy). Two-year estimated overall and disease-specific survival was 42% and 50%, respectively, for all 30 patients (intent-to-treat group) and 49% and 58%, respectively, for the minimum therapy subgroup. The 2-year estimated local and regional disease control was 87% and 90%, respectively, for the intent-to-treat group, and 100% and 90% for the minimum therapy subgroup. Functional organ preservation was achieved in 92% of patients. Conclusions: Locoregional disease control achieved with this regimen appears to be significantly improved over that described in the literature for similarly staged tonsil cancer. Survival, on the other hand, remains comparable. EBM rating: C [Copyright &y& Elsevier]

A SiGe micromixer for 2.4/5.2/5.7-GHz multiband WLAN applications is demonstrated for the first time. Our experimental results show that the input return loss |S11| is below -18 dB from DC to 20 GHz with voltage gains of 32, 26, and 25 dB at frequencies of 2.4, 5.2, and 5.7 GHz, respectively. The wideband matching characteristic makes the micromixer very suitable for multiband applications. Input P1dB = -14 dBm and IIP3 = -6 dBm. Port-to-port isolation is also quite satisfactory. In addition, the single-to-differential input stage in the Gilbert micromixer eliminates the need for common-mode rejection. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 343–346, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20136 [ABSTRACT FROM AUTHOR]

A 1.2-V fully integrated 0.35-μm inductively degenerated common source CMOS low-noise amplifier has been demonstrated at 2.4 GHz in this paper. A simple common source configuration can be operated at lower voltage and has lower output impedance when compared with a conventional high output impedance cascode LNA circuit topology. The input matching inductance, output matching inductance, and source degeneration inductance are integrated on a single chip. The fully integrated 2.4-GHz CMOS LNA has 5.27-dB power gain, 17-dB input return loss, 15-dB output return loss, 4-dB noise figure, and -1-dBm IIP1dB and 8-dBm IIP3 at Vdd = 1.2 V and Idd = 10 mA, respectively. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 136–139, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10699 [ABSTRACT FROM AUTHOR]