HBsAg may reappear following reactivation in individuals with spontaneous HBsAg seroclearance 8 years previously.

HBsAg reappearance may constitute not only a risk for liver disease but also an infectious source. We aimed to determine whether HBsAg may reappear after spontaneous HBsAg seroclearance. A cohort of 2999 HBsAg-positive subjects aged 30-55 years was recruited in Guangxi, China in 2004. HBsAg was tested every 6 months from July 2004 to June 2007, then, one more time in December 2013. The results showed that spontaneous HBsAg seroclearance occurred in 41 subjects in the first 3 years, giving a 0·54% annual seroclearance rate. Thirteen of the 41 subjects were randomly tested for HBsAg in 2013. Four subjects became HBsAg positive. S gene sequences of HBV were analysed from serum collected before seroclearance and after reappearance, respectively, for subject QS840 (11 and 12 clones), subject TN98 (13 and 13 clones) and subject WX227 (10 and 8 clones). Serotype, subgenotype and amino-acid substitution pattern in each sample collected after reappearance was observed in the sample collected before HBsAg seroclearance. Nucleotide similarity between the two sequences from each subject was >99% and five sequences from subject TN98 were the same. In conclusion, following reactivation, HBsAg may reappear in individuals with spontaneous HBsAg seroclearance many years previously.

The prevalence of mutations in the major hydrophilic region of the surface antigen of hepatitis B virus varies with subgenotype.

Mutations in the major hydrophilic region (MHR) of the surface antigen of hepatitis B virus (HBV) may result in vaccine escape, failure of immunotherapy and antiviral resistance. These mutants may be transmitted and constitute a public health threat. We aimed to determine the prevalence of MHR mutations of HBV in areas of high endemicity in Guangxi, China. HBV surface gene was analysed from 278 HBsAg-positive asymptomatic individuals recruited from Guangxi using cluster sampling. Three genotypes, B, C and I, were identified. The overall prevalence of MHR mutations is 17·6%. The prevalence of MHR mutations in genotype B (15·1%) is not significantly different from that in genotype C (16·4%). However, the prevalence in subgenotype C5 (31·1%) is significantly higher than in subgenotype C2 (13·0%) (χ 2 = 6·997, P < 0·05). The prevalence of escape mutations and overlapping polymerase substitutions in subgenotype C5 is significantly higher than in subgenotypes B2 and C2. In total, 7·9% of MHR mutants are escape mutations and 72·1% of MHR mutations produced amino-acid changes in the overlapping polymerase, including resistance mutations to entecavir. Our results suggest that the prevalence of MHR mutations varies with subgenotype. The prevalence of escape mutations and polymerase mutations may be associated with subgenotype.

Evaluation of an antigen-capture EIA for the diagnosis of hepatitis E virus infection.

An enzyme immunoassay (EIA) has been developed for hepatitis E virus (HEV) antigen (HEV-Ag) detection and marketed in China. This study aimed to evaluate the sensitivity of the assay and assess the value of HEV-Ag detection in the diagnosis of HEV infection in comparison with HEV RNA detection. Using serial dilutions of a genotype 4 HEV strain, significant correlation was found between the EIA (S/CO) and HEV RNA (IU/mL) concentration in the range 10(3.5) to 10(0.5) IU/mL HEV RNA, the Pearson correlation coefficient r approached 0.97. The EIA detection limit was 54.6 IU/mL, compared to 24 IU/mL for HEV RNA using real-time RT-PCR. In clinical samples from hepatitis E patients, the HEV-Ag and HEV RNA positivity rates were 55.6% (65/117) and 60.7% (71/117) in sera and 76.7% (56/73) and 84.9% (62/73) in stools, and the concordance of these two markers was 77.8% in sera and 80.8% in stools. In serum samples, the HEV-Ag positivity rate and the concordance between HEV-Ag and HEV RNA were inversely proportional to the presence of anti-HEV antibody. The presence of anti-HEV IgG could reduce the S/CO of the HEV-Ag EIA. These results reveal a significant correlation between the detection of HEV-Ag and HEV RNA. The sensitivity of the HEV-Ag EIA was lower than real-time RT-PCR but could be higher than conventional nested RT-PCR. Therefore, the detection of HEV-Ag in serum and faeces is valuable for the diagnosis and prognosis of HEV infection in developing regions where real-time RT-PCR is not available.

Immunogenicity and protective efficacy in rhesus monkeys of a recombinant ORF2 protein from hepatitis E virus genotype 4.

Several antigens derived from hepatitis E virus (HEV) genotype 1 strains have shown immunogenicity and efficacy against hepatitis E in primates and humans. However, the protective effect of a vaccine derived from HEV genotype 4 has not been studied. This study aimed to evaluate the immunogenicity and protective efficacy of the T1-ORF2 (56 kDa) capsid protein derived from HEV strain T1 (genotype 4) in rhesus monkeys. Two doses (40 microg) of alum-absorbed T1-ORF2 capsid protein were administered 4 weeks apart. Seroconversion occurred in all immunized monkeys 1-2 weeks after the first dose. The peak levels of anti-HEV IgG appeared at 2-3 weeks after the second dose and ranged from 5.7 to 196.0 U/ml. All monkeys showed an anamnestic antibody response to the second dose. Control monkeys immunized with saline remained negative for HEV antibodies throughout the pre-challenge period. The immunized monkeys were challenged intravenously with HEV genotypes 1 and 4. Monkeys immunized with T1-ORF2 were protected from infection and hepatitis after challenge with 5 x 10(4) genome equivalents of HEV, regardless of the genotype. After challenge with 5 x 10(5) genome equivalents of HEV genotype 4, the monkeys immunized with T1-ORF2 had a shorter period of raised alanine aminotransferase levels and a shorter duration of fecal shedding compared to control monkeys immunized with saline. In conclusion, these results suggest that, in rhesus monkeys, the T1-ORF2 capsid protein of HEV genotype 4 has similar cross-protective effects to other candidate vaccines derived from HEV genotype 1.

Exclusive branching-fraction measurements of semileptonic tau decays into three charged hadrons, into phipi(-)nu tau, and into phi K(-)nu tau.

Using a data sample corresponding to an integrated luminosity of 342 fb(-1) collected with the BABAR detector at the SLAC PEP-II electron-positron storage ring operating at a center-of-mass energy near 10.58 GeV, we measure B(tau(-)--> pi(-)pi(-)pi+nu(tau)(ex.K(S0))=(8.83+/-0.01+/-0.13)%, B(tau(-) -->K(-)pi(-)pi+nu tau(ex.K(S0))=(0.273+/-0.002+/-0.009)%, B(tau(-) -->K(-)pi(-)K+nu tau)=(0.1346+/-0.0010+/-0.0036)%, and B(tau(-) -->K(-)K(-)K+nu tau)=(1.58+/-0.13+/-0.12)x10;{-5}, where the uncertainties are statistical and systematic, respectively. These include significant improvements over previous measurements and a first measurement of B(tau(-) -->K(-)K(-)K+nu tau) in which no resonance structure is assumed. We also report a first measurement of B(tau(-) -->var phi(-)nu tau)=(3.42+/-0.55+/-0.25)x10(-5), a new measurement of B(tau(-) -->var phi K(-)nu tau)=(3.39+/-0.20+/-0.28)x10(-5) and a first upper limit on B(tau(-) -->K(-)K(-)K+nu tau(ex.var phi)).

Measurement of branching fractions and mass spectra of B-->Kpipigamma.

We present a measurement of the partial branching fractions and mass spectra of the exclusive radiative penguin processes B-->Kpipigamma in the range m(Kpipi)<1.8 GeV/c(2). We reconstruct four final states: K(+)pi(-)pi(+)gamma, K(+)pi(-)pi(0)gamma, K(S)(0)pi(-)pi(+)gamma, and K(S)(0)pi(+)pi(0)gamma, where K(S)(0)-->pi(+)pi(-). Using 232 x 10(6) e(+)e(-)-->BB events recorded by the BABAR experiment at the SLAC PEP-II asymmetric-energy storage ring, we measure the branching fractions B(B(+)-->K(+)pi(-)pi(+)gamma)=[2.95+/-0.13(stat)+/-0.20(syst)] x 10(-5), B(B(0)-->K(+)pi(-)pi(0)gamma)=[4.07+/-0.22(stat)+/-0.31(syst)] x 10(-5), B(B(0)-->K(0)pi(+)pi(-)gamma)=[1.85+/-0.21(stat)+/-0.12(syst)] x 10(-5), and B(B(+)-->K(0)pi(+)pi(0)gamma)=[4.56+/-0.42(stat)+/-0.31(syst)] x 10(-5).

Evidence of a broad structure at an invariant mass of 4.32 GeV/c2 in the reaction e+e- --> pi+pi-psi(2S) measured at BABAR.

We present a measurement of the cross section of the process e(+)e(-)-->pi(+)pi(-)psi(2S) from threshold up to 8 GeV center-of-mass energy using events containing initial-state radiation, produced at the SLAC PEP-II e(+)e(-) storage rings. The study is based on 298 fb(-1) of data recorded with the BABAR detector. A structure is observed in the cross section not far above threshold, near 4.32 GeV. We also investigate the compatibility of this structure with the Y(4260) previously reported by this experiment.

Evidence for B(0) --> rho(0)rho(0) decays and implications for the Cabibbo-Kobayashi-Maskawa angle alpha.

We search for the decays B(0) --> rho(0)rho(0), B(0) --> rho(0)f(0)(980), and B(0) --> f(0)(980)f(0)(980) in a sample of about 384 x 10(6) Upsilon(4S) --> BB[over] decays collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) collider at Stanford Linear Accelerator Center. We find evidence for B(0) --> rho(0)rho(0) with 3.5 sigma significance and measure the branching fraction B = (1.07 +/- 0.33 +/- 0.19) x 10(-6) and longitudinal polarization fraction f(L) = 0.87 +/- 0.13 +/- 0.04, where the first uncertainty is statistical, and the second is systematic. The uncertainty on the Cabibbo-Kobayashi-Maskawa quark-mixing matrix unitarity angle alpha due to penguin contributions in B --> rho rho decays is 18 degrees at the 1 sigma level. We also set upper limits on the B(0) --> rho(0)f(0)(980) and B(0) --> f(0)(980)f(0)(980) decay rates.

Measurement of the pseudoscalar decay constant fDs using charm-tagged events in e+e- collisions at square root s=10.58 GeV.

Using 230.2 fb-1 of e+e- annihilation data collected with the BABAR detector at and near the peak of the Upsilon(4S) resonance, 489+/-55 events containing the pure leptonic decay Ds+-->micro;+numicro have been isolated in charm-tagged events. The ratio of partial widths Gamma(D+-->micro+numicro)/Gamma(Ds+-->phipi+) is measured to be 0.143+/-0.018+/-0.006 allowing a determination of the pseudoscalar decay constant fDs=(283+/-17+/-7+/-14) MeV. The errors are statistical, systematic, and from the Ds+-->phipi+ branching ratio, respectively.

Branching fraction measurements of B+-->rho+gamma, B0-->rho0gamma, and B0-->omegagamma.

We present a study of the decays B+-->rho+gamma, B0-->rho0gamma, and B0-->omegagamma. The analysis is based on data containing 347 x 10(6) BB[over ] events recorded with the BABAR detector at the PEP-II asymmetric B factory. We measure the branching fractions B(B+-->rho+)gamma)=(1.10_(-0.33)(+0.37)+/-0.09)x10(-6) and B(B0-->rho0gamma)=(0.79(-0.20)(+0.22)+/-0.06)x10(-6), and set a 90% C.L. upper limit B(B0-->omegagamma)<0.78 x 10(-6). We also measure the isospin-averaged branching fraction B(B-->(rho/omega)gamma)=(1.25(-0.24)(+0.25)+/-0.09)x10(-6), from which we determine |Vtd/Vts|=0.200(-0.020)(+0.021)+/-0.015, where the first uncertainty is experimental and the second is theoretical.

Measurements of CP-violating asymmetries in B0-->a1+/-(1260)pi-/+ decays.

We present measurements of CP-violating asymmetries in the decay B(0)-->a(1)(+/-)(1260)pi(-/+) with a(1)(+/-)(1260)-->pi(-/+)pi(+/-)pi(+/-). The data sample corresponds to 384x10(6) BB[over ] pairs collected with the BABAR detector at the PEP-II asymmetric B factory at SLAC. We measure the CP-violating asymmetry A(CP)(a(1)pi)=-0.07+/-0.07+/-0.02, the mixing-induced CP violation parameter S(a(1)pi)=0.37+/-0.21+/-0.07, the direct CP violation parameter C(a(1)pi)=-0.10+/-0.15+/-0.09, and the parameters DeltaC(a(1)pi)=0.26+/-0.15+/-0.07 and DeltaS(a(1)pi)=-0.14+/-0.21+/-0.06. From these measured quantities we determine the angle alpha(eff)=78.6 degrees +/-7.3 degrees.

Observation of a Charmed Baryon Decaying to D;{0}p at a Mass Near 2.94 GeV/c;{2}.

A search for charmed baryons decaying to D(0)p reveals two states: the Lambdac(2880)+ baryon and a previously unobserved state at a mass of [2939.8+/-1.3(stat)+/-1.0(syst)] MeV/c2 and with an intrinsic width of [17.5+/-5.2(stat)+/-5.9(syst)] MeV. Consistent and significant signals are observed for the K(-)pi(+) and K(-)pi(+)pi(-)pi(+) decay modes of the D0 in 287 fb(-1) annihilation data recorded by the BABAR detector at a center-of-mass energy of 10.58 GeV. There is no evidence in the D+p spectrum of doubly charged partners. The mass and intrinsic width of the Lambdac(2880)+ baryon and relative yield of the two baryons are also measured.

Observation of CP violation in B --> eta'K0 decays.

We present measurements of the time-dependent CP-violation parameters S and C in B(0) --> eta(')K(0) decays. The data sample corresponds to 384 x 10(6) BB pairs produced by e(+)e(-) annihilation at the Upsilon(4S). The results are S=0.58+/-0.10+/-0.03 and C=-0.16+/-0.07+/-0.03. We observe mixing-induced CP violation with a significance of 5.5 standard deviations in this b --> s penguin dominated mode.

Vector-tensor and vector-vector decay amplitude analysis of B0-->phiK*0.

We perform an amplitude analysis of the decays B(0)-->phiK*(2)(1430)(0), phiK*(892)(0), and phi(Kpi)(0)(S-wave) with a sample of about 384x10(6) BB[over ] pairs recorded with the BABAR detector. The fractions of longitudinal polarization f(L) of the vector-tensor and vector-vector decay modes are measured to be 0.853(-0.069+0.061)+/-0.036 and 0.506+/-0.040+/-0.015, respectively. Overall, twelve parameters are measured for the vector-vector decay and seven parameters for the vector-tensor decay, including the branching fractions and parameters sensitive to CP violation.

Observation of B-->eta'K* and evidence for B+-->eta'rho+.

We present an observation of B-->eta'K*. The data sample corresponds to 232x10(6) BB[over ] pairs collected with the BABAR detector at the PEP-II asymmetric-energy B factory at the Stanford Linear Accelerator Center. We measure the branching fractions (in units of 10(-6)) B(B(0)-->eta'K*0)=3.8+/-1.1+/-0.5 and B(B+-->eta'K*+)=4.9(1.7)(+1.9)+/-0.8, where the first error is statistical and the second systematic. A simultaneous fit results in the observation of B-->eta'K* with B(B-->eta'K*)=4.1(-0.9)(+1.0)+/-0.5. We also search for B-->eta'rho and eta'f(0)(980)(f(0)-->pi+pi-) with results and 90% confidence level upper limits B(B+-->eta'rho+)=8.7(-2.8-1.3)(+3.1+2.3) (<14), B(B(0)-->eta'rho0)<3.7, and B(B(0)-->eta'f(0)(980)(f(0)-->pi+pi-))<1.5. Charge asymmetries in the channels with significant yields are consistent with zero.

Measurement of the CP asymmetry and branching fraction of B0-->rho0K0.

We present a measurement of the branching fraction and time-dependent CP asymmetry of B(0)-->rho0K0. The results are obtained from a data sample of 227x10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at Stanford Linear Accelerator Center. From a time-dependent maximum likelihood fit yielding 111+/-19 signal events, we find B(B(0)-->rho0K0)=(4.9+/-0.8+/-0.9)x10(-6), where the first error is statistical and the second systematic. We report the measurement of the CP parameters S(rho)(0)K(0)S=0.20+/-0.52+/-0.24 and C(rho)(0)K(0)S=0.64+/-0.41+/-0.20.

Search for lepton flavor violating decays tau(+/-) --> l(+/-)pi0, l(+/-)eta, l(+/-)eta'.

A search for lepton flavor violating decays of the tau lepton to a lighter mass lepton and a pseudoscalar meson has been performed using 339 fb;{-1} of e;{+}e;{-} annihilation data collected at a center-of-mass energy near 10.58 GeV by the BABAR detector at the SLAC PEP-II storage ring. No evidence of a signal has been found, and upper limits on the branching fractions are set at the 10;{-7} level.

Observation of decays B0-->Ds(*)+ pi- and B0-->Ds(*)- K+.

We report the observation of decays B{0}-->D{s}{(*)+}pi- and B{0}-->D{s}{(*)-}K+ in a sample of 230 x 10(6) Upsilon(4S)-->BB[over] events recorded with the BABAR detector at the SLAC PEP-II asymmetric-energy e+ e- storage ring. We measure the branching fractions B(B{0}-->D{s}{+}pi-)=(1.3+/-0.3(stat)+/-0.2(syst))x10(-5), B(B{0}-->D{s}{-} K+)=(2.5+/-0.4(stat)+/-0.4(syst))x10(-5), B(B{0}-->D{s}{*+}pi-)=(2.8+/-0.6(stat)+/-0.5(syst))x10(-5), and B(B{0}-->D{s}{*-}K+)=(2.0+/-0.5(stat)+/-0.4(syst))x10(-5). The significances of the measurements to differ from zero are 5, 9, 6, and 5 standard deviations, respectively. This is the first observation of B{0}-->D{s}{+}pi-, B{0}-->D{s}{*+}pi-, and B{0}-->D{s}{*-}K+ decays.

Measurement of the B0-->pi(-l)(+nu) form-factor shape and branching fraction, and determination of /Vub/ with a loose neutrino reconstruction technique.

We report the results of a study of the exclusive charmless semileptonic decay, B0-->pi(-l)(+nu), undertaken with approximately 227 x 10(6) BB pairs collected at the Upsilon(4S) resonance with the BABAR detector. The analysis uses events in which the signal B decays are reconstructed with an innovative loose neutrino reconstruction technique. We obtain partial branching fractions in 12 bins of q2, the momentum transfer squared, from which we extract the f + (q2) form-factor shape and the total branching fraction B(B0-->pi(-l)(+nu))=(1.46+/-0.07stat+/-0.08syst) x 10(-4). Based on a recent unquenched lattice QCD calculation of the form factor in the range q2>16 GeV2, we find the magnitude of the Cabibbo-Kobayashi-Maskawa matrix element /Vub/ to be (4.1+/-0.2stat +/- 0.2syst(+0.6)-0.4_{FF}) x 10(-3), where the last uncertainty is due to the normalization of the form factor.

Current research priorities in chronic fatigue syndrome/myalgic encephalomyelitis: disease mechanisms, a diagnostic test and specific treatments.

Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least 6 months duration, which is accompanied by various rheumatological, infectious and neuropsychiatric symptoms. A collaborative study group has been formed to deal with the current areas for development in CFS research--namely, to develop an understanding of the molecular pathogenesis of CFS, to develop a diagnostic test and to develop specific and curative treatments. Various groups have studied the gene expression in peripheral blood of patients with CFS, and from those studies that have been confirmed using polymerase chain reaction (PCR), clearly, the most predominant functional theme is that of immunity and defence. However, we do not yet know the precise gene signature and metabolic pathways involved. Currently, this is being dealt with using a microarray representing 47,000 human genes and variants, massive parallel signature sequencing and real-time PCR. It will be important to ensure that once a gene signature has been identified, it is specific to CFS and does not occur in other diseases and infections. A diagnostic test is being developed using surface-enhanced, laser-desorption and ionisation-time-of-flight mass spectrometry based on a pilot study in which putative biomarkers were identified. Finally, clinical trials are being planned; novel treatments that we believe are important to trial in patients with CFS are interferon-beta and one of the anti-tumour necrosis factor-alpha drugs.