MTCT rates in the UK and Ireland have continued to decline since 2006, reaching an all-time low of 5 per 1000 in 2010-2011. This was primarily because of a reduction in transmissions associated with late initiation or nonreceipt of antenatal cART, and an increase in the proportion of women on cART at conception.
The ZEPLIN-III experiment in the Palmer Underground Laboratory at Boulby uses a 12 kg twophase xenon time projection chamber to search for the weakly interacting massive particles (WIMPs) that may account for the dark matter of our Galaxy. The detector measures both scintillation and ionisation produced by radiation interacting in the liquid to differentiate between the nuclear recoils expected from WIMPs and the electron recoil background signals down to ∼10 keV nuclear recoil energy. An analysis of 847 kg•days of data acquired between February 27 th 2008 and May 20 th 2008 has excluded a WIMP-nucleon elastic scattering spin-independent cross-section above 8.1 × 10 −8 pb at 60 GeVc −2 with a 90% confidence limit. It has also demonstrated that the two-phase xenon technique is capable of better discrimination between electron and nuclear recoils at low-energy than previously achieved by other xenon-based experiments.
Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease and associated morbidity and mortality worldwide. Vertical and early childhood transmission are the main routes of HBV transmission globally, responsible for most chronic infectionsincluding in adults who bear the greatest burden of morbidity and mortality. Universal infant and birth dose hepatitis B immunization is the key preventative strategy for global elimination of HBV infection, and has been highly effective in reducing new vertical infections. Global progress on HBV testing and treatment, however, has been slow in adults and children. In this review, we summarize current knowledge on epidemiology, natural history, and treatment of chronic HBV infection in adolescents and children, highlighting key differences from the experience with adults, and conclude with key actions to address current policy gaps. The estimated global prevalence in children aged 5 years or less is 1.3%. Most children are in the "high replication, low level of inflammation" infection phase with normal or only minimally raised aminotransferases; cirrhosis and hepatocellular carcinoma are rare. Although entecavir is approved and recommended for children 2 to <18 years, and tenofovir for those 12 to < 18 years, a conservative approach to treatment initiation is currently recommended. Key actions to address current policy gaps include: validation of non-invasive tests for liver disease staging; additional immunopathogenesis studies in HBV infected children, and long-term follow-up of children on nucleoside analogue regimens to inform guidance on when to start treatment; evaluation of different treatment strategies for children with high levels of replication; and establishment of paediatric treatment registries and international consortia to promote collaborative research.
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have now transformed treatment for HCV infection. Since the launch in 2016 of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on treatment of adults, who bear the greatest burden of morbidity and mortality of HCV related chronic liver disease. There has been much less attention paid to addressing response to HCV in children and adolescents, in part because of the lack of data to inform specific paediatric management practices and policy. In this review, we summarize current knowledge on epidemiology, natural history, and treatment of chronic HCV infection in adolescents and children, and highlight key differences from infection acquired in adulthood. The estimated global prevalence and burden in children aged 1 to 19 years is 0•15% and 3•5 (3•1-3•9) million, respectively. HCV infection is usually asymptomatic during childhood, and cirrhosis and hepatocellular carcinoma are rare. Sofosbuvir, ledipasvir and ribavirin have now received regulatory approval and guidelines recommend their use in adolescents ages >12 years with HCV infection. Key actions to address the current policy gaps and achieve treatment scale-up comparable to that in adults include: establishment of a testing and treatment access campaign targeted at children and adolescents; fast-track evaluation of pangenotypic regimens and accelerated approval of paediatric formulations. Research gaps that need to be addressed include age-specific seroprevalence studies of HCV viraemia in priority countries; further validation of non-invasive tests in children; and establishment of paediatric treatment registries and international consortia to promote collaborative research agenda.
HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes.Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV.ConclusionData on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings.
Results are presented from the first underground data run of ZEPLIN-II, a 31 kg two-phase xenon detector developed to observe nuclear recoils from hypothetical weakly interacting massive dark matter particles. Discrimination between nuclear recoils and background electron recoils is afforded by recording both the scintillation and ionisation signals generated within the liquid xenon, with the ratio of these signals being different for the two classes of event. This ratio is calibrated for different incident species using an AmBe neutron source and 60Co γ-ray sources. From our first 31 live days of running ZEPLIN-II, the total exposure following the application of fiducial and stability cuts was 225 kg × days. A background population of radon progeny events was observed in this run, arising from radon emission in the gas purification getters, due to radon daughter ion decays on the surfaces of the walls of the chamber. An acceptance window, defined by the neutron calibration data, of 50% nuclear recoil acceptance between 5 keVee and 20 keVee, had an observed count of 29 events, with a summed expectation of 28.6 ± 4.3 γ-ray and radon progeny induced background events. These figures provide a 90% c.l. upper limit to the number of nuclear recoils of 10.4 events in this acceptance window, which converts to a WIMP nucleon spin-independent cross-section with a minimum of 6.6 × 10-7 pb following the inclusion of an energy-dependent, calibrated, efficiency. A second run is currently underway in which the radon progeny will be eliminated, thereby removing the background population, with a projected sensitivity of 2 × 10-7 pb for similar exposures as the first run
We report experimental upper limits on WIMP-nucleon elastic scattering cross sections from the second science run of ZEPLIN-III at the Boulby Underground Laboratory. A raw fiducial exposure of 1,344 kg·days was accrued over 319 days of continuous operation between June 2010 and May 2011. A total of eight events was observed in the signal acceptance region in the nuclear recoil energy range 7-29 keV, which is compatible with background expectations. This allows the exclusion of the scalar cross-section above 4.8×10 −8 pb near 50 GeV/c 2 WIMP mass with 90% confidence. Combined with data from the first run, this result improves to 3.9×10 −8 pb. The corresponding WIMP-neutron spin-dependent cross-section limit is 8.0×10 −3 pb. The ZEPLIN programme reaches thus its conclusion at Boulby, having deployed and exploited successfully three liquid xenon experiments of increasing reach.
Scintillation and ionisation yields for nuclear recoils in liquid xenon above 10 keV nr (nuclear recoil energy) are deduced from data acquired using broadband Am-Be neutron sources. The nuclear recoil data from several exposures to two sources were compared to detailed simulations. Energy-dependent scintillation and ionisation yields giving acceptable fits to the data were derived. Efficiency and resolution effects are treated using a light collection Monte Carlo, measured photomultiplier response profiles and hardware trigger studies. A gradual fall in scintillation yield below ∼ 40 keV nr is found, together with a rising ionisation yield; both are in agreement with the latest independent measurements. The analysis method is applied to the most recent ZEPLIN-III data, acquired with a significantly upgraded detector and a precision-calibrated Am-Be source, as well as to the earlier data from the first run in 2008. A new method for deriving the recoil scintillation yield, which includes sub-threshold S1 events, is also presented which confirms the main analysis.
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