Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses.

Intracellular Ca(2+) transients are considered a primary signal by which astrocytes interact with neurons and blood vessels. With existing commonly used methods, Ca(2+) has been studied only within astrocyte somata and thick branches, leaving the distal fine branchlets and endfeet that are most proximate to neuronal synapses and blood vessels largely unexplored. Here, using cytosolic and membrane-tethered forms of genetically encoded Ca(2+) indicators (GECIs; cyto-GCaMP3 and Lck-GCaMP3), we report well-characterized approaches that overcome these limitations. We used in vivo microinjections of adeno-associated viruses to express GECIs in astrocytes and studied Ca(2+) signals in acute hippocampal slices in vitro from adult mice (aged ∼P80) two weeks after infection. Our data reveal a sparkling panorama of unexpectedly numerous, frequent, equivalently scaled, and highly localized Ca(2+) microdomains within entire astrocyte territories in situ within acute hippocampal slices, consistent with the distribution of perisynaptic branchlets described using electron microscopy. Signals from endfeet were revealed with particular clarity. The tools and experimental approaches we describe in detail allow for the systematic study of Ca(2+) signals within entire astrocytes, including within fine perisynaptic branchlets and vessel-associated endfeet, permitting rigorous evaluation of how astrocytes contribute to brain function

Comparison of Travoprost and Bimatoprost plus timolol fixed combinations in open-angle glaucoma patients previously treated with latanoprost plus timolol fixed combination

To compare the ocular hypotensive effect of bimatoprost plus timolol and travoprost plus timolol fixed combinations in glaucoma patients whose disease was controlled but had not reached their target intraocular pressure (IOP) with the fixed combination of latanoprost plus timolol

Neutron-Proton Differential Flow as a Probe of Isospin-Dependence of Nuclear Equation of State

The neutron-proton differential flow is shown to be a very useful probe of the isospin-dependence of the nuclear equation of state (EOS). This novel approach utilizes constructively both the isospin fractionation and the nuclear collective flow as well as their sensitivities to the isospin-dependence of the nuclear EOS. It also avoids effectively uncertainties associated with other dynamical ingredients of heavy-ion reactions at intermediate energies.Comment: 10 pages + 3 figures. Phys. Rev. Lett. (2000) in pres

Equation of state of asymmetric nuclear matter and collisions of neutron-rich nuclei

The ratio of pre-equilibrium neutrons to protons from collisions of neutron-rich nuclei is studied as a function of their kinetic energies. This ratio is found to be sensitive to the density dependence of the nuclear symmetry energy, but is independent of the compressibility of symmetric nuclear matter and the in-medium nucleon-nucleon cross sections. The experimental measurement of this ratio thus provides a novel means for determining the nuclear equation of state of asymmetric nuclear matter.Comment: 11 pages + 3 postscript figures, Phys. Rev. Lett. (1997) in pres

QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting.

To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania. Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB. Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline. QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting

Challenges of Loss to Follow-up in Tuberculosis Research.

In studies evaluating methods for diagnosing tuberculosis (TB), follow-up to verify the presence or absence of active TB is crucial and high dropout rates may significantly affect the validity of the results. In a study assessing the diagnostic performance of the QuantiFERON®-TB Gold In-Tube test in TB suspect children in Tanzania, factors influencing patient adherence to attend follow-up examinations and reasons for not attending were examined. In 160 children who attended and 102 children who did not attend scheduled 2-month follow-up baseline health characteristics, demographic data and risk factors for not attending follow-up were determined. Qualitative interviews were used to understand patient and caretakers reasons for not returning for scheduled follow-up. Being treated for active tb in the dots program (OR: 4.14; 95% CI:1.99-8.62;p-value<0.001) and receiving money for the bus fare (OR:129; 95% CI 16->100;P-value<0.001) were positive predictors for attending follow-up at 2 months, and 21/85(25%) of children not attending scheduled follow-up had died. Interviews revealed that limited financial resources, i.e. lack of money for transportation and poor communication, were related to non-adherence. Patients lost to follow-up is a potential problem for TB research. Receiving money for transportation to the hospital and communication is crucial for adherence to follow-up conducted at a study facility. Strategies to ensure follow-up should be part of any study protocol

Proton Differential Elliptic Flow and the Isospin-Dependence of the Nuclear Equation of State

Within an isospin-dependent transport model for nuclear reactions involving neutron-rich nuclei, we study the first-order direct transverse flow of protons and their second-order differential elliptic flow as a function of transverse momentum. It is found that the differential elliptic flow of mid-rapidity protons, especially at high transverse momenta, is much more sensitive to the isospin dependence of the nuclear equation of state than the direct flow. Origins of these different sensitivities and their implications to the experimental determination of the isospin dependence of the nuclear equation of state by using neutron-rich heavy-ion collisions at intermediate energies are discussed.Comment: 15 pages, 6 figures. Phys. Rev. C (2001) in pres

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day