Passive Versus Active Tuberculosis Case Finding and Isoniazid Preventive Therapy Among Household Contacts in a Rural District of Malawi.

SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis

Diagnosis and management of anaemia and iron deficiency in patients with haematological malignancies or solid tumours in France in 2009-2010: the AnemOnHe study

OBJECTIVE: To describe the management of anaemia in 2009-2010 in France in patients with haematological malignancies (HM) or solid tumours (ST). METHODS: Retrospective observational study in 57 centres, enrolling adult patients with HM or ST treated for an episode of anaemia (duration of the episode >/= 3 months occurring in the last 12 months). RESULTS: 220 patients with ST (breast, 18%; lung, 18%) and 56 with HM (lymphoma, 60%) were included (median age, 68 years; female, 53%). Mean haemoglobin level at anaemia diagnosis was 9.3 +/- 1.4 g/dL (<8 g/dL for 16%) and 9.8 +/- 1.1g/dL (<8 g/dL for 6%) in HM and ST patients, respectively. At least one parameter of iron deficiency (ferritin, transferrin saturation) was assessed in 26% of HM and 19% of ST patients. Treatment of anaemia included erythropoiesis-stimulating agents (ESA) for 98% of HM and 89% of ST patients. Iron was prescribed to 14% (oral, 12%; intravenous, 2%) of HM patients and to 42% (oral, 17%; intravenous, 25%) of ST patients. The rates of blood transfusions were high: 70% in HM and 46% in ST patients; transfusions alone or administrated with ESA were more frequent in patients with Hb <8 g/dL. CONCLUSION: Although recent guidelines recommend evaluating iron deficiency and correcting anaemia by using intravenous iron, our study in cancer patients evidenced that ESA and blood transfusions are still frequently used as the treatment of anaemia in cancer patients. Iron deficiency is insufficiently assessed (only one patient among five) and as a consequence iron deficiency is most likely insufficiently treated

Multibarrier tunneling

We study the tunneling through an arbitrary number of finite rectangular opaque barriers and generalize earlier results by showing that the total tunneling phase time depends neither on the barrier thickness nor on the inter-barrier separation. We also predict two novel peculiar features of the system considered, namely the independence of the transit time (for non resonant tunneling) and the resonant frequency on the number of barriers crossed, which can be directly tested in photonic experiments. A thorough analysis of the role played by inter-barrier multiple reflections and a physical interpretation of the results obtained is reported, showing that multibarrier tunneling is a highly non-local phenomenon.Comment: RevTex, 7 pages, 1 eps figur

Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome

Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. The genetic basis of LSS is currently unknown. LSS shows phenotypic overlap with Haas-type polysyndactyly (HTS) regarding the digital phenotype. Here we report on five unrelated families with overlapping microduplications encompassing the Sonic hedgehog (SHH) limb enhancer ZPA regulatory sequence (ZRS) on chromosome 7q36. Clinically, the patients show polysyndactyly phenotypes and various types of lower limb malformations ranging from syndactyly to mirror image polydactyly with duplications of the fibulae. We show that larger duplications of the ZRS region (>80 kb) are associated with HTS, whereas smaller duplications (<80 kb) result in the LSS phenotype. On the basis of our data, the latter can be clearly distinguished from HTS by the presence of mirror image polysyndactyly of the feet with duplication of the fibula. Our results expand the clinical phenotype of the ZRS-associated syndromes and suggest that smaller duplications (<80 kb) are associated with a more severe phenotype. In addition, we show that these small microduplications within the ZRS region are the underlying genetic cause of Laurin-Sandrow syndrome

Possibility of the tunneling time determination

We show that it is impossible to determine the time a tunneling particle spends under the barrier. However, it is possible to determine the asymptotic time, i.e., the time the particle spends in a large area including the barrier. We propose a model of time measurements. The model provides a procedure for calculation of the asymptotic tunneling and reflection times. The model also demonstrates the impossibility of determination of the time the tunneling particle spends under the barrier. Examples for delta-form and rectangular barrier illustrate the obtained results.Comment: 8 figure

Transmission time of wave packets through tunneling barriers

The transmission of wave packets through tunneling barriers is studied in detail by the method of quantum molecular dynamics. The distribution function of the times describing the arrival of a tunneling packet in front of and behind a barrier and the momentum distribution function of the packet are calculated. The behavior of the average coordinate of a packet, the average momentum, and their variances is investigated. It is found that under the barrier a part of the packet is reflected and a Gaussian barrier increases the average momentum of the transmitted packet and its variance in momentum space.Comment: 23 pages, 5 figure

Measurement of Superluminal optical tunneling times in double-barrier photonic bandgaps

Tunneling of optical pulses at 1.5 micron wavelength through double-barrier periodic fiber Bragg gratings is experimentally investigated. Tunneling time measurements as a function of barrier distance show that, far from the resonances of the structure, the transit time is paradoxically short, implying Superluminal propagation, and almost independent of the distance between the barriers. These results are in agreement with theoretical predictions based on phase time analysis and also provide an experimental evidence, in the optical context, of the analogous phenomenon expected in Quantum Mechanics for non-resonant superluminal tunneling of particles across two successive potential barriers. [Attention is called, in particular, to our last Figure]. PACS nos.: 42.50.Wm, 03.65.Xp, 42.70.Qs, 03.50.De, 03.65.-w, 73.40.GkComment: LaTeX file (8 pages), plus 5 figure

Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve Split-Hand/Foot Malformation type 3

Split-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigated the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice. We show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice resulted in restructuring of the chromatin architecture. This led to an ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern. Artificial repositioning of the AER-specific enhancers of Fgf8 was sufficient to induce misexpression of Lbx1 and Btrc. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression and dosage in the developing limb. Our results reveal new insights into the molecular mechanism underlying SHFM3 and provide novel conceptual framework for how genomic rearrangements can cause gene misexpression and disease

Tunneling Violates Special Relativity

Experiments with evanescent modes and tunneling particles have shown that i) their signal velocity may be faster than light, ii) they are described by virtual particles, iii) they are nonlocal and act at a distance, iv) experimental tunneling data of phonons, photons, and electrons display a universal scattering time at the tunneling barrier front, and v) the properties of evanescent, i.e. tunneling modes is not compatible with the special theory of relativity

Quantum Tunneling in the Wigner Representation

Time dependence for barrier penetration is considered in the phase space. An asymptotic phase-space propagator for nonrelativistic scattering on a one - dimensional barrier is constructed. The propagator has a form universal for various initial state preparations and local potential barriers. It is manifestly causal and includes time-lag effects and quantum spreading. Specific features of quantum dynamics which disappear in the standard semi-classical approximation are revealed. The propagator may be applied to calculation of the final momentum and coordinate distributions, for particles transmitted through or reflected from the potential barrier, as well as for elucidating the tunneling time problem.Comment: 18 pages, LATEX, no figure