A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein.

Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection

Low-Dose DDAVP in Nocturnal Enuresis

A five-year experience with the vasopressin analogue desmopressin acetate (DDAVP) for nocturnal enuresis is described in 59 children. The initial starting dose of 5 μg at bedtime is lower than that reported in other series. Eighty-one percent of patients required 10 μg or less to achieve improvement or resolution of bedwetting.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67971/2/10.1177_000992289203100507.pd

Effects of COVID-19 pandemic on glaucoma appointment scheduling in a tertiary hospital in London, UK

PURPOSE: To investigate the impact of the delay in patient appointments caused by the COVID-19 pandemic and the triage system on the glaucomatous disease of patients in a London tertiary hospita METHODS: Observational retrospective study that randomly selected 200 glaucoma patients with more than 3 months of unintended delay for their post-COVID visit and other inclusion and exclusion criteria. Demographic information, clinical data, number of drugs, best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) mean deviation (MD), and global peripapillary retinal nerve fibre layer (pRNFL) thickness were obtained from the pre- and post-COVID visit. At the post-COVID visit, the clinical outcomes subjective clinical concern and change of treatment or need for surgery were also annotated. The variables were stratified by glaucoma severity (according to the MD into early, moderate and advanced) and by delay time (more and less than 12 months) and analysed using SPSS. RESULTS: We included 121 eyes (from 71 patients). The median patient age was 74 years (interquartile range -IQR- 15), 54% were males and 52% Caucasians. Different glaucoma types and all glaucoma severities were included. When data was stratified for glaucoma severity, at the pre-COVID visit, significant differences in BCVA, CCT and IOP were observed and there were significantly higher values in the early glaucoma group. The median follow-up delay was 11 months (IQR 8), did not differ between the glaucoma severity groups and did not correlate to the glaucoma severity. At the post-COVID visit, significant differences in BCVA, IOP, and Global pRNFL thickness were observed between the glaucoma severity groups, as lower BCVA and higher IOP and pRNFL thickness were observed in the early glaucoma group. At the post-COVID visit there was cause for concern in 40 eyes: 5 were followed more closely, 22 had a change of treatment and 13 were booked for surgery (3 for cataract and 10 for glaucoma surgery). However, the number of eyes with causes for concern were similar between the glaucoma severity groups and there was no correlation between these clinical outcomes and the delay of the post-COVID visit. The number of topical hypotensive medications increased significantly after the post-COVID visit, higher number of medications were observed in the advanced glaucoma group. When differences of IOP, MD and pRNFL thickness between the pre and post-COVID visit, only the MD difference was significantly different between the glaucoma severity groups because it was higher in the severe group. When data was stratified for delay longer or shorter than 12 months, no differences were observed between the groups except at the pre-COVID visit, when the numbers of patients with MD deviation >−6 dB had longer delay time. When differences in IOP, MD and RNFL thickness were calculated, only the pRNFL thickness showed significant differences between the delay groups, because it was higher in the longer delay group. Finally, when paired analysis of the variables at the pre- and post-COVID visits, stratified by glaucoma severity and delay were conducted, although there were no significant differences in IOP in any group, the BCVA decreased significantly in the overall group and in the longer delay groups, the number of hypotensive drugs increased significantly overall and in the moderate and advanced glaucoma, the MD of the VF worsened significantly in the overall group and in the early glaucoma and longer delay groups and the pRNFL thickness decreased significantly in all groups. CONCLUSIONS: We document that delayed care impacts negatively on the glaucomatous disease of our patients because at the post-COVID visit there were reasons for clinical concern in a third of eyes that resulted in change of treatment or surgery. However, these clinical consequences were not related to IOP, glaucoma severity or delay time and reflect that the triage methods implemented worked adequately. The most sensitive parameter to indicate progression in our sample was the pRNFL thickness

Glaucoma Rose Plot Analysis: detecting early structural progression using angular histograms

Purpose To evaluate the novel Rose Plot Analysis (RPA) in the analysis and presentation of glaucoma structural progression data. Design Case-control image analysis study using retrospective retinal imaging series. Subjects Subjects with open-angle glaucoma with at least 5 registered spectral-domain OCT scans. Methods Glaucoma RPA was developed, combining a novel application of angular histograms and dynamic cluster analysis of circumpapillary retinal nerve fiber layer (cRNFL) OCT data. Rose Plot Analysis plots were created for each eye and each visit. Significant clusters of progression were indicated in red. Three masked clinicians categorized all RPA plots (progressing, not progressing), in addition to measuring the significant RPA area. A masked OCT series assessment with linear regression of averaged global and sectoral cRNFL thicknesses was conducted as the clinical imaging standard. Main Outcome Measures Interobserver agreement was compared between RPA and the clinical imaging standard. Discriminative ability was assessed using receiver-operating characteristic curves. The time to detection of progression was compared using a Kaplan–Meier survival analysis, and the agreement of RPA with the clinical imaging standard was calculated. Results Seven hundred fourty-three scans from 98 eyes were included. Interobserver agreement was significantly greater when categorizing RPA (κ, 0.86; 95% confidence interval [CI], 0.81–0.91) compared with OCT image series (κ, 0.66; 95% CI, 0.54–0.77). The discriminative power of RPA to differentiate between eyes that were progressing and not progressing (area under the curve [AUC], 0.97; 95% CI, 0.92–1.00) was greater than that of global cRNFL thickness (AUC, 0.71; 95% CI, 0.59–0.82; P < 0.0001) and equivalent to that of sectoral cRNFL regression (AUC, 0.97; 95% CI, 0.92–1.00). A Kaplan–Meier survival analysis showed that progression was detected 8.7 months sooner by RPA than by global cRNFL linear regression (P < 0.0001) in progressing eyes but was not sooner than with sectoral cRNFL (P = 0.06). Rose Plot Analysis showed substantial agreement with the presence of significant thinning on sectoral cRNFL linear regression (κ, 0.715; 95% CI, 0.578–0.853). Conclusions Rose Plot Analysis has been shown to provide accurate and intuitive, at-a-glance data analysis and presentation that improve interobserver agreement and may aid early diagnosis of glaucomatous disease progression

High Energy Gamma-Ray Emission From Blazars: EGRET Observations

We will present a summary of the observations of blazars by the Energetic Gamma Ray Experiment Telescope (EGRET) on the Compton Gamma Ray Observatory (CGRO). EGRET has detected high energy gamma-ray emission at energies greater than 100 MeV from more that 50 blazars. These sources show inferred isotropic luminosities as large as $3\times 10^{49}$ ergs s$^{-1}$. One of the most remarkable characteristics of the EGRET observations is that the gamma-ray luminosity often dominates the bolometric power of the blazar. A few of the blazars are seen to exhibit variability on very short time-scales of one day or less. The combination of high luminosities and time variations seen in the gamma-ray data indicate that gamma-rays are an important component of the relativistic jet thought to characterize blazars. Currently most models for blazars involve a beaming scenario. In leptonic models, where electrons are the primary accelerated particles, gamma-ray emission is believed to be due to inverse Compton scattering of low energy photons, although opinions differ as to the source of the soft photons. Hardronic models involve secondary production or photomeson production followed by pair cascades, and predict associated neutrino production.Comment: 16 pages, 7 figures, style files included. Invited review paper in "Observational Evidence for Black Holes in the Universe," 1999, ed. S. K. Chakrabarti (Dordrecht: Kluwer), 215-23

Sliding charge density wave in manganites

The so-called stripe phase of the manganites is an important example of the complex behaviour of metal oxides, and has long been interpreted as the localisation of charge at atomic sites. Here, we demonstrate via resistance measurements on La_{0.50}Ca_{0.50}MnO_3 that this state is in fact a prototypical charge density wave (CDW) which undergoes collective transport. Dramatic resistance hysteresis effects and broadband noise properties are observed, both of which are typical of sliding CDW systems. Moreover, the high levels of disorder typical of manganites result in behaviour similar to that of well-known disordered CDW materials. Our discovery that the manganite superstructure is a CDW shows that unusual transport and structural properties do not require exotic physics, but can emerge when a well-understood phase (the CDW) coexists with disorder.Comment: 13 pages; 4 figure

Long gamma-ray bursts and core-collapse supernovae have different environments

When massive stars exhaust their fuel they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even more brilliant relativistic explosion known as a long-duration gamma-ray burst. One would then expect that long gamma-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the long gamma-ray bursts are far more concentrated on the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long gamma-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration gamma-ray bursts are associated with the most massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long gamma-ray bursts are relatively rare in galaxies such as our own Milky Way.Comment: 27 pages, 4 figures, submitted to Nature on 22 August 2005, revised 9 February 2006, online publication 10 May 2006. Supplementary material referred to in the text can be found at http://www.stsci.edu/~fruchter/GRB/locations/supplement.pdf . This new version contains minor changes to match the final published versio

Hypernovae and Other Black-Hole-Forming Supernovae

During the last few years, a number of exceptional core-collapse supernovae (SNe) have been discovered. Their kinetic energy of the explosions are larger by more than an order of magnitude than the typical values for this type of SNe, so that these SNe have been called `Hypernovae'. We first describe how the basic properties of hypernovae can be derived from observations and modeling. These hypernovae seem to come from rather massive stars, thus forming black holes. On the other hand, there are some examples of massive SNe with only a small kinetic energy. We suggest that stars with non-rotating black holes are likely to collapse "quietly" ejecting a small amount of heavy elements (Faint supernovae). In contrast, stars with rotating black holes are likely to give rise to very energetic supernovae (Hypernovae). We present distinct nucleosynthesis features of these two types of "black-hole-forming" supernovae. Hypernova nucleosynthesis is characterized by larger abundance ratios (Zn,Co,V,Ti)/Fe and smaller (Mn,Cr)/Fe. Nucleosynthesis in Faint supernovae is characterized by a large amount of fall-back. We show that the abundance pattern of the most Fe deficient star, HE0107-5240, and other extremely metal-poor carbon-rich stars are in good accord with those of black-hole-forming supernovae, but not pair-instability supernovae. This suggests that black-hole-forming supernovae made important contributions to the early Galactic (and cosmic) chemical evolution.Comment: 49 pages, to be published in "Stellar Collapse" (Astrophysics and Space Science; Kluwer) ed. C. L. Fryer (2003

Supernova 2007bi as a pair-instability explosion

Stars with initial masses 10 M_{solar} < M_{initial} < 100 M_{solar} fuse progressively heavier elements in their centres, up to inert iron. The core then gravitationally collapses to a neutron star or a black hole, leading to an explosion -- an iron-core-collapse supernova (SN). In contrast, extremely massive stars (M_{initial} > 140 M_{solar}), if such exist, have oxygen cores which exceed M_{core} = 50 M_{solar}. There, high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs prior to oxygen ignition, and leads to a violent contraction that triggers a catastrophic nuclear explosion. Tremendous energies (>~ 10^{52} erg) are released, completely unbinding the star in a pair-instability SN (PISN), with no compact remnant. Transitional objects with 100 M_{solar} < M_{initial} < 140 M_{solar}, which end up as iron-core-collapse supernovae following violent mass ejections, perhaps due to short instances of the pair instability, may have been identified. However, genuine PISNe, perhaps common in the early Universe, have not been observed to date. Here, we present our discovery of SN 2007bi, a luminous, slowly evolving supernova located within a dwarf galaxy (~1% the size of the Milky Way). We measure the exploding core mass to be likely ~100 M_{solar}, in which case theory unambiguously predicts a PISN outcome. We show that >3 M_{solar} of radioactive 56Ni were synthesized, and that our observations are well fit by PISN models. A PISN explosion in the local Universe indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic limit, perhaps resulting from star formation processes similar to those that created the first stars in the Universe.Comment: Accepted version of the paper appearing in Nature, 462, 624 (2009), including all supplementary informatio

Hematocrit and the Risk of Recurrent Venous Thrombosis: A Prospective Cohort Study

BACKGROUND: Venous thromboembolism (VTE) is a multicausal disease which recurs. Hematocrit is associated with a thrombotic risk. We aimed to investigate if hematocrit is associated with the recurrence risk. METHODS: Patients with a first VTE were followed after anticoagulation. Patients with VTE provoked by a transient risk factor, natural inhibitor deficiency, lupus anticoagulant, homozygous or double heterozygous defects, cancer, or long-term antithrombotic treatment were excluded. The study endpoint was recurrent VTE. RESULTS: 150 (23%) of 653 patients had recurrence. Only high hematocrit was significantly associated with recurrence risk [hazard ratio (HR) for 1% hematocrit increase with the third tertile 1.08; 95% CI 1.01-1.15]. No or only a weak association for hematocrits within the first and second tertile was seen (HR 1.03; 95% CI 0.97-1.09, and 1.07; 95% CI 1.00-1.13). Hematocrit was associated with recurrence risk only among women. After five years, the probability of recurrence was 9.9% (95% CI 3.7%-15.7%), 15.6% (95% CI 9.7%-21.2%) and 25.5% (95% CI 15.1%-34.6%) in women, and was 29.2% (95% CI 21.1%-36.5%), 30.1% (95% CI 24.1%-35.7%) and 30.8% (95% CI 22.0%-38.7%) in men for hematocrits in the first, second and third tertile, respectively. Men had a higher recurrence risk (1.9; 95% CI 1.1-2.7; p = 0.03), which dropped by 23.5% after adjustment for hematocrit. Hematocrit was not a significant mediator of the sex-difference in recurrence risk (p = 0.223). CONCLUSIONS: High hematocrit is associated with the recurrence only in women. The different recurrence risk between men and women is possibly partly explained by hematocrit