Moonshine: Diurnally varying hydration through natural distillation on the Moon, detected by the Lunar Exploration Neutron Detector (LEND).

The Lunar Exploration Neutron Detector (LEND), on the polar-orbiting Lunar Reconnaissance Orbiter (LRO) spacecraft, has detected suppression in the Moon's naturally-occurring epithermal neutron leakage flux that is consistent with the presence of diurnally varying quantities of hydrogen in the regolith near the equator. Peak hydrogen concentration (neutron flux suppression) is on the dayside of the dawn terminator and diminishes through the dawn-to-noon sector. The minimum concentration of hydrogen is in the late afternoon and dusk sector. The chemical form of hydrogen is not determinable from these measurements, but other remote sensing methods and anticipated elemental availability suggest water molecules or hydroxyl ions. Signal-to-noise ratio at maximum contrast is 5.6σ in each of two detector systems. Volatiles are deduced to collect in or on the cold nightside surface and distill out of the regolith after dawn as rotation exposes the surface to sunlight. Liberated volatiles migrate away from the warm subsolar region toward the nearby cold nightside surface beyond the terminator, resulting in maximum concentration at the dawn terminator. The peak concentration within the upper ~1 m of regolith is estimated to be 0.0125 ± 0.0022 weight-percent water-equivalent hydrogen (wt% WEH) at dawn, yielding an accumulation of 190 ± 30 ml recoverable water per square meter of regolith at each dawn. Volatile transport over the lunar surface in opposition to the Moon's rotation exposes molecules to solar ultraviolet radiation. The short lifetime against photolysis and permanent loss of hydrogen from the Moon requires a resupply rate that greatly exceeds anticipated delivery of hydrogen by solar wind implantation or by meteoroid impacts, suggesting that the surface inventory must be continually resupplied by release from a deep volatile inventory in the Moon. The natural distillation of water from the regolith by sunlight and its capture on the cold night surface may provide energy-efficient access to volatiles for in situ resource utilization (ISRU) by direct capture before volatiles can enter the surface, eliminating the need to actively mine regolith for volatile resource recovery.

Hydrogen mapping of the lunar south pole using the LRO neutron detector experiment LEND.

Hydrogen has been inferred to occur in enhanced concentrations within permanently shadowed regions and, hence, the coldest areas of the lunar poles. The Lunar Crater Observation and Sensing Satellite (LCROSS) mission was designed to detect hydrogen-bearing volatiles directly. Neutron flux measurements of the Moon's south polar region from the Lunar Exploration Neutron Detector (LEND) on the Lunar Reconnaissance Orbiter (LRO) spacecraft were used to select the optimal impact site for LCROSS. LEND data show several regions where the epithermal neutron flux from the surface is suppressed, which is indicative of enhanced hydrogen content. These regions are not spatially coincident with permanently shadowed regions of the Moon. The LCROSS impact site inside the Cabeus crater demonstrates the highest hydrogen concentration in the lunar south polar region, corresponding to an estimated content of 0.5 to 4.0% water ice by weight, depending on the thickness of any overlying dry regolith layer. The distribution of hydrogen across the region is consistent with buried water ice from cometary impacts, hydrogen implantation from the solar wind, and/or other as yet unknown sources.

Improving measurement in clinical handover.

BACKGROUND: Poor clinical handover creates discontinuities in care leading to patient harm. However, the field of handover research continues to lack standardised definitions and reliable measurement tools to identify factors that would lead to harm reduction and improved safety strategies. OBJECTIVE: This paper introduces a conceptual framework to underpin a research agenda around the important patient safety topic of clinical handover. METHODS: Five frameworks with potential application to clinical handover were identified in a consultation process with clinicians, researchers and policy makers. RESULTS: The framework consists of three key handover elements-information, responsibility and/or accountability and system-in relation to three key measurement elements-policy, practice and evaluation. Using this framework an analysis of current "gaps" in the measurement of handover was completed. CONCLUSION: The paper argues that measurement will identify gaps in knowledge about handover practice and promote rigor in the design and evaluation of interventions to reduce patient harm.

Cornulin, a marker of late epidermal differentiation, is down-regulated in eczema.

BACKGROUND: Eczema is a common chronic inflammatory skin disorder which shows strong genetic predisposition. To identify new potential molecular determinants of the disease pathogenesis, we performed a gene expression study in an eczema mouse model. This analysis identified a marked down regulation of the cornulin gene (CRNN), a member of the epidermal differentiation complex, in the eczema-like skin. We then investigated CRNN as an eczema candidate gene and studied its polymorphism and the expression in the skin of eczema patients. METHODS: An eczema-like phenotype was induced in mice by allergen (Der p2) patching. Gene expression analysis was performed with the subtractive suppression hybridization method and validated by real time PCR and the transmission disequilibrium test was used to test for genetic associations in 406 multiplex eczema families. RESULTS: Der p 2 patched mice developed a localized eczema and a Th 2 skewed systemic response. Real time PCR analysis confirmed a down regulation of CRNN mRNA in eczema-like skin in the mouse model and in human eczema. The CRNN polymorphism rs941934 was significantly associated with atopic eczema in the genetic analysis (P = 0.006), though only as part of an extended haplotype including a known associated variant (2282del4) in the filaggrin gene. CONCLUSIONS: CRNN mRNA expression is decreased in eczematous skin. Further studies are needed to verify whether the associated cornulin polymorphism contribute to the genetic susceptibility in eczema.

Experiment LEND of the NASA Lunar Reconnaissance Orbiter for high-resolution mapping of neutron emission of the Moon.

The scientific objectives of neutron mapping of the Moon are presented as 3 investigation tasks of NASA's Lunar Reconnaissance Orbiter mission. Two tasks focus on mapping hydrogen content over the entire Moon and on testing the presence of water-ice deposits at the bottom of permanently shadowed craters at the lunar poles. The third task corresponds to the determination of neutron contribution to the total radiation dose at an altitude of 50 km above the Moon. We show that the Lunar Exploration Neutron Detector (LEND) will be capable of carrying out all 3 investigations. The design concept of LEND is presented together with results of numerical simulations of the instrument's sensitivity for hydrogen detection. The sensitivity of LEND is shown to be characterized by a hydrogen detection limit of about 100 ppm for a polar reference area with a radius of 5 km. If the presence of ice deposits in polar "cold traps" is confirmed, a unique record of many millions of years of lunar history would be obtained, by which the history of lunar impacts could be discerned from the layers of water ice and dust. Future applications of a LEND-type instrument for Mars orbital observations are also discussed.

The value of serum neopterin, interferon-gamma levels and interleukin-12B polymorphisms in predicting acute renal allograft rejection.

Acute rejection remains a poor predictor of graft outcome. In this study, we measured serum levels of interferon (IFN)-gamma and neopterin by enzyme-linked immunosorbent assay and a single nucleotide polymorphism (SNP) within the 3' untranslated region of the interleukin (IL)-12 B gene (1188 A/C) to determine whether either of these factors could predict acute rejection in renal transplantation. Significantly higher early post-transplant neopterin levels (days 5-7; 35.7 versus 19.9 nmol/l) were observed in recipients who subsequently rejected their grafts. Post-transplant neopterin levels showed a strong positive correlation with 1-month creatinine levels (Spearman's correlation 0.62, P < 0.001), suggesting macrophage activation early after transplantation. Pretransplant neopterin and IFN-gamma levels and the IL-12B gene SNP did not predict acute rejection in this small retrospective study. The ability to predict acute rejection non-invasively early after transplantation could lead to individual tailoring of immunosuppressive regimens and perhaps lead eventually to longer graft survival.

The results of radiofrequency catheter ablation of supraventricular tachycardia in children.

BACKGROUND: Radiofrequency (RF) catheter ablation represents a major advance in the management of children with cardiac arrhythmias and has rapidly become the standard of care for the first-ling therapy of supraventricular tachycardias (SVTs). The purpose of this study was to investigate the results of the RF catheter ablation of SVTs in pediatric patients. METHODS: From December 1989 to August 2005, a total of 228 pediatric patients (age: 9 +/- 7 years, range: 5-18 years; male:female = 117:111) with clinically documented SVT underwent an electrophysiologic study and RF catheter ablation at our institution. RESULTS: The arrhythmias included atrioventricular reentrant tachycardia (AVRT; n = 140, 61%), atrioventricular nodal reentrant tachycardia (AVNRT; n = 66, 29%), atrial tachycardia (AT; n = 11, 5%), and atrial flutter (AFL; n = 11, 5%). The success rate of the RF catheter ablation was 92% for AVRT, 97% for AVNRT, 82% for AT, and 91% for AFL, respectively. Procedure-related complications were infrequent (8.7%; major complications: high grade AV block (2/231, 0.9%); minor complications: first degree AV block (6/231, 2.6%), reversible brachial plexus injury (2/231, 0.9%), and local hematomas or bruises (10/231, 4.3%)). The recurrence rate was 4.7% (10/212) during a follow-up period of 86 +/- 38 months (0.5-185 months). CONCLUSIONS: The RF catheter ablation was a safe and effective method to manage children with paroxysmal and incessant tachycardia. The substrates of the arrhythmias differed between the pediatric and adult patients. However, the success rate of the ablation, complications, and recurrence during childhood were similar to those of adults.

Predictive value of thrombocytopaenia in the diagnosis of dengue infection in outpatient settings.

Thrombocytopaenia is often relied upon as an important criterion for the diagnosis of dengue infection among patients presenting with an acute non-specific febrile illness. This study was aimed to assess usefulness of thrombocytopaenia in the diagnosis of acute dengue virus infection. This was a clinic based prospective cohort study from May to November 2003. Consecutive patients presenting with acute non-specific febrile illness of less than two weeks were selected from two urban primary care centres. We did full blood count examination (FBC) on the day of visit and dengue serology on day five of illness for all patients enrolled. We repeated the FBC examination for patients who had initial normal platelet counts. Thrombocytopaenia was defined as platelet count < 150 X 10(9)/L. Eighty-seven patients enrolled in the study. Complete data was available for 73 patients. The prevalence of acute dengue virus infection was 27.6%. The sensitivity and specificity were 88% and 71% respectively. The likelihood of acute dengue infection in the presence of thrombocytopaenia was 2.52 and likelihood of not having dengue infection in normal platelet count patients was 5.22. Thrombocytopaenia has fair predictive value in diagnosing acute dengue virus infection. It was more useful to exclude than to diagnose dengue infection.

Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency.

Although the physiological role of tissue-specific translational control of gene expression in mammals has long been suspected on the basis of biochemical studies, direct evidence has been lacking. Here, we report on the targeted disruption of the gene encoding the heme-regulated eIF2alpha kinase (HRI) in mice. We establish that HRI, which is expressed predominantly in erythroid cells, regulates the synthesis of both alpha- and beta-globins in red blood cell (RBC) precursors by inhibiting the general translation initiation factor eIF2. This inhibition occurs when the intracellular concentration of heme declines, thereby preventing the synthesis of globin peptides in excess of heme. In iron-deficient HRI(-/-) mice, globins devoid of heme aggregated within the RBC and its precursors, resulting in a hyperchromic, normocytic anemia with decreased RBC counts, compensatory erythroid hyperplasia and accelerated apoptosis in bone marrow and spleen. Thus, HRI is a physiological regulator of gene expression and cell survival in the erythroid lineage.

Differential expression of transforming growth factor-beta receptors I and II and activation of Smad 3 in keloid fibroblasts.

Keloids represent a dysregulated response to cutaneous wounding that results in an excessive deposition of extracellular matrix, especially collagen. However, the molecular mechanisms regulating this pathologic collagen deposition still remain to be elucidated. A previous study by this group demonstrated that transforming growth factor (TGF)-beta1 and -beta2 ligands were expressed at greater levels in keloid fibroblasts when compared with normal human dermal fibroblasts (NHDFs), suggesting that TGF-beta may play a fibrosis-promoting role in keloid pathogenesis.To explore the biomolecular mechanisms of TGF-beta in keloid formation, the authors first compared the expression levels of the type I and type II TGF-beta receptors in keloid fibroblasts and NHDFs. Next, they investigated the phosphorylation of Smad 3, an intracellular TGF-beta signaling molecule, in keloid fibroblasts and NHDFs. Finally, they examined the regulation of TGF-beta receptor II by TGF-beta1, TGF-beta2, and TGF-beta3 ligands. Our findings demonstrated an increased expression of TGF-beta receptors (types I and II) and increased phosphorylation of Smad 3 in keloid fibroblasts relative to NHDFs. These data support a possible role of TGF-beta and its receptors as fibrosis-inducing growth factors in keloids. In addition, all three isoforms of recombinant human TGF-beta proteins could further stimulate the expression of TGF-beta receptor II in both keloids and NHDFs. Taken together, these results substantiate the hypothesis that the elevated levels of TGF-beta ligands and receptors present in keloids may support increased signaling and a potential role for TGF-beta in keloid pathogenesis.

Ontogeny of expression of transforming growth factor-beta 1 (TGF-beta 1), TGF-beta 3, and TGF-beta receptors I and II in fetal rat fibroblasts and skin.

Fetal cutaneous wounds that occur in early gestation heal without scar formation. Although much work has been done to characterize the role of transforming growth factor-beta (TGF-beta) isoforms in the adult wound repair process, their function in fetal scarless wound repair is not well understood. The authors hypothesized that the pattern of expression for TGF-beta isoforms and their receptors may influence the phenotypic transition from scarless to scar-forming repair observed during fetal gestation. Using time-dated fetal Sprague-Dawley rat fibroblasts and unwounded skin at gestational ages 14, 16, 18, and 21 days postcoitum of the scarless (< or =16 days) and scar-forming (>16 days) periods of gestation (term = 21.5 days), the authors analyzed the endogenous messenger RNA (mRNA) levels of TGF-beta 1 and TGF-beta 3 and their signaling receptors TGF-beta-RI and TGF-beta-RII. Northern blot analyses in both fibroblasts and unwounded skin revealed that levels of TGF-beta 1 were not differentially expressed, whereas more TGF-beta 3 mRNA transcript was found in early than in late gestation. Fibroblast expression of TGF-beta-RI showed no substantial differences, whereas expression of TGF-beta-RII increased during gestation. In contrast, expression of both TGF-beta-RI and TGF-beta-RII in unwounded skin showed decreasing levels as a function of gestational age. The differential levels of TGF-beta 1 and TGF-beta 3 suggest that the ratio of these cytokines may provide a predominantly antiscarring or profibrotic signal upon wounding during the scar-free or scar-forming periods of gestation, respectively. Furthermore, lower amounts of the ligand-binding TGF-beta-RII seen in early gestation fibroblasts suggest a decreased ability to perceive ligand during the period of scarless repair.

Discoidin domain receptors and their ligand, collagen, are temporally regulated in fetal rat fibroblasts in vitro.

The biochemical regulation of collagen deposition during adult cutaneous wound repair is poorly understood. Likewise, how collagen is perceived and modulated in fetal scarless healing remains unknown. Recently, discoidin domain receptors-1 and 2 (DDR1 and DDR2) with tyrosine kinase activity have been identified as novel receptors for collagen. In light of these findings, it was speculated that the production of collagen receptors DDR1 and DDR2 by fetal fibroblasts may be temporally regulated to correlate with the ontogeny of embryonic scar formation. More specifically, because DDRs directly bind collagen and transmit the signals intracellularly, it was hypothesized that they may play an important role in fetal scarless healing by ultimately regulating and modulating collagen production and organization. As part of a fundamental assessment to elucidate the role of DDRs in scarless fetal wound repair, the endogenous expression of DDR1, DDR2, collagen I, and total collagen, as a function of fetal Sprague-Dawley rat skin fibroblasts of different gestational ages, representing scar-free (E16.5) periods was determined. Using explanted dermal fibroblasts of gestational days E13.5, E16.5, E18.5, and E21.5 (term gestation = 21.5 days) fetuses (n = 92), [3H]proline incorporation assay and Northern and Western blotting analysis were performed to compare the expressions of these molecules with scar-free and scar-forming stages of embryonic development. These results revealed a pattern of increasing collagen production with increasing gestational ages, whereas DDR1 expression decreased with increasing gestational age. This observation suggests that elevated levels of DDR1 may play an important role in scarless tissue regeneration by early gestation fetal fibroblasts. In contrast, DDR2 was expressed by fetal rat fibroblasts at a similar level throughout gestation. These data demonstrate for the first time the temporal expression of collagen and DDR tyrosine kinases in fetal rat fibroblasts as a function of gestational ages. Overall, these data suggest that differential temporal expression of the above-mentioned molecules during fetal skin development may play an important role in the ontogeny of scar formation. Future studies will involve the characterization of the biomolecular functions of these receptor kinases during fetal wound repair.

C. elegans mre-11 is required for meiotic recombination and DNA repair but is dispensable for the meiotic G(2) DNA damage checkpoint.

We investigated the roles of Caenorhabditis elegans MRE-11 in multiple cellular processes required to maintain genome integrity. Although yeast Mre11 is known to promote genome stability through several diverse pathways, inviability of vertebrate cells that lack Mre11 has hindered elucidation of the in vivo roles of this conserved protein in metazoan biology. Worms homozygous for an mre-11 null mutation are viable, allowing us to demonstrate in vivo requirements for MRE-11 in meiotic recombination and DNA repair. In mre-11 mutants, meiotic crossovers are not detected, and oocyte chromosomes lack chiasmata but appear otherwise intact. gamma-irradiation of mre-11 mutant germ cells during meiotic prophase eliminates progeny survivorship and induces chromosome fragmentation and other cytologically visible abnormalities, indicating a defect in repair of radiation-induced chromosome damage. Whereas mre-11 mutant germ cells are repair-deficient, they retain function of the meiotic G(2) DNA damage checkpoint that triggers germ cell apoptosis in response to ionizing radiation. Although mre-11/mre-11 animals derived from heterozygous parents are viable and produce many embryos, there is a marked drop both in the number and survivorship of embryos produced by succeeding generations. This progressive loss of fecundity and viability indicates that MRE-11 performs a function essential for maintaining reproductive capacity in the species.