Measurement of the

The cross section of the ^{13}C(α,n)^{16}O reaction is needed for nuclear astrophysics and applications to a precision of 10% or better, yet inconsistencies among 50 years of experimental studies currently lead to an uncertainty of ≈15%. Using a state-of-the-art neutron detection array, we have performed a high resolution differential cross section study covering a broad energy range. These measurements result in a dramatic improvement in the extrapolation of the cross section to stellar energies potentially reducing the uncertainty to ≈5% and resolving long standing discrepancies in higher energy data.

Nonfuel Antineutrino Contributions in the High Flux Isotope Reactor.

Reactor neutrino experiments have seen major improvements in precision in recent years. With the experimental uncertainties becoming lower than those from theory, carefully considering all sources of ν ¯ e is important when making theoretical predictions. One source of ν ¯ e that is often neglected arises from the irradiation of the nonfuel materials in reactors. The ν ¯ e rates and energies from these sources vary widely based on the reactor type, configuration, and sampling stage during the reactor cycle and have to be carefully considered for each experiment independently. In this article, we present a formalism for selecting the possible ν ¯ e sources arising from the neutron captures on reactor and target materials. We apply this formalism to the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory, the ν ¯ e source for the the Precision Reactor Oscillation and Spectrum Measurement (PROSPECT) experiment. Overall, we observe that the nonfuel ν ¯ e contributions from HFIR to PROSPECT amount to 1% above the inverse beta decay threshold with a maximum contribution of 9% in the 1.8-2.0 MeV range. Nonfuel contributions can be particularly high for research reactors like HFIR because of the choice of structural and reflector material in addition to the intentional irradiation of target material for isotope production. We show that typical commercial pressurized water reactors fueled with low-enriched uranium will have significantly smaller nonfuel ν ¯ e contribution.

Measurement of the Antineutrino Spectrum from

This Letter reports the first measurement of the ^{235}U ν[over ¯]_{e} energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85 MW_{th} highly enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) ν[over ¯]_{e}-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to ^{235}U. Despite broad agreement, comparison of the Huber ^{235}U model to the measured spectrum produces a χ^{2}/ndf=51.4/31, driven primarily by deviations in two localized energy regions. The measured ^{235}U spectrum shape is consistent with a deviation relative to prediction equal in size to that observed at low-enriched uranium power reactors in the ν[over ¯]_{e} energy region of 5-7 MeV.

First Search for Short-Baseline Neutrino Oscillations at HFIR with PROSPECT.

This Letter reports the first scientific results from the observation of antineutrinos emitted by fission products of ^{235}U at the High Flux Isotope Reactor. PROSPECT, the Precision Reactor Oscillation and Spectrum Experiment, consists of a segmented 4 ton ^{6}Li-doped liquid scintillator detector covering a baseline range of 7-9 m from the reactor and operating under less than 1 m water equivalent overburden. Data collected during 33 live days of reactor operation at a nominal power of 85 MW yield a detection of 25 461±283 (stat) inverse beta decays. Observation of reactor antineutrinos can be achieved in PROSPECT at 5σ statistical significance within 2 h of on-surface reactor-on data taking. A reactor model independent analysis of the inverse beta decay prompt energy spectrum as a function of baseline constrains significant portions of the previously allowed sterile neutrino oscillation parameter space at 95% confidence level and disfavors the best fit of the reactor antineutrino anomaly at 2.2σ confidence level.

Calciphylaxis in a patient with normal renal function: response to treatment with sodium thiosulfate.

Calciphylaxis is a rare, life-threatening cause of skin necrosis. The condition is primarily reported in patients with end-stage renal disease, and is associated with significant morbidity and mortality. Treatment has mainly been empirical. We report a case of calciphylaxis in a patient with normal renal function and hypoparathyroidism, who responded to treatment with sodium thiosulfate. To our knowledge, this is the first reported case of the use of sodium thiosulfate to treat calciphylaxis in a patient with normal renal function.

Tinea capitis in a paediatric population.

Tinea capitis is an increasing problem in Europe. The pattern of infection is changing with an increase in pathogenic anthropophilic dermatophytes particularly Trichophyton tonsurans. We aimed to determine the frequency of tinea capitis in a paediatric population attending dermatology outpatients and examine the clinical spectrum of disease. A retrospective analysis was performed of all laboratory proven tinea capitis cases presenting to the dermatology outpatient department at The Children's University Hospital, Temple Street over an 18-month period (1st January 2004 to 30th of June 2005 inclusive). Sixty-two children had tinea capitis of whom 53 (85.5%) were of African descent. Thirty-five (56%) were male and 27 female (44%). The average age at presentation was 4.02 years (age range 1-163 months) with five cases occurring in children less than one year of age. The most common pathogen was the anthropophilic dermatophyte Trichophyton tonsurans, accounting for 47 (75.8%) of all cases of tinea capitis. Eight (12.9%) were secondary to Microsporum ferrigineum, 2 (3.2%) secondary to Trichophyton violaceum, both Trichophyton soudanese and Trichophyton verruosum accounted for 1.6% each. The zoophilic organism Microsporum canis was diagnosed in 3 cases (4.8%). Presenting signs included scaling of the scalp (35.47%), scaling of the scalp and alopecia (53.24%), and alopecia and kerion (11.29%/o). The duration of symptoms was recorded in 52 patients with the average duration 8.38 months (range 0.5-72 months). In 20 cases an associated skin involvement on other areas of the body was recorded. All patients at diagnosis were either on no, suboptimal or inappropriate treatment. The prevalence of tinea capitis is increasing in this hospital based cohort. The main pathogen is now Trichophyton tonsurans. Children of African descent are at increased risk of infection. The diagnosis is poorly recognized and needs to be highlighted as a public health issue. There is a need for community based prevalence studies.

Ribosomal DNA internal transcribed spacer (ITS2) sequences differentiate Anopheles funestus and An. rivulorum, and uncover a cryptic taxon.

Differentiation among the closely related Afrotropical species comprising the Funestus Group is difficult by traditional taxonomic measures. Anopheles rivulorum is the second most abundant and widespread species in the Funestus Group, and is occasionally collected indoors along with the dominant member and major malaria vector, An. funestus. The prospect of misidentification of An. rivulorum as An. funestus prompted the development of a rapid, polymerase chain reaction (PCR)-based method for identifying these two species. The ribosomal internal transcribed spacer 2 (ITS2) was amplified from thirty-five specimens of An. rivulorum collected from the extremes of its range: Eastern Africa (Kenya), Southern Africa (South Africa) and Western Africa (Burkina Faso). The ITS2 region of An. rivulorum ( approximately 380 bp) is sufficiently different in size from the ITS2 of An. funestus ( approximately 700 bp) that these species can be distinguished by agarose gel electrophoresis of PCR products without further manipulation. Comparison of the An. rivulorum and An. funestus ITS2 nucleotide sequences revealed such extensive divergence that meaningful alignment was impossible, except for a 25 bp island near the 5' end. Intraspecific sequence comparisons revealed no variation among An. rivulorum individuals collected from the same country. However, sequence divergence was 2% between specimens from South Africa and Kenya, and nearly tenfold higher ( approximately 19%) between specimens from Burkina Faso and either South Africa or Kenya, an unprecedented level of intraspecific ITS2 divergence in Anopheles. Taken together, these data suggest that the Burkina Faso sample is not An. rivulorum, but rather a cryptic taxon within the Funestus Group.

Left-right axis malformations in man and mouse.

The study of left-right axis malformations in man and mouse has greatly advanced understanding of the mechanisms regulating vertebrate left-right axis formation. Recently, the roles of the TGF-beta family, Sonic hedgehog and fibroblast growth factor signaling, homeobox genes, and cilia in left-right axis determination have been more clearly defined. The identification of genes and environmental factors affecting left-right axis formation has important implications for understanding human laterality defects.

Mutation of the mouse hepatocyte nuclear factor/forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry.

Winged helix transcription factors play important roles in cellular differentiation and cell-specific gene expression. To define the role of the winged helix factor hepatocyte nuclear factor/forkhead homologue (HFH)-4, a targeted mutation was created in the mouse hfh-4 gene. No expression of HFH-4 was detected in hfh-4(-)/- mice by RNA blot analysis, in situ hybridization, or RT-PCR. hfh-4(-)/- mice were noted to have abnormalities of organ situs consistent with random determination of left-right asymmetry. In addition, a complete absence of cilia was noted in hfh-4(-)/- mice. The hfh-4 gene is thus essential for nonrandom determination of left-right asymmetry and development of ciliated cells. Homozygous mutant mice also exhibited prenatal and postnatal growth failure, perinatal lethality and, in some cases, hydrocephalus. RT-PCR revealed an absence of left-right dynein (lrd) expression in the embryonic lungs of hfh-4(-)/- mice, suggesting that HFH-4 may act by regulating expression of members of the dynein family of genes. The abnormalities in ciliary development and organ situs in hfh-4(-)/- mice are similar to those observed in human congenital syndromes such as Kartagener syndrome. Targeted mutation of hfh-4 thus provides a model for elucidating the mechanisms regulating ciliary development and determination of left-right asymmetry.

Intraoperative localization of small intestinal bleeding in an infant by methylene blue injection: a case report.

During the evaluation of patients with profuse gastrointestinal bleeding, it is often difficult to accurately localize bleeding sites in the small intestine. Moreover, during laparotomy, there may be no intraoperative findings to allow identification and resection of the bleeding lesion. Here the authors report a case of severe intestinal bleeding in an infant in whom the intraoperative injection of methylene blue dye into a terminal branch of the superior mesenteric artery was critical in determining the exact location of bleeding. After accurate localization of the bleeding source and segmental intestinal resection, the child recovered uneventfully with no recurrence of gastrointestinal bleeding. To the authors' knowledge, this is the first reported use of this technique in infancy.

A human forkhead/winged-helix transcription factor expressed in developing pulmonary and renal epithelium.

Members of the forkhead/winged-helix transcription factor family play crucial roles during vertebrate development. A human hepatocyte nuclear factor/forkhead homolog (HFH)-4 cDNA encoding a 421-amino acid protein was isolated from a human fetal lung cDNA library. By Southern blot analysis of human-rodent somatic cell hybrid genomic DNA, the human HFH-4 gene localizes to chromosome 17q23-qter. This is the locus of another forkhead/winged-helix gene, the interleukin enhancer binding factor gene. RNA blot analysis revealed a 2.5-kilobase human HFH-4 transcript in fetal lung, kidney, and brain as well as in adult reproductive tissues, lung, and brain. By in situ hybridization, HFH-4 expression is associated with differentiation of the proximal pulmonary epithelium, starting during the pseudoglandular stage of human lung development. During human renal morphogenesis, HFH-4 is expressed in the developing epithelial cells of the ureteric duct, glomerulus, and epithelial vesicles. The unique pattern of HFH-4 expression during human fetal development suggests a role for this forkhead/winged-helix factor during pulmonary and renal epithelial development.

Serum amyloid A gene expression in rabbit, mink and mouse.

The expression of serum amyloid A (SAA) protein, a major acute-phase reactant in most species, was examined by in situ hybridization in multiple organs of rabbit, mink and mouse. In livers of unstimulated mice and rabbits a heterogeneous pattern of SAA expression in hepatocytes was observed. In all three species, lipopolysaccharide (LPS) administration resulted in extensive uniform hybridization of SAA probes to hepatocytes and in the rabbit SAA transcripts were detected in cells in the white pulp of the spleen, the adrenal cortex and ovary as well as in the mucosa and lymphatic vessels of the small intestine. Examination of hybridizing SAA signals in the rabbit myocardium showed a speckled distribution in myocytes. The rabbit endocardium was strongly positive, and in the kidney rabbit SAA mRNA was mainly confined to epithelial cells of the proximal and distal convoluted tubules. In the unstimulated mouse, SAA mRNA was detected in the liver and epithelial cells of the small and large intestine. After stimulation of an acute-phase response with LPS a strong response was seen in these organs as well as in the convoluted tubules of the kidney. In extrahepatic organs of the mink, no SAA mRNA was detectable in unstimulated animals, while the convoluted tubules of the kidney and uterine endometrium were strongly positive after systemic LPS injection.

Structural characterization of the mouse Hfh4 gene, a developmentally regulated forkhead family member.

Hepatocyte nuclear factor-3/forkhead homologue 4 (HFH-4) is a forkhead/winged-helix transcription factor family member that has a unique temporal and spatial pattern of gene expression in the developing and adult lung, choroid plexus, testis, and oviduct. To characterize HFH-4 further, mouse genomic clones were isolated and analyzed. The Hfh4 gene is encoded on a 5.5-kb region located on the distal end of mouse chromosome 11 and consists of two exons and one intron. Unlike most forkhead genes, the DNA binding domain is divided between two exons, and the intron position corresponds precisely to the site of gene translocations involving two known human forkhead homologues. Multiple putative transcription start sites are identified in a G+C-rich sequence that does not contain TATA or CAAT boxes. Within 2.1 kb of 5' flanking sequence are three identical E boxes and multiple putative transcription factor binding sites. Transfection of plasmids containing Hfh4 5' flanking sequence linked to a reporter gene results in promoter activity in lung epithelial cells but not in epithelial-like fibrosarcoma cells, suggesting that this 5' flanking sequence can function as a promoter with the proper cell-type specificity.

Mechanisms of gene expression and cell fate determination in the developing pulmonary epithelium.

The pulmonary epithelium is a derivative of the foregut endoderm. Proliferation and differentiation of the primitive pulmonary epithelium result in an array of epithelial cell phenotypes that determine lung function and the response of the lung to injury, infection, or neoplastic transformation. The establishment of a cell phenotype requires the presence of transcription factors that activate or repress expression of specific genes. Members of the forkhead family of transcription factors, in particular HNF-3 alpha, HNF-3 beta, HFH-4; the homeodomain protein TTF-1; and N-myc, are all expressed in the developing pulmonary epithelium and may play important regulatory roles during development. Two genes specific to the pulmonary epithelium, the surfactant protein A and Clara cell secretory protein genes, serve as useful paradigms for understanding the mechanisms regulating cell-specific gene expression in the pulmonary epithelium.

Are health undertakings effective in the follow-up of migrants for tuberculosis?

OBJECTIVE: To determine the rate of compliance of migrants issued with a health undertaking for tuberculosis requiring them to report within one month after arrival in Australia. DESIGN: Compliance was monitored prospectively between 1 November 1992 and 31 October 1993. SETTING: The Australian Government Health Service in Melbourne. PARTICIPANTS: 1660 migrants with a health undertaking for tuberculosis. MAIN OUTCOME MEASURE: Compliance with the undertaking (making initial contact and presenting for examination). RESULTS: The overall compliance rate was 58%, but 89% of those who made contact complied with their undertakings. There were significant differences in the compliance rates according to country of application (P < 0.001). It was estimated that about 150 people a year who require treatment for tuberculosis could be failing to comply with a health undertaking, eight of whom may require a full course of antituberculous chemotherapy. CONCLUSIONS: The administration of the current system of health undertakings for tuberculosis for migrants needs to be strengthened to increase compliance.

Role of hepatocyte nuclear factor-3 alpha and hepatocyte nuclear factor-3 beta in Clara cell secretory protein gene expression in the bronchiolar epithelium.

The 5' flanking region of the Clara cell secretory protein (CCSP) gene contains two cis-acting elements which bind hepatocyte nuclear factor (HNF)-3 alpha and HNF-3 beta in vitro. To determine the role of these proteins in mediating CCSP gene expression in the bronchiolar epithelium, chimeric CCSP-reporter gene constructs containing various regions of the CCSP 5' flanking region were co-transfected into H-441 cells with HNF-3 alpha or HNF-3 beta expression plasmids. These studies indicate that each of these transcription factors positively regulates CCSP gene expression and revealed that CCSP region I (-132 to -76) is sufficient to mediate this effect. Gel-mobility-shift assays with oligonucleotides corresponding to CCSP region I, nuclear extract from bronchiolar epithelial cells and HNF-3-specific antibodies indicate that HNF-3 alpha and HNF-3 beta are the only proteins in bronchiolar epithelial cells which directly interact with this region. Consistent with these observations, HNF-3 alpha and HNF-3 beta transcripts were found to be enriched in this cell population and in situ hybridization of adult lung revealed HNF-3 gene expression in non-ciliated bronchiolar epithelial cells expressing the CCSP gene. Finally, experiments with CCSP region I and a heterologous promoter indicate that this region acts in a promoter-specific context, suggesting that additional factors interacting via the minimal CCSP promoter region are essential in determining the effects of HNF-3 on cell-specific CCSP gene expression in the bronchiolar epithelium.

Primary structure of hepatocyte nuclear factor/forkhead homologue 4 and characterization of gene expression in the developing respiratory and reproductive epithelium.

Members of the winged helix/forkhead family of transcription factors are believed to play a role in cell-specific gene expression. A cDNA encoding a member of this family of proteins, termed hepatocyte nuclear factor/forkhead homologue 4 (HFH-4), has been isolated from rat lung and rat testis cDNA libraries. This cDNA contains an open reading frame of 421 amino acids with a conserved DNA binding domain and several potential transactivating regions. During murine lung development, a single species of HFH-4-specific transcript (2.4 kb long) is first detected precisely at the start of the late pseudoglandular stage (embryonic day 14.5) and, by in situ hybridization, is specifically localized to the proximal pulmonary epithelium. The unique temporal and spatial pattern of HFH-4 gene expression in the developing lung defines this protein as a marker for the initiation of bronchial epithelial cell differentiation and suggests that it may play an important role in cell fate determination during lung development. In addition to expression in the pulmonary epithelium, RNA blot analysis reveals 2.4-kb HFH-4 transcripts in the testis and oviduct. By using mice with genetic defects in spermatogenesis, HFH-4 expression in the testis is found to be associated with the appearance of haploid germ cells and in situ hybridization studies indicate that HFH-4 expression is confined to stages I-VII of spermatogenesis. This pattern of HFH-4 gene expression during the early stages of differentiation of haploid germ cells suggests that HFH-4 may play a role in regulating stage-specific gene expression and cell-fate determination during lung development and in spermatogenesis.

5' flanking region of the Clara cell secretory protein gene specifies a unique temporal and spatial pattern of gene expression in the developing pulmonary epithelium.

Expression of a transgene containing 2.25 kb of the 5' flanking region of the rat Clara cell secretory protein gene and the human growth hormone gene was examined in developing mice. Despite an absolute preservation of tissue specificity based on RNA blot analysis, transgene-specific transcripts were detectable as early as 12.5 days of gestation, at least 4 days prior to endogenous Clara cell secretory protein gene expression. As differentiation proceeded, in situ hybridization revealed an increasingly restricted pattern of transgene expression in the developing pulmonary epithelium, such that by day 16.5 of gestation endogenous and transgene expression were confined to identical cells within the bronchiolar epithelium. The temporal discordance in transgene expression suggests the presence of unique cis-acting elements within the Clara cell secretory protein gene, not present in the transgene, which transduce developmental timing within pulmonary epithelium by actively repressing Clara cell secretory protein gene expression during early development. The unique expression of this transgene serves as a lineage marker in the respiratory epithelium and unmasks a temporal and spatial pattern of gene expression not observed in any pulmonary genes.