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ABSTRACT We report on the detection of an extremely bright (∼37 mJy at 1100 μm and ∼91 mJy at 880 μm) submillimetre galaxy (SMG), AzTEC-ASTE-SXDF1100.001 (hereafter referred to as SXDF1100.001 or Orochi), discovered in the 1100 μm observations of the Subaru/ XMM-Newton Deep Field using AzTEC on ASTE. Subsequent CARMA 1300-μm and SMA 880-μm observations successfully pinpoint the location of Orochi and suggest that it has two components, one extended [full width at half-maximum (FWHM) of ∼4 arcsec] and one compact (unresolved). Z-Spec on CSO has also been used to obtain a wide-band spectrum from 190 to 308 GHz, although no significant emission/absorption lines were found. The derived upper limit to the line-to-continuum flux ratio is 0.1-0.3 (2σ) across the Z-Spec band. Based on the analysis of the derived spectral energy distribution from optical to radio wavelengths of possible counterparts near the SMA/CARMA peak position, we suggest that Orochi is a lensed, optically dark SMG lying at z ∼ 3.4 behind a foreground, optically visible (but red) galaxy at z ∼ 1.4. The deduced apparent (i.e., no correction for magnification) infrared luminosity ( LIR) and star formation rate (SFR) are 6 × 1013 L⊙ and 11 000 M⊙ yr−1, respectively, assuming that the LIR is dominated by star formation. These values suggest that Orochi will consume its gas reservoir within a short time-scale (3 × 107 yr), which is indeed comparable to those in extreme starbursts like the centres of local ultraluminous infrared galaxies (ULIRGs). [ABSTRACT FROM AUTHOR]

Abstract: We report the success of our first engineering run with Z-Spec, a new millimeter spectrograph on the 10m Caltech Submillimeter Telescope during the first week of June 2005. The bolometric instrument is indeed the first of its kind, covering the atmospheric window from 187 to 310GHz at the spectral resolution of 250–400, and will provide a critical follow-up study for discoveries by SCUBA and Bolocam. We present the spectrum of an ultra-luminous infrared galaxy NGG 6240 obtained by Z-Spec. Z-Spec serves as a prototype for future far-IR spectrometers on a cold space telescope where large gains in sensitivity are expected. [Copyright &y& Elsevier]

Background: Pertussis can cause a serious respiratory bacterial infection, especially in infants. Between January 1 and December 31, 2015, there was an increase in the number of reported pertussis cases in Nova Scotia (NS). Surveillance practices for pertussis in NS were challenging because immunization coverage data are not available and rate information was neither timely nor precise with respect to geography. Public health officials in NS decided to adopt a new surveillance technique to inform public health actions across the Province., Objective: To assess the use of a 40-day rolling incidence rate to monitor pertussis activity in Nova Scotia., Intervention: A 40-day rolling incidence rate was calculated for pertussis by age groups and various levels of geography. Public health authorities continued to anticipate new cases of pertussis if the contacts of known cases were still within the incubation period (range between six and 20 days). The 40-day incubation period was chosen to reflect twice the incubation period's upper range. Rates were calculated using Statistics Canada population projections for 2014 and then compared with traditional case counts and cumulative incidences. The usefulness of the statistics was assessed by public health decision makers., Outcomes: Increased pertussis activity was noted across NS, most notably in the South West region. The use of a 40-day rolling incidence rate as a surveillance tool provided more timely and geographically precise descriptions of ongoing trends in pertussis activity and helped to inform appropriate public health action. Health officials valued the information provided from the rolling incidence because it allowed them to manage activities based on weekly estimates at various levels of geography., Conclusion: Rolling incidence proved to be a useful tool to monitor a cyclical increase in pertussis cases in Nova Scotia and to inform related public health actions. The rolling incidence provided geographically precise and timely information that was useful to estimate new cases in the absence of reliable immunization coverage information. This method could supplement traditional epidemiological surveillance of future communicable disease events, especially those characterized by long incubation periods and low case counts., Competing Interests: Conflict of interest: None.

Massive present-day early-type (elliptical and lenticular) galaxies probably gained the bulk of their stellar mass and heavy elements through intense, dust-enshrouded starbursts--that is, increased rates of star formation--in the most massive dark-matter haloes at early epochs. However, it remains unknown how soon after the Big Bang massive starburst progenitors exist. The measured redshift (z) distribution of dusty, massive starbursts has long been suspected to be biased low in z owing to selection effects, as confirmed by recent findings of systems with redshifts as high as ~5 (refs 2-4). Here we report the identification of a massive starburst galaxy at z = 6.34 through a submillimetre colour-selection technique. We unambiguously determined the redshift from a suite of molecular and atomic fine-structure cooling lines. These measurements reveal a hundred billion solar masses of highly excited, chemically evolved interstellar medium in this galaxy, which constitutes at least 40 per cent of the baryonic mass. A 'maximum starburst' converts the gas into stars at a rate more than 2,000 times that of the Milky Way, a rate among the highest observed at any epoch. Despite the overall downturn in cosmic star formation towards the highest redshifts, it seems that environments mature enough to form the most massive, intense starbursts existed at least as early as 880 million years after the Big Bang.

Objective: To assess the current prevalence of depression and anxiety among Ontario family medicine residents, and to describe their coping strategies., Design: Surveys mailed to residents integrated DSM-IV diagnostic criteria and a previously validated Patient Health Questionnaire., Setting: Ontario family medicine programs from June to August 2002., Participants: Residents entering, advancing in, or graduating from residency programs: approximately 216 yearly for a total of 649 residents., Main Outcome Measures: Types and frequency of coping skills used by residents; prevalence of depressive and anxiety disorders., Results: Response rate for residents entering programs was 46% and for graduating residents was 30% (37% response rate overall). Prevalence of depressive disorders was 20% (13% major depressive disorders, 7% other depressive syndromes)(odds ratio [OR] 3.4, confidence interval [CI] 2.7 to 7.5, P < .001). Prevalence of generalized anxiety disorder was 12%, and 2% of residents met criteria for panic syndrome (OR 4.3, CI 1.6 to 11.8, P = .002). Rates were similar for men and women. Medical training was commonly identified as a negative influence on the mental health of troubled residents. Residents most often turned to family and friends when they needed help (43.7% of respondents). About 17.3% saw their family doctors, 15.4% counselors, and 7.9% psychiatrists. Some residents (13.4%) used medication to deal with their affective symptoms, 7.1% underwent cognitive-behavioural therapy, and 8.3% required a leave of absence from their programs. More than half (61.8%) indicated recreational use of alcohol and drugs, 1.2% identified use due to addiction, and 5.9% used drugs to help cope with their problems. Four respondents admitted concern that they might commit suicide during residency; a different three had made previous attempts., Conclusion: Affective disorders (both depression and anxiety syndromes) are three to four times more common among Ontario family practice residents than in the general population; male and female residents are equally affected. Most residents with these problems report negative effects on their function at work. Medical training is the most commonly identified negative influence on mental health. While residents most often obtain help from family members and friends, many seek professional help.

Objective: We tested the hypothesis that a 6-week course of a nasal glucocorticoid spray would decrease the severity of obstructive sleep apnea in children with adenotonsillar hypertrophy., Study Design: We conducted a randomized, triple-blind, placebocontrolled, parallel-group trial of nasal fluticasone propionate versus placebo in 25 children aged 1 to 10 years with obstructive sleep apnea proven on polysomnography. The primary outcome was the change from baseline in the frequency of mixed and obstructive apneas and hypopneas., Results: Thirteen children received fluticasone, and 12 received placebo. The mixed/obstructive apnea/hypopnea index decreased from 10.7 +/- 2.6 (SE) to 5.8 +/- 2.2 in the fluticasone group but increased from 10.9 +/- 2.3 to 13.1 +/- 3.6 in the placebo group, P =.04. The mixed/obstructive apnea/hypopnea index decreased in 12 of 13 subjects treated with fluticasone versus 6 of 12 treated with placebo, P =.03. The frequencies of hemoglobin desaturation and respiratory movement/arousals also decreased more in the fluticasone group. Changes from baseline in tonsillar size, adenoidal size, and symptom score were not significantly different between groups., Conclusion: Nasal fluticasone decreased the frequency of mixed and obstructive apneas and hypopneas, suggesting that topical corticosteroids may be helpful in ameliorating pediatric obstructive sleep apnea.

Objective: Pulmonary fibrosis, a frequent manifestation of systemic sclerosis (SSc), is considered incurable. Our aim was to assess the effect of therapy with intravenous (i.v.) cyclophosphamide on the course of pulmonary fibrosis in patients with SSc., Methods: Five patients with SSc and clinical, laboratory, or radiographic findings of interstitial lung disease were treated with cyclophosphamide (1 g) administered i.v. monthly for 48 weeks. The dyspnea score, pulmonary function tests, arterial blood oxygen content, radiologic abnormalities, and bronchoalveolar lavage (BAL) fluid cellularity were determined before and after therapy., Results: The dyspnea score decreased by 42% after 48 weeks of therapy. Forced vital capacity (FVC, percentage of predicted) increased by 7%, and carbon monoxide diffusing capacity (DLCO) decreased by 12%, but these changes were not statistically significant. Arterial blood oxygenation remained unchanged. At baseline, high resolution computed tomography of the lungs showed honeycombing, reticulonodular, or ground glass patterns in each patient examined. These radiologic abnormalities did not improve during treatment. A marked decrease in BAL fluid cell number, but not in the percentage of neutrophils, was observed after therapy. Nausea and leukopenia were frequent but mild side effects. One patient developed hemorrhagic cystitis., Conclusion: The results suggest that intermittent treatment with i.v. cyclophosphamide reduces the severity of dyspnea, but fails to improve FVC or DLCO, or cause resolution of radiologic abnormalities, in patients with SSc.

Though preventive health care can be beneficial, many children do not receive regular well-child care. To gain insight into the reasons for the underuse of well-child care, this qualitative study elicited consumers' views by examining how mothers in a rural state perceive well-child care, its benefits, and barriers to obtaining it. Twenty-one women in two Wyoming counties were interviewed about their knowledge and beliefs about well-child care and the care their children had received. Five categories of responses for the definition of well-child care, 10 categories of benefits, and seven categories of barriers were identified. Most of the informants valued well-child as providing maternal reassurance, information, identification of problems, developmental testing, preventive care, and health maintenance, and would obtain the recommended care if the barriers they perceived, such as financial limitations and inconvenience, were removed or reduced. Primary care providers can promote the use of well-child care in numerous ways, including educating consumers on the purposes, benefits, and schedule for preventive care, providing services that consumers value, providing high quality care, and providing cues-to-action to promote consumers to make and keep appointments.

Objective: Fibrosing alveolitis is a prominent feature of systemic sclerosis (SSc), and accounts for much of the morbidity and mortality of this disease. Sensitive techniques for the detection and monitoring of fibrosing alveolitis could target patients for early therapeutic intervention. The objective of this small pilot study was to assess the frequency and clinical significance of abnormal lung uptake of Tc-99m MIBI, a novel radionuclide imaging agent that selectively accumulates in cells rich in mitochondria., Methods: Sixteen patients with SSc and evidence of pulmonary involvement were studied. The uptake of radionuclide in the lungs, and the ratio of pulmonary to cardiac uptake were evaluated after intravenous injection of Tc-99m MIBI. Results were correlated with clinical and laboratory parameters., Results: Lung uptake of Tc-99m MIBI was increased in all 16 SSc patients compared to control patients with coronary heart disease but no evidence of pulmonary abnormality. The degree of isotope uptake in the lungs was correlated with the extent of maximal skin induration and with radiologic evidence of interstitial lung disease, but not with other clinical or laboratory parameters of disease activity or extent of pulmonary involvement. The ratio of pulmonary to cardiac uptake of isotope was also increased in patients with SSc compared to controls., Conclusion: Accumulation of Tc-99m MIBI is abnormally elevated in the lungs of SSc patients with pulmonary involvement. Isotope accumulation in the lungs may be related to activation of fibroblasts or endothelial cells. The specificity and sensitivity of Tc-99m MIBI scanning in the detection and monitoring of pulmonary involvement, and its potential role in the management of SSc, deserve further investigation.

Objective: To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blood and affected tissues, in patients with diffuse and limited cutaneous forms of systemic sclerosis (SSc)., Methods: Levels of the eosinophil-derived major basic protein (MBP), a marker of eosinophil degranulation, were determined in sera from 46 SSc patients, from patients with rheumatoid arthritis and giant cell arteritis, and from healthy volunteers, and in bronchoalveolar lavage fluid from 4 SSc patients. Extracellular tissue deposition of MBP was evaluated in biopsy specimens from affected skin or lung of 11 SSc patients., Results: Patients with diffuse cutaneous SSc (dcSSc) had elevated serum MBP levels compared with normal individuals (mean +/- SD 762 +/- 271 ng/ml versus 534 +/- 144 ng/ml; P = 0.0004). MBP levels were positively correlated with the extent of cutaneous involvement, and negatively correlated with pulmonary function and duration of disease (r = -0.20). By immunohistochemical analysis, modest extracellular MBP deposition could be demonstrated in involved skin in 7 of 10 biopsy specimens, and MBP staining was prominent in affected lung tissues in 2 patients., Conclusion: Eosinophil degranulation appears to be increased in some patients with dcSSc, as indicated by elevated serum levels of MBP and extracellular accumulation of MBP in the lung. Eosinophil granule proteins may contribute to the development of cutaneous and pulmonary fibrosis in SSc.

Objective: To describe the clinical, radiologic, and pathologic features of coexistent systemic sclerosis (SSc) and sarcoidosis, 2 conditions of unknown cause associated with altered cellular immune response., Methods: We reviewed clinical information, results from laboratory and radiologic studies, and lung or lymph node biopsy samples of 7 patients with concurrent SSc and sarcoidosis evaluated at 2 academic referral centers between 1989 and 1993., Results: Each patient fulfilled American College of Rheumatology criteria for the classification of SSc. SSc and sarcoidosis developed simultaneously in 4 patients, whereas in 3 others sarcoidosis was diagnosed more than 6 years after the onset of SSc. The onset of sarcoidosis was characterized by fever, weight loss, or increasing respiratory symptoms. Each patient had radiographic evidence of intrathoracic lymphadenopathy and/or interstitial lung disease. Examination of lung or lymph node biopsies demonstrated noncaseating granulomas. Treatment with corticosteroids was associated with improved lung function., Conclusion: Since sarcoidosis coexists with SSc more frequently than previously suggested, it should be considered in patients with SSc presenting with new pulmonary symptoms. Recognizing sarcoidosis in patients with SSc is important, since these patients may benefit from corticosteroid therapy.

Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer which has been reported to induce a statistically significant increase in the incidence of hepatocellular carcinomas in female Fischer-344 rats (8/50) when administered in the diet at 12 000 p.p.m. for two years. Numerous studies with cells in culture have failed to show any genotoxic activity associated with DEHP. Because DEHP induces multiple changes in the liver, such as peroxisomal proliferation, it was possible that these alterations could result in genotoxic effects in the treated whole animal that would not be seen in cells in culture. Accordingly, the ability of DEHP to induce DNA damage or repair was examined in rat hepatocytes in vivo and in vitro and in human hepatocytes in vitro. Unscheduled DNA synthesis was measured by incorporation of [3H]thymidine into primary hepatocyte cultures immediately isolated from treated animals or hepatocyte cultures incubated directly with DEHP. DNA damage was measured by alkaline elution of cellular DNA from the same cultures. In vivo-in vitro treatment regimens were: (i) female rats, 12 000 p.p.m. DEHP in the diet for 30 days; (ii) female rats, 12 000 p.p.m. in the diet for 30 days, followed by 500 mg/kg DEHP by gavage 2 h before sacrifice; (iii) male rats, 500 mg/kg DEHP by gavage 2, 12, 24, or 48 h before sacrifice; and (iv) male rats, 150 mg/kg/day by gavage for 14 days. In vitro conditions were 0.1, 1.0 and 10.0 mM DEHP in the cultures for 18 h. Primary cultures of human hepatocytes were prepared from freshly discarded surgical material and exposed to the same concentration of DEHP. Concentrations up to 0.5 mM mono(2-ethylhexyl)phthalate, a principal metabolite of DEHP, were also examined in the human hepatocyte assay. No chemically induced DNA damage or repair was observed in vivo or in vitro in rat or human hepatocytes under any of the conditions employed. However, an increase in the percentage of cells in S-phase in the animals given DEHP was observed. These data indicate that DEHP does not exhibit direct genotoxic activity in the animals even with a treatment regimen which eventually produced tumors in a long term bioassay, and that both rat and human hepatocytes are similar in their lack of a genotoxic response to DEHP exposure in culture.

Often results from toxicological studies using rodent models cannot be directly extrapolated to probable effects in human beings. In order to examine the genotoxic potential of chemicals in human liver cells, a human hepatocyte DNA repair assay has been defined. Procedures were optimized to prepare primary cultures of human hepatocytes from discarded surgical material. On eight different occasions human hepatocyte cultures of sufficient viability to measure DNA repair were successfully prepared by collagenase perfusion techniques. The cells were allowed to attach to plastic or collagen substrata for periods of 1.5 to 24 h and subsequently incubated with [3H]thymidine and test chemicals for periods of 18 to 24 h. Chemically induced DNA repair, measured as unscheduled DNA synthesis, was quantitated autoradiographically. The following compounds were tested: 2-acetylaminofluorene, aflatoxin B1, 2-aminobenzyl alcohol, aniline, benzo(a)pyrene, carbon tetrachloride, chloroform, 2,4-diaminotoluene, 2,6-diaminotoluene, di(2-ethylhexyl)phthalate, dimethylnitrosamine, 1,6-dinitropyrene, 2,4-dinitrotoluene, 2,6-dinitrotoluene, methyl chloride, 5-methylchrysene, mono(2-ethylhexyl)phthalate, 2-methyl-2-P-(1,2,3,4-tetrahydro-1-naphthyl)phenoxypropionic acid (nafenopin), beta-naphthylamine, nitrobenzene, 2-nitrobenzyl alcohol, 2-nitrotoluene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, unleaded gasoline, and 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14,643). In only one of eight cases did some of the chemicals generally regarded as genotoxic fail to give a positive response. For purposes of comparison, all test chemicals were evaluated in the in vitro rat hepatocyte DNA repair assay. Individual-to-individual variation in the DNA repair response was far greater for the human cultures than for cultures derived from rats. For only three chemicals was there a qualitative difference in the response between the rodent and the human cells; beta-naphthylamine was positive in the rat but in none of the human cultures examined, whereas the opposite was seen for 2,6-diaminotoluene and 5-methylchrysene. Clofibric acid, mono(2-ethylhexyl)phthalate, and Wy-14,643 induced enzymes indicative of peroxisomal proliferation in primary rat hepatocyte cultures, but not in two human hepatocyte cultures. These results indicate that, in general, the in vitro rat hepatocyte DNA repair assay is a valid model for predicting potential genotoxic effects in human beings. However, rodent hepatocytes may not be appropriate for assessing the potential of chemicals to elicit nongenotoxic effects in human beings such as the induction of hepatocyte peroxisomal proliferation.

Exposure of rats to nitrobenzene produces a degeneration of the seminiferous epithelium of the testes. Sperm production was continuously monitored in rats surgically prepared by anastomosing the vas deferentia with the urinary bladder to evaluate the reversibility of nitrobenzene toxicity. Rates of sperm production were monitored by collecting urine and counting sperm microscopically with a hemocytometer. Six weeks after surgery, rats were dosed p.o. with a single dose of 300 mg/kg of nitrobenzene in corn oil. Sperm were not detected in the urine of treated rats between 32 and 48 days after treatment. Despite the fact that degenerative changes in the seminiferous tubules were observed histologically as early as 3 days after dosing, there was a 32-day lag period between treatment and cessation of sperm output in treated rats. Histological examination showed that pachytene spermatocytes and step 1-2 spermatids were the most susceptible cell stages to nitrobenzene and were observed forming into giant cells as early as 3 days after treatment. However, repair was substantial by 3 weeks after treatment and by days 76-100, the rate of sperm output reached 78% of the control group. By 100 days after treatment, there was greater than 90% regeneration of the seminiferous epithelium. Thus, a single oral dose of nitrobenzene induced testicular degeneration and approximately a 17-day period of aspermia resulted. Back-dating of the aspermic period to the timing of the spermatogenic cycle closely corresponded with the same germ cell stages that were observed degenerating in histologic examinations. Thus, changes in sperm output from vasocystotomized rats correlated well with histopathologic changes, demonstrating the value of this technique for toxicity studies.