Neutrophil gelatinase-associated lipocalin: its response to hypoxia and association with acute mountain sickness.

Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly (P < 0.001) from 68 ± 14 (60-102) at 1300 m to 183 ± 107 (65-519); 143 ± 66 (60-315) and 150 ± 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS

Preface

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 103 (2014): 1-5, doi:10.1016/j.dsr2.2014.02.007.The Gulf of Maine (GOM) is a continental shelf sea in the northwest Atlantic, USA that supports highly-productive shellfisheries that are frequently contaminated by toxigenic Alexandrium fundyense blooms and outbreaks of paralytic shellfish poisoning (PSP), resulting in significant economic and social impacts. Additionally, an emerging threat to these resources is from blooms of toxic Pseudo-nitzschia species that produce domoic acid, the toxin responsible for amnesic shellfish poisoning (ASP). Nearshore shellfish toxins are monitored by state agencies, whereas most offshore stocks have had little or no routine monitoring. As a result, large areas of federal waters have been indefinitely closed or their shellfish beds underexploited because of the potential risk these toxins pose and the lack of scientific understanding and management tools. Patterns and dynamics of Alexandrium blooms and the resulting shellfish toxicity in nearshore waters were examined in a number of research projects, the largest being the Ecology and Oceanography of Harmful Algal Blooms (ECOHAB)-Gulf of Maine (GOM), a five-year regional program emphasizing field surveys, laboratory studies and numerical modeling. At the completion of the ECOHAB-GOM program (documented in Anderson et al., 2005), great progress was made in understanding A. fundyense blooms and resulting shellfish toxicity in nearshore waters, but there were major unknowns that still required investigation. For example, little was known about A. fundyense bloom dynamics in the waters south and east of Cape Cod, Massachusetts, and in particular, about the link between blooms in surface waters and toxicity in deep offshore shellfish. Large areas of offshore shellfish beds were off limits to harvest, including a 40,000 km2 region closed during the 2005 bloom and a much larger zone (~80,000 km2) including portions of Georges Bank was closed in 1990 after high levels of PSP toxicity were detected. In recent years, pressures were mounting from industry to open those offshore areas and to develop management strategies so that surfclam (Spisula solidissima), ocean quahog (Arctica islandica), and roe-on sea scallop (Placopecten magellanicus) fisheries could be opened. In response to these unknowns and societal needs, a new multi-investigator program, GOMTOX (Gulf of Maine Toxicity), was formulated and ultimately funded through the NOAA ECOHAB program. GOMTOX was a regional observation and modeling program that investigated the patterns and mechanisms underlying A. fundyense and Pseudo-nitzschia blooms and the resulting toxicity in shellfish in the southern GOM and its adjacent New England shelf waters, with special emphasis on the delivery pathways, mechanisms, and dynamics of offshore shellfish toxicity. The GOMTOX team of investigators included 16 principal investigators from eight institutions and, continuing in the ECOHAB-GOM tradition, strong participation from federal and state resource managers as well as representatives of the shellfish industry. This team worked together for over five years, running numerous large-scale survey cruises of Alexandrium cells and cysts, and also supporting industry cruises to collect shellfish from offshore sites including Georges Bank. Other efforts included participation in National Marine Fisheries Service surveys for shellfish (sea scallops, surfclams, and ocean quahogs), numerical modeling studies, deployment of sediment traps, and laboratory and ship-based experiments to investigate grazing and other processes that might regulate blooms and deliver toxins to shellfish in deeper waters. A smaller-scale but concurrent effort collected samples to characterize Pseudo-nitzschia species and their potential toxicity in the region.We gratefully acknowledge the support of NOAA through the ECOHAB program. Partial support for some of the studies contained herein was provided by NSF and NIEHS through the Woods Hole Center for Oceans and Human Health. Funding for J.L. Martin’s contributions from the Bay of Fundy was provided by Fisheries and Oceans Canada and NERACOOS, which is a part of the U.S. Integrated Ocean Observing System, funded in part by National Oceanic and Atmospheric Administration (NOAA)

Sustaining entrepreneurial business: a complexity perspective on processes that produce emergent practice

This article examines the management practices in an entrepreneurial small firm which sustain the business. Using a longitudinal qualitative case study, four general processes are identified (experimentation, reflexivity, organising and sensing), that together provide a mechanism to sustain the enterprise. The analysis draws on concepts from entrepreneurship and complexity science. We suggest that an entrepreneur’s awareness of the role of these parallel processes will facilitate their approaches to sustaining and developing enterprises. We also suggest that these processes operate in parallel at multiple levels, including the self, the business and inter-firm networks. This finding contributes to a general theory of entrepreneurship. A number of areas for further research are discussed arising from this result

A population of isolated hard X-ray sources near the supernova remnant Kes 69

Recent X-ray observations of the supernova remnant IC443 interacting with molecular clouds have shown the presence of a new population of hard X-ray sources related to the remnant itself, which has been interpreted in terms of fast ejecta fragment propagating inside the dense environment. Prompted by these studies, we have obtained a deep {\sl XMM-Newton} observation of the supernova remnant (SNR) Kes 69, which also shows signs of shock-cloud interaction. We report on the detection of 18 hard X-ray sources in the field of Kes 69, a significant excess of the expected galactic source population in the field, spatially correlated with CO emission from the cloud in the remnant environment. The spectra of 3 of the 18 sources can be described as hard power laws with photon index <2 plus line emission associated to K-shell transitions. We discuss the two most promising scenarios for the interpretation of the sources, namely fast ejecta fragments (as in IC443) and cataclysmic variables. While most of the observational evidences are consistent with the former interpretation, we cannot rule out the latter.Comment: 9 pages, 5 figures, A&A in pres

Adjuvant use of laser in eyes with macular retinoblastoma treated with primary intravenous chemotherapy

Background Adjuvant use of laser with systemic chemotherapy for treatment of retinoblastoma may reduce recurrence rates while also causing local side effects. Information is lacking on the effect of laser on visual outcomes. Methods A retrospective review of two retinoblastoma centres in the United Kingdom was conducted. Patients were included if there was a macular tumour in at least one eye. Eyes that received chemotherapy alone were compared with eyes that received chemotherapy plus adjuvant laser. Results A total of 76 patients and 91 eyes were included in the study. Systemic chemotherapy alone was used in 71 eyes while chemotherapy plus laser was used in 20 eyes. Demographic characteristics of both groups were similar. Macular relapse rates were similar between groups: 22/71 (31%) eyes in chemotherapy group and 9/20 (45%) eyes in laser group (p=0.29). There was no increase in vitreous relapses in the laser group (2/20 eyes), compared with the chemotherapy group 10/71 eyes (p=0.99). Survival analysis demonstrated similar time to first relapse between groups. Final visual acuity was equal between groups with 6/15 or better present in 31.1% of eyes in the chemotherapy group and 37.5% of eyes in the laser group (p=0.76). Presence of tumour at the fovea was predictive of final visual acuity, regardless of treatment group. Conclusion Adjuvant laser in the treatment of retinoblastoma is safe and does not lead to increased rate of vitreous recurrence. Final visual acuity is determined by the presence of tumour at the fovea and not the use of laser

Herschel/HIFI observations of spectrally resolved methylidyne signatures toward the high-mass star-forming core NGC6334I

In contrast to extensively studied dense star-forming cores, little is known about diffuse gas surrounding star-forming regions. We study molecular gas in the high-mass star-forming region NGC6334I, which contains diffuse, quiescent components that are inconspicuous in widely used molecular tracers such as CO. We present Herschel/HIFI observations of CH toward NGC6334I observed as part of the CHESS key program. HIFI resolves the hyperfine components of its J=3/2-1/2 transition, observed in both emission and absorption. The CH emission appears close to the systemic velocity of NGC6334I, while its measured linewidth of 3 km/s is smaller than previously observed in dense gas tracers such as NH3 and SiO. The CH abundance in the hot core is 7 10^-11, two to three orders of magnitude lower than in diffuse clouds. While other studies find distinct outflows in, e.g., CO and H2O toward NGC6334I, we do not detect outflow signatures in CH. To explain the absorption signatures, at least two absorbing components are needed at -3.0 and +6.5 km/s with N(CH)=7 10^13 and 3 10^13 cm^-2. Two additional absorbing clouds are found at +8.0 and 0.0 km/s, both with N(CH)=2 10^13 cm^-2. Turbulent linewidths for the four absorption components vary between 1.5 and 5.0 km/s in FWHM. We constrain physical properties of our CH clouds by matching our CH absorbers with other absorption signatures. In the hot core, molecules such as H2O and CO trace gas that is heated and dynamically influenced by outflow activity, whereas CH traces more quiescent material. The four CH absorbers have column densities and turbulent properties consistent with diffuse clouds: two are located near NGC6334, and two are unrelated foreground clouds. Local density and dynamical effects influence the chemical composition of physical components of NGC6334, causing some components to be seen in CH but not in other tracers, and vice versa.Comment: Accepted by A&A Letters; 5 pages, 1 figure; v2: minor textual and typographical change

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study)

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types

Far-Infrared detection of methylene

We present a clear detection of CH2 in absorption towards the molecular cloud complexes Sagittarius B2 and W49 N using the ISO Long Wavelength Spectrometer. These observations represent the first detection of its low excitation rotational lines in the interstellar medium. Towards Sagittarius B2, we detect both ortho and para transitions allowing a determination of the total CH2 column density of N(CH2)=(7.5+/-1.1)x10^14 cm^-2. We compare this with the related molecule, CH, to determine [CH/CH2]=2.7+/-0.5. Comparison with chemical models shows that the CH abundance along the line of sight is consistent with diffuse cloud conditions and that the high [CH/CH2] ratio can be explained by including the effect of grain-surface reactions.Comment: 11 pages, 4 figures, accepted for publication in A&

Female responses to experimental removal of sexual selection components in Drosophila melanogaster

Despite the common assumption that multiple mating should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies

Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase

Meiotic crossovers are produced when programmed double-strand breaks (DSBs) are repaired by recombination from homologous chromosomes (homologues). In a wide variety of organisms, meiotic HORMA-domain proteins are required to direct DSB repair towards homologues. This inter-homologue bias is required for efficient homology search, homologue alignment, and crossover formation. HORMA-domain proteins are also implicated in other processes related to crossover formation, including DSB formation, inhibition of promiscuous formation of the synaptonemal complex (SC), and the meiotic prophase checkpoint that monitors both DSB processing and SCs. We examined the behavior of two previously uncharacterized meiosis-specific mouse HORMA-domain proteins-HORMAD1 and HORMAD2-in wild-type mice and in mutants defective in DSB processing or SC formation. HORMADs are preferentially associated with unsynapsed chromosome axes throughout meiotic prophase. We observe a strong negative correlation between SC formation and presence of HORMADs on axes, and a positive correlation between the presumptive sites of high checkpoint-kinase ATR activity and hyper-accumulation of HORMADs on axes. HORMADs are not depleted from chromosomes in mutants that lack SCs. In contrast, DSB formation and DSB repair are not absolutely required for depletion of HORMADs from synapsed axes. A simple interpretation of these findings is that SC formation directly or indirectly promotes depletion of HORMADs from chromosome axes. We also find that TRIP13 protein is required for reciprocal distribution of HORMADs and the SYCP1/SC-component along chromosome axes. Similarities in mouse and budding yeast meiosis suggest that TRIP13/Pch2 proteins have a conserved role in establishing mutually exclusive HORMAD-rich and synapsed chromatin domains in both mouse and yeast. Taken together, our observations raise the possibility that involvement of meiotic HORMA-domain proteins in the regulation of homologue interactions is conserved in mammals