50 research outputs found
CXCL12/CXCR4 Blockade Induces Multimodal Antitumor Effects That Prolong Survival in an Immunocompetent Mouse Model of Ovarian Cancer
Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter
Climate change and human pressures are changing the global distribution and the ex‐
tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the
global river network area. IRES are characterized by periods of flow cessation, during
which channel substrates accumulate and undergo physico‐chemical changes (precon‐
ditioning), and periods of flow resumption, when these substrates are rewetted and
release pulses of dissolved nutrients and organic matter (OM). However, there are no
estimates of the amounts and quality of leached substances, nor is there information
on the underlying environmental constraints operating at the global scale. We experi‐
mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐
bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES
from five major climate zones. We determined the amounts and qualitative character‐
istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds.
In addition, we evaluated the variance in leachate characteristics in relation to selected
environmental variables and substrate characteristics. We found that sediments, due
to their large quantities within riverbeds, contribute most to the overall flux of dis‐
solved substances during rewetting events (56%–98%), and that flux rates distinctly
differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐
uted most to the areal fluxes. The largest amounts of leached substances were found
in the continental climate zone, coinciding with the lowest potential bioavailability of
the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐
ables expected to be modified under climate change (i.e. potential evapotranspiration,
aridity, dry period duration, land use) were correlated with the amount of leached sub‐
stances, with the strongest relationship found for sediments. These results show that
the role of IRES should be accounted for in global biogeochemical cycles, especially
because prevalence of IRES will increase due to increasing severity of drying event
Differential effects of systemically administered nor-binaltorphimine (nor-BNI) on κ-opioid agonists in the mouse writhing assay
The opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) were evaluated against the kappa agonists CI-977, U69,593, U50,488, ethylketocyclazocine (EKC), Mr2034 and bremazocine, the mu agonist morphine and the alkaloid delta agonist BW-373U86 in the acetic acid-induced writhing assay in mice. All eight agonists completely and dose-dependently inhibited writhing. Antagonism of CI-977 was apparent 1 h after administration of 32 mg/kg nor-BNI, peaking after 4 h and was maintained for at least 4 weeks; no antagonist effects of nor-BNI were apparent after 8 weeks. Nor-BNI (32 mg/kg) caused little or no antagonism of morphine or BW-373U86 at 1 h and none at 24 h after nor-BNI administration. Subsequently, dose-effect curves for CI-977, U50,488, U69,593, EKC, Mr2034 and bremazocine were determined 24 h after pretreatment with 3.2, 10 and 32 mg/kg nor-BNI. Pretreatment with 3.2 mg/kg nor-BNI produced significant antagonism of all six kappa agonists, suggesting that their antinociceptive effects were mediated at least in part by nor-BNI-sensitive kappa receptors. At higher doses, nor-BNI dose-depend-ently shifted the agonist dose-effect curves of CI-977, U50,488, U69,593 and bremazocine, but not those of EKC and Mr2034, suggesting that the latter compounds may be producing effects via nor-BNI-insensitive receptors. Mu receptor involvement was demonstrated following a 24 h pretreatment with 32 mg/kg β -FNA in combination with nor-BNI, which significantly increased the degree of antagonism of Mr2034 and EKC from that seen with nor-BNI alone. Hence, SC administered nor-BNI selectively antagonized agonist activity mediated through kappaopioid receptors without differentiating between kappa subtypes. Nor-BNI also enabled the mu agonist activity of proposed kappa agonists to be measured.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46343/1/213_2005_Article_BF02245071.pd
IMPACT-Global Hip Fracture Audit: Nosocomial infection, risk prediction and prognostication, minimum reporting standards and global collaborative audit. Lessons from an international multicentre study of 7,090 patients conducted in 14 nations during the COVID-19 pandemic
AIMS: This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. METHODS: A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1(st) March-31(st) May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. RESULTS: A total of 7090 patients were included, with a mean age of 82.2 (range 50-104) years and 4959 (70%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) became positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p=0.001), residential care (OR 2.15, p<0.001), inpatient fall (OR 2.23, p=0.003), cancer (OR 0.63, p=0.009), ASA grade 4-5 (OR 1.59, p=0.008; OR 8.28, p<0.001), and longer admission (OR 1.06 for each increasing day, p<0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p<0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p<0.001). Increasing age (HR 1.03, p=0.028), male sex (HR 2.35, p<0.001), renal disease (HR 1.53, p=0.017), and pulmonary disease (HR 1.45, p=0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. CONCLUSION: The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher mortality risk
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Precarious creativity: Changing attitudes towards craft and creativity in the British independent television production sector
This article focuses on television workers’ attitudes towards craft and creative practice within the field of factual television production in the British independent television production sector (ITPS). Based on longitudinal qualitative research, it argues that a radical shift has occurred in the professional values that television producers’ associate with their creative work, by focusing on ethical and professional norms within factual television production. By considering the historical and contemporary discourse of ‘craft’ within this area of creative work, the article interrogates the nature of the changes that have taken place. The wider significance of these changes is also considered, through an engagement with theoretical concerns about the place of craft within late modernity (Sennett 2006), and with debates about the changes that have taken place within the political economy of independent television production. The article’s findings have contextual significance within contemporary debates about creative work (Hesmondhalgh & Baker, 2010). Despite the celebratory policy rhetoric of the ‘creative industries’ (DCMS 1998), the transformed production environment within contemporary British television has had a detrimental effect on skills retention and development, as well as on the potential for creativity within the industry
Hepatocellular Carcinoma Risk in Alaska Native Children and Young Adults with Hepatitis B Virus: Retrospective Cohort Analysis
OBJECTIVES: To evaluate the hepatocellular carcinoma (HCC) risk in hepatitis B virus (HBV)-infected Alaska Native (AN) children and young adults. STUDY DESIGN: Retrospective analysis of a population-based cohort of HBV-infected AN persons followed during 1982–2012. All HBV-infected persons were offered HCC screening regardless of age using alpha-fetoprotein (AFP) every 6 months; persons with an elevated AFP or persons at high-risk for HCC, such as cirrhosis, family history of HCC, were offered ultrasound. We calculated the HCC incidence/1,000 person-years from date of cohort entry until death, diagnosis of HCC, or attaining the age of 40 years (males) or 50 years (females). RESULTS: We followed 1083 HBV-infected persons (56% male) comprising 5 genotypes (A2 [12.5%], B6 [1.7%], C [5.3%], D [49.7%], F1 [18.6%], unknown [12.4%]) for a median of 23.4 years/person. We observed 22 HCC cases (incidence/1,000 person-years follow-up: 1.0); 19 HCC cases among persons with genotype F1. There was no significant difference in HCC incidence between males (1.4) and females (0.6). The HCC incidence was significantly higher for persons with genotype F1 (4.4) compared with genotype A2 (0.4) and D (0.2) and remained higher among persons with HBV genotype F1 excluding persons with HCC family history/cirrhosis (1.9). CONCLUSIONS: HBV genotype F1-infected AN children and young adults are at high risk for HCC and should receive HCC surveillance. For HBV-infected males and females age <40 and <50 years, respectively, in regions of the world with a high genotype F prevalence, testing/confirming genotype F can identify persons who could benefit from HCC surveillance
