Group behavioural responses of cyprinids to artificial acoustic stimuli: implications for fisheries management

Physical screens are considered a necessary mitigation strategy, restricting access to hazardous areas (e.g. turbine intakes or extraction points) and guiding fish to safer preferred routes. Whilst this precautionary approach is considered fit for purpose, fish interactions at such interfaces have been observed to cause stress, injury and mortalities where high sweeping approach velocities exist. Alternative or collaborative systems may allow for improvements where effectiveness of physical screens alone are limited (e.g. repelling small sized larval/ juvenile stages). A number of acoustic guidance systems have been deployed to date, however efficiencies of such devices are measured using relatively simplistic metrics (e.g.percentage deflection or attraction). Results are highly variable, with some systems observing little to no deflection. Current approaches testing efficiencies are based on methods which provide limited information surrounding the wild behaviour of migratory fish. Furthermore, many studies investigating fish bioacoustics pay limited attention to the entirety of the acoustic field to which fish are exposed. The auditory system is exceptionally important to most aquatic species due to its information provisioning, however various challenges need addressed to extrapolate useful informative data which could develop working behavioural deterrents. Life-history strategies, life-stages, species specific hearing capabilities (i.e. directivity index, sensitivity, and critical ratio), and the propensity for a sound to elicit a repeatedly effective behavioural response (i.e. signal detection theory and effects of habituation) are all areas that require thorough investigation. Utilising model cyprinid species (in possession of morphological hearing specialisations), groups of fish were video recorded under controlled conditions and exposed to differing acoustic stimuli. Behaviours were quantified and analysed, alongside appropriate mapping of tested acoustic fields. This talk summarises past and ongoing experiments of a PhD project investigating group behavioural responses to sound. Results may better inform fisheries engineering design of acoustic behavioural deterrents for conservation and control purposes

The Application of Reversible Intramolecular Sulfonamide Ligation to Modulate Reactivity in Organometallic Ruthenium(II) Diamine Complexes

Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5?-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner

Cycle threshold values are inversely associated with poorer outcomes in hospitalised patients with Covid-19:a prospective, observational cohort study conducted at a UK tertiary hospital

ABSTRACT: This single-centre observational study demonstrated that lower cycle threshold (Ct) values (indicating higher viral loads) on admission to hospital were associated with poorer outcomes in unvaccinated, hospitalized patients with coronavirus disease 2019 (COVID-19). Demographic and outcome data were collected prospectively for all adult patients who tested positive for severe acute respiratory syndrome coronavirus-2 on admission to the University Hospitals North Midlands NHS Trust between 1 February and 1 July 2020. Nasopharyngeal swab samples were obtained, and a valid Ct value was determined for all patients using the Viasure reverse transcription polymerase chain reaction assay, validated by Public Health England, on admission to hospital. Multi-variable logistic regression results based on data from 618 individuals demonstrated a significant inverse relationship between the odds of death and Ct values (adjusted odds ratio 0.95, 95% confidence interval 0.92–0.98, P=0.001). The association remained highly significant after adjusting for known clinical risk factors for COVID-1

Cycle threshold values are inversely associated with poorer outcomes in hospitalized patients with COVID-19:a prospective, observational cohort study conducted at a UK tertiary hospital

This single-centre observational study demonstrated that lower cycle threshold (Ct) values (indicating higher viral loads) on admission to hospital were associated with poorer outcomes in unvaccinated, hospitalized patients with coronavirus disease 2019 (COVID-19). Demographic and outcome data were collected prospectively for all adult patients who tested positive for severe acute respiratory syndrome coronavirus-2 on admission to the University Hospitals North Midlands NHS Trust between 1 February and 1 July 2020. Nasopharyngeal swab samples were obtained, and a valid Ct value was determined for all patients using the Viasure reverse transcription polymerase chain reaction assay, validated by Public Health England, on admission to hospital. Multi-variable logistic regression results based on data from 618 individuals demonstrated a significant inverse relationship between the odds of death and Ct values (adjusted odds ratio 0.95, 95% confidence interval 0.92–0.98, P=0.001).</p

Estimating global mean sea-level rise and its uncertainties by 2100 and 2300 from an expert survey

Sea-level rise projections and knowledge of their uncertainties are vital to make informed mitigation and adaptation decisions. To elicit projections from members of the scientific community regarding future global mean sea-level (GMSL) rise, we repeated a survey originally conducted five years ago. Under Representative Concentration Pathway (RCP) 2.6, 106 experts projected a likely (central 66% probability) GMSL rise of 0.30–0.65 m by 2100, and 0.54–2.15 m by 2300, relative to 1986–2005. Under RCP 8.5, the same experts projected a likely GMSL rise of 0.63–1.32 m by 2100, and 1.67–5.61 m by 2300. Expert projections for 2100 are similar to those from the original survey, although the projection for 2300 has extended tails and is higher than the original survey. Experts give a likelihood of 42% (original survey) and 45% (current survey) that under the high-emissions scenario GMSL rise will exceed the upper bound (0.98 m) of the likely range estimated by the Fifth Assessment Report of the Intergovernmental Panel on Climate Change, which is considered to have an exceedance likelihood of 17%. Responses to open-ended questions suggest that the increases in upper-end estimates and uncertainties arose from recent influential studies about the impact of marine ice cliff instability on the meltwater contribution to GMSL rise from the Antarctic Ice Sheet. © 2020, The Author(s)

Author Correction: Estimating global mean sea-level rise and its uncertainties by 2100 and 2300 from an expert survey

Correction to: NPJ Climate and Atmospheric Science https://doi.org/10.1038/s41612-020-0121-5, published online 08 May 202

HST Observations of Chromospheres in Metal Deficient Field Giants

HST high resolution spectra of metal-deficient field giants more than double the stars in previous studies, span about 3 magnitudes on the red giant branch, and sample an abundance range [Fe/H]= -1 to -3. These stars, in spite of their age and low metallicity, possess chromospheric fluxes of Mg II (2800 Angstrom) that are within a factor of 4 of Population I stars, and give signs of a dependence on the metal abundance at the lowest metallicities. The Mg II k-line widths depend on luminosity and correlate with metallicity. Line profile asymmetries reveal outflows that occur at lower luminosities (M_V = -0.8) than detected in Ca K and H-alpha lines in metal-poor giants, suggesting mass outflow occurs over a larger span of the red giant branch than previously thought, and confirming that the Mg II lines are good wind diagnostics. These results do not support a magnetically dominated chromosphere, but appear more consistent with some sort of hydrodynamic, or acoustic heating of the outer atmospheres.Comment: 36 pages, 12 figures, 7 tables, and accepted for publication in The Astronomical Journa

Anakinra reduces blood pressure and renal fibrosis in one kidney/DOCA/salt-induced hypertension

OBJECTIVE: To determine whether a clinically-utilised IL-1 receptor antagonist, anakinra, reduces renal inflammation, structural damage and blood pressure (BP) in mice with established hypertension. METHODS: Hypertension was induced in male mice by uninephrectomy, deoxycorticosterone acetate (2.4mg/d,s.c.) and replacement of drinking water with saline (1K/DOCA/salt). Control mice received uninephrectomy, a placebo pellet and normal drinking water. 10days post-surgery, mice commenced treatment with anakinra (75mg/kg/d, i.p.) or vehicle (0.9% saline, i.p.) for 11 days. Systolic BP was measured by tail cuff while qPCR, immunohistochemistry and flow cytometry were used to measure inflammatory markers, collagen and immune cell infiltration in the kidneys. RESULTS: By 10 days post-surgery, 1K/DOCA/salt-treated mice displayed elevated systolic BP (148.3+/-2.4mmHg) compared to control mice (121.7+/-2.7mmHg; n=18, P\u3c0.0001). The intervention with anakinra reduced BP in 1K/DOCA/salt-treated mice by approximately 20mmHg (n=16, P\u3c0.05), but had no effect in controls. In 1K/DOCA/salt-treated mice, anakinra modestly reduced ( approximately 30%) renal expression of some (CCL5, CCL2; n=7-8; P\u3c0.05) but not all (ICAM-1, IL-6) inflammatory markers, and had no effect on immune cell infiltration (n=7-8, P \u3e 0.05). Anakinra reduced renal collagen content (n=6, P\u3c0.01) but paradoxically appeared to exacerbate the renal and glomerular hypertrophy (n=8-9, P\u3c0.001) that accompanied 1K/DOCA/salt-induced hypertension. CONCLUSION: Despite its anti-hypertensive and renal anti-fibrotic actions, anakinra had minimal effects on inflammation and leukocyte infiltration in mice with 1K/DOCA/salt-induced hypertension. Future studies will assess whether the anti-hypertensive actions of anakinra are mediated by protective actions in other BP-regulating or salt-handling organs such as the arteries, skin and brain

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer

IMPORTANCE Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. OBJECTIVE To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. INTERVENTION Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. MAIN OUTCOMES AND MEASURES The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. RESULTS The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45–83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63–86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%–92%) and 62% (95% CI, 43%–77%), respectively. Median overall survival was 25 months (95% CI, 12–32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%–66%) and 30% (95% CI, 16%–45%), respectively. CONCLUSIONS AND RELEVANCE Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT0119052