Population pharmacokinetics of a single daily intramuscular dose of gentamicin in children with severe malnutrition

Article published in Journal of Antimicrobial ChemotherapyObjectives: The World Health Organization recommends that all children admitted with severe malnutrition should routinely receive parenteral ampicillin and gentamicin; despite this, mortality remains high. Since this population group is at risk of altered volume of distribution, we aimed to study the population pharmacokinetics of once daily gentamicin (7.5 mg/kg) in children with severe malnutrition and to evaluate clinical factors affecting pharmacokinetic parameters. Methods: Thirty-four children aged 0.5–10 years were studied. One hundred and thirty-two gentamicin concentrations (median of four per patient), drawn 0.4–24.6 h after administration of the intramuscular dose, were analysed. The data were fitted by a two-compartment model using the population package NONMEMw. Results: Gentamicin was rapidly absorbed and all concentrations measured within the first 2 h after administration were >8 mg/L (indicating that satisfactory peak concentrations were achieved). Ninetyeight percent of samples measured more than 20 h after the dose were <1 mg/L. The best model included weight, and it was found that high base deficit, high creatinine concentration and low temperature (all markers of hypovolaemic shock) reduced clearance (CL/F). Weight influenced volume of the central (V1/F) and peripheral (V2/F) compartments, and high base deficit reduced V2/F and intercompartmental CL (Q/F). Interindividual variability in CL was 26%, in V1/F 33% and in V2/F and Q/F was 52%. Individual estimates of CL/F ranged from 0.02 to 0.16 (median 0.10) L/h/kg and those of Vss/F from 0.26 to 1.31 (median 0.67) L/kg. Initial half-lives had a median of 1.4 h and elimination half-lives and a median of 14.9 h. Excessive concentrations were observed in one patient who had signs of renal impairment and shock. Conclusions: Although a daily dose of 7.5 mg/kg achieves satisfactory gentamicin concentrations in the majority of patients, patients with renal impairment and shock may be at risk of accumulation with 24 hourly dosing. Further studies of gentamicin pharmacokinetics in this group are now needed to inform future international guideline recommendations

Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis

Background: Pneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya. Methods: We linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45000 children younger than 5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January, 2011. In Kilifi, there was a three-dose catch-up campaign for infants (aged \u3c1 \u3eyear) and a two-dose catch-up campaign for children aged 1–4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends. Findings: Between May 1, 2002 and March 31, 2015, 44771 children aged 2–143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses’ strikes. In 2002–03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2–59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2–11 months had received at least two doses of PCV10 and 23298 (62·3%) of 37416 children aged 12–59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologicallyconfirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32–0·86), 0·73 (0·54–0·97), and 0·63 (0·31–1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100000; this value was reduced by 329 per 100000 at the point of PCV10 introduction. Interpretation: Over 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10

EPOCHS VIII. An Insight into MIRI-selected Galaxies in SMACS-0723 and the Benefits of Deep MIRI Photometry in Revealing AGN and the Dusty Universe

We present the analysis of the stellar population and star formation history of 181 MIRI selected galaxies at redshift 0-3.5 in the massive galaxy cluster field SMACS J0723.3-7327, commonly referred to as SMACS0723, using the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI). We combine the data with the JWST Near Infrared Camera (NIRCam) catalogue, in conjunction with the Hubble Space Telescope (HST) WFC3/IR and ACS imaging. We find that the MIRI bands capture PAH features and dust emission, significantly enhancing the accuracy of photometric redshift and measurements of the physical properties of these galaxies. The median photo-z's of galaxies with MIRI data are found to have a small 0.1% difference from spectroscopic redshifts and reducing the error by 20 percent. With MIRI data included in SED fits, we find that the measured stellar masses are unchanged, while the star formation rate is systematically lower by 0.1 dex. We also fit the median SED of active galactic nuclei (AGN) and star forming galaxies (SFG) separately. MIRI data provides tighter constraints on the AGN contribution, reducing the typical AGN contributions by ~14 percent. In addition, we also compare the median SED obtained with and without MIRI, and we find that including MIRI data yields steeper optical and UV slopes, indicating bluer colours, lower dust attenuation, and younger stellar populations. In the future, MIRI/MRS will enhance our understanding by providing more detailed spectral information and allowing for the study of specific emission features and diagnostics associated with AGN.Comment: 15 pages, 14 figures and 1 table, submitted to MNRA

An Unbiased Survey of 500 Nearby Stars for Debris Disks: A JCMT Legacy Program

We present the scientific motivation and observing plan for an upcoming detection survey for debris disks using the James Clerk Maxwell Telescope. The SCUBA-2 Unbiased Nearby Stars (SUNS) Survey will observe 500 nearby main sequence and sub-giant stars (100 of each of the A, F, G, K and M spectral classes) to the 850 micron extragalactic confusion limit to search for evidence of submillimeter excess, an indication of circumstellar material. The survey distance boundaries are 8.6, 16.5, 22, 25 and 45 pc for M, K, G, F and A stars, respectively, and all targets lie between the declinations of -40 deg to 80 deg. In this survey, no star will be rejected based on its inherent properties: binarity, presence of planetary companions, spectral type or age. This will be the first unbiased survey for debris disks since IRAS. We expect to detect ~125 debris disks, including ~50 cold disks not detectable in current shorter wavelength surveys. A substantial amount of complementary data will be required to constrain the temperatures and masses of discovered disks. High resolution studies will likely be required to resolve many of the disks. Therefore, these systems will be the focus of future observational studies using a variety of observatories to characterize their physical properties. For non-detected systems, this survey will set constraints (upper limits) on the amount of circumstellar dust, of typically 200 times the Kuiper Belt mass, but as low as 10 times the Kuiper Belt mass for the nearest stars in the sample (approximately 2 pc).Comment: 11 pages, 7 figures (3 color), accepted by the Publications of the Astronomical Society of the Pacifi

Diarrhoea Complicating Severe Acute Malnutrition in Kenyan Children: A Prospective Descriptive Study of Risk Factors and Outcome

BACKGROUND: Severe acute malnutrition (SAM) accounts for two million deaths worldwide annually. In those hospitalised with SAM, concomitant infections and diarrhoea are frequent complications resulting in adverse outcome. We examined the clinical and laboratory features on admission and outcome of children with SAM and diarrhoea at a Kenyan district hospital. METHODS: A 4-year prospective descriptive study involving 1,206 children aged 6 months to 12 years, hospitalized with SAM and managed in accordance with WHO guidelines. Data on clinical features, haematological, biochemical and microbiological findings for children with diarrhoea (≥ 3 watery stools/day) were systematically collected and analyzed to identify risk factors associated with poor outcome. RESULTS: At admission 592 children (49%) had diarrhoea of which 122 (21%) died compared to 72/614 (12%) deaths in those without diarrhoea at admission (Χ(2) = 17.6 p&lt;0.001). A further 187 (16%) children developed diarrhoea after 48 hours of admission and 33 died (18%). Any diarrhoea during admission resulted in a significantly higher mortality 161/852 (19%) than those uncomplicated by diarrhoea 33/351 (9%) (Χ(2) = 16.6 p&lt;0.001). Features associated with a fatal outcome in children presenting with diarrhoea included bacteraemia, hyponatraemia, low mid-upper arm circumference &lt;10 cm, hypoxia, hypokalaemia and oedema. Bacteraemia had the highest risk of death (adjusted OR 6.1; 95% C.I 2.3, 16.3 p&lt;0.001); and complicated 24 (20%) of fatalities. Positive HIV antibody status was more frequent in cases with diarrhoea at admission (23%) than those without (15%, Χ(2) = 12.0 p = 0.001) but did not increase the risk of death in diarrhoea cases. CONCLUSION: Children with SAM complicated by diarrhoea had a higher risk of death than those who did not have diarrhoea during their hospital stay. Further operational and clinical research is needed to reduce mortality in children with SAM in the given setting

Multi-core fibre-fed integral-field unit (MCIFU):Overview and first-light

The Multi-Core Integral-Field Unit (MCIFU) is a new diffraction-limited near-infrared integral-field unit for exoplanet atmosphere characterization with extreme adaptive optics (xAO) instruments. It has been developed as an experimental pathfinder for spectroscopic upgrades for SPHERE+/VLT and other xAO systems. The wavelength range covers 1.0 um to 1.6um at a resolving power around 5000 for 73 points on-sky. The MCIFU uses novel astrophotonic components to make this very compact and robust spectrograph. We performed the first successful on-sky test with CANARY at the 4.2 meter William Herschel Telescope in July 2019, where observed standard stars and several stellar binaries. An improved version of the MCIFU will be used with MagAO-X, the new extreme adaptive optics system at the 6.5 meter Magellan Clay telescope in Chile. We will show and discuss the first-light performance and operations of the MCIFU at CANARY and discuss the integration of the MCIFU with MagAO-X.</p

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

EPOCHS Paper II: The Ultraviolet Luminosity Function from 7.5<z<13.57.5<z<13.5 using 110 square arcminutes of deep, blank-field data from the PEARLS Survey and Public Science Programmes

We present an analysis of the ultraviolet luminosity function (UV LF) and star formation rate density of distant galaxies ($7.5 < z < 13.5$) in the `blank' fields of the Prime Extragalactic Areas for Reionization Science (PEARLS) survey combined with Early Release Science (ERS) data from the CEERS, GLASS and NGDEEP surveys/fields. We use a combination of SED fitting tools and quality cuts to obtain a reliable selection and characterisation of high-redshift ($z>6.5$) galaxies from a consistently processed set of deep, near-infrared imaging. Within an area of 110 arcmin$^{2}$, we identify 214 candidate galaxies at redshifts $z>6.5$ and we use this sample to study the ultraviolet luminosity function (UV LF) in four redshift bins between $7.5<z<13.5$. The measured number density of galaxies at $z=8$ and $z=9$ match those of past observations undertaken by the em Hubble Space Telescope (HST). However, towards higher redshifts we find that the evolution of the UV LF is mild, resulting in higher measured number densities of UV luminous galaxies at $z=10.5$ and $z=12.5$ compared to predictions from simulations and past HST observations. When examining the star formation rate density of galaxies at this time period, our observations are still consistent with a constant star formation efficiency, are slightly lower than previous early estimations using JWST and support galaxy driven reionization at $z\sim8$.Comment: 28 Pages, 4 Tables, 9 Figures, Submitted to Ap

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI