Establishing the impact of powerful AGN on their host galaxies

Establishing the role of active galactic nuclei (AGN) during the formation of galaxies remains one of the greatest challenges of galaxy formation theory. Towards addressing this, we summarise our recent work investigating: (1) the physical drivers of ionised outflows and (2) observational signatures of the impact by jets/outflows on star formation and molecular gas content in AGN host galaxies. We confirm a connection between radio emission and extreme ionised gas kinematics in AGN hosts. Emission-line selected AGN are significantly more likely to exhibit ionised outflows (as traced by the [O III] emission line) if the projected linear extent of the radio emission is confined within the spectroscopic aperture. Follow-up high resolution radio observations and integral field spectroscopy of 10 luminous Type 2 AGN reveal moderate power, young (or frustrated) jets interacting with the interstellar medium. We find that these sources live in highly star forming and gas rich galaxies. Additionally, by combining ALMA-derived dust maps with integral field spectroscopy for eight host galaxies of z~2 X-ray AGN, we show that H-alpha emission is an unreliable tracer of star formation. For the five targets with ionised outflows we find no dramatic in-situ shut down of the star formation. Across both of these studies we find that if these AGN do have a negative impact upon their host galaxies, it must be happening on small (unresolved) spatial scales and/or an observable galaxy-wide impact has yet to occur.Comment: Invited Contribution to IAU Symposium 359 (T. Storchi-Bergmann, R. Overzier, W. Forman & R. Riffel, eds.

Profile: The Kilifi Health and Demographic Surveillance System (KHDSS).

The Kilifi Health and Demographic Surveillance System (KHDSS), located on the Indian Ocean coast of Kenya, was established in 2000 as a record of births, pregnancies, migration events and deaths and is maintained by 4-monthly household visits. The study area was selected to capture the majority of patients admitted to Kilifi District Hospital. The KHDSS has 260 000 residents and the hospital admits 4400 paediatric patients and 3400 adult patients per year. At the hospital, morbidity events are linked in real time by a computer search of the population register. Linked surveillance was extended to KHDSS vaccine clinics in 2008. KHDSS data have been used to define the incidence of hospital presentation with childhood infectious diseases (e.g. rotavirus diarrhoea, pneumococcal disease), to test the association between genetic risk factors (e.g. thalassaemia and sickle cell disease) and infectious diseases, to define the community prevalence of chronic diseases (e.g. epilepsy), to evaluate access to health care and to calculate the operational effectiveness of major public health interventions (e.g. conjugate Haemophilus influenzae type b vaccine). Rapport with residents is maintained through an active programme of community engagement. A system of collaborative engagement exists for sharing data on survival, morbidity, socio-economic status and vaccine coverage

Entomological indices of malaria transmission in Chikhwawa district, Southern Malawi

Abstract Background Although malaria is highly prevalent throughout Malawi, little is known of its transmission dynamics. This paper describes the seasonal activity of the different vectors, human biting indices, sporozoite rates and the entomological inoculation rate in a low-lying rural area in southern Malawi. Methods Vectors were sampled over 52 weeks from January 2002 to January 2003, by pyrethrum knockdown catch in two villages in Chikhwawa district, in the Lower Shire Valley. Results In total, 7,717 anophelines were collected of which 55.1% were Anopheles gambiae sensu lato and 44.9% were Anopheles funestus. Three members of the An. gambiae complex were identified by PCR: Anopheles arabiensis (75%) was abundant throughout the year, An. gambiae s.s. (25%) was most common during the wet season and Anopheles quadriannulatus occurred at a very low frequency (n=16). An. funestus was found in all samples but was most common during the dry season. Anopheles gambiae s.s. and An. funestus were highly anthropophilic with human blood indices of 99.2% and 96.3%, respectively. Anopheles arabiensis had fed predominantly on humans (85.0%) and less commonly on cattle (10.9%; 1.2% of blood meals were of mixed origin). Plasmodium falciparum (192/3,984) and Plasmodium malariae (1/3,984) sporozoites were detected by PCR in An. arabiensis (3.2%) and An. funestus (4.5%), and in a significantly higher proportion of An. gambiae s.s. (10.6%)(pP. falciparum sporozoite rate was 4.8%, resulting in estimated inoculation rates of 183 infective bites/ person per annum, or an average rate of ~15 infective bites/person/month. Conclusions The results demonstrate the importance of An. gambiae s.s., An. arabiensis and An. funestus in driving the high levels of malaria transmission in the south of Malawi. Sustained and high coverage or roll out of current approaches to malaria control (primarily insecticide-treated bed nets and indoor residual house spraying) in the area are likely to reduce the observed high malaria transmission rate and consequently the incidence of human infections, unless impeded by increasing resistance of vectors to insecticides.</p

Bacterial Meningitis in Malawian Adults, Adolescents, and Children During the Era of Antiretroviral Scale-up and Haemophilus influenzae Type b Vaccination, 2000-2012

Background We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART). Methods We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 2000 and 2012. Results There was a significant decline in the total number of CSF isolates over 12 years (incident rate ratio [IRR], 0.93; 95% CI, .92–.94; P < .001). This decline was entirely in children aged <5 years (IRR, 0.87; 95% CI, .85–.88; P < .001) and coincided with the introduction of Hib vaccination. The number of adult isolates has remained unchanged (IRR, 0.99; 95% CI, .97–1.0; P = .135) despite rapid scale-up of ART provision. In children aged <5 years, Streptococcus pneumoniae, nontyphoidal salmonellae (NTS), and Hib were the most frequently isolated pathogens, and have declined over this time period. Streptococcus pneumoniae was the most frequently isolated pathogen in older children and adults. Estimated incidence of bacterial meningitis in 2012 was 20 per 100 000 cases in children aged <14 years, 6 per 100 000 adolescents, and 10 per 100 000 adults. Conclusions Rates of bacterial meningitis have declined in children, but not adults, coinciding with the introduction of Hib vaccination. The highly successful rollout of ART has not yet resulted in a reduction in the incidence in adults where the burden remains high. Long-term surveillance of bacterial meningitis outside of the epidemic “meningitis belt” in Africa is essential

Performance Characteristics of Combinations of Host Biomarkers to Identify Women with Occult Placental Malaria: A Case-Control Study from Malawi

Because of its propensity to sequester in the placental intervillous space, Plasmodium falciparum can evade detection by peripheral smear in women with placental malaria (PM). We evaluated host biomarkers as potential indicators of occult PM infections.Using a case-control design, we evaluated the ability of biomarkers to identify PM in the absence of circulating peripheral parasites (n = 24) compared to placental smear-negative controls (n = 326). We measured levels of biomarkers (C3a, C5a, CRP, angiopoietin-1, angiopoietin-2, sTie-2, sEndoglin, VEGF, sFlt-1, tissue factor, and leptin) in maternal peripheral plasma at delivery. Using ROC curve analysis, we assessed the ability of clinical parameters and biomarkers to accurately detect PM infections identified by placental smear. We show that decreases in sFlt-1 and leptin and increases in CRP were associated with occult PM infections (p<0.01) and correlated with placental parasitaemia (p<0.01). Individually, all markers had moderate ability to diagnose occult PM infections with areas under the ROC between 0.62 and 0.72. In order to improve diagnostic performance, we generated simple scoring systems to identify PM infections using either a clinical score (0-2), a biomarker score (0-3) or a clinical plus biomarker score (0-5). The combinatorial model that incorporated both clinical parameters and biomarkers had an area under curve (AUC) of 0.85 (95% CI, 0.81-0.89), which was significantly better at identifying occult PM infections than the clinical score alone (p = 0.001).These data suggest that host biomarkers in the maternal peripheral blood may improve the detection of PM in the absence of peripheral parasitaemia

Point-of-care measurement of blood lactate in children admitted with febrile illness to an African District Hospital.

BACKGROUND: Lactic acidosis is a consistent predictor of mortality owing to severe infectious disease, but its detection in low-income settings is limited to the clinical sign of "deep breathing" because of the lack of accessible technology for its measurement. We evaluated the use of a point-of-care (POC) diagnostic device for blood lactate measurement to assess the severity of illness in children admitted to a district hospital in Tanzania. METHODS: Children between the ages of 2 months and 13 years with a history of fever were enrolled in the study during a period of 1 year. A full clinical history and examination were undertaken, and blood was collected for culture, microscopy, complete blood cell count, and POC measurement of blood lactate and glucose. RESULTS: The study included 3248 children, of whom 164 (5.0%) died; 45 (27.4%) of these had raised levels of blood lactate (>5 mmol/L) but no deep breathing. Compared with mortality in children with lactate levels of ≤ 3 mmol/L, the unadjusted odds of dying were 1.6 (95% confidence interval [CI].8-3.0), 3.4 (95% CI, 1.5-7.5), and 8.9 (95% CI, 4.7-16.8) in children with blood lactate levels of 3.1-5.0, 5.1-8.0, or >8.0 mmol/L, respectively. The prevalence of raised lactate levels (>5 mmol/L) was greater in children with malaria than in children with nonmalarial febrile illness (P < .001) although the associated mortality was greater in slide-negative children. CONCLUSIONS: POC lactate measurement can contribute to the assessment of children admitted to hospital with febrile illness and can also create an opportunity for more hospitals in resource-poor settings to participate in clinical trials of interventions to reduce mortality associated with hyperlactatemia

A New Large-Well 1024x1024 Si:As Detector for the Mid-Infrare

We present a description of a new 1024x1024 Si:As array designed for ground-based use from 5 - 28 microns. With a maximum well depth of 5e6 electrons, this device brings large-format array technology to bear on ground-based mid-infrared programs, allowing entry to the megapixel realm previously only accessible to the near-IR. The multiplexer design features switchable gain, a 256x256 windowing mode for extremely bright sources, and it is two-edge buttable. The device is currently in its final design phase at DRS in Cypress, CA. We anticipate completion of the foundry run in the beginning of 2006. This new array will enable wide field, high angular resolution ground-based follow up of targets found by space-based missions such as the Spitzer Space Telescope and the Widefield Infrared Survey Explorer (WISE).Comment: 8 pages, 9 figures, 2005 San Diego SPI

Differential var gene expression in the organs of patients dying of falciparum malaria

Sequestration of parasitized erythrocytes in the microcirculation of tissues is thought to be important in the pathogenesis of severe falciparum malaria. A major variant surface antigen, var/Plasmodium falciparum erythrocyte membrane protein 1, expressed on the surface of the infected erythrocyte, mediates cytoadherence to vascular endothelium. To address the question of tissue-specific accumulation of variant types, we used the unique resource generated by the clinicopathological study of fatal paediatric malaria in Blantyre, Malawi, to analyse var gene transcription in patients dying with falciparum malaria. Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients. These major var types differed between organs. However, identical var types were expressed in the brains of multiple patients from a single malaria season. These results provide the first evidence of organ-specific accumulation of P. falciparum variant types and suggest that parasitized erythrocytes can exhibit preferential binding in the body, supporting the hypothesis of cytoadherence-linked pathogenesis

Taking roles in interdisciplinary collaborations: Reflections on working in post-ELSI spaces in the UK synthetic biology community

Based on criticism of the “ethical, legal and social implications” (ELSI) paradigm, researchers in science and technology studies (STS) have begun to create and move into “post-ELSI” spaces. In this paper, we pool our experiences of working towards collaborative practices with colleagues in engineering and science disciplines in the f eld of synthetic biology. We identify a number of dif erent roles that we have taken, been assumed to take, or have had foisted upon us as we have sought to develop postELSI practices. We argue that the post-ELSI situation is characterised by the demands placed on STS researchers and other social scientists to f uctuate between roles as contexts shift in terms of power relations, af ective tenor, and across space and over time. This leads us to posit four orientations for post-ELSI collaborative practices that could help establish more fruitful negotiations around these roles

Prediction of 60 day case-fatality after aneurysmal subarachnoid haemorrhage: results from the International Subarachnoid Aneurysm Trial (ISAT)

Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with substantial case-fatality. Our purpose was to examine which clinical and neuro-imaging characteristics, available on admission, predict 60 day case-fatality in aSAH and to evaluate performance of our prediction model. We performed a secondary analysis of patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomised multicentre trial to compare coiling with clipping in aSAH patients. Multivariable logistic regression analysis was used to develop a prognostic model to estimate the risk of dying within 60 days from aSAH based on clinical and neuro-imaging characteristics. The model was internally validated with bootstrapping techniques. The study population comprised of 2,128 patients who had been randomised to either endovascular coiling or neurosurgical clipping. In this population 153 patients (7.2%) died within 60 days. World Federation of Neurosurgical Societies (WFNS) grade was the most important predictor of case-fatality, followed by age, lumen size of the aneurysm and Fisher grade. The model discriminated reasonably between those who died within 60 days and those who survived (c statistic = 0.73), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.70). Several strong predictors are available to predict 60 day case-fatality in aSAH patients who survived the early stage up till a treatment decision; after external validation these predictors could eventually be used in clinical decision making