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The past few decades have seen the burgeoning of wide-field, high-cadence surveys, the most formidable of which will be the Legacy Survey of Space and Time (LSST) to be conducted by the Vera C. Rubin Observatory. So new is the field of systematic time-domain survey astronomy; however, that major scientific insights will continue to be obtained using smaller, more flexible systems than the LSST. One such example is the Gravitational-wave Optical Transient Observer (GOTO) whose primary science objective is the optical follow-up of gravitational wave events. The amount and rate of data production by GOTO and other wide-area, high-cadence surveys presents a significant challenge to data processing pipelines which need to operate in near-real time to fully exploit the time domain. In this study, we adapt the Rubin Observatory LSST Science Pipelines to process GOTO data, thereby exploring the feasibility of using this ‘off-the-shelf’ pipeline to process data from other wide-area, high-cadence surveys. In this paper, we describe how we use the LSST Science Pipelines to process raw GOTO frames to ultimately produce calibrated coadded images and photometric source catalogues. After comparing the measured astrometry and photometry to those of matched sources from PanSTARRS DR1, we find that measured source positions are typically accurate to subpixel levels, and that measured L-band photometries are accurate to $\sim50$ mmag at $m_L\sim16$ and $\sim200$ mmag at $m_L\sim18$. These values compare favourably to those obtained using GOTO’s primary, in-house pipeline, gotophoto, in spite of both pipelines having undergone further development and improvement beyond the implementations used in this study. Finally, we release a generic ‘obs package’ that others can build upon, should they wish to use the LSST Science Pipelines to process data from other facilities.
Both patient composition and medical care received in clinical trials may not be representative of clinical practice, yet health technology assessments (HTAs) commonly use extrapolation results from trials to estimate incremental benefit. Due to data limitations, external validation of trial extrapolations are uncommon. With the goal of better estimating the benefit of new therapies in practice, we compared long-term survival estimated from real-world patients who received therapy similar to the comparator arm of the OAK trial, a phase III study of patients with advanced non-small cell lung cancer (aNSCLC) who progressed following initial chemotherapy, to standard estimation approaches.
We estimated long-term survival from: (i) direct extrapolation of trial survival curves; and (ii) aNSCLC patients from the United States Flatiron Health Electronic Health Record ()-derived de-identified database diagnosed between January 2011 and August 2019 who received docetaxel monotherapy after platinum-doublet and had adequate organ function as well as functional status. Patients with unknown organ function and functional status were also included. Standard parametric extrapolations were applied and selected based on visual inspection and goodness-of-fit tests for each cohort.
Using a log-logistic model to extrapolate the trial comparator arm (N = 425), estimated lifetime mean overall survival was 19.2 months (95% confidence interval [95% CI]: 16.5–22.6), and 14.4 months (95% CI: 12.4–17.0) for the real-world cohort (N = 415). Estimated 5-year overall survival rates were 5.4 percent (95% CI: 3.9–7.3) for the trial patients, compared to 3.7 percent (95% CI: 2.6–5.0) among real-world cohort patients.
Our results suggest that directly extrapolating observed survival for trial patients may overestimate the long-term survival compared to the experience of patients treated in routine practice. Our findings have implications for those wishing to estimate the incremental benefit for novel versus established treatments. We plan to compare our results to a generic patient cohort from national cancer registry. Further EHR-based studies utilizing real world data are needed to confirm our findings and to extend beyond this use case for other cancer types and anti-neoplastic therapies.
Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055–0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191–0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.
Selective pressure exerted by the widespread use of antibacterial drugs is accelerating the development of resistant bacterial populations. The purpose of this scoping review was to summarise the range of studies that use dynamic models to analyse the problem of bacterial resistance in relation to antibacterial use in human and animal populations. A comprehensive search of the peer-reviewed literature was performed and non-duplicate articles (n = 1486) were screened in several stages. Charting questions were used to extract information from the articles included in the final subset (n = 81). Most studies (86%) represent the system of interest with an aggregate model; individual-based models are constructed in only seven articles. There are few examples of inter-host models outside of human healthcare (41%) and community settings (38%). Resistance is modelled for a non-specific bacterial organism and/or antibiotic in 40% and 74% of the included articles, respectively. Interventions with implications for antibacterial use were investigated in 67 articles and included changes to total antibiotic consumption, strategies for drug management and shifts in category/class use. The quality of documentation related to model assumptions and uncertainty varies considerably across this subset of articles. There is substantial room to improve the transparency of reporting in the antibacterial resistance modelling literature as is recommended by best practice guidelines.
The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.
the maternally inherited MTTL1 A3243G mutation in the mitochondrial genome causes MelaS (Mitochondrial encephalopathy lactic acidosis with Stroke-like episodes), a condition that is multisystemic but affects primarily the nervous system. Significant intra-familial variation in phenotype and severity of disease is well recognized.
retrospective and ongoing study of an extended family carrying the MTTL1 A3243G mutation with multiple symptomatic individuals. tissue heteroplasmy is reviewed based on the clinical presentations, imaging studies, laboratory findings in affected individuals and pathological material obtained at autopsy in two of the family members.
there were seven affected individuals out of thirteen members in this three generation family who each carried the MTTL1 A3243G mutation. the clinical presentations were varied with symptoms ranging from hearing loss, migraines, dementia, seizures, diabetes, visual manifestations, and stroke like episodes. three of the family members are deceased from MelaS or to complications related to MelaS.
the results of the clinical, pathological and radiological findings in this family provide strong support to the current concepts of maternal inheritance, tissue heteroplasmy and molecular pathogenesis in MelaS. neurologists (both adult and paediatric) are the most likely to encounter patients with MelaS in their practice. genetic counselling is complex in view of maternal inheritance and heteroplasmy. newer therapeutic options such as arginine are being used for acute and preventative management of stroke like episodes.
Previous evidence has suggested an association between cryptosporidiosis and consumption of unfiltered drinking water from Loch Katrine in Scotland. Before September 2007, the water was only micro-strained and chlorinated; however, since that time, coagulation and rapid gravity filtration have been installed. In order to determine risk factors associated with cryptosporidiosis, including drinking water, we analysed data on microbiologically confirmed cases of cryptosporidiosis from 2004 to 2010. We identified an association between the incidence of cryptosporidiosis and unfiltered Loch Katrine drinking water supplied to the home (odds ratio 1·86, 95% confidence interval 1·11–3·11, P = 0·019). However, while filtration appears to be associated with initially reduced rates of cryptosporidiosis, evidence suggests it may paradoxically make those consumers more susceptible to other transmission routes in the long-term. These findings support implementation of similar treatment for other unfiltered drinking-water supplies, as a means of reducing cryptosporidiosis associated with drinking water.
The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7–11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0·26%, 95% confidence interval (CI) 0·14–0·44]. The estimated average annual incidence of hepatitis B was estimated to be 29·26/100 000 children (95% CI 16·00–49·08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5·00 and 12·49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.
Cyclospora cayetanensis is an emerging infectious agent. The aim of this study was to describe an outbreak that occurred in 250 adults exposed to contaminated food, focusing on the duration and relapses of symptoms, complications and evidence of local transmission. This outbreak affected workers who ate in a restaurant in June 2005. Cyclospora sp. was observed in the stools of 20 cases and 122 probable cases were identified. The attack rate was estimated at 89%. Main symptoms were diarrhoea (96%), nausea (88%), fatigue (87%), abdominal cramps (85%), fever (52%) and headaches (45%). Contaminated fresh basil originating from a Mexican farm, used to prepare an uncooked appetizer, was identified as the source. In this non-endemic population of immunocompetent adults, Cyclospora infection presents with watery diarrhoea lasting from 4 to 18 days and fatigue lasting from 11 to 42 days. For a small proportion of affected persons, recovery can be delayed.
Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean litres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0·001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.
In 1964, the Medical Research Council undertook a trial of measles vaccine in over 36000 United Kingdom children; 9577 of whom received live vaccine, 10625 received inactivated followed by live vaccine, and 16328 acted as unvaccinated controls. Participants in this study have been followed to determine the long term protection from measles vaccine and follow-up data were available on 4194, 4638 and 274 respectively. During the 5–year period 1986–90, the protective efficacy of live measles vaccine has remained high at 87%, but the 95% confidence interval was wide ( –43 to 99%) due to the small numbers of cases. Between 1976 and 1990, however, the overall efficacy of the live vaccine was 92% (95% confidence interval 86 to 95%) and there was no evidence of a decline in efficacy (P = 0.13) over the 15–year period. This study suggests that the protection from live measles vaccine persists for up to 27 years after vaccination, and that no change in the current United Kingdom measles immunization policy should be made on the grounds of waning immunity.
The consequences of vocal fold paralysis include voice change, airway problems and difficulty swallowing. Medialisation procedures using injected material have been used for many decades, with varying outcomes, mainly secondary to lifespan, tissue reaction or migration. Newer materials have recently become clinically available which are easier to manage and supposedly less likely to elicit foreign body reaction.
Method of study:
We report a case of foreign body reaction and possible migration of polymethylsiloxane gel (Bioplastique™), one such material, after vocal fold injection. To our knowledge, this is the second such case described.
This case highlights the fact that the risk of foreign body reaction and migration is still present for this material, albeit low. We also highlight the fact that, although this material can cause foreign body reactions and may possibly migrate, it is removable by microlaryngoscopy via the microflap technique, with vocal improvement.
In “The Strategic Logic of Suicide Terrorism,” Robert Pape (2003) presents an analysis of his suicide terrorism data. He uses the data to draw inferences about how territorial occupation and religious extremism affect the decision of terrorist groups to use suicide tactics. We show that the data are incapable of supporting Pape's conclusions because he “samples on the dependent variable.”—The data only contain cases in which suicide terror is used. We construct bounds (Manski, 1995) on the quantities relevant to Pape's hypotheses and show exactly how little can be learned about the relevant statistical associations from the data produced by Pape's research design.
This study evaluated the first use of a combination of the lyophilized components of the conjugated group C vaccine Menjugate™ reconstituted with the liquid group B outer membrane vesicle (OMV) vaccine MeNZB™. At 6-week intervals, healthy residential students received three doses of MeNZB alone or concomitantly with one dose of Menjugate (MeNZB+MenC). Short-lasting injection-site reactions of mild or moderate intensity were frequent in both groups. There were no vaccine-related serious adverse events. After three doses, the percentage of subjects with serum bactericidal assay (SBA) titres ⩾1:8 against the serogroup B strain NZ98/254 was 82% for MeNZB+MenC and 78% for MeNZB. All subjects in the MeNZB+MenC group achieved SBA titres ⩾1:8 against serogroup strain C11 and 67% in the MeNZB group. All SBA and ELISA responses of the combined vaccine were at least as good as for MeNZB alone. After vaccination, the pharyngeal carriage rate of any meningococcus in the vaccinated group had declined from 40% to 21%.
The Seiland Igneous Province (SIP) of northern Norway comprises a suite of mainly gabbroic plutons, with subordinate ultramafic, syenitic and felsic intrusions. Several intrusions from the Seiland Igneous Province have been dated by ID-TIMS U–Pb zircon and monazite analyses. The Hasvik Gabbro on the island of Sørøy, previously assigned an age of 700±33 Ma by Sm–Nd, yields a U–Pb zircon age of 562±6 Ma, within error of the Storelv Gabbro (569±5 Ma) and a diorite associated with the Breivikbotn Gabbro (571±4 Ma). Various intrusions on the Øksfjord peninsula give nearly identical ages of 565±9 Ma (gabbro), 566±4 Ma (monzonite), 565±5 Ma (monzodiorite), 570±9 Ma (norite), and 566±1 Ma (orthopyroxenite). These ages overlap with those from Sørøy, and define a single and short-lived period of gabbroic (to felsic) magmatism for the region between 570 and 560 Ma, pre-dating a subordinate episode of alkalic magmatism at 530–520 Ma. The U–Pb ages contradict the previous geochronological interpretation for the Finnmark area, which implied a period of 250 m.y. for the emplacement of the SIP intrusions. The new age data also clearly distinguish the Seiland intrusions, emplaced into the Sørøy Group metasediments of the Kalak Nappe Complex, from several older granitic intrusions (c. 850 to 600 Ma) that cut the Sørøy Group farther east and south. The coincident ages of the different Seiland intrusive bodies also contradict the previous structural model for the area, which posits that the different gabbro bodies were emplaced at intervals, with compressional deformation affecting the gabbros between periods of intrusion. The short time span between the main plutonic phases strongly suggests that the mechanism for the emplacement of mafic magma operated in a single, probably extensional, tectonic regime. The mafic intrusions were later deformed and metamorphosed to at least amphibolite facies, most likely by the Scandian (420 Ma) phase of the Caledonian Orogeny.