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Parameterized counting of partially injective homomorphisms
No full textWe study the parameterized complexity of the problem of counting graph homomorphisms with given partial injectivity constraints, i.e., inequalities between pairs of vertices, which subsumes counting of graph homomorphisms, subgraph counting and, more generally, counting of answers to equi-join queries with inequalities. Our main result presents an exhaustive complexity classification for the problem in fixed-parameter tractable and # W[1] -complete cases. The proof relies on the framework of linear combinations of homomorphisms as independently discovered by Chen and Mengel (PODS 16) and by Curticapean, Dell and Marx in the recent breakthrough result regarding the exact complexity of the subgraph counting problem (STOC 17). Moreover, we invoke Rota’s NBC-Theorem to obtain an explicit criterion for fixed-parameter tractability based on treewidth. The abstract classification theorem is then applied to the problem of counting locally injective graph homomorphisms from small pattern graphs to large target graphs. As a consequence, we are able to fully classify its parameterized complexity depending on the class of allowed pattern graphs
Impact of precipitation and increasing temperatures on drought trends in eastern Africa
No full textIn eastern Africa droughts can cause crop failure and lead to food insecurity. With increasing temperatures, there is an a priori assumption that droughts are becoming more severe. However, the link between droughts and climate change is not sufficiently understood. Here we investigate trends in long-term agricultural drought and the influence of increasing temperatures and precipitation deficits.
Using a combination of models and observational datasets, we studied trends, spanning the period from 1900 (to approximate pre-industrial conditions) to 2018, for six regions in eastern Africa in four drought-related annually averaged variables: soil moisture, precipitation, temperature, and evaporative demand (E0). In standardized soil moisture data, we found no discernible trends. The strongest influence on soil moisture variability was from precipitation, especially in the drier or water-limited study regions; temperature and E0 did not demonstrate strong relations to soil moisture. However, the error margins on precipitation trend estimates are large and no clear trend is evident, whereas significant positive trends were observed in local temperatures. The trends in E0 are predominantly positive, but we do not find strong relations between E0 and soil moisture trends. Nevertheless, the E0 trend results can still be of interest for irrigation purposes because it is E0 that determines the maximum evaporation rate.
We conclude that until now the impact of increasing local temperatures on agricultural drought in eastern Africa is limited and we recommend that any soil moisture analysis be supplemented by an analysis of precipitation deficit
Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season
No full textBackground
Influenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions.
Aim
To evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings.
Methods
We conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data.
Results
Compared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome.
Conclusion
Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks
Induced normothermia ameliorates the procoagulant host response in human endotoxaemia
No full textBackground
Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers.
Methods
Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg−1) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model.
Results
In control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x109 L−1([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide.
Conclusion
In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states
“I have dropped out three times”: why young people in Ethiopia often repeat years in school
No full textThis policy brief draws on qualitative research relating to young people in five communities (both rural and urban) who are part of the Young Lives longitudinal study of 3,000 children and young people in Ethiopia.
It shows how difficult children and young people have found it to complete their education without repeating one or more years, dropping out temporarily or leaving school early, and the impacts on this of location, economic background and gender.
This policy brief is based on the following working paper: Tafere, Y. and A. Tiumelissan (2020) Slow Progression: Educational Trajectories of Young Men and Women in Ethiopia, Young Lives Working Paper 192. Oxford: Young Lives. It is one of a set of eight policy briefs summarising key findings and policy implications from eight corresponding working papers based on the research for the Young Lives fifth-wave qualitative survey in 2019
Social Democratic Party exceptionalism and transnational policy linkages
No full textPolitical parties learn from successful foreign parties. But does the scope of this crossnational policy diffusion vary with party family? We use a heuristics framework to argue that
party family conditions transnational policy learning when it makes information on the
positions of sister parties more readily available and relevant. Both conditions apply to social
democracy, which, unlike other party families, faced major competitive challenges from the
1970s in the context of exceptionally strong transnational organizations – factors that, as we
contend, uniquely facilitate cross-national policy learning from successful parties within the
family. We analyze parties’ policy positions using spatial methods and find that social
democratic parties are indeed exceptional as they emulate one another across borders more
than other families. These findings have important implications for our understanding of
political representation and of social democratic parties’ election strategies over the last forty
years
Prognostication using SpO2/FiO2 in invasively ventilated ICU patients with ARDS due to COVID-19 – Insights from the PRoVENT-COVID study
No full textBackground: The SpO2/FiO2 is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO2/FiO2 for mortality in patients with ARDS due to COVID–19.
Methods: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID–19. The primary endpoint was 28–day mortality.
Results: In 869 invasively ventilated patients, 28–day mortality was 30.1%. The SpO2/FiO2 on day 1 had no prognostic value. The SpO2/FiO2 on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO2/FiO2 on day 2 (OR, 0.66 [95%–CI 0.46–0.96]) and on day 3 (OR, 0.70 [95%–CI 0.51–0.96]) were associated with 28–day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76–0.79]). The measured PaO2/FiO2 and the PaO2/FiO2 calculated from SpO2/FiO2 were strongly correlated (Spearman's r = 0.79).
Conclusions: In this cohort of patients with ARDS due to COVID–19, the SpO2/FiO2 on day 2 and day 3 are independently associated with and have prognostic capacity for 28–day mortality. The SpO2/FiO2 is a useful metric for risk stratification in invasively ventilated COVID–19 patients
Morphogens and growth factor signalling in the myeloma bone-lining niche
No full textMultiple myeloma is a malignancy caused by the clonal expansion of abnormal plasma cells. Myeloma cells have proven to be incredibly successful at manipulating their microenvironment to promote growth and to evade modern therapies. They have evolved to utilise the integral signalling pathways of the bone and bone marrow to drive disease progression. The bone marrow is often described in the context of a single structure that fills the bone cavity and supports normal haematopoiesis. However, within that structure exists two anatomically different niches, the perivascular niche and the endosteal niche. These contain different cell types functioning to support normal immune and blood cell production as well as healthy bone. These cells secrete numerous signalling molecules that can influence myeloma cell biology and behaviour. The endosteal niche is home to specific bone cell lineages and plays a pivotal role in myeloma cell establishment and survival. This review will concentrate on some of the signalling pathways that are hijacked by myeloma cells to shape a favourable environment, and the different influences myeloma cells are exposed to depending on their spatial location within the bone marrow
Massive transfusion experience, current practice and decision support: A survey of Australian and New Zealand anaesthetists
No full textMassive transfusions guided by massive transfusion protocols are commonly used to manage critical bleeding, when the patient is at significant risk of morbidity and mortality, and multiple timely decisions must be made by clinicians. Clinical decision support systems are increasingly used to provide patient-specific recommendations by comparing patient information to a knowledge base, and have been shown to improve patient outcomes. To investigate current massive transfusion practice and the experiences and attitudes of anaesthetists towards massive transfusion and clinical decision support systems, we anonymously surveyed 1000 anaesthetists and anaesthesia trainees across Australia and New Zealand. A total of 228 surveys (23.6%) were successfully completed and 227 were analysed for a 23.3% response rate. Most respondents were involved in massive transfusions infrequently (88.1% managed five or fewer massive transfusion protocols per year) and worked at hospitals which have massive transfusion protocols (89.4%). Massive transfusion management was predominantly limited by timely access to point-of-care coagulation assessment and by competition with other tasks, with trainees reporting more significant limitations compared to specialists. The majority of respondents reported that they were likely, or very likely, both to use (73.1%) and to trust (85%) a clinical decision support system for massive transfusions, with no significant difference between anaesthesia trainees and specialists (P = 0.375 and P = 0.73, respectively). While the response rate to our survey was poor, there was still a wide range of massive transfusion experience among respondents, with multiple subjective factors identified limiting massive transfusion practice. We identified several potential design features and barriers to implementation to assist with the future development of a clinical decision support system for massive transfusion, and overall wide support for a clinical decision support system for massive transfusion among respondents
