Risk assessment and decision making about in-labour transfer from rural maternity care: a social judgment and signal detection analysis

Background: The importance of respecting women's wishes to give birth close to their local community is supported by policy in many developed countries. However, persistent concerns about the quality and safety of maternity care in rural communities have been expressed. Safe childbirth in rural communities depends on good risk assessment and decision making as to whether and when the transfer of a woman in labour to an obstetric led unit is required. This is a difficult decision. Wide variation in transfer rates between rural maternity units have been reported suggesting different decision making criteria may be involved; furthermore, rural midwives and family doctors report feeling isolated in making these decisions and that staff in urban centres do not understand the difficulties they face. In order to develop more evidence based decision making strategies greater understanding of the way in which maternity care providers currently make decisions is required. This study aimed to examine how midwives working in urban and rural settings and obstetricians make intrapartum transfer decisions, and describe sources of variation in decision making. Methods: The study was conducted in three stages. 1. 20 midwives and four obstetricians described factors influencing transfer decisions. 2. Vignettes depicting an intrapartum scenario were developed based on stage one data. 3. Vignettes were presented to 122 midwives and 12 obstetricians who were asked to assess the level of risk in each case and decide whether to transfer or not. Social judgment analysis was used to identify the factors and factor weights used in assessment. Signal detection analysis was used to identify participants' ability to distinguish high and low risk cases and personal decision thresholds. Results: When reviewing the same case information in vignettes midwives in different settings and obstetricians made very similar risk assessments. Despite this, a wide range of transfer decisions were still made, suggesting that the main source of variation in decision making and transfer rates is not in the assessment but the personal decision thresholds of clinicians. Conclusions: Currently health care practice focuses on supporting or improving decision making through skills training and clinical guidelines. However, these methods alone are unlikely to be effective in improving consistency of decision making

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Novel Chlamydiales genotypes identified in ticks from Australian wildlife

Background: Members of the order Chlamydiales are known for their potential as human and veterinary bacterial pathogens. Despite this recognition, epidemiological factors such as routes of transmission are yet to be fully defined. Ticks are well known vectors for many other infections with several reports recently describing the presence of bacteria in the order Chlamydiales in these arthropods. Australian wildlife are hosts to an extensive range of tick species. Evidence is also growing that the marsupial hosts these ticks parasitise can also be infected by a number of bacteria in the order Chlamydiales, with at least one species, Chlamydia pecorum, posing a significant conservation threat. In the current study, we investigated the presence and identity of Chlamydiales in 438 ixodid ticks parasitizing wildlife in Australia by screening with a pan-Chlamydiales specific targeting the 16S rRNA gene. Results: Pan-Chlamydiales specific PCR assays confirmed the common presence of Chlamydiales in Australian ticks parasitising a range of native wildlife. Interestingly, we did not detect any Chlamydiaceae, including C. pecorum, the ubiquitous pathogen of the koala. Instead, the Chlamydiales diversity that could be resolved indicated that Australian ticks carry at least six novel Chlamydiales genotypes. Phylogenetic analysis of the 16S rRNA sequences (663 bp) of these novel Chlamydiales suggests that three of these genotypes are associated with the Simkaniaceae and putatively belong to three distinct novel strains of Fritschea spp. and three genotypes are related to the "Ca. Rhabdochlamydiaceae" and putatively belong to a novel genus, Rhabdochlamydia species and strain, respectively. Conclusions: Sequence results suggest Australian wildlife ticks harbour a range of unique Chlamydiales bacteria that belong to families previously identified in a range of arthropod species. The results of this work also suggest that it is unlikely that arthropods act as vectors of pathogenic members of the family Chlamydiaceae, including C. pecorum, in Australian wildlife. The biology of novel Chlamydiales identified in arthropods remain unknown. The pathogenic role of the novel Chlamydiales identified in this study and the role that ticks may play in their transmission needs to be explored further

A transcriptome resource for the koala (Phascolarctos cinereus): insights into koala retrovirus transcription and sequence diversity

Background The koala, Phascolarctos cinereus, is a biologically unique and evolutionarily distinct Australian arboreal marsupial. The goal of this study was to sequence the transcriptome from several tissues of two geographically separate koalas, and to create the first comprehensive catalog of annotated transcripts for this species, enabling detailed analysis of the unique attributes of this threatened native marsupial, including infection by the koala retrovirus. Results RNA-Seq data was generated from a range of tissues from one male and one female koala and assembled de novo into transcripts using Velvet-Oases. Transcript abundance in each tissue was estimated. Transcripts were searched for likely protein-coding regions and a non-redundant set of 117,563 putative protein sequences was produced. In similarity searches there were 84,907 (72%) sequences that aligned to at least one sequence in the NCBI nr protein database. The best alignments were to sequences from other marsupials. After applying a reciprocal best hit requirement of koala sequences to those from tammar wallaby, Tasmanian devil and the gray short-tailed opossum, we estimate that our transcriptome dataset represents approximately 15,000 koala genes. The marsupial alignment information was used to look for potential gene duplications and we report evidence for copy number expansion of the alpha amylase gene, and of an aldehyde reductase gene. Koala retrovirus (KoRV) transcripts were detected in the transcriptomes. These were analysed in detail and the structure of the spliced envelope gene transcript was determined. There was appreciable sequence diversity within KoRV, with 233 sites in the KoRV genome showing small insertions/deletions or single nucleotide polymorphisms. Both koalas had sequences from the KoRV-A subtype, but the male koala transcriptome has, in addition, sequences more closely related to the KoRV-B subtype. This is the first report of a KoRV-B-like sequence in a wild population. Conclusions This transcriptomic dataset is a useful resource for molecular genetic studies of the koala, for evolutionary genetic studies of marsupials, for validation and annotation of the koala genome sequence, and for investigation of koala retrovirus. Annotated transcripts can be browsed and queried at http://koalagenome.or

Evaluation of a biosecurity survey approach for contamination by Chlamydia pecorum in koala rehabilitation, field capture, and captive settings

Transmission of Chlamydia pecorum between koalas is a potential risk in field capture or rehabilitation settings, where koalas are held in proximity to each other, or equipment is shared between animals. Given the impact of C. pecorum on koala welfare and population viability it is surprising that quarantine and disinfection protocols in a koala rehabilitation facility or capture settings have not previously been evaluated. This study aimed to evaluate an approach, based on the detection of chlamydial DNA and cell viability, to determine the degree of environmental contamination within a koala care facility. Various fomite sites associated with koala care at a koala rehabilitation facility in New South Wales, Australia were identified as potential sources of chlamydial contamination, following exposure to koalas known to be infected with C. pecorum. Fomite sites were swabbed following exposure, and again after decontamination procedures were carried out. Samples were tested for the presence of chlamydial DNA using qPCR and viability using both RT-qPCR and cell culture. From a total of 239 sampling events, 30 tested qPCR positive for chlamydial DNA, with 19 and 11 samples corresponding to pre-decontamination and post-decontamination events respectively. Detection of chlamydial DNA appeared to be most common in the examination room, especially on fomite sites in direct contact with koalas. Physical removal of chlamydial DNA, or its degradation by the elements, appeared to be more common on outdoor enclosures, clothing, and hands. Based on the cell culture assay, of the pre-decontamination samples with chlamydial DNA, eight had viable chlamydial cells, two of these at low levels. Of the post-decontamination samples with chlamydial DNA, one had a moderate number, and one had a very low number of viable chlamydial cells. RT-qPCR was unsuccessful in determining cell viability due to low yields of RNA and high levels of contaminants from the environmental samples. The outcomes of this study provide a knowledge base for the design of future biosecurity evaluation guidelines in captive and koala rehabilitation facilities. The higher incidence of chlamydial DNA detection by qPCR than viable organism highlights the need to use viability assays in similar studies. However, further investment is still needed to optimise these methods and improve sensitivity for complex environmental samples

Additional file 1: Table S1. of Novel Chlamydiales genotypes identified in ticks from Australian wildlife

Summary of wildlife host and species, number and location of adult female Ixodidae ticks screened for Chlamydiales in this study. (DOCX 14 kb

L'Écho de Paris : revue littéraire, historique, scientifique, industrielle et moniteur des expropriations

août 19051905/08 (N7)