Indigenous Cultural Identity of Research Authors Standard: research and reconciliation with Indigenous Peoples in rural health journals.

The Indigenous Cultural Identity of Research Authors Standard (ICIRAS) is based on a gap in research publishing practice where Indigenous peoples' identity is not systematically and rigorously recognised in rural health research publications. There are widespread reforms, in different research areas, to counter the reputation of scientific research as a vehicle of racism and discrimination. Reflecting on these broader movements, the editorial teams of three rural health journals - Rural and Remote Health, the Australian Journal of Rural Health, and the Canadian Journal of Rural Medicine - adopted a policy of 'Nothing about Indigenous Peoples, without Indigenous Peoples'. This meant changing practices so that Indigenous Peoples' identity could be embedded in authorship credentials - such as in the byline. An environmental scan of literature about the inclusion of Indigenous Peoples in research revealed many ways in which editorial boards of journals could improve their process to signal to readers that Indigenous voices are included in rural health research publication governance. Improving the health and wellbeing of Indigenous peoples worldwide requires high-quality research evidence. This quality benchmark needs to explicitly signal the inclusion of Indigenous authors. The ICIRAS is a call to action for research journals and institutions to rigorously improve research governance and leadership to amplify the cultural identity of Indigenous peoples in rural health research.

Exploring Dentist Opinions on the Provision of Intravenous Sedation in Primary Dental Care for UK Armed Forces Personnel.

INTRODUCTION: Anxiety toward dental treatment can lead to preventable morbidity, most notably oral pain and infection. This is of concern to the UK Armed Forces (UK AF), as dental care may not be immediately accessible during deployments and exercises, necessitating aeromedical evacuation. Current Defence Policy states that serving UK AF personnel requiring sedation to tolerate routine dental treatment are to have their Joint Medical Employment Standard (JMES) reviewed to restrict their deployability and employability. This article explores current sedation delivery, dentist opinion, and adherence to policy. MATERIALS AND METHODS: The total number and type of intravenous (IV) sedation appointments over a 6-month period was assessed using surgical logbooks. Questionnaires were sent to all dentists in primary care responsible for treating military patients to ascertain their attitudes toward the requirement for sedation in support of recruitment and deployability. Ten-year retrospective data analyses were used to identify current trends in sedation use in the UK AF. RESULTS: Responses were received from 117/137 (85%) dentists. All of the responding Civilian Dental Practitioners felt that there was a requirement for IV sedation in contrast to the Royal Navy (RN), where over a quarter (28%) disagreed. The majority, 48 (81%), of Army dentists felt that military patients unable to tolerate routine treatment under local anesthesia alone should not deploy on operations, compared with 7 (63%) of their civilian counterparts. Overall, 72 (62%) respondents felt that patients unable to tolerate routine treatment without sedation should not be recruited. CONCLUSIONS: Civilian Dental Practitioners in the sample indicated that they were less likely to recommend a patient for JMES review, less likely to prevent patients from deploying and less likely to believe that individuals requiring sedation for routine treatment should not be recruited into the UK AF. These attitudes are contrary to current Defence direction and could increase the risk of UK AF personnel experiencing morbidity on deployment requiring aeromedical evacuation. Over the longer term, civilianization of Defence dentistry is likely to reduce collective operational experience and Defence must ensure that clinicians understand the management of anxious patients in the military context and their responsibilities in relation to JMES. Furthermore, policy limiting the recruitment of personnel with significant dental anxiety is not being robustly adhered to. Based on the number of dental procedures undertaken under IV sedation in the UK AF, consistent application of this policy would not affect recruitment at an organizational level, but would limit the risk of deploying these personnel. Further work is required to understand dental anxiety within the UK Armed Forces so that the operational morbidity risks can be quantified and provision appropriately planned.

A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease.

The most common treatment for patients with sickle cell disease (SCD) is the chemotherapeutic hydroxyurea, a therapy with pleiotropic effects, including increasing fetal hemoglobin (HbF) in red blood cells and reducing adhesion of white blood cells to the vascular endothelium. Hydroxyurea has been proposed to mediate these effects through a mechanism of increasing cellular cGMP levels. An alternative path to increasing cGMP levels in these cells is through the use of phosphodiesterase-9 inhibitors that selectively inhibit cGMP hydrolysis and increase cellular cGMP levels. We have developed a novel, potent and selective phosphodiesterase-9 inhibitor (IMR-687) specifically for the treatment of SCD. IMR-687 increased cGMP and HbF in erythroid K562 and UT-7 cells and increased the percentage of HbF positive erythroid cells generated in vitro using a two-phase liquid culture of CD34+ progenitors from sickle cell blood or bone marrow. Oral daily dosing of IMR-687 in the Townes transgenic mouse SCD model, increased HbF and reduced red blood cell sickling, immune cell activation and microvascular stasis. The IMR-687 reduction in red blood cell sickling and immune cell activation was greater than that seen with physiological doses of hydroxyurea. In contrast to other described phosphodiesterase-9 inhibitors, IMR-687 did not accumulate in the central nervous system, where it would inhibit phosphodiesterase-9 in neurons, or alter rodent behavior. IMR-687 was not genotoxic or myelotoxic and did not impact fertility or fetal development in rodents. These data suggest that IMR-687 may offer a safe and effective oral alternative for hydroxyurea in the treatment of SCD.

Differential Regulation of Genes Involved in Root Morphogenesis and Cell Wall Modification is Associated with Salinity Tolerance in Chickpea.

Salinity is a major constraint for intrinsically salt sensitive grain legume chickpea. Chickpea exhibits large genetic variation amongst cultivars, which show better yields in saline conditions but still need to be improved further for sustainable crop production. Based on previous multi-location physiological screening, JG 11 (salt tolerant) and ICCV 2 (salt sensitive) were subjected to salt stress to evaluate their physiological and transcriptional responses. A total of ~480 million RNA-Seq reads were sequenced from root tissues which resulted in identification of 3,053 differentially expressed genes (DEGs) in response to salt stress. Reproductive stage shows high number of DEGs suggesting major transcriptional reorganization in response to salt to enable tolerance. Importantly, cationic peroxidase, Aspartic ase, NRT1/PTR, phosphatidylinositol phosphate kinase, DREB1E and ERF genes were significantly up-regulated in tolerant genotype. In addition, we identified a suite of important genes involved in cell wall modification and root morphogenesis such as dirigent proteins, expansin and casparian strip membrane proteins that could potentially confer salt tolerance. Further, phytohormonal cross-talk between ERF and PIN-FORMED genes which modulate the root growth was observed. The gene set enrichment analysis and functional annotation of these genes suggests they may be utilised as potential candidates for improving chickpea salt tolerance.

A high-density SNP genotyping array for Brassica napus and its ancestral diploid species based on optimised selection of single-locus markers in the allotetraploid genome.

KEY MESSAGE: The Brassica napus Illumina array provides genome-wide markers linked to the available genome sequence, a significant tool for genetic analyses of the allotetraploid B. napus and its progenitor diploid genomes. A high-density single nucleotide polymorphism (SNP) Illumina Infinium array, containing 52,157 markers, was developed for the allotetraploid Brassica napus. A stringent selection process employing the short probe sequence for each SNP assay was used to limit the majority of the selected markers to those represented a minimum number of times across the highly replicated genome. As a result approximately 60 % of the SNP assays display genome-specificity, resolving as three clearly separated clusters (AA, AB, and BB) when tested with a diverse range of B. napus material. This genome specificity was supported by the analysis of the diploid ancestors of B. napus, whereby 26,504 and 29,720 markers were scorable in B. oleracea and B. rapa, respectively. Forty-four percent of the assayed loci on the array were genetically mapped in a single doubled-haploid B. napus population allowing alignment of their physical and genetic coordinates. Although strong conservation of the two positions was shown, at least 3 % of the loci were genetically mapped to a homoeologous position compared to their presumed physical position in the respective genome, underlying the importance of genetic corroboration of locus identity. In addition, the alignments identified multiple rearrangements between the diploid and tetraploid Brassica genomes. Although mostly attributed to genome assembly errors, some are likely evidence of rearrangements that occurred since the hybridisation of the progenitor genomes in the B. napus nucleus. Based on estimates for linkage disequilibrium decay, the array is a valuable tool for genetic fine mapping and genome-wide association studies in B. napus and its progenitor genomes.

Sequence and structure of Brassica rapa chromosome A3.

BACKGROUND: The species Brassica rapa includes important vegetable and oil crops. It also serves as an excellent model system to study polyploidy-related genome evolution because of its paleohexaploid ancestry and its close evolutionary relationships with Arabidopsis thaliana and other Brassica species with larger genomes. Therefore, its genome sequence will be used to accelerate both basic research on genome evolution and applied research across the cultivated Brassica species. RESULTS: We have determined and analyzed the sequence of B. rapa chromosome A3. We obtained 31.9 Mb of sequences, organized into nine contigs, which incorporated 348 overlapping BAC clones. Annotation revealed 7,058 protein-coding genes, with an average gene density of 4.6 kb per gene. Analysis of chromosome collinearity with the A. thaliana genome identified conserved synteny blocks encompassing the whole of the B. rapa chromosome A3 and sections of four A. thaliana chromosomes. The frequency of tandem duplication of genes differed between the conserved genome segments in B. rapa and A. thaliana, indicating differential rates of occurrence/retention of such duplicate copies of genes. Analysis of 'ancestral karyotype' genome building blocks enabled the development of a hypothetical model for the derivation of the B. rapa chromosome A3. CONCLUSIONS: We report the near-complete chromosome sequence from a dicotyledonous crop species. This provides an example of the complexity of genome evolution following polyploidy. The high degree of contiguity afforded by the clone-by-clone approach provides a benchmark for the performance of whole genome shotgun approaches presently being applied in B. rapa and other species with complex genomes.

Clinical trials in ventilator treatment: current perspectives and future challenges.

PURPOSE OF REVIEW: Mortality/morbidity-based end points have been useful in evaluating treatments that modulate 'mediator variables' with a large effect size. Ventilation is usually a supportive measure, and hence is best seen as a 'moderator variable'. It can, therefore, have only a modest impact on disease-specific mortality. In this context, over reliance on final outcome-based end points (mortality, length of stay, etc.) risks the abandonment of several potentially useful developments. These concepts are important in considering how future developments should be evaluated. MAIN FINDINGS: A modest effect size implies that large sample sizes will be necessary to demonstrate mortality/morbidity benefits. Recruiting large numbers over geographically/culturally/economically heterogeneous areas over long periods (during which clinical practice is unlikely to remain constant) has several limitations. Furthermore, manifestations of critical illness are based on nonlinear interactions between insult, host responses and other moderator variables. In such nonlinear systems the final outcome is unpredictable and does not follow simple linear assumptions. Such 'unexpected' events occurring in clinical trials involving moderator variables, may potentially lead to erroneous conclusions. SUMMARY: It is crucial that a more dynamic approach, not based on final outcome alone, is considered in designing new clinical trials involving new ventilation strategies.