Signatures of an eccentric disc cavity: Dust and gas in IRS 48

We test the hypothesis that the disc cavity in the `transition disc' Oph IRS 48 is carved by an unseen binary companion. We use 3D dust-gas smoothed-particle hydrodynamics simulations to demonstrate that marginally coupled dust grains concentrate in the gas over-density that forms in in the cavity around a low binary mass ratio binary. This produces high contrast ratio dust asymmetries at the cavity edge similar to those observed in the disc around IRS 48 and other transition discs. This structure was previously assumed to be a vortex. However, we show that the observed velocity map of IRS 48 displays a peculiar asymmetry that is not predicted by the vortex hypothesis. We show the unusual kinematics are naturally explained by the non-Keplerian flow of gas in an eccentric circumbinary cavity. We further show that perturbations observed in the isovelocity curves of IRS 48 may be explained as the product of the dynamical interaction between the companion and the disc. The presence of a $\sim$0.4 M$_{\odot}$ companion at a $\sim$10 au separation can qualitatively explain these observations. High spatial resolution line and continuum imaging should be able to confirm this hypothesis.Comment: 9 pages, 7 figures, accepted for publication in MNRA

Association between diabetes overtreatment in older multimorbid patients and clinical outcomes: an ancillary European multicentre study.

BACKGROUND Diabetes overtreatment is a frequent and severe issue in multimorbid older patients with type 2 diabetes (T2D). OBJECTIVE This study aimed at assessing the association between diabetes overtreatment and 1-year functional decline, hospitalisation and mortality in older inpatients with multimorbidity and polypharmacy. METHODS Ancillary study of the European multicentre OPERAM project on multimorbid patients aged ≥70 years with T2D and glucose-lowering treatment (GLT). Diabetes overtreatment was defined according to the 2019 Endocrine Society guideline using HbA1c target range individualised according to the patient's overall health status and the use of GLT with a high risk of hypoglycaemia. Multivariable regressions were used to assess the association between diabetes overtreatment and the three outcomes. RESULTS Among the 490 patients with T2D on GLT (median age: 78 years; 38% female), 168 (34.3%) had diabetes overtreatment. In patients with diabetes overtreatment as compared with those not overtreated, there was no difference in functional decline (29.3% vs 38.0%, P = 0.088) nor hospitalisation rates (107.3 vs 125.8/100 p-y, P = 0.115) but there was a higher mortality rate (32.8 vs 21.4/100 p-y, P = 0.033). In multivariable analyses, diabetes overtreatment was not associated with functional decline nor hospitalisation (hazard ratio, HR [95%CI]: 0.80 [0.63; 1.02]) but was associated with a higher mortality rate (HR [95%CI]: 1.64 [1.06; 2.52]). CONCLUSIONS Diabetes overtreatment was associated with a higher mortality rate but not with hospitalisation or functional decline. Interventional studies should be undertaken to test the effect of de-intensifying GLT on clinical outcomes in overtreated patients

Overtreatment and associated risk factors among multimorbid older patients with diabetes.

BACKGROUND In multimorbid older patients with type 2 diabetes mellitus (T2DM), the intensity of glucose-lowering medication (GLM) should be focused on attaining a suitable level of glycated hemoglobin (HbA1c ) while avoiding side effects. We aimed at identifying patients with overtreatment of T2DM as well as associated risk factors. METHODS In a secondary analysis of a multicenter study of multimorbid older patients, we evaluated HbA1c levels among patients with T2DM. Patients were aged ≥70 years, with multimorbidity (≥3 chronic diagnoses) and polypharmacy (≥5 chronic medications), enrolled in four university medical centers across Europe (Belgium, Ireland, Netherlands, and Switzerland). We defined overtreatment as HbA1c  < 7.5% with ≥1 GLM other than metformin, as suggested by Choosing Wisely and used prevalence ratios (PRs) to evaluate risk factors of overtreatment in age- and sex-adjusted analyses. RESULTS Among the 564 patients with T2DM (median age 78 years, 39% women), mean ± standard deviation HbA1c was 7.2 ± 1.2%. Metformin (prevalence 51%) was the most frequently prescribed GLM and 199 (35%) patients were overtreated. The presence of severe renal impairment (PR 1.36, 1.21-1.53) and outpatient physician (other than general practitioner [GP], i.e. specialist) or emergency department visits (PR 1.22, 1.03-1.46 for 1-2 visits, and PR 1.35, 1.19-1.54 for ≥3 visits versus no visits) were associated with overtreatment. These factors remained associated with overtreatment in multivariable analyses. CONCLUSIONS In this multicountry study of multimorbid older patients with T2DM, more than one third were overtreated, highlighting the high prevalence of this problem. Careful balancing of benefits and risks in the choice of GLM may improve patient care, especially in the context of comorbidities such as severe renal impairment, and frequent non-GP healthcare contacts

Genome-enabled insights into the biology of thrips as crop pests

Background The western flower thrips, Frankliniella occidentalis (Pergande), is a globally invasive pest and plant virus vector on a wide array of food, fiber, and ornamental crops. The underlying genetic mechanisms of the processes governing thrips pest and vector biology, feeding behaviors, ecology, and insecticide resistance are largely unknown. To address this gap, we present the F. occidentalis draft genome assembly and official gene set. Results We report on the first genome sequence for any member of the insect order Thysanoptera. Benchmarking Universal Single-Copy Ortholog (BUSCO) assessments of the genome assembly (size = 415.8 Mb, scaffold N50 = 948.9 kb) revealed a relatively complete and well-annotated assembly in comparison to other insect genomes. The genome is unusually GC-rich (50%) compared to other insect genomes to date. The official gene set (OGS v1.0) contains 16,859 genes, of which ~ 10% were manually verified and corrected by our consortium. We focused on manual annotation, phylogenetic, and expression evidence analyses for gene sets centered on primary themes in the life histories and activities of plant-colonizing insects. Highlights include the following: (1) divergent clades and large expansions in genes associated with environmental sensing (chemosensory receptors) and detoxification (CYP4, CYP6, and CCE enzymes) of substances encountered in agricultural environments; (2) a comprehensive set of salivary gland genes supported by enriched expression; (3) apparent absence of members of the IMD innate immune defense pathway; and (4) developmental- and sex-specific expression analyses of genes associated with progression from larvae to adulthood through neometaboly, a distinct form of maturation differing from either incomplete or complete metamorphosis in the Insecta. Conclusions Analysis of the F. occidentalis genome offers insights into the polyphagous behavior of this insect pest that finds, colonizes, and survives on a widely diverse array of plants. The genomic resources presented here enable a more complete analysis of insect evolution and biology, providing a missing taxon for contemporary insect genomics-based analyses. Our study also offers a genomic benchmark for molecular and evolutionary investigations of other Thysanoptera species

EurOP2E – the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers

Purpose Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. Methods CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Results Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Conclusion Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system

Genome Sequence of the Pea Aphid Acyrthosiphon pisum

Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems

Hepcidin, Serum Iron, and Transferrin Saturation in Full-Term and Premature Infants during the First Month of Life: A State-of-the-Art Review of Existing Evidence in Humans.

Neonates regulate iron at birth and in early postnatal life. We reviewed literature from PubMed and Ovid Medline containing data on umbilical cord and venous blood concentrations of hepcidin and iron, and transferrin saturation (TSAT), in human neonates from 0 to 1 mo of age. Data from 59 studies were used to create reference ranges for hepcidin, iron, and TSAT for full-term-birth (FTB) neonates over the first month of life. In FTB neonates, venous hepcidin increases 100% over the first month of life (to reach 61.1 ng/mL; 95% CI: 20.1, 102.0 ng/mL) compared with umbilical cord blood (29.7 ng/mL; 95% CI: 21.1, 38.3 ng/mL). Cord blood has a high concentration of serum iron (28.4 μmol/L; 95% CI: 26.0, 31.1 μmol/L) and levels of TSAT (51.7%; 95% CI: 46.5%, 56.9%). After a short-lived immediate postnatal hypoferremia, iron and TSAT rebounded to approximately half the levels in the cord by the end of the first month. There were insufficient data to formulate reference ranges for preterm neonates

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired