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Ultra-narrow bandwidth single-photon sources operating at room temperature are of vital importance for viable optical quantum technologies at scale, including quantum key distribution, cloud-based quantum information processing networks, and quantum metrology. Here we show a room-temperature single-photon source generating polarised photons at a rate of 5MHz based on an inorganic CsPbI3 perovskite quantum dot embedded in a tunable open optical microcavity. When coupled to the mode of the optical cavity, the quantum dot room-temperature emission becomes single-mode and the spectrum narrows down to just ∼ 1 nm. The excellent directionality of the optical modes enables high single-mode collection at RT, offering promising performance for photonic and quantum technology applications. We measure 94% single-photon purity under pulsed and continuous-wave (CW) excitation.

Differentiation of cells that compose the kidney arterioles is crucial for the formation of a functioning kidney. A group of stromal cells expressing the Forkhead Box D1 ( FoxD1 ) transcription factor (TF) will give rise to the metanephric progenitors for the mural cells of the kidneys arteries and arterioles. We investigated the molecular mechanisms that instruct the FoxD1 progenitors to adopt different cell fates to properly assemble the developing kidney vasculature. We generated FoxD1GC;R26R mT/mG mice, where all the FoxD1 descendant’s cells are labeled with green fluorescent protein (GFP). GFP+ cells were isolated by FACS from kidney cortices and performed either single-cell RNA-Seq (scRNA-Seq) or single-cell Assay for Transposase-Accessible Chromatin (scATAC-Seq ) at different developmental ages: embryos (E12 and E18) and post-natal (P5 and P30) . The integrative analysis of scRNA-Seq and scATAC-Seq identified the FoxD1 derivative cell populations and their respective accessible chromatin areas over the developmental pathway. Motif analysis revealed the binding sites to putative TFs repertoire for each of the FoxD1 descendants. Therefore, we generated differentiation trajectories to track the transcriptome and epigenetics changes that occur along the differentiation pathway. At E12, the FoxD1 progenitor cells harbor open chromatin to bind TFs such as Zeb1, Maz, Snai2 and Pbx1 (p_adjusted_value (padj).: 6.7E-40; 3.6E-40; 4.1E-28; 2.5E-5; respectively) . The gene expression levels of these TFs were also significant (padj.: 5.7E-68; 6.2E-53; 4.4E-49; 2.6E-47, respectively ) . All these TFs are strongly correlated to embryogenesis. As development progresses, new open chromatin areas emerge within a different transcriptome. Interestingly, from E18 ahead, all the FoxD1 decendants exhibited the Mef2 family of TFs as the highest enriched motifs. At P30, among all the FoxD1 decendants, the Juxtaglomerular Cells have the highest enrichment score for all the Mef2 family members (padj.: 0). Thus, as the cells differentiate they acquire distinct chromatin landscapes and TF repertoires. In addition to these unique landscapes Mef2 family of TFs are prominent for the FoxD1 descendants differentiation and kidney vascular development.

Downy mildew, caused by Peronospora sparsa, is an economically important disease of boysenberries. Sporangia produced on infected tissue initiate berry infections; however the timing of sporangial release under New Zealand environmental conditions is unknown. The number of P. sparsa sporangia trapped on Vaseline®-coated slides placed weekly in three boysenberry gardens in the Nelson region from October to December in 2010 and September to December in 2011 was determined. Climate data were used to determine environmental factors that promoted sporangia production/release. Incidence of dryberry symptoms and sporulation on tissue samples incubated at 15 or 20°C under high relative humidity (RH) were assessed. Peronospora sparsa sporangia were observed on slides from all three sites, with peak sporangial numbers in mid-November in both years. Sites with the highest numbers of sporangia trapped in November had higher dryberry incidence in December. Data indicated that sporangial release was triggered by percentage of rainy days, RH and warm temperatures (16–23°C) in early spring, where high moisture periods promoted sporulation and a subsequent dry period allowed sporangial release. This study improves understanding of the timing of sporangial release to inform management practices.

Contemporary conditions in Lake Michigan where cisco (Coregonus artedi) populations are expanding are vastly different from those encountered by the historic fish community. Invasive species introductions have substantially altered the Lake Michigan ecosystem in the last half century. Successful management efforts for cisco in Lake Michigan hinge on our ability to understand their contemporary ecology, especially diet. We collected 725 cisco stomachs opportunistically from commercial fisheries (2%) and in agency surveys (98%) over six years (2014–2019). The majority (70%) of stomachs were from East Grand Traverse Bay and 96% of these were collected at Elk Rapids. Additional samples were collected from Charlevoix (8%), Little Traverse Bay (11%), other sites in northern Lake Michigan (4%), Central Lake Michigan (6%), and Green Bay (1%). Our results indicated a high degree of piscivory, in contrast to historical and contemporary accounts of planktivory for cisco in the other Laurentian Great Lakes. The top three prey items by mass were not native to the Great Lakes and these accounted for 87% of all observed prey mass consumed: round goby (Neogobius melanostomus) (58%), Bythotrephes longimanus (15%), and alewife (Alosa pseudoharengus) (14%). Round goby dominated the prey in the spring and summer, while B. longimanus and alewife occurred more in summer and fall diets. The contemporary population of cisco in Lake Michigan has been able to uniquely capitalize on abundant invasive prey resources, which may be less limiting and more energy-rich than a more typical planktivorous cisco diet.

Cs2LiLaBr6- x Cl x :Ce (CLLBC) has high energy resolution for gamma detection and high sensitivity for neutron detection. It is one of the neutron-gamma dual-mode scintillators developed in recent years. This work studies the performance of an 18-mm CLLBC cube for gamma and neutron detection for temperatures between − 20 °C and 50 °C. In addition, the scintillator was coupled to the SensL J- and C-series silicon photomultipliers (SiPMs) for comparison. Throughout the temperature range, better energy resolution is observed for the scintillator coupled to the J-series SiPMs which can be attributed to the higher photon detection efficiency. For thermal neutron detection, the output of the detector was recorded by a waveform digitizer and analyzed offline on a computer. To distinguish neutrons from gammas, a pulse shape discrimination technique was utilized. A good separation between neutrons and gammas is observed for all the temperatures. However, separating neutrons from the intrinsic alphas is somewhat difficult at low temperatures. In spite of this, this 18-mm CLLBC cube is a high-performance scintillator and is suitable for deployment in radiation detectors for nuclear security and safeguards applications.

Up to 80% of breast cancers (BCa) rely on the estrogen receptor (ER) for their growth and progression. This dependence on ER has led to many hormonal therapies that target this receptor. However, almost 40% of these cancers will acquire resistance over the course of the treatment period. One potential cause of resistance is mutations in the estrogen binding site (EBS) of ER. As such, there is an increasing need for novel inhibitors that targets ER at a site separate from the EBS. Here, we propose targeting the activation-function (AF2) pocket of ER that is important for cofactor binding and transcription activation. Billions of compounds were screened through an in-silico deep docking method, and potential AF2 inhibitors were then validated in cell-based and biophysical assays. We tested the effect of potential AF2 inhibitors on ER transcriptional activity using luciferase reporter assay in ER-positive T47D-kbluc cells. We then evaluated the effect of molecules on cell viability of ER-positive T47D and ER-negative MDA-MB-231 cells using PrestoBlue assays in order to exclude off-target effects. From these cell-based assays, we identified several inhibitors that effectively reduced transcriptional activity and viability in ER-positive T47D cells at low micromolar concentrations. We conducted PGC-1α peptide displacement assay to confirm their AF2 binding and estradiol displacement assays to exclude any binding to the EBS. Proximity ligation assay (PLA) showed disruption of the interaction between ER and coactivator SRC-3 upon treatment with ER-AF2 inhibitors in T47D cells. Current work focuses on confirming the direct binding between the compounds and recombinant ER-ligand binding domain by various biophysical assays (MST, BLI, and ITC). Future work aims to solve the structure of ER-LBD in a complex with our lead compound by X-ray crystallography. We predict that the use of potent ER-AF2 inhibitors along with current treatments, will provide a novel tactic that can act as a complementary therapeutic to target treatment resistance in ER+ BCa. Citation Format: Jane Foo, Francesco Gentile, Joseph Lee, Helene Morin, Shabnam Massah, Maria Guo, Jason Smith, Fuqiang Ban, Artem Cherkasov, Nada Lallous. Characterization of ER-AF2 inhibitors in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3079.

Telephone-administered cognitive assessments are a cost-effective, feasible, and sometimes necessary alternative to in-person assessments. However, there is a scarcity of information in large cohort studies concerning mode effects, or differences in cognitive performance attributable to assessment method instead of underlying cognition, as a potential measurement threat. We evaluated mode effects on individual cognitive items and overall cognitive score using a population-based sample of community-living older adults aged 65-79 in the US in the 2014 Health and Retirement Study for whom interview mode was randomized (n=6825). We assessed mode differences in test means and reliability, whether mode modifies associations of cognition with criterion variables, and formal measurement invariance testing by mode. Relative to those assessed face-to-face, people assessed by telephone tended to have higher scores for memory and calculation items (0.06 to 0.013 standard deviations (SD)) and lower scores for non-memory items (-0.09 to -0.01 SD). We also found evidence that estimated cognition was significantly differentially related to IADL score depending on mode of assessment, observing a stronger association among participants completing telephone interviews. Measurement invariance testing identified the largest mode differences in memory and attention items: immediate noun recall, delayed noun recall, and serial 7s scores were higher when administered by telephone. Differences by telephone vs face-to-face mode of administration are apparent in cognitive measurement in older adults, and most pronounced for tests of memory and attention that can be easier to answer via telephone. Future investigations are warranted to further evaluate methods to correct for such differences.

In a perovskite semiconductor tunable cavity, we observe spin multistability and polarization switches breaking detailed balance. These phenomena are facilitated by the system’s large spin splitting and strong self- and cross-interactions of orthogonally polarized modes.

Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and for advancement of tools for eight other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways., This collaborative effort was supported by the Gordon and Betty Moore Foundation EMS Program of the Marine Microbiology Initiative (grant nos. GBMF4972 and 4972.01 to F.-Y.B.; GBMF4970 and 4970.01 to M.A. and A.Z.W.; GBMF3788 to A.Z.W.; GBMF 4968 and 4968.01 to H.C.; GBMF4984 to V.H.; GBMF4974 and 4974.01 to C. Brownlee; GBMF4964 to Y. Hirakawa; GBMF4961 to T. Mock; GBMF4958 to P.S.; GBMF4957 to A.T.; GBMF4960 to G.J.S.; GBMF4979 to K.C.; GBMF4982 and 4982.01 to J.L.C.; GBMF4964 to P.J.K.; GBMF4981 to P.v.D.; GBMF5006 to A.E.A.; GBMF4986 to C.M.; GBMF4962 to J.A.F.R.; GBMF4980 and 4980.01 to S.L.; GBMF 4977 and 4977.01 to R.F.W.; GBMF4962.01 to C.H.S.; GBMF4985 to J.M.; GBMF4976 and 4976.01 to C.H.; GBMF4963 and 4963.01 to V.E.; GBMF5007 to C.L.D.; GBMF4983 and 4983.01 to J.L.; GBMF4975 and 4975.01 to A.D.T.; GBMF4973 and 4973.01 to I.R.-T. and GBMF4965 to N.K.), by The Leverhulme Trust (RPG-2017-364) to T. Mock and A. Hopes, and by ERD funds (16_019/0000759) from the Czech Ministry of Education to J.L.

Background Motor vehicle collisions (MVCs), particularly those associated with entrapment, are a common cause of major trauma. Current extrication methods are focused on spinal movement minimisation and mitigation, but for many patients self-extrication may be an appropriate alternative. Older drivers and passengers are increasingly injured in MVCs and may be at an increased risk of entrapment and its deleterious effects. The aim of this study is to describe the injuries, trapped status, outcomes, and potential for self-extrication for patients following an MVC across a range of age groups. Methods This is a retrospective study using the Trauma Audit and Research Network (TARN) database. Patients were included if they were admitted to an English hospital following an MVC from 2012 to 2019. Patients were excluded when their outcomes were not known or if they were secondary transfers. Simple descriptive analysis was used across the age groups: 16–59, 60–69, 70–79 and 80+ years. Logistic regression was performed to develop a model with known confounders, considering the odds of death by age group, and examining any interaction between age and trapped status with mortality. Results 70,027 patients met the inclusion criteria. Older patients were more likely to be trapped and to die following an MVC (p p Conclusions Patients over the age of 80 are more likely to die when trapped following an MVC. Self-extrication should be considered the primary route of egress for patients of all ages unless it is clearly impracticable or unachievable. For those patients who cannot self-extricate, a minimally invasive extrication approach should be employed to minimise entrapment time.

In strategic cumulative effects assessments, significant methodological challenges exist for classifying and aggregating impacts when using multiple indicators to determine relative risks upon ecological values from anthropogenic developments. We present a strategic spatial modeling case study CEA (2012–2112) in a 909,000 ha forested landscape of Southwestern British Columbia. We explore decisions needed to calculate and aggregate modeled indicators of cumulative anthropogenic footprints on landscape conditions by examining the choice of quantitative methods. We compare how aggregated impact conclusions may differ for seven indicators grouped in two ways to represent three ecological values (Forest Ecosystems, Riparian Ecosystems and Species at Risk): four expert-defined policy-driven valued components (VCs) or three analytically derived environmental resource factors (ERFs). By explicitly demonstrating methodological choices at each step of impact estimation and aggregation, we outline a practical systematic approach to customize strategic CEAs of this type and retain transparency for interpreting impacts among values. Aggregated impacts for VCs appeared dominated by those estimated from “condition” indicators describing the degree of expected deviations in indicator states from desired conditions; aggregated impacts of ERFs were dominated by “pressure” indicators linked to underlying causal processes assumed important for describing changes in future ecological conditions. High spatial congruence occurred between impact statements for some VCs compared to ERFs representing the same ecological value; poor congruence between others likely occurred because they represented different ecological processes. Aggregated impact classifications may usefully signal impact severity and risk but are dependent on indicator grouping, hence choices for aggregation are integral to the assessment process.

Here, we report the case of a patient who presented to our institution with severe, destructive, and un-reconstructable prosthetic valve endocarditis which required the planned implantation of a total artificial heart (TAH) to function as a bridge to cardiac transplantation.

European canker, Neonectria ditissima, is a worldwide apple tree disease killing shoots, branches and trees, and treatment with phosphorous acid is a possible control option. The effect of six postharvest phosphorous acid (PA) treatments on fruit residues the following season was studied in Tasman on two trial sites growing ‘Scifresh’ or ‘Scilate’ apple trees. Spray treatments consisted of number (0–3) and timing (early, mid and/or late) of PA applications. Additionally, leaf-scar wounds were artificially inoculated with N. ditissima spores at the ‘Scilate’ site on 1 and 8 June 2017 to determine disease control. Symptom expression was checked regularly between October 2017 and February 2018. None of the treatments caused a statistically significant reduction in the incidence of canker development compared with the control. Two or more PA applications resulted in PA residues in fruit, at harvest, the following season. Higher PA residues were found in fruit following early applications than with late applications. More applications of PA resulted in higher residues. This finding has important implications for exporting fruit to markets that have no tolerance for PA residues.

As the base of almost all marine food webs, phytoplankton play a dominant role in determining the productivity of marine ecosystems. Recent studies have highlighted the dynamic variability of phytoplankton abundance in nearshore ecosystems over synoptic time scales. Therefore, a greater understanding of the physical mechanisms that contribute to this variability is required to assess impacts of current as well as future weather patterns on these ecosystems. In this study, chlorophyll fluorescence data from a nearshore location in southern Monterey Bay was used to identify the timing and duration of increases in phytoplankton concentrations. Regional physical parameters, including wind stress, wave height and water temperature were analyzed to determine what, if any, physical processes are associated with observed blooms. A significant negative correlation between water temperature and chlorophyll (high chlorophyll associated with cold water) was found for the two summer seasons studied (2012, 2013). The timing of high chlorophyll events coincided with relaxations of upwelling favorable wind conditions. Analysis of surface current data suggests that the incoming cold water masses are the result of poleward currents from the south of Monterey Bay. A conceptual model is proposed in which phytoplankton are advected into southern Monterey Bay during wind relaxation events preceded by upwelling events of great enough duration to establish well defined circulation patterns. The reversal of circulation patterns transports cold, phytoplankton-rich water into the bay from south of the Monterey Peninsula. This study demonstrates that wind relaxation events can be an important driver of localized high phytoplankton biomass events on the inner shelf by advecting recently upwelled water into coastal embayments that are relatively sheltered from strong upwelling favorable winds.

Aims, Objectives and BackgroundThe use of pre-hospital blood components in the early resuscitation of patients with life-threatening bleeding is becoming more common. Understanding the national utilisation of pre-hospital blood is key to developing research strategies in these systems. The aim of this study was to report the blood resuscitation practices of UK Air Ambulances (AAs).Method and DesignTwo sequential surveys were emailed to all UK AAs using the REDCap (research electronic data capture) „system. Data were collected for 12 months during 2019 including: number of patients transported, timings, products carried, and number of patients transfused by aetiology. Data are reported as number (percentage), and mean (± standard deviation).Results and ConclusionNineteen (95.0%) AAs responded, and transported a total of 12,170 patients to hospital during 2019. The mean pre-hospital time (999-call to hospital arrival) was 92.2 (±18.6) minutes. 18 (94.7%) AAs routinely carried blood products, including combinations of red cells, thawed plasma, freeze-dried plasma, and fibrinogen concentrate, table 1. The mean units of red cells and plasma carried were 2.6 (±0.9) and 3.0 (±1.1) respectively.709 (5.8%) adult patients received a prehospital transfusion, of which n=669 (94.4%) had a traumatic aetiology; n=384 (57.4%) and n=183 (27.4%) were transfused ≥2 and ≥4 units respectively. Forty adults received prehospital blood for non-traumatic aetiologies, including: n=18 vascular, n=10 gastrointestinal, n=6 obstetric, n=6 other. In addition, n=24 paediatric patients received a prehospital transfusion; n=23 (95.8%) following trauma.Fifteen (79.0%) UK AAs surveyed wanted to take part in future research investigating the effectiveness of whole blood transfusion.Abstract 1767 Table 1Blood component combinations carried by UK Air Ambulances in 2019, n=19Blood component combinationsNumber of Air Ambulances (% of total)Red cells and freeze-dried plasma7 (36.8%)Red cells and thawed plasma*6 (31.6%)Red cells only3 (15.8%)Freeze-dried plasma only1 (5.3%)Red cells in thawed plasma (RCP)**1 (5.3%)No products1 (5.3%)* One air ambulance carried fibrinogen concentrate in addition to a combination of red cells and thawed plasma. ** RCP was being carried as part of a feasibility trial during 2019.This survey defines current pre-hospital blood transfusion practice in the UK. The majority of AAs carry a combination of red cells and plasma, which are predominantly utilised following traumatic injury. Over three-quarters of UK AAs showed interest in participating in future whole blood research.

UK National Guidelines stress the importance of reducing waiting times for mental health assessments and interventions for children. They stress the importance of early help, multidisciplinary working, and collaboration with families regarding treatment plans. We piloted a new assessment model (CARM) within a CAMHS service to: reduce non-attendance rates and subsequently waiting times; increase staff and patient satisfaction; and improve the quality of assessment. All waiting list patients and new referrals over a three-month period were contacted to self-book an hour session to meet two clinicians who utilised collaborative reflection and formulation to produce a care plan (CARM). Results revealed that non-attendance rates dropped from 33% over the month prior to CARM to 7% during CARM. Satisfaction levels were high. Qualitative feedback regarding satisfaction revealed the most common themes was feeling listened to and having the opportunity to listen to staff reflections. The themes of staff satisfaction included ‘feeling more supported’ and ‘feeling safer in their decision making’. All assessments were completed in the one appointment. A formulation-driven care plan was developed and discussed with the family. This approach has the potential to make services more effective, efficient and satisfying for both staff and families.