Rescuing the profession we love: general practice training sector recommendations for improving the attractiveness of general practice training. A qualitative analysis.

OBJECTIVES: To investigate the views of the general practice training sector about responding to recruitment challenges, with the aim of identifying effective initiatives and other solutions. STUDY DESIGN: Qualitative study; focus group discussion of recommendations from a medical educator workshop. SETTING, PARTICIPANTS: An initial online appreciative enquiry workshop for medical educators followed by focus group discussions by a broader selection of people involved in general practitioner training (Royal Australian College of General Practitioners fellows, supervisors, practice managers, medical educators, registrars). MAIN OUTCOME MEASURES: Key overarching themes and major recommendations for increasing recruitment derived from focus group responses to workshop recommendations, based on qualitative descriptive analysis. RESULTS: The 26 medical educators at the workshop made four major recommendations: increase the number of student and junior doctor clinical placements in general practice; increase exposure of students and junior doctors to general practitioner teachers and educators; improve general practitioner trainee pay and entitlements; and improve the integration of general practice and hospital patient care and professional relationships. Thirty-four semi-structured focus group participants broadly supported the recommendations, provided that supervisors and training practices were adequately compensated for the effects on workloads, income, and patient care. Two overarching themes infused participant responses: "rescuing the profession we love" (reflecting participants' passion for general practice and their sense of threat), and "no idea what general practitioners do" (perceptions of being misunderstood and misrepresented by hospital-based practitioners). CONCLUSIONS: Clinicians, educators, and policy makers should work together to increase the number of high quality, adequately supported student and junior doctor placements in general practice, improve intra-professional relationships, and trial new models of general practitioner trainee payment and conditions.

TAVAC: comprehensive review of currently available hemostatic products as adjunct to surgical hemostasis.

BACKGROUND: The use of hemostatic agents by general surgeons during abdominal operations is commonplace as an adjunctive measure to minimize risks of postoperative bleeding and its downstream complications. Proper selection of products can be hampered by marginal understanding of their pharmacokinetics and pharmacodynamics. While a variety of hemostatic agents are currently available on the market, the choice of those products is often confusing for surgeons. This paper aims to summarize and compare the available hemostatic products for each clinical indication and to ultimately better guide surgeons in the selection and proper use of hemostatic agents in daily clinical practice. METHODS: We utilized PubMed electronic database and published product information from the respective pharmaceutical companies to collect information on the characteristics of the hemostatic products. RESULTS: All commercially available hemostatic agents in the US are described with a description of their mechanism of action, indications, contraindications, circumstances in which they are best utilized, and expected results. CONCLUSION: Hemostatic products come with many different types and specifications. They are valuable tools to serve as an adjunct to surgical hemostasis. Proper education and knowledge of their characteristics are important for the selection of the right agent and optimal utilization.

Prediction of general practice licensure/certification examination performance by a measure of 'questionable' activities in clinical practice: a retrospective cohort study.

PURPOSE: 'Low-value' clinical care and medical services are 'questionable' activities, being more likely to cause harm than good or with disproportionately low benefit relative to cost. This study examined the predictive ability of the QUestionable In Training Clinical Activities Index (QUIT-CAI) for general practice (GP) registrars' (trainees') performance in Australian GP Fellowship examinations (licensure/certification examinations for independent GP). METHODS: The study was nested in ReCEnT, an ongoing cohort study in which Australian GP registrars document their in-consultation clinical practice. Outcome factors in analyses were individual registrars' scores on the three Fellowship examinations ('AKT', 'KFP', and 'OSCE' examinations) and pass/fail rates during 2012-21. Analyses used univariable and multivariable regression (linear or logistic, as appropriate). The study factor in each analysis was 'QUIT-CAI score percentage'-the percentage of times a registrar performed a QUIT-CAI clinical activity when 'at risk' (i.e. when managing a problem where performing a QUIT-CAI activity was a plausible option). RESULTS: A total of 1265, 1145, and 553 registrars sat Applied Knowledge Test, Key Features Problem, and Objective Structured Clinical Exam examinations, respectively. On multivariable analysis, higher QUIT-CAI score percentages (more questionable activities) were significantly associated with poorer Applied Knowledge Test scores (P = .001), poorer Key Features Problem scores (P = .003), and poorer Objective Structured Clinical Exam scores (P = .005). QUIT-CAI score percentages predicted Royal Australian College of General Practitioner exam failure [odds ratio 1.06 (95% CI 1.00, 1.12) per 1% increase in QUIT-CAI, P = .043]. CONCLUSION: Performing questionable clinical activities predicted poorer performance in the summative Fellowship examinations, thereby validating these examinations as measures of actual clinical performance (by our measure of clinical performance, which is relevant for a licensure/certification examination).

Improving feedback literacy in a primary care rotation.

Primary care education is a unique clinical experience for medical students. It is community-based and provides an opportunity for students to learn consultation skills with multiple sources of workplace-based feedback. Meaningful and demonstrable utilisation of this feedback by students remains an educational challenge. We showcase achievable changes to educational tasks in an established curriculum, which aim to improve student feedback literacy and create a feedback loop which improves on previous provision of unidirectional, terminal feedback. The changes have been well-received, with student and educator engagement being positive. Students have demonstrated critical reflection on feedback, and development in consultation and clinical reasoning skills.

Registrars as teachers: a qualitative study exploring the experiences of Australian general practice registrars in teaching roles.

BACKGROUND: GP registrars (specialist vocational trainees in general practice) are interested in teaching, and there are considerable benefits to teaching during training. There are, however, significant barriers for registrars as teachers, including inadequate funding, time pressures, and limited teacher training. Current evidence does not include medical educator (ME) perspectives or compare teaching settings (e.g. university vs. in-practice). Further evidence is needed to inform programs supporting registrar teaching roles. This project aimed to explore the experiences of Australian GP registrars as teachers in different contexts and from multiple stakeholder perspectives. METHODS: A qualitative study with GP registrars, GP supervisors, MEs, and medical students was conducted. Participants were registrars and new (within 12 months) Fellows with teaching experience during training, supervisors who supervised a registrar in the preceding 12 months, Royal Australian College of General Practitioner MEs, and medical students with experiences of being taught by registrars. Recruitment was open to participants nationwide and sampling was purposive, aiming for a maximum variation sample. Data collection was performed via videoconference and analysed using reflexive thematic analysis. FINDINGS: Interviews were conducted with 15 registrars, 10 supervisors, and one ME. Two focus groups involved four MEs and five medical students respectively. Registrar participants taught in a variety of settings, including in-practice, universities, hospitals, and at educational workshop days. Three had experience in GP academic posts and one as a registrar ME. There were four major themes. 1) Near-peer teaching by registrars is valuable - both for medical students and registrars. 2) Teaching makes you a better GP - participants noted the transferability of teaching skills to clinical practice. 3) The importance of the teaching context - this was identified as an important determinant for registrars in teaching roles. 4) Registrar teaching strengthens the GP workforce - participants noted that teaching could elevate general practice as a specialty and increase interest in GP training. CONCLUSIONS: Study participants saw teaching as a core skill for GPs, with transferability to their clinical practice. Registrar participants wanted greater promotion and support for teaching opportunities that counted towards attainment of Fellowship. These findings have implications for teaching practices, MEs, universities, and training providers.

Factors associated with early-career GPs' retention as independent specialists in former training practices.

INTRODUCTION: Retention of general practice registrars in their training practices is important for addressing the GP workforce deficit and maldistribution of GPs. Given that rural and remote general practices are disproportionately affected by low retention, identifying the factors that promote retention may be as important as developing recruitment strategies in these areas. Quantifying the impact of relevant factors on registrar retention will enable a better understanding of how to incentivise retention and attenuate the loss of the rural workforce to other areas. We sought to establish the prevalence and associations of retention of general practice registrars in their training practices. METHODS: This analysis was a component of the New alumni Experience of Training and independent Unsupervised Practice (NEXT-UP) study: a cross-sectional questionnaire-based study of early-career GPs in conjunction with evaluation of data contemporaneously recorded as part of vocational training. Participants were former registrars of three regional training organisations delivering general practice training in New South Wales, Tasmania, the Australian Capital Territory and Eastern Victoria, who had attained Fellowship of the Royal Australian College of General Practitioners or the Australian College of Rural and Remote Medicine between January 2016 and July 2018. The outcome measured was whether the registrar had previously worked at their current practice during vocational training. Multivariable logistic regression was used to estimate the association between relevant explanatory variables and the outcome. RESULTS: A total of 354 alumni responded (response rate 28%), of whom 322 provided data regarding previous training practice retention, with 190 (59%) having previously worked at their current practice as registrars. Among respondents who reported currently working in a regional-rural practice location (n=100), 69% reported having previously worked at their current practice during training. GPs were more likely to be retained by a practice they had trained at if it was of lower socioeconomic status (adjusted odds ratio (aOR) 0.82 (95% confidence interval (CI) 0.73-0.91), p<0.001 for each decile of socioeconomic status) and if the practice provided two or more of home visits, nursing home visits or after-hours services (aOR 4.29 (95%CI 2.10-8.75), p<0.001). They were less likely to be retained by the practice if training was completed in a regional-rural area (aOR 0.35 (95%CI 0.17-0.72), p=0.004). CONCLUSION: Regional-rural training location is associated with reduced odds of subsequent retention of general practice registrars. This is occurring despite significant government investment in expansion of general practice training in regional and rural areas. The practice factor most strongly associated with GP retention was the provision of out-of-practice and after-hours care. There may be altruistic, rather than monetary, reasons that explain this finding. Such training opportunities, if provided to all trainees, especially in regional and rural areas, would be a learning opportunity, a way of promoting holistic community-based care and an incentive for subsequent retention within the practice and community as an established GP.

Antimicrobial Resistance Laboratory Network's multisite evaluation of the ThermoFisher Sensititre GN7F broth microdilution panel for antimicrobial susceptibility testing.

In 2017, the Centers for Disease Control and Prevention (CDC) established the Antimicrobial Resistance Laboratory Network to improve domestic detection of multidrug-resistant organisms. CDC and four laboratories evaluated a commercial broth microdilution panel. Antimicrobial susceptibility testing using the Sensititre GN7F (ThermoFisher Scientific, Lenexa, KS) was evaluated by testing 100 CDC and Food and Drug Administration AR Isolate Bank isolates [40 Enterobacterales (ENT), 30 Pseudomonas aeruginosa (PSA), and 30 Acinetobacter baumannii (ACB)]. We assessed multiple amounts of transfer volume (TV) between the inoculum and tubed 11-mL cation-adjusted Mueller-Hinton broth: 1 µL [tribe Proteeae (P-tribe) only] and 10, 30, and 50 µL, resulting in respective CFU per milliter of 1 × 104, 1 × 105, 3 × 105, and 5 × 105. Four TV combinations were analyzed: standard (STD) [1 µL (P-tribe) and 10 µL], enhanced standard (E-STD) [1 µL (P-tribe) and 30 µL], 30 µL, and 50 µL. Essential agreement (EA), categorical agreement, major error (ME), and very major error (VME) were analyzed by organism then TVs. For ENT, the average EA across laboratories was <90% for 7 of 15 ß-lactams using STD and E-STD TVs. As TVs increased, EA increased (>90%), and VMEs decreased. For PSA, EA improved as TVs increased; however, MEs also increased. For ACB, increased TVs provided slight EA improvements; all TVs yielded multiple VMEs and MEs. For ENT and ACB, Minimum inhibitory concentrations (MICs) trended downward using a 1 or 10 µL TV; there were no obvious MIC trends by TV for PSA. The public health and clinical consequences of missing resistance warrant increased TV of 30 µL for the GN7F, particularly for P-tribe, despite being considered "off-label" use.

Photoluminescent Nanoparticles for Chemical and Biological Analysis and Imaging.

Research related to the development and application of luminescent nanoparticles (LNPs) for chemical and biological analysis and imaging is flourishing. Novel materials and new applications continue to be reported after two decades of research. This review provides a comprehensive and heuristic overview of this field. It is targeted to both newcomers and experts who are interested in a critical assessment of LNP materials, their properties, strengths and weaknesses, and prospective applications. Numerous LNP materials are cataloged by fundamental descriptions of their chemical identities and physical morphology, quantitative photoluminescence (PL) properties, PL mechanisms, and surface chemistry. These materials include various semiconductor quantum dots, carbon nanotubes, graphene derivatives, carbon dots, nanodiamonds, luminescent metal nanoclusters, lanthanide-doped upconversion nanoparticles and downshifting nanoparticles, triplet-triplet annihilation nanoparticles, persistent-luminescence nanoparticles, conjugated polymer nanoparticles and semiconducting polymer dots, multi-nanoparticle assemblies, and doped and labeled nanoparticles, including but not limited to those based on polymers and silica. As an exercise in the critical assessment of LNP properties, these materials are ranked by several application-related functional criteria. Additional sections highlight recent examples of advances in chemical and biological analysis, point-of-care diagnostics, and cellular, tissue, and in vivo imaging and theranostics. These examples are drawn from the recent literature and organized by both LNP material and the particular properties that are leveraged to an advantage. Finally, a perspective on what comes next for the field is offered.

'Low-value' clinical care in general practice: a cross-sectional analysis of low-value care in early-career GPs' practice.

Nonevidence-based and 'low-value' clinical care and medical services are 'questionable' clinical activities that are more likely to cause harm than good or whose benefit is disproportionately low compared with their cost. This study sought to establish general practitioner (GP), patient, practice, and in-consultation associations of an index of key nonevidence-based or low-value 'questionable' clinical practices. The study was nested in the Registrar Clinical Encounters in Training study-an ongoing (from 2010) cohort study in which Australian GP registrars (specialist GP trainees) record details of their in-consultation clinical and educational practice 6-monthly. The outcome factor in analyses, performed on Registrar Clinical Encounters in Training data from 2010 to 2020, was the score on the QUestionable In-Training Clinical Activities Index (QUIT-CAI), which incorporates recommendations of the Australian Choosing Wisely campaign. A cross-sectional analysis used negative binomial regression (with the model including an offset for the number of times the registrar was at risk of performing a questionable activity) to establish associations of QUIT-CAI scores. A total of 3206 individual registrars (response rate 89.9%) recorded 406 812 problems/diagnoses where they were at risk of performing a questionable activity. Of these problems/diagnoses, 15 560 (3.8%) involved questionable activities being performed. In multivariable analyses, higher QUIT-CAI scores (more questionable activities) were significantly associated with earlier registrar training terms: incidence rate ratios (IRRs) of 0.91 [95% confidence interval (CI) 0.87, 0.95] and 0.85 (95% CI 0.80, 0.90) for Term 2 and Term 3, respectively, compared to Term 1. Other significant associations of higher scores included the patient being new to the registrar (IRR 1.27; 95% CI 1.12, 1.45), the patient being of non-English-speaking background (IRR 1.24; 95% CI 1.04, 1.47), the practice being in a higher socioeconomic area decile (IRR 1.01; 95% CI 1.00, 1.02), small practice size (IRR 1.05; 95% CI 1.00, 1.10), shorter consultation duration (IRR 0.99 per minute; 95% CI 0.99, 1.00), and fewer problems addressed in the consultation (IRR 0.84; 95% CI 0.79, 0.89) for each additional problem]. Senior registrars' clinical practice entailed less 'questionable' clinical actions than junior registrars' practice. The association of lower QUIT-CAI scores with a measure of greater continuity of care (the patient not being new to the registrar) suggests that continuity should be supported and facilitated during GP training (and in established GPs' practice).

Clinical pharmacy practitioners' semi-visible labor: building referral relationships in interprofessional collaborative care.

Clinical pharmacy practitioners (CPP) in the Veterans Health Administration (VHA) prescribe medications and help manage chronic conditions such as diabetes, and they are increasingly working as part of interprofessional clinical teams. The challenges of integrating a new role in a clinical team are documented, but we know less about strategies new healthcare providers use to overcome these challenges. We studied how clinical pharmacy practitioners integrated into clinical teams. We conducted telephone interviews with clinical pharmacy practitioners (n = 53) and members of their clinical teams (n = 74), which were recorded, transcribed, and coded for concepts and themes. We identified four major themes. We found CPP perceived VHA as a "safe haven" for interprofessional care but found it necessary to build other prescribers' trust and confidence in their clinical skills to establish the referral relationships they needed for full integration. To facilitate their integration, CPP engaged in relational, untracked labor, which we characterize as semi-visible labor. While both CPP and clinical team members perceived CPPs' semi-visible labor as vital for implementing and maintaining strong interprofessional collaborations, such labor may be unsustainable as a long-term strategy for integrating CPP in clinical teams.

Exam prediction and the general Practice Registrar Competency Assessment Grid (GPR-CAG).

BACKGROUND: In GP training, identifying early predictors of poor summative examination performance can be challenging. We aimed to establish whether external clinical teaching visit (ECTV) performance, measured using a validated instrument (GP Registrar Competency Assessment Grid, GPR-CAG) is predictive of Royal Australian College of General Practitioners (RACGP) Fellowship examination performance. METHODS: A retrospective cohort study including GP registrars in New South Wales/Australian Capital Territory with ECTV data recorded during their first training term (GPT1), between 2014 and 2018, who attempted at least one Fellowship examination. Independent variables of interest included the four GPR-CAG factors assessed in GPT1 ('patient-centredness/caring', 'formulating hypotheses/management plans', 'professional responsibilities', 'physical examination skills'). Outcomes of interest included individual scores of the three summative examinations (Applied Knowledge Test (AKT); Key Feature Problem (KFP); and the Objective Structured Clinical Examination (OSCE)) and overall Pass/Fail status. Univariable and multivariable regression analyses were performed. RESULTS: Univariably, there were statistically significant associations (p < 0.01) between all four GPR-CAG factors and all four summative examination outcomes, except for 'formulating hypotheses/management plans' and OSCE score (p = 0.07). On multivariable analysis, each factor was significantly associated (p < 0.05) with at least one exam outcome, and 'physical examination skills' was significantly associated (p < 0.05) with all four exam outcomes. DISCUSSION: ECTV performance, via GPR-CAG scores, is predictive of RACGP Fellowship exam performance. The univariable findings highlight the pragmatic utility of ECTVs in flagging registrars who are at-risk of poor exam performance, facilitating early intervention. The multivariable associations of GPR-CAG scores and examination performance suggest that these scores provide predictive ability beyond that of other known predictors.

Early-career general practitioners' perceptions of the utility of vocational training for subsequent independent practice.

PURPOSE: To evaluate Australian early-career general practitioners' perceptions of the utility of their prior vocational training in preparing them for independent specialist practice. We hypothesised that in-practice teaching would be perceived as more useful than formal education delivered by Regional Training Organisations (RTOs). METHODS AND MATERIALS: A cross-sectional questionnaire-based study of early-career general practitioners (RTO 'alumni'). The outcomes were Likert scale ratings of alumni's perceived impact of RTO education versus in-practice training on their preparedness for independent practice. Ratings were compared using Wilcoxon signed-rank tests. Multivariable linear regression was used to establish alumni characteristics associated with perceptions of utility of in-practice versus RTO-delivered education. RESULTS: Three hundred and fifty-four alumni responded (response rate 28%). In-practice training was rated statistically significantly higher than RTO education for minor procedural skills, teaching skills, professional responsibilities, tolerating clinical uncertainty, and preparing for managing child and adolescent health, aged care, chronic disease, multi-morbidity and mental health. RTO education rated higher than in-practice training for practising evidence-based medicine and Aboriginal and Torres Strait Islander health. For a number of further areas, there was no statistically significant difference in alumni ratings of utility. CONCLUSIONS: In-practice or RTO-led teaching was perceived as more useful for some components of independent practice, whilst for others there was no significant difference. The findings support recognition of the individual educational components of a blended education/training structure.

Manifestations of circulatory assist devices in noninvasive arterial duplex evaluation: A pictorial review.

Spectral Doppler and plethysmographic waveforms vary significantly in the presence of circulatory assist devices. Understanding the effect these devices have on the waveforms and flow characteristics is necessary for the appropriate interpretation of duplex ultrasound and other noninvasive vascular studies. We review the different arterial waveforms that can be seen with circulatory assist devices.

Transitions in general practice training: quantifying epidemiological variation in trainees' experiences and clinical behaviours.

BACKGROUND: General Practice training in Australia is delivered through the apprenticeship model. General Practice supervisors support trainees transitioning from hospital-based work towards competent independent community-based practice. The timing and manner in which support should be provided is still not well understood. This study aimed to establish the variation in clinical and educational experiences and behaviours, and location, of general practice trainees' consultations by stage of their vocational training. It was hypothesised that change is greater in earlier stages of training. METHODS: A cross-sectional analysis of data (2010-2018) from the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing cohort study of Australian GP registrars' in-consultation clinical and educational experience and behaviours. Multinomial logistic regression assessed the association of demographic, educational, and clinical factors in different stages of training. The outcome factor was the training term. RESULTS: Two thousand four hundred sixteen registrars contributed data for 321,414 patient consultations. For several important variables (seeing patients with chronic disease; new patients; seeking in-consultation information or assistance; ordering pathology and imaging; and working in a small or regional practice), odds ratios were considerably greater for comparisons of Term 1 and 3, relative to comparisons of Term 2 and 3. CONCLUSION: Differences experienced in demographic, clinical and educational factors are significantly more pronounced earlier in registrars' training. This finding has educational and training implications with respect to resource allocation, trainee supervision and curriculum design. Sociocultural learning theory enables an understanding of the impact of transitions on, and how to support, general practice trainees and supervisors.

Polymer Dots with Enhanced Photostability, Quantum Yield, and Two-Photon Cross-Section using Structurally Constrained Deep-Blue Fluorophores.

Semiconducting polymer dots (Pdots) have emerged as versatile probes for bioanalysis and imaging at the single-particle level. Despite their utility in multiplexed analysis, deep blue Pdots remain rare due to their need for high-energy excitation and sensitivity to photobleaching. Here, we describe the design of deep blue fluorophores using structural constraints to improve resistance to photobleaching, two-photon absorption cross sections, and fluorescence quantum yields using the hexamethylazatriangulene motif. Scanning tunneling microscopy was used to characterize the electronic structure of these chromophores on the atomic scale as well as their intrinsic stability. The most promising fluorophore was functionalized with a polymerizable acrylate handle and used to give deep-blue fluorescent acrylic polymers with Mn > 18 kDa and D < 1.2. Nanoprecipitation with amphiphilic polystyrene-graft-(carboxylate-terminated poly(ethylene glycol)) gave water-soluble Pdots with blue fluorescence, quantum yields of 0.81, and molar absorption coefficients of (4 ± 2) × 108 M-1 cm-1. This high brightness facilitated single-particle visualization with dramatically improved signal-to-noise ratio and photobleaching resistance versus an unencapsulated dye. The Pdots were then conjugated with antibodies for immunolabeling of SK-BR3 human breast cancer cells, which were imaged using deep blue fluorescence in both one- and two-photon excitation modes.

Near-Infrared-Emitting Boron-Difluoride-Curcuminoid-Based Polymers Exhibiting Thermally Activated Delayed Fluorescence as Biological Imaging Probes.

Near-infrared-emitting polymers were prepared using four boron-difluoride-curcuminoid-based monomers using ring-opening metathesis polymerization (ROMP). Well-defined polymers with molecular weights of ≈20 kDa and dispersities <1.07 were produced and exhibited near-infrared (NIR) emission in solution and in the solid state with photoluminescence quantum yields (ΦPL ) as high as 0.72 and 0.18, respectively. Time-resolved emission spectroscopy revealed thermally activated delayed fluorescence (TADF) in polymers containing highly planar dopants, whereas room-temperature phosphorescence dominated with twisted species. Density functional theory demonstrated that rotation about the donor-acceptor linker can give rise to TADF, even where none would be expected based on calculations using ground-state geometries. Incorporation of TADF-active materials into water-soluble polymer dots (Pdots) gave NIR-emissive nanoparticles, and conjugation of these Pdots with antibodies enabled immunofluorescent labeling of SK-BR3 human breast-cancer cells.

Dextran-Functionalized Semiconductor Quantum Dot Bioconjugates for Bioanalysis and Imaging.

The prerequisites for maximizing the advantageous optical properties of colloidal semiconductor quantum dots (QDs) in biological applications are effective surface functionalization and bioconjugation strategies. Functionalization with dextran has been highly successful with some nanoparticle materials, but has had very limited application with QDs. Here, we report the preparation, characterization, and proof-of-concept applications of dextran-functionalized QDs. Multiple approaches to dextran ligands were evaluated, including performance with respect to colloidal stability across a range of pH, nonspecific binding with proteins and cells, and microinjection into cells and viability assays. Multiple bioconjugation strategies were demonstrated and applied, including covalent coupling to develop a simple pH sensor, binding of polyhistidine-tagged peptides to the QD for energy transfer-based proteolytic activity assays, and binding with tetrameric antibody complexes (TACs) to enable a sandwich immunoassay and cell immunolabeling and imaging. Our results show that dextran ligands are highly promising for the functionalization of QDs, and that the design of the ligands is tailorable to help optimally meet the requirements of applications.

Evaluation of 1,1-cyclopropylidene as a thioether isostere in the 4-thio-thienopyrimidine (TTP) series of antimalarials.

The 4-(heteroarylthio)thieno[2,3-d]pyrimidine (TTP) series of antimalarials, represented by 1 and 17, potently inhibit proliferation of the 3D7 strain of P. falciparum (EC50 70-100 nM), but suffer from oxidative metabolism. The 1,1-cyclopropylidene isosteres 6 and 16 were designed to obviate this drawback. They were prepared by a short route that features a combined Peterson methylenation / cyclopropanation transformation of, e. g., ketone 7. Isosteres 6 and 16 possess significantly attenuated antimalarial potency relative to parents 1 and 17. This outcome can be rationalized based on the increased out-of-plane steric demands of the latter two. In support of this hypothesis, the relatively flat ketone 7 retains some of the potency of 1, even though it appears to be a comparatively inferior mimic with respect to electronics and bond lengths and angles. We also demonstrate crystallographically and computationally an apparent increase in the strength of the intramolecular sulfur hole interaction of 1 upon protonation.

SARS-CoV-2 and pulmonary embolism: who stole the platelets?

BACKGROUND: Patients infected with SARS-CoV-2 often develop venous and arterial thrombosis. The high patient mortality is partly attributed to thrombotic events. An emerging trend is the presence of immunological phenomena including antiphospholipid antibodies which may promote thrombosis. The mechanism for these observations is not clear though many patients with SARS-CoV-2 develop thrombocytopenia. CASE PRESENTATION: We describe a patient with SARS-CoV-2 pneumonitis who presented with intermediate risk pulmonary embolism (PE). Careful attention to his daily platelet count suggested the possibility of immune mediated heparin-induced thrombocytopenia (HIT) which was confirmed by laboratory testing and resolved when anticoagulation was switched to a direct thrombin inhibitor. CONCLUSIONS: Since excessive platelet activation and in situ thrombosis occur in HIT, this case underscores the need to consider that thrombocytopenia in patients with SARS-CoV-2-most of whom receive heparinoids-may be unrecognized HIT. A central role for the platelet in the etiology of thrombosis during the COVID-19 pandemic should be explored.

Magnetization dynamics and its scattering mechanism in thin CoFeB films with interfacial anisotropy.

Studies of magnetization dynamics have incessantly facilitated the discovery of fundamentally novel physical phenomena, making steady headway in the development of magnetic and spintronics devices. The dynamics can be induced and detected electrically, offering new functionalities in advanced electronics at the nanoscale. However, its scattering mechanism is still disputed. Understanding the mechanism in thin films is especially important, because most spintronics devices are made from stacks of multilayers with nanometer thickness. The stacks are known to possess interfacial magnetic anisotropy, a central property for applications, whose influence on the dynamics remains unknown. Here, we investigate the impact of interfacial anisotropy by adopting CoFeB/MgO as a model system. Through systematic and complementary measurements of ferromagnetic resonance (FMR) on a series of thin films, we identify narrower FMR linewidths at higher temperatures. We explicitly rule out the temperature dependence of intrinsic damping as a possible cause, and it is also not expected from existing extrinsic scattering mechanisms for ferromagnets. We ascribe this observation to motional narrowing, an old concept so far neglected in the analyses of FMR spectra. The effect is confirmed to originate from interfacial anisotropy, impacting the practical technology of spin-based nanodevices up to room temperature.