A phase 1/2 study of pepinemab in children, adolescents, or young adults with recurrent or refractory solid tumors: A children's oncology group consortium report (ADVL1614).

PURPOSE: Pepinemab, a humanized IgG4 monoclonal antibody, targets the SEMA4D (CD100) antigen to inhibit binding to its high-affinity receptors (plexin B1/PLXNB1, plexin B2/PLXNB2) and low-affinity receptor (CD72). SEMA4D blockade leads to increased cytotoxic T-cell infiltration, delayed tumor growth, and durable tumor rejection in murine tumor models. Pepinemab was well tolerated and improved T cell infiltration in clinical studies in adults with refractory tumors. SEMA4D was identified as a strong candidate proto-oncogene in a model of osteosarcoma. Based on these preclinical and clinical data, we conducted a phase 1/2 study to determine the recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics, and immunogenicity, of pepinemab in pediatric patients with recurrent/refractory solid tumors, and activity in osteosarcoma. EXPERIMENTAL DESIGN: Pepinemab was administered intravenously on Days 1 and 15 of a 28-day cycle at 20 mg/kg, the adult RP2D. Part A (phase 1) used a Rolling 6 design; Part B (phase 2) used a Simon 2-stage design in patients with osteosarcoma. Pharmacokinetics and target saturation were evaluated in peripheral blood. RESULTS: Pepinemab (20 mg/kg) was well tolerated and no dose-limiting toxicities were observed during Part A. There were no objective responses. Two patients with osteosarcoma achieved disease control and prolonged stable disease. Pepinemab pharmacokinetics were similar to adults. CONCLUSIONS: Pepinemab (20 mg/kg) is safe, well tolerated and resulted in adequate and sustained target saturation in pediatric patients. Encouraging disease control in two patients with osteosarcoma warrants further investigation with novel combination strategies to modulate the tumor microenvironment and antitumor immune response. CLINICAL TRIAL REGISTRY: This trial is registered as NCT03320330 at Clinicaltrials.gov. DISCLAIMER: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Position-Controlled Telecom Single Photon Emitters Operating at Elevated Temperatures.

A key resource in quantum-secured communication protocols are single photon emitters. For long-haul optical networks, it is imperative to use photons at wavelengths compatible with telecom single mode fibers. We demonstrate high purity single photon emission at 1.31 µm using deterministically positioned InP photonic waveguide nanowires containing single InAsP quantum dot-in-a-rod structures. At excitation rates that saturate the emission, we obtain a single photon collection efficiency at first lens of 27.6% and a probability of multiphoton emission of g(2)(0) = 0.021. We have also evaluated the performance of the source as a function of temperature. Multiphoton emission probability increases with temperature with values of 0.11, 0.34, and 0.57 at 77, 220 and 300 K, respectively, which is attributed to an overlap of temperature-broadened excitonic emission lines. These results are a promising step toward scalably fabricating telecom single photon emitters that operate under relaxed cooling requirements.

Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma.

Tanshinone IIA (T2A) is a bioactive compound that provides promise in the treatment of glioblastoma multiforme (GBM), with a range of molecular mechanisms including the inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy. Recently, T2A has been demonstrated to function through sestrin 2 (SESN) to inhibit mTORC1 activity, but its possible impact on autophagy through this pathway has not been investigated. Here, the model system Dictyostelium discoideum and GBM cell lines were employed to investigate the cellular role of T2A in regulating SESN to inhibit mTORC1 and activate autophagy through a GATOR2 component MIOS. In D. discoideum, T2A treatment induced autophagy and inhibited mTORC1 activity, with both effects lost upon the ablation of SESN (sesn-) or MIOS (mios-). We further investigated the targeting of MIOS to reproduce this effect of T2A, where computational analysis identified 25 novel compounds predicted to strongly bind the human MIOS protein, with one compound (MIOS inhibitor 3; Mi3) reducing cell proliferation in two GBM cells. Furthermore, Mi3 specificity was demonstrated through the loss of potency in the D. discoideum mios- cells regarding cell proliferation and the induction of autophagy. In GBM cells, Mi3 treatment also reduced mTORC1 activity and induced autophagy. Thus, a potential T2A mimetic showing the inhibition of mTORC1 and induction of autophagy in GBM cells was identified.

Risk for Infection in Humans after Exposure to Birds Infected with Highly Pathogenic Avian Influenza A(H5N1) Virus, United States, 2022.

During February 7─September 3, 2022, a total of 39 US states experienced outbreaks of highly pathogenic avian influenza A(H5N1) virus in birds from commercial poultry farms and backyard flocks. Among persons exposed to infected birds, highly pathogenic avian influenza A(H5) viral RNA was detected in 1 respiratory specimen from 1 person.

Evaluation of Digitalisation in Healthcare and the Quantification of the "Unmeasurable".

Evaluating healthcare digitalisation, where technology implementation and adoption transforms existing socio-organisational processes, presents various challenges for outcome assessments. Populations are diverse, interventions are complex and evolving over time, meaningful comparisons are difficult as outcomes vary between settings, and outcomes take a long time to materialise and stabilise. Digitalisation may also have unanticipated impacts. We here discuss the limitations of evaluating the digitalisation of healthcare, and describe how qualitative and quantitative approaches can complement each other to facilitate investment and implementation decisions. In doing so, we argue how existing approaches have focused on measuring what is easily measurable and elevating poorly chosen values to inform investment decisions. Limited attention has been paid to understanding processes that are not easily measured even though these can have significant implications for contextual transferability, sustainability and scale-up of interventions. We use what is commonly known as the McNamara Fallacy to structure our discussions. We conclude with recommendations on how we envisage the development of mixed methods approaches going forward in order to address shortcomings.

The Impact of Pre-Operative Anaemia on One Year Amputation Free Survival and Re-Admissions in Patients Undergoing Vascular Surgery for Peripheral Arterial Disease: a National Vascular Registry Study.

OBJECTIVE: Anaemia is common among patients undergoing surgery, but its association with post-operative outcomes in patients with peripheral arterial disease (PAD) is unclear. The aim of this observational population based study was to examine the association between pre-operative anaemia and one year outcomes after surgical revascularisation for PAD. METHODS: This study used data from the National Vascular Registry, linked with an administrative database (Hospital Episode Statistics), to identify patients who underwent open surgical lower limb revascularisation for PAD in English NHS hospitals between January 2016 and December 2019. The primary outcome was one year amputation free survival. Secondary outcomes were one year re-admission rate, 30 day re-intervention rate, 30 day ipsilateral major amputation rate and 30 day death. Flexible parametric survival analysis and generalised linear regression were performed to assess the effect of anaemia on one year outcomes. RESULTS: The analysis included 13 641 patients, 57.9% of whom had no anaemia, 23.8% mild, and 18.3% moderate or severe anaemia. At one year follow up, 80.6% of patients were alive and amputation free. The risk of one year amputation or death was elevated in patients with mild anaemia (adjusted HR 1.3; 95% CI 1.15 - 1.41) and moderate or severe anaemia (aHR 1.5; 1.33 - 1.67). Patients with moderate or severe anaemia experienced more re-admissions over one year (adjusted IRR 1.31; 1.26 - 1.37) and had higher odds of 30 day re-interventions (aOR 1.22; 1.04 - 1.45), 30 day ipsilateral major amputation (aOR 1.53; 1.17 - 2.01), and 30 day death (aOR 1.39; 1.03 - 1.88) compared with patients with no anaemia. CONCLUSION: Pre-operative anaemia is associated with lower one year amputation free survival and higher one year re-admission rates following surgical revascularisation in patients with PAD. Research is required to evaluate whether interventions to correct anaemia improve outcomes after lower limb revascularisation.

Editor's Choice - Outcomes of Surgery for Patients with Peripheral Arterial Disease During the COVID-19 Pandemic in the United Kingdom: A Population Based Study.

OBJECTIVE: There is limited information on changes in the patterns of care and outcomes for patients who had vascular procedures after the first wave of the COVID-19 pandemic. The aim of this population based study was to examine the patterns of care and outcomes for vascular lower limb procedures in the UK during the COVID-19 pandemic. METHODS: Lower limb revascularisations and major amputations performed from January 2019 to April 2021 in the UK and entered in the National Vascular Registry were included in the study. The primary outcome was in hospital post-operative death and secondary outcomes were complications and re-interventions. The study was divided into Pre-pandemic (1 January 2019 - 29 February 2020), Wave 1 (1 March - 30 June 2020), Respite (1 July - 31 October 2020), Wave 2/3 (1 November 2020 - 30 April 2021). RESULTS: The study included 36 938 procedures (7 245 major amputations, 16 712 endovascular, 12 981 open revascularisations), with 15 501 procedures after March 2020, a 27.7% reduction compared with pre-pandemic. The proportion of open surgical procedures performed under general anaesthetic was lower in Wave 1 and after compared with pre-pandemic (76.7% vs. 81.9%, p < .001). Only 4.6% of patients in the cohort had SARS-CoV-2 infection (n = 708), but their in hospital post-operative mortality rate was 25.0% (n = 177), six times higher than patients without SARS-CoV-2 (adjusted odds ratio 5.88; 95% CI 4.80 - 7.21, p < .001). The in hospital mortality rate was higher during the pandemic than pre-pandemic after elective open and endovascular revascularisation (respectively 1.6% vs. 1.1%, p = .033, and 0.9% vs. 0.5%, p = .005) and after major amputations (10.4% during Wave 2/3 vs. 7.7% pre-pandemic, p = .022). CONCLUSION: There was excess post-operative mortality rate for patients undergoing lower limb vascular procedures during the pandemic, which was associated with SARS-CoV-2 infections. Further research should be conducted on long term outcomes of patients operated on during the COVID-19 pandemic period.

Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling.

Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Here, we determined whether mTORC1 signaling is also a target for decanoic acid, a key component of the medium-chain triglyceride (MCT) ketogenic diet. Using a tractable model system, Dictyostelium, we show that decanoic acid can decrease mTORC1 activity, under conditions of constant glucose and in the absence of insulin, measured by phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). We determine that this effect of decanoic acid is dependent on a ubiquitin regulatory X domain-containing protein, mediating inhibition of a conserved Dictyostelium AAA ATPase, p97, a homolog of the human transitional endoplasmic reticulum ATPase (VCP/p97) protein. We then demonstrate that decanoic acid decreases mTORC1 activity in the absence of insulin and under high-glucose conditions in ex vivo rat hippocampus and in tuberous sclerosis complex (TSC) patient-derived astrocytes. Our data therefore indicate that dietary decanoic acid may provide a new therapeutic approach to down-regulate mTORC1 signaling.

Socio-Organizational Dimensions: The Key to Advancing the Shared Care Record Agenda in Health and Social Care.

Integrating health and social care delivery with the help of digital technologies is a grand challenge. We argue that previous attempts have largely failed to achieve their objectives because implementers and decision makers disregard the complex socio-organizational dimensions of change associated with initiatives. These include structural and organizational complexity inhibiting the development of shared care pathways; professional jurisdictions, interests, and expertise; and existing data and governance structures. We provide an overview of those dimensions that can inform strategic decisions going forward, thereby contributing to the chances of success of shared care initiatives.

Learning From Experience and Finding the Right Balance in the Governance of Artificial Intelligence and Digital Health Technologies.

Artificial intelligence (AI) and machine learning medical tools have the potential to be transformative in care delivery; however, this change will only be realized if accompanied by effective governance that ensures patient safety and public trust. Recent digital health initiatives have called for tighter governance of digital health. A correct balance must be found between ensuring product safety and performance while also enabling the innovation needed to deliver better approaches for patients and affordable efficient health care for society. This requires innovative, fit-for-purpose approaches to regulation. Digital health technologies, particularly AI-based tools, pose specific challenges to the development and implementation of functional regulation. The approaches of regulatory science and "better regulation" have a critical role in developing and evaluating solutions to these problems and ensuring effective implementation. We describe the divergent approaches of the European Union and the United States in the implementation of new regulatory approaches in digital health, and we consider the United Kingdom as a third example, which is in a unique position of developing a new post-Brexit regulatory framework.

Optimising ePrescribing in hospitals through the interoperability of systems and processes: a qualitative study in the UK, US, Norway and the Netherlands.

BACKGROUND: Investment in the implementation of hospital ePrescribing systems has been a priority in many economically-developed countries in order to modernise the delivery of healthcare. However, maximum gains in the safety, quality and efficiency of care are unlikely to be fully realised unless ePrescribing systems are further optimised in a local context. Typical barriers to optimal use are often encountered in relation to a lack of systemic capacity and preparedness to meet various levels of interoperability requirements, including at the data, systems and services levels. This lack of systemic interoperability may in turn limit the opportunities and benefits potentially arising from implementing novel digital heath systems. METHODS: We undertook n = 54 qualitative interviews with key stakeholders at nine digitally advanced hospital sites across the UK, US, Norway and the Netherlands. We included hospitals featuring 'standalone, best of breed' systems, which were interfaced locally, and multi-component and integrated electronic health record enterprise systems. We analysed the data inductively, looking at strategies and constraints for ePrescribing interoperability within and beyond hospital systems. RESULTS: Our thematic analysis identified 4 main drivers for increasing ePrescribing systems interoperability: (1) improving patient safety (2) improving integration & continuity of care (3) optimising care pathways and providing tailored decision support to meet local and contextualised care priorities and (4) to enable full patient care services interoperability in a variety of settings and contexts. These 4 interoperability dimensions were not always pursued equally at each implementation site, and these were often dependent on the specific national, policy, organisational or technical contexts of the ePrescribing implementations. Safety and efficiency objectives drove optimisation targeted at infrastructure and governance at all levels. Constraints to interoperability came from factors such as legacy systems, but barriers to interoperability of processes came from system capability, hospital policy and staff culture. CONCLUSIONS: Achieving interoperability is key in making ePrescribing systems both safe and useable. Data resources exist at macro, meso and micro levels, as do the governance interventions necessary to achieve system interoperability. Strategic objectives, most notably improved safety, often motivated hospitals to push for evolution across the entire data architecture of which they formed a part. However, hospitals negotiated this terrain with varying degrees of centralised coordination. Hospitals were heavily reliant on staff buy-in to ensure that systems interoperability was built upon to achieve effective data sharing and use. Positive outcomes were founded on a culture of agreement about the usefulness of access by stakeholders, including prescribers, policymakers, vendors and lab technicians, which was reflected in an alignment of governance goals with system design.

From ACEs to early relational health: Implications for clinical practice.

Children grow and develop in an environment of relationships. Safe, stable, nurturing relationships help build resilience and buffer the negative impact of adverse experiences. Promoting relational health in clinical practice shifts the focus from adverse childhood experiences (ACEs) to positive childhood experiences (PCEs). This approach evaluates a family's strengths and assets, and can be incorporated into both well-child and subspecialty care. While the optimal window for such interventions is in the prenatal period or as early as possible within the first 3 years of life, it is never too late to start. This statement describes how clinicians can bring a relational health approach to any medical encounter by understanding: what toxic stress is and how it can affect the developing brain, family relationships, and child development; how positive relationships, experiences, and behaviours can help buffer such effects and build resilience; observable signs of relational health and risk in parent-child interactions; the attributes of trustful, therapeutic relationships with families; and how to optimize these benefits through conversation and clinical practice.

Des expériences négatives de l'enfance à la santé relationnelle précoce : les conséquences pour la pratique clinique.

Les enfants grandissent et se développent dans un environnement de relations. Des relations sécuritaires, stables et bienveillantes contribuent à consolider la résilience et à atténuer les répercussions des expériences négatives. La promotion de la santé relationnelle en pratique clinique recentre l'attention accordée aux expériences négatives de l'enfance sur les expériences positives de l'enfance. Cette approche, qui évalue les forces et les atouts d'une famille, peut être intégrée à la fois aux rendez-vous réguliers de l'enfant en santé et aux soins surspécialisés. Il est optimal de réaliser de telles interventions pendant la période prénatale ou le plus rapidement possible avant l'âge de trois ans, mais il n'est jamais trop tard pour les entreprendre. Le présent document de principes décrit comment les cliniciens peuvent adopter une approche de santé relationnelle lors de chacune de leurs rencontres médicales s'ils comprennent ce qu'est le stress toxique et ses effets sur le cerveau en développement, les relations familiales et le développement de l'enfant; à quel point les relations, expériences et comportements positifs peuvent en atténuer les effets et renforcer la résilience; quels sont les signes observables de la santé relationnelle et des risques relationnels dans les interactions entre les parents et l'enfant; quelles sont les caractéristiques de relations thérapeutiques de confiance avec les familles et comment en optimiser les avantages par les échanges et la pratique clinique.

Neutropenia in pediatric solid organ transplant.

Neutropenia is generally defined as an absolute neutrophil count in the circulation of less than 1500/mm3 and occurs in up to 25%-30% of pediatric solid organ transplant recipients (SOT) within the first year after transplantation. In the SOT population, neutropenia is most often a result of drug-induced bone marrow suppression but can also be secondary to viral infection, nutritional deficiencies, lymphoproliferative infiltrate, and inherited causes. Outcomes for patients with neutropenia vary by degree of neutropenia and type of solid organ transplant. Management of neutropenia should begin by addressing the underlying cause, including reducing or removing medications when appropriate, treating infections, and addressing nutrient deficiencies; however, consultation with an experienced pediatric hematologist and use of granulocyte colony-stimulating factor (G-CSF) may be helpful in some cases. Overall, data on clinical outcomes for G-CSF use remain limited, but observational studies may support its use in patients with infections or severe neutropenia.

Social Deprivation and the Association With Survival Following Fenestrated Endovascular Aneurysm Repair.

BACKGROUND: Social deprivation is associated with poor clinical outcomes. It is known to have an impact on length of stay and post-operative mortality across a number of other surgical specialties. This study evaluates the impact of social deprivation on outcomes following fenestrated endovascular aneurysm repair (FEVAR). METHODS: All elective FEVARs performed between 2010 and 2018 at a tertiary vascular center were analyzed. Deprivation (index of multiple deprivation [IMD]) data was sourced from the English indices of deprivation 2019, by postcode. Primary outcome was overall survival by Kaplan-Meier. Secondary outcomes included length of hospital stay (LOS) and complications. Cox-proportional hazard analyses were conducted. RESULTS: Some 132 FEVAR patients were followed-up for 3.7 (SD 2.2) years. Fifty-seven patients lived in areas with high levels of deprivation (IMD 1-3), 34 in areas with moderate deprivation (IMD 4-6) and 41 in areas with the lowest level (IMD 7-10) of deprivation. Groups were comparable for Age, BMI, AAA diameter and co-morbidity. A higher proportion of patients from deprived areas had renal failure (15% [26.3%] vs. 9% [11.8%] P = 0.019) but no overall difference in procedure time was observed (200 min [155-250] vs. 180 min [145-240] P = 0.412). Kaplan-Meier analysis demonstrated significantly poorer survival for patients living in areas with high levels of deprivation (IMD 1-3) (P = 0.03). Mortality was comparable for IMD 4-6 and 7-10 groups. Patients from the most deprived areas had longer hospital stay (6 days [4-9] vs. 5 [3-7] P = 0.005) and higher all-cause complication rates (21 [36.8%] vs. 14 [18.4%] P = 0.02). Decreasing IMD was associated with worse survival (HR -0.85 [0.75-0.97] [P = 0.02]). CONCLUSIONS: Social deprivation was associated with increased mortality, length of stay and all-cause complication rates in patients undergoing FEVAR for complex abdominal aortic aneurysm (AAA). These results may help direct preoptimization measures to improve outcomes in higher risk sub-groups.

Compatibility of intravenous acetaminophen with morphine, fentanyl and ketamine in acute pediatric pain setting.

BACKGROUND: Intravenous acetaminophen and opioid analgesics are routinely given concurrently to children after major surgery, where intravenous access can be limited. There is limited information about the compatibility of acetaminophen with opioid analgesics and ketamine in concentrations commonly used in pediatric setting. AIMS: We aimed to determine the physical and chemical compatibility in mixtures of intravenous acetaminophen 10 mg/mL with morphine (0.025, 0.05, 0.1, 0.2, 1, and 2 mg/ml), fentanyl (0.5, 0.75, 1, 1.5, 2, and 5 mcg/ml) and ketamine (0.01, 0.1, 0.5, 1, 1.5, and 3 mg/ml). METHODS: Acetaminophen was mixed with all 18 solutions and was examined at time 0, 15, 30, and 60 min. In Phase one of the study, we used a colorimetric method to assess preliminary feasibility and acetaminophen recovery. In Phase two study, we used high-performance liquid chromatography to evaluate the recovery of all components of the mixtures. RESULTS: All solutions tested, for both acetaminophen and the three analgesics, had more than 90% of the drug recovery, up to 60 min after mixing. CONCLUSION: Our data demonstrated the stability of acetaminophen, in combination with fentanyl, morphine, and ketamine at clinical concentrations used in acute pediatric pain setting.

Dissecting the Management and Outcomes of Thoracic Aortovascular Disease During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic has forced the cancellation of planned surgery and led to significant surgical service reductions. Early intervention in aortovascular disease is often critical and cannot be deferred despite these reductions. There is urgent need to evaluate the provision and outcomes of thoracic aortovascular intervention during the peak of the pandemic. METHODS: Prospective data was collected for patients receiving open and endovascular thoracic aortovascular intervention over two-time points; January-May 2020 and January-May 2019 at three tertiary cardiovascular centres. Baseline demographics, cardiovascular risk and COVID-19 screening results were noted. Primary outcomes were median length of intensive care unit and hospital stay, intra-operative mortality, 30-day mortality, post-operative stroke, and spinal cord injury. RESULTS: Patients operated in 2020 (41) had significantly higher median EuroSCORE II than 2019 (53) (7.44 vs. 5.86, P = 0.032) and rates of previous cardiac (19.5% vs. 3.8%, P = 0.019), aortic (14.6% vs. 1.9%, P = 0.041), and endovascular (22.0% vs. 3.8%, P = 0.009) intervention. There was an increase in proportion of urgent cases in 2020 (31.7% vs. 18.9%). There were no intra-operative deaths in 2020 and 1 in 2019 (P = 1.00). There were no significant differences (P ≥ 0.05) in 30-day mortality (4.9% vs. 13.2%), median intensive care unit length of stay (72 vs. 70 hr), median hospital length of stay (8 vs. 9 days), post-operative stroke (3 vs. 6), or spinal cord injury (2 vs. 1) between 2020 and 2019 respectively. CONCLUSIONS: Despite the increased mortality risk of patients and urgency of cases during COVID-19, complicated by the introduction of cohorting and screening regimens, thoracic aortovascular intervention remained safe with comparable in outcomes to pre-COVID-19.

Understanding Public Perceptions of COVID-19 Contact Tracing Apps: Artificial Intelligence-Enabled Social Media Analysis.

BACKGROUND: The emergence of SARS-CoV-2 in late 2019 and its subsequent spread worldwide continues to be a global health crisis. Many governments consider contact tracing of citizens through apps installed on mobile phones as a key mechanism to contain the spread of SARS-CoV-2. OBJECTIVE: In this study, we sought to explore the suitability of artificial intelligence (AI)-enabled social media analyses using Facebook and Twitter to understand public perceptions of COVID-19 contact tracing apps in the United Kingdom. METHODS: We extracted and analyzed over 10,000 relevant social media posts across an 8-month period, from March 1 to October 31, 2020. We used an initial filter with COVID-19-related keywords, which were predefined as part of an open Twitter-based COVID-19 dataset. We then applied a second filter using contract tracing app-related keywords and a geographical filter. We developed and utilized a hybrid, rule-based ensemble model, combining state-of-the-art lexicon rule-based and deep learning-based approaches. RESULTS: Overall, we observed 76% positive and 12% negative sentiments, with the majority of negative sentiments reported in the North of England. These sentiments varied over time, likely influenced by ongoing public debates around implementing app-based contact tracing by using a centralized model where data would be shared with the health service, compared with decentralized contact-tracing technology. CONCLUSIONS: Variations in sentiments corroborate with ongoing debates surrounding the information governance of health-related information. AI-enabled social media analysis of public attitudes in health care can help facilitate the implementation of effective public health campaigns.

Interorganizational Knowledge Sharing to Establish Digital Health Learning Ecosystems: Qualitative Evaluation of a National Digital Health Transformation Program in England.

BACKGROUND: The English Global Digital Exemplar (GDE) program is one of the first concerted efforts to create a digital health learning ecosystem across a national health service. OBJECTIVE: This study aims to explore mechanisms that support or inhibit the exchange of interorganizational digital transformation knowledge. METHODS: We conducted a formative qualitative evaluation of the GDE program. We used semistructured interviews with clinical, technical, and managerial staff; national program managers and network leaders; nonparticipant observations of knowledge transfer activities through attending meetings, workshops, and conferences; and documentary analysis of policy documents. The data were thematically analyzed by drawing on a theory-informed sociotechnical coding framework. We used a mixture of deductive and inductive methods, supported by NVivo software, to facilitate coding. RESULTS: We conducted 341 one-on-one and 116 group interviews, observed 86 meetings, and analyzed 245 documents from 36 participating provider organizations. We also conducted 51 high-level interviews with policy makers and vendors; performed 77 observations of national meetings, workshops, and conferences; and analyzed 80 national documents. Formal processes put in place by the GDE program to initiate and reinforce knowledge transfer and learning have accelerated the growth of informal knowledge networking and helped establish the foundations of a learning ecosystem. However, formal networks were most effective when supported by informal networking. The benefits of networking were enhanced (and costs reduced) by geographical proximity, shared culture and context, common technological functionality, regional and strategic alignments, and professional agendas. CONCLUSIONS: Knowledge exchange is most effective when sustained through informal networking driven by the mutual benefits of sharing knowledge and convergence between group members in their organizational and technological setting and goals. Policy interventions need to enhance incentives and reduce barriers to sharing across the ecosystem, be flexible in tailoring formal interventions to emerging needs, and promote informal knowledge sharing.

Multiplexed Single-Photon Source Based on Multiple Quantum Dots Embedded within a Single Nanowire.

Photonics-based quantum information technologies require efficient, high emission rate sources of single photons. Position-controlled quantum dots embedded within a broadband nanowire waveguide provide a fully scalable route to fabricating highly efficient single-photon sources. However, emission rates for single-photon devices are limited by radiative recombination lifetimes. Here, we demonstrate a multiplexed single-photon source based on a multidot nanowire. Using epitaxially grown nanowires, we incorporate multiple energy-tuned dots, each optimally positioned within the nanowire waveguide, providing single photons with high efficiency. This linear scaling of the single-photon emission rate with number of emitters is demonstrated using a five-dot nanowire with an average multiphoton emission probability of <4% when excited at saturation. This represents the first ever demonstration of multiple single-photon emitters deterministically incorporated in a single photonic device and is a major step toward achieving GHz single-photon emission rates from a scalable multi-quantum-dot system.