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Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Abstract We report on a quantum interface linking a diamond NV center quantum network node and 795nm photonic time-bin qubits compatible with Thulium and Rubidium quantum memories. The interface makes use of two-stage low-noise quantum frequency conversion and waveform shaping to match temporal and spectral photon profiles. Two-photon quantum interference shows high indistinguishability between converted 795nm photons and the native NV center photons. We use the interface to demonstrate quantum teleportation including real-time feedforward from an unbiased set of 795nm photonic qubit input states to the NV center spin qubit, achieving a teleportation fidelity well above the classical bound. This proof-of-concept experiment shows the feasibility of interconnecting different quantum network hardware.

Stereotypes can exert a powerful influence on our interactions with others, potentially leading to prejudice when factual evidence is ignored. Here, we identify neuroanatomical and developmental factors that influence the real-time integration of stereotypes and factual evidence during live social interactions. The study uses precisely quantified communicative exchanges in a longitudinal cohort of seventeen-year-olds followed since infancy, testing their ability to moderate stereotype tendencies toward children as contrary evidence accumulates. Our results indicate that the impact of stereotypes on communicative behavior is linked to individual variations in gray matter density and cortical thickness in the right anterior cingulate gyrus. In contrast, the ability to moderate stereotype tendencies is influenced by developmental exposure to social interactions during the initial years of life, beyond the effects of familial environment and later experiences. These findings pinpoint a key brain structure underlying stereotype tendencies and suggest that early-life social experiences have lasting consequences on how individuals integrate factual evidence in interpersonal communication.

Abstract Purpose To investigate whether the same health state results in the same distribution of responses on the EQ-5D youth and adult descriptive systems. Methods Adolescents aged 13–18 years with a range of health conditions and from the general school going population were recruited in South Africa (ZA) and Ethiopia (ET). In ZA participants completed the English EQ-5D-3L, EQ-5D-Y-3L and EQ-5D-5L in parallel. Whereas in ET participants completed the Amharic EQ-5D-5L and EQ-5D-Y-5L in parallel. Analysis aimed to describe the transition between youth and adult instruments and not differences between countries. Results Data from 592 adolescents completing the EQ-5D-3L, EQ-5D-Y-3L and EQ-5D-5L (ZA) and 693 completing the EQ-5D-5L and EQ-5D-Y-5L (ET) were analysed. Adolescents reported more problems on the youth versions compared to the adult version for the dimension of mental health. 13% and 4% of adolescents who reported no problems on the EQ-5D-3L and EQ-5D-5L reported some problems on the EQ-5D-Y-3L respectively. This was less notable with transition between the five level versions with 4% of adolescents reporting more problems on the EQ-5D-Y-5L than the EQ-5D-5L. Very few adolescents reported severe problems (level 3 on the EQ-5D-3L or EQ-5D-Y-3L and level 4 and level 5 on the EQ-5D-5L or EQ-5D-5L) thus there was little variation between responses between the versions. In ZA, discriminatory power, measured on the Shannon’s Index, was higher for Y-3L compared to 3L for pain/discomfort (ΔH′=0.11) and anxiety/depression (ΔH′=0.04) and across all dimensions for Y-3L compared to 5L. Similarly, in ET discriminatory power was higher for Y-5L than 5L (ΔH′ range 0.05–0.09). Gwet’s AC showed good to very good agreement across all paired (ZA) 3L and (ET) 5L dimensions. The summary score of all EQ-5D versions were able to differentiate between known disease groups. Conclusion Despite the overall high levels of agreement between EQ-5D instruments for youth and for adults, they do not provide identical results in terms of health state, from the same respondent. The differences were most notable for anxiety/depression. These differences in the way individuals respond to the various descriptive systems need to be taken into consideration for descriptive analysis, when transitioning between instruments, and when comparing preference-weighted scores.

Abstract Background Onchocerciasis is endemic in 14 of Sierra Leone's 16 districts with high prevalence (47–88.5%) according to skin snips at baseline. After 11 rounds of mass treatment with ivermectin with good coverage, an impact assessment was conducted in 2017 to assess the progress towards eliminating onchocerciasis in the country. Methods A cluster survey was conducted, either integrated with lymphatic filariasis (LF) transmission assessment survey (TAS) or standalone with the LF TAS sampling strategy in 12 (now 14) endemic districts. Finger prick blood samples of randomly selected children in Grades 1–4 were tested in the field using SD Bioline Onchocerciasis IgG4 rapid tests. Results In total, 17,402 children aged 4–19 years in 177 schools were tested, and data from 17,364 children aged 4–14 years (14,230 children aged 5–9 years) were analyzed. Three hundred forty-six children were confirmed positive for Ov-16 IgG4 antibodies, a prevalence of 2.0% (95% CI 1.8–2.2%) in children aged 4–14 years with prevalence increasing with age. Prevalence in boys (2.4%; 95% CI 2.1–2.7%) was higher than in girls (1.6%; 95% CI 1.4–1.9%). There was a trend of continued reduction from baseline to 2010. Using data from children aged 5–9 years, overall prevalence was 1.7% (95% CI 1.5–1.9%). The site prevalence ranged from 0 to 33.3% (median prevalence = 0.0%): 5%) was predicted in some focal areas, centered in Karene, Kailahun and Moyamba/Tonkolili. Conclusions Low Ov-16 IgG4 antibody prevalence was shown in most areas across Sierra Leone. In particular, low seroprevalence in children aged 5–9 years suggests that the infection was reduced to a low level after 11 rounds of treatment intervention. Sierra Leone has made major progress towards elimination of onchocerciasis. However, attention must be paid to those high prevalence focal areas. Graphical Abstract

Background: As the available treatments for moderate-to-severe atopic dermatitis (AD) expand, understanding patient and physician preferences becomes crucial for informed decision-making.Objective: To quantify patient and physician preferences for biologics and oral systemic AD treatment attributes.Materials and methods: We conducted a cross-sectional, online discrete choice experiment (DCE) involving 306 AD patients and 206 physicians throughout the United Kingdom and Germany. Qualitative interviews identified the key attributes for inclusion in the DCE. Each choice task comprised two hypothetical patient profiles. Data were analyzed using a random-parameters logit model.Results: Results indicated a significant emphasis on efficacy, with reducing sleep disturbance and itch ranking first and second among patients, and the reverse for physicians. Time to itch relief was the third most important efficacy attribute for both groups, but relatively more important for patients than for physicians. For both groups, the risk of eye problems was the most important safety concern of those included. Mode of administration was not of great importance compared to efficacy and safety attributes.Conclusions: Our findings suggest patients prioritize sleep disturbance, an attribute not captured in prior preference studies in AD, time to itch relief and itch. These findings emphasize the importance of addressing sleep-related issues, whilst also targeting fast itch control, to enhance patients’ well-being.

Objective To study the role of perivascular adipose tissue (PVAT) in the reactivity of rat and human vessels.Methods Iliac and mesenteric arteries were obtained from normotensive Sprague-Dawley rats, hypertensive transgenic (mRen2)27 rats overexpressing mouse renin, and (mRen2)27 rats made diabetic with streptozotocin. Human coronary arteries were obtained from donors. Concentration-response curves were constructed to endothelin-1 and acetylcholine with and without PVAT. The contribution of NO and endothelium-dependent hyperpolarization (EDH) were determined making use of the NO synthase inhibitor L-NAME and the EDH inhibitors apamin + TRAM-34. The endothelin type A and type B (ETA, ETB) receptor blockers BQ123 and BQ788, the chemerin inhibitors α-NETA and pravastatin, and the angiotensin receptor blocker losartan were also used.Results In rat iliac arteries, PVAT diminished endothelin-induced constriction, while the opposite was true in human coronaries. Coronary effects were unaltered by α-NETA, pravastatin, or losartan. ETB receptor-mediated relaxation in iliac arteries occurred only with PVAT, and BQ123 blocked endothelin-1-induced constriction. Diabetes upregulated the anticontractile effects of PVAT. In rat mesenteric arteries, acetylcholine-induced relaxation with PVAT relied on NO, and on NO + EDH without PVAT. Diabetes upregulated the EDH component exclusively with PVAT.Conclusion PVAT modulates ET-1-induced constriction in a vessel type-dependent manner. Its enhancing effects in coronaries involved neither chemerin nor angiotensin II. Its anticontractile effects in rat iliac arteries involved ETB receptor-mediated relaxation. Diabetes upregulated PVAT’s anticontractile effects. In mesenteric arteries, PVAT counterbalanced the EDH component of the relaxant effect of acetylcholine. Diabetes reversed this effect by upregulating the EDH component.

ABSTRACTBackground: Young adult sexual minority women (SMW) are at elevated risk for sexual assault (SA), posttraumatic stress disorder (PTSD), and inadequate social support. While SA and PTSD can lead to reductions in social support from close significant others, the impact of SA and PTSD on SMWs’ social support has not previously been assessed.Objective: This study examined the associations of past year SA and PTSD with SMW’s social support from intimate partners, family, and friends. It was hypothesized that SA and PTSD would be negatively associated with support from partners, family and friends, and that PTSD would moderate the effect of SA on support in early adulthood.Method: Young adult SMW in the United States (N = 235) who were M = 23.93 (SD = 2.15) years old, primarily lesbian or bisexual (n = 186, 79.1%) and White (n = 176, 74.9%) completed measures on past year exposure to SA and non-SA trauma, PTSD, and social support from intimate partners, family and friends.Results: PTSD was associated with less social support from partners, ([Formula: see text] = −0.06, SE = 0.02, p = .010, R2change = .02), family, ([Formula: see text] = −0.06, SE = 0.03, p = .025, R2change = .02), and friends, ([Formula: see text] = −0.07, SE = 0.02, p = .008, R2change = .02). There was a significant interaction between PTSD and SA on social support from partners ([Formula: see text] = −0.01, SE = 0.01, p = .047, R2change = .01). Neither non-SA nor SA trauma was associated with support from family or friends.Conclusions: Results underscore the potential impact of recent SA on intimate partnerships for young adult SMW with more severe PTSD. Future work should explore how addressing PTSD and improving social support quality may help SMW recover from traumatic experiences and ameliorate the effects of SA on intimate partnerships.

BackgroundThe World Health Organization's 2021-2030 Road Map for Neglected Tropical Diseases boosted global commitment towards the elimination of onchocerciasis, but the timeline to elimination will vary strongly between countries in Africa. To assess progress towards elimination in the Republic of Togo, we reviewed the history of control and time trends in infection.Methodology/principal findingsWe collated all available programmatic, entomological, and epidemiological data since the initiation of the Onchocerciasis Control Programme (OCP) in Togo through different data sources. We then visualised data trends over time, to assess the impact of interventions on infection and transmission levels. Vector control was initiated by OCP from 1977 (northern and central parts of Togo) or 1988 (southern regions) up to 2002 (most areas) or 2007 ("special intervention zones" [SIZ], parts of Northern and Central Togo). Between 1988 and 1991, Togo initiated ivermectin mass drug administration (MDA) in eligible communities. The impact of vector control was high in most river basins, resulting in low annual biting rates and annual transmission potential declining to very low levels; the impact was lower in river basins designated as SIZ. Repeated, longitudinal ivermectin mass treatments have overall strongly reduced onchocerciasis transmission in Togo. Epidemiological surveys performed between 2014 and 2017 showed that the prevalence of skin microfilariae (mf) and anti-OV16 IgG4 antibodies had declined to low levels in several districts of the Centrale, Plateaux, and Maritime region. Yet, relatively high mf prevalences (between 5.0% and 32.7%) were still found in other districts during the same period, particularly along the Kéran, Mô and Ôti river basins (SIZ areas).Conclusions/significanceTrends in infection prevalence and intensity show that onchocerciasis levels have dropped greatly over time in most areas. This demonstrates the large impact of long-term and wide-scale interventions, and suggest that several districts of Togo are approaching elimination.

Abstract Control of soil-transmitted helminths relies heavily on regular large-scale deworming of high-risk groups (e.g., children) with benzimidazole derivatives. Although drug resistance has not yet been documented in human soil-transmitted helminths, regular deworming of cattle and sheep has led to widespread benzimidazole resistance in veterinary helminths. Here we predict the population dynamics of human soil-transmitted helminth infections and drug resistance during 20 years of regular preventive chemotherapy, using an individual-based model. With the current preventive chemotherapy strategy of mainly targeting children in schools, drug resistance may evolve in soil-transmitted helminths within a decade. More intense preventive chemotherapy strategies increase the prospects of soil-transmitted helminths elimination, but also increase the speed at which drug efficacy declines, especially when implementing community-based preventive chemotherapy (population-wide deworming). If during the last decade, preventive chemotherapy against soil-transmitted helminths has led to resistance, we may not have detected it as drug efficacy has not been structurally monitored, or incorrectly so. These findings highlight the need to develop and implement strategies to monitor and mitigate the evolution of benzimidazole resistance.

During the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully understood. Governmental non-pharmaceutical interventions (NPI’s), an increase in community treated exacerbations, or healthcare avoidance by patients, are potential reasons. For the current study, the impact of Dutch governmental NPI’s on the COPD exacerbations and respiratory infections rate in patients with severe alpha-1 antitrypsin deficiency (AATD) was analyzed. The patients participated in the NCT04204252 study, a randomized controlled trial evaluating the efficacy and safety of inhaled alpha-1 antitrypsin. Data collected in the time-period from March 2020 until February 2022 was analyzed. In this period the Dutch government imposed variable NPI’s to contain the spread of SARS-CoV-2. Patients were required to document their daily symptoms in an electronic diary. The strictness of the governmental NPI’s was measured by the COVID-19 Stringency Index. 19 patients participated in this study during the analysis period. A total of 40 respiratory infections and COPD exacerbations occurred. The Spearman’s correlation coefficient of the monthly average COVID-19 Stringency Index and respiratory infections and COPD exacerbations rate was −0.316 (p = 0.132). When months known for a low respiratory infection rate were excluded, the correlation coefficient was −0.625 (p = 0.010). This study showed a significant negative correlation between the COPD exacerbations and respiratory infection rate and the COVID-19 Stringency Index in patients with AATD related COPD in the autumn-winter months.

Emphysema in patients with chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation. Preclinical studies suggest that lung volume reduction surgery (LVRS) and mesenchymal stromal cell (MSC) treatment dampen inflammation. We investigated the effects of bone marrow-derived MSC (BM-MSC) and LVRS on circulating and pulmonary immune cell profiles in emphysema patients using mass cytometry. Blood and resected lung tissue were collected at the first LVRS (L1). Following 6–10 weeks of recovery, patients received a placebo or intravenous administration of 2 × 106 cells/kg bodyweight BM-MSC (n = 5 and n = 9, resp.) in week 3 and 4 before the second LVRS (L2), where blood and lung tissue were collected. Irrespective of BM-MSC or placebo treatment, proportions of circulating lymphocytes including central memory CD4 regulatory, effector memory CD8 and γδ T cells were higher, whereas myeloid cell percentages were lower in L2 compared to L1. In resected lung tissue, proportions of Treg (p = 0.0067) and anti-inflammatory CD163− macrophages (p = 0.0001) were increased in L2 compared to L1, while proportions of pro-inflammatory CD163+ macrophages were decreased (p = 0.0004). There were no effects of BM-MSC treatment on immune profiles in emphysema patients. However, we observed alterations in the circulating and pulmonary immune cells upon LVRS, suggesting the induction of anti-inflammatory responses potentially needed for repair processes.

Recent advances in synthetic drug manufacturing have introduced a new dynamic to the European regulatory system, with chemically synthesized polypeptide products using biological originator products as their reference medicine. Whereas biosimilars are subject to a dedicated regulatory framework in the EU, synthetically produced follow-on products are not eligible for assessment through this pathway, requiring approval via the traditional generic pathway under Article 10 (1), or via the hybrid pathway under Article 10 (3). This review presents an overview of recent developments in the field of synthetic peptides referencing biological originators in the EU. The use of different regulatory procedures can have potential implications for regulatory assessments, clinical practice and pharmacovigilance. As more complex synthetic products referencing recombinant originator products are expected in the coming years, this study promotes more transparency as well as global alignment about regulatory procedures for chemically synthesised products referencing biological originator products to ensure approval of safe and high-quality generics.

Abstract Background The availability of population norms from generic health-related quality of life (HRQoL) instruments can support the interpretation of health outcomes. This study aimed to provide Indonesian youth population norms for the generic HRQoL measures: EQ-5D-Y-3 L, EQ-5D-Y-5 L, and the PedsQL Generic Core Scales. In addition the opportunity arising from the generation of a large representative sample was taken to explore the relationships between HRQoL, health, and socio-economic factors. Methods A representative sample of 1103 Indonesian children (aged 8–16 years) completed EQ-5D-Y-3 L, EQ-5D-Y-5 L, the PedsQL Generic Core Scales, and questions related to demographic data and self-reported health status. A stratified quota sampling design was used to represent Indonesian children in terms of residence, age, gender, and geographical area. Family expenses per capita per month were retrieved from parents to determine a child’s economic status. Results The total sample was representative of the Indonesian youth general population. The proportions of participants who reported problems were 43.35% (EQ-5D-Y-3 L), 44.10% (EQ-5D-Y-5 L), and 94.93% (PedsQL Generic), with 31.7% of children reporting health complaints. Older children (13–16 years) reported more problems than younger children (8–12 years). Children living in urban areas reported more problems than children living in rural areas. The lowest value health state reported was ‘12332’ (valued at 0.54), and the minimum EQ VAS score was 60.00. Moderate correlations were found between EQ-5D-Y-3 L values to EQ VAS scores and to PedsQL Total Score. Hierarchical regression analysis showed that females, older age, and having health complaints contributed to a lower level of HRQoL as measured by EQ-5D-Y-3 L values, EQ VAS, and PedsQL Total Score. Remarkably, children with high economic status had lower EQ VAS and PedsQL Total Scores. Among symptoms, ‘having stress’ had the largest influence with respect to lower EQ-5D-Y-3L values, EQ VAS, and PedsQL Total Score. Conclusions Population norms for children’s HRQoL as measured by EQ-5D-Y-3 L, EQ-5D-Y-5 L, and the PedsQL Generic Scales are now available for Indonesia. Age, gender, economic status, and health complaints were related to children’s HRQoL. These results provide a basis for health studies and health policy for the youth population of Indonesia.

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.

Cancer vaccines have emerged as a potent strategy to improve cancer immunity, with or without the combination of checkpoint blockade. In our investigation, liposomal formulations containing synthetic long peptides and α-Galactosylceramide, along with a DC-SIGN-targeting ligand, Lewis Y (LeY), were studied for their anti-tumor potential. The formulated liposomes boosted with anti-CD40 adjuvant demonstrated robust invariant natural killer (iNKT), CD4+, and CD8+ T-cell activation in vivo. The incorporation of LeY facilitated the targeting of antigen-presenting cells expressing DC-SIGN in vitro and in vivo. Surprisingly, mice vaccinated with LeY-modified liposomes exhibited comparable tumor reduction and survival rates to those treated with untargeted counterparts despite a decrease in antigen-specific CD8+ T-cell responses. These results suggest that impaired induction of antigen-specific CD8+ T-cells via DC-SIGN targeting does not compromise anti-tumor potential, hinting at alternative immune activation routes beyond CD8+ T-cell activation.

AimsThe primary aim was to explore the age dependency of health state values derived via trade-offs between health-related quality of life (HRQoL) and life years in a discrete choice experiment (DCE). The secondary aim was to explore if people weigh life years and HRQoL differently for children, adolescents, adults, and older adults.MethodsParticipants from the general population of the Netherlands and China first completed a series of choice tasks offering choices between two EQ-5D-Y states with a given lifespan. The choice model captured the value of a year in full health, disutility determined by EQ-5D-Y, and a discount rate. Next, they received a slightly different choice task, offering choices between two lives that differed in HRQoL and life expectancy but produced the same number of quality-adjusted life years (QALYs). Participants were randomly assigned to fill out the survey for three or four age frames: a hypothetical person of 10, 15, 40, and 70 years (the last one only applicable to China) to allow the age dependency of the responses to be explored.ResultsA total of 1,234 Dutch and 1,818 Chinese people administered the survey. Controlling for time preferences, we found that the agreement of health state values for different age frames was generally stronger in the Netherlands than in China. We found no clear pattern of differences in the QALY composition in both samples. The probability distribution over response options varied most when levels for lifespan or severity were at the extremes of the spectrum.Conclusion/discussionThe magnitude and direction of age effects on values seemed dimension- and country specific. In the Netherlands, we found a few differences in dimension-specific weights elicited for 10- and 15-year-olds compared to 40-year-olds, but the overall age dependency of values was limited. A stronger age dependency of values was observed in China, where values for 70-year-olds differed strongly from the values for other ages. The appropriateness of using existing values beyond the age range for which they were measured needs to be evaluated in the local context.

Adequate lung epithelial repair relies on supportive interactions within the epithelial niche, including interactions with WNT-responsive fibroblasts. In fibroblasts from patients with chronic obstructive pulmonary disease (COPD) or upon in vitro cigarette smoke exposure, Wnt/β-catenin signalling is distorted, which may affect interactions between epithelial cells and fibroblasts resulting in inadequate lung repair. We hypothesized that cigarette smoke (CS), the main risk factor for COPD, interferes with Wnt/β-catenin signalling in fibroblasts through induction of cellular stress responses, including oxidative- and endoplasmic reticulum (ER) stress, and thereby alters epithelial repair support potential. Therefore, we assessed the effect of CS-exposure and the ER stress inducer Thapsigargin (Tg) on Wnt/β-catenin signalling activation in MRC-5 fibroblasts, and on their ability to support lung epithelial organoid formation. Exposure of MRC-5 cells for 15 min with 5 AU/mL CS extract (CSE), and subsequent 6 h incubation induced oxidative stress (HMOX1). Whereas stimulation with 100 nM Tg increased markers of both the integrated stress response (ISR - GADD34/PPP1R15A, CHOP) and the unfolded protein response (UPR - XBP1spl, GADD34/PPP1R15A, CHOP and HSPA5/BIP), CSE only induced GADD34/PPP1R15A expression. Strikingly, although treatment of MRC-5 cells with the Wnt activator CHIR99021 upregulated the Wnt/β-catenin target gene AXIN2, this response was diminished upon CSE or Tg pre-exposure, which was confirmed using a Wnt-reporter. Furthermore, pre-exposure of MRC-5 cells to CSE or Tg, restricted their ability to support organoid formation upon co-culture with murine pulmonary EpCam+ cells in Matrigel at day 14. This restriction was alleviated by pre-treatment with CHIR99021. We conclude that exposure of MRC-5 cells to CSE increases oxidative stress, GADD34/PPP1R15A expression and impairs their ability to support organoid formation. This inhibitory effect may be restored by activating the Wnt/β-catenin signalling pathway.

Abstract Background Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www.clinicaltrials.gov (ID: NCT04180319)

Abstract Scaling current quantum communication demonstrations to a large-scale quantum network will require not only advancements in quantum hardware capabilities, but also robust control of such devices to bridge the gap in user demand. Moreover, the abstraction of tasks and services offered by the quantum network should enable platform-independent applications to be executed without the knowledge of the underlying physical implementation. Here we experimentally demonstrate, using remote solid-state quantum network nodes, a link layer, and a physical layer protocol for entanglement-based quantum networks. The link layer abstracts the physical-layer entanglement attempts into a robust, platform-independent entanglement delivery service. The system is used to run full state tomography of the delivered entangled states, as well as preparation of a remote qubit state on a server by its client. Our results mark a clear transition from physics experiments to quantum communication systems, which will enable the development and testing of components of future quantum networks.

Background Medication administration errors (MAEs) are a major cause of morbidity and mortality. An updated barcode medication administration (BCMA) technology on infusion pumps is implemented in the operating rooms to automate double check at a syringe exchange.Objective The aim of this mixed-methods before-and-after study is to understand the medication administrating process and assess the compliance with double check before and after implementation.Methods Reported MAEs from 2019 to October 2021 were analysed and categorised to the three moments of medication administration: (1) bolus induction, (2) infusion pump start-up and (3) changing an empty syringe. Interviews were conducted to understand the medication administration process with functional resonance analysis method (FRAM). Double check was observed in the operating rooms before and after implementation. MAEs up to December 2022 were used for a run chart.Results Analysis of MAEs showed that 70.9% occurred when changing an empty syringe. 90.0% of MAEs were deemed to be preventable with the use of the new BCMA technology. The FRAM model showed the extent of variation to double check by coworker or BCMA.Observations showed that the double check for pump start-up changed from 70.2% to 78.7% postimplementation (p=0.41). The BCMA double check contribution for pump start-up increased from 15.3% to 45.8% (p=0.0013). The double check for changing an empty syringe increased from 14.3% to 85.0% (p