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Indoor device-free object sensing can be utilized in many applications such as occupant-centered control of building utilities and assisted living. To satisfy the mathematical requirement of many observation points for arbitrary indoor layout and furnishing, radio-frequency identification (RFID) offers a low-cost solution with a plethora of maintenance-free passive tags. Both the received signal strength indicator and carrier phase from tag backscattering can be assembled to generate the voxel reflectivity distribution by the inverse method. We adopt the regularized truncated pseudo-inverse method, and devise the strategies for optimal selection of the critical parameters. Compared with conventional matched filtering, our method is more robust against random noises in the collected data. An experimental prototype was established to evaluate the system robustness and performance, and the dipole antennas were used to replace patch antennas to enhance the system signal-to-noise ratio (SNR). The regularized truncated pseudo-inverse method together with the improved system SNR has successfully shown higher locating accuracy and lower computational cost.

Longitudinal studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses in patients with cancer are needed to optimize clinical care. In a prospective cohort study of 366 (291 vaccinated) patients, we measured antibody levels [anti-spike (IgG-(S-RBD) and anti-nucleocapsid immunoglobulin] at three time points. Antibody level trajectories and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination. IgG-(S-RBD) at peak response (median = 42 days after dose 2) was higher (P = 0.002) and remained higher after 4 to 6 months (P = 0.003) in patients receiving mRNA-1273 compared with BNT162b2. Patients with solid tumors attained higher peak levels (P = 0.001) and sustained levels after 4 to 6 months (P < 0.001) compared with those with hematologic malignancies. B-cell targeted treatment reduced peak (P = 0.001) and sustained antibody responses (P = 0.003). Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (P = 0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities, with important implications for vaccine booster timing and patient selection. Significance: Long-term studies of immunogenicity of SARS-CoV-2 vaccines in patients with cancer are needed to inform evidence-based guidelines for booster vaccinations and to tailor sequence and timing of vaccinations to elicit improved humoral responses.

BACKGROUND: Patients awaiting heart transplantation (HTx) often need bridging therapies to reduce worsening and progression of underlying disease. Limited data are available regarding the use of the MitraClip procedure in secondary mitral regurgitation for this clinical condition. METHODS: We evaluated an international, multicenter (17 centers) registry including 119 patients (median age: 58 years) with moderate-to-severe or severe secondary mitral regurgitation and advanced heart failure (HF) (median left ventricular ejection fraction: 26%) treated with MitraClip as a bridge strategy according to 1 of the following criteria: (1) patients active on HTx list (in list group) (n = 31); (2) patients suitable for HTx but awaiting clinical decision (bridge to decision group) (n = 54); or (3) patients not yet suitable for HTx because of potentially reversible relative contraindications (bridge to candidacy group) (n = 34). RESULTS: Procedural success was achieved in 87.5% of cases, and 30-day survival was 100%. At 1 year, Kaplan-Meier estimates of freedom from the composite primary end-point (death, urgent HTx or left ventricular assist device implantation, first rehospitalization for HF) was 64%. At the time of last available follow-up (median: 532 days), 15% of patients underwent elective transplant, 15.5% remained or could be included in the HTx waiting list, and 23.5% had no more indication to HTx because of clinical improvement. CONCLUSIONS: MitraClip procedure as a bridge strategy to HTx in patients with advanced HF with significant mitral regurgitation was safe, and two thirds of patients remained free from adverse events at 1 year. These findings should be considered exploratory and hypothesis-generating to guide further study for percutaneous intervention in high-risk patients with advanced HF. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

Background: Central obesity is a major manifestation of metabolic syndrome, which is a common health problem in middle-aged and older adults. Objective: To examine the therapeutic efficacy of tai chi for management of central obesity. Design: Randomized, controlled, assessor-blinded trial. (ClinicalTrials.gov: NCT03107741) Setting: A single research site in Hong Kong between 27 February 2016 and 28 February 2019. Participants: Adults aged 50 years or older with central obesity. Intervention: 543 participants were randomly assigned in a 1:1:1 ratio to a control group with no exercise intervention (n = 181), conventional exercise consisting of aerobic exercise and strength training (EX group) (n = 181), and a tai chi group (TC group) (n = 181). Interventions lasted 12 weeks. Measurements: Outcomes were assessed at baseline, week 12, and week 38. The primary outcome was waist circumference (WC). Secondary outcomes were body weight; body mass index; high-density lipoprotein cholesterol (HDL-C), triglyceride, and fasting plasma glucose levels; blood pressure; and incidence of remission of central obesity. Results: The adjusted mean difference in WC from baseline to week 12 in the control group was 0.8 cm (95% CI, -4.1 to 5.7 cm). Both intervention groups showed reductions in WC relative to control (adjusted mean differences: TC group vs. control, -1.8 cm [CI, -2.3 to -1.4 cm]; P

BACKGROUND Tricuspid regurgitation (TR) has a poor prognosis and limited treatment options and is frequently accompanied by right ventricular (RV) dysfunction. Transcatheter tricuspid valve interventions (TTVI) to reduce TR have been shown to be safe and feasible with encouraging early results. Patient selection for TTVI remains challenging, with the role of right ventricular (RV) function being unknown. AIMS The aims of this study were 1) to investigate survival in a TTVI-treated patient population and a conservatively treated TR population, and 2) to evaluate the outcome of TTVI as compared to conservative treatment stratified according to the degree of RV function. METHODS We studied 684 patients from the multicentre TriValve cohort (TTVI cohort) and compared them to 914 conservatively treated patients from two tertiary care centres. Propensity matching identified 213 pairs of patients with severe TR. As we observed a non-linear relationship of RV function and TTVI outcome, we stratified patients according to tricuspid annular plane systolic excursion (TAPSE) to preserved (TAPSE >17 mm), mid-range (TAPSE 13-17 mm) and reduced (TAPSE

We explored the relationships between the use of Angiotensin II receptor blockers (ARBs), Angiotensin I-converting enzyme (ACE) genetic polymorphisms and memory performance in older adults, whilst controlling for confounders. Retrospective observational case-control study. 104 patients over 60 years of age (mean age 74) without known cognitive disorder were included, 52 cases (ARB users) and 52 controls (non-users). ACE insertion/deletion (ACE I/D) polymorphism was determined in all patients. The Wechsler Memory Scale (memory quotient) was used to evaluate cognition. We measured years of education, Charlson Comorbidity Index (CCI) and total number of medications taken. The mean (SD) age in cases and controls were: 75.3 (7.5) and 72.0 (7.0) respectively (p = 0.020). Cases had higher CCI (p = 0.006) and took more medications (p < 0.001). Cases had a higher memory quotient: 99.6 (5.9) and 95.3 (6.7) (p < 0.001). In the I/I group, cases had higher memory quotient [99.5 (5.5) vs. 95.0 (5.7), p = 0.005]. No significant difference in memory performance was found between cases and controls within genotype ACE I/D (p = 0.056) and D/D (p = 0.290). A multiple linear regression predicting memory score in n = 104 (predictors: ARB use, age, female sex, years of education, CCI, number of medications, ACE I/I status, interaction ARB user ACE I/I status) suggested that only ARB use (p = 0.001) and higher education (p < 0.001) were significant predictors of higher memory performance. Despite ARB users being older and more comorbid, their memory was better even when controlling for the ACE I/I risk genotype. Education may confer cognitive reserve. The protective role of ARBs merits further investigation.

With the proliferation of the Internet of Things and radio-frequency identification (RFID), the ambient radio signals can be leveraged for indoor occupant monitoring. In this article, we have employed passive RFID tags in the ambient for occupant counting by a deep-learning solution. The reader collects both carrier phase and received signal strength from each tag, which are inputs to a convolutional neural network. A novel background calibration is proposed to reduce phase offsets and noises in the presence of heavy multipath, which further improves model accuracy. Our results show satisfactory performance, with 0.82 probability for detecting the correct number of occupants, and 1.0 if ±1 error is permitted. The model also exhibits occupant location and posture independent learning, allowing limited and faster training data collection. To demonstrate generalized learning without strong bias to indoor setup, we have also transferred this pre-trained model to another similar-sized room, achieving 0.85 – 1.0 accuracy for different tag-receiver placements and furnishing.

Objectives We investigated the durability of tricuspid regurgitation (TR) reduction and the clinical outcomes through 12 months after transcatheter tricuspid valve repair (TTVr) with the PASCAL Transcatheter Valve Repair System. Background TTVr has rapidly developed and demonstrated favorable acute outcomes, but longer follow-up data are needed. Methods Overall, 30 patients (age 77 ± 6 years; 57% female) received PASCAL implantation from September 2017 to May 2019 and completed a clinical follow-up at 12 months. Results The TR etiology was functional in 25 patients (83%), degenerative in three (10%), and mixed in two (7%). All patients had TR severe or greater (massive or torrential in 80%) and heart failure symptoms (90% in NYHA III or IV) under optimal medical treatment. Single-leaflet device attachment occurred in two patients. Moderate or less TR was achieved in 23/28 patients (82%) at 30 days, which was sustained at 12 months (86%). Two patients underwent repeat TTVr due to residual torrential TR (day 173) and recurrence of severe TR (day 280), respectively. One-year survival rate was 93%; 6 patients required rehospitalization due to acute heart failure. NYHA functional class I or II was achieved in 90% and 6-minute walk distance improved from 275 ± 122 m at baseline to 347 ± 112 m at 12-month (+72 ± 82 m, p

We present a low-power wireless radio-frequency (RF) sensor to perform continuous vital-sign monitoring for chelonians in various stages of brumation. Due to their unique body structure, vital signs of chelonians cannot be recorded without substantial animal handling in previous methods, which would severely bias the brumation condition. In contrast, our sensor on harness can couple significant RF energy into various body parts to evaluate the heartbeat, respiration and activity levels. The self-contained unit is lightweight for ease of wearable deployment and low power to avoid unnecessary heat generation as well as frequent battery replacement. We recorded the shell temperature, heart rate, respiration rate and activity levels of a Russian tortoise during the entire brumation cycle and found that the heart rate correlated with the ambient temperature well, while the breath rate did not significantly reduce during brumation. This experimental study is minimally invasive and thus least biased.

Indoor device-free object detection has many applications, such as assisted living, home security, and occupant-centered building utility control. To accommodate 3-D room layout variations and improve accuracy, multiple observation units with spatial diversity are often required, which will unavoidably cause a significant increase in the component and deployment cost if each unit needs wired power or battery. In this article, we present an indoor device-free object detection system implemented by a commercial radio frequency identification reader and many passive tags around the room. The passive tag as a dispersed observation point offers a cost-effective solution for the necessary spatial diversity. The tag backscattering phase is assembled to generate the reflectivity image inside the capture volume using Fourier-based reconstruction. A new calibration technique is proposed to compensate for multiplicative path losses and subtract the effect of background clutters, such as furniture. Noisy channels and channels with their line-of-sight blocked by the target are also filtered out during postprocessing to improve locating accuracy and mitigate ambiguity. A 1:6 room model was first used to study the effects of the indoor materials and room layout, where occupant recognition and centimeter-level locating were successfully demonstrated. Real-scale rooms were then tested, where decimeter-level 3-D location error was achieved for a single occupant, and useful information for occupant posture can also be evaluated.

Peroneal muscle fatigue could result in ankle inversion sprain injuries. This study investigated the peroneal muscle reaction time during a simulated prolonged football protocol. Nine male footballers completed a 105-minute simulated prolonged football protocol. The peroneal muscle reaction time to an ankle inversion perturbation was measured every 15 minutes by a surface electromyography system sampling at 1000 Hz. One-way repeated ANOVA with post-hoc paired t-test showed a steady upward trend starting from 48.9 ms at baseline to 57.1 ms at the end of the first half, followed by a recovery back to 50.9 ms at the start of the second half and a further delay in the last 30 minutes to 60.2 ms at the end of the protocol. Delayed peroneal muscle reaction was found after 30 minutes of the first half and 15 minutes of the second half of a football match. The risk of ankle sprain could increase in the latter minutes in each half protocol. Thus, prevention injury training strategies should focus on these specific durations in football matches.

Objectives: Two phase III studies using docetaxel, cisplatin and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CCRT) have reported survival benefit compared to CCRT. However, TPF was used at 80% of the conventional dose in the Chinese study due to the concern of tolerability. We aim to explore the tolerability of TPF using standard dose in Chinese patients with stage IVA (AJCC 8th edition) nasopharyngeal carcinoma and report on its preliminary efficacy. Methods: Consecutive patients treated with induction chemotherapy (IC) TPF followed by CCRT between 2017 and 2020 were reviewed. TPF regimen consisted of three cycles of Docetaxel 75 mg/m2 D1; Cisplatin 75 mg/m2 D1; 5-fluorouracil 750 mg/m2 D1-5 every 3 weeks; with G-CSF D7-11. Radiotherapy consisted of 70 Gy in 35 fractions with concomitant cisplatin 100 mg/m2 every 3 weeks. Results: 28 patients were identified. 92.8% patients completed three cycles of IC. 79% patients received concomitant cisplatin of ? 200 mg/m2 . The most common grade 3 or 4 acute toxicity was diarrhea (25%). Grade 3 or 4 neutropenia occurred in 10.7% of patients, of which only 3.6% resulted in febrile neutropenia. Median follow-up was 2 years. The 2-year overall survival, locoregional failure-free survival and distant failure-free survival were 100%, 96.4% and 91.3% respectively. Conclusion: IC using standard dose TPF was well tolerated in Chinese patients with manageable toxicities and allowed adequate delivery of subsequent concurrent cisplatin. Survival outcomes were encouraging and unnecessary dose reduction of TPF should be avoided.

Background: Epidemiological studies have shown an association between the ACE gene I/D polymorphism with arterial hypertension, specifically the DD genotype, in different populations. The objective of this study is to evaluate the association between ACE polymorphisms (Insertion, Deletion or I/D) and essential hypertension in a population of Lima, Peru. Material and methods: This is a study of cases (essential arterial hypertension) and controls, with determination of the ACE I/D genotype. Results: Cases (65) and controls (39) had a mean age (standard deviation) of 74.3 (7.9) and 72.6 (6.5) (p = 0.24). In cases, the genotype frequencies DD, ID, and II were 6 (9.2%), 28 (43.1%) and 31 (47.7%), respectively. In controls, the genotype frequencies DD, ID, and II were 6 (15.4%), 14 (35.9%) and 19 (48.7%). The Hardy-Weinberg equilibrium analysis in cases and controls was p = 0.93 and p = 0.23, respectively. No significant associations between genotype DD vs. ID + II (OR = 0.56, 95% CI: 0.17–1.87, p = 0.34) or II vs. DD + ID (OR = 0.95, 95% CI: 0.43–2.12, p = 0.92) and essential hypertension were found. Conclusions: The ACE I/D polymorphism was not associated with hypertension in our sample.

Gastrointestinal bleeding (GIB) is a common cause of morbidity among patients supported by left ventricular assist devices (LVADs). The aim of this study was to identify if pre-LVAD right ventricular (RV) dysfunction is associated with risk of GIB after LVAD implantation. Of 398 patients implanted with LVADs between July 2008 and July 2016, 130 (33%) developed GIB at a median of 2.6 months following LVAD implantation. Arteriovenous malformations (AVMs) were found in 42 (34%) GIB patients. Patients with GIB were older and more likely to have hypertension, diabetes, and ischemic cardiomyopathy. On pre-LVAD echocardiography, GIB patients had increased RV diastolic dimension (4.7 ± 0.8 vs. 4.4 ± 0.9 cm, p = 0.02), a higher rate of greater than mild tricuspid valve (TV) regurgitation (73 [60%] vs. 120 [47%], p = 0.006), and underwent TV repair more often (38 [30%] vs. 43 [16%], p = 0.0006) during LVAD implantation. After multivariable adjustment, preoperative greater than mild RV enlargement (hazard ratio [HR] 2.32, 95% CI 1.12-5.03; p = 0.03), TV regurgitation (HR 1.83, CI 1.02-3.44; p = 0.01), and TV repair (HR 3.76, confidence interval [CI] 1.02-4.44; p = 0.01) remained associated with risk of GIB. This finding was driven by the AVM-GIB subgroup. Preoperative RV enlargement and TV regurgitation are associated with post-LVAD AVM-related GIB.

Supplemental Digital Content is available in the text., This study reports the first analysis regarding cost-effectiveness of left ventricular assist device (LVAD) implantation via thoracotomy. Cost-effectiveness of LVADs implanted via the traditional surgical approach of sternotomy has been improved through the years because of technological advances, along with understanding the importance of patient selection and postimplant management have on positively affecting outcomes. Given the positive clinical outcomes of the thoracotomy approach, we seek to study the cost-effectiveness of a centrifugal LVAD via this less invasive approach. We developed a Markov model. Survival and quality of life inputs (QALY) for the LVAD arm were based on data from the LATERAL clinical trial. For the Medical Management arm, survival was derived from the Seattle Heart Failure Model. The heart transplant probability was derived from INTERMACS. Survival after heart transplantation used International Society for Heart and Lung Transplantation data. Cost inputs were calculated based on Medicare data and past literature. The incremental cost-effectiveness ratio was found to be $64,632 per quality adjusted life year and $57,891 per life year in the bridge to transplant indication. These results demonstrate further improvement in the overall cost-effectiveness of LVAD therapy and confirm implantation of LVADs via a less invasive approach as being cost-effective.

Trametinib is an extremely potent allosteric inhibitor of mitogen-activated protein kinase (MAPK)/extracellular-signal–regulated kinase (ERK) (MEK) 1/2, which has been approved for treatment of metastatic melanoma and anaplastic thyroid cancer in patients with confirmed BRAF(V600E)/K mutations. Though trametinib is highly efficacious, adverse side effects, including skin, gastrointestinal, and hepatic toxicity, are dose-limiting and can lead to treatment termination. Development of a noninvasive tool to visualize and quantify the delivery and distribution of trametinib (either as a single agent or in combination with other therapeutics) to tumors and organs would be helpful in assessing therapeutic index, personalizing individual dose, and potentially predicting resistance to therapy. Methods: To address these issues, we have developed a radiolabeled trametinib and evaluated the in vitro and in vivo properties. (123)I-, (124)I-, and (131)I-trametinib, pure tracer analogs to trametinib, were synthesized in more than 95% purity, with an average yield of 69.7% and more than 100 GBq/μmol specific activity. Results: Overall, (124)I-trametinib uptake in a panel of cancer cell lines can be blocked with cold trametinib, confirming specificity of the radiotracer in vitro and in vivo. (124)I-trametinib was taken up at higher rates in KRAS and BRAF mutant cell lines than in wild-type KRAS cancer cell lines. In vivo, biodistribution revealed high uptake in the liver 2 h after injection, followed by clearance through the gastrointestinal tract over 4 d. Importantly, uptake higher than expected was observed in the lung and heart for up to 24 h. Peak uptake in the skin and gastrointestinal tract was observed between 6 and 24 h, whereas in B16F10 melanoma–bearing mice peak tumor concentrations were achieved between 24 and 48 h. Tumor uptake relative to muscle and skin was relatively low, peaking at 3.4- to 8.1-fold by 72 h, respectively. The biodistribution of (124)I-trametinib was significantly reduced in mice on trametinib therapy, providing a quantitative method to observe MEK inhibition in vivo. Conclusion: (124)I-trametinib serves as an in vivo tool to personalize the dose instead of using the current single-fixed-dose scheme and, when combined with radiomic data, to monitor the emergence of therapy resistance. In addition, the production of iodinated trametinib affords researchers the ability to measure drug distribution for improved drug delivery studies.

An approach to avoid patent infringement is to review patent documents prior to ideation. However, doing so can lead to design fixation and design distraction. Hence, this paper examines whether reviewing just the patent claim instead of the full patent document can mitigate design fixation and design distraction. 329 undergraduate engineering students were involved in this study. It was found that reviewing just the patent claim can reduce fixation on the design feature reviewed but not on the function of the design feature. In addition, reviewing just the patent claim did not reduce design distraction. The findings of this work can be used to shape the way patent documents are reviewed.

Objectives The interference of a transtricuspid cardiac implantable electronic device (CIED) lead with tricuspid valve function may contribute to the mechanism of tricuspid regurgitation (TR) and poses specific therapeutic challenges during transcatheter tricuspid valve intervention (TTVI). Feasibility and efficacy of TTVI in presence of a CIED is unclear. Background Feasibility of TTVI in presence of a CIED lead has never been proven on a large basis. Methods The study population consisted of 470 patients with severe symptomatic TR from the TriValve (Transcatheter Tricuspid Valve Therapies) registry who underwent TTVI at 21 centers between 2015 and 2018. The association of CIED and outcomes were assessed. Results Pre-procedural CIED was present in 121 of 470 (25.7%) patients. The most frequent location of the CIED lead was the posteroseptal commissure (44.0%). As compared with patients without a transvalvular lead (no-CIED group), patients having a tricuspid lead (CIED group) were more symptomatic (New York Heart Association functional class III to IV in 95.9% vs. 92.3%; p = 0.02) and more frequently had previous episodes of right heart failure (87.8% vs. 69.0%; p = 0.002). No-CIED patients had more severe TR (effective regurgitant orifice area 0.7 ± 0.6 cm2 vs. 0.6 ± 0.3 cm2; p = 0.02), but significantly better right ventricular function (tricuspid annular plane systolic excursion = 16.7 ± 5.0 mm vs. 15.9 ± 4.0 mm; p = 0.04). Overall, 373 patients (79%) were treated with the MitraClip (Abbott Vascular, Santa Clara, California) (106 [87.0%] in the CIED group). Among them, 154 (33%) patients had concomitant transcatheter mitral repair (55 [46.0%] in the CIED group, all MitraClip). Procedural success was achieved in 80.0% of no-CIED patients and in 78.6% of CIED patients (p = 0.74), with an in-hospital mortality of 2.9% and 3.7%, respectively (p = 0.70). At 30 days, residual TR ≤2+ was observed in 70.8% of no-CIED and in 73.7% of CIED patients (p = 0.6). Symptomatic improvement was observed in both groups (NYHA functional class I to II at 30 days: 66.0% vs. 65.0%; p = 0.30). Survival at 12 months was 80.7 ± 3.0% in the no-CIED patients and 73.6 ± 5.0% in the CIED patients (p = 0.30). Conclusions TTVI is feasible in selected patients with CIED leads and acute procedural success and short-term clinical outcomes are comparable to those observed in patients without a transtricuspid lead.

CONTEXT: This review synthesizes the findings of previous research studies on the cardiovascular and metabolic benefits of aerobic exercise for individuals with tetraplegia secondary to spinal cord injury. They are often less active due to muscular paralysis, sensory loss, and sympathetic nervous system dysfunction that result from injury. Consequently, these persons are at higher risk for exercise intolerance and secondary health conditions. OBJECTIVE: To evaluate the evidence concerning efficacy of aerobic exercise training for improving health and exercise performance in persons with tetraplegia from cervical injury. METHODS: The search engines PubMed and Google Scholar were used to locate published research. The final 75 papers were selected on the basis of inclusion criteria. The studies were then rank-ordered using Physiotherapy Evidence Database. RESULTS: Studies combining individuals with tetraplegia and paraplegia show that voluntary arm-crank training can increase mean peak power output by 33%. Functional electrical stimulation leg cycling was shown to induce higher peak cardiac output and stroke volume than arm-crank exercise. A range of peak oxygen uptake (VO(2peak)) values have been reported (0.57–1.32 L/min). Both VO(2peak) and cardiac output may be enhanced via increased muscle pump in the legs and venous return to the heart. Hybrid exercise (arm-crank and functional electrical stimulation leg cycling) can result in greater peak oxygen uptake and cardiovascular responses. CONCLUSION: Evidence gathered from this systematic review of literature is inconclusive due to the lack of research focusing on those with tetraplegia. Higher power studies (level 1–3) are needed with the focus on those with tetraplegia.

Cathepsin L1 (CTSL1) and B (CTSB) are lysosomal proteases, of which the expression and activity are impaired in adipose tissue (AT) of obese rodents, indicating AT lysosomal dysfunction. Here we assess the relation between abdominal subcutaneous AT (SCAT) CTSL1 and CTSB gene expression (qRT-PCR), body composition and tissue-specific insulin resistance in 77 overweight/obese (BMI: 225.6-38.6 kg/m(2)) well phenotyped men and women (61 M/16 F). A two-step hyperinsulinemic-euglycemic clamp was performed to assess AT, hepatic and skeletal muscle insulin sensitivity. Our data show that reduced CTSB expression is associated with markers of insulin resistance (standardized beta = -0.561, p

Introduction: Very little is known about possible clinical sequelae that may persist after resolution of the acute Coronavirus Disease 2019 (COVID-19). A recent longitudinal cohort from Italy including 143 patients recovered after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60 day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical ICU patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. Methods and analysis: This is an international open-access prospective, observational multi-site study. It will enrol patients following a diagnosis of COVID-19. Tier 1 is developed for following up patients day 28 post-discharge, additionally at 3 to 6 months intervals. This module can be used to identify sub-sets of patients experiencing specific symptomatology or syndromes for further follow up. A Tier 2 module will be developed for in-clinic, in-depth follow up. The primary aim is to characterise physical consequences in patients post-COVID-19. Secondary aim includes estimating the frequency of and risk factors for post-COVID-19 medical sequalae, psychosocial consequences and post-COVID-19 mortality. A subset of patients will have sampling to characterize longer term antibody, innate and cell-mediated immune responses to SARS-CoV-2. Ethics and dissemination: This collaborative, open-access study aims to characterize the frequency of and risk factors for long-term consequences and characterise the immune response over time in patients following a diagnosis of COVID-19 and facilitate standardized and longitudinal data collection globally. The outcomes of this study will inform strategies to prevent long term consequences; inform clinical management, direct rehabilitation, and inform public health management to reduce overall morbidity and improve outcomes of COVID-19.

Today, more than ever before, we must all be able to think creatively, manage change, and solve complex, open-ended problems. Education today is different in its structure and practice than it was in any previous generation, not just because of the impact of technology and the Internet, but also because, across the lifespan, every person studies, works, and plays in a global community that was previously unknown to most generations. Although organizations worldwide recognize that their success both now and in the future depends on a workforce capable of effective thinking, problem solving, and innovation, educational practice still lags behind our knowledge in these areas. Educating for Creativity and Innovation is a powerful resource to close the gap between research and practice and to promote understanding and effective practice relating to creativity and innovation. In short, this is a book whose time is now!

Ecosystem degradation represents one of today’s major global challenges, threatening human well-being and livelihoods worldwide. To reverse continuing degradation, we need to understand its socio-economic consequences so that these can be incorporated into ecosystem management decisions. This requires links to be made between our understanding of how ecosystems function and change, with socially meaningful representations of those changes. While increasing attempts are being made at such integration, the interface or translation between those two strands remains largely undiscussed. This carries the risk that key aspects of the socio-ecological interactions become ‘lost in translation’. In this paper, we document and discuss how models of ecosystem change may be combined with socially meaningful outcomes exposing and discussing the translation process itself (i.e. the ‘translation key’). For this, we use an exemplar based on peatland condition. We employ a process-based model, DigiBog, to simulate the effects of land use on blanket peatlands, which we relate to estimates of changes to the public’s well-being derived from peatland degradation and restoration, obtained as monetary values from a choice experiment survey in Scotland (UK). By quantifying linkages between environmental conditions and social values, we make the translation between these system components transparent and allow value estimates to be recalculated under different ecological scenarios, or as new evidence emerges. This enhances the replicability of the research and can better inform decision-making. By using peatlands as the exemplar ecosystem, this paper also contributes to a limited body of evidence on the socio-economic impacts of changes to the most space-effective carbon store in the terrestrial biosphere.

Based on several randomized clinical trials, it has been suggested that baseline glucose homeostasis interacts with the influence of diet composition on weight loss and weight loss maintenance. In this secondary analysis of the YoYo study, a study investigating predictors of weight loss maintenance, we tested the hypothesis that (self-selected) dietary carbohydrate and/or fibre intake interact with the glucose homeostasis parameters for weight loss maintenance. Sixty-one overweight or obese individuals lost around 10 kg of body weight on an energy-restricted diet and were then followed for 9 months. During this period, participants were advised to maintain their body weight and eat a healthy diet without further recommendations on calorie intake or diet composition. Contrary to our hypothesis, carbohydrate intake showed no positive association with weight regain after weight loss, and no interaction with baseline fasting glucose concentration was found. There was a non-significant negative association between fibre intake and weight regain (B = −0.274, standard error (SE) 0.158, p = 0.090), but again, no interaction with fasting plasma glucose was found. In conclusion, the data from the YoYo study do not support a role for baseline glucose homeostasis in determining the association between self-reported carbohydrate and/or fibre intake and weight regain after weight loss.

Objectives The purpose of this observational first-in-human experience was to investigate the feasibility and safety of the PASCAL transcatheter valve repair system and its impact on short-term clinical outcomes in patients with severe tricuspid regurgitation (TR). Background Transcatheter repair of severe TR is a promising treatment option for patients at prohibitive surgical risk. Large leaflet coaptation gaps and tethering represent common features that challenge the application of transcatheter repair techniques. Methods Twenty-eight patients with severe TR were treated with the PASCAL system in a compassionate use experience at 6 sites. All patients had heart failure due to severe TR and were deemed at high surgical risk by institutional heart teams. The primary outcome was procedural success, defined as the implantation of at least 1 device with post-procedural TR grade ≤2+, without mortality or conversion to surgery. Results All patients (mean age 78 ± 6 years, 54% women) were at high surgical risk (mean European System for Cardiac Operative Risk Evaluation II score 6.2 ± 5.2%). TR etiology was functional in 92%, with mean tricuspid annular diameter of 49.5 ± 6 mm and mean coaptation gap of 6.9 ± 3 mm. Procedural success was 86%, with 1.4 ± 0.6 devices implanted per patient. There were no intraprocedural complications. At 30-day follow-up, mortality was 7.1%, 88% of patients were in New York Heart Association functional class I or II, with TR grade ≤2+ in 85%. There were 2 single-leaflet device attachments, which were managed conservatively. Six-min walk distance improved from 240 m (interquartile range: 172 to 337 m) to 335 m (interquartile range: 251 to 385 m) (p Conclusions This first-in-human experience evaluating transcatheter tricuspid repair with the PASCAL system demonstrated high procedural success, acceptable safety, and significant clinical improvement. Larger prospective studies with long-term follow-up are needed to confirm these initial promising results and further define the impact of PASCAL tricuspid repair on clinical outcomes.

Introduction Stroke‐associated pneumonia (SAP) is a major cause of mortality in patients who have suffered from severe ischemic stroke. Although multifactorial in nature, stroke‐induced immunosuppression plays a key role in the development of SAP. Previous studies using a murine model of transient middle cerebral artery occlusion (tMCAO) have shown that focal ischemic stroke induction results in functional defects of lymphocytes in the spleen, thymus, and peripheral blood, leading to spontaneous bacterial infection in the lungs without inoculation. However, how ischemic stroke alters immune cell niche and the expression of cytokines and chemokines in the lungs has not been fully characterized. Methods Ischemic stroke was induced in mice by tMCAO. Immune cell profiles in the brain and the lungs at 24‐ and 72‐hour time points were compared by flow cytometric analysis. Cytokine and chemokine expression in the lungs were determined by multiplex bead arrays. Tissue damage and bacterial burden in the lungs following tMCAO were evaluated. Results Ischemic stroke increases the percentage of alveolar macrophages, neutrophils, and CD11b+ dendritic cells, but reduces the percentage of CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and eosinophils in the lungs. The alteration of immune cell niche in the lungs coincides with a significant reduction in the levels of multiple chemokines in the lungs, including CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, CXCL5, CXCL9, and CXCL10. Spontaneous bacterial infection and tissue damage following tMCAO, however, were not observed. Conclusion This is the first report to demonstrate a significant reduction of lymphocytes and multiple proinflammatory chemokines in the lungs following ischemic stroke in mice. These findings suggest that ischemic stroke directly impacts pulmonary immunity.

This paper proposed a Dickson RF-to-DC rectifier based on floating-gate MOS diodes with tunable threshold voltages to improve RF input sensitivity and to counter process variation in logic CMOS foundry technology. When compensation by active circuits is excluded for system reasons, prior works relied on the availability of diodes with nearly zero threshold voltage in a mixed-signal process, but was unavoidably susceptible to process variation and leakage currents at low thresholds. Our proposed rectifier can have each constituent diode tuned to its optimal threshold at the wafer testing stage to maximize the operational output voltage at various loads and to compensate device-level variations. An optimization algorithm was implemented to automatically take the output voltage as feedback for system calibration in a short duration. The measurements of the tunable-threshold rectifier show > 4dB improvement in input sensitivity compared to the rectifier built by foundry-provided zero-threshold transistors. The proposed circuits can be combined with other techniques including high- ${Q}$ impedance matching for input voltage boosting and hierarchical tandem stages for further improvement on operating conditions. With a ${Q}\,\,{=}$ 10 matching network, −26 dBm sensitivity and 22% efficiency can be achieved for about 0.5 V dc output to a $500~{k} {\Omega }$ load at 570 MHz.

For the same BMI, South Asians have a higher body fat percentage than Caucasians. There might be differences in the fatty acid (FA) handling in adipose tissue when both ethnicities are exposed to high-fat overfeeding. The objective of the present study was to investigate the molecular adaptation in relation to FA metabolism in response to overfeeding with a high-fat diet (OHFD) in South Asian and Caucasian men. Ten South Asian men (BMI 18–29 kg/m2) and ten Caucasian men (BMI 22–33 kg/m2), matched for body fat percentage, aged 20–40 years were included. A weight-maintenance diet (30 % fat, 55 % carbohydrate and 15 % protein) was given for 3 d followed by 3 d of overfeeding (150 % energy requirement) with a high-fat diet (60 % fat, 25 % carbohydrate and 15 % protein) while staying in a respiration chamber. Before and after overfeeding, abdominal subcutaneous fat biopsies were taken. Proteins were isolated, analysed and quantified for short-chain 3-hydroxyacyl-CoA dehydrogenase (HADH), carnitine palmitoyl-transferase 1α (CPT1a), adipose TAG lipase, perilipin A (PLINA), perilipin B, lipoprotein lipase and fatty acid binding protein 4 using Western blotting. OHFD decreased the HADH level (P< 0·05) in Caucasians more than in Asians (P< 0·05), but the baseline and after intervention HADH level was relatively higher in Caucasians. The level of CPT1a decreased in South Asians and increased in Caucasians (P< 0·05). PLINA did not change with diet but the level was higher in South Asians (P< 0·05). The observed differences in HADH and PLINA levels as well as in CPT1a response may be important for differences in the long-term regulation of energy (fat) metabolism in these populations.

The HeartWare centrifugal-flow ventricular assist device system (HVAD) is a viable option for treatment of advanced heart failure. There is a growing trend toward the use of less invasive techniques in cardiac surgery, and the thoracotomy technique for HVAD implantation may provide benefits not available with conventional approaches.The LATERAL trial is a multicenter, prospective, non-randomized, single-arm trial that utilized data from 144 patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database at 26 centers in the United States and Canada. The primary composite end-point was success at 180 days defined as alive on the originally implanted device and free from disabling stroke (modified Rankin Scale score3), transplanted or explanted for recovery. The key secondary end-point was mean length of initial hospital stay.The primary end-point was successfully achieved in 88.1% of patients and was significantly greater than the pre-defined performance goal of 77.5% set from historical sternotomy data (p = 0.0012). The key secondary end-point-mean length of initial hospital stay -was 18 days and was significantly shorter than the pre-defined performance goal of 26.1 days obtained from historical sternotomy data (p0.0001). The adverse event profile further demonstrated the safety of the thoracotomy approach. The overall patient survival was good, and bleeding requiring reoperation was significantly less frequent than that observed in previous studies using the sternotomy approach.This prospective clinical trial provides validation that implantation of the HVAD system via the thoracotomy approach used in the LATERAL study represents a safe and effective alternative to median sternotomy in selected patients intended for a bridge-to-transplant indication.

Acute myeloid leukaemia (AML) is a fatal disease for most patients. We have found that ferumoxytol (Feraheme®), a FDA approved iron oxide nanoparticle for iron deficiency treatment, demonstrates an anti-leukaemia effect in vitro and in vivo. Using leukaemia cell lines and primary AML patient samples, we show that low expression of the iron exporter ferroportin (FPN) results in a susceptibility of these cells by an increase in intracellular iron from ferumoxytol. The reactive oxygen species produced by free ferrous iron leads to increased oxidative stress and cell death. Ferumoxytol treatment results in a significant reduction of disease burden in a murine leukaemia model and patient-derived xenotransplants (PDX) bearing leukaemia cells with low FPN expression. Our findings show how a clinical nanoparticle considered previously largely biologically inert could be rapidly incorporated into clinical trials for patients with leukaemia with low FPN levels., One Sentence Summary: Administration of the clinically approved iron oxide nanoparticle drug ferumoxytol in vitro results in an anti-leukaemia effect and in vivo extended overall survival in part due to the low expression of the iron export protein ferroportin.

The accurate sensing of the location of specific objects in an indoor setting is critical for applications including robotic feedback control and non-intrusive structural integrity monitoring. Current optical and ultrasound approaches often suffer from insufficient accuracy, obstruction by other objects, and ambiguous identification. Alternatively, conventional radar-like radio-frequency (RF) methods can suffer from problems such as multipath ambiguity, small time of flight, and limited item recognition. Attachment of a passive RF identification (RFID) tag can provide a unique marker by modulating the backscattering signal, but current systems struggle with high interference and noise, and thus have poor ranging accuracy. Here we show that a 1 GHz harmonic RFID system can provide a ranging resolution of less than 50 micrometres with a sampling rate of greater than 1 kHz. The fundamental limits on ranging precision in our system are traced to the phase noise of the RF source and the aperture jitter of the data converter. The small passive tag required for the approach can be embedded in indoor or underwater objects, as well as within building structures. A 1 GHz harmonic radio-frequency identification system can provide a ranging resolution of less than 50 μm with a sampling rate of greater than 1 kHz.

Despite the increasing knowledge of the long-term adverse consequence of severe tricuspid regurgitation (TR), most patients with moderate- to-severe TR are still treated conservatively because of the high risk of surgery. Percutaneous procedures have emerged as an attractive alternative treatment. Transcatheter edge-to-edge repair is a validated technique to treat mitral regurgitation. In recent years, the same concept has been applied to patients with TR and prohibitive operative risk. Early trials have shown feasibility and safety. More clinical experiences and long-term results are still being gathered. In this article, we provide an overview of transcatheter edge-to-edge repair and look at the current evidence and clinical results regarding procedure.

One of the biggest challenges in the management of obesity is the prevention of weight regain after successful weight loss. Weight regain after weight loss has large interindividual variation. Although many factors probably contribute to this variation, we hypothesize that variability in biological responses associated with weight loss-induced shrinking of subcutaneous adipocytes has an important role. In this Review, we show that weight loss-induced variations in cellular stress, extracellular matrix remodelling, inflammatory responses, adipokine secretion and lipolysis seem to be associated with the amount of weight that is regained after successful weight loss. Weight regain could therefore, at least in part, depend on a combination of these factors. Further research on the causality of these associations could aid the development of effective strategies to prevent weight regain after successful weight loss. In obesity management, the prevention of weight regain after weight loss is a major challenge. In this Review, the authors discuss mechanisms associated with adipose tissue that are connected to weight regain, including cellular stress, extracellular matrix remodelling and inflammation.

Dietary berries are a rich source of several nutrients and phytochemicals and in recent years, accumulating evidence suggests they can reduce risks of several chronic diseases, including type 2 diabetes (T2D). The objective of this review is to summarize and discuss the role of dietary berries (taken as fresh, frozen, or other processed forms) on insulin resistance and biomarkers of T2D in human feeding studies. Reported feeding trials involve different berries taken in different forms, and consequently differences in nutritional or polyphenol composition must be considered in their interpretation. Commonly consumed berries, especially cranberries, blueberries, raspberries and strawberries, ameliorate postprandial hyperglycemia and hyperinsulinemia in overweight or obese adults with insulin resistance, and in adults with the metabolic syndrome (MetS). In non-acute long-term studies, these berries either alone, or in combination with other functional foods or dietary interventions, can improve glycemic and lipid profiles, blood pressure and surrogate markers of atherosclerosis. Studies specifically in people with T2D are few, and more knowledge is needed. Nevertheless, existing evidence, although sparse, suggests that berries have an emerging role in dietary strategies for the prevention of diabetes and its complications in adults. Despite the beneficial effects of berries on diabetes prevention and management, they must be consumed as part of a healthy and balanced diet.

Objectives The aim of this study was to assess the additional utility of measuring left atrial (LA) pressure as a complement to transesophageal echocardiography (TEE) and Doppler imaging. Background The efficacy of the MitraClip (MC) is assessed intraoperatively by TEE. However, TEE measures are operator dependent and can be influenced by left ventricular (LV) function and changes in LA compliance. Methods Fifty patients undergoing MC therapy with continuous left-sided heart pressure measurements were analyzed. LA V-wave pressure (LAvP), LA mean pressure (LAmP), LV systolic pressure, and LV end-diastolic pressure were measured continuously. LA pressures were indexed to LV pressures to account for changes in afterload during the procedure. Results Most patients (70%) had degenerative mitral regurgitation (MR). TEE MR grade decreased from 3+ to 0+. LAvP (p Conclusions This study demonstrates the value of real-time monitoring of LA pressure during MC therapy to predict clinical outcomes. An increase in LAmP was a predictive of worse clinical outcomes at short-term follow-up, independent from echocardiographic findings.

Objectives A large, prospective international registry was developed to evaluate the initial clinical applications of transcatheter tricuspid valve intervention (TTVI) with different devices. Background TTVI for native tricuspid valve dysfunction has been emerging during the last few years as an alternative therapeutic option to serve a large high-risk population of patients with severe symptomatic tricuspid regurgitation (TR). Methods The TriValve Registry included 312 high-risk patients with severe TR (76.4 ± 8.5 years of age; 57% female; EuroSCORE II 9 ± 8%) at 18 centers. Interventions included repair at the level of the leaflets (MitraClip, Abbott Vascular, Santa Clara, California; PASCAL Edwards Lifesciences, Irvine, California), annulus (Cardioband, Edwards Lifesciences; TriCinch, 4tech, Galway, Ireland; Trialign, Mitraling, Tewksbury, Massachusetts), or coaptation (FORMA, Edwards Lifesciences) and replacement (Caval Implants, NaviGate, NaviGate Cardiac Structures, Lake Forest, California). Clinical outcomes were prospectively determined during mid-term follow-up. Results A total of 108 patients (34.6%) had prior left heart valve intervention (84 surgical and 24 transcatheter, respectively). TR etiology was functional in 93%, and mean annular diameter was 46.9 ± 9 mm. In 75% of patients the regurgitant jet was central (vena contracta 1.1 ± 0.5; effective regurgitant orifice area 0.78 ± 0.6 cm2). Pre-procedural systolic pulmonary artery pressure was 41 ± 14.8 mm Hg. Implanted devices included: MitraClip in 210 cases, Trialign in 18 cases, TriCinch first generation in 14 cases, caval valve implantation in 30 cases, FORMA in 24 cases, Cardioband in 13 cases, NaviGate in 6 cases, and PASCAL in 1. In 64% of the cases, TTVI was performed as a stand-alone procedure. Procedural success (defined as the device successfully implanted and residual TR ≤2+) was 72.8%. Greater coaptation depth (odds ratio: 24.1; p = 0.002) was an independent predictor of reduced device success. Thirty-day mortality was 3.6% and was significantly lower among patients with procedural success (1.9% vs. 6.9%; p = 0.04); Actuarial survival at 1.5 years was 82.8 ± 4% and was significantly higher among patients who had procedural success achieved. Conclusions TTVI is feasible with different technologies, has a reasonable overall procedural success rate, and is associated with low mortality and significant clinical improvement. Mid-term survival is favorable in this high-risk population. Greater coaptation depth is associated with reduced procedural success, which is an independent predictor of mortality.

The emergence of the Internet and its future massification, puts journalism and communications generally in new scenarios, which are used by Digital Journalism, recognizing the new demands of the audience, which has allowed the successful integration of traditional journalistic practices and benefits that allows the internet to include audio, images, photos and texts. The Network completely revolutionized when the dynamics of mass information media appeared in the spectrum, which is why those who at the time became media consumers are now content generators. The audience is no longer seen as a mere receiver, now it is about users, who not only consume content, but are increasingly willing to generate it by being much more participatory; Through theirs comments, through blogs and social networks, by submitting ideas, videos, and photos, what Alvin Toffler once called Prosumers. This research seeks to know how digital journalism develops in the Ica region and how it promotes the emergence of Prosumers among students of the Faculty of Communications Sciences, Tourism and Archeology of the National University "San Luis Gonzaga" of Ica.

The present research deals with the theme of administrative workers from a public University during 2019, the aim was to determine how the organizational communication and administrative management is perceived by administrative workers of the San Luis Gonzaga National University of Ica, during the year 2019. The study was carried out considering a sample of 114 administrative servants, the type of research was basic descriptive and with a correlational level, the study designed was non-experimental and cross-sectional, using a hypothetical deductive method. The technique used was the survey and as an instrument a questionnaire. IT could be determined that there is a direct relationship between the organizational communication and the administrative management which is perceived by the workers of the San Luis Gonzaga National University, obtaining information on a perception of efficiency in administrative management of .57.75% and a perception efficiency in organizational communication of 73.99%. Considering organizational communication, it is important to express that the most important way of communication is the horizontal communication 82.07%, followed by ascending communication and finally descending communication 64.91%. In relation to administrative management, it is concluded that administrative workers consider efficient knowledge about planning 60.09%; about Organization 61.93%; on Management 46.68%, and on control 51.23%.

In the Fall of 2020, university campuses in the United States resumed on-campus instruction and implemented wastewater monitoring for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While quantitative polymerase chain reaction (qPCR) tests were deployed successfully to detect viral RNA in wastewater across campuses, the feasibility of detecting viral variants from a residential building like a dormitory was unclear. Here, we demonstrate that wastewater surveillance from a dormitory with at least three infected students could lead to the identification of viral genomes with more than 95% coverage. Our results indicate that viral variant detection from wastewater is achievable at a dormitory and that coronavirus disease 2019 (COVID-19) wastewater surveillance programs will benefit from the implementation of viral whole genome sequencing at universities., Graphical abstract Unlabelled Image

Supplemental Digital Content is available in the text., Background: The LATERAL trial validated the safety and efficacy of the thoracotomy approach for implantation of the HeartWare HVAD System, leading to Food and Drug Administration approval. We sought to analyze 24-month adverse event (AE) rates, including a temporal analysis of the risk profile, associated with the thoracotomy approach for the HVAD system. Methods: AEs from the LATERAL trial were evaluated over 2 years postimplant. Data was obtained from the Interagency Registry for Mechanically Assisted Circulatory Support database for 144 enrolled United States and Canadian patients. Temporal AE profiles were expressed as events per patient year. Results: During 162.5 patient years of support, there were 25 driveline infections (0.15 events per patient year), 50 gastrointestinal bleeds (0.31 events per patient year), and 21 strokes (0.13 events per patient year). Longitudinal AE analysis at follow-up intervals of

Despite the emergence of endovascular aneurysm repair (EVAR) as the most common approach to abdominal aortic aneurysm repair, open aneurysm repair (OAR) remains an important option. This study seeks to define the indications for OAR in the EVAR era and how these indicatioxns effect outcomes.A retrospective cohort study was performed of all OAR at a single institution from 2004 to 2019. Preoperative computed tomography scans and operative records were assessed to determine the indication for OAR. These reasons were categorized into anatomical contraindications, systemic factors (connective tissue disorders, contraindication to contrast dye), and patient or surgeon preference (patients who were candidates for both EVAR and OAR). Perioperative and long-term outcomes were compared between the groups.We included 370 patients in the analysis; 71.6% (265/370) had at least one anatomic contraindication to EVAR and 36% had two or more contraindications. The most common anatomic contraindications were short aortic neck length (51.6%), inadequate distal seal zone (19.2%), and inadequate access vessels (15.7%). The major perioperative complication rate was 18.1% and the 30-day mortality was 3.0%. No single anatomic factor was identified as a predictor of perioperative complications. Sixty-one patients (16.5%) underwent OAR based on patient or surgeon preference; these patients were younger, had lower incidences of coronary artery disease and chronic obstructive pulmonary disease, and were less likely to require suprarenal cross-clamping compared with patients who had anatomic and/or systemic contraindications to EVAR. The patient or surgeon preference group had a lower incidence of perioperative major complications (8.2% vs 20.1%; P = .034), shorter length of stay (6 days vs 8 days; P .001) and no 30-day mortalities. The multivariable adjusted risk for 15-year mortality was lower for patient or surgeon preference patients (adjusted hazard ratio, 0.44; 95% confidence interval, 0.24-0.80; P = .007) compared with those anatomic or systemic contraindications.Within a population of patients who did not meet instruction for use criteria for EVAR, no single anatomic contraindication was a marker for worse outcomes with OAR. Patients who were candidates for both aortic repair approaches but elected to undergo OAR owing to patient or surgeon preference have very low 30-day mortality and morbidity, and superior long-term survival rates compared with those patients who underwent OAR owing to anatomic and/or systemic contraindications to EVAR.

Evidence before this studyIt is emerging that long-term symptoms are often present in people who have had acute COVID-19 disease. These symptoms affect a range of organ systems including respiratory, cardiovascular and neurological systems. It is not clear how many patients who required hospitalisation develop these symptoms and the impact they have on quality of life. We searched PubMed on 24th March 2021 using the terms ‘COVID-19’, ‘long-Covid’, ‘long-term’ and ‘outcomes’. This was supplemented by hand searching relevant references and news reports. We identified several small studies focussing on specific symptoms or diseases, studies of patients in community settings and studies of patients who were hospitalised for acute COVID-19 in Italy, Russia and China. There were no peer-reviewed published data at the time of searching which captured outcomes of patients within the United Kingdom.Added Value of this studyWe found that over half of patients reported not feeling fully recovered several months after onset of Covid-19 symptoms. The most common symptoms reported were fatigue, followed by breathlessness. Patients reported significant increases in new or worse disability, increases in MRC dyspnoea scale and worse quality of life as measured by EQ5D-5L summary index at the time of follow-up compared to before onset of acute COVID-19 symptoms. Our study found that women, in particular women under the age of 50 were significantly more likely to not feel fully recovered, were more breathless, more fatigued and had higher rates of new or worsened disability, even after taking severity of acute disease into account when compared to men of the same age.Implications of all available evidenceLong-term symptoms following hospitalisation for COVID-19 are very common and have significant impacts on quality of life. Women under 50 were most likely to have the worst outcomes. Policy makers need to ensure there is long-term support for people experiencing long-Covid and should plan for lasting long-term population morbidity. Funding for research to understand mechanisms underlying long-Covid and identify potential interventions for testing in randomised trials is urgently required.Structured AbstractBackgroundThis study sought to establish the long-term effects of Covid-19 following hospitalisation.Methods327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L).Findings55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse at follow-up (median difference 0.1 points on a scale of 0 to 1, IQR: −0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age.InterpretationSurvivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.Role of the funder: The study sponsors and funders had no role in the study design, collection, analysis, interpretation of data, writing of the report, or the decision to submit the article for publication. Investigators were independent from funders and the authors have full access to all of the data, including any statistical analysis and tables.

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Malalties infeccioses; Salut pública Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Enfermedades infecciosas; Salud pública Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Infectious diseases; Public health Introduction Very little is known about possible clinical sequelae that may persist after resolution of acute COVID-19. A recent longitudinal cohort from Italy including 143 patients followed up after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60-day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical intensive care unit patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. The primary aim of this study is to characterise physical and psychosocial sequelae in patients post-COVID-19 hospital discharge. Methods and analysis This is an international open-access prospective, observational multisite study. This protocol is linked with the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) and the WHO’s Clinical Characterisation Protocol, which includes patients with suspected or confirmed COVID-19 during hospitalisation. This protocol will follow-up a subset of patients with confirmed COVID-19 using standardised surveys to measure longer term physical and psychosocial sequelae. The data will be linked with the acute phase data. Statistical analyses will be undertaken to characterise groups most likely to be affected by sequelae of COVID-19. The open-access follow-up survey can be used as a data collection tool by other follow-up studies, to facilitate data harmonisation and to identify subsets of patients for further in-depth follow-up. The outcomes of this study will inform strategies to prevent long-term consequences; inform clinical management, interventional studies, rehabilitation and public health management to reduce overall morbidity; and improve long-term outcomes of COVID-19. Ethics and dissemination The protocol and survey are open access to enable low-resourced sites to join the study to facilitate global standardised, longitudinal data collection. Ethical approval has been given by sites in Colombia, Ghana, Italy, Norway, Russia, the UK and South Africa. New sites are welcome to join this collaborative study at any time. Sites interested in adopting the protocol as it is or in an adapted version are responsible for ensuring that local sponsorship and ethical approvals in place as appropriate. The tools are available on the ISARIC website (www.isaric.org). Protocol registration number osf.io/c5rw3/ Protocol version 3 August 2020 EuroQol ID 37035. This work was supported by the Department for International Development and Wellcome (215091/Z/18/Z) and the Bill & Melinda Gates Foundation (OPP1209135). CP would like to acknowledge the support of the Liverpool Experimental Cancer Medicine Centre (Grant Reference: C18616/A25153) and The Clatterbridge Cancer Centre Charity. CB acknowledges the support from British Heart Foundation RE/18/6134217. LS would like to acknowledge the support of PREPARE funded by the European Commission’s FP7 Programme grant number 602525.

In a cohort of BNT162b2 (Pfizer–BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar between groups after the second dose., Virus-specific antibody levels after a single dose of the BNT162b2 vaccine in individuals previously infected with SARS-CoV-2 are similar to levels after two doses of the vaccine in infection-naive individuals.

Aminoacyl-tRNA synthetases (ARSs) are crucial enzymes for protein translation. Mutations in genes encoding ARSs are associated with human disease. Tyrosyl-tRNA synthetase is encoded by YARS which is ubiquitously expressed and implicated in an autosomal dominant form of Charcot-Marie-Tooth and autosomal recessive YARS-related multisystem disease. We report on a former 34-week gestational age male who presented at 2 months of age with failure to thrive (FTT) and cholestatic hepatitis. He was subsequently diagnosed with hyperinsulinemic hypoglycemia with a negative congenital hyperinsulinism gene panel and F-DOPA positron-emission tomography (PET) scan that did not demonstrate a focal lesion. Autopsy findings were notable for overall normal pancreatic islet size and morphology. Trio whole exome sequencing identified a novel homozygous variant of uncertain significance in YARS (c.611A > C, p.Tyr204Cys) with each parent a carrier for the YARS variant. Euglycemia was maintained with diazoxide (max dose, 18 mg/kg/day), and enteral dextrose via gastrostomy tube (G-Tube). During his prolonged hospitalization, the patient developed progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay. Such multisystem features have been previously reported in association with pathogenic YARS mutations. Although hypoglycemia has been associated with pathogenic YARS mutations, this report provides more conclusive data that a YARS variant can cause hyperinsulinemic hypoglycemia. This case expands the allelic and clinical heterogeneity of YARS-related disease. In addition, YARS-related disease should be considered in the differential of hyperinsulinemic hypoglycemia associated with multisystem disease.