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CRISPR-Cas9 is rapidly entering molecular biology and biomedicine as a promising gene-editing tool. A unique feature of CRISPR-Cas9 is a single guide RNA directing a Cas9 nuclease towards its genomic target. Herein, we highlight new approaches for improving cellular uptake and endosomal escape of CRISPR-Cas9. As opposed to other recently published works, this review is focused on non-viral carriers as a means to facilitate the cellular uptake of CRISPR-Cas9 through endocytosis. The majority of non-viral carriers, such as gold nanoparticles, polymer nanoparticles, lipid nanoparticles and nanoscale zeolitic imidazole frameworks, are developed with a focus towards optimizing the endosomal escape of CRISPR-Cas9 by taking advantage of the acidic environment in the late endosomes. Among the most broadly used methods for in vitro and ex vivo ribonucleotide protein transfection are electroporation and microinjection. Thus, other delivery formats are warranted for in vivo delivery of CRISPR-Cas9. Herein, we specifically revise the use of peptide and nanoparticle-based systems as platforms for CRISPR-Cas9 delivery in vivo. Finally, we highlight future perspectives of the CRISPR-Cas9 gene-editing tool and the prospects of using non-viral vectors to improve its bioavailability and therapeutic potential.

We assessed the prevalence of Lyme neuroborreliosis in children with acute facial nerve palsy in a Lyme-endemic region and patient characteristics associated with this. All children visiting one of three participating hospitals between January 2010 and December 2016 were included in the study. Of 104 children referred to the hospital with facial nerve palsy, 43% had Lyme neuroborreliosis and 57% idiopathic facial palsy. Characteristics significantly associated with Lyme neuroborreliosis were headache (55% versus 18%), meningeal irritation (21% versus 5%), presentation in summer months (69% versus 37%), and a previous tick bite (33% versus 7%).

The aim of the present study was to evaluate if the vancomycin (1 mg/ml) is effective for the prevention of septic arthritis after ACL reconstruction. The hypothesis was that local antibiotic prophylaxis by soaking ACL grafts in vancomycin results in significantly less infections than ACL reconstruction without local antibiosis. In group 1, 636 patients who were operated between 1.9.2014 and 31.8.2016 received no local antibiotic treatment with vancomycin. In group 2, 536 patients who were operated between 1.9.2016 and 31.8.2018 received local antibiotic treatment with vancomycin (1 mg/ml). In this group the graft was soaked in the vancomycin solution for 10 min prior to graft passage and fixation. In group 1 (ACL reconstruction without vancomycin application), a postoperative infection was detected in ten patients (infection rate: 1.6%). In group 2 (ACL reconstruction with 1 mg/ml vancomycin), no postoperative infection was detected (infection rate: 0%). The statistical analysis showed a clear significant difference between the two groups (p = 0.002). The re-rupture rate and the rate of arthrofibrosis differed not significantly between the two treatment groups (p = 0.526). The results of the present study show that graft soaking in vancomycin (1 mg/ml) is effective for the prevention of septic arthritis after ACL reconstruction. III.

ObjectiveTo examine the joint associations of daily time spent in different intensities of physical activity, sedentary behaviour and sleep with all-cause mortality.MethodsFederated pooled analysis of six prospective cohorts with device-measured time spent in different intensities of physical activity, sedentary behaviour and sleep following a standardised compositional Cox regression analysis.Participants130 239 people from general population samples of adults (average age 54 years) from the UK, USA and Sweden.Main outcomeAll-cause mortality (follow-up 4.3–14.5 years).ResultsStudies using wrist and hip accelerometer provided statistically different results (I2=92.2%, Q-test pConclusionThis federated analysis shows a joint dose–response association between the daily balance of time spent in physical activity of different intensities and sedentary behaviour with all-cause mortality, while sleep duration does not appear to be significant. The strongest association is with time spent in moderate to vigorous physical activity, but it is modified by the balance of time spent in light physical activity relative to sedentary behaviour.

Among thermoplastics, polypropylene (PP) is outstanding with respect to its high versatility in terms of its tailoring property profiles for diversified applications, high resource and energy effic...

Fused filament fabrication (FFF) of polyethylene (PE) reactor blends containing high amounts of nanophase-separated disentangled ultrahigh molar mass polyethylene (UHMWPE) generates self-reinforced...

Background Many prodromal Alzheimer’s disease trials collect two types of data: the time until clinical diagnosis of dementia and longitudinal patient information. These data are often analysed separately, although they are strongly associated. By combining the longitudinal and survival data into a single statistical model, joint models can account for the dependencies between the two types of data. Methods We illustrate the major steps in a joint modelling approach, motivated by data from a prodromal Alzheimer’s disease study: the LipiDiDiet trial. Results By using joint models we are able to disentangle baseline confounding from the intervention effect and moreover, to investigate the association between longitudinal patient information and the time until clinical dementia diagnosis. Conclusions Joint models provide a valuable tool in the statistical analysis of clinical studies with longitudinal and survival data, such as in prodromal Alzheimer’s disease trials, and have several added values compared to separate analyses. Electronic supplementary material The online version of this article (10.1186/s12874-019-0791-z) contains supplementary material, which is available to authorized users.

ZusammenfassungFür Deutschland liegen bisher keine systematisch erhobenen Daten zur Betreuung von Migrantinnen mit Gestationsdiabetes (GDM) vor, obwohl die Anzahl von Migrantinnen in deutschen Geburtskliniken seit den 1980er Jahren kontinuierlich zunimmt. Methodik Auf Grundlage der Fallzahlschätzung für diese prospektive Studie wurde der Einschluss von 160 GDM-Patientinnen+/- einer Drop-Out-Rate von 10 GDM-Patientinnen pro Gruppe, 90 mit Migrationshintergrund (MH) und 90 ohne MH, angestrebt. Die Datenerhebung erfolgte mittels Fragebogen zur Erhebung soziodemografischer Daten, Migration, Akkulturation und Ernährungsverhalten, sowie der Erfassung relevanter Perinataldaten (z. B. pränatales Schätzgewicht, Geburtsmodus, etc.) aus der peripartalen Betreuung. Ergebnisse Zwischen Januar 2017 und Mai 2019 wurden 198 GDM-Patientinnen untersucht. Hiervon hatten 110 GDM-Patientinnen einen und 88 keinen MH. Die Indikation zur Geburtseinleitung aufgrund der Verdachtsdiagnose einer fetalen Makrosomie wurde ungefähr gleich häufig für die GDM-Patientinnen mit sowie ohne MH gestellt (mit MH 3,6% vs. ohne MH 4,6%, p=1,0, OR 1,73; 95%-KI 0,79–3,89, p=0,17). GDM-Patientinnen mit MH gebaren ihr Kind häufiger spontan (mit MH 55,5% vs. ohne MH 40,9%, p=0,05). Das perinatale Outcome war in beiden Gruppen vergleichbar. Schlussfolgerungen Die Hypothese, dass bei GDM-Patientinnen mit MH häufiger Geburtseinleitungen aufgrund der Verdachtsdiagnose eines makrosomen Fetus erforderlich sind, wurde nicht bestätigt. Wesentliche neonatale Parameter wie Geburtsgewicht oder Verlegung der Neugeborenen waren ohne signifikante Unterschiede im Gruppenvergleich.

The open abdomen requires intensive and specific treatment efforts. Long hospital admissions, treatment duration, high mortality rates, deferred and delayed wound closures with alloplastic materials or elaborate closure techniques, and the need for subsequent surgical procedures justify and call for implementation of new therapy options. The case presented here demonstrates the use of a new product (Fasciotens Abdomen) to prevent fascial retraction in the open abdomen of an extubated, conscious patient with four-quadrant peritonitis after perforated appendicitis. Controlled, anteriorly directed fascial traction of 50-60 Newtons prevented fascial retraction during open treatment of the abdomen. Once edema was reduced, abdominal closure was completed without difficulty. This new form of therapy was well tolerated by the patient and led to a markedly more rapid abdominal closure without mesh or abdominal wall reconstruction.

BACKGROUND Nonspecific symptoms in children suspected of Lyme borreliosis (LB) are challenging for clinicians. We assessed whether nonspecific symptoms are more prevalent among children with positive immunoglobulin G (IgG) serology or a history of clinical LB. METHODS We included children (

Background Inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. Ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. This provides a good rationale to monitor respiratory drive in ventilated patients. Respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. A disadvantage is that both techniques are invasive. Therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. The aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm. Methods Activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. Electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. Pressure support (PS) levels were reduced from 15 to 3 cmH2O every 5 min with steps of 3 cmH2O. The magnitude and timing of respiratory muscle activity were assessed. Results We included 17 ventilated patients. Diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower PS levels (36 ± 6% increase for the diaphragm, 30 ± 6% parasternal intercostals, 41 ± 6% scalene, 40 ± 8% sternocleidomastoid, 43 ± 6% alae nasi and 30 ± 6% genioglossus). Changes in diaphragm activity correlated best with changes in alae nasi activity (r2 = 0.49; P < 0.001), while there was no correlation between diaphragm and sternocleidomastoid activity. The agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. Onset of alae nasi activity preceded the onset of all other muscles. Conclusions Extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. However, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (EMG) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm.

The internet is an indispensable aspect of modern society. It facilitates long distance communication, access to information, health care interventions, as well as multiple opportunities for social participation. Despite increasing pervasiveness of this technology, persistent inequalities exist in who has access to the internet. In particular, older adults lag behind in having internet access, thus putting them at risk for social exclusion. In order to gain a better understanding about the determinants of thisgrey digital divide, the current study contrasts influencing factors of internet access, comparing samples from 2002 to 2014 across age groups (40 to 54 years, 55 to 69 years and 70 to 85 years) using data from the German Ageing Survey (DEAS). Logistic regression confirmed that the likelihood of having internet access was lower with higher age at both time points. However, the percentages of people with internet access grew primarily in the middle and older age groups between 2002 and 2014. Furthermore, being male and having a higher education were both associated with greater odds of internet access. However, gender and education differences in internet access were significantly less pronounced in 2014 in contrast to 2002. Finally, both greater income and cognitive ability were associated with greater odds of internet access, while providing care for a grandchild was significantly associated with internet access only among the oldest age group. In an attempt towards bridging the grey digital divide, the current study serves as a basis for identifying groups mostly affected by this increasingly important form of social inequality.

Summary: Insights into the immunopathogenesis of chronic HBV infections are fundamental in the quest for novel treatment approaches aimed at a functional cure. While much is known about the ineffective HBV-specific T-cell responses that characterise persistent HBV replication, B cells have been left largely understudied. However, an important role for humoral immunity during the natural history of HBV infections, as well as after functional cure, has been inadvertently revealed by the occurrence of HBV flares following B cell-depleting treatments. Herein, we review our current understanding of the role of the humoral immune response in chronic HBV, both at the level of HBV-specific antibody production and at the phenotypic and broader functional level of B cells. The recent development of fluorescently labelled HBV proteins has given us unprecedented insights into the phenotype and function of HBsAg- and HBcAg-specific B cells. This should fuel novel research into the mechanisms behind dysfunctional HBsAg-specific and fluctuating, possibly pathogenic, HBcAg-specific B-cell responses in chronic HBV. Finally, novel immunomodulatory treatments that partly target B cells are currently in clinical development, but a detailed assessment of their impact on HBV-specific B-cell responses is lacking. We plead for a rehabilitation of B-cell studies related to both the natural history of HBV and treatment development programmes.

Objective To determine the response to a pulmonary rehabilitation (PR) program and minimal important differences (MIDs) for the Short Physical Performance Battery (SPPB) subtests and SPPB summary score in patients with chronic obstructive pulmonary disease (COPD). Design Retrospective analysis using distribution- and anchor-based methods. Setting PR center in the Netherlands including a comprehensive 40-session 8-week inpatient or 14-week outpatient program. Participants A total of 632 patients with COPD (age, 65±8y; 50% male; forced expiratory volume in the first second=43% [interquartile range, 30%-60%] predicted). Interventions Not applicable. Main Outcome Measure Baseline and post-PR results of the SPPB, consisting of 3 balance standing tests, 4-meter gait speed (4MGS), and 5-repetition sit-to-stand (5STS). The chosen anchors were the 6-Minute Walk Test and COPD Assessment Test. Patients were stratified according to their SPPB summary scores into low-performance, moderate-performance, and high-performance groups. Results 5STS (∆=−1.14 [−4.20 to −0.93]s) and SPPB summary score (∆=1 [0-2] points) improved after PR in patients with COPD. In patients with a low performance at baseline, balance tandem and 4MGS significantly increased as well. Based on distribution-based calculations, the MID estimates ranged between 2.19 and 6.33 seconds for 5STS and 0.83 to 0.96 points for SPPB summary score. Conclusions The 5STS and SPPB summary score are both responsive to PR in patients with COPD. The balance tandem test and 4MGS are only responsive to PR in patients with COPD with a low performance at baseline. Based on distribution-based calculations, an MID estimate of 1 point for the SPPB summary score is recommended in patients with COPD. Future research is needed to confirm MID estimates for SPPB in different centers.

Accurate and low-cost sleep measurement tools are needed in both clinical and epidemiological research. To this end, wearable accelerometers are widely used as they are both low in price and provide reasonably accurate estimates of movement. Techniques to classify sleep from the high-resolution accelerometer data primarily rely on heuristic algorithms. In this paper, we explore the potential of detecting sleep using Random forests. Models were trained using data from three different studies where 134 adult participants (70 with sleep disorder and 64 good healthy sleepers) wore an accelerometer on their wrist during a one-night polysomnography recording in the clinic. The Random forests were able to distinguish sleep-wake states with an F1 score of 73.93% on a previously unseen test set of 24 participants. Detecting when the accelerometer is not worn was also successful using machine learning ($$\hbox {F1-score} > 93.31\%$$ F1-score > 93.31 % ), and when combined with our sleep detection models on day-time data provide a sleep estimate that is correlated with self-reported habitual nap behaviour ($$\hbox {r}=.60$$ r = . 60 ). These Random forest models have been made open-source to aid further research. In line with literature, sleep stage classification turned out to be difficult using only accelerometer data.

BackgroundThe endurance shuttle walk test (ESWT) is used to evaluate exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). The recommended pre-intervention tolerated duration (Tlim) is between 3-8 minutes for optimal interpretation of treatment effects. However, this window may be exceeded and factors determining ESWT Tlim are not completely understood. Therefore, we aimed to determine whether pulmonary function, physical and incremental shuttle walk test (ISWT) performance measures are associated with ESWT Tlim in COPD patients.MethodsAssessment data from patients eligible for pulmonary rehabilitation was retrospectively analyzed. Inclusion criteria were: diagnosis of COPD and complete data availability regarding ESWT and ISWT. Patients performed an ESWT at 85% of ISWT speed and were divided into three groups (ESWT Tlim: 8 minutes). Subject characteristics, severity of complaints, pulmonary function, physical capacity and activity, exercise tolerance and quadriceps muscle strength were evaluated.Results245 COPD patients (FEV1 38 (29-52)% predicted) were included. Median ESWT Tlim was 6.0 (3.7-10.3) minutes, 41 (17%) patients walked 8 minutes. Body mass index, maximal oxygen consumption, Tlim on constant work rate cycle test, physical activity level, maximal ISWT speed, dyspnoea Borg score at rest and increase of leg fatigue Borg score during ISWT independently predicted Tlim in multivariate regression analysis (R-2 = 0.297, p

Background Moderate-to-vigorous physical activity (MVPA) is proposed as key for cardiovascular diseases (CVD) prevention. At older ages, the role of sedentary behaviour (SB) and light intensity physical activity (LIPA) remains unclear. Evidence so far is based on studies examining movement behaviours as independent entities ignoring their co-dependency. This study examines the association between daily composition of objectively-assessed movement behaviours (MVPA, LIPA, SB) and incident CVD in older adults. Methods Whitehall II accelerometer sub-study participants free of CVD at baseline (N = 3319, 26.7% women, mean age = 68.9 years in 2012–2013) wore a wrist-accelerometer from which times in SB, LIPA, and MVPA during waking period were extracted over 7 days. Compositional Cox regression was used to estimate the hazard ratio (HR) for incident CVD for daily compositions of movement behaviours characterized by 10 (20 or 30) minutes greater duration in one movement behaviour accompanied by decrease in another behaviour, while keeping the third behaviour constant, compared to reference composition. Analyses were adjusted for sociodemographic, lifestyle, cardiometabolic risk factors and multimorbidity index. Results Of the 3319 participants, 299 had an incident CVD over a mean (SD) follow-up of 6.2 (1.3) years. Compared to daily movement behaviour composition with MVPA at recommended 21 min per day (150 min/week), composition with additional 10 min of MVPA and 10 min less SB was associated with smaller risk reduction – 8% (HR, 0.92; 95% CI, 0.87–0.99) – than the 14% increase in risk associated with a composition of similarly reduced time in MVPA and more time in SB (HR, 1.14; 95% CI, 1.02–1.27). For a given MVPA duration, the CVD risk did not differ as a function of LIPA and SB durations. Conclusions Among older adults, an increase in MVPA duration at the expense of time in either SB or LIPA was found associated with lower incidence of CVD. This study lends support to public health guidelines encouraging increase in MVPA or at least maintain MVPA at current duration.

Background Reliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic. Aim We estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy. Methods We reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/EEA). Results Pooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one point-of-care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area. Conclusion Continuous monitoring of clinical performance within more clearly defined target populations is needed.

Significance: Intraplaque hemorrhage (IPH) is an important indicator of plaque vulnerability. Early detection could aid the prevention of stroke. Aim: We aim to detect IPH with single wavelength PA imaging in vivo and to improve image quality. Approach: We developed a singular value decomposition (SVD)-based filter to detect the nonstationary and stationary components in ultrasound data. A PA mask was created to detect stationary (IPH) sources. The method was tested ex vivo using phantoms and in vivo in patients. Results: The flow and IPH channels were successfully separated in the phantom data. We can also detect the PA signals from IPH and reject signals from the carotid lumen in vivo. Generalized contrast-to-noise ratio improved in both ex vivo and in vivo in US imaging. Conclusions: SVD-based filtering can successfully detect IPH using a single laser wavelength, opening up opportunities for more economical and cost-effective laser sources.

Background: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. Aim: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion. Methods: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium. Results: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. Conclusion: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss. Foundation Against Cancer Belgium, Grant/Award Number: 2014-087

Objective(s): Blood cultures (BC), when performed in children seen in the emergency department with community-acquired pneumonia (CAP), are most of the time sterile. We described the diagnostic accuracy of white blood cells (WBC), absolute neutrophils count (ANC), C-reactive protein (CRP), and procalcitonin (PCT) to predict blood culture (BC) result in childhood CAP.Study Design: Secondary analysis of a prospective study carried out in eight pediatric emergency departments (France, 2009–2018), including children (≤15 years) with CAP. Analyses involved univariate comparisons and ROC curves.Results: We included 13,752 children with CAP. BC was positive in 137 (3.6%) of the 3,829 children (mean age 3.7 years) in whom it was performed, mostly with Streptococcus pneumoniae (n = 107). In children with bacteremia, ANC, CRP and PCT levels were higher (median 12,256 vs. 9,251/mm3, 223 vs. 72 mg/L and 8.6 vs. 1.0 ng/mL, respectively; p ≤ 0.002), but WBC levels were not. The area under the ROC curve of PCT (0.73 [95%CI 0.64–0.82]) was significantly higher (p ≤ 0.01) than that of WBC (0.51 [0.43–0.60]) and of ANC (0.55 [0.46–0.64]), but not than that of CRP (0.66 [0.56–0.76]; p = 0.21). CRP and PCT thresholds that provided a sensitivity of at least 90% were 30 mg/L and 0.25 ng/mL, respectively, for a specificity of 25.4 and 23.4%, respectively. CRP and PCT thresholds that provided a specificity of at least 90% were 300 mg/L and 20 ng/mL, respectively, for a sensitivity of 31.3 and 28.9%, respectively.Conclusions: PCT and CRP are the best routinely available predictive biomarkers of bacteremia in childhood CAP.

Background Moderate-to-vigorous physical activity (MVPA) is proposed as key for cardiovascular diseases (CVD) prevention. At older ages, the role of sedentary behavior (SB) and light intensity physical activity (LIPA) remains unclear. Evidence so far is based on studies examining movement behaviors as independent entities ignoring their co-dependency. This study aims to examine the association between daily composition of objectively-assessed movement behaviors (MVPA, LIPA, SB) and incident CVD in older adults. Methods Whitehall II accelerometer sub-study participants free of CVD at baseline (N = 3319, 26.7% women, mean age=68.9 years in 2012-2013) wore a wrist-accelerometer from which times in SB, LIPA, and MVPA were extracted. Compositional Cox regression was used to estimate the hazard ratio (HR) for incident CVD for daily compositions of movement behaviors characterized by 10 (20 or 30) minutes greater duration in one movement behavior accompanied by decrease in another behavior, while keeping the third behavior constant, compared to reference composition. Results Of the 3319 participants, 299 had an incident CVD over a mean (SD) follow-up of 6.2 (1.3) years. Compared to individuals with daily movement behavior composition composed with MVPA at recommended 21 minutes per day (150 minutes/week), composition with additional 10 minutes of MVPA and 10 minutes less SB were associated with smaller risk reduction -8% (HR, 0.92; 95% CI, 0.87-0.99) - than the 14% increase in risk associated with a composition of similarly reduced time in MVPA and more time in SB (HR, 1.14; 95% CI, 1.02-1.27). For a given MVPA duration, the CVD risk did not differ as a function of LIPA and SB durations. Conclusions An increase in MVPA duration at the expense of time in either SB or LIPA was associated with lower risk of incident CVD. This study lends support to public health guidelines encouraging increase in MVPA or at least maintain MVPA at their current duration. Key messages Older adults should be encouraged to increase their moderate-to-vigorous physical activity or at least maintain at their current levels to lower risk of incident cardiovascular disease. Highly sedentary older adults should increase their moderate-to-vigorous physical activity by decreasing sedentary time rather than light-intensity activity to prevent cardiovascular disease.

Background: The Short Physical Performance Battery (SPPB) is commonly used in patients with chronic obstructive pulmonary disease (COPD) to assess mobility and balance. However, information about the response to pulmonary rehabilitation (PR) and minimal clinical important differences (MCIDs) of SPPB subtests and summary score in these patients is limited. Aim: To determine the response to PR and MCIDs for the SPPB subtests and SPPB summary score in patients with COPD. Methods: Retrospective analysis of 632 patients with COPD (age: 65±8 years, 50% male, FEV1: 43 (27-47)% predicted) following a PR program was performed. The SPPB consisted of three balance standing tests, 4-meter gait speed (4MGS) test and 5-repetition sit-to-stand (5STS) test. MCIDs were estimated with anchor-based (anchors: COPD Assessment Test and 6-minute walk test) and distribution-based methods. Results: 5STS (∆=1.14 (-4.20- -0.93) sec) and SPPB summary score (∆=1 (0-2) points) improved significantly after PR. Anchor-based method could not determine MCIDs as there were no significant correlations between the anchors and SPPB scores. Based on distribution-based calculations, the MCID estimates range between 0.51-0.67 sec for balance side-by-side, 0.64-0.78 sec for semi-tandem, 1.80-2.03 sec for tandem, 0.05-0.31 m/s for 4MGS, 2.19-6.33 sec for 5STS and 0.81-0.96 points for SPPB summary score. Conclusions: The 5STS and SPPB summary score are both responsive to PR in patients with COPD. Based on distribution-based calculations, a MCID estimate of 1 point for the SPPB summary score is recommended in these patients. Future research is needed to confirm MCID estimates for the SPPB subtests in different centres.

Predicting subjective visual interpretation is important for several prominent tasks in computer vision, including multimedia retrieval. Many approaches reduce this problem to the prediction of adjective or attribute labels from images while neglecting attribute semantics and only processing the image in a holistic manner. Furthermore, there is a lack of relevant datasets with fine-grained subjective labels and sufficient scale for machine learning. In this paper, we explain the Focus–Aspect–Value (FAV) model to break down the process of subjective image interpretation into three steps and describe a dataset following this way of modeling. We train and evaluate several deep learning methods on this dataset, while we extend the experiments of the paper originally introducing FAV by adding a new evaluation metric, improving the concatenation approach and adding Multiplicative Fusion as another method. In our experiments, Tensor Fusion is among the best performing methods across all measures and outperforms the default way of information fusion (concatenation). In addition, we find that the way of combining information in neural networks not only affects prediction performance but can drastically change other properties of the model as well.

„Fast-Track-Konzepte“ dienen der Verminderung des Risikos fur peri- und postoperative Komplikationen nach Implantation einer Knievollprothese. Die beschriebenen Konzepte werden eingesetzt bei Patienten mit der Indikation zur Implantation einer Knievollprothese. Kontraindikationen fur „Fast-Track-Konzepte“ sind: hochbetagte Patienten, Demenz, ASA-Klasse IV (gemas American Society of Anesthesiologists), Implantation groser Revisions- oder Tumorprothesen. Kontraindikationen fur Tranexamsaure sind: Blutungen im Harntrakt, Vorsicht bei bekannter Epilepsie, individuelle Risikoabwagung bei bestehenden Thrombosen bzw. erhohtem Thromboserisiko, frischer Herzinfarkt, Z. n. frischer Lungenembolie, Z. n. perkutaner transluminaler Koronarangioplastie (PTCA) oder Z. n. Stentimplantation. Kontraindikationen fur Ropivacain sind: Uberempfindlichkeit (Allergie) gegen Ropivacain und andere Lokalanasthetika vom Amidtyp, Hypovolamie. Praoperativ wird die Gabe von 1 g Tranexamsaure und intraoperativ eine lokale Infiltrationsanasthesie durchgefuhrt. Dazu erfolgt nach der femoralen und tibialen Knochenresektion, vor der Zementierung der femoralen und tibialen Komponenten, die Injektion von etwa 40 ml Ropivacain (2 %) in die posteriore Kapsel. Weiter erfolgt die Injektion von jeweils etwa 20 ml Lokalanasthetikum in die medialen und lateralen Seitenbander und die Infiltration des Hoffa-Fettkorpers sowie des Streckapparats mit ebenfalls etwa 20 ml Lokalanasthetikum. Nach der Zementierung wird das Subkutangewebe mit etwa 50 ml Ropivacainlosung infiltriert. Noch am Operationstag wird der Patient unter krankengymnastischer Anleitung mobilisiert. Dabei soll der Patient, wenn moglich, bereits einige Schritte an 2 Unterarmgehstutzen gehen. Die systemische analgetische Therapie erfolgt nach WHO-Stufenschema II mit einem schwach wirksamen Opioid und Nichtopioidanalgetika der ersten Stufe (nichtsteroidale Antirheumatika, NSAR, und/oder Metamizol). Als adjuvante Komedikation kann Gabapentin eingesetzt werden. Die medikamentose Thromboseprophylaxe erfolgt fur 2 Wochen postoperativ mit einem niedermolekularen Heparin. Bei 100 Patienten, die praoperativ 1 g Tranexamsaure sowie eine intraartikulare Infiltrationsanasthesie erhalten hatten, lag der Schmerz am Abend des Op.-Tags auf der numerischen Ratingskala (NRS) durchschnittlich bei 2,1 (±1,8). Bei einem Patienten bestand ein sensibles Defizit am Unterschenkel und Fus. Ein motorischer Ausfall wurde nicht beobachtet. Es konnten 90 Patienten das gestreckte Bein anheben. Am Op.-Tag konnten 68 Patienten mehr als 10 Schritte gehen, 22 Patienten konnten in den Stand mobilisiert werden. Die mittlere stationare Verweildauer lag bei 6,6 Tagen (5–11 Tage). Infektionen, Thrombosen und Lungenembolien traten nicht auf.

Ziel der Operation ist es, eine varische Beinachse zu korrigieren. Es erfolgt eine Langsinzision medial der Tuberositas tibiae. Das mediale Kollateralband (sMCL) wird im Bereich des distalen Ansatzes subperiostal abgelost. Die Osteotomieebene wird mit K‑Drahten knapp oberhalb des Pes anserinus markiert und mit dem BV kontrolliert. Die K‑Drahtspitze sollte im oberen Anteil des Tibiofibulargelenkes liegen. Dann erfolgt die biplanare Osteotomie unter sorgfaltiger Kuhlung bis ca. 5 mm vor die laterale Kortikalis. Die Tuberositas tibiae kann proximal oder auch distal untersagt werden. Dann wird der Osteotomiespalt langsam mit grosen Lambott-Meiseln unter Beachtung der Tibiareklination gespreizt. Die Osteosynthese erfolgt dann mit einem winkelstabilen Plattenfixateur. Der Osteotomiespalt kann fakultativ ab einer Hohe von 12 mm mit allogenem oder autologem Knochen aufgefullt werden. Belastung mit 10 Kg Teilkorpergewicht fur 2 bis 6 Wochen, freie Beweglichkeit.

Ziel der Operation ist es, das vordere Kreuzband (VKB) mit einem autologen Sehnentransplantat zu ersetzen (Semitendinosussehne). Der femorale Tunnel wird uber ein tiefes anteromediales Portal unter arthroskopischer Kontrolle gebohrt. Das Knie muss beim Bohren mehr als 110° gebeugt sein. Als Landmarken dienen die Linea intercondylaris und die Knorpel-Knochen-Grenze. Die Position des Tunnels sollte uber das mediale Portal kontrolliert werden (medialer Portalblick). An der Tibia dient das Ausenmeniskusvorderhorn als Landmarke. Zur Fixation des Transplantates wird femoral ein Kippanker und tibial eine Interferenzschraube ggf. mit zusatzlichem extrakortikalem Knopf verwendet. Die Nachbehandlung erfolgt in verschiedenen Phasen. Die Progression bis zur Wiederkehr zum Sport sollte kriterienbasiert erfolgen.

Die Neigung des Tibiaplateaus in der Sagittalebene („Slope“) beeinflusst die Stabilitat des Kniegelenks. Aufgrund der nach hinten abfallenden Gelenkflache gleitet die Tibia unter Last nach anterior. Ein erhohter „Slope“ kann daher zu vorderen Instabilitaten beitragen. Auch Deformitaten in der Frontalebene konnen eine Auswirkung auf die Stabilitat des Kniegelenks haben. Anterolaterale Begleitinstabilitaten konnen bei vorbestehender ossarer Varusdeformitat eine zusatzliche ligamentare Varuskomponente induzieren (Doppelvarussituation). Das radiologische Klaffen des lateralen Gelenkspalts wird als „Varus-thrust“-Phanomen bezeichnet. Aus diesen Grunden mussen Deformitaten in der Sagittal- und Frontalebene bei der Therapie ligamentarer Instabilitaten beachtet werden. Das betrifft insbesondere Falle, bei denen eine Bandplastik des vorderen Kreuzbands (VKB) bereits versagt hat (Revisionen). Zur Korrektur dieser Deformitaten eignen sich extendierende und valgisierende Tibiakopfosteotomien. Durch die Verwendung winkelstabiler Implantate zur Stabilisierung der Osteotomie ist meist eine fruhfunktionelle Nachbehandlung moglich. Diese Eingriffe konnen einzeitig oder zweizeitig mit Kreuzbandplastiken kombiniert werden. Die bisherigen klinischen Erfahrungen mit diesen Eingriffen sind zwar limitiert, aber erfolgversprechend.

Wiederherstellung der Kniestabilitat nach Reruptur einer vorderen Kreuzband-(VKB-)Plastik. Akute und chronische funktionelle Instabilitat mit Reruptur eines VKB-Transplantats bei anatomischen oder nichtanatomischen Knochentunneln ohne Tunnelweitung. Partiell anatomische Knochentunnel der vorherigen Operation, signifikante Tunnelweitung anatomischer Knochentunnel, lokale Infektion im Bereich des Kniegelenks, lokale Weichteilschadigung. Geeignete Revisionstransplantate sind die autologen Beugesehnen (M. semitendinosus, M. gracilis), die Quadrizepssehne, die Patellarsehne sowie ein Peroneussehnen-Split-Graft. Bei anatomischen Tunneln sorgfaltiges Debridement bis auf die Tunnelwand; bei nichtanatomischen Tunneln der Voroperation Bohren des femoralen Kanals uber ein tiefes anteromediales Portal bei mehr als 110° gebeugtem Knie im VKB-Insertionsgebiet. Eine schonende Tunnelpraparation gelingt mit Dilatatoren. An der Tibia dient das Ausenmeniskusvorderhorn bei fehlendem VKB-Stumpf als Landmarke. Sondieren der gelenkfernen Tunneloffnung mit einem Zieldraht und schrittweises Aufbohren der Tunnel bis zum Erreichen der Tunnelwand, die mit einem Loffel oder Synovialresektor debridiert wird. Dabei Entfernen von Transplantatresten und Implantaten aus dem Tunnel. Die femorale Fixation erfolgt mit einem Kippanker, einer Interferenzschraube oder bei einem Knochenblocktransplantat auch implantatfrei. Transplantatfixierung tibial mit resorbierbarer Interferenzschraube und Fixationsknopf. Nachbehandlungsschema besteht aus 4–5 Phasen. Entzundungsphase I (1.–2. Woche): Schmerz- und Ergussprophylaxe (Kuhlung, isometrische Anspannungsubungen, 20-kg-Teilbelastung). Phase II (2.–6. Woche): Langsame Steigerung von Belastung und Beweglichkeit mit Ubungen in geschlossener Kette (Ziel: Extension/Flexion 0–0–120°). Phase III (ab der 6. Woche): Kraftaufbau und Koordinationsubungen. Phase IV: Balance, Kraft und Sprungubungen. Wiederkehr zum Wettkampfsport nicht vor dem 6.–10. postoperativen Monat. Nachuntersucht wurden 51 Patienten mit Rezidivinstabilitat nach VKB-Plastik, bei denen ein primarer Reersatz des VKB mit ipsilateralem Knochen-Quadrizepssehnen-Transplantat oder kontralateralem Semitendinosus-Gracilis-Transplantat durchgefuhrt wurde. Alle Patienten hatten anatomische oder nichtanatomische Bohrkanalpositionen ohne signifikante Bohrkanalweitung (>11 mm). Nach 2 Jahren betrug der Seit-zu-Seit-Unterschied fur die anteriore Translation gemessen mit dem KT-1000-Arthrometer 2,0 ± 1,2 mm fur die Quadrizeps-Gruppe und 3,0 ± 2,9 mm fur die Semitendinosus-Gracilis-Gruppe (P = 0,461). Kein Unterschied in der Rate positiver Pivot-Shift-Tests (P = 0,661), kein signifikanter Unterschied in den einzelnen Subscores des KOOS (Knee Injury and Osteoarthritis Outcome Score) sowie beim vorderen Knieschmerz.

Objective The Gore Excluder Iliac Branch Endoprosthesis (IBE) was developed to preserve perfusion in the hypogastric artery after endovascular repair of aorto-iliac aneurysms. This study reports the 12 month technical and clinical outcomes of treatment with this device. Methods This study was a physician initiated international multicentre, prospective cohort study. The primary endpoint was primary patency of the hypogastric branch at 12 months. Secondary endpoints included technical and clinical outcomes. Patients with an indication for elective treatment with the Gore Excluder IBE were enrolled between March 2015 and August 2018. Baseline and procedural characteristics, imaging data, physical examinations and questionnaire data (Walking Impairment Questionnaire [WIQ], EuroQol-5-Dimensions [EQ5D], International Index of Erectile Function 5 [IIEF-5]) were collected through 12 month follow up. Results One hundred patients were enrolled of which 97% were male, with a median age of 70.0 years (interquartile range [IQR] 64.5 – 75.5 years). An abdominal aortic aneurysm (AAA) above threshold for treatment was found in 42.7% and in the remaining patients the iliac artery diameter was the indication for treatment. The maximum common iliac artery (CIA) diameter on the Gore Excluder IBE treated side was 35.5 mm (IQR 30.8 – 42.0) mm. Twenty-two patients received a bilateral and seven patients had an isolated IBE. Median procedural time was 151 minutes (IQR 117 – 193 minutes) with a median hospital stay of four days (IQR 3 – 5 days). Primary patency of the IBE at 12 month follow up was 91.3%. Primary patency for patients treated inside and outside the instructions for use were 91.8% and 85.7%, respectively (p = .059). Freedom from secondary interventions was 98% and 97% at 30 days and 12 months, respectively. CIA and AAA diameters decreased significantly through 12 months. IIEF-5 and EQ5D scores remained stable through follow up. Patency of the contralateral internal iliac artery led to better IIEF-5 outcomes. WIQ scores decreased at 30 days and returned to baseline values through 12 months. Conclusion Use of the Gore Excluder IBE for the treatment of aorto-iliac aneurysms shows a satisfactory primary patency through 12 months, with significant decrease of diameters, a low re-intervention rate, and favourable clinical outcomes.

Environmental Sound Classification (ESC) is a rapidly evolving field that recently demonstrated the advantages of application of visual domain techniques to the audio-related tasks. Previous studies indicate that the domain-specific modification of cross-domain approaches show a promise in pushing the whole area of ESC forward. In this paper, we present a new time-frequency transformation layer that is based on complex frequency B-spline (fbsp) wavelets. Being used with a high-performance audio classification model, the proposed fbsp-layer provides an accuracy improvement over the previously used Short-Time Fourier Transform (STFT) on standard datasets. We also investigate the influence of different pre-training strategies, including the joint use of two large-scale datasets for weight initialization: ImageNet and AudioSet. Our proposed model out-performs other approaches by achieving accuracies of 95.20 % on the ESC-50 and 89.14 % on the UrbanSound8K datasets. Additionally, we assess the increase of model robustness against additive white Gaussian noise and reduction of an effective sample rate introduced by the proposed layer and demonstrate that the fbsp-layer improves the model's ability to withstand signal perturbations, in comparison to STFT-based training. For the sake of reproducibility, our code is made available., Comment: submitted IJCNN 2021

During the COVID-19 pandemic, healthcare workers (HCW) have been subjected to greater workloads. We conducted a cross-sectional online survey to assess the impact of the COVID-19 pandemic on Brazilian HCW. Data were collected between 11 August and 1 November 2020. Of the 295 respondents, 95 (32.2%) were medical doctors, 82 (27.8%) administrative staff, 53 (18.0%) nurses, 27 (9.2%) laboratory staff, and 38 (12.9%) were other staff. COVID-19-related restructuring at the health facilities was reported by 207 (70.2%) respondents, and 69 (23.4%) had their tasks changed. Preventive measures were well respected when seeing suspected patients. Overall, 167 (56.6%) HCW screened positive for anxiety and 137 (46.4%) for depression, 109 (36.9%) screened positive for both conditions. Of the 217 (73.6%) HCW who had been tested for COVID-19, at least one positive result was reported in 49 (22.6%). Following a positive COVID-19 test, 45/49 (91.8%) stopped working and stayed home. In conclusion, we found a high incidence of COVID-19 infection among Brazilian HCW with high rates of anxiety and depression despite a good self-reported adherence to COVID-19 preventive measures. As such, our study highlights the urgent need for interventions to mitigate the psychosocial risks HCW in Brazil encounter during the COVID-19 pandemic.

This contribution presents the on-ground characterization and video chain development of the CMOS detector implemented in SPEXone, the five-angle space spectro-polarimeter for the NASA PACE observatory scheduled for launch in 2023. SPEXone is a Dutch compact payload contribution developed in a partnership between SRON and ADSN, and supported by TNO. Making use of spectral modulation, this polarimeter will enable in-depth and global characterization of the microphysical properties of fine particulate matter or aerosols in the atmosphere from low Earth orbit. In SPEXone, the spectrally modulated images are captured by means of a commercial-off-the-shelf detector module (DEM) from 3Dplus, which is equipped with a CMOS image sensor with integrated front-end-electronics. Video chain developments, including DEM firmware, read-out, flexible binning and DEM interfacing through SpaceWire have been carried out in-house. Making use of the firmware, the optimal detector parameters with associated random noise, full-well capacity, and photo response non-uniformity (PRNU) of the DEM were determined by placing the DEM in front of an integrating sphere fiber-fed with a stable white light source with accurately adjustable intensity and a highly linear reference detector, providing highly uniform illumination of the whole detector area at well-known relative light intensities. The rationale behind the measurement sequences is explained, and the full-well and read noise performance under different gain settings is described. The full-well capacity of the DEM is found to be not constant, but increasing significantly with illumination intensity.

Objective Various functional muscle properties affect different aspects of functional exercise capacity in people with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the contribution of quadriceps muscle strength, endurance, and power to 6-Minute Walking Distance (6MWD) and 1-minute sit-to-stand test (1STS) performance in people with COPD. Methods The study was a prospective, multicenter, cross-sectional study. Anthropometrics, Medical Research Council dyspnea scale, lung function, 6MWD, and 1STS number of repetitions were assessed. Isometric quadriceps strength and endurance, isotonic quadriceps endurance, isokinetic quadriceps strength, and power were assessed on a computerized dynamometer while functional quadriceps power was determined during 5 sit-to-stand repetitions. Univariate and multivariate analyses were performed to determine the contribution of functional muscle properties to the 6MWD and the 1STS number of repetitions. Results The study included 70 people with COPD (mean % predicted forced expiratory volume in 1 second = 58.9 [SD = 18.2]). The 6MWD correlated with each functional muscle property except the isometric quadriceps endurance. The number of repetitions during the 1STS correlated with each functional muscle property except isometric measurements. Multivariate models explained 60% and 39% of the variance in the 6MWD and 1STS number of repetitions, respectively, with quadriceps power determined during 5 sit-to-stand repetitions being the muscle functional property with the strongest contribution to the models. Conclusion Except for isometric endurance, quadriceps strength, endurance, and power were associated with functional exercise capacity in people with moderate COPD. Among these functional muscle properties, muscle power contributed the most to the 6MWD and 1STS number of repetitions, suggesting that muscle power is more relevant to functional exercise capacity than muscle strength or endurance in people with COPD. Impact Understanding the individual contribution of muscle properties to functional status is important to designing interventions. This study provides the guidance that muscle power may be more important to functional exercise capacity than muscle strength or endurance in people with COPD.

Objectives Woman with a history of a previous cesarean section (CS) can choose between an elective repeat CS (ERCS) and a trial of labor (TOL), which can end in a vaginal birth after cesarean (VBAC) or an unplanned CS. Guidelines describe women’s rights to make an informed decision between an ERCS or a TOL. However, the rates of TOL and vaginal birth after CS varies greatly between and within countries. The objective of this study is to asses nation-wide implementation of counselling with a decision aid (DA) including a prediction model, on intended delivery compared to care as usual. We hypothesize that this may result in a reduction in practice variation without an increase in cesarean rates or complications. Methods In a multicenter controlled before and after cohort study we evaluate the effect of nation-wide implementation of a DA. Practice variation was defined as the standard deviation (SD) of TOL percentages. Results A total of 27 hospitals and 1,364 women were included. A significant decrease was found in practice variation (SD TOL rates: 0.17 control group vs. 0.10 intervention group following decision aid implementation, p=0.011). There was no significant difference in the ERCS rate or overall CS rates. A 21% reduction in the combined maternal and perinatal adverse outcomes was seen. Conclusions Nationwide implementation of the DA showed a significant reduction in practice variation without an increase in the rate of cesarean section or complications, suggesting an improvement in equality of care.

The field of explainable AI (XAI) has quickly become a thriving and prolific community. However, a silent, recurrent and acknowledged issue in this area is the lack of consensus regarding its terminology. In particular, each new contribution seems to rely on its own (and often intuitive) version of terms like "explanation" and "interpretation". Such disarray encumbers the consolidation of advances in the field towards the fulfillment of scientific and regulatory demands e.g., when comparing methods or establishing their compliance with respect to biases and fairness constraints. We propose a theoretical framework that not only provides concrete definitions for these terms, but it also outlines all steps necessary to produce explanations and interpretations. The framework also allows for existing contributions to be re-contextualized such that their scope can be measured, thus making them comparable to other methods. We show that this framework is compliant with desiderata on explanations, on interpretability and on evaluation metrics. We present a use-case showing how the framework can be used to compare LIME, SHAP and MDNet, establishing their advantages and shortcomings. Finally, we discuss relevant trends in XAI as well as recommendations for future work, all from the standpoint of our framework.

Objectives Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales’ genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. Materials and methods In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates’ ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. Results All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). Conclusions Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

The main indicator for endarterectomy is the grade of stenosis, which results in severe overtreatment. Photoacoustic imaging (PAI) can provide patient-specific assessment of plaque morphology, and thereby vulnerability. A pilot study of PAI on carotid plaques in patients (n=16) was performed intraoperatively with a hand-held PAI system. By compensating for motion, the photoacoustic (PA) signal-to-noise ratio (SNR) could be increased by 5 dB in vivo. PA signals from hemorrhagic plaques had different characteristics compared to the signals from the carotid blood pool. This study is a key step towards a non-invasive application of PAI to detect vulnerable plaques.

Sleep dysregulation is a feature of dementia but it remains unclear whether sleep duration prior to old age is associated with dementia incidence. Using data from 7959 participants of the Whitehall II study, we examined the association between sleep duration and incidence of dementia (521 diagnosed cases) using a 25-year follow-up. Here we report higher dementia risk associated with a sleep duration of six hours or less at age 50 and 60, compared with a normal (7 h) sleep duration, although this was imprecisely estimated for sleep duration at age 70 (hazard ratios (HR) 1.22 (95% confidence interval 1.01–1.48), 1.37 (1.10–1.72), and 1.24 (0.98–1.57), respectively). Persistent short sleep duration at age 50, 60, and 70 compared to persistent normal sleep duration was also associated with a 30% increased dementia risk independently of sociodemographic, behavioural, cardiometabolic, and mental health factors. These findings suggest that short sleep duration in midlife is associated with an increased risk of late-onset dementia., Sleep dysregulation has been linked to dementia, but it is unknown whether sleep duration earlier in life is associated with dementia risk. Here, the authors show higher dementia risk associated with short sleep duration (six hours or less) in a longitudinal study of middle and older age adults.

COVID-19 affects persons living with HIV (PLWH) both directly (via morbidity/mortality) and indirectly (via disruption of HIV care). From July–November 2020, an online survey was conducted to investigate the psychosocial well-being of PLWH and changes in HIV care during the second semester of the COVID-19 outbreak. Data were collected on the socio-demographic characteristics of PLWH, their psychosocial well-being, impact of COVID-19 preventive measures on their daily routines and HIV follow-up. Of the 247 responses analyzed (mean age: 44.5 ± 13.2 years, 73.7% male), 67 (27.1%) and 69 (27.9%) respondents screened positive for anxiety (GAD-2 score ≥ 3) and depression (PHQ-2 score ≥ 3), respectively. HIV care had returned to pre-COVID-19 state for 48.6% PLWH, and 108 (43.7%) had no HIV follow-up during the past month. Over three quarters (76.1%) of respondents expressed willingness to receive the COVID-19 vaccine. Compared to previous findings in April 2020, substance use increased from 58.6% to 67.2% (p &lt, 0.001). Our findings suggest that the well-being and medical follow-up of PLWH are still affected after almost a year into the COVID-19 outbreak. Remote HIV follow-up (telemedicine) with psychosocial support should be envisaged in the medium to long-term. Given that most PLWH accept COVID-19 vaccination, they may be prioritized for this intervention.