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Objective To assess the value of a morphine Patient Controlled Intravenous Analgesia (PCIA) after Tonsillectomies (TE). Methods 30 adult patients were treated with oral analgesics (protocol group) and compared to 30 patients treated with a morphine PCIA for the first 3 Postoperative Days (PODs) after TE. Average and maximum pain severities (Numeric Rating Scale – NRS: 0–10) on PODs 1–3, analgesic score, quality of life, patient satisfaction and side effects were defined as outcome measures. Results Average pain severities of the protocol and the PCIA group were of similar magnitude (NRS) (POD1: 4.48 vs. 4.71 [p = 0.68], POD2: 4.75 vs. 4.22 [p = 0.32] and POD3: 4.44 vs. 4.25 [p = 0.71]). Maximum pain intensities on POD1 (p = 0.92), POD2 (p = 0.51) and POD3 (p = 0.36) were also comparable between both groups. Patients with a PCIA consumed significantly more opioids (p = 0.001) without significant more side-effects. Conclusion The PCIA did not provide a superior pain control compared to oral analgesics. In view of the considerable effort and the high opioid consumption, it cannot be recommended as a standardized application for pain control after TE.

We estimate impacts of exposure to an infant health intervention trialled in Sweden in the early 1930s using purposively digitised birth registers linked to school catalogues, census files and tax records to generate longitudinal data that track individuals through four stages of the life-course, from birth to age 71. This allows us to measure impacts on childhood health and cognitive skills at ages 7 and 10, educational choice during young adulthood, employment, earnings and occupation at age 36{40, and pension income at age 71. Leveraging quasi-random variation in eligibility by birth date and birth parish, we estimate that an additional year of exposure was associated with substantial increases in earnings and (public sector) employment among women, alongside no improvements for men. Earnings gains for women were concentrated in the top quintile of the distribution. The earnings results appear to be related to the intervention having made it more likely that primary school test scores for girls were in the top quintile of the distribution and, related, that they attended secondary school. The greater investments of women in education are consistent with their comparative advantage in cognitive tasks, but opportunities are also likely to have played a role. Our sample cohorts were exposed to a massive expansion of the Swedish welfare state, which created unprecedented employment opportunities for women.

Pedestrians represent acutely complex and agile targets whose accident prevention has the highest priority concerning highly automated vehicles in urban traffic. Consequently, detection and tracking methods are necessary to determine motion behavior quickly and with high precision. With advancing microelectronics, powerful radar sensors and novel antenna structures are available for pedestrian detection systems, which can utilize unique features such as micro-Doppler signatures in several dimensions and high resolution. This paper presents a micro-Doppler based leg tracking framework that enables behavioral indications in a few sensor cycles. An adaptive motion model representing the kinematic locomotion of a human is derived to propagate the foot motion. Joint probabilistic data association assigns the detections to the respective leg and allows its temporal filtering of the position, micro-Doppler velocity, and kinematic parameters using an extended Kalman filter yielding real-time implementation capability. The presented approach provides the entire signal chain from raw radar data processing to extended multi-object state estimation based on highly relevant safety-critical motion maneuvers measured with radar parameterization corresponding to current serial short-range sensors.

Background/purpose Rotational atherectomy (RA) plays a central role in the treatment of heavily calcified coronary artery lesions. Our aim was to compare periprocedural characteristics and outcomes of planned (PA) vs. bailout (BA) rotational atherectomy. Methods We conducted a systematic review and performed a meta-analysis on studies which compared PA vs. BA strategy. Results Five studies fulfilled the inclusion criteria, pooling a total of 2120 patients. There was no difference in procedural success, PA vs. BA risk ratio (RR) 1.03 and 95% confidence interval (95% CI) 0.99–1.07. Compared to BA, PA was associated with a shorter procedural time [mean difference (MD) -25.88 min, 95% CI -35.55 to −16.22], less contrast volume (MD -43.71 ml, 95% CI -69.17 to −18.25), less coronary dissections (RR 0.50, 95% CI 0.26–0.99), fewer stents (MD -0.20, 95% CI -0.29 to −0.11), and a trend favouring less periprocedural myocardial infarctions (MI) (RR 0.77, 95% CI 0.54–1.11). There was no difference in major adverse cardiovascular events on follow-up (RR 1.04, 95% CI 0.62–1.74), death (RR 0.98, 95% CI 0.59–1.64), MI (RR 1.16, 95% CI 0.62–2.18), target vessel revascularization (RR 1.40, 95% CI 0.83 to 2.36), stroke (RR 1.50, 95% CI 0.46–4.86) or stent thrombosis (RR 0.82, 95% CI 0.06–10.74); all PA vs. BA comparisons. Conclusions Compared to bailout RA, planned RA resulted in significantly shorter procedural times, less contrast use, lesser dissection rates and fewer stents used. The bailout RA approach appears to enhance periprocedural risk, but there is no difference on mid-term outcomes.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes., Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p

Background Innovation and human adaptation in the face of unfolding catastrophe is the cornerstone of an effective systemwide response. Capturing, analysing, and disseminating this is fundamental in developing resilience for future events. The aim of this study was to understand the characteristics of adaptations to practice early in a paediatric major trauma centre during a mass casualty incident. Methods A qualitative interview study of 40 healthcare staff at a paediatric major trauma centre in the immediate aftermath of a terrorist bombing was conducted. An inductive thematic analysis approach was used, followed by a deductive analysis of the identified adaptations informed by constructs of resilience engineering. Results Five themes of adaptations to practice that enhanced the resilient performance of the hospital were identified: teamworking; psychologically supporting patients, families, and staff; reconfiguring infrastructure; working around the hospital electronic systems; and maintaining hospital safety. Examples of resilience potential in terms of respond, monitor, anticipate, and learn are presented. Conclusions Our study shows how adaptations to practice sustained the resilient performance of a paediatric major trauma centre during a mass casualty incident. Rapid, early capture of these data during a mass casualty incident provides key insights into enhancing future emergency preparedness, response, and resilience planning.

This study aimed to compare the traditional bulb aspirator with a nasal-oral aspirator in the treatment of bronchiolitis.This was a single-center, single-blind, randomized controlled trial. Patients with bronchiolitis discharged from the emergency department were randomized to receive a bulb or nasal-oral aspirator for home use.Data regarding return visits, hydration, respiratory relief, parental satisfaction, device preference, and adverse events were gathered using a predistribution questionnaire, diary, poststudy questionnaire, and chart review.There was not a statistically significant difference in the rate of unscheduled return visits (bulb vs nasal-oral, 28.2% vs 20.7%; P = 0.26). No difference was seen in hydration or respiratory relief in either the diary or poststudy questionnaire. The nasal-oral aspirator had higher satisfaction rates (bulb vs nasal-oral, 68.8% vs 93.9%; P0.01). When asked which device was preferred with regard to all devices ever tried, 57.2% of respondents reported the nasal-oral aspirator. More adverse events were seen with the bulb compared with the nasal-oral aspirator (bulb vs nasal-oral, 50.0% vs 17.5%; P0.01).No difference was appreciated between the bulb and nasal-oral aspirators in unscheduled return rates. The nasal-oral aspirator demonstrated higher parental satisfaction and preference rates, and fewer adverse effects compared with the bulb aspirator. Medical providers should have a cost-benefit discussion with caregivers when recommending home aspirators for the treatment of bronchiolitis.Registry ClinicalTrials.gov Identifier: NCT03288857. Comparison of the Bulb Aspirator With a Nasal-Oral Aspirator in the Treatment of Bronchiolitis.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

Abstract. Background: The evidence of nonpharmacological interventions promoting urinary continence in Parkinson’s disease is low and rehabilitation nurses do not give it a high priority. Aim: To examine the effects of a urinary incontinence management program on continence and quality of life in persons with Parkinson’s disease in inpatient rehabilitation. The acceptance of the intervention and the knowledge of the nurses were also of interest. Methods: A nonrandomized experimental study was conducted. The data collection commenced with a control group followed by an intervention group. A structured urinary incontinence management was performed in the intervention phase. This includes incontinence assessment, care planning, individual interventions, discharge planning, and telephone support at home. Results: Urinary continence and quality of life were enhanced in both groups; however, improvements were higher in the intervention group but the differences were not significant. Knowledge of the nurses about urinary incontinence improved during the study duration. The acceptance of the intervention was high. Conclusions: A structured urinary continence management may improve urinary continence in persons suffering from Parkinson’s disease. In clinical practice it is important to perform a detailed assessment to identify problems regarding urinary incontinence.

Cage instability or highly dynamic cage movement can have a strong influence on the performance of rolling bearings. In addition to very loud and disturbing noises (“squealing”), bearing failure du...

We present the case of a cognitively unimpaired 77-year-old man with elevated, asymmetric, and longitudinally increasing Flortaucipir tau PET despite normal (visually negative) amyloid PET. His atypical tau PET signal persisted and globally increased in a follow-up scan five years later. Across eight years of observations, temporoparietal atrophy was observed consistent with tau PET patterns, but he retained the cognitively unimpaired classification. Altogether, his atypical tau PET signal is not explained by any known risk factors or alternative pathologies, and other imaging findings were not remarkable. He remains enrolled for further observation.

ObjectivesTo improve teen contraceptive use, the SpeakOut intervention combines structured counseling, online resources, and text reminders to encourage teens to share their experiences using intrauterine contraception (IUC) or an implant with peers.Study designTo evaluate the effectiveness of remote delivery of the SpeakOut intervention in increasing teen contraceptive use, we conducted a cluster randomized trial involving female adolescents who were recruited online. Primary participants (n=520) were randomly assigned to receive SpeakOut or an attention control; each primary participant recruited a cluster of up to 5 female peers as secondary participants (n=581). We assessed contraceptive communication, knowledge, and use, at baseline, 3 and 9 months after participants enrolled. We examined differences between study groups, controlling for clustering by primary participant and baseline characteristics.ResultsThe trial's primary outcome, contraceptive use by secondary participants, was similar between groups at both 3 and 9 months postintervention. Compared to controls, primary participants receiving SpeakOut tended to be less likely to discontinue contraception within 9 months (4.8% vs 7.8%, p=0.11 for IUC; 7.8% vs 9.8%, p=0.45 for implants), but this did not reach statistical significance. SpeakOut failed to increase contraceptive communication; regardless of study group, most secondary participants reported peer communication about contraception (86% vs 88%, p=0.57). Most secondary participants were aware of the hormonal IUC (91.4% vs 90.4%, p=0.72), copper IUC (92.9% vs 88.6%, p=0.13), and implant (96.5% vs 96.1%, p=0.83) 3 months after enrolling, regardless of the intervention their primary participant received. However, contraceptive knowledge remained incomplete in all study groups.ConclusionRemote delivery of the SpeakOutintervention did not improve contraceptive communication, knowledge or use among participating teens or their peers.ImplicationsEfforts to support teen-to-teen contraceptive communication and ensure that teens have accurate information about the full range of contraceptive methods, including highly effective reversible contraceptives, require refinement.

SUMMARY OF RECOMMENDATIONS: 1. Oxytocin for induction or augmentation of labor should not be started when there is a previous scar on the body of the uterus (such as previous classical cesarean section, uterine perforation or myomectomy when uterine cavity is reached) or in any other condition where labor or vaginal delivery are contraindicated. (Moderate quality evidence +++-; Strong recommendation). 2. Oxytocin should not be started before at least 1 h has elapsed since amniotomy, 6 h since the use of dinoprostone (30 min if vaginal insert) and 4 h since the use of misoprostol (Low quality evidence ++- -; Moderate recommendation). 3. Cardiotocography (CTG) should be performed and a normal pattern without tachysystole should be documented for at least 30 min before oxytocin is used. Continuous CTG, with adequate monitoring of both fetal heart rate and uterine contractions, should be maintained for as long as oxytocin is used, and thereafter until delivery (Low ++- - to moderate +++- quality evidence; Strong recommendation). 4. For labor induction, at least 1-h should be allowed after amniotomy before oxytocin infusion is started, to evaluate whether adequate uterine contractility has meanwhile ensued. For augmentation of labor, if the membranes are intact and there are conditions for a safe amniotomy, the latter should be considered before oxytocin is started (Very low quality evidence +- --; Weak recommendation). 5. Oxytocin should be administered intravenously using the following regimen: 5 IU oxytocin diluted in 500 mL of 0.9% normal saline (NaCl) (each mL contains 10 mIU of oxytocin), in an infusion pump at increasing rates, as shown in Table 1, until a frequency of 3-4 contractions per 10 min is reached, a non-reassuring CTG pattern ensues, or maximum rates are reached (Low quality evidence ++ - -; Strong recommendation). If the frequency of contractions exceeds 5 in 10 min, the infusion rate should be reduced, even if a normal CTG pattern is present. With a non-reassuring CTG pattern, urgent clinical assessment by an obstetrician is indicated, and strong consideration should be given to reducing or stopping the oxytocin infusion. The minimal effective dose of oxytocin should always be used. (Low ++- - to Moderate +++- - quality evidence; Strong recommendation). 6. Use of oxytocin for induction and augmentation of labor should be regularly audited (Low quality evidence ++--; Strong recommendation).

Background: Evidence from clinical trials suggests a differential effect of sex on the effectiveness and safety of direct oral anticoagulants (DOACs) for stroke prophylaxis in atrial fibrillation (AF). Methods: This population-based cohort study examined the independent effect of sex on hemorrhage and ischemic stroke in 23,884 patients (55% females; age ≥ 66 years) with AF starting apixaban or rivaroxaban treatment in Ontario, Canada. Patients were followed for 90 days after their DOAC prescription. Using female sex as the exposure of interest, differences in baseline characteristics were balanced between sexes using inverse probability weights based on propensity scores. Applying weighted modified Poisson regression, risk ratios (RRs) were estimated for major hemorrhage, ischemic stroke/systemic embolism/transient ischemic attack (hereafter stroke), myocardial infarction, and all-cause mortality, with males as a reference. Results: Females were older, had higher predicted stroke risk (based on CHADS2 score), and had fewer comorbidities than did males. Males had a higher prevalence of coronary artery disease, diabetes, and cancer, and similar predicted bleeding risk (based on HAS-BLED score). After weighting, baseline characteristics were well balanced. The 90-day risks for hemorrhage (RR 0.96; 95% confidence interval [CI] 0.80-1.15; P = 0.69) and stroke (RR 1.01; 95% CI 0.86-1.19; P = 0.94) were similar between sexes, which remained true when assessing each DOAC separately by dosing regimen. Compared to males, females had a lower risk for myocardial infarction (RR 0.66; 95% CI 0.52-0.84; P = 0.0008), and for all-cause mortality (RR 0.76; 95% CI 0.67-0.87; P < 0.0001). Conclusions: Our findings do not suggest an association of sex with the 90-day risk of hemorrhage or ischemic stroke in older AF patients prescribed apixaban or rivaroxaban. Résumé: Contexte: Les données probantes issues des essais cliniques donnent à penser que l’efficacité et l’innocuité des anticoagulants oraux directs (AOD) utilisés pour la prophylaxie des accidents vasculaires cérébraux (AVC) dans un contexte de fibrillation auriculaire (FA) varient selon le sexe du patient. Méthodologie: Cette étude de cohorte populationnelle a examiné l’effet indépendant du sexe sur l’hémorragie et l’AVC ischémique chez 23 884 patients (55 % de femmes; âge ≥ 66 ans) atteints de FA ayant amorcé un traitement par l’apixaban ou le rivaroxaban en Ontario (Canada). Les patients ont été suivis pendant 90 jours après avoir reçu une ordonnance d’AOD. Le sexe féminin constituant l’exposition d’intérêt, les différences quant aux caractéristiques initiales ont été réparties de façon équilibrée entre les sexes au moyen d’une pondération par probabilité inverse reposant sur le score de propension. La régression de Poisson modifiée avec pondération a servi à estimer les rapports de risques (RR) d’hémorragie majeure, d’AVC ischémique/d’embolie systémique/d’accident ischémique transitoire (ci-après AVC), d’infarctus du myocarde et de mortalité toutes causes confondues, les hommes formant la population de référence. Résultats: Les femmes étaient plus âgées, présentaient un risque prévu d’AVC plus élevé (d’après le score CHADS2) et présentaient moins de maladies concomitantes que les hommes. Les hommes présentaient une prévalence plus élevée de coronaropathie, de diabète et de cancer, et un risque prévu d’hémorragie similaire (compte tenu du score HAS-BLED). Après la pondération, la répartition des caractéristiques initiales des patients était bien équilibrée. Le risque d’hémorragie (RR : 0,96; intervalle de confiance [IC] à 95 % : 0,80-1,15; P = 0,69) et d’AVC (RR : 1,01; IC à 95 % : 0,86-1,19; P = 0,94) sur 90 jours était similaire pour les deux sexes, et il en était de même lorsque chaque AOD a été évalué séparément en fonction du schéma posologique. Par rapport aux hommes, les femmes présentaient un risque plus faible d’infarctus du myocarde (RR : 0,66; IC à 95 % : 0,52-0,84; P = 0,0008) et de mortalité toutes causes confondues (RR : 0,76; IC à 95 % : 0,67-0,87; P < 0,0001). Conclusions: Nos résultats ne laissent présumer aucune association entre le sexe et le risque d’hémorragie ou d’AVC ischémique sur une période de 90 jours chez les patients âgés atteints de FA à qui l’apixaban ou le rivaroxaban sont prescrits.

Background Diffusion-weighted imaging (DWI) provides specific in vivo information about tissue microstructure, which is increasingly recognized for various applications outside the central nervous system. However, standard sequence parameters are commonly adopted from optimized central nervous system protocols, thus potentially neglecting differences in tissue-specific diffusional behavior. Purpose To characterize the optimal tissue-specific diffusion imaging weighting scheme over the b domain in peripheral nerves under physiologic and pathologic conditions. Materials and Methods In this prospective cross-sectional study, 3-T MR neurography of the sciatic nerve was performed in healthy volunteers (n = 16) and participants with type 2 diabetes (n = 12). For DWI, 16 b values in the range of 0-1500 sec/mm2 were acquired in axial and radial diffusion directions of the nerve. With a region of interest-based approach, diffusion-weighted signal behavior as a function of b was estimated using standard monoexponential, biexponential, and kurtosis fitting. Goodness of fit was assessed to determine the optimal b value for two-point DWI/diffusion tensor imaging (DTI). Results Non-Gaussian diffusional behavior was observed beyond b values of 600 sec/mm2 in the axial and 800 sec/mm2 in the radial diffusion direction in both participants with diabetes and healthy volunteers. Accordingly, the biexponential and kurtosis models achieved a better curve fit compared with the standard monoexponential model (Akaike information criterion >99.9% in all models), but the kurtosis model was preferred in the majority of cases. Significant differences between healthy volunteers and participants with diabetes were found in the kurtosis-derived parameters Dk and K. The results suggest an upper bound b value of approximately 700 sec/mm2 for optimal standard DWI/DTI in peripheral nerve applications. Conclusion In MR neurography, an ideal standard diffusion-weighted imaging/diffusion tensor imaging protocol with b = 700 sec/mm2 is suggested. This is substantially lower than in the central nervous system due to early-occurring non-Gaussian diffusion behavior and emphasizes the need for tissue-specific b value optimization. Including higher b values, kurtosis-derived parameters may represent promising novel imaging markers of peripheral nerve disease. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Jang and Du in this issue.

Background The diagnosis and treatment of Aspergillus fumigatus (Af)-related conditions remain a challenge in cystic fibrosis (CF) due to overlapping features of disease and absence of clinical guidelines for Af-related conditions outside of ABPA. Objective To investigate the differences of clinical practice in the diagnosis and management of Af-related conditions in CF. Methods We conducted an international survey to CF clinicians to ascertain the screening, diagnostic, and treatment practices for Af-related conditions in CF. Respondents were grouped into geographical regions and regional comparisons using chi-square tests of independence or Fisher's tests were performed. Results A total of 319 survey responses from 35 countries were analyzed. We observed differences in use and frequency of fungus culture, Aspergillus-specific IgE and IgG, skin prick testing, and pulmonary function testing as screening for Af-related conditions between the geographical regions. ABPA and Aspergillus bronchitis diagnostic criteria selection differed by region; significantly greater proportion of United States (US) and Canadian clinicians were unable to define Aspergillus bronchitis compared to Europe and other regions. Decision to treat ABPA was uniform across regions, but the consideration of Aspergillus bronchitis as a clinical disease warranting therapy differed between regions. The use of glucocorticoid and itraconazole was the first-line treatment of ABPA among clinicians; however, prednisone monotherapy was more common in US and Canada. Conclusions Significant variability in the diagnosis and management of Aspergillus-related conditions in CF was observed. Future studies are necessary to better harmonize the approach to Af-related disease in CF.

BackgroundCollecting lymphatic vessel (CLV) dysfunction has been implicated in various diseases, including rheumatoid arthritis (RA). Previous studies in the tumor necrosis factor-transgenic (TNF-Tg) mouse model of inflammatory-erosive arthritis have demonstrated reduced joint-draining CLV contractility that correlates with arthritic severity. Clinically, RA patients with active hand arthritis exhibit significantly reduced lymphatic clearance of the web spaces adjacent to the metacarpophalangeal (MCP) joints and a reduction in total and basilic-associated CLVs on the dorsal surface of the hand by dynamic near-infrared (NIR) imaging of indocyanine green (ICG). In this pilot study, we assessed direct lymphatic drainage from MCP joints, and aimed to visualize the total lymphatic anatomy using novel dual-agent relaxation contrast magnetic resonance lymphography (DARC-MRL) in the upper extremity of healthy human subjects.MethodsTwo healthy male subjects participated in the study. We performed NIR imaging following intra-dermal web space and intra-articular MCP joint injections of ICG to visualize the CLV anatomy on the dorsal surface of the hand and antecubital fossa. Subsequently, we performed conventional or DARC-MRL after intra-dermal web space and intra-articular MCP joint injections of gadolinium to evaluate the total lymphatic anatomy of the upper extremity and compare with NIR-ICG imaging.ResultsNIR-ICG imaging demonstrated that web space and MCP lymphatics drain via distinct CLV tributaries. Web space draining CLVs tended to be associated with the cephalic side of the antecubital fossa, while MCP draining CLVs were localized to the basilic side of the forearm. The DARC-MRL methods used in this study did not adequately nullify the contrast in the blood vessels, and limited gadolinium-filled CLVs could be identified.ConclusionThrough the use of NIR-ICG imaging, we found that MCP joints predominantly drain into basilic CLVs in the forearm, which may explain the reduction in basilic-associated CLVs in the hands of RA patients. In healthy subjects, current DARC-MRL techniques have limited ability in identifying lymphatic structures and further refinement in this technique is necessary.

BACKGROUND The aim of this study was to investigate the axillary nerve's location along superficial anatomical landmarks, and to define a convenient risk zone. METHODS A total of 123 upper extremities were evaluated. After dissection of the axillary nerve, the vertical distance between the upper border of the anterolateral edge of the acromion and the proximal border of the nerve was measured. Furthermore, the interval between the proximal border and the distal border of the axillary nerve's branches was evaluated. The interval between the distal border of the branches and the most distal part of the lateral humeral epicondyle was measured. The distance between the anterolateral edge of the acromion and the lateral humeral epicondyle was evaluated. Measurements were expressed as proportions with respect to the distance between the acromion and the lateral humeral epicondyle. RESULTS The distance between the acromion and the proximal border of the axillary nerve's branches was at a height of 10 percent of the distance between the acromion and the lateral humeral epicondyle, starting from the acromion (90 percent when starting from the lateral humeral epicondyle). The interval between the proximal and distal margins of the axillary nerve's branches was between 10 percent and 30 to 35 percent of this interval, starting from the acromion (65 to 70 percent when starting from the lateral humeral epicondyle). CONCLUSIONS The authors were able to locate the branches of the axillary nerve at an interval between 10 and 35 percent of the distance between the acromion and the lateral humeral epicondyle, starting from the acromion. This makes the proximal third of this distance an easily applicable risk zone during shoulder surgery.

Adolescents and young adults (AYAs, 15-39 years) are the largest uninsured population in the Unites States, increasing the likelihood of late-stage cancer diagnosis and poor survival. We evaluated the associations between the Affordable Care Act (ACA), insurance coverage, stage at diagnosis and survival among AYAs with lymphoma. We used data from the California Cancer Registry linked to Medicaid enrollment files on AYAs diagnosed with a primary non-Hodgkin (NHL; n=5959) or Hodgkin (n=5378) lymphoma pre-ACA and in the early and full ACA eras. Health insurance was categorized as continuous Medicaid, discontinuous Medicaid, Medicaid enrollment at diagnosis/uninsurance, other public and private. We used multivariable regression models for statistical analyses. The proportion of AYAs uninsured/Medicaid enrolled at diagnosis decreased from 13.4% pre-ACA to 9.7% with full ACA implementation, while continuous Medicaid increased from 9.3% to 29.6% during this time (P

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

BACKGROUND: Little is known about the airway microbiome in intubated mechanically ventilated children. We sought to characterize the airway microbiome longitudinally and in association with clinical variables and possible ventilator-associated infection (VAI). METHODS: Serial tracheal aspirate samples were prospectively obtained from mechanically ventilated subjects under 3 years old from eight pediatric intensive care units in the United States from June 2017 to July 2018. Changes in the tracheal microbiome were analyzed by sequencing bacterial 16S ribosomal RNA gene relative to subject demographics, diagnoses, clinical parameters, outcomes, antibiotic treatment, and the Ventilator-Associated InfectioN (VAIN) score. RESULTS: A total of 221 samples from 58 patients were processed and 197 samples met the >1000 reads criteria (89%), with an average of 43,000 reads per sample. The median number of samples per subject was 3 (interquartile range [IQR]: 2–5), with a median VAIN score of 2 (IQR: 1–3). Proteobacteria was the highest observed phyla throughout the intubation period, followed by Firmicutes and Actinobacteria. Alpha diversity was negatively associated with days of intubation (p = .032) and VAIN score (p = .016). High VAIN scores were associated with a decrease of Mycobacterium obuense, and an increase of Streptococcus peroris, Porphyromonadaceae family (unclassified species), Veillonella atypica, and several other taxa. No specific pattern of microbiome composition related to clinically diagnosed VAIs was observed. CONCLUSIONS: Our data demonstrate decreasing alpha diversity with increasing VAIN score and days of intubation. No specific microbiome pattern was associated with clinically diagnosed VAI.

Objective A small but relevant proportion of patients with cystic fibrosis develop severely asymmetric chest cavities during the course of their disease. For these patients, the best surgical approach for lung transplantation (LTx) and optimal size matching strategies are controversial. Methods All cystic fibrosis patients with asymmetric chest cavities who underwent LTx at the Medical University of Vienna between 2003 and 2017 were identified (n = 13). Patients were grouped according to different surgical strategies: unilateral full-size and contralateral lobar transplantation (n = 4), standard double LTx after mobilization/repositioning of the mediastinum (n = 3), oversized single LTx followed by pneumonectomy on the smaller contralateral side (n = 4), and single LTx after a remote contralateral pneumonectomy (n = 2). Results Compared with cystic fibrosis patients with symmetric chests (n = 276, control group), the perioperative management of patients with asymmetric chests was often more complicated. Consequently, 90-day mortality was heightened (23.1% vs 6.5%). Despite this, long-term survival was good with a 5-year survival rate of 69% compared with 78%. Of note, outcome seemed superior for patients who surgery was undertaken with a bilateral compared with a unilateral approach. Conclusions Severely asymmetric chest cavities present challenges in regard to the surgical strategy, size matching, and postoperative management. However, in carefully selected patients, LTx provides an adequate long-term outcome.

Early guidance is required to match Industry 4.0 ambitions with an understanding of the evolving Industrial Internet of Things (IIoT) system and its capabilities. Considering IIoT systems and operational methodologies within steel manufacturing, a three-stage evolving IIoT system is proposed. IIoT requirements for selected Industry 4.0 applications are presented and generalized guidance matches the application with the relative support level of each evolutionary stage. The guidance specifically considers digital twins, cyber-physical systems, horizontal and vertical integration, integrated worker health and safety, increased workforce mobility, and advanced maintenance. To demonstrate how the evolving IIoT system aids or potentially prevents Industry 4.0 applications, the feasibility of advanced maintenance strategies within steel manufacturing are presented, including predictive and self-maintenance.

OBJECTIVE Chronic subdural hematoma (cSDH) is a common and challenging pathology to treat due to both the historically high recurrence rate following surgical evacuation and the medical comorbidities inherent in the aging patient population that it primarily affects. Middle meningeal artery (MMA) embolization has shown promise in the treatment of cSDHs, most convincingly to avoid surgical evacuation in relatively asymptomatic patients. Symptomatic patients requiring surgical evacuation may also benefit from perioperative MMA embolization to prevent cSDH recurrence. The goal of this study was to determine the utility of perioperative MMA embolization for symptomatic cSDH requiring surgical evacuation and to assess if there is a decrease in the cSDH recurrence rate compared to historical recurrence rates following surgical evacuation alone. METHODS Symptomatic cSDHs were evacuated using a subdural evacuating port system (SEPS) with 5-mm twist-drill craniostomy in an intensive care unit or by performing a craniotomy in the operating room, using either a small (silver dollar, < 4 cm) or large (≥ 4 cm) craniotomy. MMA embolization was performed perioperatively using angiography, selective catheterization of the MMA, and infusion of polyvinyl particles. Outcomes were assessed clinically and radiographically with interval head CT imaging. RESULTS There were 44 symptomatic cSDHs in 41 patients, with 3 patients presenting with bilateral symptomatic cSDH. All cSDHs were evacuated using an SEPS (n = 18), a silver-dollar craniotomy (n = 16), or a large craniotomy (n = 10). Prophylactic MMA embolization was performed successfully in all cSDHs soon after surgical evacuation. There were no deaths and no procedural complications. There was an overall reduction of greater than 50% or resolution of cSDH in 40/44 (90.9%) cases, regardless of the evacuation procedure used. Of the 44 prophylactic cases, there were 2 (4.5%) cases of cSDH recurrence that required repeat surgical evacuation at the 1-year follow-up. These 2 cSDHs were initially evacuated using an SEPS and subsequently required a craniotomy, thereby representing an overall 4.5% recurrence rate of treated cSDH requiring repeat evacuation. Most notably, of the 26 patients who underwent surgical evacuation with a craniotomy followed by MMA embolization, none had cSDH recurrence requiring repeat intervention. CONCLUSIONS Perioperative prophylactic MMA embolization in the setting of surgical evacuation, via either craniotomy or SEPS, may help to lower the recurrence rate of cSDH.

OBJECTIVE Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high-throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS Sera from 58 SFN patients and 20 age- and gender-matched healthy controls (HCs) were screened against >1,600 immune-related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC��=���2.99 and 3.07, respectively, p��=���0.003, q��=���0.076), DBNL (FC��=��2.11 and 2.16, respectively, p��=���0.009, q��

Biomimetic antenna arrays inspired by the fly Ormia ochracea showed a promising improvement of the angle estimation capabilities of radar sensors. So far, there is usually a loss of output power associated with this improvement decreasing the detectability of weak radar targets. In this paper, an electronically switchable two-element biomimetic antenna array is presented for the first time. This array provides the possibility to switch between a biomimetic antenna mode with enhanced phase sensitivity and a conventional antenna mode with better SNR. Circuit requirements are discussed, the design process is described, and a realization in the 77-GHz range using PIN diodes as switching elements is presented. Radar measurements verify the concept. By switching, the phase sensitivity of the realized array can be enhanced by a factor of 3 with a relative power loss of maximum 14 dB.

In this work, infrared thermography is used to detect defects on a 3D hybrid aluminium-CFRP composite structure. First, radiometric calibration and geometric distortion correction are performed for 3D inspection. Second, we propose a new unsupervised probabilistic low-rank component factorization thermographic de-noising model to improve image performance and defect visualization. Signal profiles and standard deviation analysis is used to assess the results, and x-ray CT inspections are compared to the infrared inspection results. Finally, we can conclude that the proposed algorithm can detect voids and resin rich areas presenting a better image performance if compared to direct infrared inspection results.

By inhibiting the growth of pathogenic bacteria and modulating the local intestinal immune system, probiotics may reduce bacterial translocation and systemic endotoxaemia, factors partially responsible for post-operative complications following liver resection for hepatocellular carcinoma in patients with cirrhosis. Patients with resectable hepatocellular carcinoma developed in the setting of chronic liver disease were prospectively divided into two equal-sized groups: one receiving probiotic treatment 14 days prior to surgery and the other receiving placebo. The primary endpoint was the level of circulating endotoxins after hepatectomy. Secondary endpoints were systemic inflammation (inflammatory cytokine levels), post-operative liver function and overall post-operative complication rate. From May 2013 to December 2018, 64 patients were randomized, and 54 patients were included in the analysis, 27 in each arm. No significant change in endotoxin levels was observed over time in either group (P = 0.299). No difference between the groups in terms of post-operative liver function and overall complication rates was observed. The only differences observed were significant increases in the levels of TNFalpha (P = 0.019) and interleukin 1-b (P = 0.028) in the probiotic group in the post-operative period. Contrary to the modest data reported in the literature, the administration of probiotics before minor liver resection for hepatocellular carcinoma developed in the setting of compensated chronic liver disease does not seem to have an impact on circulating endotoxin levels or post-operative complication rates. Trial registration: NCT02021253.

BACKGROUND Psoriasis (Pso) and atopic dermatitis (AD) are chronic skin diseases that result in significant physical and psychological impairment, financial burden, and loss of quality of life. According to previous data, there are regional differences in healthcare. OBJECTIVES The aim was to analyse the epidemiology as well as the treatment of insured people with Pso and AD in Germany in a regional comparison. METHODS Data of the insurance company Techniker Krankenkasse for the year 2019 regarding treatment prevalences as well as drug prescriptions on the regional level for all physicians were examined. RESULTS In 2019 the overall prevalence of Pso was 2.5% (about 2 million insured people in Germany) and AD was 4.2% (about 3.6 million insured people). In Pso, new guideline-compliant drugs were frequently utilised, yet systemic glucocorticosteroids (GCS) were still disproportionally prescribed. Regionally, there were pronounced disparities with higher prescription rates of the new drugs in the north and east. Insured people with AD most frequently received topical GCS (approx. 88%), of which most were class III (66%), and significantly less frequently calcineurin inhibitors (

The prognostic significance of delaminated rotator cuff tears remains controversial. However, as the surgical goal is to maximize the contact area between layers, the macroscopic appearance of partial delaminated rotator cuff tears is essential. The aim of this anatomical study was to investigate the morphology of delaminated rotator cuff tears. We hypothesized that delamination zones at the intersection of the supraspinatus and infraspinatus tendon fibers are the origin of articular-side degenerative rotator cuff tears. Forty anatomical specimens were evaluated in this study. The supraspinatus and infraspinatus muscles were dissected, the origins were meticulously worked out and followed to their insertions at the humeral head. Fiber exchanges, overlays and delamination zones between the supraspinatus and infraspinatus muscles were photographically documented and measured. Delamination of rotator cuff tears can be classified into articular-side and bursal-side tears. The articular-layer consists of capsuloligamentous tissue, which included the rotator-cable/rotator-crescent complex, the joint capsule and a small part of the supraspinatus tendon. The bursal-side layer represents the tendinous tissue, which consists of the parallel, tendinous parts of the supraspinatus and infraspinatus muscles. Delamination of rotator cuff tears can be classified into articular-side and bursal-side tears. Present model of degenerative tears might explain the high prevalence of articular-side tears, which expand into the rotator-cable/rotator-crescent complex. It may be important for surgeons to incorporate these anatomical findings and considerations into the surgical planning.

Craft breweries that tend to convince consumers with new interpretations of (ancient) beer styles increasingly influence the traditional beer market. Thereby, also ingredients not directly compliant with German beer purity laws come into use. Official food control currently faces the general problem of verifying food authenticity based on instrumental analytical methods. Related tasks in this field are the detection of non-labelled ingredients and the verification of product claims such as special food processing methods. For that purpose, chemometric analysis of high-resolution 1H NMR spectra was applied for the differentiation of related beer styles including also special beers. It could be shown that pilsner style beers, wheat beers, India pale ales, sour beers, and special beers can be easily differentiated applying consecutive principal component analysis. Thereby, it turned out that crafted pilsner style beers are distinguishable from industrial pilsner style beers based on their organic acid profiles. Furthermore, three conspicuous compounds present in two different batches of only one of the beer samples were identified as allyl alcohol, 1,3-propanediol, and 3-hydroxypropionic acid directly from the NMR spectra without any further analytical efforts. Finally, the present paper serves as a proof of concept that NMR-based quantification is also possible using chemical shift information instead of signal intensities/integrals—at least in special cases.

Introduction Turoctocog alfa (NovoEight® ) is a B-domain-truncated recombinant factor VIII (FVIII) approved for patients with haemophilia A. Aim To investigate the long-term safety and efficacy of turoctocog alfa in routine clinical practice. Methods Guardian 5 was a prospective, multinational, non-interventional, post-authorisation safety study. Male previously treated patients (> 150 exposure days [EDs]) of any age with severe/moderately severe haemophilia A (FVIII ≤ 2%) and a negative inhibitor test prior to first dosing (independent of FVIII-inhibitor history) were included to receive prophylaxis or on-demand treatment. The primary endpoint was the proportion of patients developing FVIII inhibitors (≥.6 Bethesda Units [BU]) after baseline visit, measured as per routine practice of each study site during clinic visits. Secondary endpoints included haemostatic effect, annualised bleeding rate (ABR), and adverse reactions assessment. The study concluded when 50 patients reached 100 EDs/patient minimum. Results Seventy patients were screened and 68 exposed to turoctocog alfa; 63 (92.6%) were on prophylaxis and five received on-demand treatment. Six (8.8%) patients reported a history of positive inhibitors. During the study, patients were exposed to turoctocog alfa for a mean (standard deviation) of 131.9 (99.0) days/patient. Fifty-five of 58 patients who completed the study were tested for FVIII inhibitors; no positive tests were reported. Overall success rate of turoctocog alfa for treatment of bleeds was 87.3%. Among patients receiving prophylaxis, median (range) ABR was 1.97 (.0-25.5) bleeds/year; estimated ABR (negative binomial model) was 3.65 (95% confidence interval: 2.53-5.25). Conclusion Turoctocog alfa was safe and efficacious for haemophilia A treatment in routine clinical practice.

Histologic sections from patients with inflammatory bowel disease (IBD) usually exhibit crypts with architectural distortions and branching crypts. It has been postulated that crypt branching should be assessed only in well-oriented, upright crypts. However, those crypts are mostly found in sections from colectomy specimens and colon mucosectomies. Sections from endoscopic biopsies are fortuitously cut in a horizontal plane, a procedure mostly revealing cross-cut crypt rings. In endoscopic biopsies from UC patients we previously detected cross-cut crypts heralding the crest domain of branching crypts. Recently, the scrutiny of biopsies from IBD patients revealed that branching-crest domains concurred either with crypts in symmetric branching, typified by twin, amalgamating back-to-back isometrics crypt-rings, or with crypts in asymmetric branching, characterized by ≥2 amalgamating anisometric crypt-rings; both symmetric and asymmetric branching-crest domains were encased by a thin muscularis mucosae. Quantitative studies in biopsies from Swedish and German patients with IBD showed that crypts in asymmetric branching outnumbered those in symmetric branching. Because crypt-branching seldom occurs in the normal colon in adults and considering that colon crypts typically divide once or twice during a lifetime, the accruing of asymmetric branching crypts in IBD biopsies emerges as a significant histologic parameter. Although the biological significance of asymmetric crypt-branching in IBD remains at present elusive, their occurrence deserves to be further investigated. The future policy will be to include in our pathologic reports, the number of crypts in asymmetric branching, in order to monitor their frequency in prospective surveillance biopsies in patients with IBD.

Focused clinical question The purpose of this technical note is to present the principles for combined therapy as well as to illustrate the step-by-step approach of this procedure to efficiently manage peri-implantitis. Summary Peri-implantitis is the primary threat that compromises the longevity of dental implants. This entity is regarded as a biofilm-mediated inflammatory condition. As such, the arrestment of disease is conditioned by the elimination of the etiological factor and the clinical resolution of inflammation by eliminating pathogenic pockets. It was suggested that the therapy of peri-implantitis relies upon defect configuration. In this sense, defect configuration is, in part, conditioned by the dimensions of the alveolar bone and implant position. In the clinical basis, it is frequent to identify combined defects exhibiting area(s) where reconstructive therapy is inefficient due to uncontained defect morphology. These situations represent clinical indications for combined therapy. Conclusion This therapeutic modality is based on the combination of reconstructive therapy in the infra-osseous defect component and surface modification for the area of the implant within the supra-crestal component or outside the reparative potential. This article is protected by copyright. All rights reserved.

OBJECTIVES There is no information today about the impact of abutment type on the crestal bone stability. This retrospective study was aimed to evaluate the crestal bone levels (CBL) and failures of implants with prefabricated and customized abutments after the long term. MATERIALS AND METHODS The mesial and distal CBL around dental implants with prefabricated and custom abutments were recorded. Measures were completed at 5- and 10-year endpoints. RESULTS Sixty-three patients with 249 implants were included. One hundred twenty-seven implants (51%) were restored with prefabricated and 122 implants (49%) with customized abutments. All the patients received fixed restorations. The results showed that the CBL was higher in patients with custom abutments than the CBL of patients with prefabricated abutments. The mean bone loss around implants with prefabricated abutments was 0.29 mm mesial/0.45 mm distal after 10 years. Meanwhile, the mean bone loss at implants with custom abutments was 1.19 mm mesial/1.27 mm distal (p

The recent increase in Renewable Generation (RG) has prompted many states, utilities, and other stakeholders to improve the methods used to determine the value of RG in efforts of replacing the Net Metering approach. However, these studies result in a wide range of values. This paper proposes a methodology based on the RG valuation studies conducted in recent years. The method includes the most common cost and benefit components considered in these studies and adopts a comprehensive method to calculate each component. The main categories include avoided energy, avoided generation capacity, avoided transmission capacity, avoided system losses, price hedging benefits, environmental benefits, and grid integration costs. A realistic case study emulating a large utility is also conducted to illustrate the application of the proposed method. The results show that all the main components can be estimated based on detailed system models or simulations. The results also illustrate some of the data challenges associated with such a study.

Background Levofloxacin inhalation solution is the most recently approved inhaled antibiotic in Europe and Canada for adult cystic fibrosis patients. Its efficacy and safety have been assessed in randomized controlled trials. Our aim was to evaluate real life experience and outcomes in our treatment centre. Methods We evaluated the efficacy of inhaled levofloxacin solution in 86 patients with cystic fibrosis in terms of the following outcome parameters: changes in %-predicted forced expiratory volume in one second (FEV1), body-mass index (BMI), and exacerbation rate. We conducted an intraindividual analysis of patients who received levofloxacin inhalation solution twice daily 240 mg for at least 4 weeks. Results Change in FEV1% predicted for the treatment period was +2.27% (p=0.0027) after 4 weeks. There was no change in BMI for overall group, but exacerbation rate compared to one year before initiation of inhaled levofloxacin decreased significantly (p=0.0024) after 1 year of treatment (3.23 ± 1.39 versus 2.71 ± 1.58). Conclusions In patients with cystic fibrosis, inhaled levofloxacin solution has the potential to improve FEV1 and to reduce the number of bronchopulmonary exacerbations.

In this report, we describe a case of bilateral lactational mastitis in a primigravid, Spanish-speaking woman who exclusively pumped breast milk for a hospitalized, critically ill infant in the NICU within a free-standing children's hospital. The case follows her clinical presentation, assessments, diagnostics, and therapeutic interventions during the 45-day postpartum period. This case report highlights the situational and environmental context of the woman's experiences and emphasizes potential disconnections of care. Regarding her mastitis, the maternity care providers relied on the woman to provide all relevant information without knowledge of her hospitalized infant's health status. Traditionally during the postpartum period, infants hospitalized in the NICU and their mothers are cared for by separate provider teams. Clinicians must acknowledge that when women transition from recent patients to parent visitors after birth, they will likely have ongoing medical, obstetric, and psychosocial care needs.

Epidemiology and potential risk factors for cystic fibrosis arthropathy (CFA) were studied in a relevant cystic fibrosis (CF) patient cohort.Cohort study of patients included in the German CF registry in 2016-2017. Descriptive analysis, exploratory tests and multivariable logistic regression were used to assess prevalence of CFA and associated potential risk factors for adult patients with/without chronic Pseudomonas aeruginosa infection.6069 CF patients aged from 0 to 78 years were analysed. CFA was observed in 4.9% of the patients. Prevalence was significantly higher in adult patients (8.4%) compared to patients18 years (0.7%; p0.0001). Logistic regression analyses in adult patients (n=3319) showed that CFA was significantly associated with increasing age (OR=1.04; 95% CI: 1.02-1.05; p0.0001), female gender (OR=2.10; 95%CI:1.52-2.90; p0.0001), number of hospitalizations (OR=1.24; 95%CI:1.12-1.36; p0.0001), chronic P. aeruginosa infection (OR=1.83; 95%CI:1.28-2.61; p=0.0009), CF-related diabetes (OR=1.69; 95%CI:1.23-2.33; p=0.0013), pancreatic insufficiency (OR=2.39; 95%CI:1.28-4.46; p=0.0060) and sinusitis/polyps (OR=1.91; 95%CI:1.39-2.62; p0.0001). In a subgroup analysis of adults without chronic P. aeruginosa infection (n=1550) CFA was also significantly associated with increasing age, female gender, increasing number of hospitalizations, pancreatic insufficiency as well as sinusitis/polyps; antimycotic treatment associated only in this subgroup while association with CF-related diabetes was not significant.CFA is a frequent and clinically relevant co-morbidity particularly in adult CF patients. CFA is significantly more common in patients with chronic P. aeruginosa colonization but associations with other indicators for a more severe disease course were identified regardless of P. aeruginosa colonization status.

Aims To test the effectiveness of a 28‐week group‐walking intervention for person with dementia. Participants were accompanied by trained volunteers. The effectiveness was assessed according to the quality of life, ability to perform activities of daily living, independence, mobility, cognition, challenging behaviours and the burden on their caregiving relatives. Design Quasi‐experimental, one‐group, pretest–posttest trial. Methods Thirty‐two persons with dementia and their caregiving relatives were recruited. The nursing intervention consists on easy walking tours lasting three and a half hours. The walks were performed biweekly and each person with dementia had support from one or two trained volunteer helpers. Results The quality of life was stable through all seasons. The secondary outcomes were uneven. While the impairment (WHODAS) and the dependence (IADL) increased, the challenging behaviours and the burden on the caregivers were stable through all seasons.

To assess whether positive flow cytometry quantification of fetal red blood cells is associated with adverse maternal and neonatal outcomes in cases of mild trauma during pregnancy.A retrospective database study was conducted at a single tertiary center between 2013 and 2019. All pregnant women with viable gestation involved in trauma who underwent flow cytometry quantification of fetal red blood cells were included in the study. Flow cytometry was considered positive (≥0.03/≥30 ml). Composite adverse maternal and neonatal outcome was defined as one or more of the following: intrauterine fetal death, placental abruption, pre-term birth 37 weeks of gestation, immediate premature rupture of the membranes, and immediate delivery following trauma. Univariate analysis was performed followed by multivariate logistic regression analysis controlling for potential confounders, to assess the role of flow cytometry in predicting adverse maternal and neonatal outcome. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated.During the study period 1023 women met inclusion and exclusion criteria. The mechanisms of injury were motor vehicle accident in 387 women (38%), falls in 367 (36%), direct abdominal injury in 353 (35%) and in 14 women (1%) other mechanism of injury. Flow cytometry was considered positive (≥0.03/≥30 ml) in 119 women (11.6%) with median result of 0.03 [0.03-0.04], and negative in 904 women (88.4%) ((≤0.03/≤30 ml) with median result of 0.01 [0.01-0.02]. Composite adverse outcome occurred in 8% of the women involved in trauma during pregnancy, with no difference between the groups with vs. without positive flow cytometry (4.2% vs. 8.5%; p = 0.1). Positive flow cytometry was not associated with any adverse maternal or neonatal outcome. This was confirmed on multivariate analysis controlling for potential confounders.Flow cytometry result is not related to adverse maternal and fetal/neonatal outcome of women involved in minor trauma during pregnancy. We suggest that flow cytometry should not be routinely assessed in pregnant women involved in minor trauma.

Sexual harassment in field settings brings unique challenges for prevention and response, as field research occurs outside “typical” workplaces, often in remote locations that create additional safety concerns and new team dynamics. We report on a project that has 1) trained field project participants to recognize, report, and confront sexual harassment, and 2) investigated the perceptions, attitudes, and experiences of field researchers regarding sexual harassment. Precampaign surveys from four major, multi-institutional, domestic, and international field projects indicate that the majority of sexual harassment reported prior to the field campaigns was hostile work environment harassment, and women were more likely to be the recipients, on average reporting two to three incidents each. The majority of those disclosing harassment indicated that they coped with past experiences by avoiding their harasser or downplaying incidents. Of the incidences reported (47) in postcampaign surveys of the four field teams, all fell under the category of hostile work environment and included incidents of verbal, visual, and physical harassment. Women’s harassment experiences were perpetrated by men 100% of the time, and the majority of the perpetrators were in more senior positions than the victims. Men’s harassment experiences were perpetrated by a mix of women and men, and the majority came from those at the same position of seniority. Postproject surveys indicate that the training programs (taking place before the field projects) helped participants come away with more positive than negative emotions and perceptions of the training, the leadership, and their overall experiences on the field campaign.

The vibration on the stator core of hydrogenerators caused by electromagnetic forces is an important factor affecting the reliability and long-lasting operation of a machine. For a suitable addressment of the problem, it is necessary to accurately predict the eigenmodes and eigenfrequencies of the mechanical system. However, different results for the eigenfrequencies can be achieved depending on the applied model and material parameters. This work contributes to solving this issue by investigating the impact of different input parameters on the eigenmodes and eigenfrequencies calculated by analytical and numerical models. The results are discussed and compared to measurements performed on a prototyped 732 kVA hydrogenerator.

Brain–heart synchronization is fundamental for emotional-well-being and brain–heart desynchronization is characteristic for anxiety disorders including specific phobias. Recording BOLD signals with functional magnetic resonance imaging (fMRI) is an important noninvasive diagnostic tool; however, 1–2% of fMRI examinations have to be aborted due to claustrophobia. In the present study, we investigated the information flow between regions of interest (ROI’s) in the cortex and brain stem by using a frequency band close to 0.1 Hz. Causal coupling between signals important in brain–heart interaction (cardiac intervals, respiration, and BOLD signals) was studied by means of Directed Transfer Function based on the Granger causality principle. Compared were initial resting states with elevated anxiety and final resting states with low or no anxiety in a group of fMRI-naïve young subjects. During initial high anxiety the results showed an increased information flow from the middle frontal gyrus (MFG) to the pre-central gyrus (PCG) and to the brainstem. There also was an increased flow from the brainstem to the PCG. While the top-down flow during increased anxiety was predominant, the weaker ascending flow from brainstem structures may characterize a rhythmic pacemaker-like activity that (at least in part) drives respiration. We assume that these changes in information flow reflect successful anxiety processing.

Background Heterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation. Methods This is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19–BNT162b2 vaccination with a 10–12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD–ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay. Findings Between Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19–BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1–71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8–55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6–58·5) of 104 recipients of ChAdOx1 nCov-19–BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8–5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3–5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1–6·1) in recipients of ChAdOx1 nCov-19– BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19–BNT162b2 (956·6, 95% CI 835·6–1095, against alpha and 417·1, 349·3–498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2–344·4, against alpha and 48·5, 28·4–82·8, against beta; both p

To assess adolescent awareness of the safety of self-removal of intrauterine contraception (IUC) and explore associations with sociodemographic characteristics, IUC knowledge, and personal experience using an IUC.We recruited women aged 15 to 20 years from 21 U.S. states and Washington, D.C. Participants completed an online survey assessing their communication with peers about contraception and knowledge and use of IUCs.Few (11%, 95% CI 9%-13%) adolescents knew that IUC self-removal is safe, whether or not they had personally used an IUC (14% vs 8%, p = 0.01). Knowledge that IUCs do not protect users from sexually transmitted infections (99% vs 91%, p0.001) and that IUCs can be removed early (99% vs 88%, p0.001) was higher among adolescents who had used an IUC than those who had not. Knowledge that IUC use does not adversely affect fertility after IUC removal (86% vs 63%, p0.001) and that IUCs are more effective than birth control pills (82% vs 50%, p0.001) also differed by personal experience with an IUC. Awareness of the safety of IUC self-removal was not associated with overall knowledge of IUCs. However, adolescents who knew that IUCs are more effective than birth control pills were more likely to be aware of the safety of IUC self-removal (OR = 1.85, 95% CI 1.12-3.05).Adolescent women in the U.S. possess incomplete knowledge of many important aspects of IUC use, and awareness of the safety of IUC self-removal is particularly low, even among those who have used an IUC.Efforts to increase adolescent knowledge of IUC should include information about the safety of IUC self-removal in order to safeguard adolescents' reproductive autonomy.

Organizational constraints (OCs) represent work conditions that interfere with employees’ performance. Although employees share the same work environment, perceptions of OCs may vary among team members. In this study, we examined employee–teammate perceptual congruence and incongruence regarding three types of OCs (i.e., social, structural, and infrastructure) and the associated consequences for employee work engagement among health care employees from two Spanish hospitals (N = 141). Multilevel polynomial regression with response surface analyses revealed that the perceptual congruence and incongruence effects depended on the type of OCs. Congruence in perceptions was linked with greater work engagement only for social OCs. Incongruence had an effect in cases of social and structural OCs, but not infrastructure OCs: work engagement was worse when an employee rated OCs as higher (i.e., more problematic) than their teammates did. Our findings suggest that the negative effects of OCs are additionally exacerbated by perceptual incongruence with teammates and indicate the need to include social contexts in the study of work environment perceptions.

DNA damage is a constant event in every cell caused by exogenous factors such as ultraviolet and ionizing radiation (UVR/IR) and intercalating drugs, or endogenous metabolic and replicative stress. Proteins of the DNA damage response (DDR) network sense DNA lesions and induce cell cycle arrest, DNA repair, and apoptosis. Genetic defects of DDR or DNA repair proteins can be associated with immunodeficiency, bone marrow failure syndromes, and cancer susceptibility. Although various diagnostic tools are available to evaluate DNA damage, their quality to identify DNA repair deficiencies differs enormously and depends on affected pathways. In this study, we investigated the DDR biomarkers γH2AX (Ser139), p-ATM (Ser1981), and p-CHK2 (Thr68) using flow cytometry on peripheral blood cells obtained from patients with combined immunodeficiencies due to non-homologous end-joining (NHEJ) defects and ataxia telangiectasia (AT) in response to low-dose IR. Significantly reduced induction of all three markers was observed in AT patients compared to controls. However, delayed downregulation of γH2AX was found in patients with NHEJ defects. In contrast to previous reports of DDR in cellular models, these biomarkers were not sensitive enough to identify ARTEMIS deficiency with sufficient reliability. In summary, DDR biomarkers are suitable for diagnosing NHEJ defects and AT, which can be useful in neonates with abnormal TREC levels (T cell receptor excision circles) identified by newborn screening. We conclude that DDR biomarkers have benefits and some limitations depending on the underlying DNA repair deficiency., publishedVersion