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Myofascial trigger point therapy (MTrP) is a widely used therapeutic approach, although the underlying mechanisms remain unclear. Mechanisms discussed include peripheral involvement of muscles as well as central pain modulating processes such as the conditioned pain modulation (CPM). The aim of this study was to investigate whether the analgesic response of MTrP and the analgesic response of CPM correlate in asymptomatic participants in order to identify shared underlying mechanisms of MTrP and CPM. Both, CPM and MTrP protocols consisted of heat-based test stimuli (heat pain thresholds before and after the intervention) and pressure-based (conditioning) stimuli. Asymptomatic participants (n = 94) were randomly assigned to receive either mild, intense or no pressure stimuli (between-group design) to both the fingernail and the MTrP of the infraspinatus muscle (within-group design). Pressure stimuli at both locations (fingernail, MTrP) were applied with a pressure algometer for 120 s and continuously adjusted to maintain a constant pain intensity of mild or intense pain. All thermal stimuli were applied on the lower leg with a thermal stimulator. A significant correlation was shown between the analgesic effect of CPM and MTrP therapy for mild (r = 0.53, p = 0.002) and intensive stimuli (r = 0.73, p < 0.001). 17.3% of the variance of the MTrP effect were explained by CPM after mild stimulation, and 47.1% after intense stimulation. Pain-related characteristics did not explain the variance within the analgesic response using a regression analysis. Between the analgesic responses following MTrP and CPM paradigms, a moderate to strong correlation was observed, suggesting shared underlying mechanisms. • Correlation between trigger point analgesia and conditioned pain modulation. • Equivalence between the magnitude of both paradigms' hypoalgesia. • Hypoalgesic responses were not be explained by clinical features of pain. [ABSTRACT FROM AUTHOR]

For logistical reasons, some high-volume centers have developed surgical programs wherein 1 surgical team performs 2 pancreatoduodenectomies on a single day. It is unclear whether this practice has a negative impact on surgical outcome. We conuducted a retrospective analysis including all consecutive open pancreatoduodenectomies in a single high-volume center (2014–2021). Pancreatoduodenectomies were grouped as the first (pancreatoduodenectomy-1) or second (pancreatoduodenectomy-2) pancreatoduodenectomy on a single day (ie, paired pancreatoduodenectomies) and as pancreatoduodenectomy-3 whenever 1 pancreatoduodenectomy was performed per day (ie, unpaired). Patients undergoing minimally invasive procedures were excluded. The primary outcomes were major morbidity (ie, Clavien-Dindo grade ≥IIIa) and mortality. Among 689 patients, 151 patients had undergone minimally invasive pancreatoduodenectomy, leaving 538 patients after open pancreatoduodenectomy for inclusion. The overall rate of major morbidity was 37.4% (n = 200/538) and in-hospital/30-day mortality 1.7% (n = 9/538). Overall, 136 (25.3%) patients were operated in 68 pancreatoduodenectomy-1/ pancreatoduodenectomy-2 pairs and 402 (74.7%) patients as unpaired pancreatoduodenectomy (pancreatoduodenectomy-3). No differences were found between pancreatoduodenectomy-1 and pancreatoduodenectomy-2 regarding the rates of major morbidity (35.3% vs 26.5%; P =.265) and mortality (1.5% vs 0%; P =.999). Between the 68 pancreatoduodenectomy-1/ pancreatoduodenectomy-2 pairs and the 402 unpaired pancreatoduodenectomies, the rates of major morbidity (30.9% vs 39.6%; P =.071) and mortality (0.7% vs 2.0%; P =.461) did not differ significantly. In multivariable logistic regression analysis, pancreatoduodenectomy-1 was not associated with major morbidity (odds ratio = 0.913 [95% confidence interval 0.515–1.620]; P =.756), whereas pancreatoduodenectomy-2 was associated with less major morbidity (odds ratio = 0.522 [95% confidence interval 0.277–0.983]; P =.045). In a high-volume setting, performing 2 consecutive open pancreatoduodenectomies on a single operating day appears to be safe. This approach may be an option when logistically required. [ABSTRACT FROM AUTHOR]

Evaluation of morbidity and mortality after hepatic resection often lacks stratification by extent of resection or diagnosis. Although a liver resection for different indications may have technical similarities, postoperative outcomes differ. The aim of this systematic review and meta-analysis was to determine the risk of major complications and mortality after resection of intrahepatic cholangiocarcinoma. Meta-analysis was performed to assess postoperative mortality (in-hospital, 30-, and 90-day) and major complications (Clavien-Dindo grade ≥III). A total of 32 studies that reported on 19,503 patients were included. Pooled in-hospital, 30-day, and 90-day mortality were 5.9% (95% confidence interval 4.1–8.4); 4.6% (95% confidence interval 4.0–5.2); and 6.1% (95% confidence interval 5.0–7.3), respectively. Pooled proportion of major complications was 22.2% (95% confidence interval 17.7–27.5) for all resections. The pooled 90-day mortality was 3.1% (95% confidence interval 1.8–5.2) for a minor resection, 7.4% (95% confidence interval 5.9–9.3) for all major resections, and 11.4% (95% confidence interval 6.9–18.7) for extended resections (P =.001). Major complications were 38.8% (95% confidence interval 29.5–49) after a major hepatectomy compared to 11.3% (95% confidence interval 5.0–24.0) after a minor hepatectomy (P =.001). Asian studies had a pooled 90-day mortality of 4.4% (95% confidence interval 3.3–5.9) compared to 6.8% (95% confidence interval 5.6–8.2) for Western studies (P =.02). Cohorts with patients included before 2000 had a pooled 90-day mortality of 5.9% (95% confidence interval 4.8–7.3) compared to 6.8% (95% confidence interval 5.1–9.1) after 2000 (P =.44). When informing patients or comparing outcomes across hospitals, postoperative mortality rates after liver resection should be reported for 90-days with consideration of the diagnosis and the extent of liver resection. [ABSTRACT FROM AUTHOR]

Presence of multiple hepatic lesions in intrahepatic cholangiocarcinoma (iCCA) is included in staging as a negative prognostic factor, but both prognostic value and therapeutic implications remain debated. The aim of this study was to systematically review the prognostic influence of multiple lesions on survival after resection for iCCA, with stratification for distribution and number of lesions. Medline and Embase were systematically searched to identify records (2010–2021) reporting survival for patients undergoing primary resection for iCCA. Included were original articles reporting overall survival, with data on multiple lesions including tumour distribution (satellites/other multiple lesions) and/or number. For meta-analysis, the random effects model and inverse variance method were used. PRISMA 2020 guidelines were followed. Thirty-one studies were included for review. For meta-analysis, nine studies reporting data on the prognostic influence of satellite lesions (2737 patients) and six studies reporting data on multiple lesions other than satellites (1589 patients) were included. Satellite lesions (hazard ratio 1.89, 95% confidence interval 1.67–2.13) and multiple lesions other than satellites (hazard ratio 2.41, 95% confidence interval 1.72–3.37) were significant negative prognostic factors. Data stratified for tumour number, while limited, indicated increased risk per additional lesion. Satellite lesions, as well as multiple lesions other than satellites, was a negative prognostic factor in resectable iCCA. Considering the prognostic impact, both tumour distribution and number of lesions should be evaluated together with other risk factors to allow risk stratification for iCCA patients with multiple lesions, rather than precluding resection for the entire patient group. • Both satellite lesions and other multiple lesions found to be prognostic factors • Tumor distribution and number should be reported in intrahepatic cholangiocarcinoma • Evaluation of both tumor distribution and number could improve risk stratification [ABSTRACT FROM AUTHOR]

The wearable cardioverter defibrillator (WCD) is increasingly used in patients at elevated risk for ventricular arrhythmias but not fulfilling the indications for an implantable cardioverter defibrillator (ICD). Currently, there is an insufficient risk prediction of fatal arrhythmias in patients at risk. In this study, we assessed the prognostic role of baseline electrocardiogram (ECG) in WCD patients. WCD patients from diverse clinical institutions in Germany (n = 227) were retrospectively enrolled and investigated for the incidences of death or ventricular arrhythmias during WCD wearing. In addition, the widely accepted ECG predictors of adverse outcome were analyzed in patients with arrhythmic events. Life-threatening arrhythmias occurred in 22 (9.7 %) patients, mostly in subjects with ischemic heart disease (15 of 22). There was no difference in baseline left ventricular ejection fraction (LVEF) in subjects with and without arrhythmic events (31.3 ± 7.9 % vs. 32.6 ± 8.3 %; p = 0,24). Patients with arrhythmia exhibited significantly longer QRS duration (109.5 ± 23.1 ms vs. 100.6 ± 22.3 ms, p = 0,04), Tpeak-Tend (Tp-e) (103.1 ± 15.6 ms vs. 93.2 ± 19.2 ms, p = 0,01) and QTc (475.0 ± 60.0 ms vs. 429.6 ± 59.4 ms, p < 0,001) intervals. In contrast, no significant differences were found for incidences of fragmented QRS (27.3 % vs. 24 %, p = 0.79) and inverted/biphasic T-waves (16.6 % vs. 22.7 %, p = 0,55). In multivariate regression analysis both Tp-e (HR 1.03; 95 % CI 1.001–1.057; p = 0.02) and QTc (HR 1.02; 95 % CI 1.006–1.026; p < 0.001) were identified as independent predictors of ventricular arrhythmias. After WCD use, the prophylactic ICD was indicated in 76 patients (33 %) with uneventful clinical course but persistent LVEF ≤35 %. The ECG analysis in these subjects did not reveal any relevant changes in arrhythmogenesis markers. ECG repolarization markers Tp-e and QTc are associated with malignant arrhythmias in WCD patients and may be used - in addition to other established risk markers - to identify appropriate patients for ICD implantation. [Display omitted] • The wearable cardioverter defibrillator is safe and effective in patients with elevated risk for fatal arrhythmias. • Tp-e and QTc are independent electrocardiographic (ECG) predictors of adverse events in these patients. • ECG can serve as an additional risk stratification tool in this high-risk subgroup. [ABSTRACT FROM AUTHOR]

Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery. This was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment. 2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score ≥3 (aOR 0.70, CI 0.51–0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44–0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34–0.94, p = 0.02), Charlson Comorbidity Index ≥2 (aOR 0.73, CI 0.54–0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36–0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed. TO differs between indications for liver resection and can be used to assess between hospital and network differences. [ABSTRACT FROM AUTHOR]

Currently, the potential benefits of additional resection after positive proximal intraoperative frozen sections (IFS) in perihilar cholangiocarcinoma (pCCA) on residual disease and oncological outcome remain uncertain. Therefore, the aim of this study is to investigate the number of R0 resections after additional resection of a positive proximal IFS and the influence of additional resections on overall survival (OS) in patients with pCCA. A retrospective, multicenter, matched case-control study was performed, including patients undergoing resection for pCCA between 2000 and 2019 at three tertiary centers. Primary outcome was the number of achieved 'additional' R0 resections. Secondary outcomes were OS, recurrence, severe morbidity and mortality. Forty-four out of 328 patients undergoing resection for pCCA had a positive proximal IFS. An additional resection was performed in 35 out of 44 (79.5%) patients, which was negative in 24 (68.6%) patients. Nevertheless, seven out of these 24 patients were eventually classified as R1 resection due to other positive resection margins. Therefore, 17 (48.6%) patients could be classified as "true" R0 resection after additional resection. Ninety-day mortality after R1 resections was high (25%) and strongly influenced OS. After correction for 90-day mortality, median OS after negative additional resection was 33 months (95%CI:29.5–36.5) compared to 30 months (95%CI:24.4–35.6) after initial R1 (P = 0.875) and 46 months (95%CI:32.7–59.3) after initial R0 (P = 0.348). There were only 17 patients (out of a total of 328 patients) that potentially benefitted from routine IFS. Additional resection for a positive IFS leading to R0 resection was not associated with improved long-term survival. [ABSTRACT FROM AUTHOR]

Glycans associated with biopharmaceutical drugs play crucial roles in drug safety and efficacy, and therefore, their reliable detection and quantification is essential. Our study introduces a multi-level quantification approach for glycosylation analysis in monoclonal antibodies (mAbs), focusing on minor abundant glycovariants. Mass spectrometric data is evaluated mainly employing open-source software tools. Released N- glycan and glycopeptide data form the basis for integrating information across different structural levels up to intact glycoproteins. Comprehensive comparison showed that indeed, variations across structural levels were observed especially for minor abundant species. Utilizing modification finder (MoFi), a tool for annotating mass spectra of intact proteins, we quantify isobaric glycosylation variants at the intact protein level. Our workflow's utility is demonstrated on NISTmAb, rituximab and adalimumab, profiling their minor abundant variants for the first time across diverse structural levels. This study enhances understanding and accessibility in glycosylation analysis, spotlighting minor abundant glycovariants in therapeutic antibodies. [Display omitted] • Quantification of minor abundant glycovariants occurring in monoclonal antibodies. • Integration of quantitative data across protein structural levels. • Quantification of MS data at the raw data level by open-source software tools. • Site-specific discrepancies exist at diverse structural levels for minor species. • Comprehensive meta-data study on glycosylation analyses in literature. [ABSTRACT FROM AUTHOR]

Sepsis is a dysregulated host response of severe bloodstream infections, and given its frequency of occurrence and high mortality rate, therapeutic improvements are imperative. A reliable biomimetic strategy for the targeting and separation of bacterial pathogens in bloodstream infections involves the use of the broad-spectrum binding motif of human GP-340, a pattern-recognition receptor of the scavenger receptor cysteine rich (SRCR) superfamily that is expressed on epithelial surfaces but not found in blood. Here we show that these peptides, when conjugated to superparamagnetic iron oxide nanoparticles (SPIONs), can separate various bacterial endotoxins and intact microbes (E. coli, S. aureus, P. aeruginosa and S. marcescens) with high efficiency, especially at low and thus clinically relevant concentrations. This is accompanied by a subsequent strong depletion in cytokine release (TNF, IL-6, IL-1β, Il-10 and IFN-γ), which could have a direct therapeutic impact since escalating immune responses complicates severe bloodstream infections and sepsis courses. SPIONs are coated with aminoalkylsilane and capture peptides are orthogonally ligated to this surface. The particles behave fully cyto- and hemocompatible and do not interfere with host structures. Thus, this approach additionally aims to dramatically reduce diagnostic times for patients with suspected bloodstream infections and accelerate targeted antibiotic therapy. Sepsis is often associated with excessive release of cytokines. This aspect and slow diagnostic procedures are the major therapeutic obstacles. The use of magnetic particles conjugated with small peptides derived from the binding motif of a broad-spectrum mucosal pathogen recognition protein GP-340 provides a highly efficient scavenging platform. These peptides are not found in blood and therefore are not subject to inhibitory mechanisms like in other concepts (mannose binding lectine, aptamers, antibodies). In this work, data are shown on the broad bacterial binding spectrum, highly efficient toxin depletion, which directly reduces the release of cytokines. Host cells are not affected and antibiotics not adsorbed. The particle bound microbes can be recultured without restriction and thus be used directly for diagnostics. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the incidence and risk factors of primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma. All patients who underwent a major liver resection for presumed perihilar cholangiocarcinoma between 2000 and 2020 at 2 tertiary-referral hospitals were included. Liver failure was defined according to the International Study Group for Liver Surgery criteria, and only grade B/C was considered clinically relevant. Primary liver failure was defined as failure without any underlying postoperative cause, and secondary liver failure was defined as liver failure with an onset after an underlying postoperative complication as a cause. The incidence of liver failure and 90-day mortality were 20.9% and 17.0% in the 253 included patients, respectively. The incidences of primary liver failure was 9.1% and secondary liver failure was 11.9%. Abdominal sepsis, portal vein thrombosis, and arterial thrombosis were the most frequent causes. The absence of preoperative remnant liver assessment and blood loss were independent risk factors for primary liver failure. Independent risk factors for secondary liver failure were Eastern Cooperative Oncology group performance status, percutaneous biliary drainage, and preoperative cholangitis. Liver failure after major liver resection for perihilar cholangiocarcinoma occurred in 1 of every 5 patients. The proposed subdivision into primary and secondary liver failure could help to understand differences in outcomes between centers and help to reduce liver failure. [ABSTRACT FROM AUTHOR]

Approximately 15% of patients undergoing resection for presumed perihilar cholangiocarcinoma (PHC) have benign disease at final pathological assessment. Molecular imaging targeting tumor-specific biomarkers could serve as a novel diagnostic tool to reduce these futile surgeries. Imaging agents have been developed, selectively binding integrin α ν β 6, a cell receptor upregulated in pancreatobiliary malignancies, for both (preoperative) PET and (intraoperative) fluorescent imaging. Here, expression of integrin α ν β 6 is evaluated in PHC, intrahepatic cholangiocarcinoma (ICC), hepatocellular carcinoma (HCC) and benign disease mimicking PHC using immunohistochemistry. Three tissue microarrays (TMA) including 103 PHC tumor cores and sixty tissue samples were selected from resection specimens of pathologically proven PHC (n = 20), ICC (n = 10), HCC (n = 10), metastatic PHC lymph nodes (n = 10) and benign disease (presumed PHC with benign disease at pathological assessment, n = 10). These samples were stained for integrin α ν β 6 and quantified using the H-score. Immunohistochemical staining for integrin α ν β 6 showed membranous expression in all twenty PHC whole mount slides (100%) and 93 out of 103 (92%) PHC tumor cores. Mean H-score of PHC samples was 195 ± 71, compared to a mean H-score of 126 ± 57 in benign samples (p = 0.013). In both benign and PHC samples, inflammatory infiltrates and pre-existent peribiliary glands showed integrin α ν β 6 expression. The mean H-score across ten ICC was 33 ± 53, which was significantly lower compared to PHC (p < 0.001) but too weak to consistently discriminate ICC from HCC (H-score 0)(p = 0.062). Integrin α ν β 6 is abundantly expressed in PHC and associated metastatic lymph nodes. Expression is significantly higher in PHC as compared to benign disease mimicking PHC, ICC and HCC, emphasizing its potential as a target for tumor-specific molecular imaging. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate psychosocial long-term outcome in patients diagnosed with psychogenic nonepileptic seizures (PNES) and to predict outcome of PNES, economic status, and quality of life (QoL) at follow-up.Methods: Patients diagnosed with PNES in the video-EEG-monitoring unit at our Epilepsy center between 2002-2016 were contacted by phone 1-16 years after communicating the diagnosis. Patients underwent a structured interview asking for current PNES status, psychosocial situation (economic status, marital status, setting of living, driving), depression, and QoL.Results: Of 70 PNES patients without comorbid epilepsy (age: 41.1 ± 13.5 years; 74 % female, follow-up: 5.2 ± 4.2 years), 23 patients (33 %) reported to be free of PNES during the last 12 months. Patients with cessation of PNES were younger at PNES onset (p < .01) and diagnosis (p < .01) and had a higher education (p < .05). At follow-up, the proportion of economically active patients only increased in individuals with cessation of PNES (p < .001) while an increased number of patients with persisting PNES relied on governmental support (p < .001). Cessation of PNES was associated with better mood (p < .01) and QoL (p < .001). In multiple regression models, cessation of PNES was only predicted by younger age at onset, while good economic outcome was determined by younger age and good economic status at diagnosis and cessation of PNES at follow-up. Good QoL at follow-up was predicted by low depressive symptoms, freedom of PNES, and economic activity at follow-up.Conclusion: Long-term outcome in patients with PNES remains to be poor and the majority of patients continue to have PNES. Cessation of PNES was associated with good economic outcome, mood, and QoL. [ABSTRACT FROM AUTHOR]

Adequate preoperative biliary drainage (PBD) is recommended in most patients with resectable perihilar cholangiocarcinoma (pCCA). Most expert centers use endoscopic plastic stents rather than self-expandable metal stents (SEMSs). In the palliative setting, however, use of SEMSs has shown longer patency and superior survival. The aim of this retrospective study was to compare stent dysfunction of SEMSs versus plastic stents for PBD in resectable pCCA patients. In this multicenter international retrospective cohort study, patients with potentially resectable pCCAs who underwent initial endoscopic PBD from 2010 to 2020 were included. Stent failure was a composite end point of cholangitis or reintervention due to adverse events or insufficient PBD. Other adverse events, surgical outcomes, and survival were recorded. Propensity score matching (PSM) was performed on several baseline characteristics. A total of 474 patients had successful stent placement, of whom 61 received SEMSs and 413 plastic stents. PSM (1:1) resulted in 2 groups of 59 patients each. Stent failure occurred significantly less in the SEMSs group (31% vs 64%; P <. 001). Besides less cholangitis after SEMSs placement (15% vs 31%; P =.012), other PBD-related adverse events did not differ. The number of patients undergoing surgical resection was not significantly different (46% vs 49%; P =.71). Complete intraoperative SEMSs removal was successful and without adverse events in all patients. Stent failure was lower in patients with SEMSs as PBD compared with plastic stents in patients with resectable pCCA. Removal during surgery was quite feasible. Surgical outcomes were similar. [ABSTRACT FROM AUTHOR]

The threshold to perform total pancreatectomy is rather high, predominantly because of concerns for long-term consequences of brittle diabetes on patients' quality of life. Contemporary data on postoperative outcomes, diabetes management, and long-term quality of life after total pancreatectomy from large nationwide series are, however, lacking. We performed a nationwide, retrospective cohort study among adults who underwent total pancreatectomy in 17 Dutch centers (2006–2016). Morbidity and mortality were analyzed, and long-term quality of life was assessed cross-sectionally using the following generic and disease-specific questionnaires: the 5-level version European quality of life 5-dimension and the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire Cancer. Several questionnaires specifically addressing diabetic quality of life included the Problem Areas in Diabetes Scale 20, the Diabetes Treatment Satisfaction Questionnaire-status version, and the Hypoglycemia Fear Survey-II. Results were compared with the general population and patients with type 1 diabetes. Overall, 148 patients after total pancreatectomy were included. The annual nationwide volume of total pancreatectomy increased from 5 in 2006 to 32 in 2015 (P <. 05). The 30-day and 90-day mortality were 5% and 8%, respectively. The major complication rate was 32%. Quality of life questionnaires were completed by 60 patients (85%, median follow-up of 36 months). Participants reported lower global (73 vs 78, P =.03) and daily health status (0.83 vs 0.87, P <. 01) compared to the general population. Quality of life did not differ based on time after total pancreatectomy (<3, 3–5, or >5 years). In general, patients were satisfied with their diabetes therapy and experienced similar diabetes-related distress as patients with type 1 diabetes. This nationwide study found increased use of total pancreatectomy with a relatively high 90-day mortality. Long-term quality of life was lower compared to the general population, although differences were small. Diabetes-related distress and treatment satisfaction were similar to patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Most interface materials for organic solar cells (OSCs) were originally optimized for fullerene-based systems and are now being adapted for non-fullerene acceptor (NFA) based solar cells. This reliance on established interface materials results in a limited choice of interface materials for NFA based OSCs. For vacuum processed organic devices, the concept of doped interface materials is exceptionally successful, but has not yet been translated to modern NFA based devices due to solution processing constraints requiring orthogonal solubility. Herein, we report a novel concept for the development of solution-processed HTL in inverted n-i-p architecture OSCs using doped organic nanoparticles (D -NPs), overcoming solvent compatibility limitations and enabling scalable production processes. We demonstrate that the functional key interface properties of D -NPs HTLs can be tailored independently over a wide regime. Specifically, conductivity and work function can be optimized separately by varying the dopant concentration and the material system. By using D -NPs as HTL in the n-i-p architecture, power conversion efficiencies (PCE) of over 12 % are achieved for PM6:Y6 based devices. The D -NPs HTL concept is successfully applied to a variety of organic semiconductors used in photovoltaics and opens a new class of tailorable interface materials for solution-processed HTL materials. [Display omitted] • Doped organic nanoparticles for HTL are demonstrated for the first time. • The HTL possesses tailorable properties, and good compatibility with blade coating. • High performance OSC device with inverted structure is achieved. [ABSTRACT FROM AUTHOR]

Background & Aims Biomarkers are needed for early detection of Crohn’s disease (CD) and ulcerative colitis (UC) or to predict patient outcomes. Glycosylation is a common and complex posttranslational modification of proteins that affects their structure and activity. We compared plasma N -glycosylation profiles between patients with CD or UC and healthy individuals (controls). Methods We analyzed the total plasma N -glycomes of 2635 patients with inflammatory bowel diseases and 996 controls by mass spectrometry with a linkage-specific sialic acid derivatization technique. Plasma samples were acquired from 2 hospitals in Italy (discovery cohort, 1989 patients with inflammatory bowel disease [IBD] and 570 controls) and 1 medical center in the United States (validation cohort, 646 cases of IBD and 426 controls). Sixty-three glycoforms met our criteria for relative quantification and were extracted from the raw data with the software MassyTools. Common features shared by the glycan compositions were combined in 78 derived traits, including the number of antennae of complex-type glycans and levels of fucosylation, bisection, galactosylation, and sialylation. Associations of plasma N -glycomes with age, sex, CD, UC, and IBD-related parameters such as disease location, surgery and medication, level of C-reactive protein, and sedimentation rate were tested by linear and logistic regression. Results Plasma samples from patients with IBD had a higher abundance of large-size glycans compared with controls, a decreased relative abundance of hybrid and high-mannose structures, lower fucosylation, lower galactosylation, and higher sialylation (α2,3- and α2,6-linked). We could discriminate plasma from patients with CD from that of patients with UC based on higher bisection, lower galactosylation, and higher sialylation (α2,3-linked). Glycosylation patterns were associated with disease location and progression, the need for a more potent medication, and surgery. These results were replicated in a large independent cohort. Conclusions We performed high-throughput analysis to compare total plasma N -glycomes of individuals with vs without IBD and to identify patterns associated with disease features and the need for treatment. These profiles might be used in diagnosis and for predicting patients’ responses to treatment. Graphical abstract [ABSTRACT FROM AUTHOR]

Abstract Vascular calcification displays a major cause of death worldwide, which involve mainly vascular smooth muscle cells (VSMCs). Since 2007, there are increasing numbers of protocols to obtain different cell types from human induced-pluripotent stem cells (iPSCs), however a protocol for calcification is missing. Few protocols exist today for the differentiation of iPSCs towards VSMCs and none are known for their calcification. Here we present a protocol for the calcification of iPSC-derived VSMCs. We successfully differentiated iPSCs into VSMCs based on a modified protocol. Calcification in VSMCs is induced by a commercial StemXVivo™ osteogenic medium. Calcification was verified using Calcein and Alizarin Red S staining or Calcium assays, and molecular analyses showed enhanced expression of calcification-associated genes. The presented method could help to study genetic risk variants, using the CRISPR/Cas technology through the introduction of Knockouts or Knockins of risk variants. Finally, this method can be applied for drug screening. Highlights • Here we present the first protocol for the calcification of iPSC-derived VSMCs • The differentiation protocol of iPSCs into VSMCs was improved resulting in a much higher differentiation efficiency • We validated the protocol at molecular level • The differentiation protocol was successfully applied to two independent donor cell lines [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category with different molecular subtypes defined by distinct gene expression patterns and divergent mechanisms of oncogenic activation. Several studies have suggested an inferior survival for patients of the activated B-cell-like (ABC) versus the germinal center B-cell-like (GCB) DLBCL subtype which has led to increasing interest in investigating pharmacological inhibition of signaling pathways which contribute to lymphomagenesis and that are specifically utilized by ABC DLBCL cells. One of these signaling cascades is the B-cell receptor (BCR) pathway and several approaches in clinical trials to target this cascade have demonstrated promising therapeutic activity. This review discusses our current understanding of the role of BCR signaling in different DLBCL subtypes, including primary central nervous system lymphoma (PCNSL), a subgroup of DLBCL that is particularly dependent on BCR signaling. One specific aim of this review is to highlight novel approaches to therapeutically target BCR signaling in DLBCL. [ABSTRACT FROM AUTHOR]

Proper travel demand models aim to create an equilibrium between expected travel times in the planning phase and simulated travel times after mapping the road traffic on the road network. While agent-based travel demand models (ABM) focus on the trip generation mainly based on pre-calculated travel times, traffic flow models simulate these trips and compute travel times taking into account speed restrictions and road capacities. This leads to deviations between the simulated travel times and the initially expected ones especially during rush hour so that both models are not in equilibrium state. Due to the complexity and limited computational resources, combinations of these two models are often simplified in either one or both parts. In this work we present an iteratively combined simulation model with feedback of travel times. We couple an ABM with a queue-based traffic flow model which simulates the set of trips for each agent. The ABM used adjusts its activity generation, destination choice and mode choice according to the re-calculated travel times resulting in more realistic day plans. The traffic flow model takes the sequential character of the trips into account and propagates the delay to the subsequent trips of each modelled agent, resulting in feasible trips. We show that equilibrium of travel time between these two models can be achieved with a low number of iterations. Our approach is sensitive to new travel times in destination and mode choice and results in trips which are consistent for a whole day for each modelled agent. [ABSTRACT FROM AUTHOR]

Background Previous studies suggest that immediate reconstruction following mastectomy produces superior results over delayed procedures. However, for medical or oncological reasons, some patients may be poor candidates for immediate reconstruction. We compared complications and patient-reported outcomes between immediate and delayed breast reconstructions in a prospective, multicenter study. Methods 1957 patients (1806 immediate, 151 delayed) met eligibility criteria. Demographic data, major complications, infections, and reconstructive failure rates were evaluated. Patient-reported outcomes were assessed with BREAST-Q, PROMIS, and EORTC QLQ-BR23 surveys, pre- and two years post-operatively. Subscale scores were compared across cohorts using mixed-effects regression models, controlling for patient characteristics and hospitals. Findings Complete data were available in 1639 immediate and 147 delayed reconstruction patients. There were significant baseline differences between immediate and delayed cohorts in age, BMI, prevalence of diabetes, lymph node management, use of radiation, and chemotherapy. Controlling for clinical covariates, the delayed group had lower odds of any (OR 0.38, p < 0.001) and major (OR 0.52, p = 0.016) complications, compared with immediate patients. Furthermore, delayed reconstruction was associated with a significantly lower failure rates (6% vs. 1.3%, p = 0.032). However, multivariate analyses found no significant differences in patient satisfaction or in psychosocial, sexual, or physical well-being at two years. Conclusions Compared with immediate techniques, delayed reconstruction following mastectomy was associated with lower rates of overall and major complication, while providing equivalent patient satisfaction and quality of life benefits. Although immediate reconstruction is still the preferred choice of most patients and surgeons, delaying reconstruction does not appear to compromise clinical or patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Investment in education technology (EdTech) is a complex decision problem for universities during the post-Covid era. With the objective to assess the quality and adoptability of education supply chain, a novel analytical evaluation model approach is proposed, based on quality function deployment and combinative distance-based assessment. To deal with uncertainty in the evaluation process, fuzzy theory is integrated into the model. To establish the house of quality matrix, technology-based stakeholders' requirements were identified and classified in four dimensions: economic and financial, technology adoption, sustainability, competencies. Moreover, nine supplier criteria were assumed. Based on expert evaluations, the results suggest that financial credit and supplier collaboration are the most prominent attributes to evaluate suppliers, while environmental commitment is sorted as the least important criterion. The results reveal that the three dominant suppliers, which provide the best response to the identified criteria, are providers of cloud service technology. • A study to choose supplier selection for education technology is proposed • QFD and CODAS with integrated fuzzy theory • Financial credit and supplier collaboration best attributes for supplier evaluation • Dominant suppliers with the best response are providers of cloud service technology • Novel analytical evaluation model approach under uncertainty [ABSTRACT FROM AUTHOR]

Currently, different technologies are being employed to remove CO 2 and H 2 S from the natural gas. Based on chemical phenomenon, the absorption using alkanolamines is probably the most extended process for the acid gas removal. However, membrane technologies are considered as an alternative in specific cases for their better performances, cleanness, energy requirements, operative costs and location flexibility. The aim of this article is to estimate, compare and analyze the energy requirements, greenhouse gases (GHG) emissions and investment costs of three Natural Gas Sweetening processes. For the study, a regular process using methyldiethanolamine (MDEA), the absorption process using recompressed vapor and a membrane system were simulated using Aspen Hysys v8.8. For the first case, real data from the gas plant Aguaragüe (Argentina) was used to validate the model. To establish a proper comparison, a natural gas with 4 mol.% of CO 2 is considered as the inlet stream of each configuration. Specifically, compression and pump power, specific total heat, removed CO 2 , CH 4 wastes and capital costs were estimated and compared for each case. Additionally, a discussion including different aspects in regard to the energy efficiency of the processes was conducted. Although the proposed membrane system demonstrated to reduce the energy requirements (77% and 72%) and emissions (80% and 76%) in respect to both absorption processes, the CH 4 losses were higher by more than 6 factor. Moreover, the investment cost of the technology is 12% higher than the required capital of a conventional amine process. [ABSTRACT FROM AUTHOR]

Morphological control over the bulk heterojunction (BHJ) microstructure of a high-efficiency small molecule photovoltaic system composed of a quinquethiophene based molecule (DRCN5T) as electron donor and [6,6]-phenyl-C71-butyric acid methyl ester (PC 70 BM) as electron acceptor is demonstrated using three different post-processing strategies, including thermal annealing (TA), solvent vapor annealing (SVA), and two-step annealing (TA-SVA) treatments. We systematically analyze the processing condition-microstructure-device property relationships, explore the corresponding morphology evolution and their effects on carrier transport and recombination dynamics in BHJs as well as understand the nature of phase-separation process resulting in light-induced degradation mechanisms. Within the investigated results, the causative relations between annealing sequence, photovoltaic parameters, morphology evolution and charge carrier dynamics are for the first time delineated. In addition, the observed trade-offs in device efficiency and stability with respect to the well-defined morphologies are highlighted. The in-depth picture of the bulk microstructure formation and its kinetic evolution as a function of the specific post-processing approaches is a valuable asset for the design of new photovoltaic materials and thin film nanoscale architectures that are more efficient and better aid future commercialization efforts. [ABSTRACT FROM AUTHOR]

Background Microscopically radical (R0) resection of pancreatic, periampullary, or colon cancer may occasionally require a pancreatoduodenectomy with colon resection (PD-colon), but the benefits of this procedure have been disputed, and multicenter studies on morbidity and oncologic outcomes after PD-colon are lacking. This study aimed to assess complications and survival after PD-colon. Methods Patients who had undergone PD-colon from 2004–2014 in 1 of 13 centers were analyzed retrospectively. Ninety-day morbidity was scored using the Clavien-Dindo score and the Comprehensive Complication Index (CCI, 0 = no complications, 100 = death). Survival was analyzed per histopathologic diagnosis. Results After screening 3,218 consecutive PDs, 50 (1.6%) PD-colon patients (median age 66 years [interquartile range 55–72], 33 [66%] men) were included. Twenty-three (46%) patients had pancreatic ductal adenocarcinoma (PDAC), 19 (38%) other pathology, and 8 (16%) colon cancer. Ninety-day Clavien-Dindo ≥3 complications occurred in 30 (60%) patients without differences per diagnosis ( P > .99); mean CCI was 39 (standard deviation 27). Colonic anastomosis leak, pancreatic fistula, and 90-day mortality occurred in 3 (6%), 2 (4%), and 4 (8%) patients, respectively. A total of 11/23 (48%) patients with PDAC and 8/8 (100%) patients with colon cancer underwent an R0 resection. Patients with PDAC had a median postoperative survival of 13 months (95% confidence interval = 5–21). One-, 3-, and 5-year cumulative survival was 56%, 21%, and 14%, respectively. Median survival after R0 resection for PDAC was 21 months (95% confidence interval = 6–35). All patients with colon cancer were alive at end of follow-up (median 24 months [95% confidence interval = 9–110]). Conclusion In this retrospective, multicenter study, PD-colon was associated with considerable complications and acceptable survival rates when a tumor negative resection margin was achieved. [ABSTRACT FROM AUTHOR]

Background Acute type A aortic dissection (AAD) is a life-threatening disorder with a high rate of mortality and complications. All cannulation techniques currently used to establish arterial flow for cardiopulmonary bypass are associated with a considerable risk of organ malperfusion, stroke, or access site trauma. Here, we report the impact of transatrial cannulation of the left ventricle on patient outcome after surgical treatment of AAD. Methods Between 2010 and 2013, 46 patients underwent emergency surgery for AAD using transatrial cannulation of the left ventricle. Their outcome was retrospectively compared with that of 73 age- and sex-matched patients operated on for AAD between 2006 and 2010 before introduction of the new technique. Results No differences concerning preoperative details were found. Arterial flow before 2010 was established after preparation of the femoral artery in 46 patients (63.0%) or by direct cannulation of the ascending aorta in 27 patients (37.0%). Operation times were significantly lower in the transatrial cannulation group (271.2 ± 75.4 versus 308.3 ± 78.2; p = 0.02). Postoperatively, we observed a significantly reduced stroke rate in the group with transatrial cannulation (6.5% versus 26.5%; p = 0.007) and a decreased rate of acute renal failure (20.0% versus 32.4%; p = 0.003). Intraoperative mortality (0% versus 6.8%; p = 0.16), 30-day mortality (8.9% versus 10.3%; p = 1.00), and mortality during follow-up (9.8% versus 34.4%; p = 0.08) did not differ. However, overall mortality was significantly lower in the group after transatrial cannulation (17.7% versus 45.2%; p = 0.003). Conclusions In patients undergoing surgery for AAD, transatrial cannulation of the left ventricle proved to be a safe and easy cannulation method that significantly reduced postoperative complications. [ABSTRACT FROM AUTHOR]

Chemical processes simulation is an important instrument for the design, optimization and control of industrial plants. Simulation cases can be accomplished with relatively low costs and the absence of risks for the operators. However, the precision of the results depends on the similarity between the simulation performed and the process considered. In this article, two simulators, Aspen Hysys V8.6 and Aspen Plus V8.6, are employed to simulate the process of natural gas sweetening using diethanolamine (DEA). Additionally, a parametric sensitivity analysis is performed to define the optimal operative range for the process. The required data and the conditions of the operating units are taken from a gas conditioning plant in northern Argentina. Finally, a comparison between the block of obtained results from both simulations is also detailed. [ABSTRACT FROM AUTHOR]

Many modern types of solar cells that rely exclusively on earth-abundant non-toxic materials include interfaces between a heavier metal chalcogenide and another type of semiconductor. Often, the chemical (adhesion) and physical (charge transfer) characteristics of those interfaces are the defining factors for the final device performance. Here, we describe that a ZnS adhesion layer is not sufficient to prevent the dewetting of Sb 2 S 3 upon annealing a thin layer of it on an oxidic surface if the substrate is not planar and features highly curved surfaces. An ALD-coated sacrificial capping layer of ZnO prevents the morphological rearrangements of Sb 2 S 3 during thermal crystallization and can be removed subsequently. When implemented towards a photovoltaic p-i-n heterojunction, this strategy furnishes perfect conformality of the layer stack but unsatisfactory performance. The correlation of interface chemistry with the electrical properties and the device performance identifies a reducing effect of ZnO atomic layer deposition chemistry on the Sb 2 S 3 surface as the cause of Zn diffusion into the light absorbing semiconductor. This deleterious doping can be prevented by a preliminary oxidative treatment of the Sb 2 S 3 surface with ozone. When applied to a structured substrate consisting of ordered arrays of nanospheres, this approach yields the first ever concentric p-i-n heterojunction solar cells with photonic light trapping effect—a geometry which in comparison with standard scattering layers'on top' inherently generates a very large refractive index contrast. In the red part of the visible spectrum, light absorption amounts to the value expected with four passes through a planar layer of the thickness used here (35 nm Sb 2 S 3). This effect allows us to demonstrate > 5% overall solar energy conversion efficiency with only 35 nm of a simple light absorber phase that uses no toxic, rare materials. [Display omitted] • A confined crystallization method yields conformal stibnite Sb 2 S 3 coatings. • Fine tuning of the interface chemistry can either resolve or promote interface reactions and gradient doping. • Efficient ultrathin solar cells on nanosphere concentric p-i-n heterojunctions. • Light trapping by photonic nanostructure increases photocurrent with 35 nm absorber. [ABSTRACT FROM AUTHOR]

Objectives This study sought to evaluate the role of esmolol-induced tight sympathetic control in patients with ST-segment elevation myocardial infarction (STEMI). Background Elevated sympathetic drive has a detrimental effect on patients with acute STEMI. The effect of beta-blocker-induced heart rate mediated sympathetic control on myocardial damage is unknown. Methods The authors conducted a prospective, randomized, single-blind trial involving patients with STEMI and successful percutaneous intervention (Killip class I and II). Patients were randomly allocated to heart rate control with intravenous esmolol for 24 h or placebo. The primary outcome was the maximum change in troponin T release as a prognostic surrogate marker for myocardial damage. A total of 101 patients were enrolled in the study. Results There was a significant difference between patients allocated to placebo and those who received sympathetic control with esmolol in terms of maximum change in troponin T release: the median serum troponin T concentration increased from 0.2 ng/ml (interquartile range [IQR] 0.1 to 0.7 ng/ml) to 1.3 ng/ml (IQR: 0.6 to 4.7 ng/ml) in the esmolol group and from 0.3 ng/ml (IQR: 0.1 to 1.2 ng/ml) to 3.2 ng/ml (IQR: 1.5 to 5.3 ng/ml) in the placebo group (p = 0.010). The levels of peak creatine kinase (CK), CK subunit MB (CK-MB), and n-terminal brain natriuretic peptide (NT-proBNP) were lower in the esmolol group compared with placebo (CK 619 U/l [IQR: 250–1,701 U/l] vs. 1,308 U/l [IQR: 610 to 2,324 U/l]; p = 0.013; CKMB: 73.5 U/l [IQR: 30 to 192 U/l] vs. 158.5 U/l [IQR: 74 to 281 U/l]; p = 0.005; NT-proBNP: 1,048 pg/ml (IQR: 623 to 2,062 pg/ml] vs. 1,497 pg/ml [IQR: 739 to 3,318 pg/ml]; p = 0.059). Cardiogenic shock occurred in three patients in the placebo group and in none in the esmolol group. Conclusions Esmolol treatment statistically significantly decreased troponin T, CK, CK-MB and NT-proBNP release as surrogate markers for myocardial injury in patients with STEMI. (Heart Rate Control After Acute Myocardial Infarction; DRKS00000766 ) [ABSTRACT FROM AUTHOR]

Resumo Introdução A anestesiologia é a única especialidade médica que prescreve, dilui e administra os fármacos sem conferência de outro profissional. Somando‐se a alta frequência de administração de fármacos, cria‐se o cenário propício aos erros. Objetivo Verificar a prevalência dos erros de administração de medicamentos durante anestesia, entre anestesiologistas catarinenses, as circunstâncias em que ocorreram e possíveis fatores associados. Materiais e métodos Um questionário eletrônico foi enviado a todos os anestesiologistas da Sociedade de Anestesiologia do Estado de Santa Catarina contendo respostas diretas ou de múltipla escolha sobre dados demográficos e perfil da prática anestésica do entrevistado; prevalência de erros, tipo e consequência do erro; e fatores que possivelmente contribuíram para os erros. Resultados Dos entrevistados, 91,8% afirmaram ter cometido erro de administração, somando total de erros de 274 e média de 4,7 (6,9) erros por entrevistado. O erro mais comum foi substituição (68,4%), seguido por erro de dose (49,1%) e omissão (35%). Apenas 7% dos entrevistados referiram erros de administração no neuroeixo. Quanto às circunstâncias dos erros, ocorreram principalmente no período matutino (32,7%), na manutenção da anestesia (49%), com 47,8% sem danos ao paciente e 1,75% com maior morbidade com dano irreversível e em 87,3% dos casos a identificação imediata. Quanto aos possíveis fatores contribuintes, os mais frequentes foram: distração e fadiga (64,9%) e leitura errada dos rótulos de ampolas ou seringas (54,4%). Conclusão A maioria dos anestesiologistas entrevistados cometeu mais de um erro de administração em anestesia, principalmente justificado como distração ou fadiga, de baixa gravidade. Introduction Anesthesiology is the only medical specialty that prescribes, dilutes, and administers drugs without conferral by another professional. Adding to the high frequency of drug administration, a propitious scenario to errors is created. Objective Access the prevalence of drug administration errors during anesthesia among anesthesiologists from Santa Catarina, the circumstances in which they occurred, and possible associated factors. Materials and methods An electronic questionnaire was sent to all anesthesiologists from Sociedade de Anestesiologia do Estado de Santa Catarina, with direct or multiple choice questions on responder demographics and anesthesia practice profile; prevalence of errors, type and consequence of error; and factors that may have contributed to the errors. Results Of the respondents, 91.8% reported they had committed administration errors, adding the total error of 274 and mean of 4.7 (6.9) errors per respondent. The most common error was replacement (68.4%), followed by dose error (49.1%), and omission (35%). Only 7% of respondents reported neuraxial administration error. Regarding circumstances of errors, they mainly occurred in the morning (32.7%), in anesthesia maintenance (49%), with 47.8% without harm to the patient and 1.75% with the highest morbidity and irreversible damage, and 87.3% of cases with immediate identification. As for possible contributing factors, the most frequent were: distraction and fatigue (64.9%) and misreading of labels, ampoules, or syringes (54.4%). Conclusion Most respondents committed more than one error in anesthesia administration, mainly justified as a distraction or fatigue, and of low gravity. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAH), as a part of dissolved organic matter (DOM), are environmental pollutants of the marine compartment. This study investigates the origin of PAH, which is supposed to derive mainly from anthropogenic activities, and their alteration along the salinity gradient of the Baltic Sea. Pyrolysis in combination with gas chromatography and two mass selective detectors in one measurement cycle are utilized as a tool for an efficient trace analysis of such complex samples, by which it is possible to detect degradation products of high molecular structures. Along the north–south transect of the Baltic Sea a slightly rising trend for PAH is visible. Their concentration profiles correspond to the ship traffic as a known anthropogenic source, underlined by the value of special isomer ratios such as phenanthrene and anthracene (0.31–0.45) or pyrene and fluoranthene (0.44–0.53). The detection of naphthalene and the distribution of its alkylated representatives support this statement. [ABSTRACT FROM AUTHOR]

We report on the development of a novel nano-composite transparent electrode material to be used in various energy applications e.g. as contacts for solar cells, composed of a wet-chemically synthesized silver nanowire (AgNW) network encapsulated in a transparent conductive oxide (TCO) which was deposited with nano-scale precision by atomic layer deposition (ALD). The AgNWs form a random network on a substrate of choice when being drop casted. ALD encapsulation of AgNWs guarantees a conformal and thickness controlled coating of the wires e.g. by the selected aluminum doped zinc oxide (AZO). Annealing of the AgNWs prior to ALD coating, yield a local sintering of AgNWs at their points of intersection, which improves the conductivity of the composite electrodes by reducing their sheet resistance. To demonstrate the performance of these AgNW/AZO composite transparent electrodes, they were used as a top electrode on wafer-based silicon (Si) - solar cells. A novel combination of scanning electron microscopy and image processing is used to determine the degree of percolation of the AgNWs on large areas of the nano-composite AgNW/AZO electrodes. Our results show that the solar cell with percolated AgNW/AZO electrode show the highest short circuit current density (28 mA/cm 2 ) and a series resistance in the same order of magnitude compared to reference solar cells with a thermally evaporated silver grid electrode. The electrode example we chose reveals that the developed AgNW/AZO electrode is a technologically relevant and cheap alternative to conventional solar cell screen printed grid electrodes, which contain ~95% more Ag per device area, with a high potential to be further systematically optimized by the presented image processing method. [ABSTRACT FROM AUTHOR]

Background Median sternotomy may be associated with postoperative complications such as nonunion after conventional metal wire closure. The Sternal Talon device (KLS Martin, Jacksonville, FL) has recently been introduced as an alternative for osteosynthesis after median sternotomy and may also be beneficial for patients with persistent sternal nonunion. Methods A consecutive series of 24 patients underwent Sternal Talon repair for sternal nonunion or acute mediastinitis, or both, after sternal wire closure. Patient data—including demographics, surgical history, and indication for operation, as well as outcomes—were obtained and analyzed by retrospective chart review. Results The average patient age was 61.3 years and 23 patients were men (95.8%). The most common median sternotomy procedure was coronary artery bypass grafting (CABG) in 19 patients (79.2%). Secondary closure using the Sternal Talon was indicated for sternal nonunion or infection, or both, in all patients. Eight patients underwent simultaneous muscle flap procedures during the placement of the Sternal Talon (33.3%). Sternal union was eventually achieved in 23 of 24 patients (95.8%). Subsequent reoperation was required in 4 patients (16.7%). Conclusions The data presented suggest that the osteosynthesis using the Sternal Talon device is a safe and effective modality for treating symptomatic sternal nonunion or acute dehiscence associated with infection (mediastinitis.) [ABSTRACT FROM AUTHOR]

Background A variety of therapeutic options are available for mycosis fungoides, the most prevalent subtype of cutaneous T cell lymphomas, but thus far, no regimen has been proven to be curative. A combination of treatments is a well-established strategy to increase the therapeutic efficacy. However, data from clinical trials analyzing such combinations for the treatment of mycosis fungoides are scarce. Objective To analyze the available evidence on combination therapies with emphasis on the combination of psoralen with UVA phototherapy (PUVA), interferon-alpha and bexarotene with another treatment. Methods Systematic literature review of the databases Embase, Cochrane, Medline, and Medline in Process. Results Combination of PUVA with interferon-alpha or retinoids did not result in an increased overall response rate. Addition of methotrexate but not retinoids to interferon-alpha may increase the overall response rate. Bexarotene was investigated in one trial each with vorinostat, methotrexate or gemcitabine, whereby only methotrexate possibly enhanced the effect of bexarotene. Conclusion For mycosis fungoides, no combination treatment has been demonstrated to be superior to monotherapy. Based on our analysis, we conclude that in certain clinical situations, patients may benefit from a combination of PUVA with interferon-alpha or a retinoid or a combination of the latter two. Furthermore, patients in advanced stages may benefit from the combination of methotrexate and interferon-alpha or bexarotene. Finally, the combination of bexarotene with either vorinostat or gemcitabine did not increase the overall response rate but resulted in more pronounced side effects and cannot be recommended. [ABSTRACT FROM AUTHOR]

Zusammenfassung Leitsymptom ist eine Schwäche der Muskeln mit variablem Schwerpunkt, die tageszeitlich oder auch belastungsabhängig sein kann. Störungen der Sensibilität kommen nicht vor. Die Diagnostik bei Myopathien oder myasthenen Syndromen sind typische Domänen der Elektromyo- und Elektroneurografie. Die typischen Befunde werden vorgestellt und erklärt. Summary Leading symptom is a muscular weakness with variable location which may depend on day time or on exercise. Sensory disturbances do not occur. Diagnostic management for myopathis and myasthenic syndromes are domains of electromyography and nerve conduction studies. Typical results are presented and explained. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the safety and efficacy of percutaneous or open irreversible electroporation (IRE) in a prospective cohort of patients with locally advanced, unresectable perihilar cholangiocarcinoma (PHC).Materials and Methods: In a multicenter Phase I/II study, patients with unresectable PHC due to extensive vascular involvement or N2 lymph node metastases or local recurrence after resection for PHC were included and treated by open or percutaneous IRE combined with palliative chemotherapy (current standard of care). The primary outcome was the number of major adverse events occurring within 90 d after IRE (grade ≥3), and the upper limit was predefined at 60%. Secondary outcomes included technical success rate, hospital stay, and overall survival (OS).Results: Twelve patients (mean age, 63 y ± 12) were treated with IRE. The major adverse event rate was 50% (6 of 12 patients), and no 90-d mortality was observed. All procedures were technically successful, with no intraprocedural adverse events requiring additional interventions. The median OS from diagnosis was 21 mos (95% confidence interval, 15-27 mos), with a 1-y survival rate of 75% after IRE.Conclusions: Percutaneous IRE in selected patients with locally advanced PHC seems feasible, with a major adverse event rate of 50%, which was below the predefined upper safety limit in this prospective study. Future comparative research exploring the efficacy of IRE is warranted. [ABSTRACT FROM AUTHOR]

Abstract: This study demonstrates – based on a dynamical simulation of a global, decentralized 100% renewable electricity supply scenario – that a global climate-neutral electricity supply based on the volatile energy sources photovoltaics (PV), wind energy (onshore) and concentrated solar power (CSP) is feasible at decent cost. A central ingredient of this study is a sophisticated model for the hourly electric load demand in >160 countries. To guarantee matching of load demand in each hour, the volatile primary energy sources are complemented by three electricity storage options: batteries, high-temperature thermal energy storage coupled with steam turbine, and renewable power methane (generated via the Power to Gas process) which is reconverted to electricity in gas turbines. The study determines – on a global grid with 1°x1° resolution – the required power plant and storage capacities as well as the hourly dispatch for a 100% renewable electricity supply under the constraint of minimized total system cost (LCOE). Aggregating the results on a national level results in an levelized cost of electricity (LCOE) range of 80-200 EUR/MWh (on a projected cost basis for the year 2020) in this very decentralized approach. As a global average, 142 EUR/MWh are found. Due to the restricted number of technologies considered here, this represents an upper limit for the electricity cost in a fully renewable electricity supply. [Copyright &y& Elsevier]

Objective: To evaluate 2 sternal intraosseous access devices as alternatives to emergency intravenous access for dentists, using a manikin and a cadaver model. Study Design: A group of 37 students performed a sternal intraosseous access on a manikin using a Vidacare kit including a puncture template and a prepuncture skin incision. Five months later, 9 of the students used the Vidacare and 8 used an Illinois needle (without template and incision) on adult human cadavers. India ink was injected as a tracer. Results: Shorter times were recorded on cadavers compared with manikins in both systems. One Vidacare puncture ended subcutaneously. Two Illinois needle punctures perforated the sternum, one with intense mediastinal ink traces. Vidacare punctures took longer compared with Illinois needle punctures (medians, 32 vs 12 seconds; P = .0002). Conclusions: Template use to identify the sternal puncture position, combined with additional prepuncture skin incision, may be more efficient and less predisposed to severe complications for dentists' emergency use. [Copyright &y& Elsevier]

Abstract: Microbial communities in biogas batch fermentations, using straw and hay as co-substrates, were analyzed at the gene and protein level by metagenomic and metaproteomic approaches. The analysis of metagenomic data revealed that the Clostridiales and Bacteroidales orders were prevalent in the community. However, the number of sequences assigned to the Clostridiales order decreased during fermentation, whereas the number of sequences assigned to the Bacteroidales order increased. In addition, changes at the functional level were monitored and the metaproteomic analyses detected transporter proteins and flagellins, which were expressed mainly by members of the Bacteroidetes and Firmicutes phyla. A high number of sugar transporters, expressed by members of the Bacteroidetes, proved their potential to take up various glycans efficiently. Metagenome data also showed that methanogenic organisms represented less than 4% of the community, while 20–30% of the identified proteins were of archeal origin. These data suggested that methanogens were disproportionally active. In conclusion, the community studied was capable of digesting the recalcitrant co-substrate. Members of the Firmicutes phylum seemed to be the main degraders of cellulose, even though expression of only a few glycoside hydrolases was detected. The Bacteroidetes phylum expressed a high number of sugar transporters and seemed to specialize in the digestion of other polysaccharides. Finally, it was found that key enzymes of methanogenesis were expressed in high quantities, indicating the high metabolic activity of methanogens, although they only represented a minor group within the microbial community. [Copyright &y& Elsevier]

Abstract: The Bird’s Head Seascape located in eastern Indonesia is the global epicenter of tropical shallow water marine biodiversity with over 600 species of corals and 1,638 species of coral reef fishes. The Seascape also includes critical habitats for globally threatened marine species, including sea turtles and cetaceans. Since 2001, the region has undergone rapid development in fisheries, oil and gas extraction, mining and logging. The expansion of these sectors, combined with illegal activities and poorly planned coastal development, is accelerating deterioration of coastal and marine environments. At the same time, regency governments have expanded their marine protected area networks to cover 3,594,702ha of islands and coastal waters. Low population numbers, relatively healthy natural resources and a strong tenure system in eastern Indonesia provide an opportunity for government and local communities to collaboratively manage their resources sustainably to ensure long-term food security, while meeting their development aspirations. [Copyright &y& Elsevier]