The Role of Liposomal Bupivacaine in Multimodal Pain Management Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: Faster and Farther With Less Opioids.

STUDY DESIGN: Retrospective controlled cohort. OBJECTIVE: To evaluate the effect of intraoperative liposomal bupivacaine (LB) infiltration on postsurgical pain management in adolescent idiopathic scoliosis (AIS) patients by analyzing postoperative opioid consumption, ambulation, and length of stay (LOS). SUMMARY OF BACKGROUND DATA: Optimal postoperative pain control for AIS patients undergoing posterior spinal fusion (PSF) is challenging. Multimodal pain management protocols provide adequate analgesia while decreasing opioid consumption. LB was recently approved for pediatric patients; however, use in AIS patients is understudied. METHODS: 119 consecutive patients with AIS who underwent PSF were included. Patients were divided into 2 groups: patients who received LB as erector spinae block in addition to the standard postoperative pain management protocol (Group A), and patients who received only the standard postoperative pain protocol (Group B). Oral morphine equivalents, intravenous opioid and valium consumption, pain scores (VAS), nausea/vomiting, ambulation distance and LOS were assessed. RESULTS: Group A experienced significantly lower total opioid consumption compared to Group B (44.5 mg vs. 70.2 mg). Morphine use was lower in Group A on postoperative day (POD) 0, and oxycodone use was lower in Group A on PODs 1 and 2. There was a higher proportion of patients who used only oral opioids in Group A (81% vs. 41%). Of patients requiring any intravenous opioids, 79% did not receive LB. A significantly higher proportion of LB patients were discharged on POD 2 (55% vs. 27%); therefore, LOS was shorter for Group A. Group A ambulated further postoperatively. There were no differences in pain scores, valium requirements or nausea/vomiting. CONCLUSIONS: LB was associated with decreased total opioid use, shorter LOS, and improved ambulation in AIS patients undergoing PSF. Including LB in multimodal pain management protocols proved effective in reducing opioid use while increasing mobilization in the immediate postoperative period. LEVEL OF EVIDENCE: 3.

Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

Nivolumab for locally advanced and metastatic cutaneous squamous cell carcinoma (NIVOSQUACS study)-Phase II data covering impact of concomitant haematological malignancies.

BACKGROUND: Monoclonal antibodies, such as cemiplimab and pembrolizumab, against the programmed death receptor (PD)-1 have become the current standard of care and first-line treatment of advanced cutaneous squamous cell carcinoma (cSCC), proving remarkable clinical benefit and acceptable safety. OBJECTIVES: To assess efficacy and safety of the anti-PD-1 antibody nivolumab in patients with locally advanced and metastatic cSCC. METHODS: Patients received open-label nivolumab 240 mg intravenously every 2 weeks for up to 24 months. Patients with concomitant haematological malignancies (CHMs), either non-progressing or stable under active therapy, were eligible for inclusion. RESULTS: Of 31 patients with a median age of 80 years, 22.6% of patients achieved an investigator assessed complete response, resulting in an objective response rate (ORR) of 61.3% and a disease control rate (DCR) of 64.5%. Progression-free survival (PFS) was 11.1 months, and the median overall survival (OS) was not reached after 24 weeks of therapy. Median follow-up was 23.82 months. Subgroup analysis of the CHM cohort (n = 11; 35%) revealed an ORR of 45.5%, a DCR of 54.5%, a median PFS of 10.9 months, and median OS of 20.7 months. Treatment related adverse events were reported in 58.1% of all patients (19.4% grade 3, the remaining grade 1 or 2). PD-L1 expression and CD-8+ T-cell infiltration did not significantly correlate with clinical response, although a trend towards a shorter PFS of 5.6 months was observed with PD-L1 negativity and low CD8+ intratumoral infiltration. CONCLUSION: This study demonstrated robust clinical efficacy of nivolumab in patients with locally advanced and metastatic cSCCs and a tolerability comparable to data of other anti-PD-1 antibodies. Favourable outcomes were obtained despite involving the oldest hitherto reported study cohort for anti-PD-1 antibodies and a significant proportion of CHM patients prone to high risk tumours and an aggressive course otherwise typically excluded from clinical trials.

SAR user guide to the rectal MR synoptic report (primary staging).

Rectal MR is the key diagnostic exam at initial presentation for rectal cancer patients. It is the primary determinant in establishing clinical stage for the patient and greatly impacts the clinical decision-making process. Consequently, structured reporting for MR is critically important to ensure that all required information is provided to the clinical care team. The SAR initial staging reporting template has been constructed to address these important items, including locoregional extent and factors impacting the surgical approach and management of the patient. Potential outputs to each item are defined, requiring the radiologist to commit to a result. This provides essential information to the surgeon or oncologist to make specific treatment deisions for the patient. The SAR Initial Staging MR reporting template has now been officially adopted by the NAPRC (National Accreditation Program for Rectal Cancer) under the American College of Surgery. With the recent revisions to the reporting template, this user guide has been revamped to improve its practicality and support to the radiologist to complete the structured report. Each line item of the report is supplemented with clinical perspectives, images, and illustrations to help the radiologist understand the potential implications for a given finding. Common errors and pitfalls to avoid are highlighted. Ideally, rectal MR interpretation should not occur in a vacuum but in the context of a multi-disciplinary tumor board to ensure that healthcare providers use common terminology and share a solid understanding of the strengths and weaknesses of MR.

Beliefs regarding COVID-19 vaccines among Canadian workers in the intellectual disability sector prior to vaccine implementation.

BACKGROUND: Workers supporting adults with intellectual disabilities (ID) experience significant stress in their essential role during COVID-19 due to the high risk of their clients contracting COVID-19 and having adverse outcomes. The purpose of the current study was to describe the attitudes of workers towards COVID-19 vaccination prior to vaccination rollout, with a view to informing strategies to promote vaccine uptake within this high-risk sector. METHODS: An online survey was sent via email to workers supporting adults with ID in Ontario, Canada, between January 21 and February 3, 2021 by agency leadership and union representatives. RESULTS: Three thousand and three hundred and seventy-one workers, representing approximately 11.2% of Ontario workers supporting adults with ID completed an online survey. Most reported that they were very likely (62%) or likely (20%) to get a COVID-19 vaccine (vaccination intent) although 18% reported they were less likely to do so (vaccination nonintent). Workers with vaccination nonintent were younger and were more likely to endorse the beliefs that (1) it will not benefit them or those around them, (2) it was not part of their job, (3) rapid development confers uncertainties and risks, and (4) they were scared of potential vaccine side effects. CONCLUSIONS: There is need to address common misconceptions among workers supporting adults with ID to help activate them as vaccine advocates in the communities they serve. Partnered efforts between workers, unions and agency leadership with public health experts to address concerns are required.

Molecular diagnosis of polymicrobial brain abscesses with 16S-rDNA-based next-generation sequencing.

OBJECTIVES: Brain abscesses lead to high mortality despite antibiotic and surgical treatment. Identification of causative bacteria is important to guide antibiotic therapy, but culture-based methods and molecular diagnostics by Sanger sequencing of 16S PCR products are hampered by antibiotic treatment and the often polymicrobial nature of brain abscesses. We have applied 16S-rRNA-based next-generation sequencing (NGS) for metagenomic analysis of intracranial abscess (brain and epidural) and meningitis samples. METHODS: Seventy-nine samples from 54 patients with intracranial abscesses or meningitis were included. DNA was subjected to 16S PCR. Amplicons were analysed with the Illumina MiSeq system, sequence reads were blasted versus the NCBI 16S bacterial database and analysed using MEGAN software. Results were compared to those of gram-staining, culture and Sanger sequencing. RESULTS: The NGS workflow was successful for 51 intracranial abscesses (46 brain and five epidural) and nine meningitis samples. Inclusion of (mono)bacterial meningitis samples allowed us to establish a cut-off criterion for the exclusion of contaminating sequences. In total 86 bacterial taxa were identified in brain abscesses by NGS, with Streptococcus intermedius and Fusobacterium nucleatum as most prevalent species; Propionibacterium and Staphylococcus spp. were associated with epidural abscesses. NGS identified two or more bacterial taxa in 31/51 intracranial abscesses, revealing the polymicrobial nature of these infections and allowing the discrimination of up to 16 bacterial taxa per sample. CONCLUSION: These results extend earlier studies showing that NGS methods expand the spectrum of bacteria detected in brain abscesses and demonstrate that the MiSeq platform is suitable for metagenomic diagnostics of this severe infection.

Increased tumour cell PD-L1 expression, macrophage and dendritic cell infiltration characterise the tumour microenvironment of ulcerated primary melanomas.

BACKGROUND: Primary melanoma ulceration is an unfavourable prognostic factor included in current staging systems. Yet, the immunological and molecular alterations responsible for this adverse outcome have not been fully elucidated. OBJECTIVES: We aimed to identify immunological differences between ulcerated and non-ulcerated primary melanomas concerning both innate and adaptive immunity and to correlate these with clinical outcome. METHODS: Formalin-fixed paraffin-embedded primary melanomas from 112 patients (pts) were analysed by immunohistochemistry. The expression of various markers identifying tumour-infiltrating lymphocytes, macrophages and dendritic cells was evaluated semi-quantitatively by three independent investigators. Tumour cell expression of programmed death-ligand 1 (PD-L1), transporter of antigen processing 1 and the MxA protein was also analysed. RESULTS: Recurrence occurred in 21/56 pts (37.5%) with ulcerated vs. 14/56 pts (25.0%) with non-ulcerated tumours (P = 0.15). Tumour ulceration was associated with more frequent development of brain metastasis (17.6 vs. 3.6% of pts, P = 0.015). Immunohistochemistry showed an association of ulceration with the presence of intratumoural CD68+ macrophages (P = 0.028) as well as with increased numbers of intratumoural CD11c+ dendritic cells (P = 0.014) and CD163+ macrophages (P = 0.001). PD-L1 positivity (expression in >1% of tumour cells) was more frequent in ulcerated than non-ulcerated tumours [40 (72.7%) vs. 25 (44.6%), P = 0.003]. A positive correlation between intratumoural CD11c+ (Spearman's correlation coefficient ρ: 0.42) and CD163+ (ρ: 0.31) cell count and frequency of tumour cell PD-L1 expression was detected. CONCLUSIONS: Our results confirm the adverse clinical outcome associated with primary melanoma ulceration, particularly concerning the risk of recurrence and subsequent development of brain metastases. The observed immunological differences suggest a conceivable role of increased intratumoural macrophage and dendritic cell counts associated with enhanced tumour cell PD-L1 expression potentially contributing to the immunosuppressive, growth-promoting microenvironment of ulcerated primary melanomas.

Optical spectroscopy as a diagnostic tool for metal ion beam production with an ECRIS.

At GSI, the CAPRICE ECRIS is used to provide heavy ion beams to the UNILAC (Universal Linear Accelerator) accelerator. In order to satisfy the demand of metal ion beams, a resistively heated oven is routinely used. This evaporation technique allows the ion beam production from natural and enriched solid elements or compounds with high efficiency and low material consumption. Often it is required to provide high charge state ion beams from rare or extremely rare isotopes as 48Ca, e.g., for the investigation of super heavy elements. In order to maintain the ion beam stable for the entire scheduled beam time, the plasma inside the ion source must remain as stable as possible. The tuning of ion source parameters and oven power affecting the oven temperature and, in turn, the evaporation rate is necessary. A strong relationship between the microwave power and the oven heating was observed, thus affecting the power control, the plasma stability, and the material consumption. Hence, it was investigated how an optical spectrometer can be used as a predictive diagnostic tool to detect ion source instabilities. Furthermore, the effect of parasitic oven heating by coupling of microwaves was investigated. Optical emission spectroscopy was performed by analyzing the light from the plasma and from the oven through the extraction aperture. The measurements enabled us to distinguish between resistive heating and microwave heating. The results of this investigation are presented.

Intestinal macrophages in mucosal immunity and their role in systemic lupus erythematosus disease.

Monocytes play an important role in inducing host systemic immunity against invading pathogens and inflammatory responses. After activation, monocytes migrate to tissue sites, where they initiate both innate and adaptive immune responses, and become macrophages. Although mucosal macrophages produce inflammatory cytokines in response to pathogens, the perturbations in innate immune signaling pathway have been implicated in autoimmune diseases such as systemic lupus erythematosus (SLE). In this review, we focus on the role of human macrophages in intestinal innate immune responses, homeostasis, and SLE disease. We further discuss sex differences in the intestinal macrophages and their role in the physiology and pathogenesis of SLE.

A statistical shape model of the left ventricle from real-time 3D echocardiography and its application to myocardial segmentation of cardiac magnetic resonance images.

OBJECT: We present in this paper the application of a statistical shape model of the left ventricle (LV) built from transthoracic real time 3D echocardiography (3DE) to segment the LV endocardium and epicardium in cardiac magnetic resonance (CMR) images. MATERIAL AND METHODS: The LV model was built from a training database constituted by over 9000 surfaces obtained from retrospectively selected 3DE examination of 435 patients with various pathologies. Three-dimensional segmentation of the endocardium and the epicardium was obtained by processing CMR images acquired in 30 patients with a dedicated active shape modelling (ASM) algorithm using the proposed LV model. RESULTS: The segmentation results obtained with the proposed method were compared with those obtained by the manual reference technique; similarity was proven by computing: i) point to surface distance (<2 mm), ii) Dice similarity coefficient (>89%), iii) Hausdorff distance (∼5 mm). This was furthermore confirmed by equivalence testing, linear regression and Bland Altman analysis applied on derived clinical parameters, such as LV volumes and mass. CONCLUSIONS: This study showed the potential usefulness of the proposed inter-modal ASM approach featuring a 3DE-based LV model for the 3D segmentation of the LV myocardium in CMR images.

[Application of vascular replacement technique with allogenic blood vessel in radical resection for pancreatic carcinoma: a report of 33 cases].

Objective: To analyze the application of vascular replacement technique with allogenic blood vessel in radical resection for pancreatic carcinoma. Methods: The clinical data of 33 patients with vascular invasion of pancreatic carcinoma who underwent radical resection from April 2013 to April 2017 in Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital were retrospectively analyzed. There were 14 males and 19 females with age of (62.5±10.6)years(ranging from 35 to 78 years). Vascular replacement technique with allogenic blood vessel was used on all patients who underwent radical resection for pancreatic carcinoma. The operation procedure was made according to the specific location of the carcinoma, and the allogenic blood vessel was selected according to the type of vascular invasion. The matching vessel was selected for replacement to the patient who was invaded only one vessel. And the "Y" type of iliac vein was selected for replacement to the patient who was invaded the confluence of portal vein, splenic vein and superior mesenteric vein. After the operation, the patients were followed up by telephone and outpatient review. Results: All of 33 patients were successfully completed the operations. There were 28 patients underwent pancreaticoduodenectomy with vascular replacement, and 5 patients underwent total pancreatectomy with vascular replacement. All the patients were confirmed pancreatic carcinoma and R0 resection according to the postoperative pathology. There were 16 patients with the carcinoma invasion the confluence of portal vein, splenic vein and superior mesenteric vein, 12 patients with the carcinoma invasion the superior mesenteric vein, and 5 patients with the carcinoma invasion the portal vein. There was no perioperative death in this group and no complications related to allogenic blood vessel. The incidence of postoperative complications was 18.2% (6/33), and the incidence of pancreatic fistula was 6.1% (2/33), all of which were biochemical fistula. There were 32 patients were followed up, and the follow-up rate was 96.9%. The median survival time was 14.6 months. The half-year, 1-year and 2-year survival rates were 75.6%, 37.6% and 27.4%. Conclusion: The application of vascular replacement technique with allogenic blood vessel for pancreatic carcinoma has a great significance for improving the R0 resection rate and the prognosis of patients.

Targeted sequencing of ABCA7 identifies splicing, stop-gain and intronic risk variants for Alzheimer disease.

Several variants in the gene ABCA7 have been identified as potential causal variants for late-onset Alzheimer's disease (LOAD). In order to replicate these findings, and search for novel causal variants, we performed targeted sequencing of this gene in cohorts of non-Hispanic White (NHW) and African-American (AA) LOAD cases and controls. We sequenced the gene ABCA7 in 291 NHW LOAD cases and 103 controls. Variants were prioritized for rare, damaging variants and previously reported variants associated with LOAD, and were follow-up genotyped in 4076 NHW and 1157 AA cases and controls. We confirm three previously associated ABCA7 risk variants and extend two of these associations to other populations, an intronic variant in NHW (P=3.0×10-3) (originally reported in a Belgian population), and a splice variant originally associated in the Icelandic population, which was significantly associated in the NHW cohort (P=1.2×10-6) and nominally associated in the AA cohort (P=0.017). We also identify a 3'-UTR splice variant that segregates in four siblings of one family and is nominally associated with LOAD (P=0.040). Multiple variants in ABCA7 contribute to LOAD risk.

Cross-sectional study on allergic sensitization of Austrian adolescents using molecule-based IgE profiling.

BACKGROUND: Allergen-specific IgE antibodies are a hallmark of type I allergy. The aim of this cross-sectional study was to analyze the sensitization profiles of an Austrian adolescent population utilizing molecule-based IgE diagnosis. METHODS: Serum samples of 501 nonselected pupils from Salzburg, Austria, were tested in ImmunoCAP ISAC® for IgE reactivity to 112 single allergens. Sensitization profiles were assessed and statistically coordinated with reported allergies. RESULTS: In the population aged 12-21 years, 53.5% showed IgE reactivity to at least one allergen tested. The highest prevalence was found for Phl p 1 from grass pollen (26.5%), group 2 mite allergens (18.2%), Bet v 1 from birch pollen (16.3%) and Fel d 1 from cat (14.4%). The majority of participants showed a complex sensitization profile and reacted on average to 9 allergens. Pollen sensitization was highly prevalent (41.7%) and mainly driven by group I grass and PR-10 allergens of the Betulaceae family, while Pla l 1 represented the most relevant weed. Diagnosed and self-reported allergies were noted in 21.9% and 45.5% of participants, respectively, and correlated well with in vitro results. Among atopic individuals, 71.4% reported to suffer from at least one allergy; concordance was found for grass and cat sensitization, while venom- and weed pollen-positive individuals were frequently asymptomatic. CONCLUSIONS: More than half of the tested adolescent population had already established an atopic status presenting a complex IgE reactivity profile dominated by pollen sensitization. Detailed molecule-based analysis allows determining relevant biomarkers and monitoring of the atopic status in populations.

Food-induced anaphylaxis and cofactors - data from the anaphylaxis registry.

Food allergens are frequent causes of anaphylaxis. In particular in children and adolescents they are the most frequent elicitors of severe allergic reactions, and in adults food allergens rank third behind insect venom and drugs. Since July 2006 severe allergic reactions from Germany, Austria, and Switzerland are collected in the anaphylaxis registry. Currently 78 hospitals and private practises are connected. From July 2006 until February 2009 1,156 severe allergic reactions were registered. Among children and adolescents (n = 187, age range from 3 months to 17 years) food allergens were the most frequent triggers, comprising 58% of cases. In the adult group (n = 968, 18 - 85 years) food allergens were in the third position (16.3%) behind insect venom and drugs. In children legumes (31%) and in particular peanuts were frequently responsible food allergens, followed by tree nuts (25%) with hazelnut being the most frequent elicitor. In adults fruits (13.4%) most often induced severe food-dependent anaphylaxis, but also animal products (12.2%); among these most frequently crustaceans and molluscs. Cofactors were often suspected in food-dependent anaphylaxis, namely in 39% of the adult group and in 14% of the pediatric group. In adults drugs (22%) and physical activity (10%) were reported to be the most frequent cofactors, in children physical activity was suspected in 8.7% and drugs in 2.6%. Concomitant diseases like atopic dermatitis, allergic asthma, or allergic rhinoconjunctivitis were reported in 78% of children and adolescents and in 67% of the adults. In conclusion, food-induced anaphylaxis, its cofactors and concomitant diseases are age-dependent. The data offers to identify risk factors of anaphylaxis.

Epidural Versus Paravertebral Nerve Block for Postoperative Analgesia in Patients Undergoing Open Liver Resection: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Although many studies have found no difference between thoracic epidural block and unilateral thoracic paravertebral block after thoracotomy, no previous studies have compared epidural block with bilateral thoracic paravertebral block (bTPVB) in patients undergoing open liver resection. We aimed to investigate whether there was a significant analgesic advantage of thoracic epidural over bTPVB after liver resection. METHODS: This randomized, prospective, open-label study included adult patients undergoing elective open liver resection. Patients were randomized to receive either thoracic epidural block or bTPVB, through which ropivacaine (0.2%) was infused for 3 days. The primary outcome was pain Verbal Rating Scale (VRS) score (0-10) at rest and with postoperative incentive spirometry. Secondary outcomes included VRS at rest, inspired volumes during incentive spirometry, patient-controlled analgesia hydromorphone utilization, measures of hemodynamic stability, and postoperative bowel function. RESULTS: Eighty patients completed the study and received thoracic epidural block (n = 41) or bTPVBs (n = 39). No catheter-related complications were noted. The primary outcome, pain (VRS) with incentive spirometry, was significantly lower in the epidural group (epidural vs bTPVB, mean [SD]) (4.5 [2.7] vs 5.4 [2.7] at 24 hours postoperatively, and 3.2 [2.1] vs 4.6 [2.4] at 48 hours postoperatively). Maximal inspired volumes at 24 hours postoperatively (917 [379] vs 1042 [468] mL) and cumulative utilization of patient-controlled analgesia hydromorphone during the first 48 hours postoperatively (10.7 [7.9] vs 13.6 [8.5] mg) were not significantly different between groups. Decrease in mean arterial pressure from baseline at 24 hours postoperatively was greater for the epidural group (-12.6 [15.8] vs -3.8 [16.2]; P = 0.016). CONCLUSIONS: This study suggests that there is a modest analgesic advantage of thoracic epidural over bTPVBs for patients after open liver resection.

Inactivation of Salmonella enteritidis on shell eggs by coating with phytochemicals.

Salmonella enteritidis (SE) is a major foodborne pathogen that causes human infections largely by consumption of contaminated eggs. The external surface of eggs becomes contaminated with SE from multiple sources, highlighting the need for effective egg surface disinfection methods. This study investigated the efficacy of three GRAS-status, phytochemicals, namely carvacrol (CR), eugenol (EG), and ß-resorcylic acid (BR) applied as pectin or gum arabic based coating for reducing SE on shell eggs. White-shelled eggs, spot inoculated with a 5-strain mixture of nalidixic acid (NA) resistant SE (8.0 log CFU/mL) were coated with pectin or gum arabic solution containing each phytochemical (0.0, 0.25, 0.5, or 0.75%), and stored at 4°C for 7 days. SE on eggs was enumerated on days 0, 1, 3, and 7 of storage. Approximately 4.0 log CFU/egg of SE was recovered from inoculated and pectin or gum arabic coated eggs on day 0. All coating treatments containing CR and EG, and BR at 0.75% reduced SE to undetectable levels on day 3 (P < 0.05). Results suggest that the aforementioned phytochemicals could effectively be used as a coating to reduce SE on shell eggs, but detailed studies on the sensory and quality attributes of coated eggs need to be conducted before recommending their use.

Investigation of pulsed mode operation with the frequency tuned CAPRICE ECRIS.

In order to increase the intensity of the highly charged ions produced by the Electron Cyclotron Resonance Ion Sources (ECRISs), techniques like the frequency tuning and the afterglow mode have been developed and in this paper the effect on the ion production is shown for the first time when combining both techniques. Recent experimental results proved that the tuning of the operating frequency of the ECRIS is a promising technique to achieve higher ion currents of higher charge states. On the other hand, it is well known that the afterglow mode of the ECRIS operation can provide more intense pulsed ion beams in comparison with the continuous wave (cw) operation. These two techniques can be combined by pulsing the variable frequency signal driving the traveling wave tube amplifier which provides the high microwave power to the ECRIS. In order to analyze the effect of these two combined techniques on the ion source performance, several experiments were carried out on the pulsed frequency tuned CAPRICE (Compacte source A Plusiers Résonances Ionisantes Cyclotron Electroniques)-type ECRIS. Different waveforms and pulse lengths have been investigated under different settings of the ion source. The results of the pulsed mode have been compared with those of cw operation.

Ion beam emittance from an ECRIS.

Simulation of ion beam extraction from an Electron Cyclotron Resonance Ion Source (ECRIS) is a fully 3 dimensional problem, even if the extraction geometry has cylindrical symmetry. Because of the strong magnetic flux density, not only the electrons are magnetized but also the Larmor radius of ions is much smaller than the geometrical dimension of the plasma chamber (Ø 64 × 179 mm). If we assume that the influence of collisions is small on the path of particles, we can do particle tracking through the plasma if the initial coordinates of particles are known. We generated starting coordinates of plasma ions by simulation of the plasma electrons, accelerated stochastically by the 14.5 GHz radio frequency power fed to the plasma. With that we were able to investigate the influence of different electron energies on the extracted beam. Using these assumptions, we can reproduce the experimental results obtained 10 years ago, where we monitored the beam profile with the help of viewing targets. Additionally, methods have been developed to investigate arbitrary 2D cuts of the 6D phase space. To this date, we are able to discuss full 4D information. Currently, we extend our analysis tool towards 5D and 6D, respectively.