Final results of the real-life observational VICTOR-6 study on metronomic chemotherapy in elderly metastatic breast cancer (MBC) patients.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

The largest prehistoric mound in Europe is the Bronze-Age Hill of Udine (Italy) and legend linked its origin to Attila the Hun.

Prehistoric monuments often constitute evident landmarks and sometimes, after falling into disuse, fascinated local people enough to stimulate speculations about their origin over time. According to legend, the Hill of Udine (NE Italy) was built by Attila the Hun's soldiers, but its origin (natural or anthropogenic) has been debated until now. Our research analyzed five new 40-m long stratigraphic cores, investigating for the first time the total thickness of the hill and compared the data with the available archaeological information. Moreover, we considered other hills and mounds in northern Italy and other European regions where folklore traditions relate their origin to Attila. The geoarchaeological and ethnographic data prove that the Hill of Udine is a Bronze Age anthropogenic mound erected between 1400 and 1150 BCE and that, later, folklore has transformed the ancestral memory of its origin into legend. By measuring 30 m in height and over 400,000 m3 in volume, the flat-topped hill is the largest prehistoric mound in Europe. This discovery reveals unprecedented skills in earth construction and confirms significant anthropogenic modifications of the environment during Bronze Age.

Global Cushing's disease epidemiology: a systematic review and meta-analysis of observational studies.

PURPOSE: Cushing's disease (CD), 70% of endogenous hypercortisolism cases, is a rare disease caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. To date, no systematic reviews and meta-analyses on its global epidemiology have been published. We provide a systematic review and meta-analysis of CD global epidemiology, also evaluating the quality of study reporting for the identified studies. METHODS: MEDLINE and EMBASE databases were searched for studies on CD epidemiology from inception until November 30th, 2020, including original observational studies in English about CD prevalence and/or incidence for well-defined geographic areas. Two reviewers independently extracted data and assessed reporting quality. CD prevalence/incidence pooled estimates were derived from a random-effects meta-analysis. Reporting quality was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases, heterogeneity using the Cochran's Q-test and its derived measure of inconsistency (I2). RESULTS: Thirteen studies were included. The pooled CD prevalence was 2.2 [95% CI 1.1-4.8] per 100,000, while the incidence rate was 0.24 [95% CI 0.15-0.33] per 100,000 person-years. For both parameters, considerable between-studies heterogeneity was found (I2 = 78.8% and 87.8%, respectively). The quality of study reporting was rated as medium for 11 (84.6%) studies and as low for 2 (15.4%). CONCLUSION: Overall, our systematic meta-analysis demonstrated CD epidemiology to be similarly reported across different areas of the world, with some exceptions regarding regional differences or observation period intervals. Keeping into account the methodological differences between each paper, large-scale studies on CD epidemiology are warranted. Setting up national specific registries, based on standardized diagnostic and clinical parameters, with clearly defined selection and analysis criteria, and a strong cooperation between the scientific national societies for endocrinology is crucial to exclude other causes of variability (i.e. geographical differences due to other factors like (epi)genetic changes), and to support public health decision making.

Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.

PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients.

BACKGROUND: Proton-pump-inhibitors (PPIs) are frequently prescribed for the management of anticancer drug-related gastrointestinal symptoms. Palbociclib is a weak base with pH-dependent solubility and potential drug-drug interaction at the absorption level may affect clinical pharmacokinetics. The current study was aimed at investigating the effect of co-administration of PPIs and palbociclib on progression-free survival (PFS) in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: Patients affected by estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, who were candidates for first-line treatment with palbociclib, were enrolled in this retrospective observational study. Patients were defined as 'no concomitant PPIs' if no PPIs were administered during palbociclib treatment, and as 'concomitant PPIs' if the administration of PPIs covered the entire or not less than two-thirds of treatment with palbociclib. All clinical interventions were made according to clinical practice. RESULTS: A total of 112 patients were enrolled in the study; 56 belonged to the 'no concomitant PPIs' group and 56 to the 'concomitant PPIs' group. Seventy-one patients were endocrine-sensitive and received palbociclib and letrozole, and 43 were endocrine-resistant and were treated with palbociclib and fulvestrant. The most prescribed PPI was lansoprazole. Patients taking PPIs had a shorter PFS than those taking palbociclib and endocrine therapy alone (14.0 versus 37.9 months, P < 0.0001). Multivariate analysis confirmed concomitant PPIs as the only independent predictive factor for shorter PFS (P = 0.0002). PFS was significantly longer in estrogen-sensitive mBC with no concomitant PPIs compared with patients taking PPIs or estrogen-resistant patients, with and without PPIs (P < 0.0001). No correlation with adverse events was found when considering grade >2 hematological toxicities [Common Terminology Criteria for Adverse Events (CTCAE) scale]. CONCLUSIONS: The present study demonstrates that concomitant use of PPIs in mBC patients treated with palbociclib has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPIs with caution in these patients, strictly adhering to the indications in the summary of product characteristics (RCP).

Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE.

BACKGROUND: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. PATIENTS AND METHODS: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. CONCLUSIONS: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.

Transcriptomes of the interaction between Fusarium verticillioides and a Streptomyces strain reveal the fungal defense strategy under the pressure of a potential biocontrol agent.

The actinobacteria Streptomyces sp. AV05 appears to be a potential biocontrol agent (BCA) against mycotoxigenic fungi. It was found to significantly inhibit F. verticillioides growth and mycotoxin production during their co-cultivation. F. verticillioides growth was durably affected while the decrease of the toxin production levels was reversible, suggesting different BCA actions. The study of both transcriptomes brought useful information on the microbial interaction. RNA-seq data indicated that the dual interaction modified genetic expression of both microorganisms as 18.5 % of the genes were differentially expressed for the fungus against 3.8 % for the actinobacteria. Fungal differentially expressed genes (DEGs) were equally up and down regulated while bacterial ones were mainly upregulated. We especially focused the analysis of DEGs on fungal defense reaction to bacterial attack. For example, if this potential BCA implements a strategy of antibiosis with the over expression of 'siderophore-interacting protein' linked to the production of bacteriocins, the fungus in a state of stress is able to adapt its metabolism by up-regulation of amidase. It could correspond to the induction of resistance gene clusters and suggest a detoxification process. Moreover fumonisins-related pathway appears underexpressed in the presence of Streptomyces that explain the reduction of fumonisin accumulation observed.

Liposomes embedded with differentiating factors as a new strategy for enhancing DPSC osteogenic commitment.

Human dental pulp stem cell (DPSC) differentiation toward the osteoblastic phenotype is enhanced when culture media are supplemented with differentiating factors, i.e. ascorbic acid, ß-glycerophosphate and dexamethasone. Liposomes, spherical vesicles formed by a phospholipid bilayer, are frequently used as carriers for drugs, growth factors and hydrophobic molecules. The aim of this work was to speed up DPSC commitment to the osteogenic lineage by embedding differentiating factors within liposomes. Firstly, liposomes were prepared by rehydrating a phospholipidic thin film and characterised in terms of dimensions. Secondly, liposome-exposed DPSCs were characterised by their immunophenotypic profile. Levels of CD90 were significantly decreased in the presence of liposomes filled with ascorbic acid, ß-glycerophosphate and dexamethasone (Lipo-Mix) with respect to normal differentiation medium (DM), while CD73 and CD29 expression were enhanced, suggesting osteogenic commitment. Additionally, an appreciable extracellular matrix deposition is detected. Thirdly, the Lipo-Mix formulation better increases alkaline phosphatase activity and levels of Collagen I secretion with respect to DM. In parallel, the new liposome formulation is capable of decreasing the release of H2O2 and of triggering a precocious antioxidant cell response, redressing the redox balance required upon mesenchymal stem cell commitment to osteogenesis. It can be therefore hypothesised that Lipo-Mix could represent a suitable tool for clinical regenerative purposes in the field of tissue engineering by speeding up DPSC osteogenic commitment, mineralised matrix deposition and remodelling.

Electrostimulation of hyperthermophile Thermotoga neapolitana cultures.

Hyperthermophile bioelectrochemical systems are seldom investigated although their superior control of microbial consortium and thermodynamic advantages. Hyperthermophilic Thermotogales, for instance, are able to produce hydrogen and lactic acid from wastes better than mesophilic bacteria. Here, the electrostimulation of Thermotoga neapolitana in single-chamber electrochemical bioreactors is studied. The glucose fermentation under CO2 pressure, as model metabolism, was tested at 80 °C. Results show that a dynamic polarization (±0.8 to ±1.2 V) drives glucose fermentation and biofilm stasis on electrodes. Under this condition, production of lactic acid (33 vs 12 mM) and yields of acetate and hydrogen (with lactic/acetic acid ratio of 1.18) were higher than those achieved with static polarization or open-circuit. Dynamic polarization is possibly exploitable to stimulate T. neapolitana in a hyperthermophile electrochemical system for various applications including control of power-to-gas processes or production of value-added products (hydrogen and lactic acid) from sugary wastes.

Bickerstaff's brainstem encephalitis in childhood: a literature overview.

OBJECTIVE: This is a review on clinical presentation, diagnosis, and treatment of reported cases of Bickerstaff brain encephalitis. MATERIALS AND METHODS: Cases of pediatric Bickerstaff's brainstem encephalitis collected from PubMed, Cochrane Library and Scopus Web of Science databases were reviewed. The inclusion criteria of the cases were based on age ≤ 18 years and the clinical characteristics of the disorder. RESULTS: Twenty-seven articles on Bickerstaff's brainstem encephalitis, including 236 children from a total of 42 from January 1990 to January 2020, were selected. The phenotype of the pediatric cases confirmed those described in the previously published articles. Almost half of the cases demonstrated the positivity of anti-GQ1b antibody titers, but the antibodies' presence was not linked to longer healing time. However, it was found that individuals with neuroimaging changes needed a longer time to recovery. Overall, patients treated with any type of immunotherapy (intravenous immunoglobulins, steroid or plasmapheresis) demonstrated faster resolution of symptoms than supportive care. CONCLUSIONS: Bickerstaff's brainstem encephalitis is an uncommon disorder, the short-term and long-term prognoses depend on the clinical presentation of the disorder, co-morbidity, instrumental investigations, and precocity of treatment.

Primary headache in childhood associated with psychiatric disturbances: an update.

OBJECTIVE: Primary headache disorders in children are one of the most prominent topics in the pediatric neurology literature. However, there are many unsolved aspects, including the conditions associated with migraine. The present study aims to report on the frequency of behavioral comorbidities in the setting of primary headache in childhood. PATIENTS AND METHODS: In this study, we enlisted 475 children (290 males and 185 females; ratio 1.6:1), aged 4 to 14 years, who were affected by primary headache. In direct interviews, children and parents gave information on the association of their headache with, attention-deficit/hyperactivity disorder, learning disabilities, tics, anxiety, depression, and obsessive-compulsive disorder. Other 475 children with no history of headache or recognized neurological conditions were matched for age, sex, race, and socioeconomic status and were used as controls. RESULTS: A significant association of primary headache was found with anxiety and depression (p-value <0.001); overall, behavioral disorders were more common in children who experienced headache than in controls (p-value <0.001). CONCLUSIONS: Primary headache in children is not associated with most of the common behavioral conditions. On the contrary, there was a significant association with anxiety and depression, as reported in adults.

Mid-transverse colon cancer and extended versus transverse colectomy: Results of the Italian society of surgical oncology colorectal cancer network (SICO CCN) multicenter collaborative study.

INTRODUCTION: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. MATERIALS AND METHODS: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. RESULTS: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). CONCLUSIONS: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.

Interobserver and intraobserver reliability of a new radiological classification for femoroacetabular impingement syndrome.

PURPOSE: Radiological evaluation of femoroacetabular impingement is based on single-plane parameters such as the alpha angle or the center edge angle, or complex software reconstruction. A new simple classification for cam and pincer morphologies, based on a two-plane radiological evaluation, is presented in this study. The determination of the intraobserver and interobserver reliability of this new classification is the purpose of this study. METHODS: We retrospectively reviewed the three-view hip study in patient undergoing hip arthroscopy for FAI syndrome between October 2015 and April 2016. Any case having protrusio acetabuli, coxa profunda or which has undergone previous osteotomic surgery was excluded. Five observers used our proposed classification to identify three different stages for the cam and pincer morphologies. Inter- and intraobserver agreement of classification was determined using average pairwise Cohen's kappa coefficient. RESULTS: The interobserver agreement for the pincer and cam morphologies was excellent. For the pincer morphology classification, the average Kappa agreement was 0.838 (range 0.764-0.944). For the cam morphology, the average pairwise Cohen's kappa coefficient was 0.846 (range 0.734-0.929). The intraobserver agreement was excellent as well. The average percent pairwise agreement was 0.870 and 0.845 for pincer and cam type, respectively. CONCLUSIONS: The new classification system shows excellent levels of inter- and intraobserver agreement for both deformities. This classification is demonstrated to be a useful tool in planning hip arthroscopy. Further studies are needed to correlate the classification itself with specific intraoperative findings.

Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Survival prediction models in motor neuron disease.

BACKGROUND AND PURPOSE: This study aimed to assess the predictive value of multimodal brain magnetic resonance imaging (MRI) on survival in a large cohort of patients with motor neuron disease (MND), in combination with clinical and cognitive features. METHODS: Two hundred MND patients were followed up prospectively for a median of 4.13 years. At baseline, subjects underwent neurological examination, cognitive assessment and brain MRI. Grey matter volumes of cortical and subcortical structures and diffusion tensor MRI metrics of white matter tracts were obtained. A multivariable Royston-Parmar survival model was created using clinical and cognitive variables. The increase of survival prediction accuracy provided by MRI variables was assessed. RESULTS: The multivariable clinical model included predominant upper or lower motor neuron presentations and diagnostic delay as significant prognostic predictors, reaching an area under the receiver operating characteristic curve (AUC) of a 4-year survival prediction of 0.79. The combined clinical and MRI model including selected grey matter fronto-temporal volumes and diffusion tensor MRI metrics of the corticospinal and extra-motor tracts reached an AUC of 0.89. Considering amyotrophic lateral sclerosis patients only, the clinical model including diagnostic delay and semantic fluency scores provided an AUC of 0.62, whereas the combined clinical and MRI model reached an AUC of 0.77. CONCLUSION: Our study demonstrated that brain MRI measures of motor and extra-motor structural damage, when combined with clinical and cognitive features, are useful predictors of survival in patients with MND, particularly when a diagnosis of amyotrophic lateral sclerosis is made.

Serum vitamin D deficiency in subjects with severe acquired brain injury and relationship with functional severity.

BACKGROUND: Vitamin D may be important for the development and function of the nervous system. Low serum vitamin D levels have been detected in several neurological diseases. OBJECTIVE: To ascertain the relationship between 25(OH)D serum level and disability in subjects with severe acquired brain injury (sABI). DESIGN: Prospective cross-sectional study Methods: Consecutive subjects with sABI admitted to neuro-rehabilitation were enrolled. A sample of subjects from the neurological ward was considered the control group. Vitamin D serum levels and blood parameters were measured at admission. Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS), and Level of Cognitive Functioning (LCF) were used in assessing disability. RESULTS: A total of 104 subjects (34 F, 70 M; mean age 53.9 ± 15.2 years) were enrolled: 54 (19 F, 35 M) with sABI and 50 (15 F, 35 M) subjects as control group. Deficient mean serum levels of vitamin D (19.2 ± 9.4 ng/mL) were detected in the subjects with sABI and a significant inverse correlation between vitamin D serum levels and DRS score was detected (p = 0.04). CONCLUSION: Subjects with sABI showed vitamin D deficiency that might correlate to disability severity. The reason is unclear and might represent a secondary phenomenon resulting from the inflammatory process.

AEgIS at ELENA: outlook for physics with a pulsed cold antihydrogen beam.

The efficient production of cold antihydrogen atoms in particle traps at CERN's Antiproton Decelerator has opened up the possibility of performing direct measurements of the Earth's gravitational acceleration on purely antimatter bodies. The goal of the AEgIS collaboration is to measure the value of g for antimatter using a pulsed source of cold antihydrogen and a Moiré deflectometer/Talbot-Lau interferometer. The same antihydrogen beam is also very well suited to measuring precisely the ground-state hyperfine splitting of the anti-atom. The antihydrogen formation mechanism chosen by AEgIS is resonant charge exchange between cold antiprotons and Rydberg positronium. A series of technical developments regarding positrons and positronium (Ps formation in a dedicated room-temperature target, spectroscopy of the n=1-3 and n=3-15 transitions in Ps, Ps formation in a target at 10 K inside the 1 T magnetic field of the experiment) as well as antiprotons (high-efficiency trapping of [Formula: see text], radial compression to sub-millimetre radii of mixed [Formula: see text] plasmas in 1 T field, high-efficiency transfer of [Formula: see text] to the antihydrogen production trap using an in-flight launch and recapture procedure) were successfully implemented. Two further critical steps that are germane mainly to charge exchange formation of antihydrogen-cooling of antiprotons and formation of a beam of antihydrogen-are being addressed in parallel. The coming of ELENA will allow, in the very near future, the number of trappable antiprotons to be increased by more than a factor of 50. For the antihydrogen production scheme chosen by AEgIS, this will be reflected in a corresponding increase of produced antihydrogen atoms, leading to a significant reduction of measurement times and providing a path towards high-precision measurements.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

On Molière and Fermi-Eyges scattering theories in hadrontherapy.

We consider the evaluation of lateral spread distributions of charged particle beams at therapeutic energies, due to an absorber in the form of a homogeneous slab or of a stack. We show that the Molière theory has the same degree of flexibility as the Fermi-Eyges, but is much more accurate and does not present particular computing difficulties with the energy loss formula we have employed. It is also shown that the non-Gaussian shape of the projected one dimensional (1D) distributions is not a complication for passing from the projected to the spatial two-dimensional (2D) distribution, if one assumes circular symmetry. All the calculations are compared with the results of the FLUKA code. The nuclear interaction is not considered here, because it is outside of the scope of this work.