Design of additively manufactured moulds for expanded polymers

The traditional tools used in steam-chest moulding technologies for the shaping of expanded polymers can be replaced today by lighter moulds, accurately designed and produced exploiting the additive manufacturing technology. New paradigms have to be considered for mould design, assuming that additive manufacturing enables the definition of different architectures that are able to improve the performance of the moulding process. This work describes the strategies adopted for the design and manufacturing by Laser powder bed fusion of the moulds, taking into specific consideration their functional surfaces, which rule the heat transfer to the moulded material, hence the quality of the products and the overall performance of the steamchest process. The description of a case study and the comparison between the performance of the traditional solution and the new moulds are also presented to demonstrate the effectiveness of the new approach. This study demonstrates that the redesign and optimization of the mould shape can lead to a significant reduction of the energy demand of the process, thanks to a homogeneous delivery of the heating steam throughout the part volume, which also results in a remarkable cutting of the cycle time

Disarming the guarded prognosis: predicting survival in newly referred patients with incurable cancer

People affected by cancer want information about their prognosis but clinicians have trouble estimating and talking about it. We sought to determine the nature and accuracy of medical oncologists' estimates of life expectancy in newly referred patients with incurable cancer. With reference to each patient, medical oncologists estimated how long they thought 90, 50, and 10% of similar patients would live. These proportions were chosen to reflect worst case, predicted, and best case scenarios suitable for discussions. After a median follow-up of 35 months, 86 of the 102 patients had died with an observed median survival of 12 months. Oncologists' estimates of each patient's worst case, predicted and best case scenarios were well-calibrated: 10% of patients lived for fewer months than estimated for the worst 10% of similar patients; 50% lived for at least as long as estimated for 50% of similar patients (predicted survival), and 17% lived for more months than estimated for the best 10% of similar patients. Oncologists' estimates of each patient's predicted survival were imprecise: 29% were within 0.67–1.33 times the patient's actual survival, 35% were too optimistic (>1.33 times the actual survival), and 39% were too pessimistic (<0.67 times the actual survival). The proportions of patients with actual survival times bounded by simple multiples of their predicted survival were as follows: 61% between half to double their predicted, 6% at least three to four times their predicted, and 4% no more than 1/6 of their predicted; similar to the proportions in an exponential distribution (about 50%, 10% and 10% respectively). Ranges based on simple multiples of the predicted survival time appropriately convey prognosis and its uncertainty in newly referred people with incurable cancer

ASO Author Reflections: The Liver-First Approach: A New Standard for Patients with Multiple Bilobar Colorectal Metastases?

The best surgical strategy for patients with colorectal cancer and synchronous liver metastases is a matter of endless debate. Technical and oncological issues must be considered but have often been confounded. In 2006, Mentha et al.1 proposed an innovative and convincing oncosurgical approach, whereby they reversed the strategy, focusing attention on the prognostically most relevant target, i.e. the liver. Even if appealing, the liver-first approach struggled to find its role and failed to demonstrate a benefit, except for the inclusion of chemoradiotherapy in the treatment schedule of patients with locally advanced rectal tumors. The proposers themselves reported non-inferiority (and not superiority) of the reverse strategy in comparison with the standard primary-first approach.2 A recent network meta-analysis ranked the liver-first approach as the best treatment option for its relative efficacy based on 5-year overall survival outcomes,3 but the evidence is too weak to impact current clinical practice

A strongly magnetized pulsar within grasp of the Milky Way's supermassive black hole

The center of our Galaxy hosts a supermassive black hole, Sagittarius (Sgr) A*. Young, massive stars within 0.5 pc of SgrA* are evidence of an episode of intense star formation near the black hole a few Myr ago, which might have left behind a young neutron star traveling deep into SgrA*'s gravitational potential. On 2013 April 25, a short X-ray burst was observed from the direction of the Galactic center. Thanks to a series of observations with the Chandra and the Swift satellites, we pinpoint the associated magnetar at an angular distance of 2.4+/-0.3 arcsec from SgrA*, and refine the source spin period and its derivative (P=3.7635537(2) s and \dot{P} = 6.61(4)x10^{-12} s/s), confirmed by quasi simultaneous radio observations performed with the Green Bank (GBT) and Parkes antennas, which also constrain a Dispersion Measure of DM=1750+/-50 pc cm^{-3}, the highest ever observed for a radio pulsar. We have found that this X-ray source is a young magnetar at ~0.07-2 pc from SgrA*. Simulations of its possible motion around SgrA* show that it is likely (~90% probability) in a bound orbit around the black hole. The radiation front produced by the past activity from the magnetar passing through the molecular clouds surrounding the Galactic center region, might be responsible for a large fraction of the light echoes observed in the Fe fluorescence features.Comment: ApJ Letters in pres

Process development and validation of expanded regulatory T cells for prospective applications: an example of manufacturing a personalized advanced therapy medicinal product

Background: A growing number of clinical trials have shown that regulatory T (Treg) cell transfer may have a favorable effect on the maintenance of self-tolerance and immune homeostasis in different conditions such as graft-versus-host disease (GvHD), solid organ transplantation, type 1 diabetes, and others. In this context, the availability of a robust manufacturing protocol that is able to produce a sufficient number of functional Treg cells represents a fundamental prerequisite for the success of a cell therapy clinical protocol. However, extended workflow guidelines for nonprofit manufacturers are currently lacking. Despite the fact that different successful manufacturing procedures and cell products with excellent safety profiles have been reported from early clinical trials, the selection and expansion protocols for Treg cells vary a lot. The objective of this study was to validate a Good Manufacturing Practice (GMP)-compliant protocol for the production of Treg cells that approaches the whole process with a risk-management methodology, from process design to completion of final product development. High emphasis was given to the description of the quality control (QC) methodologies used for the in-process and release tests (sterility, endotoxin test, mycoplasma, and immunophenotype). Results: The GMP-compliant protocol defined in this work allows at least 4.11 7 109 Treg cells to be obtained with an average purity of 95.75 \ub1 4.38% and can be used in different clinical settings to exploit Treg cell immunomodulatory function. Conclusions: These results could be of great use for facilities implementing GMP-compliant cell therapy protocols of these cells for different conditions aimed at restoring the Treg cell number and function, which may slow the progression of certain diseases

Terminal ileum ileoscopy and histology in patients undergoing high-definition colonoscopy with virtual chromoendoscopy for chronic nonbloody diarrhea : a prospective, multicenter study

Background and aims: Ileo-colonoscopy is the procedure of choice for chronic nonbloody diarrhea (CNBD) of unknown origin. Histological evaluation at different colonic sites is mandatory to assess the presence of microscopic colitis. However, the value of routine ileal biopsy on normal-appearing mucosa as assessed by means of standard-resolution white-light ileoscopy is controversial given its reported low diagnostic yield. Hence, we have assessed for the first time the accuracy of retrograde ileoscopy using high-definition and dyeless chromoendoscopy (HD + DLC), thereby calculating the impact and cost of routine ileal biopsy in CNBD. Methods: Patients with CNBD of unknown origin were prospectively enrolled for ileo-colonoscopy with HD + DLC at five referral centers. Multiple biopsies were systematically performed on each colorectal segment and in the terminal ileum for histopathological analysis. Results: Between 2014 and 2017, 546 consecutive patients were recruited. Retrograde ileoscopy success rate was 97.6%. A total of 492 patients (mean age: 53 \ub1 18 years) fulfilled all the inclusion criteria: Following endoscopic and histopathological work-up, 7% had lymphoid nodular hyperplasia and 3% had isolated ileitis. Compared to the histopathology as the gold standard, retrograde ileoscopy with HD + DLC showed 93% sensitivity, 98% specificity and 99.8% negative predictive value. In patients with normal ileo-colonoscopy, ileum histology had no diagnostic gain and resulted in a cost of US $26.5 per patient. Conclusions: Retrograde ileoscopy with HD + DLC predicts the presence of ileitis in CNBD with excellent performance. The histopathological evaluation of the terminal ileum is the gold standard for the diagnostic assessment of visible lesions but has no added diagnostic value in CNBD patients with negative ileo-colonoscopy inspection using modern endoscopic imaging techniques

Retinal vascular impairment in Wolfram syndrome: an optical coherence tomography angiography study

To evaluate differences in macular and optic disc circulation in patients affected by Wolfram Syndrome (WS) employing optical coherence tomography-angiography (OCTA) imaging. In this retrospective study, 18 eyes from 10 WS patients, 16 eyes of 8 patients affected by type I diabetes and 17 eyes from 17 healthy controls were enrolled. All patients were imaged through OCT and OCTA and vascular parameters, as perfusion density (PD) and vessel length density (VLD) were measured. OCTA showed reduced PD in WS patients at the macular superficial capillary plexus (SCP, 27.8 ± 5.3%), deep vascular complex (DVC, 33.2 ± 1.9%) and optic nerve head (ONH, 21.2 ± 9.1%) compared to both diabetic patients (SCP 33.9 ± 1.9%, P &lt; 0.0001; DVC 33.2 ± 0.7%, P = 1.0; ONH 33.9 ± 1.3, P &lt; 0.0001) and healthy controls (SCP 31.6 ± 2.5, P = 0.002; DVC 34.0 ± 0.7%, P = 0.089; ONH 34.6 ± 0.8%, P &lt; 0.0001). Similarly, VLD was lower in WS patients at the SCP (10.9 ± 2.7%) and ONH levels (7.5 ± 4.1%) compared to diabetic patients (SCP 13.8 ± 1.2%, P = 0.001; DVC 13.8 ± 0.2%, P &lt; 0.0001; ONH 13.0 ± 0.7%, P = &lt; 0.0001), but higher in DVC (15.7 ± 1.2%, P &lt; 0.0001). Furthermore, VLD was lower in WS patients in all the vascular parameters compared to controls (SCP 13.8 ± 1.5%, P &lt; 0.0001; DVC 17.3 ± 0.6%, P &lt; 0.0001; ONH 15.7 ± 0.5%, P &lt; 0.0001). A significant microvasculature impairment in the macular SCP and ONH microvasculature was demonstrated in eyes affected by WS. Microvascular impairment may be considered a fundamental component of the neurodegenerative changes in WS

The prevention of analgesic opioids abuse: expert opinion

Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship

The role of basiliximab induction therapy in adult-to-adult living-related transplantation and deceased donor liver transplantation: a comparative retrospective analysis of a single-center series

Basiliximab in association with tacrolimus and steroids is effective in reducing episodes of acute cellular rejection (ACR) and increasing ACR-free survival after ALRLT and DDLT. No difference in patient and graft survival was found between group 1 and 2, nor was there any difference in the incidence of ACR between the 2 groups. However, less risk of HCV recurrence was present in the LRLT group

The new magnetar SGR J1830-0645 in outburst

The detection of a short hard X-ray burst and an associated bright soft X-ray source by the Swift satellite in 2020 October heralded a new magnetar in outburst, SGR J1830-0645. Pulsations at a period of ~10.4 s were detected in prompt follow-up X-ray observations. We present here the analysis of the Swift/BAT burst, of XMM-Newton and the Nuclear Spectroscopic Telescope Array observations performed at the outburst peak, and of a Swift/XRT monitoring campaign over the subsequent month. The burst was single-peaked, lasted ~6 ms, and released a fluence of ~5e-9 erg cm^-2 (15-50 keV). The spectrum of the X-ray source at the outburst peak was well described by an absorbed double-blackbody model plus a power-law component detectable up to ~25 keV. The unabsorbed X-ray flux decreased from ~5e-11 to ~2.5e-11 erg cm^-2 s^-1 one month later (0.3-10 keV). Based on our timing analysis, we estimate a dipolar magnetic field ~5.5e14 G at pole, a spin-down luminosity ~2.4e32 erg s^-1, and a characteristic age ~24 kyr. The spin modulation pattern appears highly pulsed in the soft X-ray band, and becomes smoother at higher energies. Several short X-ray bursts were detected during our campaign. No evidence for periodic or single-pulse emission was found at radio frequencies in observations performed with the Sardinia Radio Telescope and Parkes. According to magneto-thermal evolutionary models, the real age of SGR J1830-0645 is close to the characteristic age, and the dipolar magnetic field at birth was slightly larger, ~1e15 G.Comment: 10 pages, 4 figures, 2 tables. Accepted for publication in The Astrophysical Journal Letter