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

Eddy covariance methane measurements at a Ponderosa pine plantation in California

Long term methane flux measurements have been mostly performed with plant or soil enclosure techniques on specific components of an ecosystem. New fast response methane analyzers make it possible to use the eddy covariance (EC) technique instead. The EC technique is advantageous because it allows continuous flux measurements integrating over a larger and more representative area including the complete ecosystem, and allows fluxes to be observed as environmental conditions change naturally without disturbance. We deployed the closed-path Fast Methane analyzer (FMA) from Los Gatos Research Ltd and demonstrate its performance for EC measurements at a Ponderosa pine plantation at the Blodgett Forest site in central California. The fluctuations of the CH<sub>4</sub> concentration measured at 10 Hz appear to be small and their standard deviation is comparable to the magnitude of the signal noise (±5 ppbv). Consequently, the power spectra typically have a white noise signature at the high frequency end (a slope of +1). Nevertheless, in the frequency range important for turbulent exchange, the cospectra of CH<sub>4</sub> compare very well with all other scalar cospectra confirming the quality of the FMA measurements are good for the EC technique. We furthermore evaluate the complications of combined open and closed-path measurements when applying the Webb-Pearman-Leuning (WPL) corrections (Webb et al., 1980) and the consequences of a phase lag between the water vapor and methane signal inside the closed path system. The results of diurnal variations of CH<sub>4</sub> concentrations and fluxes are summarized and compared to the monthly results of process-based model calculations

Risk of internet addiction in adolescents: A confrontation between traditional teaching and online teaching

Background: The technological evolution has given the opportunities to develop new models of education, like online teaching. However, Internet Problematic Use and Internet Addiction are becoming frequently represented among adolescents with a prevalence that varies worldwide from 2% to 20% of the high school population. Objective: The aim of this study was to analyse the risk of Internet Addiction in a High Schools student sample comparing two different types of schools (online and traditional teaching) and analyzing the associations between pathological use of Internet and socio-demographic factors connected to the different educational orientations and to the daily usage of Internet. Methods: Students were enrolled from four different orientation school programs (different high school, technical and economical Institute, vocational schools). Each student completed a self-reported test to collect socio-demographic data and th Internet Addiction Test (IAT) from K. Young to assess the risk of Internet Addiction. The Mann-Whitney test for quantitative variables was used for statistical analysis. Results: 522 students were enrolled, 243 students from online teaching and 279 from traditional teaching schools. Internet Addiction was observed in 1,16% of the total sample, while 53.83% of subjects was at risk of development Internet Addiction. No significant difference was found between the two different types of teaching, nor considering gender. Considering the amount of time spent on the web in portion of the sample at risk of developing Internet Addiction, the Traditional Teaching group spent between 4 and 7 hours a day on the Web, while the Online Teaching group between 1 to 3 hours/daily. However, no statistically significant difference was found. Conclusion: Although our data demonstrate that there is no clear association between online education and problematic use of Internet, the excessive use of Internet is linked to a massive waste of personal energy in terms of time and social life

The X-ray outburst of the Galactic Center magnetar over six years of Chandra observations

The magnetar SGR J1745-2900 discovered at parsecs distance from the Milky Way central black hole, Sagittarius A*, represents the closest pulsar to a supermassive black hole ever detected. Furthermore, its intriguing radio emission has been used to study the environment of the black hole, as well as to derive a precise position and proper motion for this object. The discovery of SGR J1745-2900 has opened interesting debates about the number, age and nature of pulsars expected in the Galactic center region. In this work, we present extensive X-ray monitoring of the outburst of SGR J1745-2900 using the Chandra X-ray Observatory, the only instrument with the spatial resolution to distinguish the magnetar from the supermassive black hole (2.4" angular distance). It was monitored from its outburst onset in April 2013 until August 2019, collecting more than fifty Chandra observations for a total of more than 2.3 Ms of data. Soon after the outburst onset, the magnetar emission settled onto a purely thermal emission state that cooled from a temperature of about 0.9 to 0.6 keV over 6 years. The pulsar timing properties showed at least two changes in the period derivative, increasing by a factor of about 4 during the outburst decay. We find that the long-term properties of this outburst challenge current models for the magnetar outbursts.Comment: 11 pages, 6 figures. Accepted by Ap

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

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

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

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