A small satellite mission devoted to mid-low latitude earth observation

This paper aims at assessing the feasibility of a small mission devoted to observe the mid-low latitude regions. The satellite will be equipped with three optical sensors: a medium-high spatial resolution VIS-NIR multi-spectral sensor, allowing the surface monitoring and land-use and land-cover studies; a medium spatial-resolution 3-bands thermal (MIR-TIR) sensor allowing the surface temperature (LST, SST) estimate and hot-spots (fires, volcanic eruption, etc.) detection; a panchromatic VIS-NIR camera for night-time observation able to reveal artificial and natural lights. The selected orbit, called multi-sun-synchronous (MSS), represents an innovation with respect to the classical sun-synchronous orbit much suitable for observing tropical regions, allowing an enhanced revisit frequency. Further, such an orbit allows the observation of the same region of the Earth at different local-time. In this way, the diurnal cycle of surface temperatures can be reconstructed with a 2-hours local-time step. An analysis of the capability of the selected ground stations to acquire the data gathered by the remote sensing sensors has been carried out. Orbital perturbations have been taken into account and an estimate of the propellant required for ground track control has been performed in order to verify its compatibility with a small mission requirements

Involvement of electrophysiological localization of the subthalamic nucleus in deep brain stimulation for Parkinson’s disease

We studied the involvement of the electrophysiological localization of the subthalamic nucleus (NST) using a multi-unit recording technique by means of semi-microelectrode in a set of thirty Parkinson’s patients who benefited from a bilateral stimulation of the NST and who were operated on under local or general anesthesia. The multi-unit recording technique by means of semi-microelectrodes appeared efficient,capable of improving the localization of the NST and leading to improvement in clinical results. We believe that the use of our technique will allow for time savings while providing good results, and that the choice of the angle of the trajectory will allow for improved localization of the NST and thus improved clinical results

Body composition with dual energy X-ray absorptiometry : from basics to new tools

Dual-energy X-ray absorptiometry (DXA) in nowadays considered one of the most versatile imaging techniques for the evaluation of metabolic bone disorders such as osteoporosis, sarcopenia and obesity. The advantages of DXA over other imaging techniques are the very low radiation dose, its accuracy and simplicity of use. In addition, fat mass (FM) and lean mass (LM) values by DXA shows very good accuracy compared to that of computed tomography and magnetic resonance imaging. In this review we will explain the technical working principles of body composition with DXA, together with the possible limitations and pitfalls that should be avoided in daily routine to produce high-quality DXA examinations. We will also cover the current clinical practical application of whole body DXA values, with particular emphasis on the use of LM indices in the diagnostic workup of reduced muscle mass, sarcopenia and osteosarcopenic obesity according to the most recent guidelines. The possible use of adipose indices will be considered, such as the fat mass index (FMI) or the android/gynoid ratio, as well as lipodystrophy indices and the evaluation of visceral adipose tissue (VAT). Whenever available, we will provide possible cut-off diagnostic values for each of these LM and FM indices, according to current literature and guidelines

Hypoxia shapes autophagy in LPS-activated dendritic cells

During their lifespan, dendritic cells (DCs) are exposed to different pO2 levels that affect their differentiation and functions. Autophagy is one of the adaptive responses to hypoxia with important implications for cell survival. While the autophagic machinery in DCs was shown to impact signaling of TLRs, its regulation by the MD-2/TLR4 ligand LPS is still unclear. The aim of this study was to evaluate whether LPS can induce autophagy in DCs exposed to either aerobic or hypoxic conditions. Using human monocyte-derived DCs and the combination of immunofluorescence confocal analysis, measure of mitochondrial membrane potential, Western blotting, and RT-qPCR, we showed that the ability of LPS to modulate autophagy was strictly dependent upon pO2 levels. Indeed, LPS inhibited autophagy in aerobic conditions whereas the autophagic process was induced in a hypoxic environment. Under hypoxia, LPS treatment caused a significant increase of functional lysosomes, LC3B and Atg protein upregulation, and reduction of SQSTM1/p62 protein levels. This selective regulation was accompanied by activation of signalling pathways and expression of cytokines typically associated with DC survival. Bafilomycin A1 and chloroquine, which are recognized as autophagic inhibitors, confirmed the induction of autophagy by LPS under hypoxia and its impact on DC survival. In conclusion, our results show that autophagy represents one of the mechanisms by which the activation of the MD-2/TLR4 ligand LPS promotes DC survival under hypoxic conditions

Forecasting Effusive Dynamics and Decompression Rates by Magmastatic Model at Open-vent Volcanoes

Effusive eruptions at open-conduit volcanoes are interpreted as reactions to a disequilibrium induced by the increase in magma supply. By comparing four of the most recent effusive eruptions at Stromboli volcano (Italy), we show how the volumes of lava discharged during each eruption are linearly correlated to the topographic positions of the effusive vents. This correlation cannot be explained by an excess of pressure within a deep magma chamber and raises questions about the actual contributions of deep magma dynamics. We derive a general model based on the discharge of a shallow reservoir and the magmastatic crustal load above the vent, to explain the linear link. In addition, we show how the drastic transition from effusive to violent explosions can be related to different decompression rates. We suggest that a gravity-driven model can shed light on similar cases of lateral effusive eruptions in other volcanic systems and can provide evidence of the roles of slow decompression rates in triggering violent paroxysmal explosive eruptions, which occasionally punctuate the effusive phases at basaltic volcanoes

Bone strain index as a predictor of further vertebral fracture in osteoporotic women: An artificial intelligence-based analysis

Background Osteoporosis is an asymptomatic disease of high prevalence and incidence, leading to bone fractures burdened by high mortality and disability, mainly when several subsequent fractures occur. A fragility fracture predictive model, Artificial Intelligence-based, to identify dual X-ray absorptiometry (DXA) variables able to characterise those patients who are prone to further fractures called Bone Strain Index, was evaluated in this study. Methods In a prospective, longitudinal, multicentric study 172 female outpatients with at least one vertebral fracture at the first observation were enrolled. They performed a spine X-ray to calculate spine deformity index (SDI) and a lumbar and femoral DXA scan to assess bone mineral density (BMD) and bone strain index (BSI) at baseline and after a follow-up period of 3 years in average. At the end of the follow-up, 93 women developed a further vertebral fracture. The further vertebral fracture was considered as one unit increase of SDI. We assessed the predictive capacity of supervised Artificial Neural Networks (ANNs) to distinguish women who developed a further fracture from those without it, and to detect those variables providing the maximal amount of relevant information to discriminate the two groups. ANNs choose appropriate input data automatically (TWIST-system, Training With Input Selection and Testing). Moreover, we built a semantic connectivity map usingthe Auto Contractive Map to provide further insights about the convoluted connections between the osteoporotic variables under consideration and the two scenarios (further fracture vs no further fracture). Results TWIST system selected 5 out of 13 available variables: age, menopause age, BMI, FTot BMC, FTot BSI. With training testing procedure, ANNs reached predictive accuracy of 79.36%, with a sensitivity of 75% and a specificity of 83.72%. The semantic connectivity map highlighted the role of BSI in predicting the risk of a further fracture. Conclusions Artificial Intelligence is a useful method to analyse a complex system like that regarding osteoporosis, able to identify patients prone to a further fragility fracture. BSI appears to be a useful DXA index in identifying those patients who are at risk of further vertebral fractures. Copyright

Nuovo protocollo riabilitativo dopo intervento di protesi totale di caviglia nel paziente emofilico: caso clinico preliminare

Nuovo protocollo riabilitativo a seguito di artroplastica totale della caviglia in pazienti emo- filici: caso clinico preliminare - Barbieri V [1], Rebagliati GAA [1], Russo G [1], Ulivieri FM [2], Previtera AM [1]. [1] Scuola di Specializzazione in Medicina Fisica e Riabilitativa, Universit\ue0 degli studi di Milano. [2] Bone Metabolic Unit, Uo Medicina Nucleare, IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milano. - L\u2019artropatia emofilica in stadio terminale si presenta come non responsiva ai trattamenti conserva- tivi e comporta un dolore di difficile controllo, grave deterioramento delle articolazioni interessate e significative disabilit\ue0. Le articolazioni pi\uf9 colpite sono gomiti, ginocchia e caviglie [1]. Per quanto riguarda l\u2019artropatia di caviglia, il trattamento chirurgico \ue8 ad oggi rappresentato prin- cipalmente da due tecniche: l\u2019artrodesi di caviglia (AA), efficace nel ridurre il dolore e la frequenza degli episodi di emartro, con tuttavia perdita di mobilit\ue0 e possibile sovraccarico delle altre artico- lazioni dell\u2019arto inferiore (con occasionale necessit\ue0 di ulteriori correzioni chirurgiche) [3] e l\u2019artro- plastica di caviglia (TAR), che presenta il vantaggio di conservare la mobilit\ue0, ma \ue8 gravata da un maggior numero di complicanze, tra cui mobilizzazione asettica e infezioni dovute alla scarsa qualit\ue0 ossea nella sede di impianto [2,3]. Nel breve termine, entrambe le opzioni portano a sollievo dal dolore [2,3]. Le misure di outcome della TAR, per quanto parziali [2], sono incoraggianti, spaziando dal sollievo dal dolore alla migliorata mobilit\ue0 nella maggior parte dei casi [3]. Al contrario, la ge- stione post- operatoria presenta aspetti controversi a causa dell\u2019alto tasso di complicanze precoci e della necessit\ue0 di cure multidisciplinari. Non esiste al momento un univoco standard di cura riabi- litativo che consenta di monitorare e ottimizzare il processo di guarigione. Per questo motivo \ue8 stato proposto un nuovo protocollo sperimentale di riabilitazione precoce, volto alla minimizzazione delle complicanze post-chirurgiche. Abbiamo posto a confronto outcome clinico, funzionale e strumentale di un paziente emofilico sot- toposto a TAR e al nuovo protocollo con tre pazienti emofilici, che dopo TAR hanno seguito il proto- collo in uso presso IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico di Milano. La procedura di riabilitazione \u201ctradizionale\u201d si divide in: fase di breve termine, alla dimissione dalla UO di Ortopedia, in cui al paziente viene posizionato uno stivaletto gessato (valutazione della mo- bilit\ue0 e degli ausili, riduzione delle asimmetrie corporee, verticalizzazione assistita, cammino in sca- rico); fase di medio termine, svolta a domicilio per un mese (riduzione del rischio di lesioni terziarie, raggiungimento di parziale autonomia in ADL e IADL, verticalizzazione e controllo dell\u2019equilibrio) e fase di lungo termine, svolta in una struttura riabilitativa dedicata (deambulazione autonoma com- prendente la salita delle scale, autonomia nel ADL e IADL, reintroduzione nel contesto di prove- nienza). Il nuovo protocollo riabilitativo, al contrario, prende avvio quando il paziente si trova ancora nel reparto di Ortopedia, con il posizionamento di uno stivaletto rimovibile, che consente la mobilizza- zione dell\u2019articolazione coxo-femorale, del ginocchio e delle dita del piede, oltre a massaggio dell\u2019apo- neurosi plantare e un primo tentativo di flessione ed estensione della caviglia. Alla dimissione, il programma prosegue con sessioni bisettimanali di fisioterapia domiciliare, durante le quali viene impostata dapprima deambulazione in scarico con bastoncini canadesi, successivamente viene ese- guito trattamento manuale della ferita chirurgica e, al 17mo giorno post-operatorio, un primo ten- tativo di pronazione e supinazione della caviglia, seguito da un iniziale carico parziale della pianta del piede con progressivo aumento del carico in supervisione. A partire dalla trentesima giornata il protocollo continua in una struttura dedicata come nel percorso tradizionale. I tre controlli programmati hanno compreso un esame ortopedico, una densitometria ossea con un software dedicato \u201cmetal removal\u201d ed una valutazione funzionale con scala HJHS [4,5,6,7,8], che misura lo stato di salute nella struttura e nella funzione delle articolazioni pi\uf9 comunemente sog- gette a sanguinamento. Il paziente oggetto di studio ha mostrato una minore perdita di BMD al follow-up del quarto mese rispetto ai controlli. Ci\uf2 potrebbe suggerire una migliore efficacia nel mantenimento di una adeguata mineralizzazione ossea nel periodo immediatamente post-operatorio, offrendo una migliore stabilit\ue0 protesica e potenzialmente un minor numero di complicanze. La valutazione funzionale, con HJHS eseguito prima dell\u2019intervento e a distanza di un anno dallo stesso, ha evidenziato un miglioramento dello score totale sia nel caso che nei controlli, oltre che una sostanziale stabilit\ue0 nello score specifico per l\u2019articolazione. Tale dato potrebbe indicare una non inferiorit\ue0 del nuovo protocollo rispetto a quello in uso sul lungo termine. Il nuovo protocollo potrebbe quindi rappresentare una valida strategia per ridurre il numero delle complicanze legate alla TAR e suggerire due parametri strumentali e funzionali potenzialmente tra loro correlati come nuove misure di outcome nel primo periodo post-operatorio. Tali ipotesi neces- sitano di conferma tramite trial multicentrico controllato, possibilmente randomizzato, eseguito su un numero di casi statisticamente significativo. [1] Vulpen, LFD, Holstein, K, Martinoli, C. Joint disease in haemophilia: Pathophysiology, pain and imaging. Haemophilia. 2018; 24(Suppl. 6): 44\u2013 49. [2] Solimeno LP, Pasta G. Knee and Ankle Arthroplasty in Hemophilia. J Clin Med. 2017;6(11):107. [3] Rodriguez\u2010Merchan, E. C. (2014), End\u2010stage haemophilic arthropathy of the ankle: ankle fu- sion or total ankle replacement. Haemophilia, 20: e106-e107. [4] Fischer, K., et al. (2017), Choosing outcome assessment tools in haemophilia care and re- search: a multidisciplinary perspective. Haemophilia, 23: 11-24. [5] Feldman BM, Funk S, Bergstrom B-M, Zourikian N, Hilliard P, van der Net J, Engelbert RHH, Petrini P, van den Berg M , Manco-Johnson M, Rivard GE, Abad A, and Blanchette VS. Validation of a new pediatric joint scoring system from the International Hemophilia Prophylaxis Study Group: Validity of the Hemophilia Joint Health Score (HJHS). Arthritis Care & Research 2011 Feb; 63 (2):223-30. [6] Hilliard P, Funk S, Zourikian N. Bergstrom BM, Bradley CS, McLimont M, Manco-Johnson M, Petrini P, Van Den Berg M, Feldman BM. Hemophilia joint health score reliability study. Haemo- philia 2006; 12(5):pp 518-525. [7] Feldman BM. Funk S, Hilliard P, Van Der Net J, Zourikian N, Berstrom B-M, Engelbert RHH, Abad A, Petrini P, Manco-Johnson M, and On behalf of the International Prophylaxis Study Group. The Haemophilia Joint Health Score (HJHS) International Validation Study. XXVIIIth In- ternational Congress of the World Federation of Hemophilia, Istanbul, Turkey. Haemophilia 2008; 14 (Suppl. 2):pp 83. [8] Hilliard P, Blanchette VS, Doria A, Blanchette C, Hang M, Feldman BM. The Hemophilia Joint Health Score (HJHS) correlates highly with radiographic damage. XXVIIIth International Congress of the World Federation of Hemophilia, Istanbul, Turkey. Haemophilia 2008; 14 (Suppl. 2):pp 80

Phase Ib study of poly-epitope peptide vaccination to thymidylate synthase (TSPP) and GOLFIG chemo-immunotherapy for treatment of metastatic colorectal cancer patients

ABSTRACT: Thymidylate synthase (TS) is a tumor-associated enzyme critical for DNA replication and main 5′-fluorouracil (5′-FU) target. TSPP/VAC1 is a multi-arm trial phase-Ib trial program aimed to investigate the toxicity and biomodulatory activity of a poly-epitope-peptide vaccine to TS (TSPP) in cancer patients (pts). Here, we present the results of the TSPP/VAC1/arm C trial aimed to evaluate TSPP in combination with chemo-immunotherapy in pretreated metastatic colo-rectal cancer (mCRC) pts. Twenty-nine pts, 14 males and 15 females, received poly-chemotherapy with gemcitabine [GEM; 1,000 mg/sqm, day-1], oxaliplatin [OX; 80 mg/sqm, day-2], levofolinate [100 mg/sqm, days 1–2], bolus/infusional 5′-FU [400 mg/800 mg/sqm, days 1–2], sargramostim [50 μg, days 3–7/q30], and interleukin-2 [sc. 0.5 MIU twice a day, days 8–14/18–30] [GOLFIG-regimen]. Seventeen pts received sc. TSPP injections at escalating dosage [3 pts, 100 µg (DL-1); 3 pts, 200 µg (DL-2) and 11pts, 300 µg (DL-3)] one week after each chemotherapy cycle (concomitant module), while 10 out 12 pts received TSPP (300 µg) after 12 GOLFIG courses [dose level (DL)-0] (sequential module). TSPP MTD was not achieved. Adverse events consisted in swelling/erythema at injection sites (17 cases), G1–2 haematological (16 cases) and gastro-enteric events (12), fever, rhinitis, conjunctivitis, and poly-arthralgia and rise in auto-antibodies [ANA, ENA, c-ANCA, p-ANCA in the DL1–3 pts]. Both treatment-modules showed immunomodulating and antitumor activity (disease-control-rate, DL1–3 and DL0 were 70.6% and 83.3%, respectively) with a better survival recorded in the second group [median OS DL1–3 vs. DL0 = 8 vs. 16 mo, p = 0.049]. The promising long-term survival produced by the sequential treatment module deserves further phase II evaluation