•Two-phase olive-mill waste and cattle manure were anaerobically co-digested.•Start-up and stabilization stages were studied in semicontinuous stirred tank reactor.•Propionic accumulation was the key ...factor in the methanogenic phase inhibition.•Total period of 140 days was required to start-up and stabilization the process.•During the stable period the methane productivity was 0.34 LCH4/LRd at 40-d HRT.
In this work, the start-up and stabilization stages of mesophilic anaerobic co-digestion of 2POMW and CM in a semi-continuously fed stirred tank reactor (SSTR) were analyzed. Volatile fatty acids (VFAs) were monitored and used as the main control parameter for the start-up and stabilization stages, as well as to evaluate the potential inhibition episodes. The results showed that accumulation of propionic acid was the key factor in the inhibition of the methanogenic phase, leading to process imbalance. To avoid the problems associated with inhibition by high VFA concentrations, several reinoculations were performed using a suitable inoculum adapted to VFA degradation. The start-up phase was carried out in batch conditions for 97 days, reaching a final concentration of propionic acid of 12.77 mg/L. From that moment, the reactor was fed in a semi-continuous mode with a hydraulic retention time (HRT) of 40 days. A total period of 140 days was required to achieve a stable performance of the reactor with a methane productivity of 0.34 LCH4/LRd.
•Two-phase olive-mill waste and cattle manure were anaerobically co-digested.•Biogas production was optimized in semicontinuous regime of feeding.•Optimal and critical hydraulic retention time (HRT) ...were determined for the process.•Maximum methane productivity (0.94 LCH4/LRd) was obtained at 15-day HRT (optimal).•Methane production and organic matter removal decrease at 12-day HRT (critical).
Anaerobic co-digestion of organic wastes is an effective technology for the management of two or more substrates with different characteristics. In this context, the main objective of this work was the optimization of biogas production for the treatment of a mixture of two-phase olive-mill waste (2POMW) and cattle manure (CM) (60:40 w/w) at mesophilic temperature range (35 °C). The effect of hydraulic retention time (HRT) on the performance and stability of the digestion process was studied. A decreasing series of HRTs in the range of 40–12 days was analyzed. The corresponding organic loading rates (OLR) were in the range 2.01–6.07 gVS/LR·d. Pseudo steady-state operation of the reactor was established for HRTs between 40 and 15 days. For 15-days HRT, the maximum values of methane productivity (0.94 LCH4/LR·d) and specific methane yield (0.52 LCH4/gVSremoved) were obtained while total acidity (measured as acetic acid) in the effluent were<150 mg/L, verifying process stability. In addition, the removal efficiencies of volatile solids (VS) and dissolved organic carbon (DOC) were 38 and 67 %, respectively. At 12-days HRT, decreases in methane production and organic matter removal efficiencies were observed, with values of 27 and 47 % for VS and DOC removal, respectively. Therefore, 12-days HRT was considered as inadequate for the anaerobic co-digestion of 2POMW and CM because a clear increase in volatile fatty acids was observed at the end of this period, leading to process destabilization and a decrease in biogas production.
Converging evidence suggests that peripersonal space has dynamic properties, that can be influenced by motor and cognitive factors. Here, we investigated whether changes in self-perception may impact ...upon peripersonal representation. Specifically, employing non-invasive brain stimulation, we tested whether corticospinal excitability elicited by objects placed in the vertical peripersonal vs extrapersonal space can be influenced by changes in self-perception after recalling a personal experience inducing the feeling of high power (vs. positivity vs. low power).
In a preliminary study (Study 1, N = 39) participants were presented with an object, whose position was manipulated in the horizontal vs vertical space. We assessed corticospinal excitability by measuring Motor Evoked Potentials (MEPs) using Transcranial Magnetic Stimulation with Electromyography co-registration (TMS-EMG). In the horizontal condition, we replicated the well-known motor facilitation induced by objects falling in the peri vs extrapersonal space, while in the vertical dimension MEPs were higher in the extrapersonal space.
In the main experiment (Study 2), participants (N = 55) were randomly assigned to feel high power, low power, or a general positive emotion and were asked to observe the same object positioned either in the peripersonal or in the extrapersonal vertical space. Results showed that in the low power condition MEPs were higher in the extrapersonal vs peripersonal, as in Study 1, while in high power and positive conditions MEPs were not influenced by distance.
Taken together, our findings suggest a dissociable pattern of motor facilitation underlying vertical vs horizontal space perception and, crucially, that changes in self-perception can influence such a representation.
•We explored the effect of self-perception on space representation.•Object's positions along the horizontal vs vertical axis differently modulates MEPs.•Recalling positive events influences surrounding space representation.•Perceiving ourself in a positive/powerful way expands peri-personal space boundaries.
Summary
Background
Quisinostat is a hydroxamate, second‐generation, orally available pan‐histone deacetylase inhibitor.
Objectives
To evaluate the efficacy and safety of oral quisinostat in patients ...with previously treated cutaneous T‐cell lymphoma (CTCL).
Methods
Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21‐day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression‐free survival (PFS), pruritus relief, safety and pharmacodynamic markers.
Results
Eight of 26 (25 evaluable) patients achieved ≥ 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2·8 to 6·9 months. Median PFS was 5·1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty‐one of 26 (81%) patients were withdrawn from the study before or at clinical cut‐off; five (19%) continued to receive treatment with quisinostat. The most common drug‐related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug‐related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia.
Conclusions
Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate.
What's already known about this topic?
Histone deacetylase inhibitors (HDAC‐Is) have been associated with significant clinical activity in different neoplastic disorders. Vorinostat and romidepsin have been approved by the U.S. Food and Drug Administration for treatment of cutaneous T‐cell lymphoma (CTCL).
Quisinostat is a hydroxamate, second‐generation, orally available pan‐HDAC‐I.
What does this study add?
Oral quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, and has an acceptable safety profile.
There was a low global response rate of 8% vs. a cutaneous response rate of 24%.
Combination therapy of quisinostat with other novel agents may be appropriate in patients who relapse following current conventional approaches.
Linked Comment: Scarisbrick. Br J Dermatol 2016; 175:14–15
Plain language summary available online
Context.
The origin of Galactic cosmic rays remains a matter of debate, but supernova remnants are commonly considered to be the main place where high-energy cosmic rays are accelerated. ...Nevertheless, current models predict cosmic-ray spectra that do not match observations and the efficiency of the acceleration mechanism is still undetermined. On the other hand, the contribution of other kinds of sources to the Galactic cosmic-ray population is still unclear, and merits investigation.
Aims.
In this work we explore a novel mechanism through which microquasars might produce cosmic rays. In this scenario, microquasar jets generate relativistic neutrons, which escape and decay outside the system; protons and electrons, created when these neutrons decay, escape to the interstellar medium as cosmic rays.
Methods.
We introduce the relativistic neutron component through a coupling term in the transport equation that governs the jet proton population. We compute the escape rate and decay distribution of these neutrons, and follow the propagation of the decay products until they escape the system and become cosmic rays. We then compute the spectra of these cosmic rays.
Results.
Neutrons can drain only a small fraction of the jet power as cosmic rays. The most promising scenarios arise in extremely luminous systems (
L
jet
∼ 10
40
erg s
−1
), in which the fraction of jet power deposited in cosmic rays can reach ∼0.001. Slow jets (Γ ≲ 2, where Γ is the bulk Lorentz factor) favour neutron production. The resulting cosmic-ray spectrum is similar for protons and electrons, which share the power in the ratio given by neutron decay. The spectrum peaks at roughly half the minimum energy of the relativistic protons in the jet; it is soft (spectral index ∼3) above this energy, and almost flat below.
Conclusions.
The proposed mechanism produces more energetic cosmic rays from microquasars than those presented by previous works in which the particles escape through the jet terminal shock. Values of spectral index steeper than 2 are possible for cosmic rays in our model and these indeed agree with those required to explain the spectral signatures of Galactic cosmic rays, although only the most extreme microquasars provide power comparable to that of a typical supernova remnant. The mechanism explored in this work may provide stronger and softer cosmic-ray sources in the early Universe, and therefore contribute to the heating and reionisation of the intergalactic medium.
In the WHO classification, subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a distinct type of T-cell lymphoma with an aggressive clinical behavior. Recent studies suggest that ...distinction should be made between SPTL with an α/β T-cell phenotype (SPTL-AB) and SPTL with a γδ T-cell phenotype (SPTL-GD), but studies are limited. To better define their clinicopathologic features, immunophenotype, treatment, and survival, 63 SPTL-ABs and 20 SPTL-GDs were studied at a workshop of the EORTC Cutaneous Lymphoma Group. SPTL-ABs were generally confined to the subcutis, had a CD4−, CD8+, CD56−, βF1+ phenotype, were uncommonly associated with a hemophagocytic syndrome (HPS; 17%), and had a favorable prognosis (5-year overall survival OS: 82%). SPTL-AB patients without HPS had a significantly better survival than patients with HPS (5-year OS: 91% vs 46%; P < .001). SPTL-GDs often showed (epi)dermal involvement and/or ulceration, a CD4−, CD8−, CD56+/−, βF1− T-cell phenotype, and poor prognosis (5-year OS: 11%), irrespective of the presence of HPS or type of treatment. These results indicate that SPTL-AB and SPTL-GD are distinct entities, and justify that the term SPTL should further be used only for SPTL-AB. SPTL-ABs without associated HPS have an excellent prognosis, and multiagent chemotherapy as first choice of treatment should be questioned.
A new analytical method for the simultaneous determination of 90 pesticides in fruit juices by ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) has been ...developed and validated. Extraction was performed with acetonitrile, applying QuEChERS methodology, and the extracts were analyzed without any further clean-up step, providing better results than solid phase extraction (SPE) procedure. Before chromatographic step, extracts were diluted with water (1:1) in order to obtain good peak shapes. Several chromatographic conditions were evaluated in order to achieve a fast separation in Multiple Reaction Monitoring (MRM) mode, obtaining a run time of only 11
min. Matrix effect was studied for different types of fruit juices (peach, orange, pineapple, apple and multifruit), indicating that multifruit juice can be selected as representative matrix for routine analysis of these food commodities. Pesticides were quantified using matrix-matched calibration with recoveries between 70.4 and 108.5% and relative standard deviation lower than 20%. Limits of quantification were lower than 5
μg
L
−1 in all the cases. The developed procedure was applied to commercial fruit juices, detecting carbendazim, cyprodinil and thiabendazol in a few samples.
The apparent flexural elastic properties of laminates are traditionally obtained from experimental testing under the supposition of same behaviour under tension and compression. However, any ...composite generally presents different response when it is submitted to these loading cases. This work is focused on the three-point bending test parallel to the fibres, in laminates of unidirectional and continuous carbon fibre-reinforced epoxy. The purpose is to evaluate the influence on the test results of the dissimilar composite behaviour under tension and compression in the fibres direction. Analytical expressions for obtaining the normal and shear stress distributions in the most loaded section are derived using the technique of the homogenised section. Subsequently, a relation between the span and the thickness of the beam is determined for estimating whether the sample will present flexural or shear failure in the experiments. Parallelepiped specimens with two different thicknesses have been tested for reviewing both failure modes by means of optical microscopy. The experimental evidences are used to evaluate the correctness of the analytical model.
Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. ...BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA.
We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h(2)g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were two-sided, except in the case of variance-explained estimation where one-sided tests were used.
We estimated a statistically significant genetic variance explained for BE (h(2)g = 35%; standard error SE = 6%; one-sided P = 1 × 10(-9)) and for EA (h(2)g = 25 %; SE = 5%; one-sided P = 2 × 10(-7)). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10(-6)), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD.
We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases.
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