Background
In staged liver resections, associating liver partition and portal ligation for staged hepatectomy (ALPPS) achieves sufficient hypertrophy of the future liver remnant (FLR) in 7 days. This ...is based on portal vein ligation and transection, and on occlusion of intrahepatic collaterals. This article presents a new surgical technique for achieving rapid hypertrophy of the FLR, which also involves adding intrahepatic collateral occlusion to portal vein transection.
Methods
Patients scheduled for two‐stage liver resection for primary or secondary liver tumours, in whom the FLR was considered too small, were enrolled prospectively. In the first stage, a tourniquet was placed around the parenchymal transection line, and the right portal vein was ligated and cut (associating liver tourniquet and portal ligation for staged hepatectomy, ALTPS). The tourniquet was placed on the umbilical ligament if a staged right trisectionectomy was planned, and on Cantlie's line for staged right hepatectomy.
Results
From September 2011, 22 ALTPS procedures were carried out (right trisectionectomy in 15, right hepatectomy in 7). Median FLR at 7 days increased from 410 to 700 ml (median increase 61 (range 33–189) per cent). The median duration of the first stage was 125 min and no patient received a blood transfusion. The median duration of the second stage was 150 min and five patients required a blood transfusion. Fourteen patients had complications, most frequently infected collections, and five patients developed postoperative liver failure. Two patients died.
Conclusion
The ALTPS technique achieved adequate hypertrophy of the FLR after 7 days. It may provide a less aggressive modification of the ALPPS procedure.
Simplification of the ALPPS procedure
Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value ...of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting.
Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 × 4 cycles followed by docetaxel 100 mg/m2 × 4 cycles EC-T) or HT (exemestane 25 mg daily × 24 weeks combined with goserelin in premenopausal patients). The primary end point was the clinical response measured by magnetic resonance imaging.
Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT.
Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.
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•Polymeric carbon nitride hydrogen peroxide adduct (PCN-H2O2) has been characterized.•PCN-H2O2 is more selective in photo-conversion of HMF to FDC than pristine PCN.•Hydroxyl radicals ...forming on NH2-sites of PCN lead to furan ring opening.•In PCN-H2O2 the NH2-species responsible for unselective HMF conversion are blocked.
Polymeric carbon nitride-hydrogen peroxide adduct (PCN-H2O2) has been prepared, thoroughly characterised and its application for selective photocatalytic conversion of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxaldehyde (FDC) in aqueous suspension has been studied. The PCN-H2O2 adduct is stable in aqueous suspension under UV and solar irradiation up to 100 °C. It is also stable up to 200 °C if heated in air, while at temperatures close to 300 °C its decomposition takes place. Based on the obtained characterisation data it has been proposed that H2O2 attaches to the non-polymerised carbon nitride species and to the heptazine nitrogen atoms, thus producing strong hydrogen bonding within the PCN-H2O2 adduct. The blockage of the surface amino-groups in PCN-H2O2 by H2O2 hinders the interaction of HMF with these sites, which are responsible for unselective substrate conversion. PCN-H2O2, although being less active, possesses a superior selectivity in natural solar light assisted oxidation of HMF to FDC reaching 80% with respect to its thermally etched PCN counterpart, which gives rise to a 40–50% selectivity. We believe that the exceptional performance of the applied photocatalyst in the selective photocatalytic conversion of HMF to a high added value FDC in a green solvent under natural illumination makes a significant contribution to the development of environmentally friendly technologies for biomass valorisation.
BACKGROUND AND PURPOSE The sigma‐1 (σ1) receptor is a ligand‐regulated molecular chaperone that has been involved in pain, but there is limited understanding of the actions associated with its ...pharmacological modulation. Indeed, the selectivity and pharmacological properties of σ1 receptor ligands used as pharmacological tools are unclear and the demonstration that σ1 receptor antagonists have efficacy in reversing central sensitization‐related pain sensitivity is still missing.
EXPERIMENTAL APPROACH The pharmacological properties of a novel σ1 receptor antagonist (S1RA) were first characterized. S1RA was then used to investigate the effect of pharmacological antagonism of σ1 receptors on in vivo nociception in sensitizing conditions and on in vitro spinal cord sensitization in mice. Drug levels and autoradiographic, ex vivo binding for σ1 receptor occupancy were measured to substantiate behavioural data.
KEY RESULTS Formalin‐induced nociception (both phases), capsaicin‐induced mechanical hypersensitivity and sciatic nerve injury‐induced mechanical and thermal hypersensitivity were dose‐dependently inhibited by systemic administration of S1RA. Occupancy of σ1 receptors in the CNS was significantly correlated with the antinociceptive effects. No pharmacodynamic tolerance to the antiallodynic and antihyperalgesic effect developed following repeated administration of S1RA to nerve‐injured mice. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of σ1 receptors attenuated the wind‐up responses in spinal cords sensitized by repetitive nociceptive stimulation.
CONCLUSIONS AND IMPLICATIONS These findings contribute to evidence identifying the σ1 receptor as a modulator of activity‐induced spinal sensitization and pain hypersensitivity, and suggest σ1 receptor antagonists as potential novel treatments for neuropathic pain.
Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are ...active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m
2
plus cyclophosphamide 600 mg/m
2
for 4 cycles) followed either by D (docetaxel 100 mg/m
2
× 4 cycles; EC–D) or DCb (docetaxel 75 mg/m
2
plus carboplatin AUC 6 × 4 cycles; EC–DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC–D, 48 EC–DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC–D and 14 patients (30 %) with EC–DCb (
P
value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56–83) in the EC–D arm and 77 % (95 % CI 65–87) in the EC–DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC–D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.
•Multi-objective optimization of tuned mass-damper-inerter (TMDI) is considered.•Performance is evaluated using multiple probabilistic life-cycle criteria.•Total cost as well as criteria related to ...risk aversion and TMDI force are examined.•Case study considers protection of a real-life 21-story structure in Santiago, Chile.•Different TMDI topological configurations are investigated.
The tuned mass-damper-inerter (TMDI) is a recently proposed passive vibration suppression device that couples the classical tuned mass-damper (TMD), comprising a secondary mass attached to the structure via a spring and dashpot, with an inerter. The latter is a two-terminal mechanical device developing a resisting force proportional to the relative acceleration of its terminals by the “inertance” constant. In a number of previous studies, optimally tuned TMDIs have been shown to outperform TMDs in mitigating earthquake-induced vibrations in building structures for the same pre-specified secondary mass. TMDI design in these studies involved simplified modeling assumptions, such as adopting a single performance objective and/or modeling seismic excitation as stationary stochastic process. This paper extends these efforts by examining a risk-informed TMDI optimization, adopting multiple objectives and using response history analysis and probabilistic life-cycle criteria to quantify performance. The first performance criterion, representing overall direct benefits, is the life-cycle cost of the system, composed of the upfront TMDI cost and the anticipated seismic losses over the lifetime of the structure. The second performance criterion, introducing risk-aversion attitudes into the design process, is the repair cost with a specific return period (i.e., probability of exceedance over the lifetime of the structure). The third performance criterion, accounting for practical constraints associated with the size of the inerter and its connection to the structure, is the inerter force with a specific return period. A particular variant of the design problem is also examined by combining the first and third performance criteria/objectives. A case study involving a 21-storey building constructed in Santiago, Chile shows that optimal TMDI configurations can accomplish simultaneous reduction of life-cycle and repair costs. However, these cost reductions come at the expense of increased inerter forces. It is further shown that connecting the inerter to lower floors provides considerable benefits across all examined performance criteria as the inerter is engaged in a more efficient way for the same inerter coefficient and attached mass ratios.
Interfacing bacteria as biocatalysts with an electrode provides the basis for emerging bioelectrochemical systems that enable sustainable energy interconversion between electrical and chemical ...energy. Electron transfer rates at the abiotic‐biotic interface are, however, often limited by poor electrical contacts and the intrinsically insulating cell membranes. Herein, we report the first example of an n‐type redox‐active conjugated oligoelectrolyte, namely COE‐NDI, which spontaneously intercalates into cell membranes and mimics the function of endogenous transmembrane electron transport proteins. The incorporation of COE‐NDI into Shewanella oneidensis MR‐1 cells amplifies current uptake from the electrode by 4‐fold, resulting in the enhanced bio‐electroreduction of fumarate to succinate. Moreover, COE‐NDI can serve as a “protein prosthetic” to rescue current uptake in non‐electrogenic knockout mutants.
The first example of an n‐type (i.e., redox cycles between reduced and neutral states) redox‐active conjugated oligoelectrolyte, COE‐NDI, has been designed and synthesized. Spontaneous membrane intercalation of COE‐NDI in Shewanella oneidensis MR‐1 amplifies inward extracellular electron transfer for more efficient bio‐electroreduction of fumarate to succinate, owing to COE‐NDI’s function as a transmembrane redox mediator.
Context. Protostellar jets and outflows are the main outcome of the star formation process, and their analysis can provide us with major clues about the ejection and accretion history of young ...stellar objects (YSOs). Aims. We aim at deriving the main physical properties of massive jets from near-infrared (NIR) observations, comparing them to those of a large sample of jets from low-mass YSOs, and relating them to the main features of their driving sources. Methods. We present a NIR imaging (H2 and Ks) and low-resolution spectroscopic (0.95−2.50 μm) survey of 18 massive jets towards GLIMPSE extended green objects (EGOs), driven by intermediate- and high-mass YSOs, which have bolometric luminosities (Lbol) between 4 × 102 and 1.3 × 105 L⊙. Results. As in low-mass jets, H2 is the primary NIR coolant, detected in all the analysed flows, whereas the most important ionic tracer is Fe ii, detected in half of the sampled jets. Our analysis indicates that the emission lines originate from shocks at high temperatures and densities. No fluorescent emission is detected along the flows, regardless of the source bolometric luminosity. On average, the physical parameters of these massive jets (i.e. visual extinction, temperature, column density, mass, and luminosity) have higher values than those measured in their low-mass counterparts. The morphology of the H2 flows is varied, mostly depending on the complex, dynamic, and inhomogeneous environment in which these massive jets form and propagate. All flows and jets in our sample are collimated, showing large precession angles. Additionally, the presence of both knots and jets suggests that the ejection process is continuous with burst episodes, as in low-mass YSOs. We compare the flow H2 luminosity with the source bolometric luminosity confirming the tight correlation between these two quantities. Five sources, however, display a lower LH2/Lbol efficiency, which might be related to YSO evolution. Most important, the inferred LH2 vs. Lbol relationship agrees well with the correlation between the momentum flux of the CO outflows and the bolometric luminosities of high-mass YSOs indicating that outflows from high-mass YSOs are momentum driven, as are their low-mass counterparts. We also derive a less stringent correlation between the inferred mass of the H2 flows and Lbol of the YSOs, indicating that the mass of the flow depends on the driving source mass. Conclusions. By comparing the physical properties of jets in the NIR, a continuity from low- to high-mass jets is identified. Massive jets appear as a scaled-up version of their low-mass counterparts in terms of their physical parameters and origin. Nevertheless, there are consistent differences such as a more variegated morphology and, on average, stronger shock conditions, which are likely due to the different environment in which high-mass stars form.
The construction industry is one of the most important socio-economic sectors of the Spanish economy and one of the most affected by workplace accidents. An analysis of the data on accident rates is ...needed, in order to identify variables related with workplace accidents and to define the measures that need to be taken for their reduction. In this study, an analysis is conducted using Bayesian Networks and data from the 7th National Survey on Working Conditions (VII NSWC), to study the relations between workplace accidents, visiting a doctor for occupational reasons, time in the company/sector, information that workers have on workplace risks in the workplace, and information and training on workplace risks that workers have received over the past two years. The NSWC survey, which is conducted every four years, was administered to 8892 workers, in Spain, in 2011. The values derived from the analysis yield certain implications involving the aforementioned variables and how to reduce the probability of workplace accidents. From among the variables under study, information on workplace risks is the most important, with the probability of suffering an accident in the construction industry doubling when such information is insufficient. In accordance with the results, these implications could also help with decision-making focused on improvements to training and on-the-job information, intended both to prevent and to reduce workplace accidents.
•We made a literature review on accident rates.•We examined a survey carried out in Spain that involved 8892 workers.•We built Bayesian Network with the variables: information, training, contract type, time on job, the sector and the accidents.•Long-term information on workplace risks has a greater effect and lowers accident rates more than training activities.•The difference between having bad or good information makes the probability of having an accident fall from 15.38% to 8.1%.
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