Sustainability perspectives: a new methodological approach for quantitative assessment

This paper proposes a new tool to assess sustainability and make the concept of sustainable development operational. It considers its multi-dimensional structure combining the information deriving from a selection of relevant sustainability indicators belonging to economic, social and environmental pillars. The main novelties of this approach are the modelling framework, a recursive-dynamic computable general equilibrium used to calculate the trend of all indicators over time throughout the world, and the aggregation methodology to reconcile them in one aggregate index to measure overall sustainability. The former allows capturing the sector and regional interactions and higher-order effects driven by background assumptions on relevant variables to depict future scenarios. The latter makes it possible to compare sustainability performances, under alternative scenarios, across countries and over time. Main results show that the current sustainability at world level differs from what the traditional measure of well-being, the GDP, depicts, highlighting the trade-offs among different components of sustainability. Moreover, in the next decade a slight decrease in world sustainability may occur, in spite of an expected increase in world domestic product. Finally, dedicated policies increase overall sustainability, showing that social and environmental benefits may be greater than the correlated economic costs

Understanding the unusual reorganization of the nanostructure of a dark conglomerate phase

The dark conglomerate (DC) phase exhibited by a bent-core liquid crystal shows remarkable properties including an electric-field tunable chiral domain structure and a large (0.045) reduction of refractive index, while maintaining an optically dark texture when observed under crossed polarizers. A detailed investigation of the system is presented, leading to a model that is fully consistent with the experimental observations. It reports the observation of two distinct regimes in the DC phase: a higher temperature regime in which the periodicity measured by small angle x-ray scattering decreases slightly (0.5%) and a lower temperature regime where it increases considerably (16%). Also, the paper discusses the unusual electric-field-induced transformations observed in both the regimes. These changes have threshold fields that are both temperature and frequency dependent, though the phenomena are observed irrespective of device thickness, geometry, and the alignment layer. The electro-optic behavior in the DC phase corresponds to a number of structural changes leading to unusual changes in physical properties including a small (1%) increase in periodicity and a doubling of the average dielectric permittivity. We propose a model of the DC phase where in the ground state the nanostructure of the phase exhibits an anticlinic antiferroelectric organization. Under an electric field, it undergoes a molecular rearrangement without any gross structural changes leading to an anticlinic ferroelectric order while keeping the overall sponge-like structure of the DC phase intact

Tailoring block copolymer nanoporous thin films with acetic acid as a small guest molecule

Block copolymers offer the fabrication of mesoporous thin films with distinct nanoscale structural features. In this contribution, we present the use of acetic acid (CH3COOH) as a low‐molecular‐weight guest molecule to tune the supramolecular assembly of poly[styrene‐block‐(4‐vinylpyridine)] (PS‐b‐P4VP), offering a versatile and straightforward method to obtain tailored nanostructured films with controlled topography and pore size. Spin‐coating toluene solutions of PS‐b‐P4VP, with a variable amount of CH3COOH, leads to micellar thin films, where the micelles contain the carboxylic acid as a guest molecule. The size can be conveniently modified in these films (from 48 to 75 nm) by varying the amount of organic acid in the starting solutions. Subsequent surface reconstruction of micellar films using ethanol leads to ring‐shaped copolymer nanoporous films with modulated diameter. Controlling the micelle reconstruction process, cylindrical porous films are also obtained. Interestingly, changing the type of aliphatic carboxylic acid leads to a modification of the observed film morphology from micelles to out‐of‐plane P4VP cylinders (or lamellae) in a PS matrix

ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic leukemic cells

B-cell precursor-acute lymphoblastic leukemia modulates the bone marrow (BM) niche to become leukemia-supporting and chemo-protective by reprogramming the stromal microenvironment. New therapies targeting the interplay between leukemia and stroma can help improve disease outcome. We identified ActivinA, a TGF-b family member with a well-described role in promoting several solid malignancies, as a factor favoring leukemia that could represent a new potential target for therapy. ActivinA resulted over-expressed in the leukemic BM and its production was strongly induced in mesenchymal stromal cells after culture with leukemic cells. Moreover, MSCs isolated from BM of leukemic patients showed an intrinsic ability to secrete higher amounts of ActivinA compared to their normal counterparts. The pro-inflammatory leukemic BM microenvironment synergized with leukemic cells to induce stromal-derived ActivinA. Gene expression analysis of ActivinA-treated leukemic cells showed that this protein was able to significantly influence motility-associated pathways. Interestingly, ActivinA promoted random motility and CXCL12-driven migration of leukemic cells, even at suboptimal chemokine concentrations, characterizing the leukemic niche. Conversely, ActivinA severely impaired CXCL12-induced migration of healthy CD34 + cells. This opposite effect can be explained by the ability of ActivinA to increase intracellular calcium only in leukemic cells, boosting cytoskeleton dynamics through a higher rate of actin polymerization. Moreover, by stimulating the invasiveness of the leukemic cells, ActivinA was found to be a leukemia-promoting factor. Importantly, the ability of ActivinA to enhance BM engraftment and the metastatic potential of leukemic cells was confirmed in a xenograft mouse model of the disease. Overall, ActivinA was seen to be a key factor in conferring a migratory advantage to leukemic cells over healthy hematopoiesis within the leukemic niche

Esophageal cancer in a young woman with bulimia nervosa: a case report

Adenocarcinoma of the esophagus has increased dramatically within the United States and continues to have a poor prognosis despite aggressive treatment. Identifying potential risk factors is critical for the early detection and treatment of this disease. The present case report describes a very young woman who developed adenocarcinoma of the esophagus after only a brief history of bulimia. These findings suggest that even in very young patients, bulimia may represent a risk factor for adenocarcinoma of the esophagus

Tuning ordered pattern of Pd species through controlled block copolymer self-assembly

We report a method for the preparation of ordered patterns of Pd species on a substrate based on the use of polystyrene-block-poly(ethylene oxide) copolymer (PS-b-PEO) templates and selective inclusion of palladium (Pd) species in the PEO domains. PS-b-PEO samples of different total molecular masses self-assemble in a cylindrical microphase-separated morphology, in which vertically aligned PEO cylinders, with different diameters depending on the molecular mass, are organized in a hexagonal array of different lateral spacings. The cylindrical nanostructure is maintained after the selective inclusion of Pd species (Pd acetate and Pd nanoparticles (NPs) after reduction of Pd ions of the salt) in the PEO cylinders so that the characteristic sizes (diameters and lateral spacings) of the included Pd species are tuned by the characteristic sizes of the block copolymer (BCP) template, which are regulated by molecular mass. Treatment of nanocomposites at elevated temperatures in air removes the polymer matrix and leads to the formation of arrays of palladium oxide (PdO) NPs covering a solid support. The patterns of PdO NPs are characterized by different particle diameters and gap distances, mirroring the patterns and characteristic nanodimensions of the parent BCPs used as templates

Patient-reported outcomes from a randomized, active-controlled, open-label, phase 3 trial of burosumab versus conventional therapy in children with X-linked hypophosphatemia

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (- 5.02, 95% CI - 9.29 to - 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline

Burosumab vs conventional therapy in children with X-linked hypophosphatemia:results of the open-label, phase 3 extension period

In a randomized, open-label phase 3 study of 61 children aged 1–12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64–88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks