Personal carbon allowances revisited

Here we discuss how personal carbon allowances (PCAs) could play a role in achieving ambitious climate mitigation targets. We argue that recent advances in AI for sustainable development, together with the need for a low-carbon recovery from the COVID-19 crisis, open a new window of opportunity for PCAs. Furthermore, we present design principles based on the Sustainable Development Goals for the future adoption of PCAs. We conclude that PCAs could be trialled in selected climate-conscious technologically advanced countries, mindful of potential issues around integration into the current policy mix, privacy concerns and distributional impacts

Processing and structural properties of random oriented lead lanthanum zirconate titanate thin films

Polycrystalline lead lanthanum zirconate titanate (PLZT) thin films have been prepared by a polymeric chemical route to understand the mechanisms of phase transformations and map the microstructure and elastic properties at the nanoscale in these films. X-ray diffraction, atomic force microscopy (AFM) and ultrasonic force microscopy (UFM) have been used as investigative tools. On one side, PLZT films with mixed-phase show that the pyrochlore phase crystallizes predominantly in the bottom film-electrode interface while a pure perovskite phase crystallizes in top film surface. On the contrary, pyrochlore-free PLZT films show a non-uniform microstrain and crystallite size along the film thickness with a heterogeneous complex grainy structure leading to different elastic properties at nanoscale

Ion microscopy based on laser-cooled cesium atoms

We demonstrate a prototype of a Focused Ion Beam machine based on the ionization of a laser-cooled cesium beam and adapted for imaging and modifying different surfaces in the few-tens nanometer range. Efficient atomic ionization is obtained by laser promoting ground-state atoms into a target excited Rydberg state, then field-ionizing them in an electric field gradient. The method allows obtaining ion currents up to 130 pA. Comparison with the standard direct photo-ionization of the atomic beam shows, in our conditions, a 40-times larger ion yield. Preliminary imaging results at ion energies in the 1–5 keV range are obtained with a resolution around 40 nm, in the present version of the prototype. Our ion beam is expected to be extremely monochromatic, with an energy spread of the order of the eV, offering great prospects for lithography, imaging and surface analysis

PARP-1 modulates amyloid beta peptide-induced neuronal damage.

Amyloid beta peptide (A beta) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with A beta(25-35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. A beta(25-35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following A beta(25-35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that A beta(25-35) induces DNA damage which in turn activates PARP-1. Challenge with A beta(25-35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, A beta(25-35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by A beta and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed

Connecting climate action with other sustainable development goals

The international community has committed to combat climate change and achieve 17 Sustainable Development Goals (SDGs). Here we explore (dis)connections in evidence and governance between these commitments. Our structured evidence review suggests that climate change can undermine 16 SDGs, while combatting climate change can reinforce all 17 SDGs but undermine efforts to achieve 12. Understanding these relationships requires wider and deeper interdisciplinary collaboration. Climate change and sustainable development governance should be better connected to maximize the effectiveness of action in both domains. The emergence around the world of new coordinating institutions and sustainable development planning represents promising progress

Discovery of AZD3199, an inhaled ultralong acting β2 receptor agonist with rapid onset of action

A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultra-long acting bronchodilators. Determination of activities at the human β-adrenoreceptors demonstrated a series of highly potent and selective β2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by; onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i. t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultra-long acting inhaled β2 receptor agonist with rapid onset of action

Real-world ANASTASE study of atezolizumab+nab-paclitaxel as first-line treatment of PD-L1-positive metastatic triple-negative breast cancer

The combination of atezolizumab and nab-paclitaxel is recommended in the EU as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer (mTNBC), based on the results of phase III IMpassion130 trial. However, ‘real-world’ data on this combination are limited. The ANASTASE study (NCT05609903) collected data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program. A retrospective analysis was conducted in 29 Italian oncology centers among patients who completed at least one cycle of treatment. Data from 52 patients were gathered. Among them, 21.1% presented de novo stage IV; 78.8% previously received (neo)adjuvant treatment; 55.8% patients had only one site of metastasis; median number of treatment cycles was five (IQR: 3–8); objective response rate was 42.3% (95% CI: 28.9–55.7%). The median time-to-treatment discontinuation was 5 months (95% CI: 2.8–7.1); clinical benefit at 12 months was 45.8%. The median duration of response was 12.7 months (95% CI: 4.1–21.4). At a median follow-up of 20 months, the median progression-free survival was 6.3 months (95% CI: 3.9–8.7) and the median time to next treatment or death was 8.1 months (95% CI: 5.5–10.7). At 12 months and 24 months, the overall survival rates were 66.3% and 49.1%, respectively. The most common immune-related adverse events included rash (23.1%), hepatitis (11.5%), thyroiditis (11.5%) and pneumonia (9.6%). Within the ANASTASE study, patients with PD-L1-positive mTNBC treated with first-line atezolizumab plus nab-paclitaxel achieved PFS and ORR similar to those reported in the IMpassion130 study, with no unexpected adverse events