Abstract. The Atmospheric Pollution and Human Health in a Chinese Megacity (APHH-Beijing) programme is an international collaborative project focusing on understanding the sources, processes and health effects of air pollution in the Beijing megacity. APHH-Beijing brings together leading China and UK research groups, state-of-the-art infrastructure and air quality models to work on four research themes: (1) sources and emissions of air pollutants; (2) atmospheric processes affecting urban air pollution; (3) air pollution exposure and health impacts; and (4) interventions and solutions. Themes 1 and 2 are closely integrated and support Theme 3, while Themes 1–3 provide scientific data for Theme 4 to develop cost-effective air pollution mitigation solutions. This paper provides an introduction to (i) the rationale of the APHH-Beijing programme and (ii) the measurement and modelling activities performed as part of it. In addition, this paper introduces the meteorology and air quality conditions during two joint intensive field campaigns – a core integration activity in APHH-Beijing. The coordinated campaigns provided observations of the atmospheric chemistry and physics at two sites: (i) the Institute of Atmospheric Physics in central Beijing and (ii) Pinggu in rural Beijing during 10 November–10 December 2016 (winter) and 21 May–22 June 2017 (summer). The campaigns were complemented by numerical modelling and automatic air quality and low-cost sensor observations in the Beijing megacity. In summary, the paper provides background information on the APHH-Beijing programme and sets the scene for more focused papers addressing specific aspects, processes and effects of air pollution in Beijing.

1022 Background: Currently, there are no standard ≥3 line regimens recommended for HER2-positive (IHC 3+, or IHC 2+/FISH+) advanced or metastatic breast cancer, and no recommended HER2-targeting treatment for HER2-low expressing (IHC 2+/FISH-, or IHC 1+) population. RC48-ADC is an innovative HER2-targeting antibody-drug conjugate with a cleavable linker and a potent microtubule inhibitor payload MMAE that has a bystanding effect in tumor cell killing. Methods: C001 CANCER (NCT02881138) was a dose-escalation phase I study (0.5, 1.0, 1.5, 2.0, and 2.5 mg/kg) with the 3+3 design among HER2-positive patients. C003 CANCER (NCT03052634) was a phase Ib study with 1.5, 2.0, and 2.5 mg/kg doses in the HER2-positive subgroup and 2.0 mg/kg dose in both IHC 2+/FISH-, and IHC 1+ HER2-low expressing subgroup. C003 CANCER is currently ongoing for IHC 1+ patients. Pooled analysis of the two studies was conducted for the efficacy and safety of RC48-ADC in HER2-positive or HER2-low expressing subgroups. Results: At the time of data cutoff (December 31, 2020), 118 female breast cancer patients were enrolled and treated with RC48-ADC. 70 patients (59.3%) were HER2-positive and 48 patients (40.7%) were HER2-low expressing. At baseline, 77 patients (65.3%) had liver metastases, 50 patients (42.4%) were ECOG PS 1, 47 patients (39.8%) had received ≥3 prior chemotherapy regimens. In the HER2-positive subgroup, ORRs for 1.5, 2.0, and 2.5 mg/kg doses were 22.2% (95% CI: 6.4%, 47.6%), 42.9% (95% CI: 21.8%, 66.0%), and 40.0% (95% CI: 21.1%, 61.3%). mPFSs for 1.5, 2.0, and 2.5 mg/kg cohorts were 4.0 months (95% CI: 2.6, 7.6), 5.7 months (95% CI: 5.3, 8.4) and 6.3 months (95% CI: 4.3, 8.8). In the HER2-low expressing subgroup, the ORR and mPFS were 39.6% (95% CI: 25.8%, 54.7%) and 5.7 months (95% CI: 4.1, 8.3). ORR and mPFS for IHC2+/FISH- patients were 42.9% (15/35) and 6.6 months (95% CI: 4.1, 8.5). For IHC1+ patients, even though the COVID-19 pandemic led to treatment postpone for some patients, ORR and mPFS reached 30.8% (4/13) and 5.5 months (95% CI: 2.7, 11.0). The common treatment-related adverse events (TRAEs) were AST increased (64.4%), ALT increased (59.3%), hypoesthesia (58.5%), white blood cell count decreased (48.3%), and neutrophil count decreased (47.5%); most were grade 1-2 in severity. Neutrophil count decreased (16.9%), GGT increased (12.7%), and fatigue (11.9%) were the grade 3 and above TRAEs occurring in ≥ 10% of the overall population. Conclusions: RC48-ADC showed consistent efficacy in HER2-positive and HER2-low expressing subgroups. The 2.0 mg/kg Q2W showed a more favorable benefit-risk ratio than other dose levels. No new safety signals were observed. Further studies are initiated to evaluate the efficacy and safety of RC48-ADC in various settings. Clinical trial information: NCT02881138; NCT03052634 .

The inaccurate quantification of personal exposure to air pollution introduces error and bias in health estimations, severely limiting causal inference in epidemiological research worldwide. Rapid advancements in affordable, miniaturised air pollution sensor technologies offer the potential to address this limitation by capturing the high variability of personal exposure during daily life in largescale studies with unprecedented spatial and temporal resolution. However, concerns remain regarding the suitability of novel sensing technologies for scientific and policy purposes. In this paper we characterise the performance of a portable personal air quality monitor (PAM) that integrates multiple miniaturised sensors for nitrogen oxides (NO x ), carbon monoxide (CO), ozone (O 3 ) and particulate matter (PM) measurements along with temperature, relative humidity, acceleration, noise and GPS sensors. Overall, the air pollution sensors showed high reproducibility (mean R 2 = 0.93, min-max: 0.80-1.00) and excellent agreement with standard instrumentation (mean R 2 = 0.82, min-max: 0.54-0.99) in outdoor, indoor and commuting microenvironments across seasons and different geographical settings. An important outcome of this study is that the error of the PAM is significantly smaller than the error introduced when estimating personal exposure based on sparsely distributed outdoor fixed monitoring stations. Hence, novel sensing technologies such as the ones demonstrated here can revolutionise health studies by providing highly resolved reliable exposure metrics at a large scale to investigate the underlying mechanisms of the effects of air pollution on health.