Urban development and sustainability challenges chronicled by a century of construction material flows and stocks in Tiexi,China

Construction materials are considerable forces of global environmental impacts, but their dynamics vis‐à‐vis urban development are poorly documented, in part because their long lifespans require elusive and sometimes nonexistent decade‐long high‐resolution data. This study analyzes the construction material flow and stock trends that shaped and were shaped by the development, decline, and renewal of the Tiexi district of Shenyang, a microcosm of China's urban transformations since the early 20th century. Chronicling building‐by‐building the material flows and stock accumulations involved in the buildup of this area, we shed light on the physical resource context of its socioeconomic history. We find that 42 million tonnes of construction materials were needed to develop the Tiexi district from 1910 to 2018, and 18 million tonnes of material outflows were generated by end‐of‐life building demolition. However, over 55% of inflows and 93% of outflows occurred since 2002 during a complete redevelopment of the district. Only small portions of end‐of‐life materials could have been reused or recycled because of temporal and typological mismatches of supply and demand and technical limitations. Our analysis reveals a dramatic decrease in median building lifetimes to as low as 6 years in the early 21st century. These findings contribute to the discussion of long‐term environmental efficiency and sustainability of societal development through construction and reflect on the challenges of urban renewal processes not only in China but also in other developing and developed countries that lost (or may lose) their traditional economic base and restructure their urban forms. This article met the requirements for a Silver/Silver JIE data openness badge described at http://jie.click/badges .     

Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results

The prognosis in advanced-stage ovarian cancer remains poor. Tumor-specific intraoperative fluorescence imaging may improve staging and debulking efforts in cytoreductive surgery and thereby improve prognosis. The overexpression of folate receptor-α (FR-α) in 90-95% of epithelial ovarian cancers prompted the investigation of intraoperative tumor-specific fluorescence imaging in ovarian cancer surgery using an FR-α-targeted fluorescent agent. In patients with ovarian cancer, intraoperative tumor-specific fluorescence imaging with an FR-α-targeted fluorescent agent showcased the potential applications in patients with ovarian cancer for improved intraoperative staging and more radical cytoreductive surgery.     

Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein

How transmitter receptors modulate neuronal signaling by regulating voltage-gated ion channel expression remains an open question. Here we report dendritic localization of mRNA of Kv4.2 voltage-gated potassium channel, which regulates synaptic plasticity, and its local translational regulation by fragile X mental retardation protein (FMRP) linked to fragile X syndrome (FXS), the most common heritable mental retardation. FMRP suppression of Kv4.2 is revealed by elevation of Kv4.2 in neurons from fmr1 knockout (KO) mice and in neurons expressing Kv4.2-3'UTR that binds FMRP. Moreover, treating hippocampal slices from fmr1 KO mice with Kv4 channel blocker restores long-term potentiation induced by moderate stimuli. Surprisingly, recovery of Kv4.2 after N-methyl-D-aspartate receptor (NMDAR)-induced degradation also requires FMRP, likely due to NMDAR-induced FMRP dephosphorylation, which turns off FMRP suppression of Kv4.2. Our study of FMRP regulation of Kv4.2 deepens our knowledge of NMDAR signaling and reveals a FMRP target of potential relevance to FXS.     

Health Professionals “Make Their Choice”: Pharmaceutical Industry Leaders’ Understandings of Conflict of Interest

Conflicts of interest, stemming from relationships between health professionals and the pharmaceutical industry, remain a highly divisive and inflammatory issue in healthcare. Given that most jurisdictions rely on industry to self-regulate with respect to its interactions with health professionals, it is surprising that little research has explored industry leaders’ understandings of conflicts of interest. Drawing from in-depth interviews with ten pharmaceutical industry leaders based in Australia, we explore the normalized and structural management of conflicts of interest within pharmaceutical companies. We contrast this with participants’ unanimous belief that the antidote to conflicts of interest with health professionals were “informed consumers.” It is, thus, unlikely that a self-regulatory approach will be successful in ensuring ethical interactions with health professionals. However, the pharmaceutical industry’s routine and accepted practices for disclosing and managing employees’ conflicts of interest could, paradoxically, serve as an excellent model for healthcare.     

Decreased efficacy of antimicrobial agents in a polymicrobial environment

The airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve through antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. In this work, we investigate how polymicrobial cultures comprised of key CF-associated pathogens respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus), and fluconazole (targets Candida albicans). We found that growth in a polymicrobial environment protects the target microorganism (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent. This decreased antimicrobial efficacy was found to have both non-heritable (physiological) and heritable (genetic) components. Whole-genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis and/or pilus biogenesis, indicating that a previously undescribed colistin resistance mechanism was in operation. This was subsequently confirmed through further genetic analyses. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.Subject terms: Clinical microbiology, Antibiotics     

Global Burden of Human Mycetoma: A Systematic Review and Meta-analysis

Mycetoma is a chronic infectious disease of the subcutaneous tissue with a high morbidity. This disease has been reported from countries between 30°N and 15°S since 1840 but the exact burden of disease is not known. It is currently unknown what the incidence, prevalence and the number of reported cases per year per country is. In order to estimate what the global burden of mycetoma is, a meta-analysis was performed. In total 50 studies were included, which resulted in a total of 8763 mycetoma cases. Most cases were found in men between 11 and 40 years of age. The foot was most commonly affected. Most cases were reported from Mexico, Sudan and India. Madurella mycetomatis was the most prevalent causative agent world-wide, followed by Actinomadura madurae, Streptomyces somaliensis, Actinomadura pelletieri, Nocardia brasiliensis and Nocardia asteroides. Although this study represents a first indication of the global burden on mycetoma, the actual burden is probably much higher. In this study only cases reported to literature could be used and most of these cases were found by searching archives from a single hospital in a single city of that country. By erecting (inter)national surveillance programs a more accurate estimation of the global burden on mycetoma can be obtained.