Nanoparticles (NPs) entering water systems are an emerging concern as NPs are more frequently manufactured and used. Single particle inductively coupled plasma-mass spectrometry (SP-ICP-MS) methods ...were validated to detect Zn- and Ce-containing NPs in surface and drinking water using a short dwell time of 0.1 ms or lower, ensuring precision in single particle detection while eliminating the need for sample preparation. Using this technique, information regarding NP size, size distribution, particle concentration, and dissolved ion concentrations was obtained simultaneously. The fates of Zn- and Ce-NPs, including those found in river water and added engineered NPs, were evaluated by simulating a typical drinking water treatment process. Lime softening, alum coagulation, powdered activated carbon sorption, and disinfection by free chlorine were simulated sequentially using river water. Lime softening removed 38–53 % of Zn-containing and ZnO NPs and >99 % of Ce-containing and CeO
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NPs. Zn-containing and ZnO NP removal increased to 61–74 % and 77–79 % after alum coagulation and disinfection, respectively. Source and drinking water samples were collected from three large drinking water treatment facilities and analyzed for Zn- and Ce-containing NPs. Each facility had these types of NPs present. In all cases, particle concentrations were reduced by a minimum of 60 % and most were reduced by >95 % from source water to finished drinking water. This study concludes that uncoated ZnO and CeO
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NPs may be effectively removed by conventional drinking water treatments including lime softening and alum coagulation.
Food and beverage companies have a very significant environmental and social impact, and this has become a global issue. The purpose of this study is to evaluate the drivers and barriers to ...implementing sustainability in large food and beverage companies and their supply chains. A total of 21 semistructured interviews were undertaken with 16 large food and beverage companies operating in Australia, including 11 multinationals. Institutional theory and extended resource‐based view (ERBV) were applied to evaluate the companies' responses to the external pressures that they faced. The lack of a government regulatory and environmental framework was seen as a major barrier, while top management commitment was generally strong across the sample companies and was seen as a key internal driver. In order to develop an effective sustainability strategy, it is important that a company understands the drivers and barriers to sustainability implementation so that the appropriate actions can be taken. To the best of the author's knowledge, this is first time that the drivers and barriers to sustainability of large food and beverage manufacturers have been evaluated.
In this study, aluminum sulfate, ferric sulfate, ferric chloride, and poly(diallyldimethylammonium chloride) (pDADMAC) coagulation removal of citrate-stabilized silver and gold nanoparticles (NPs) ...and uncoated titanium dioxide, cerium dioxide, and zinc oxide NPs was investigated using a single particle (SP) ICP-MS direct monitoring technique. Zone 2 (charge neutralization) coagulation was performed in river water and more commonly used Zone 4 (sweep floc) coagulation was performed in both river and lake water with environmentally relevant concentrations of selected NPs added. SP-ICP-MS was used to detect NP and dissolved species, characterize the size distribution, and quantify particle concentration as well as dissolved species before and after treatments. Other parameters including pH, dissolved organic carbon, turbidity, and UV254 absorbance were monitored to characterize treatment efficiency. Charge neutralization (Zone 2) coagulation resulted in 48–85% removal of citrate-stabilized NPs and 90–99% removal of uncoated NPs from river water. Sweep floc (Zone 4) coagulation in river water resulted in 36–94% removal of citrate-stabilized NPs and 91–99% removal of uncoated NPs both with and without polymer addition. Zone 4 coagulation conditions in lake water resulted in 77–98% removal of citrate-stabilized NPs and 59–96% removal of uncoated NPs without polymer. These results indicate that NP removal depends on NP surface and stability, the nature of the source water, and the coagulant type and approach.
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•Single particle ICP-MS was used to detect nanoparticles in drinking water.•Aluminum sulfate, ferric sulfate, and ferric chloride coagulants were studied.•TiO2, ZnO, CeO2, Ag, and Au nanoparticles were removed by coagulation.•Charge neutralization and sweep floc modes remove nanoparticles efficiently.•Removal of citrate-stabilized nanoparticles is less effective than uncoated ones.
Managing sustainability in the food supply chain is critical given the very large environmental and social footprint that the food industry has globally. Food industry players have also become ...increasingly involved in these issues due to stakeholder pressures, and this highlights the importance in understanding what sustainability practices and best practices are being utilised. This review identifies the current state of knowledge of how food manufacturing companies implement sustainability in their operations and across their supply chains. A thematic analysis was conducted on 130 papers that were published over a 21-year time frame from 1999 to 2020 to identify eight key sustainability themes in the literature. These themes included – life cycle assessments, drivers, barriers and incentives to sustainability, waste and recycling management, food chain logistics, sustainability practices in small and medium sized enterprises (SMEs), supplier management, partnerships and relationships and “other” sustainable supply chain management practices. Through examining the extant literature, it is clear that there remains substantial scope for research on the role of SMEs and food logistics, as there is scant research on both areas despite their critical role within sustainable supply chain management. It is also clear that large multinational companies have a critical role in supporting supply chain practices through not only driving practices but also in providing critical resources and collaboration for partners across the supply chain. Circular economy is emerging as a key research area that is experiencing increasing focus in recent years, although it is argued that future research should focus on digitisation efforts such as through Internet of Things and blockchain that has been highlighted as a major disruptive and supportive element in increasing sustainability across supply chains.
Abstract Background Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune ...checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response. Methods In this study, we analyzed two independently collected R/M HNSCC patient tissue cohorts to better understand the role of TLS in response to ICIs. Utilizing a multi-omics approach, we first performed targeted proteomic profiling using the Nanostring GeoMx Digital Spatial Profiler to quantify immune-related protein expression with spatial resolution. This was further characterized by spatially resolved whole transcriptome profiling of TLSs and germinal centers (GCs). Deeper single-cell resolved proteomic profiling of the TLSs was performed using the Akoya Biosciences Phenocycler Fusion platform. Results Our proteomic analysis revealed the presence of T lymphocyte markers, including CD3, CD45, and CD8, expressing cells and upregulation of immune checkpoint marker PD-L1 within tumor compartments of patients responsive to ICIs, indicative of ‘hot tumor’ phenotypes. We also observed the presence of antigen-presenting cells marked by expression of CD40, CD68, CD11c, and CD163 with upregulation of antigen-presentation marker HLA-DR, in patients responding to ICIs. Transcriptome analysis of TLS and GCs uncovered a marked elevation in the expression of genes related to immune modulation, diverse immune cell recruitment, and a potent interferon response within the TLS structure. Notably, the distribution of TLS-tumor distance was found to be significantly different across response groups (H = 9.28, p = 0.026). The proximity of TLSs to tumor cells was found to be a critical indicator of ICI response, implying that patients with TLSs located further from tumor cells have worse outcomes. Conclusion The study underscores the multifaceted role of TLSs in modulating the immunogenic landscape of the TME in R/M HNSCC, likely influencing the efficacy of ICIs. Spatially resolved multi-omics approaches offer valuable insights into potential biomarkers for ICI response and highlight the importance of profiling the TME complexity when developing therapeutic strategies and patient stratification.
Abstract Objective How a randomised controlled trial (RCT) is explained to patients is a key determinant of recruitment to that trial. This study developed and implemented a simple six-step model to ...fully inform patients and to support them in deciding whether to take part. Study design and setting Ninety-two consultations with 60 new patients were recorded and analysed during a pilot RCT comparing surgical and non-surgical interventions for hip impingement. Recordings were analysed using techniques of thematic analysis and focused conversation analysis. Results Early findings supported the development of a simple six-step model to provide a framework for good recruitment practice. Model steps are: 1) Explain the condition; 2) Reassure patients about receiving treatment; 3) Establish uncertainty; 4) Explain the study purpose; 5) Give a balanced view of treatments and 6) Explain study procedures. There are also two elements throughout the consultation: i) Responding to patients’ concerns and ii) showing confidence. The pilot study was successful, with 70% (n= 60) of patients approached across 9 centres agreeing to take part in the RCT, so that the full-scale trial was funded. Conclusion The six-step model provides a promising framework for successful recruitment to RCTs. Further testing of the model is now required.
Animal tolerance towards humans can be a key factor facilitating wildlife-human coexistence, yet traits predicting its direction and magnitude across tropical animals are poorly known. Using 10,249 ...observations for 842 bird species inhabiting open tropical ecosystems in Africa, South America, and Australia, we find that avian tolerance towards humans was lower (i.e., escape distance was longer) in rural rather than urban populations and in populations exposed to lower human disturbance (measured as human footprint index). In addition, larger species and species with larger clutches and enhanced flight ability are less tolerant to human approaches and escape distances increase when birds were approached during the wet season compared to the dry season and from longer starting distances. Identification of key factors affecting animal tolerance towards humans across large spatial and taxonomic scales may help us to better understand and predict the patterns of species distributions in the Anthropocene.
Soil microbes produce extracellular enzymes that degrade carbon (C)‐containing polymers in soil organic matter. Because extracellular enzyme activities may be sensitive to both increased nitrogen (N) ...and temperature change, we measured the effect of long‐term N addition and short‐term temperature variation on enzyme kinetics in soils from hardwood forests at Bear Brook, Maine, and Fernow Forest, West Virginia. We determined the Vmax and Km parameters for five hydrolytic enzymes: α‐glucosidase, β‐glucosidase, β‐xylosidase, cellobiohydrolase, and N‐acetyl‐glucosaminidase. Temperature sensitivities of Vmax and Km were assessed within soil samples subjected to a range of temperatures. We hypothesized that (1) N additions would cause microbial C limitation, leading to higher enzyme Vmax values and lower Km values; and (2) both Vmax and Km would increase at higher temperatures. Finally, we tested whether or not temperature sensitivity of enzyme kinetics is mediated by N addition. Nitrogen addition significantly or marginally significantly increased Vmax values for all enzymes, particularly at Fernow. Nitrogen fertilization led to significantly lower Km values for all enzymes at Bear Brook, but variable Km responses at Fernow Forest. Both Vmax and Km were temperature sensitive, with Q10 values ranging from 1.64–2.27 for enzyme Vmax and 1.04–1.93 for enzyme Km. No enzyme showed a significant interaction between N and temperature sensitivity for Vmax, and only β‐xylosidase showed a significant interaction between N and temperature sensitivity for Km. Our study is the first to experimentally demonstrate a positive relationship between Km and temperature for soil enzymes. Higher temperature sensitivities for Vmax relative to Km imply that substrate degradation will increase with temperature. In addition, the Vmax and Km responses to N indicate greater substrate degradation under N addition. Our results suggest that increasing temperatures and N availability in forests of the northeastern US will lead to increased hydrolytic enzyme activity, despite the positive temperature sensitivity of Km.
Oculocutaneous albinism (OCA) is a rare disorder of pigment production. Affected individuals have variably decreased global pigmentation and visual-developmental changes that lead to low vision. OCA ...is notable for significant missing heritability, particularly among individuals with residual pigmentation. Tyrosinase (TYR) is the rate-limiting enzyme in melanin pigment biosynthesis and mutations that decrease enzyme function are one of the most common causes of OCA. We present the analysis of high-depth short-read TYR sequencing data for a cohort of 352 OCA probands, ∼50% of whom were previously sequenced without yielding a definitive diagnostic result. Our analysis identified 66 TYR single-nucleotide variants (SNVs) and small insertion/deletions (indels), 3 structural variants, and a rare haplotype comprised of two common frequency variants (p.Ser192Tyr and p.Arg402Gln) in cis-orientation, present in 149/352 OCA probands. We further describe a detailed analysis of the disease-causing haplotype, p.Ser192Tyr; Arg402Gln (“cis-YQ”). Haplotype analysis suggests that the cis-YQ allele arose by recombination and that multiple cis-YQ haplotypes are segregating in OCA-affected individuals and control populations. The cis-YQ allele is the most common disease-causing allele in our cohort, representing 19.1% (57/298) of TYR pathogenic alleles in individuals with type 1 (TYR-associated) OCA. Finally, among the 66 TYR variants, we found several additional alleles defined by a cis-oriented combination of minor, potentially hypomorph-producing alleles at common variant sites plus a second, rare pathogenic variant. Together, these results suggest that identification of phased variants for the full TYR locus are required for an exhaustive assessment for potentially disease-causing alleles.
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This work finds a rare allele p.Ser192Tyr; Arg402Gln accounting for the majority of missing heritability in oculocutaneous albinism type 1B. This cis-YQ allele comprises two common variants recombined onto a single haplotype and highlights the need for haplotype-based disease allele queries to complement single-allele, frequency-based variant detection pipelines.
Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4CRBN ubiquitin ligase are a new class of cancer therapy in active clinical ...development with evidence of activity against acute myeloid leukemia in early-phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. We identified the domains of GSPT1 essential for cell survival and show that GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death. CRISPR/Cas9 screens implicated decreased translation initiation as protective following GSPT1 degradation, suggesting that cells with higher levels of translation are more susceptible to the effects of GSPT1 degradation. We defined 2 Crbn amino acids that prevent Gspt1 degradation in mice, generated a knockin mouse with alteration of these residues, and demonstrated the efficacy of GSPT1-degrading drugs in vivo with relative sparing of numbers and function of long-term hematopoietic stem cells. Our results provide a mechanistic basis for the use of GSPT1 degraders for the treatment of cancer, including TP53-mutant acute myeloid leukemia.
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