Addressing OSH challenges in non-standardized work practices in small-scale FMCG units by introducing context-specific ergonomic pouch/sachet cutting apparatus.

BACKGROUND: The FMCG manufacturing industry in industrially developing countries operates in a manual or semi-automatic setup, employing a vast labor force. Several non-standardized work activities prevail on the FMCG shop floor and remain prone to safety-related risks involving repetitive motions, forceful exertions, and awkward postures. Among those, the rework of defective pouches/sachets is an unsafe activity of prime concern. It is prone to minor nicks, cuts, and injuries due to inadequate tools being used. It involves sharp cutters/blades and extensive forceful manual hand squeezing, which leads to drudgery and safety concerns. There lies the lack of standardized tools/apparatus for rework activity, and efforts towards its mitigation are required. OBJECTIVE: Current research aims to address occupational safety-related issues in non-standardized rework activity in small-scale FMCG units through an innovative product design approach. METHODS: An ergo-audit was conducted in eight small-scale FMCG units to identify the prevailing ergonomic stressors and safety concerns. The most critical area of concern, i.e., rework activity, was chosen through card-sorting sessions and discussions held with the stakeholders. An appropriate context-specific apparatus was designed/developed to ensure better safety and occupational health utilizing a systematic product design method involving three phases: initial field survey, design and development, and field trials. RESULTS: The apparatus, which was developed and factory-trialed, was evaluated for productivity improvement and ensuring user compatibility from various human factors' perspectives. CONCLUSION: In field trials, the developed apparatus was found effective in mitigating safety concerns and various ergonomic stressors associated with FMCG rework.

KDEON WK-11: A short antipseudomonal peptide with promising potential.

The plight of antimicrobial resistance continues to limit the availability of antibiotic treatment effective in combating resistant bacterial infections. Despite efforts made to rectify this issue and minimise its effects on both patients and the wider community, progress in this area remains minimal. Here, we de-novo designed a peptide named KDEON WK-11, building on previous work establishing effective residues and structures active in distinguished antimicrobial peptides such as lactoferrin. We assessed its antimicrobial activity against an array of bacterial strains and identified its most potent effect, against Pseudomonas aeruginosa with an MIC value of 3.12 µM, lower than its counterparts developed with similar residues and chain lengths. We then determined its anti-biofilm properties, potential mechanism of action and in vitro cytotoxicity. We identified that KDEON WK-11 had a broad range of antimicrobial activity and specific capabilities to fight Pseudomonas aeruginosa with low in vitro cytotoxicity and promising potential to express anti-lipopolysaccharide qualities, which could be exploited to expand its properties into an anti-sepsis agent.

Socio-Demography, Working Conditions, and Musculoskeletal Ailments among Pineapple Farmers in Northeast India.

This study was conducted to examine the socio-demography, working conditions, and consequential musculoskeletal ailments of pineapple farmers in northeast India. A total of 152 pineapple farmers (92 males and 60 females) participated in the study. Data were collected using a pre-tested structured schedule and a standard Nordic questionnaire through personal interviews followed by direct observation. Chi-square (χ2) analysis and multiple logistic regression were conducted using SPSS software 16.0 to explore the association of various independent factors and their influences on the musculoskeletal symptoms (MSS) scores. The study revealed that a majority (>85%) of the pineapple farmers in northeast India had low to medium annual income, with more than 95% of the farmers belonging to small and marginal categories. Moreover, MSS were highly prevalent among the farmers (79.61%), and the low-back (76.32%) was the most affected body part. The results of the Chi-square (χ2) analysis highlighted that age, education level, and farming experience were significantly associated (p < 0.05) with the prevalence of overall MSS among the pineapple farmers. Among the factors, only age and gender significantly influenced the risk of complaints for the farmers' neck (OR = 6.62, 95% CI: 1.29-34.02, p ≤ 0.05) and low back (OR = 2.54, 95% CI: 1.00-6.47, p ≤ 0.05). This study's findings demonstrated the need for the urgent exploration of sustainable and innovative interventions to reduce the occurrence of MSS and improve the working conditions of the pineapple farmers in northeast India.

Mounting a smartphone on a steering-wheel to facilitate ease of visibility of the navigation screen: A systematic product design approach.

BACKGROUND: Both professional and personal car drivers use smartphones as In-Vehicle Infotainment System (IVIS) and generally mount it wherever they feel convenient. Inappropriate or sub-optimal positioning of navigation devices increases off-road eye-glance duration and fixation frequency. OBJECTIVE: The current research aimed to develop a smartphone holding device to facilitate the mobile-phone's easy mounting on the steering wheel's hub, ensuring the screen's visibility at a comfortable viewing angle in a vertical upright position irrespective of the steering wheel's rotation. METHODS: A systematic product design methodology was adopted to develop the final product. The morphological chart was adopted for generating the different concepts of the smartphone mounting device. A Pugh chart was used for screening the various concepts generated in the previous step. Finally, a prototype of the selected best concept was made. User acceptance was assessed by taking feedback from users, and System Usability Scale (SUS) was used for usability evaluation. RESULTS: The developed innovative mounting device was light-weight and easy to use (SUS score 83.5). The final prototype was very effective in changing the angle of the smartphone to facilitate easy visibility at a comfortable viewing angle through the use of a ball and socket mechanism at the base. A ball bearing system was used in the mobile-phone holder for maintaining vertical stationary position during steering wheel rotation. CONCLUSION: As the device is useful for mounting the smartphone on the steering wheel's hub, it might reduce driver distraction.

Emerging OSH Issues in Installation and Maintenance of Floating Solar Photovoltaic Projects and Their Link with Sustainable Development Goals.

OBJECTIVE: Emerging issues of occupational safety and health (OSH) in floating solar photovoltaic projects (FSPV) have rarely been addressed to achieve the Sustainable Development Goals (SDGs). The current scoping review has been planned to demonstrate OSH issues experienced by the workers engaged in the installation and maintenance of FSPV projects and existing ergonomics design interventions in the solar photovoltaic industry with a focus on the FSPV sector. METHODS: A literature review was conducted from four major electronic databases (Science Direct, Google Scholar, Web of Science, and Scopus) using predefined keywords and following the PRISMA framework for the period 1965-2020. A total of 49 studies under five headings, namely a) overview of key reasons for the emergence of floating solar photovoltaic projects, b) occupational risks of workers engaged in the solar PV industry/FSPV sector, c) occupational risks in workplaces/occupations similar to floating solar photovoltaics projects, d) availability of training modules and occupational standards, and e) design interventions/approaches in the solar PV industry/floating photovoltaics sector were analyzed. RESULTS: It emerged that workers are exposed to multifarious occupational risk factors such as heat, solar radiation, ergonomic risks, electrocution, fire, hazardous substances, adverse weather conditions, and psychosocial factors. These risks have not been adequately addressed with required interventions in the FSPV sector. Intervention opportunities include designing innovative tools, lowering of loads, redesigning workplace layouts, introducing job aids, automation, task rotation, job enlargement, design of training modules, OSH standards and changes in work organization/shift, etc. CONCLUSION: This review is a first-of-its-kind effort to highlight the contextual risk factors in the emerging FSPV sector and the need for addressing them through ergonomics design interventions for successfully achieving the Sustainable Development Goals.

A Comprehensive Review of Work-Related Musculoskeletal Disorders in the Mining Sector and Scope for Ergonomics Design Interventions.

OCCUPATIONAL APPLICATIONS Work-related Musculoskeletal Disorders (WMSDs) are prevalent in many industries worldwide, including the large and labor-intensive mining sector. A systematic review was carried out to understand problems in the mining sector issues from three broad perspectives: 1) the prevalence of WMSDs among miners; 2) the association of occupational, psychosocial, environmental, and other risk factors with WMSDs causation; and 3) ergonomics interventions already proposed or implemented, and scope for design interventions. Our review revealed that automation, job aids, and displays are methods suitable for ergonomic design interventions. Ergonomic intervention strategies at various hierarchical levels, and the successive way forward as proposed in our review, could act as a catalyst in formulating problem-specific solution strategies by the participation of diverse stakeholders to implement a more human-centric workplace.

TECHNICAL ABSTRACT Background Work-related Musculoskeletal Disorders (WMSDs) are prevalent in the mining sector. While there are numerous factors responsible for the occurrence of WMSDs in this labor-intensive sector, research pertaining to ergonomic design interventions that address various causative factors has not been thoroughly addressed. Purpose We aimed to present an overview of WMSDs in the mining sector, along with plausible intervention strategies in diverse task contexts as suggested by earlier researchers. We also sought to identify the prominent research gaps and propose a way forward to formulate context-specific solutions by involving all stakeholders. Methods Relevant research publications were identified from electronic databases (Google Scholar and ScienceDirect) using appropriate search terms applicable to the mining sector and WMSDs. The literature search was restricted to journal papers, conference proceedings, books, reports, and relevant websites in the English language published between 1990 and 2020. Results Information extracted from the literature review was categorized under three broad topics: 1) the prevalence of WMSDs among miners; 2) associations of psychosocial, occupational, environmental, and other risk factors with WMSDs; and 3) ergonomics interventions in the mining sector. Following the systematic literature review, we outline ergonomics intervention strategies at various levels and provide future research directions to assist all stakeholders in implementing appropriate and context-specific ergonomics design interventions to provide a more human-centric workplace. Conclusions Based on our findings, it is evident that there is an urgent need for formulating and applying job-related ergonomics design intervention plans for occupational safety and well-being of miners in the mining sector.

Nanomaterials in the field of design ergonomics: present status.

Application of nanotechnology and nanomaterials is not new in the field of design, but a recent trend of extensive use of nanomaterials in product and/or workplace design is drawing attention of design researchers all over the world. In the present paper, an attempt has been made to describe the diverse use of nanomaterials in product and workplace design with special emphasis on ergonomics (occupational health and safety; thermo-regulation and work efficiency, cognitive interface design; maintenance of workplace, etc.) to popularise the new discipline 'nanoergonomics' among designers, design users and design researchers. Nanoergonomics for sustainable product and workplace design by minimising occupational health risks has been felt by the authors to be an emerging research area in coming years. PRACTITIONER SUMMARY: Use of nanomaterials in the field of design ergonomics is less explored till date. In the present review, an attempt has been made to extend general awareness among ergonomists/designers about applications of nanomaterials/nanotechnology in the field of design ergonomics and about health implications of nanomaterials during their use.

Emotion and interior space design: an ergonomic perspective.

Interaction between the users and their environment is spontaneous and unavoidable. This interaction can be positive or negative. A good interior space is about considering all the physical, environmental and cognitive elements and harmonizing them to make it a space that feels right, functionally and emotionally. The important element that has to be considered the most in an interior space is the "user". Balancing all these elements is a challenging job and results in a perfect interior space design. This paper intends to bring to light the necessity of designing an optimum interior space, which is a balance of the user's choice and the mandatory standards that ought to be followed for user safety and convenience. There has to be an intervening domain of ergonomics which will guide to bring out a balance between the personal choice of the user and the usual standards followed. It should also provide a step-by-step information, guidance and direction to act to the specifications and standards systematically to adapt an integrated approach of handling all the elements holistically which will indeed result in a good interior space.

Application of digital human modeling and simulation for vision analysis of pilots in a jet aircraft: a case study.

Ergonomic evaluation of visual demands becomes crucial for the operators/users when rapid decision making is needed under extreme time constraint like navigation task of jet aircraft. Research reported here comprises ergonomic evaluation of pilot's vision in a jet aircraft in virtual environment to demonstrate how vision analysis tools of digital human modeling software can be used effectively for such study. Three (03) dynamic digital pilot models, representative of smallest, average and largest Indian pilot population were generated from anthropometric database and interfaced with digital prototype of the cockpit in Jack software for analysis of vision within and outside the cockpit. Vision analysis tools like view cones, eye view windows, blind spot area, obscuration zone, reflection zone etc. were employed during evaluation of visual fields. Vision analysis tool was also used for studying kinematic changes of pilot's body joints during simulated gazing activity. From present study, it can be concluded that vision analysis tool of digital human modeling software was found very effective in evaluation of position and alignment of different displays and controls in the workstation based upon their priorities within the visual fields and anthropometry of the targeted users, long before the development of its physical prototype.

Bone damage in rheumatoid arthritis: mechanistic insights and approaches to prevention.

In rheumatoid arthritis (RA), cells within the inflamed synovium and pannus elaborate a variety of cytokines, including tumor necrosis factor (TNF) alpha, interleukin (IL)-1, IL-6, and IL-17, that contribute to inflammation, and may directly affect bone. The receptor activator of NF-kappaB (RANK) ligand/RANK/osteoprotegerin pathway plays a critical role in regulating osteoclastogenesis in articular bone erosions in RA. Proinflammatory cytokines can modulate this pathway, and may also affect the ability of the osteoblast to repair bone at sites of articular erosion. In this review, the authors discuss the current understanding of pathogenic mechanisms of bone erosion in RA and examine current therapeutic approaches to prevent this damage.

Galectin-1 induces reversible phosphatidylserine exposure at the plasma membrane.

Cells normally undergo physiological turnover through the induction of apoptosis and phagocytic removal, partly through exposure of cell surface phosphatidylserine (PS). In contrast, neutrophils appear to possess apoptosis-independent mechanisms of removal. Here we show that Galectin-1 (Gal-1) induces PS exposure independent of alterations in mitochondrial potential, caspase activation, or cell death. Furthermore, Gal-1-induced PS exposure reverts after Gal-1 removal without altering cell viability. Gal-1-induced PS exposure is uniquely microdomain restricted, yet cells exposing PS do not display evident alterations in membrane morphology nor do they exhibit bleb formation, typically seen in apoptotic cells. Long-term exposure to Gal-1 prolongs PS exposure with no alteration in cell cycle progression or cell growth. These results demonstrate that Gal-1-induced PS exposure and subsequent phagocytic removal of living cells represents a new paradigm in cellular turnover.

Ligand reduces galectin-1 sensitivity to oxidative inactivation by enhancing dimer formation.

Galectin-1 (Gal-1) regulates leukocyte turnover by inducing the cell surface exposure of phosphatidylserine (PS), a ligand that targets cells for phagocytic removal, in the absence of apoptosis. Gal-1 monomer-dimer equilibrium appears to modulate Gal-1-induced PS exposure, although the mechanism underlying this regulation remains unclear. Here we show that monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidation. A mutant form of Gal-1, containing C2S and V5D mutations (mGal-1), exhibits impaired dimerization and fails to induce cell surface PS exposure while retaining the ability to recognize carbohydrates and signal Ca(2+) flux in leukocytes. mGal-1 also displayed enhanced sensitivity to oxidation, whereas ligand, which partially protected Gal-1 from oxidation, enhanced Gal-1 dimerization. Continual incubation of leukocytes with Gal-1 resulted in gradual oxidative inactivation with concomitant loss of cell surface PS, whereas rapid oxidation prevented mGal-1 from inducing PS exposure. Stabilization of Gal-1 or mGal-1 with iodoacetamide fully protected Gal-1 and mGal-1 from oxidation. Alkylation-induced stabilization allowed Gal-1 to signal sustained PS exposure in leukocytes and mGal-1 to signal both Ca(2+) flux and PS exposure. Taken together, these results demonstrate that monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidative inactivation and provides a mechanism whereby ligand partially protects Gal-1 from oxidation.

Galectin-1 signaling in leukocytes requires expression of complex-type N-glycans.

Dimeric galectin-1 (dGal-1) is a homodimeric lectin with multiple proposed functions. Although dGal-1 binds to diverse glycans, it is unclear whether dGal-1 preferentially binds to specific subsets of glycans on cell surfaces to transmit signals. To explore this question, we selectively inhibited major glycan biosynthetic pathways in human HL60, Molt-4, and Jurkat cells. Inhibition of N-glycan processing blocked surface binding of dGal-1 and prevented dGal-1-induced Ca(2+) mobilization and phosphatidylserine exposure. By contrast, inhibition of O-glycan or glycosphingolipid biosynthesis did not affect dGal-1 binding or dGal-1-induced Ca(2+) mobilization and phosphatidylserine exposure. These results demonstrate that dGal-1 preferentially binds to and signals through glycoproteins containing complex-type N-glycans in at least some leukocyte subsets.

Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion.

Galectin-1 (Gal-1) and galectin-3 (Gal-3) exhibit profound but unique immunomodulatory activities in animals but their molecular mechanisms are incompletely understood. Early studies suggested that Gal-1 inhibits leukocyte function by inducing apoptotic cell death and removal, but recent studies show that some galectins induce exposure of the common death signal phosphatidylserine (PS) independently of apoptosis. In this study, we report that Gal-3, but not Gal-1, induces both PS exposure and apoptosis in primary activated human T cells, whereas both Gal-1 and Gal-3 induce PS exposure in neutrophils in the absence of cell death. Gal-1 and Gal-3 bind differently to the surfaces of T cells and only Gal-3 mobilizes intracellular Ca2+ in these cells, although Gal-1 and Gal-3 bind their respective T cell ligands with similar affinities. Although Gal-1 does not alter T cell viability, it induces IL-10 production and attenuates IFN-gamma production in activated T cells, suggesting a mechanism for Gal-1-mediated immunosuppression in vivo. These studies demonstrate that Gal-1 and Gal-3 induce differential responses in T cells and neutrophils, and identify the first factor, Gal-3, capable of inducing PS exposure with or without accompanying apoptosis in different leukocytes, thus providing a possible mechanism for galectin-mediated immunomodulation in vivo.

Human galectin-1, -2, and -4 induce surface exposure of phosphatidylserine in activated human neutrophils but not in activated T cells.

Cellular turnover is associated with exposure of surface phosphatidylserine (PS) in apoptotic cells, leading to their phagocytic recognition and removal. But recent studies indicate that surface PS exposure is not always associated with apoptosis. Here we show that several members of the human galectin family of glycan binding proteins (galectins-1, -2, and -4) induce PS exposure in a carbohydrate-dependent fashion in activated, but not resting, human neutrophils and in several leukocyte cell lines. PS exposure is not associated with apoptosis in activated neutrophils. The exposure of PS in cell lines treated with these galectins is sustained and does not affect cell viability. Unexpectedly, these galectins bind well to activated T lymphocytes, but do not induce either PS exposure or apoptosis, indicating that galectin's effects are cell specific. These results suggest novel immunoregulatory contribution of galectins in regulating leukocyte turnover independently of apoptosis.

Contributions of Ca2+ to galectin-1-induced exposure of phosphatidylserine on activated neutrophils.

Apoptotic cells redistribute phosphatidylserine (PS) to the cell surface by both Ca(2+)-dependent and -independent mechanisms. Binding of dimeric galectin-1 (dGal-1) to glycoconjugates on N-formyl-Met-Leu-Phe (fMLP)-activated neutrophils exposes PS and facilitates neutrophil phagocytosis by macrophages, yet it does not initiate apoptosis. We asked whether dGal-1 initiated Ca(2+) fluxes that are required to redistribute PS to the surface of activated neutrophils. Prolonged occupancy by dGal-1 was required to maximally mobilize PS to the surfaces of fMLP-activated neutrophils. Like fMLP, dGal-1 rapidly elevated cytosolic Ca(2+) levels in Fluo-4-loaded neutrophils. An initial Ca(2+) mobilization from intracellular stores was followed by movement of extracellular Ca(2+) to the cytosolic compartment, with return to basal Ca(2+) levels within 10 min. Chelation of extracellular Ca(2+) did not prevent PS mobilization. Chelation of intracellular Ca(2+) revealed that fMLP and dGal-1 independently release Ca(2+) from intracellular stores that cooperate to induce optimal redistribution of PS. Ca(2+) mobilization by ionomycin did not permit dGal-1 to mobilize PS, indicating that fMLP initiated both Ca(2+)-dependent and -independent signals that facilitated dGal-1-induced exposure of PS. dGal-1 elevated cytosolic Ca(2+) and mobilized PS through a pathway that required action of Src kinases and phospholipase Cgamma. These results demonstrate that transient Ca(2+) fluxes contribute to a sustained redistribution of PS on neutrophils activated with fMLP and dGal-1.

Structurally distinct requirements for binding of P-selectin glycoprotein ligand-1 and sialyl Lewis x to Anaplasma phagocytophilum and P-selectin.

Colonization of neutrophils by the bacterium Anaplasma phagocytophilum causes the disease human granulocytic ehrlichiosis. The pathogen also infects mice, its natural host. Like binding of P-selectin, binding of A. phagocytophilum to human neutrophils requires expression of P-selectin glycoprotein ligand-1 (PSGL-1) and alpha1-3-fucosyltransferases that construct the glycan determinant sialyl Lewis x (sLex). Binding of A. phagocytophilum to murine neutrophils, however, requires expression of alpha1-3-fucosyltransferases but not PSGL-1. To further characterize the molecular features that A. phagocytophilum recognizes, we measured bacterial binding to microspheres bearing specific glycoconjugates or to cells expressing human PSGL-1 and particular glycosyltransferases. Like P-selectin, A. phagocytophilum bound to purified human PSGL-1 and to glycopeptides modeled after the N terminus of human PSGL-1 that presented sLex on an O-glycan. Unlike P-selectin, A. phagocytophilum bound to glycopeptides that contained sLex but lacked tyrosine sulfation or a specific core-2 orientation of sLex on the O-glycan. A. phagocytophilum bound only to glycopeptides that contained a short amino acid sequence found in the N-terminal region of human but not murine PSGL-1. Unlike P-selectin, A. phagocytophilum bound to cells expressing PSGL-1 in cooperation with sLex on both N-and O-glycans. Moreover, bacteria bound to microspheres coupled independently with glycopeptide lacking sLex and with sLex lacking peptide. These results demonstrate that, unlike P-selectin, A. phagocytophilum binds cooperatively to a nonsulfated N-terminal peptide in human PSGL-1 and to sLex expressed on PSGL-1 or other glycoproteins. Distinct bacterial adhesins may mediate these cooperative interactions.

Dimeric galectin-1 induces surface exposure of phosphatidylserine and phagocytic recognition of leukocytes without inducing apoptosis.

We report that human galectin-1 (dGal-1), a small dimeric beta-galactoside-binding protein, induces phosphatidylserine (PS) exposure, measured by Annexin V staining, on human promyelocytic HL-60 cells, T leukemic MOLT-4 cells, and fMet-Leu-Phe-activated, but not resting, human neutrophils. This effect of dGal-1 on HL-60 and MOLT-4 cells is enhanced by pretreatment of the cells with neuraminidase, but treatment of resting neutrophils with neuraminidase does not enhance their sensitivity to dGal-1. Although the induction of staining with Annexin V is often associated with apoptosis, the dGal-1-treated HL-60 cells, MOLT-4 cells, and activated neutrophils do not undergo apoptosis, and there is no detectable DNA fragmentation. HL-60 and MOLT-4 cells treated with dGal-1 continue to grow normally. By contrast, camptothecin-treated HL-60 cells, etoposide-treated MOLT-4 cells, and anti-Fas-treated neutrophils exhibit extensive DNA fragmentation and/or cell death. Lactose inhibits the dGal-1-induced effects, indicating that dGal-1-induced signaling requires binding to cell surface beta-galactosides. The dimeric form of Gal-1 is required for signaling, because a monomeric mutant form of Gal-1, termed mGal-1, binds to cells but does not cause these effects. Importantly, dGal-1, but not mGal-1, treatment of HL-60 cells and activated human neutrophils significantly promotes their phagocytosis by activated mouse macrophages. These dGal-1-induced effects are distinguishable from apoptosis, but like apoptotic agents, prepare cells for phagocytic removal. Such effects of dGal-1 may contribute to leukocyte homeostasis.

Integrin receptors and ECM proteins involved in preferential adhesion of colon carcinoma cells to lung cells.

To assess the putative role of extracellular matrix (ECM) proteins on lung cells interacting with integrin receptors on colon carcinoma cells, an in vitro adhesion assay was used to investigate these factors. Tumor necrosis factor (TNF)-alpha treatment of fetal lung cell line MRC 9, upregulated expression of ECM proteins and also supported enhanced adhesion of PTC colon carcinoma cells. Antibodies to ECM proteins significantly blocked this enhanced adhesion of PTC cells. Similarly, antibody blocking of beta1 and beta2 integrin receptors on PTC cells revealed the integrin receptors involved in this enhanced adhesion. beta1 integrin receptors like alpha2beta1, alpha4beta1 and alpha5beta1 on PTC cells were found interacting with their ECM ligands like fibronectin and laminin on TNF-alpha stimulated MRC 9 cells. Interestingly, PTC cells were found to constitutively express alphaLbeta2, which is normally expressed by leukocytes. The data from the present study indicates that expression of multiple beta1 and beta2 integrins by colon carcinoma cells putatively allows these cells to successfully adhere to secondary sites like lungs.