Within-individual changes reveal increasing social selectivity with age in rhesus macaques.

Accumulating evidence in humans and other mammals suggests older individuals tend to have smaller social networks. Uncovering the cause of these declines can inform how changes in social relationships with age affect health and fitness in later life. While age-based declines in social networks have been thought to be detrimental, physical and physiological limitations associated with age may lead older individuals to adjust their social behavior and be more selective in partner choice. Greater selectivity with age has been shown in humans, but the extent to which this phenomenon occurs across the animal kingdom remains an open question. Using longitudinal data from a population of rhesus macaques on Cayo Santiago, we provide compelling evidence in a nonhuman animal for within-individual increases in social selectivity with age. Our analyses revealed that adult female macaques actively reduced the size of their networks as they aged and focused on partners previously linked to fitness benefits, including kin and partners to whom they were strongly and consistently connected earlier in life. Females spent similar amounts of time socializing as they aged, suggesting that network shrinkage does not result from lack of motivation or ability to engage, nor was this narrowing driven by the deaths of social partners. Furthermore, females remained attractive companions and were not isolated by withdrawal of social partners. Taken together, our results provide rare empirical evidence for social selectivity in nonhumans, suggesting that patterns of increasing selectivity with age may be deeply rooted in primate evolution.

Speciation by physiological selection of environmentally acquired traits.

A chance mutation affecting a single or extremely few individuals in a continuous population will be quickly diluted through interbreeding. Charles Darwin fully appreciated this difficulty with relying on natural selection alone, and suggested an enabling role for geographical isolation in the origin of species. However, Darwin also believed in evolution by the inheritance of acquired traits and in populations of interbreeding animals, both of which would need a different isolating mechanism to overcome dilution and play a role in animal evolution. Historically disputed, the inheritance of acquired characters is now increasingly accepted as a phenomenon, and Charles Darwin himself is acknowledged as closely pre-empting the type of physiology necessary to mediate it in his hypothesis of 'pangenesis'. In this article, we question how the inheritance of acquired traits might overcome the problem of dilution by interbreeding and contribute to evolution. Specifically, we describe how Darwin's young protégé, George Romanes, developed ideas he discussed with Darwin and extended pangenesis to include a conceivable solution published after Darwin's death: physiological selection of fertility. In light of the 'rediscovery' of pangenesis, here we recount physiological selection as a testable hypothesis to explain how environmentally acquired characteristics could become coupled to the generation of species.

Rare-variant and polygenic analyses of amyotrophic lateral sclerosis in the French-Canadian genome.

PURPOSE: The genetic etiology of amyotrophic lateral sclerosis (ALS) includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both. METHODS: 335 ALS cases and 356 controls from Québec, Canada were concurrently tested by microarray genotyping and targeted sequencing of ALS genes known at the time of study inception. ALS genome-wide association studies summary statistics were used to estimate an ALS polygenic risk score (PRS). Cases and controls were subdivided into rare-variant heterozygotes and non-heterozygotes. RESULTS: Risk for ALS was significantly associated with PRS and rare variants independently in a logistic regression model. Although ALS PRS predicted a small amount of ALS risk overall, the effect was most pronounced between ALS cases and controls that were not heterozygous for a rare variant in the ALS genes surveyed. CONCLUSION: Both PRS and rare variants in ALS genes impact risk for ALS. PRS for ALS is most informative when rare variants are not observed in ALS genes.

Mitochondrial damage and impaired mitophagy contribute to disease progression in SCA6.

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease that manifests in midlife and progressively worsens with age. SCA6 is rare, and many patients are not diagnosed until long after disease onset. Whether disease-causing cellular alterations differ at different disease stages is currently unknown, but it is important to answer this question in order to identify appropriate therapeutic targets across disease duration. We used transcriptomics to identify changes in gene expression at disease onset in a well-established mouse model of SCA6 that recapitulates key disease features. We observed both up- and down-regulated genes with the major down-regulated gene ontology terms suggesting mitochondrial dysfunction. We explored mitochondrial function and structure and observed that changes in mitochondrial structure preceded changes in function, and that mitochondrial function was not significantly altered at disease onset but was impaired later during disease progression. We also detected elevated oxidative stress in cells at the same disease stage. In addition, we observed impairment in mitophagy that exacerbates mitochondrial dysfunction at late disease stages. In post-mortem SCA6 patient cerebellar tissue, we observed metabolic changes that are consistent with mitochondrial impairments, supporting our results from animal models being translatable to human disease. Our study reveals that mitochondrial dysfunction and impaired mitochondrial degradation likely contribute to disease progression in SCA6 and suggests that these could be promising targets for therapeutic interventions in particular for patients diagnosed after disease onset.

Unique case of lymphocytic hypophysitis with normal pituitary hormone serology mimicking a non-functioning pituitary adenoma.

BACKGROUND: Lymphocytic hypophysitis is a rare autoimmune condition that usually presents during pregnancy and causes inflammation of the pituitary gland. Although the pathophysiology is not well understood, it often presents with headaches, visual disturbances, and symptoms of hypopituitarism. However, not all cases may present with hypopituitarism which can make this rare disease with an incidence of ~ 1 in 9 million much more difficult to diagnose. CASE PRESENTATION: We present a 35-year-old G4P4 woman with progressive vision loss and intermittent frontal headaches during her first trimester through 2 months postpartum. She presented with no symptoms of hypopituitarism and her hormone panel only showed elevated prolactin, possibly due to her breastfeeding. She was treated with a right pterional craniotomy with decompression of both optic nerves, partial resection of the suprasellar mass, and glucocorticoid therapy for headaches and visual disturbances. CONCLUSION: This case is notable for a presentation of lymphocytic hypophysitis without symptoms of hypopituitarism. This is important for outpatient providers to be aware of, especially those that care for pregnant patients so that unfavorable outcomes can be avoided.

Polymeric surfactants at liquid-liquid interfaces: Dependence of structural and thermodynamic properties on copolymer architecture.

Polymeric surfactants are amphiphilic molecules with two or more different types of monomers. If one type of monomer interacts favorably with a liquid, and another type of monomer interacts favorably with another, immiscible liquid, then polymeric surfactants adsorb at the interface between the two liquids and reduce the interfacial tension. The effects of polymer architecture on the structural and thermodynamic properties of the liquid-liquid interface are studied using molecular simulations. The interface is modeled with a non-additive binary Lennard-Jones fluid in the two-phase region of the phase diagram. Block and gradient copolymer surfactants are represented with coarse-grained, bead-spring models, where each component of the polymer favors one or the other liquid. Gradient copolymers have a greater concentration at the interface than do block copolymers because the gradient copolymers adopt conformations partially aligned with the interface. The interfacial tension is determined as a function of the surface excess of polymeric surfactant. Gradient copolymers are more potent surfactants than block copolymers because the gradient copolymers cross the dividing surface multiple times, effectively acting as multiple individual surfactants. For a given surface excess, the interfacial tension decreases monotonically when changing from a block to a gradient architecture. The coarse-grained simulations are complemented by all-atom simulations of acrylic-acid/styrene copolymers at the chloroform-water interface, which have been studied in experiments. The agreement between the simulations (both coarse-grained and atomistic) and experiments is shown to be excellent, and the molecular-scale structures identified in the simulations help explain the variation of surfactancy with copolymer architecture.

Bubbling beyond the barrier: exosomal RNA as a vehicle for soma-germline communication.

'Weismann's barrier' has restricted theories of heredity to the transmission of genomic variation for the better part of a century. However, the discovery and elucidation of epigenetic mechanisms of gene regulation such as DNA methylation and histone modifications has renewed interest in studies on the inheritance of acquired traits and given them mechanistic plausibility. Although it is now clear that these mechanisms allow many environmentally acquired traits to be transmitted to the offspring, how phenotypic information is communicated from the body to its gametes has remained a mystery. Here, we discuss recent evidence that such communication is mediated by somatic RNAs that travel inside extracellular vesicles to the gametes where they reprogram the offspring epigenome and phenotype. How gametes learn about bodily changes has implications not only for the clinic, but also for evolutionary theory by bringing together intra- and intergenerational mechanisms of phenotypic plasticity and adaptation.

Multiple axes of visual system diversity in Ithomiini, an ecologically diverse tribe of mimetic butterflies.

The striking structural variation seen in arthropod visual systems can be explained by the overall quantity and spatio-temporal structure of light within habitats coupled with developmental and physiological constraints. However, little is currently known about how fine-scale variation in visual structures arises across shorter evolutionary and ecological scales. In this study, we characterise patterns of interspecific (between species), intraspecific (between sexes) and intraindividual (between eye regions) variation in the visual system of four ithomiine butterfly species. These species are part of a diverse 26-million-year-old Neotropical radiation where changes in mimetic colouration are associated with fine-scale shifts in ecology, such as microhabitat preference. Using a combination of selection analyses on visual opsin sequences, in vivo ophthalmoscopy, micro-computed tomography (micro-CT), immunohistochemistry, confocal microscopy and neural tracing, we quantify and describe physiological, anatomical and molecular traits involved in visual processing. Using these data, we provide evidence of substantial variation within the visual systems of Ithomiini, including: (i) relaxed selection on visual opsins, perhaps mediated by habitat preference, (ii) interspecific shifts in visual system physiology and anatomy, and (iii) extensive sexual dimorphism, including the complete absence of a butterfly-specific optic neuropil in the males of some species. We conclude that considerable visual system variation can exist within diverse insect radiations, hinting at the evolutionary lability of these systems to rapidly develop specialisations to distinct visual ecologies, with selection acting at the perceptual, processing and molecular level.

Moyamoya Disease Susceptibility Gene RNF213 Regulates Endothelial Barrier Function.

BACKGROUND: Variants in the ring finger protein 213 (RNF213) gene are known to be associated with increased predisposition to cerebrovascular diseases development. Genomic studies have identified RNF213 as a major risk factor of Moyamoya disease in East Asian descendants. However, little is known about the RNF213 (ring finger protein 213) biological functions or its associated pathogenic mechanisms underlying Moyamoya disease. METHODS: To investigate RNF213 loss-of-function effect in endothelial cell, stable RNF213-deficient human cerebral endothelial cells were generated using the CRISPR-Cas9 genome editing technology. RESULTS: In vitro assays, using RNF213 knockout brain endothelial cells, showed clear morphological changes and increased blood-brain barrier permeability. Downregulation and delocalization of essential interendothelial junction proteins involved in the blood-brain barrier maintenance, such as PECAM-1 (platelet endothelial cell adhesion molecule-1), was also observed. Brain endothelial RNF213-deficient cells also showed an abnormal potential to transmigration of leukocytes and secreted high amounts of proinflammatory cytokines. CONCLUSIONS: Taken together, these results indicate that RNF213 could be a key regulator of cerebral endothelium integrity, whose disruption could be an early pathological mechanism leading to Moyamoya disease. This study also further reinforces the importance of blood-brain barrier integrity in the development of Moyamoya disease and other RNF213-associated diseases.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.

BACKGROUND: A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant. METHODS: Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 - relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18-55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2-11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6-84·5) for B.1.1.7 and 81·5% (67·9-89·4) for non-B.1.1.7 lineages. INTERPRETATION: ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2. FUNDING: UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

Gradient copolymers versus block copolymers: self-assembly in solution and surface adsorption.

The structures of amphiphilic block and gradient copolymers in solution and adsorbed onto surfaces are surveyed using molecular-dynamics simulations. A bead-spring model is used to identify the general effects of the different architectures: block and gradient copolymers have equal numbers of solvophilic and solvophobic beads, and the gradient copolymer is represented by a linear concentration profile along the chain. Each type of isolated copolymer forms a structure with a globular head of solvophobic beads, and a coil-like tail of solvophilic beads. The radius of gyration of a gradient copolymer is found to be much more sensitive to temperature than that of a block copolymer due to an unravelling mechanism. At finite concentrations, both gradient and block copolymers self-assemble into micelles, with the gradient copolymers again showing a larger temperature dependence. The micelles are characterised using simulated scattering profiles, which compare favourably to existing experimental data. The adsorption of copolymers onto structureless surfaces is modelled with an attractive potential that is selective for the solvophobic beads, and the surface structures are characterised using the average height of the molecules, and the proportion of beads adsorbed. Both types of copolymer form adsorbed films with persistent micelle-like structures, but the gradient copolymers show a stronger dependence on the strength of the surface interactions and the temperature. Coarse-grained, bead-spring models allow a rapid survey and comparison of the block and gradient architectures, and the results set the scene for future work with atomistic simulations. A superficial but favourable comparison is made between the results from the bead-spring models, and atomistic simulations of a butyl prop-2-enoate/prop-2-enoic acid (butyl acrylate/acrylic acid) copolymer in n-dodecane at room temperature.

Microbial survival and growth on non-corrodible conductive materials.

Biofilms growing aerobically on conductive substrates are often correlated with a positive, sustained shift in their redox potential. This phenomenon has a beneficial impact on microbial fuel cells by increasing their overall power output but can be detrimental when occurring on stainless steel by enhancing corrosion. The biological mechanism behind this potential shift is unresolved and a metabolic benefit to cells has not been demonstrated. Here, biofilms containing the electroautotroph 'Candidatus Tenderia electrophaga' catalysed a shift in the open circuit potential of graphite and indium tin oxide electrodes by >100 mV. Biofilms on open circuit electrodes had increased biomass and a significantly higher proportion of 'Ca. Tenderia electrophaga' compared to those on plain glass. Addition of metabolic inhibitors showed that living cells were required to maintain the more positive potential. We propose a model to describe these observations, in which 'Ca. Tenderia electrophaga' drives the shift in open circuit potential through electron uptake for oxygen reduction and CO2 fixation. We further propose that the electrode is continuously recharged by oxidation of trace redox-active molecules in the medium at the more positive potential. A similar phenomenon is possible on natural conductive substrates in the environment.

Melanin Produced by the Fast-Growing Marine Bacterium Vibrio natriegens through Heterologous Biosynthesis: Characterization and Application.

Melanin is a pigment produced by organisms throughout all domains of life. Due to its unique physicochemical properties, biocompatibility, and biostability, there has been an increasing interest in the use of melanin for broad applications. In the vast majority of studies, melanin has been either chemically synthesized or isolated from animals, which has restricted its use to small-scale applications. Using bacteria as biocatalysts is a promising and economical alternative for the large-scale production of biomaterials. In this study, we engineered the marine bacterium Vibrio natriegens, one of the fastest-growing organisms, to synthesize melanin by expressing a heterologous tyrosinase gene and demonstrated that melanin production was much faster than in previously reported heterologous systems. The melanin of V. natriegens was characterized as a polymer derived from dihydroxyindole-2-carboxylic acid (DHICA) and, similarly to synthetic melanin, exhibited several characteristic and useful features. Electron microscopy analysis demonstrated that melanin produced from V. natriegens formed nanoparticles that were assembled as "melanin ghost" structures, and the photoprotective properties of these particles were validated by their protection of cells from UV irradiation. Using a novel electrochemical reverse engineering method, we observed that melanization conferred redox activity to V. natriegens Moreover, melanized bacteria were able to quickly adsorb the organic compound trinitrotoluene (TNT). Overall, the genetic tractability, rapid division time, and ease of culture provide a set of attractive properties that compare favorably to current E. coli production strains and warrant the further development of this chassis as a microbial factory for natural product biosynthesis.IMPORTANCE Melanins are macromolecules that are ubiquitous in nature and impart a large variety of biological functions, including structure, coloration, radiation resistance, free radical scavenging, and thermoregulation. Currently, in the majority of investigations, melanins are either chemically synthesized or extracted from animals, which presents significant challenges for large-scale production. Bacteria have been used as biocatalysts to synthesize a variety of biomaterials due to their fast growth and amenability to genetic engineering using synthetic biology tools. In this study, we engineered the extremely fast-growing bacterium V. natriegens to synthesize melanin nanoparticles by expressing a heterologous tyrosinase gene with inducible promoters. Characterization of the melanin produced from V. natriegens-produced tyrosinase revealed that it exhibited physical and chemical properties similar to those of natural and chemically synthesized melanins, including nanoparticle structure, protection against UV damage, and adsorption of toxic compounds. We anticipate that producing and controlling melanin structures at the nanoscale in this bacterial system with synthetic biology tools will enable the design and rapid production of novel biomaterials for multiple applications.

The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra-spinal paraganglioma.

Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated 17 CEPs from 11 male and 6 female patients with a median age of 38 years (range 21-82), none with a family history of neuroendocrine neoplasia. Six of the 17 tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all 17 CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on 12 of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors.

Mobile Stroke Unit in the UK Healthcare System: Avoidance of Unnecessary Accident and Emergency Admissions.

BACKGROUND: Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay. OBJECTIVE: The aim of the study was to explore the benefit of a mobile stroke unit (MSU) in the UK National Health Service (NHS) for reduction of hospital admissions. METHODS: Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea was conducted. Emergency patients categorized as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to the accident and emergency (A&E) department, rate of admission directly to target ward, and stroke management metrics were assessed. RESULTS: In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); and other conditions, n = 38 (32.8%). Pre-hospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Pre-hospital diagnosis avoided hospital admission for 29 (25.0%) patients. As hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) even directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the A&E department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40-60). CONCLUSION: This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained A&E departments.

Patient Work and Their Contexts: Scoping Review.

BACKGROUND: Having patients self-manage their health conditions is a widely promoted concept, but many patients struggle to practice it effectively. Moreover, few studies have analyzed the nature of work required from patients and how such work fits into the context of their daily life. OBJECTIVE: This study aimed to review the characteristics of patient work in adult patients. Patient work refers to tasks that health conditions impose on patients (eg, taking medications) within a system of contextual factors. METHODS: A systematic scoping review was conducted using narrative synthesis. Data were extracted from PubMed, Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO, including studies from August 2013 to August 2018. The included studies focused on adult patients and assessed one or more of the following: (1) physical health-related tasks, (2) cognitive health-related tasks, or (3) contextual factors affecting these tasks. Tasks were categorized according to the themes that emerged: (1) if the task is always visible to others or can be cognitive, (2) if the task must be conducted collaboratively or can be conducted alone, and (3) if the task was done with the purpose of creating resources. Contextual factors were grouped according to the level at which they exert influence (micro, meso, or macro) and where they fit in the patient work system (the macroergonomic layer of physical, social, and organizational factors; the mesoergonomic layer of household and community; and the microergonomic triad of person-task-tools). RESULTS: In total, 67 publications were included, with 58 original research articles and 9 review articles. A variety of patient work tasks were observed, ranging from physical and tangible tasks (such as taking medications and visiting health care professionals) to psychological and social tasks (such as creating coping strategies). Patient work was affected by a range of contextual factors on the micro, meso, or macro levels. Our results indicate that most patient work was done alone, in private, and often imposing cognitive burden with low amounts of support. CONCLUSIONS: This review sought to provide insight into the work burden of health management from a patient perspective and how patient context influences such work. For many patients, health-related work is ever present, invisible, and overwhelming. When researchers and clinicians design and implement patient-facing interventions, it is important to understand how the extra work impacts one's internal state and coping strategy, how such work fits into daily routines, and if these changes could be maintained in the long term.

Provisional green infrastructure: transdisciplinary approaches to address contamination in urban streams.

Surface water contamination has emerged as an area of major concern in rapidly growing cities in the Global South, including and especially in the Indian megacity context. We argue here that nallahs (open drainage channels in Indian megacities) should be more widely recognized as a potential locus of intervention. These combined stormwater and wastewater networks offer opportunities for flexible, frugal and inclusive retrofits to improve surface and groundwater quality. We propose and define the concept of provisional green infrastructure (PGI) as a speculative innovation typology describing in-stream interventions. We argue that PGI should be employed as a shared boundary concept guiding transdisciplinary action and research within the highly unpredictable, space-constrained, and contaminated watersheds. Citing case studies throughout the region and ongoing research in the city of Bangalore, we demonstrate in-stream modifications may be capable of achieving significant improvement in the quality of urban wastewater and may play a complementary role in closing persistent capacity gaps in the operation of both centralized and decentralized treatment practices within megacities. Anticipating the larger diffusion of PGI practices across the region by various early adopters and non-state actors, we suggest a cogent research agenda focused on identifying various generalizable 'upscaling' opportunities for deploying in-stream interventions across various organizational and spatial domains.

An interdisciplinary examination of attentional focus strategies used during running gait retraining.

The aim was to investigate the biomechanical, physiological, and perceptual responses to different motor learning strategies derived to elicit a flatter foot contact. Twenty-eight rearfoot-striking recreational runners (age 24.9 ± 2.8 years; body mass 78.8 ± 13.6 kg; height 1.79 ± 0.09 m) were matched by age, mass, and height and assigned to one verbal cue group: internal focus of attention (IF), external focus of attention (EF), and a clinically derived condition (CLIN) incorporating an IF followed by an EF statement. Participants completed two treadmill runs at 10 km h-1 for 6 minutes each: normal running (control) followed by the experimental condition (IF, EF, or CLIN). Lower limb kinematics, oxygen consumption ( V ˙ O 2 ), and central and peripheral ratings of perceived exertion (RPE) were recorded for each run. Compared to the control condition, foot angle was reduced in the IF (difference = 5.86°, d = 2.58) and CLIN (difference = 3.00°, d = 1.31) conditions, but unchanged in the EF condition (difference = 0.33°, d = 0.14), while greater knee flexion at initial contact in the EF and CLIN conditions was observed (difference = -5.19°, d = 1.97; difference = -3.66°, d = 1.39, respectively). A higher V ˙ O 2 was observed in the CLIN condition (difference = -4.56 mL kg-1  min-1 , d = 2.29), but unchanged in the IF (difference = -1.87 mL kg-1  min-1 , d = 0.94) and EF conditions (difference = -0.37 mL kg-1  min-1 , d = 0.19). All experimental conditions increased central and peripheral RPE (difference = -1.08, d = 0.54 and difference = -2.39, d = 1.33, respectively). Providing gait retraining instructions using an internally directed focus of attention was the most effective way to target specific changes in running kinematics, with no detrimental effect on physiological responses. Yet, perceptual effort responses increased regardless of the type of cue provided.

Assessing local materials for the treatment of wastewater in open drains.

In the present study, three low-cost filter aggregate materials were tested and compared for organic matter and fecal coliform (FC) removal at the laboratory scale. Setups were subjected to synthetic wastewater at two hydraulic loading rates (HLR), i.e. 4 cm/day and 40 cm/day. The hydraulic retention time (HRT) at the two HLRs varied from 4 days to 12 h, respectively. The result obtained shows that the biochemical oxygen demand (BOD5) removal efficiency of aggregate materials decreased with the increase in HLR. Both at high and low HLR, the terracotta aggregate material exhibited maximum BOD5 loading removal and without significant difference for the case of FC removal efficiency for all the three aggregate materials. At higher HLR, cell debris and biofilm loss from the aggregate material contributed to the chemical oxygen demand (COD) levels in the treated water. The terracotta aggregate material provided best organic matter removal at both HLRs. The study demonstrates the potential of incorporating inexpensive and readily available local materials into decentralized, frugal green infrastructure interventions capable of lowering the quantum of harmful biological contaminants in open storm water channels in rapidly urbanizing cities of developing countries, and that the terracotta aggregate material provided best organic removal at both HLRs.