• Labels and object categorization in six- and nine-month-olds: tracking labels across varying carrier phrases.

      Ferry, Alissa; email: alissa.ferry@manchester.ac.uk; Guellai, Bahia (2021-07-29)
      Language shapes object categorization in infants. This starts as a general enhanced attentional effect of language, which narrows to a specific link between labels and categories by twelve months. The current experiments examined this narrowing effect by investigating when infants track a consistent label across varied input. Six-month-old infants (N = 48) were familiarized to category exemplars, each presented with the exact same labeling phrase or the same label in different phrases. Evidence of object categorization at test was only found with the same phrase, suggesting that infants were not tracking the label's consistency, but rather that of the entire input. Nine-month-olds (N = 24) did show evidence of categorization across the varied phrases, suggesting that they were tracking the consistent label across the varied input. [Abstract copyright: Copyright © 2021 Elsevier Inc. All rights reserved.]
    • Lack of racial diversity within the palliative medicine workforce: does it affect our patients?

      Khiroya, Heena; orcid: 0000-0001-7613-1881; email: heenakhiroya@doctors.org.uk; Willis, Derek (2021-09-17)
    • Landslides in the Upper Submarine Slopes of Volcanic Islands: The Central Azores

      Chang, Yu‐Chun; orcid: 0000-0003-4941-5437; email: yu-chun.chang@manchester.ac.uk; Mitchell, Neil C.; orcid: 0000-0002-6483-2450; Quartau, Rui; orcid: 0000-0003-3148-7520 (2021-09-28)
      Abstract: Small landslides in the upper submarine slopes of volcanic islands present potential hazards locally because of their high frequency. We examine evidence for landsliding in high‐resolution bathymetric data from Faial, Pico, São Jorge, and Terceira islands of the Azores. Because the rugged morphology of the upper slopes makes landslides difficult to interpret, we develop two classification schemes for the 1,227 identified slope valleys. One scheme addresses how recognizable the valleys were as originating from landslides (whether scarps are prominent or indefinite), whereas the other scheme addresses valley types (whether apparently produced by single or multiple failures). Size distributions are used to assess the relative occurrence of large versus small landslides. Thirteen landslides are predicted to have generated tsunami heights at source of >1 m and one with height of >7 m. Some slopes have gradients far above 30°, the angle of repose of incohesive clastic sediment, so the seabed in those areas is strengthened perhaps by carbonate cementation, by seismic shaking or by the presence of coherent lava or lava talus. Using all types of slope valleys, Faial and Pico have smaller affected volumes per unit slope area than those of São Jorge and Terceira. These differences could be associated with varied seismic activity, with more frequent earthquakes beneath Faial and Pico preventing the build‐up of sediments on their slopes. Submarine landslide statistics are therefore potentially useful for assessing long‐term earthquake hazards of volcanic islands in seismically active environments such as the Azores.
    • Language evolution and healthiness for critical cyber‐physical systems

      Banach, Richard; orcid: 0000-0002-0243-9434; email: richard.banach@manchester.ac.uk; Zhu, Huibiao (2020-09-16)
      Abstract: In the effort to develop critical cyber‐physical systems, it is tempting to extend existing computing formalisms to include continuous behaviour. This may happen in a way that neglects elements necessary for correctly expressing continuous properties of the mathematics and correct physical properties of the real‐world physical system. A simple language is taken to illustrate these possibilities. Issues and risks latent in this kind of approach are identified and discussed under the umbrella of ‘healthiness conditions’. Modifications to the language in the light of the conditions discussed are elaborated, resulting in the language Combined Discrete and Physical Programmes in Parallel (CDPPP). An example air conditioning system is used to illustrate the concepts presented, and it is developed both in the original ‘unhealthy’ language and in the modified ‘healthier’ CDPPP. The formal semantics of the improved language is explored.
    • Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists

      Lindsay, Colin R.; email: colin.lindsay@manchester.ac.uk; Shaw, Emily C.; Moore, David A.; Rassl, Doris; Jamal-Hanjani, Mariam; Steele, Nicola; Naheed, Salma; Dick, Craig; Taylor, Fiona; Adderley, Helen; et al. (Nature Publishing Group UK, 2021-09-06)
      Abstract: Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.
    • Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists.

      Lindsay, Colin R; email: colin.lindsay@manchester.ac.uk; Shaw, Emily C; Moore, David A; Rassl, Doris; Jamal-Hanjani, Mariam; Steele, Nicola; Naheed, Salma; Dick, Craig; Taylor, Fiona; Adderley, Helen; et al. (2021-09-06)
      Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies. [Abstract copyright: © 2021. The Author(s).]
    • Laser capture microdissection coupled mass spectrometry (LCM-MS) for spatially resolved analysis of formalin-fixed and stained human lung tissues

      Herrera, Jeremy A.; orcid: 0000-0003-4845-8494; email: Jeremy.Herrera@manchester.ac.uk; Mallikarjun, Venkatesh; Rosini, Silvia; Montero, Maria Angeles; Lawless, Craig; Warwood, Stacey; O’Cualain, Ronan; Knight, David; Schwartz, Martin A.; Swift, Joe; orcid: 0000-0002-5039-9094; email: Joe.Swift@manchester.ac.uk (BioMed Central, 2020-06-17)
      Abstract: Background: Haematoxylin and eosin (H&E)—which respectively stain nuclei blue and other cellular and stromal material pink—are routinely used for clinical diagnosis based on the identification of morphological features. A richer characterization can be achieved by laser capture microdissection coupled to mass spectrometry (LCM-MS), giving an unbiased assay of the proteins that make up the tissue. However, the process of fixing and H&E staining of tissues provides challenges with standard sample preparation methods for mass spectrometry, resulting in low protein yield. Here we describe a microproteomics technique to analyse H&E-stained, formalin-fixed paraffin-embedded (FFPE) tissues. Methods: Herein, we utilize heat extraction, physical disruption, and in column digestion for the analysis of H&E stained FFPE tissues. Micro-dissected morphologically normal human lung alveoli (0.082 mm3) and human lung blood vessels (0.094 mm3) from FFPE-fixed H&E-stained sections from Idiopathic Pulmonary Fibrosis (IPF) specimens (n = 3 IPF specimens) were then subject to a qualitative and then quantitative proteomics approach using BayesENproteomics. In addition, we tested the sensitivity of this method by processing and analysing a range of micro-dissected human lung blood vessel tissue volumes. Results: This approach yields 1252 uniquely expressed proteins (at a protein identification threshold of 3 unique peptides) with 892 differentially expressed proteins between these regions. In accord with prior knowledge, our methodology approach confirms that human lung blood vessels are enriched with smoothelin, CNN1, ITGA7, MYH11, TAGLN, and PTGIS; whereas morphologically normal human lung alveoli are enriched with cytokeratin-7, -8, -18, -19, 14, and -17. In addition, we identify a total of 137 extracellular matrix (ECM) proteins and immunohistologically validate that laminin subunit beta-1 localizes to morphologically normal human lung alveoli and tenascin localizes to human lung blood vessels. Lastly, we show that this micro-proteomics technique can be applied to tissue volumes as low as 0.0125 mm3. Conclusion: Herein we show that our multistep sample preparation methodology of LCM-MS can identify distinct, characteristic proteomic compositions of anatomical features within complex fixed and stained tissues.
    • Laser solid-phase synthesis of single-atom catalysts

      Peng, Yudong; Cao, Jianyun; Sha, Yang; Yang, Wenji; Li, Lin; Liu, Zhu; email: zhu.liu@manchester.ac.uk (Nature Publishing Group UK, 2021-08-18)
      Abstract: Single-atom catalysts (SACs) with atomically dispersed catalytic sites have shown outstanding catalytic performance in a variety of reactions. However, the development of facile and high-yield techniques for the fabrication of SACs remains challenging. In this paper, we report a laser-induced solid-phase strategy for the synthesis of Pt SACs on graphene support. Simply by rapid laser scanning/irradiation of a freeze-dried electrochemical graphene oxide (EGO) film loaded with chloroplatinic acid (H2PtCl6), we enabled simultaneous pyrolysis of H2PtCl6 into SACs and reduction/graphitization of EGO into graphene. The rapid freezing of EGO hydrogel film infused with H2PtCl6 solution in liquid nitrogen and the subsequent ice sublimation by freeze-drying were essential to achieve the atomically dispersed Pt. Nanosecond pulsed infrared (IR; 1064 nm) and picosecond pulsed ultraviolet (UV; 355 nm) lasers were used to investigate the effects of laser wavelength and pulse duration on the SACs formation mechanism. The atomically dispersed Pt on graphene support exhibited a small overpotential of −42.3 mV at −10 mA cm−2 for hydrogen evolution reaction and a mass activity tenfold higher than that of the commercial Pt/C catalyst. This method is simple, fast and potentially versatile, and scalable for the mass production of SACs.
    • Late diagnosis of isolated central diabetes insipidus secondary to congenital toxoplasmosis-case report.

      Omer, Tahir; orcid: 0000-0003-1832-6204; Khan, Mustafa; Western, Thomas (2020-11-24)
      Congenital toxoplasmosis is an uncommon infection. Hypothalamic/pituitary involvement leading to isolated central diabetes insipidus is extremely rare. Making a correct diagnosis of this condition, albeit challenging, is crucial for adequate management. We present a 54-year-old female who developed central diabetes insipidus as a complication of congenital toxoplasmosis. She had polydipsia and hypernatraemia on presentation and responded to intranasal desmopressin with normalization of above-mentioned findings. Magnetic resonance imaging and cranial X-ray's showed pronounced intracranial calcifications in both choroid plexuses. Thyroid function tests, serum cortisol level and anterior pituitary function were all normal. To the best of our knowledge, this is the first reported case of isolated diabetes insipidus due to congenital toxoplasmosis in literature diagnosed late in adulthood and gives an insight into the challenges of diagnosing central diabetes insipidus and the hypothalamic/pituitary involvement in cases of congenital toxoplasmosis. [Abstract copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.]
    • Late diagnosis of isolated central diabetes insipidus secondary to congenital toxoplasmosis—case report

      Omer, Tahir; orcid: 0000-0003-1832-6204; Khan, Mustafa; Western, Thomas (Oxford University Press (OUP), 2020-11-24)
      ABSTRACT Congenital toxoplasmosis is an uncommon infection. Hypothalamic/pituitary involvement leading to isolated central diabetes insipidus is extremely rare. Making a correct diagnosis of this condition, albeit challenging, is crucial for adequate management. We present a 54-year-old female who developed central diabetes insipidus as a complication of congenital toxoplasmosis. She had polydipsia and hypernatraemia on presentation and responded to intranasal desmopressin with normalization of above-mentioned findings. Magnetic resonance imaging and cranial X-ray’s showed pronounced intracranial calcifications in both choroid plexuses. Thyroid function tests, serum cortisol level and anterior pituitary function were all normal. To the best of our knowledge, this is the first reported case of isolated diabetes insipidus due to congenital toxoplasmosis in literature diagnosed late in adulthood and gives an insight into the challenges of diagnosing central diabetes insipidus and the hypothalamic/pituitary involvement in cases of congenital toxoplasmosis.
    • Latent Class Analysis of Mental Health in Middle Childhood: Evidence for the Dual-Factor Model

      Petersen, Kimberly J.; orcid: 0000-0002-4941-6897; email: kimberly.petersen@manchester.ac.uk; Humphrey, Neil; orcid: 0000-0002-8148-9500; Qualter, Pamela; orcid: 0000-0001-6114-3820 (Springer US, 2020-07-25)
      Abstract: Mental health is complex, comprising both mental distress and well-being. This study used latent class analysis to identify common combinations of mental distress and well-being (‘mental health classes’) among schoolchildren aged 8–9 years (N = 3340). Thirteen items, measuring a range of conduct problems, emotional symptoms, and subjective well-being, were included in the analysis. Four mental health classes were identified: (1) complete mental health (n = 1895, 57%), (2) vulnerable (n = 434, 13%), (3) emotional symptoms but content (n = 606, 18%), and (4) conduct problems but content (n = 404, 12%). The classes were reliably identified across different datasets, and for males and females. Differential relations with covariates indicated that mental health classes were distinct and externally valid. The results supported the dual-factor model of mental health, suggesting that mental distress and subjective well-being are separate continua. Three of the four possible combinations of high and low distress and subjective well-being posited by the dual-factor model were found using this inductive statistical method. Importantly, our analysis also revealed two ‘symptomatic but content’ groups, differentiated by symptom domain (internalising/externalising). The covariate analyses between mental health classes and sociodemographic factors, prior academic attainment, school connectedness, and peer support, indicated that there are nuanced relations between those variables and particular constellations of mental distress and well-being. As one of the few dual-factor studies to focus on middle childhood, the current study adds important new evidence that contributes to our understanding of the complexities of mental health among schoolchildren.
    • Latest Insights on Novel Deep Eutectic Solvents (DES) for Sustainable Extraction of Phenolic Compounds from Natural Sources

      Serna-Vázquez, Julio; email: juliosernav@outlook.es; Ahmad, Mohd Zamidi; orcid: 0000-0002-8132-3818; email: mohdzamidi.ahmad@manchester.ac.uk; Boczkaj, Grzegorz; orcid: 0000-0002-5874-7591; email: grzegorz.boczkaj@pg.edu.pl; Castro-Muñoz, Roberto; orcid: 0000-0002-7657-3302; email: food.biotechnology88@gmail.com (MDPI, 2021-08-19)
      Phenolic compounds have long been of great importance in the pharmaceutical, food, and cosmetic industries. Unfortunately, conventional extraction procedures have a high cost and are time consuming, and the solvents used can represent a safety risk for operators, consumers, and the environment. Deep eutectic solvents (DESs) are green alternatives for extraction processes, given their low or non-toxicity, biodegradability, and reusability. This review discusses the latest research (in the last two years) employing DESs for phenolic extraction, solvent components, extraction yields, extraction method characteristics, and reviewing the phenolic sources (natural products, by-products, wastes, etc.). This work also analyzes and discusses the most relevant DES-based studies for phenolic extraction from natural sources, their extraction strategies using DESs, their molecular mechanisms, and potential applications.
    • Laughing with, Laughing at

      Lionis, Chrisoula; email: chrisoula.lionis@manchester.ac.uk; Efthymiou, Alkisti; email: alkisefth@gmail.com (Berghahn Books, 2021-09-01)
      The autumn of 2019 was characterised by an eruption of global protests, including Lebanon, Iraq, Ecuador, Chile, and Egypt. The velocity with which these protests emerged nurtured a sense that the Global South ‘was on the march’. At the same time as these events were rapidly unfolding, the world’s premier mass art exhibition, the Venice Biennale, was in its final weeks. Harnessing discourse analysis, participant observation, and collaborative auto-ethnography, the authors draw together a comparative study of the Chilean and Egyptian pavilions and assess the impact of ongoing and suspended revolutionary histories of both nations. Approaching art as a form of ‘practical aesthetics’ (Bennett 2012) and focusing on humour as an aesthetic quality enmeshed in complex political temporalities, this article analyses the relationship between humour, contemporary art, and revolution, demonstrating how the laughter facilitated by these two pavilions negotiates understandings of national pasts, and uprisings in the present.
    • Learning Actions From Natural Language Instructions Using an ON-World Embodied Cognitive Architecture

      Giorgi, Ioanna; email: ioanna.giorgi@manchester.ac.uk; Cangelosi, Angelo; Masala, Giovanni L. (Frontiers Media S.A., 2021-05-13)
      Endowing robots with the ability to view the world the way humans do, to understand natural language and to learn novel semantic meanings when they are deployed in the physical world, is a compelling problem. Another significant aspect is linking language to action, in particular, utterances involving abstract words, in artificial agents. In this work, we propose a novel methodology, using a brain-inspired architecture, to model an appropriate mapping of language with the percept and internal motor representation in humanoid robots. This research presents the first robotic instantiation of a complex architecture based on the Baddeley's Working Memory (WM) model. Our proposed method grants a scalable knowledge representation of verbal and non-verbal signals in the cognitive architecture, which supports incremental open-ended learning. Human spoken utterances about the workspace and the task are combined with the internal knowledge map of the robot to achieve task accomplishment goals. We train the robot to understand instructions involving higher-order (abstract) linguistic concepts of developmental complexity, which cannot be directly hooked in the physical world and are not pre-defined in the robot's static self-representation. Our proposed interactive learning method grants flexible run-time acquisition of novel linguistic forms and real-world information, without training the cognitive model anew. Hence, the robot can adapt to new workspaces that include novel objects and task outcomes. We assess the potential of the proposed methodology in verification experiments with a humanoid robot. The obtained results suggest robust capabilities of the model to link language bi-directionally with the physical environment and solve a variety of manipulation tasks, starting with limited knowledge and gradually learning from the run-time interaction with the tutor, past the pre-trained stage.
    • Learning healthcare systems and rapid learning in radiation oncology: Where are we and where are we going?

      Price, Gareth; email: gareth.price@manchester.ac.uk; Mackay, Ranald; Aznar, Marianne; McWilliam, Alan; Johnson-Hart, Corinne; van Herk, Marcel; Faivre-Finn, Corinne (2021-10-04)
      Learning health systems and rapid-learning are well developed at the conceptual level. The promise of rapidly generating and applying evidence where conventional clinical trials would not usually be practical is attractive in principle. The connectivity of modern digital healthcare information systems and the increasing volumes of data accrued through patients' care pathways offer an ideal platform for the concepts. This is particularly true in radiotherapy where modern treatment planning and image guidance offers a precise digital record of the treatment planned and delivered. The vision is of real-world data, accrued by patients during their routine care, being used to drive programmes of continuous clinical improvement as part of standard practice. This vision, however, is not yet a reality in radiotherapy departments. In this article we review the literature to explore why this is not the case, identify barriers to its implementation, and suggest how wider clinical application might be achieved. [Abstract copyright: Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.]
    • Lifestyle-dependent microglial plasticity: training the brain guardians

      Augusto-Oliveira, Marcus; email: marcusadeoliveira@outlook.com; Verkhratsky, Alexei; orcid: 0000-0003-2592-9898; email: alexej.verkhratsky@manchester.ac.uk (BioMed Central, 2021-08-05)
      Abstract: Lifestyle is one of the most powerful instruments shaping mankind; the lifestyle includes many aspects of interactions with the environment, from nourishment and education to physical activity and quality of sleep. All these factors taken in complex affect neuroplasticity and define brain performance and cognitive longevity. In particular, physical exercise, exposure to enriched environment and dieting act through complex modifications of microglial cells, which change their phenotype and modulate their functional activity thus translating lifestyle events into remodelling of brain homoeostasis and reshaping neural networks ultimately enhancing neuroprotection and cognitive longevity.
    • Lifestyle-dependent microglial plasticity: training the brain guardians.

      Augusto-Oliveira, Marcus; orcid: 0000-0002-4772-9929; email: marcusadeoliveira@outlook.com; Verkhratsky, Alexei; orcid: 0000-0003-2592-9898; email: alexej.verkhratsky@manchester.ac.uk (2021-08-05)
      Lifestyle is one of the most powerful instruments shaping mankind; the lifestyle includes many aspects of interactions with the environment, from nourishment and education to physical activity and quality of sleep. All these factors taken in complex affect neuroplasticity and define brain performance and cognitive longevity. In particular, physical exercise, exposure to enriched environment and dieting act through complex modifications of microglial cells, which change their phenotype and modulate their functional activity thus translating lifestyle events into remodelling of brain homoeostasis and reshaping neural networks ultimately enhancing neuroprotection and cognitive longevity.
    • Like Father Like Son: Cultural and Genetic Contributions to Song Inheritance in an Estrildid Finch

      Lewis, Rebecca N.; email: rebecca.lewis-3@manchester.ac.uk; Soma, Masayo; de Kort, Selvino R.; Gilman, R. Tucker (Frontiers Media S.A., 2021-06-04)
      Social learning of vocalizations is integral to song inheritance in oscine passerines. However, other factors, such as genetic inheritance and the developmental environment, can also influence song phenotype. The relative contributions of these factors can have a strong influence on song evolution and may affect important evolutionary processes such as speciation. However, relative contributions are well-described only for a few species and are likely to vary with taxonomy. Using archived song data, we examined patterns of song inheritance in a domestic population of Java sparrows (Lonchura oryzivora), some of which had been cross-fostered. Six-hundred and seventy-six songs from 73 birds were segmented and classified into notes and note subtypes (N = 22,972), for which a range of acoustic features were measured. Overall, we found strong evidence for cultural inheritance of song structure and of the acoustic characteristics of notes; sons’ song syntax and note composition were similar to that of their social fathers and were not influenced by genetic relatedness. For vocal consistency of note subtypes, a measure of vocal performance, there was no apparent evidence of social or genetic inheritance, but both age and developmental environment influenced consistency. These findings suggest that high learning fidelity of song material, i.e., song structure and note characteristics, could allow novel variants to be preserved and accumulate over generations, with implications for evolution and conservation. However, differences in vocal performance do not show strong links to cultural inheritance, instead potentially serving as condition dependent signals.
    • Limb preference and personality in donkeys (

      Díaz, Sergio; orcid: 0000-0002-3070-0097; Murray, Lindsay; orcid: 0000-0002-7810-9546; Rodway, Paul; orcid: 0000-0002-7667-6782 (2021-02-05)
      Interhemispheric laterality has often been linked to different behavioural styles. This study investigates the link between limb preference and personality in donkeys. The sample consisted of 47 donkeys ( ), 30 males and 17 females. Limb preference was determined using observation of the leading limb in a motionless posture and personality was measured using the Donkey Temperament Questionnaire (French, J. M. (1993). Assessment of donkey temperament and the influence of home environment. , (2), 249-257. doi:10.1016/0168-1591(93)90014-G) completed by the donkeys' keepers. A Principal Component Analysis obtained two components: Agreeableness and Extraversion. Age showed a positive relationship with Agreeableness, echoing trends in humans Donkeys did not show a population-level preference towards either side. Limb preference significantly predicted the trait : donkeys with a preference to keep the right foot forward when motionless were harder to handle. This study presents the first investigation into limb preference and personality in donkeys, although more research is needed to clarify whether there is a population-level limb preference bias in donkeys, and the relationship between limb preference and Agreeableness.
    • Limb preference and personality in donkeys (Equus asinus)

      Díaz, Sergio; orcid: 0000-0002-3070-0097; Murray, Lindsay; orcid: 0000-0002-7810-9546; Rodway, Paul; orcid: 0000-0002-7667-6782 (Informa UK Limited, 2021-02-05)