Conversational affective social robots for ageing and dementia support

Socially assistive robots (SAR) hold significant potential to assist older adults and people with dementia in human engagement and clinical contexts by supporting mental health and independence at home. While SAR research has recently experienced prolific growth, long-term trust, clinical translation and patient benefit remain immature. Affective human-robot interactions are unresolved and the deployment of robots with conversational abilities is fundamental for robustness and humanrobot engagement. In this paper, we review the state of the art within the past two decades, design trends, and current applications of conversational affective SAR for ageing and dementia support. A horizon scanning of AI voice technology for healthcare, including ubiquitous smart speakers, is further introduced to address current gaps inhibiting home use. We discuss the role of user-centred approaches in the design of voice systems, including the capacity to handle communication breakdowns for effective use by target populations. We summarise the state of development in interactions using speech and natural language processing, which forms a baseline for longitudinal health monitoring and cognitive assessment. Drawing from this foundation, we identify open challenges and propose future directions to advance conversational affective social robots for: 1) user engagement, 2) deployment in real-world settings, and 3) clinical translation

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.RCUK | Biotechnology and Biological Sciences Research Council (BBSRC): Lu Zhao, Cahir J O'Kane, BB/L021706/1; Wellcome: Martin Stofanko, Cahir J O'Kane, 08136; European Commission (EC): Lu Zhao, Niamh C O'Sullivan, Sophie Zaessinger, Olivier Blard, MCSA fellowships 220851,220874,236777,660516; Yousef Jameel Foundation: Belgin Yalçın; Singapore A*STAR Scholarship: Zi Han Kang, BM/RES/07/005; Cambridge Commonwealth, European and International Trust (Cambridge Commonwealth, European & International Trust): Belgin Yalçın, Anood Sohail; Pakistan Higher Education Council Scholarship: Anood Sohail; Motor Neurone Disease Association (MNDA): Alex L Patto, Studentship 861-792 The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication

Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.

This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007); doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile transcription and chromatin binding in a cell-type-specific manner is a powerful aid to understanding cell-fate specification and cellular function in multicellular organisms. We recently developed targeted DamID (TaDa) to enable genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins in vivo without cell isolation. As a protocol extension, this article describes substantial modifications to an existing protocol, and it offers additional applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA-binding profiles of proteins, by coupling it with the GAL4 system in Drosophila to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion proteins are expressed at very low levels, thus avoiding toxicity and potential artifacts from overexpression. The modifications to the core DamID technique presented here also increase the speed of sample processing and throughput, and adapt the method to next-generation sequencing technology. TaDa is robust, reproducible and highly sensitive. Compared with other methods for cell-type-specific profiling, the technique requires no cell-sorting, cross-linking or antisera, and binding profiles can be generated from as few as 10,000 total induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol II), TaDa can also identify transcribed genes in a cell-type-specific manner. Here we describe a detailed protocol for carrying out TaDa experiments and preparing the material for next-generation sequencing. Although we developed TaDa in Drosophila, it should be easily adapted to other organisms with an inducible expression system. Once transgenic animals are obtained, the entire experimental procedure-from collecting tissue samples to generating sequencing libraries-can be accomplished within 5 d.This work was funded by a Wellcome Trust Senior Investigator Award (103792), Wellcome Trust Programme Grant (092545) and BBSRC Project Grant (BB/L00786X/1) to A.H.B. A.H.B acknowledges core funding to the Gurdon Institute from the Wellcome Trust (092096) and CRUK (C6946/A14492).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nprot.2016.08

Therapeutic hypothermia translates from ancient history in to practice

Acute postasphyxial encephalopathy around the time of birth remains a major cause of death and disability. The possibility that hypothermia may be able to prevent or lessen asphyxial brain injury is a “dream revisited”. In this review, a historical perspective is provided from the first reported use of therapeutic hypothermia for brain injuries in antiquity, to the present day. The first uncontrolled trials of cooling for resuscitation were reported more than 50 y ago. The seminal insight that led to the modern revival of studies of neuroprotection was that after profound asphyxia, many brain cells show initial recovery from the insult during a short “latent” phase, typically lasting ~6 h, only to die hours to days later during a “secondary” deterioration phase characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Studies designed around this conceptual framework showed that mild hypothermia initiated as early as possible before the onset of secondary deterioration, and continued for a sufficient duration to allow the secondary deterioration to resolve, is associated with potent, long-lasting neuroprotection. There is now compelling evidence from randomized controlled trials that mild induced hypothermia significantly improves intact survival and neurodevelopmental outcomes to midchildhood

How Plants Sense Wounds: Damaged-Self Recognition Is Based on Plant-Derived Elicitors and Induces Octadecanoid Signaling

Background: Animal-derived elicitors can be used by plants to detect herbivory but they function only in specific insect– plant interactions. How can plants generally perceive damage caused by herbivores? Damaged-self recognition occurs when plants perceive molecular signals of damage: degraded plant molecules or molecules localized outside their original compartment. Methodology/Principal Findings: Flame wounding or applying leaf extract or solutions of sucrose or ATP to slightly wounded lima bean (Phaseolus lunatus) leaves induced the secretion of extrafloral nectar, an indirect defense mechanism. Chemically related molecules that would not be released in high concentrations from damaged plant cells (glucose, fructose, salt, and sorbitol) did not elicit a detectable response, excluding osmotic shock as an alternative explanation. Treatments inducing extrafloral nectar secretion also enhanced endogenous concentrations of the defense hormone jasmonic acid (JA). Endogenous JA was also induced by mechanically damaging leaves of lima bean, Arabidopsis, maize, strawberry, sesame and tomato. In lima bean, tomato and sesame, the application of leaf extract further increased endogenous JA content, indicating that damaged-self recognition is taxonomically widely distributed. Transcriptomic patterns obtained with untargeted 454 pyrosequencing of lima bean in response to flame wounding or the application of leaf extract or JA were highly similar to each other, but differed from the response to mere mechanical damage. W

Nursing diagnoses related to skin: operational definitions

OBJECTIVE: to validate the operational definitions of the defining characteristics and risk factors of the three NANDA International (NANDA-I) nursing diagnoses and to revise these diagnoses' definitions. METHOD: content validation of nursing diagnosis. 146 defining characteristics and risk factors were identified in the literature in Brazilian and international databases. This was followed by content validation of the definitions of these diagnoses (presented by NANDA-I) and of the operational definitions (developed by the researchers) of the defining characteristics and risk factors, carried out by six expert nurses, regarding relevance, clarity and comprehensiveness. RESULT: of the 146 defining characteristics and risk factors, 22 were considered redundant and were excluded. The experts proposed changing the definitions of the diagnoses of Impaired Tissue Integrity and Risk for Impaired Skin Integrity. It was possible to identify various defining characteristics and risk factors which are not present in the NANDA-I taxonomy but which are indicated in the literature. CONCLUSION: the process attained its objective of producing valid operational definitions for defining characteristics and risk factors, which will permit the undertaking of validation studies for these diagnoses. The study's contribution to advancing scientific knowledge consists in its presenting clearer operational definitions for these diagnoses and a higher number of defining characteristics and risk factors, which will assist the nurses in the identification and use of the same with greater accuracy in clinical practice.OBJETIVO: validar las definiciones operacionales de las características definidoras y factores de riesgo de los tres diagnósticos de enfermería relacionados a la piel de la NANDA International (NANDA-I) y revisar las definiciones de eses diagnósticos. MÉTODO: validación de contenido de diagnóstico de enfermería. Se identificaron 146 características definidoras y factores de riesgo en la literatura en las bases de datos nacionales e internacionales. Enseguida, se realizó la validación de contenido de las definiciones de estos diagnósticos, presentadas por la NANDA-I y de las definiciones operacionales, elaboradas por las investigadoras, de las características definidoras y factores de riesgo, por seis enfermeras expertas, en cuanto a la pertinencia, clareza y abarcamiento. RESULTADO: de las 146 características definidoras y factores de riesgo, 22 fueron considerados redundantes y excluidos. Los peritos propusieron alterar la definición de los diagnósticos de Integridad Tisular Dañada y Riesgo de Integridad de la Piel Dañada. Fue posible identificar varias características definidoras y factores de riesgo que no están presentes en la taxonomía de la NANDA-I, pero, que fueron apuntados por la literatura. CONCLUSIÓN: el proceso alcanzó el objetivo de producir definiciones operacionales válidas para características definidoras y factores de riesgo, lo que permitirá realizar estudios de validación de estos diagnósticos. La contribución del estudio para el avance del conocimiento científico consiste en presentar definiciones operacionales más claras de estos diagnósticos y un número mayor de características definidoras y factores de riesgo que podrá aportar con los enfermeros en la identificación y utilización de los mismos con mayor precisión en la práctica clínica.OBJETIVO: validar as definições operacionais das características definidoras e fatores de risco dos três diagnósticos de enfermagem, relacionados à pele, da NANDA International (NANDA-I), e revisar as definições desses diagnósticos. MÉTODO: validação de conteúdo de diagnóstico de enfermagem. Identificaram-se 146 características definidoras e fatores de risco na literatura, nas bases de dados nacionais e internacionais. Em seguida, realizou-se a validação de conteúdo das definições desses diagnósticos, apresentadas pela NANDA-I e das definições operacionais, elaboradas pelas pesquisadoras, das características definidoras e fatores de risco, por seis enfermeiras peritas, quanto à pertinência, clareza e abrangência. RESULTADOS: das 146 características definidoras e fatores de risco, 22 foram considerados redundantes e excluídos. Os peritos propuseram mudar a definição dos diagnósticos de Integridade Tissular Prejudicada e Risco de Integridade da Pele Prejudicada. Foi possível identificar várias características definidoras e fatores de risco que não estão presentes na taxonomia da NANDA-I, mas que foram apontados pela literatura. CONCLUSÃO: o processo atingiu o objetivo de produzir definições operacionais válidas para características definidoras e fatores de risco, o que permitirá realizar estudos de validação desses diagnósticos. A contribuição do estudo para o avanço do conhecimento científico consiste em apresentar definições operacionais mais claras desses diagnósticos e número maior de características definidoras e fatores de risco que poderão contribuir para que os enfermeiros identifiquem e se utilizem dos mesmos com maior acurácia na prática clínica

Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection

ABSTRACT: Background: Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming. Nonetheless, few in silico assessments of the effect of nutritional conditions on Mtb’s vulnerability and metabolic adaptation have been carried out. Results: A genome-scale model (GEM) of Mtb, modified from the H37Rv iOSDD890, was used to explore the metabolic reprogramming of two Mtb knockout mutants (pfkA- and icl-mutants), lacking key enzymes of central carbon metabolism, while exposed to changing nutritional conditions (oxygen, and carbon and nitrogen sources). A combination of shadow pricing, sensitivity analysis, and flux distributions patterns allowed us to identify metabolic behaviors that are in agreement with phenotypes reported in the literature. During hypoxia, at high glucose consumption, the Mtb pfkA-mutant showed a detrimental growth effect derived from the accumulation of toxic sugar phosphate intermediates (glucose-6-phosphate and fructose-6-phosphate) along with an increment of carbon fluxes towards the reductive direction of the tricarboxylic acid cycle (TCA). Furthermore, metabolic reprogramming of the icl-mutant (icl1&icl2) showed the importance of the methylmalonyl pathway for the detoxification of propionyl-CoA, during growth at high fatty acid consumption rates and aerobic conditions. At elevated levels of fatty acid uptake and hypoxia, we found a drop in TCA cycle intermediate accumulation that might create redox imbalance. Finally, findings regarding Mtb-mutant metabolic adaptation associated with asparagine consumption and acetate, succinate and alanine production, were in agreement with literature reports. Conclusions: This study demonstrates the potential application of genome-scale modeling, flux balance analysis (FBA), phenotypic phase plane (PhPP) analysis and shadow pricing to generate valuable insights about Mtb metabolic reprogramming in the context of human granulomas

A school-based physical activity promotion intervention in children: rationale and study protocol for the PREVIENE Project

The lack of physical activity and increasing time spent in sedentary behaviours during childhood place importance on developing low cost, easy-toimplement school-based interventions to increase physical activity among children. The PREVIENE Project will evaluate the effectiveness of five innovative, simple, and feasible interventions (active commuting to/from school, active Physical Education lessons, active school recess, sleep health promotion, and an integrated program incorporating all 4 interventions) to improve physical activity, fitness, anthropometry, sleep health, academic achievement, and health-related quality of life in primary school children. The PREVIENE Project will provide the information about the effectiveness and implementation of different school-based interventions for physical activity promotion in primary school children.The PREVIENE Project was funded by the Spanish Ministry of Economy and Competitiveness (DEP2015-63988-R, MINECO-FEDER). MAG is supported by grants from the Spanish Ministry of Economy and Competitivenes