Facilitating return to work through early specialist health-based interventions (FRESH): protocol for a feasibility randomised controlled trial

Background Over one million people sustain traumatic brain injury each year in the UK and more than 10 % of these are moderate or severe injuries, resulting in cognitive and psychological problems that affect the ability to work. Returning to work is a primary rehabilitation goal but fewer than half of traumatic brain injury survivors achieve this. Work is a recognised health service outcome, yet UK service provision varies widely and there is little robust evidence to inform rehabilitation practice. A single-centre cohort comparison suggested better work outcomes may be achieved through early occupational therapy targeted at job retention. This study aims to determine whether this intervention can be delivered in three new trauma centres and to conduct a feasibility, randomised controlled trial to determine whether its effects and cost effectiveness can be measured to inform a definitive trial. Methods/design Mixed methods study, including feasibility randomised controlled trial, embedded qualitative studies and feasibility economic evaluation will recruit 102 people with traumatic brain injury and their nominated carers from three English UK National Health Service (NHS) trauma centres. Participants will be randomised to receive either usual NHS rehabilitation or usual rehabilitation plus early specialist traumatic brain injury vocational rehabilitation delivered by an occupational therapist. The primary objective is to assess the feasibility of conducting a definitive trial; secondary objectives include measurement of protocol integrity (inclusion/exclusion criteria, intervention adherence, reasons for non-adherence) recruitment rate, the proportion of eligible patients recruited, reasons for non-recruitment, spectrum of TBI severity, proportion of and reasons for loss to follow-up, completeness of data collection, gains in face-to-face Vs postal data collection and the most appropriate methods of measuring primary outcomes (return to work, retention) to determine the sample size for a larger trial. Discussion To our knowledge, this is the first feasibility randomised controlled trial of a vocational rehabilitation health intervention specific to traumatic brain injury. The results will inform the design of a definitive trial

A Human Development Framework for CO2 Reductions

Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

A flexible component-based robot control architecture for hormonal modulation of behaviour and affect

This document is the Accepted Manuscritpt of a paper published in Proceedings of 18th Annual Conference, TAROS 2017, Guildford, UK, July 19–21, 2017. Under embargo. Embargo end date: 20 July 2018. The final publication is available at Springer via https://link.springer.com/chapter/10.1007%2F978-3-319-64107-2_36. © 2017 Springer, Cham.In this paper we present the foundations of an architecture that will support the wider context of our work, which is to explore the link between affect, perception and behaviour from an embodied perspective and assess their relevance to Human Robot Interaction (HRI). Our approach builds upon existing affect-based architectures by combining artificial hormones with discrete abstract components that are designed with the explicit consideration of influencing, and being receptive to, the wider affective state of the robot

Mir142 loss unlocks IDH2R140-dependent leukemogenesis through antagonistic regulation of HOX genes

AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2R140Q, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2R140Q. Our analysis suggests that IDH2R140Q is an incoherent oncogene, with both positive and negative impacts on leukemogenesis, which requires the action of cooperating mutations to alleviate repression of Hoxa genes in order to advance to leukemia. This model, therefore, provides a compelling rationale for understanding how different mutations cooperate to drive leukemogenesis and the context-dependent effects of oncogenic mutations

On the Banach lattice structure of L-w(1) of a vector measure on a delta-ring

We study some Banach lattice properties of the space L-w(1)(v) of weakly integrable functions with respect to a vector measure v defined on a delta-ring. Namely, we analyze order continuity, order density and Fatou type properties. We will see that the behavior of L-w(1)(v) differs from the case in which is defined on a sigma-algebra whenever does not satisfy certain local sigma-finiteness property.J. M. Calabuig and M. A. Juan were supported by the Ministerio de Economia y Competitividad (project MTM2008-04594). O. Delgado was supported by the Ministerio de Economia y Competitividad (project MTM2009-12740-C03-02). E. A. Sanchez Perez was supported by the Ministerio de Economia y Competitividad (project MTM2009-14483-C02-02).Calabuig Rodriguez, JM.; Delgado Garrido, O.; Juan Blanco, MA.; Sánchez Pérez, EA. (2014). On the Banach lattice structure of L-w(1) of a vector measure on a delta-ring. Collectanea Mathematica. 65(1):67-85. doi:10.1007/s13348-013-0081-8S6785651Brooks, J.K., Dinculeanu, N.: Strong additivity, absolute continuity and compactness in spaces of measures. J. Math. Anal. Appl. 45, 156–175 (1974)Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 364, 88–103 (2010)Calabuig, J.M., Juan, M.A., Sánchez Pérez, E.A.: Spaces of $$p$$ -integrable functions with respect to a vector measure defined on a $$\delta$$ -ring. Oper. Matrices 6, 241–262 (2012)Curbera, G.P.: El espacio de funciones integrables respecto de una medida vectorial. Ph. D. thesis, University of Sevilla, Sevilla (1992)Curbera, G.P.: Operators into $$L^1$$ of a vector measure and applications to Banach lattices. Math. Ann. 293, 317–330 (1992)Curbera, G.P., Ricker, W.J.: Banach lattices with the Fatou property and optimal domains of kernel operators. Indag. Math. (N.S.) 17, 187–204 (2006)G. P. Curbera and W. J. Ricker, Vector measures, integration and applications. In: Positivity (in Trends Math.), Birkhäuser, Basel, pp. 127–160 (2007)Curbera, G.P., Ricker, W.J.: The Fatou property in $$p$$ -convex Banach lattices. J. Math. Anal. Appl. 328, 287–294 (2007)Delgado, O.: $$L^1$$ -spaces of vector measures defined on $$\delta$$ -rings. Arch. Math. 84, 432–443 (2005)Delgado, O.: Optimal domains for kernel operators on $$[0,\infty )\times [0,\infty )$$ . Studia Math. 174, 131–145 (2006)Delgado, O., Soria, J.: Optimal domain for the Hardy operator. J. Funct. Anal. 244, 119–133 (2007)Delgado, O., Juan, M.A.: Representation of Banach lattices as $$L_w^1$$ spaces of a vector measure defined on a $$\delta$$ -ring. Bull. Belg. Math. Soc. Simon Stevin 19(2), 239–256 (2012)Diestel, J., Uhl, J.J.: Vector measures (Am. Math. Soc. surveys 15). American Mathematical Society, Providence (1997)Dinculeanu, N.: Vector measures, Hochschulbcher fr Mathematik, vol. 64. VEB Deutscher Verlag der Wissenschaften, Berlin (1966)Fernández, A., Mayoral, F., Naranjo, F., Sáez, C., Sánchez Pérez, E.A.: Spaces of $$p$$ -integrable functions with respect to a vector measure. Positivity 10, 1–16 (2006)Fremlin, D.H.: Measure theory, broad foundations, vol. 2. Torres Fremlin, Colchester (2001)Jiménez Fernández, E., Juan, M.A., Sánchez Pérez, E.A.: A Komlós theorem for abstract Banach lattices of measurable functions. J. Math. Anal. Appl. 383, 130–136 (2011)Lewis, D.R.: On integrability and summability in vector spaces. Ill. J. Math. 16, 294–307 (1972)Lindenstrauss, J., Tzafriri, L.: Classical Banach spaces II. Springer, Berlin (1979)Luxemburg, W.A.J., Zaanen, A.C.: Riesz spaces I. North-Holland, Amsterdam (1971)Masani, P.R., Niemi, H.: The integration theory of Banach space valued measures and the Tonelli-Fubini theorems. I. Scalar-valued measures on $$\delta$$ -rings. Adv. Math. 73, 204–241 (1989)Masani, P.R., Niemi, H.: The integration theory of Banach space valued measures and the Tonelli-Fubini theorems. II. Pettis integration. Adv. Math. 75, 121–167 (1989)Thomas, E.G.F.: Vector integration (unpublished) (2013)Turpin, Ph.: Intégration par rapport à une mesure à valeurs dans un espace vectoriel topologique non supposé localement convexe, Intègration vectorielle et multivoque, (Colloq., University Caen, Caen, 1975), experiment no. 8, Dèp. Math., UER Sci., University Caen, Caen (1975)Okada, S., Ricker, W.J., Sánchez Pérez, E.A.: Optimal domain and integral extension of operators acting in function spaces (Oper. Theory Adv. Appl.), vol. 180. Birkhäuser, Basel (2008)Zaanen, A.C.: Riesz spaces II. North-Holland, Amsterdam (1983

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Моделі процесів захисту цілісності інформаційних об’єктів з використанням коду умовних лишків. Алгоритм нулізації

The models of processes of defense of integrity of information’s holding object with application of code of conditional tailings which provide high probabilities of exposure of violations of integrity and correction of the exposed curvatures are examined