Hydroamination reactions by metal triflates: Bronsted acid vs. metal catalysis?

Catalytic hydroamination reactions involving the addition of carboxamides (X = CO), carbamates (X = CO2) and sulfonamides (X = SO2) to unactivated CC bonds are briefly reviewed. Development in this field of catalytic research is briefly charted, followed by a discussion of possible mechanisms, including arguments to support the operation of both metal and Brønsted acid catalysis in these systems. Future developments in the area are summarised. © The Royal Society of Chemistry 2010.39511711175Müller, T.E., Hultzsch, K.C., Yus, M., Foubelo, F., Tada, M., (2008) Chem. Rev., 108, p. 3795Constable, D.J.C., Dunn, P.J., Hayler, J.D., Humphrey, G.R., Leazer, J.L., Linderman, R.J., Lorenz, K., Zhang, T.Y., (2007) Green Chem., 9, p. 411Ranu, B.C., Banerjee, S., (2007) Tetrahedron Lett., 48, p. 141. , For example, seeKumar, R., Chaudhary, P., Nimesh, S., Chandra, R., (2006) Green Chem., 8, p. 356Dzhemilev, U., Tolstikov, G., Khusnutdinov, R., (2009) Russ. J. Org. Chem., 45, p. 957Quinet, C., Jourdain, P., Hermans, C., Atest, A., Lucas, I., Marko, I.E., (2008) Tetrahedron, 64, p. 1077. , See for exampleHorrillo-Martinez, P., Hultzsch, K.C., Gil, A., Branchadell, V., (2007) Eur. J. Org. Chem., p. 3311Crimmin, M.R., Arrowsmith, M., Barrett, A.G.M., Casely, I.J., Hill, M.S., Procopiou, P.A., (2009) J. Am. Chem. Soc., 131, p. 9670Hong, S., Marks, T.J., (2004) Acc. Chem. Res., 37, p. 673Walsh, P.J., Baranger, A.M., Bergman, R.G., (1992) J. Am. Chem. Soc., 114, p. 1708Müller, C., Koch, R., Doye, S., (2008) Chem.-Eur. J., 14, p. 10430Beller, M., Trauthwein, H., Eichberger, M., Breindl, C., Herwig, J., Müller, T.E., Thiel, O.R., (1999) Chem.-Eur. J., 5, p. 1306Rodriguez-Zubiri, M., Anguille, S., Brunet, J.J., (2007) J. Mol. Catal. A: Chem., 271, p. 145Bäckvall, J.E., Åkermark, B., Ljunggren, S.O., (1979) J. Am. Chem. Soc., 101, p. 2411Hahn, C., (2004) Chem.-Eur. J., 10, p. 5888. , See for exampleMotta, A., Fragala, I.L., Marks, T.J., (2006) Organometallics, 25, p. 5533Tobisch, S., (2008) Chem.-Eur. J., 14, p. 8590Aillaud, I., Collin, J., Hannedouche, J., Schulz, E., (2007) Dalton Trans., p. 5105Qian, H., Widenhoefer, R.A., (2005) Org. Lett., 7, p. 2635Karshtedt, D., Bell, A.T., Tilley, T.D., (2005) J. Am. Chem. Soc., 127, p. 12640Zhang, J., Yang, C., He, C., (2006) J. Am. Chem. Soc., 128, p. 1798Brouwer, C., He, C., (2006) Angew. Chem., Int. Ed., 45, p. 1744Giner, X., Najera, C., (2008) Org. Lett., 10, p. 2919Taylor, J.G., Whittall, N., Hii, K.K., (2005) Chem. Commun., p. 5103Taylor, J.G., Whittall, N., Hii, K.K., (2006) Org. Lett., 8, p. 3561Dias, H.V.R., Wu, J., (2008) Eur. J. Inorg. Chem., p. 509. , For a discussion of ethylene complexes ofCu(i), Ag(i) and Au(i), seeMcBee, J.L., Bell, A.T., Tilley, T.D., (2008) J. Am. Chem. Soc., 130, p. 16562Cheng, X.J., Xia, Y.Z., Wei, H., Xu, B., Zhang, C.G., Li, Y.H., Qian, G.M., Li, W., (2008) Eur. J. Org. Chem., p. 1929Rosenfeld, D.C., Shekhar, S., Takemiya, A., Utsunomiya, M., Hartwig, J.F., (2006) Org. Lett., 8, p. 4179Li, Z., Zhang, J., Brouwer, C., Yang, C.-G., Reich, N.W., He, C., (2006) Org. Lett., 8, p. 4175Wabnitz, T.C., Yu, J.Q., Spencer, J.B., (2004) Chem.-Eur. J., 10, p. 484Taylor, J.G., (2008), PhD Thesis, Imperial College LondonHuang, J.M., Wong, C.M., Xu, F.X., Loh, T.P., (2007) Tetrahedron Lett., 48, p. 3375Michaux, J., Terrasson, V., Marque, S., Wehbe, J., Prim, D., Campagne, J.M., (2007) Eur. J. Org. Chem., p. 2601Motokura, K., Nakagiri, N., Mori, K., Mizugaki, T., Ebitani, K., Jitsukawa, K., Kaneda, K., (2006) Org. Lett., 8, p. 4617Yang, L., Xu, L.W., Xia, C.G., (2008) Tetrahedron Lett., 49, p. 2882Kovacs, G., Ujaque, G., Lledos, A., (2008) J. Am. Chem. Soc., 130, p. 853Dorta, R., Egli, P., Zurcher, F., Togni, A., (1997) J. Am. Chem. Soc., 119, p. 10857Hartwig, J.F., (2004) Pure Appl. Chem., 76, p. 507. , These were shown to proceed via allylpalladium(ii) intermediates, see, and references thereinJohns, A.M., Sakai, N., Ridder, A., Hartwig, J.F., (2006) J. Am. Chem. Soc., 128, p. 9306Zhang, Z., Lee, S.D., Widenhoefer, R.A., (2009) J. Am. Chem. Soc., 131, p. 5372Anastas, P., Warner, J., (1998) Green Chemistry: Theory and Practice, , Oxford University Press, New Yor

Predicting the Microbial Risk in Flooded London Dwellings Using Microbial, Hygrothermal, and GIS Modelling

With a changing climate, London is expected to experience more frequent periods of intense rainfall and tidal surges, which will lead to an increase in the risk of flooding. Floodwater may deposit harmful microorganisms on building surfaces, while damp indoor environments in flooded dwellings can support the growth of microorganisms including mould, bacteria, and protozoa. This thesis investigates possible flood-borne and damp-related pathogens in flooded London dwellings, and the potential duration of microbial contamination risk following a flood event. Microbiological laboratory work and models are used to characterise microbial risk within flooded dwellings. Dwelling archetypes representative of the London housing stock are developed and hygrothermal simulation techniques used to model the flooding and drying behaviour of the archetypes under different scenarios in order to predict the duration of damp and microbial risk inside typical dwellings. The results of the combined biological and hygrothermal models are mapped alongside existing flood risk maps in order to predict areas in London susceptible to long-term microbial risk or prolonged displacement following a flood. Highlights of the research findings include the following (i) The persistence of bacterial contaminants on flooded materials is related to the type of floodwater, the drying conditions including temperature and drying rate, and the material drying characteristics, ii) Different dwellings in London have different drying behaviours due to their built form and dominant wall types, with modern purpose-built flats the most prone to long-term damp and microbial risk following a flood event, (iii) The flood height, external weather, and internal conditions including heating and ventilation can have a major impact on the length of time a dwelling will remain at risk of microbial contamination, and (iv) The concentration of properties vulnerable to long-term microbial exposure following major flood events is highest in areas of South and East London, particularly Southwark

Faecal contamination pathways of shallow groundwater in low-income urban areas: implications for water resource planning and management

Shallow groundwater is vulnerable to faecal contamination, especially in low-income urban areas where use of on-site sanitation facilities is high. This paper explores statistical relationships between potential factors influencing contaminant pathways (i.e., variables) and observed faecal contamination of shallow groundwater, represented by nitrate concentrations and counts of Escherichia coli (i.e., response function) in a small, growing town in Uganda over dry and wet seasons in 2018 and 2019. A statistically significant (p = 0.004) multiple linear regression model from dry-season E. coli counts in 2018 identifies medium sanitary risk levels and modes of construction as significant pathways (p = 0.01). Water source depth (10 m) to a pit latrine were also significant (p<0.05) in both hydrogeological formations. No significant linear regression models were established for NO3 during both seasons due to low pH and rapid infiltration velocities; incon-sistent sample timing during the wet season impaired the significance of the statistical models of E. coli counts. We show that modes of construction of water sources and pit latrines play key roles in determining the quality of the shallow groundwater in urban environments. Greater emphasis is therefore required to improve the functionality and sustainability of on-site water sources and pit latrines

Modelling and monitoring tools to evaluate the Urban Heat Island's contribution to the risk of indoor overheating

The growth of cit ies increases urban surface areas and anthropogenic heat generation, causing an Urban Heat Island (UHI) effect. In the UK , UHI effects may cause positive (winter) and negative (summer) health , comfort and energy consumption consequences . With the increasing focus on climate change - related heat exposure and consequent increased mortality risk, there is a need to better investigate the UHI during hot seasons. This paper reviews the current literature regarding UHI characterisation using monitoring, modelling, and remote sensing approaches, their limitations, and applications in building simulation and population heat exposure models . Ongoing and future research is briefly introduced in which downscaling techniques are proposed that provide higher temporal and spatial information to assess and locate heat - associated health risk in London

WASH conditions in a small town in Uganda: how safe are on-site facilities?

Inadequate hygiene coupled with the conjunctive use of the shallow subsurface as both a source of water and repository of faecal matter pose substantial risks to human health in low-income countries undergoing rapid urbanisation. To evaluate water, sanitation and hygiene (WASH) conditions in a small, rapidly growing town in central Uganda (Lukaya) served primarily by on-site water supply and sanitation facilities, water-point mapping, focus group discussions, sanitary-risk inspections and 386 household surveys were conducted. Household surveys indicate high awareness (82%) of domestic hygiene (e.g. handwashing, boiling water) but limited evidence of practice. WHO Sanitary Risk Surveys and Rapid Participatory Sanitation System Risk Assessments reveal further that community hygiene around water points and sanitation facilities including their maintenance is commonly inadequate. Spot sampling of groundwater quality shows widespread faecal contamination indicated by enumerated thermo-tolerant coliforms (TTCs) (Escherichia coli) ranging from 0 to 104 cfc/100 mL and nitrate concentrations that occasionally exceed 250 mg/L. As defined by the WHO/UNICEF Joint Monitoring programme, there are no safely managed water sources in Lukaya; ∼55% of improved water sources comprising primarily shallow hand-dug wells show gross faecal contamination by E. coli; and 51% of on-site sanitation facilities are unimproved. Despite the critical importance of on-site water supply and sanitation facilities in low-income countries to the realisation of UN Sustainable Goal 6 (access to safe water and sanitation for all by 2030), the analysis highlights the fragility and vulnerability of these systems where current monitoring and maintenance of communal facilities are commonly inadequate

Active immunization with myelin-derived altered peptide ligand reduces mechanical pain hypersensitivity following peripheral nerve injury

BACKGROUND: T cells have been implicated in neuropathic pain that is caused by peripheral nerve injury. Immunogenic myelin basic protein (MBP) peptides have been shown to initiate mechanical allodynia in a T cell-dependent manner. Antagonistic altered peptide ligands (APLs) are peptides with substitutions in amino acid residues at T cell receptor contact sites and can inhibit T cell function and modulate inflammatory responses. In the present study, we studied the effects of immunization with MBP-derived APL on pain behavior and neuroinflammation in an animal model of peripheral nerve injury. METHODS: Lewis rats were immunized subcutaneously at the base of the tail with either a weakly encephalitogenic peptide of MBP (cyclo-MBP(87-99)) or APL (cyclo-(87-99)[A(91),A(96)]MBP(87-99)) in complete Freund’s adjuvant (CFA) or CFA only (control), following chronic constriction injury (CCI) of the left sciatic nerve. Pain hypersensitivity was tested by measurements of paw withdrawal threshold to mechanical stimuli, regulatory T cells in spleen and lymph nodes were analyzed by flow cytometry, and immune cell infiltration into the nervous system was assessed by immunohistochemistry (days 10 and 30 post-CCI). Cytokines were measured in serum and nervous tissue of nerve-injured rats (day 10 post-CCI). RESULTS: Rats immunized with the APL cyclo-(87-99)[A(91),A(96)]MBP(87-99) had significantly reduced mechanical pain hypersensitivity in the ipsilateral hindpaw compared to cyclo-MBP(87-99)-treated and control rats. This was associated with significantly decreased infiltration of T cells and ED1+ macrophages in the injured nerve of APL-treated animals. The percentage of anti-inflammatory (M2) macrophages was significantly upregulated in the APL-treated rats on day 30 post-CCI. Compared to the control rats, microglial activation in the ipsilateral lumbar spinal cord was significantly increased in the MBP-treated rats, but was not altered in the rats immunized with the MBP-derived APL. In addition, immunization with the APL significantly increased splenic regulatory T cells. Several cytokines were significantly altered after CCI, but no significant difference was observed between the APL-treated and control rats. CONCLUSIONS: These results suggest that immune deviation by active immunization with a non-encephalitogenic MBP-derived APL mediates an analgesic effect in animals with peripheral nerve injury. Thus, T cell immunomodulation warrants further investigation as a possible therapeutic strategy for the treatment of peripheral neuropathic pain

Modelling population exposure to high indoor temperatures under changing climates, housing conditions, and urban environments in England

: The exposure of an individual to heat during hot weather depends on several factors including local outdoor temperatures and possible Urban Heat Island (UHI) effects, the thermal performance of the building they inhabit, and any actions that they are able to take in order to modify the indoor thermal conditions. There is an increasing body of research that seeks to understand how housing, UHI, and occupant profiles may alter the risk of mortality during hot weather. Housing overheating models have been of particular interest due to the amount of time spent indoors and the need to improve the energy efficiency of the UK housing stock. A number of housing overheating models have been created in order to understand how changes to the building stock and climate may alter heat exposure and risks of heatrelated mortality. We briefly describe the development of a metamodel – a model derived from the outputs of EnergyPlus dynamic thermal simulation models of building variants – and its application to a housing stock model representative of the West Midlands, UK. We model the stock under a ‘current’ scenario, as described by the 2010-2011 English Housing Survey, and then following a full energy-efficient building fabric retrofit or the installation of external window shutters. Initial results indicate a wide range of overheating risks inside dwelling variants in Birmingham, with flats and bungalows most vulnerable to overheating, and detached dwellings least vulnerable. Modelling of the full retrofit of buildings indicated that the stock would experience an overall increase in overheating, while external shutters were able to decrease overheating significantly

Differences in the imaging of Crohn's disease patients between North America and Europe: are we ready to bridge the divide?

The emphasis of treatment in Crohn's disease has evolved from a reactive model to "treat-to-target" approaches. Cross-sectional imaging has rapidly evolved in parallel, with a growing evidence base supporting its abilities for diagnosis, monitoring and prognostication. Whilst there are differences in emphasis between Europe and North America, particularly around the type of imaging modalities and patterns of multidisciplinary care, there is increasing convergence. This perspective piece provides an overview of the evolving role of cross-sectional imaging in Crohn's disease, discusses practice differences between North America and Europe and provides suggestions on areas for future collaboration and research priorities

Lower hybrid current drive and ion cyclotron range of frequencies heating experiments in H-mode plasmas in experimental advanced superconducting Tokomak

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Contemporary medical television and crisis in the NHS

This article maps the terrain of contemporary UK medical television, paying particular attention to Call the Midwife as its centrepiece, and situating it in contextual relation to the current crisis in the NHS. It provides a historical overview of UK and US medical television, illustrating how medical television today has been shaped by noteworthy antecedents. It argues that crisis rhetoric surrounding healthcare leading up to the passing of the Health and Social Care Act 2012 has been accompanied by a renaissance in medical television. And that issues, strands and clusters have emerged in forms, registers and modes with noticeable regularity, especially around the value of affective labour, the cultural politics of nostalgia and the neoliberalisation of healthcare