The medieval papacy and holy war: General crusading letters and papal authority, 1145-1213

Chapter in an edited collection on the twelfth-century papacy and its authorisation of crusades to the Near East.

Combination therapy: opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines.

The discovery of new molecular targets and the subsequent development of novel anticancer agents are opening new possibilities for drug combination therapy as anticancer treatment. Polymer-drug conjugates are well established for the delivery of a single therapeutic agent, but only in very recent years their use has been extended to the delivery of multi-agent therapy. These early studies revealed the therapeutic potential of this application but raised new challenges (namely, drug loading and drugs ratio, characterisation, and development of suitable carriers) that need to be addressed for a successful optimisation of the system towards clinical applications.

General derivative relations for anharmonic force fields

The brace notation, introduced by Allen and Csaszar (1993, J. chem. Phys., 98, 2983), provides a simple and compact way to deal with derivatives of arbitrary non-tensorial quantities. One of its main advantages is that it builds the permutational symmetry of the derivatives directly into the formalism. The brace notation is applied to formulate the general nth-order Cartesian derivatives of internal coordinates, and to provide closed forms for general, nth-order transformation equations of anharmonic force fields, expressed as Taylor series, from internal to Cartesian or normal coordinate spaces.

Characterising the variability and extremes of the stratospheric polar vortices using 2D moment analysis

The mean state, variability and extreme variability of the stratospheric polar vortices, with an emphasis on the Northern Hemisphere vortex, are examined using 2-dimensional moment analysis and Extreme Value Theory (EVT). The use of moments as an analysis to ol gives rise to information about the vortex area, centroid latitude, aspect ratio and kurtosis. The application of EVT to these moment derived quantaties allows the extreme variability of the vortex to be assessed. The data used for this study is ECMWF ERA-40 potential vorticity fields on interpolated isentropic surfaces that range from 450K-1450K. Analyses show that the most extreme vortex variability occurs most commonly in late January and early February, consistent with when most planetary wave driving from the troposphere is observed. Composites around sudden stratospheric warming (SSW) events reveal that the moment diagnostics evolve in statistically different ways between vortex splitting events and vortex displacement events, in contrast to the traditional diagnostics. Histograms of the vortex diagnostics on the 850K (∼10hPa) surface over the 1958-2001 period are fitted with parametric distributions, and show that SSW events comprise the majority of data in the tails of the distributions. The distribution of each diagnostic is computed on various surfaces throughout the depth of the stratosphere, and shows that in general the vortex becomes more circular with higher filamentation at the upper levels. The Northern Hemisphere (NH) and Southern Hemisphere (SH) vortices are also compared through the analysis of their respective vortex diagnostics, and confirm that the SH vortex is less variable and lacks extreme events compared to the NH vortex. Finally extreme value theory is used to statistically mo del the vortex diagnostics and make inferences about the underlying dynamics of the polar vortices.

The equatorial response to higher latitude forcing

The classic view, following Charney and Webster and Holton, is that significant midlatitude forcing of the Tropics can be expected only in regions with westerly winds in the upper troposphere because it is only in these regions that stationary Rossby waves will be able to propagate toward the equator. Here it is shown that higherlatitude forcing can project directly onto equatorial waves and give a significant tropical response in both easterly and westerly tropical flow. The equatorial response to higher-latitude forcing is considered in the context of a dry atmosphere and a localized higher-latitude forcing with eastward or westward phase speed. Previous ideas of the Doppler shifting of equatorial waves by zonal flows are extended to include consideration of a forcing involving a range of zonal wavenumbers. A Gill-type model suggests that there can be significant forcing of equatorial waves by either vorticity forcing or heating in higher latitudes. In agreement with the theory, the Kelvin wave response to eastward forcing is peaked at high frequencies/short periods but reduces only slowly with decreasing frequency. Primitive-equation experiments confirm the strong equatorial response associated with a deep Kelvin wave for forcing in midlatitudes. The response is strongest in the Eastern Hemisphere with its equatorial, upper-tropospheric easterlies. The possible importance of this equatorial response in the organization of large-scale, deep tropical convection and the initiation of the Madden–Julian oscillation is discussed. The ability of westward forcing in higher latitudes to trigger Rossby–gravity and Rossby waves is found in the primitive-equation model to be significant but rather less robust. These wave signatures are clearest in the lower troposphere. For shorter periods the Rossby–gravity wave dominates, and for upper-tropospheric forcing, downward and eastward wave activity propagation is seen. Upper-tropospheric westerlies are found to enhance the response.

A period 2 genetic variant interacts with plasma SFA to modify plasma lipid concentrations in adults with metabolic syndrome

Genetic variants of Period 2 (PER2), a circadian clock gene, have been linked to metabolic syndrome (MetS). However, it is still unknown whether these genetic variants interact with the various types of plasma fatty acids. This study investigated whether common single nucleotide polymorphisms (SNPs) in the PER2 locus (rs934945 and rs2304672) interact with various classes of plasma fatty acids to modulate plasma lipid metabolism in 381 participants with MetS in the European LIPGENE study. Interestingly, the rs2304672 SNP interacted with plasma total SFA concentrations to affect fasting plasma TG, TG-rich lipoprotein (TRL-TG), total cholesterol, apoC-II, apoB, and apoB-48 concentrations (P-interaction < 0.001–0.046). Carriers of the minor allele (GC+GG) with the highest SFA concentration (>median) had a higher plasma TG concentration (P = 0.001) and higher TRL-TG (P < 0.001) than the CC genotype. In addition, participants carrying the minor G allele for rs2304672 SNP and with a higher SFA concentration (>median) had higher plasma concentrations of apo C-II (P < 0.001), apo C-III (P = 0.009), and apoB-48 (P = 0.028) compared with the homozygotes for the major allele (CC). In summary, the rs2304672 polymorphism in the PER2 gene locus may influence lipid metabolism by interacting with the plasma total SFA concentration in participants with MetS. The understanding of these gene-nutrient interactions could help to provide a better knowledge of the pathogenesis in MetS.

Earth's energy imbalance since 1960 in observations and CMIP5 models

Observational analyses of running 5-year ocean heat content trends (Ht) and net downward top of atmosphere radiation (N) are significantly correlated (r~0.6) from 1960 to 1999, but a spike in Ht in the early 2000s is likely spurious since it is inconsistent with estimates of N from both satellite observations and climate model simulations. Variations in N between 1960 and 2000 were dominated by volcanic eruptions, and are well simulated by the ensemble mean of coupled models from the Fifth Coupled Model Intercomparison Project (CMIP5). We find an observation-based reduction in N of -0.31±0.21 Wm-2 between 1999 and 2005 that potentially contributed to the recent warming slowdown, but the relative roles of external forcing and internal variability remain unclear. While present-day anomalies of N in the CMIP5 ensemble mean and observations agree, this may be due to a cancellation of errors in outgoing longwave and absorbed solar radiation.

Equipped to deal with uncertainty in climate and impacts predictions: lessons from internal peer review

The quantification of uncertainty is an increasingly popular topic, with clear importance for climate change policy. However, uncertainty assessments are open to a range of interpretations, each of which may lead to a different policy recommendation. In the EQUIP project researchers from the UK climate modelling, statistical modelling, and impacts communities worked together on ‘end-to-end’ uncertainty assessments of climate change and its impacts. Here, we use an experiment in peer review amongst project members to assess variation in the assessment of uncertainties between EQUIP researchers. We find overall agreement on key sources of uncertainty but a large variation in the assessment of the methods used for uncertainty assessment. Results show that communication aimed at specialists makes the methods used harder to assess. There is also evidence of individual bias, which is partially attributable to disciplinary backgrounds. However, varying views on the methods used to quantify uncertainty did not preclude consensus on the consequential results produced using those methods. Based on our analysis, we make recommendations for developing and presenting statements on climate and its impacts. These include the use of a common uncertainty reporting format in order to make assumptions clear; presentation of results in terms of processes and trade-offs rather than only numerical ranges; and reporting multiple assessments of uncertainty in order to elucidate a more complete picture of impacts and their uncertainties. This in turn implies research should be done by teams of people with a range of backgrounds and time for interaction and discussion, with fewer but more comprehensive outputs in which the range of opinions is recorded.