Mild cognitive decline. A position statement of the Cognitive Decline Group of the European Innovation Partnership for Active and Healthy Ageing (EIPAHA)

Introduction Mild cognitive impairment (MCI) is a term used to describe a level of decline in cognition which is seen as an intermediate stage between normal ageing and dementia, and which many consider to be a prodromal stage of neurodegeneration that may become dementia. That is, it is perceived as a high risk level of cognitive change. The increasing burden of dementia in our society, but also our increasing understanding of its risk factors and potential interventions, require diligent management of MCI in order to find strategies that produce effective prevention of dementia. Aim To update knowledge regarding mild cognitive impairment, and to bring together and appraise evidence about the main features of clinical interest: definitions, prevalence and stability, risk factors, screening, and management and intervention. Methods Literature review and consensus of expert opinion. Results and conclusion MCI describes a level of impairment in which deteriorating cognitive functions still allow for reasonable independent living, including some compensatory strategies. While there is evidence for some early risk factors, there is still a need to more precisely delineate and distinguish early manifestations of frank dementia from cognitive impairment that is less likely to progress to dementia, and furthermore to develop improved prospective evidence for positive response to intervention. An important limitation derives from the scarcity of studies that take MCI as an endpoint. Strategies for effective management suffer from the same limitation, since most studies have focused on dementia. Behavioural changes may represent the most cost-effective approach.

Serum neopterin levels and gallium transferrin binding in Parkinson's disease

The unconjugated pterin neopterin is secreted by macrophages activated by interferon-gamma and hence, the level of neopterin in serum may be used as a marker of a cellular immune response in a patient. Serum neopterin levels were measured by high performance liquid chromatography (HPLC) in 28 Parkinson's disease (PD) patients and 28 age and sex matched controls. The level of serum neopterin was significantly elevated in PD compared with controls suggesting immune activation in these patients. The level of neopterin was negatively correlated with the level of binding of gallium to transferrin (Tf) but unrelated to the level of iron binding. Hence, in PD, it is possible that a cellular immune response may be important in the pathogenesis of the disease. One effect of the cellular immune response may be a reduction in the binding of metals other than iron to Tf and this could also be a factor in PD.

An examination of the calcium and strontium site distribution in bioactive glasses through isomorphic neutron diffraction, X-ray diffraction, EXAFS and multinuclear solid state NMR.

Strontium has been substituted for calcium in the glass series (SiO2)49.46(Na2O)26.38(P2O5)1.07(CaO)23.08x(SrO)x (where x = 0, 11.54, 23.08) to elucidate their underlying atomic-scale structural characteristics as a basis for understanding features related to the bioactivity. These bioactive glasses have been investigated using isomorphic neutron and X-ray diffraction, Sr K-edge EXAFS and solid state 17O, 23Na, 29Si, 31P and 43Ca magic-angle-spinning (MAS) NMR. An effective isomorphic substitution first-order difference function has been applied to the neutron diffraction data, confirming that Ca and Sr behave in a similar manner within the glass network, with residual differences attributed to solely the variation in ionic radius between the two species. The diffraction data provides the first direct experimental evidence of split Ca–O nearest-neighbour correlations in these melt quench bioactive glasses, together with an analogous splitting of the Sr–O correlations; the correlations are attributed to the metal ions correlated either to bridging or to non-bridging oxygen atoms. Triple quantum (3Q) 43Ca MAS NMR corroborates the split Ca–O correlations. Successful simplification of the 2 < r (A) < 3 region via the difference method has also revealed two distinct Na environments. These environments are attributed to sodium correlated either to bridging or to nonbridging oxygen atoms. Complementary multinuclear MAS NMR, Sr K-edge EXAFS and X-ray diffraction data supports the structural model presented. The structural sites present will be intimately related to their release properties in physiological fluids such as plasma and saliva, and hence the bioactivity of the material. Detailed structural knowledge is therefore a prerequisite for optimising material design.

Septin6 and Septin7 GTP binding proteins regulate AP-3- and ESCRT-dependent multivesicular body biogenesis

Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies.

InP-based active and passive components for communication systems at 2 μm

Progress on advanced active and passive photonic components that are required for high-speed optical communications over hollow-core photonic bandgap fiber at wavelengths around 2 μm is described in this paper. Single-frequency lasers capable of operating at 10 Gb/s and covering a wide spectral range are realized. A comparison is made between waveguide and surface normal photodiodes with the latter showing good sensitivity up to 15 Gb/s. Passive waveguides, 90° optical hybrids, and arrayed waveguide grating with 100-GHz channel spacing are demonstrated on a large spot-size waveguide platform. Finally, a strong electro-optic effect using the quantum confined Stark effect in strain-balanced multiple quantum wells is demonstrated and used in a Mach-Zehnder modulator capable of operating at 10 Gb/s.

Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Peer reviewed

Akrasia and the Aesthetic: Human Agency and the Site of Literature, 1760-1820

This study focuses on a series of foundational stylistic and formal innovations in eighteenth-century and Romantic literature, and argues that they can be cumulatively attributed to the distinct challenges authors faced in representing human action and the will. The study focuses in particular on cases of “acting against better judgment” or “failing to do what one knows one ought to do” – concepts originally theorized as “akrasia” and “weakness of the will” in ancient Greek and Scholastic thought. During the Enlightenment, philosophy increasingly conceives of human minds and bodies like systems and machines, and consequently fails to address such cases except as intractable or incoherent. Yet eighteenth-century and Romantic narratives and poetry consistently engage the paradoxes and ambiguities of action and volition in representations of akrasia. As a result, literature develops representational strategies that distinguish the epistemic capacities of literature as privileged over those of philosophy.

The study begins by centering on narratives of distempered selves from the 1760s. Jean-Jacques Rousseau’s Confessions and Laurence Sterne’s A Sentimental Journey narrate cases of knowingly and weakly acting against better judgment, and in so doing, reveal the limitations of the “philosophy of the passions” that famously informed sentimental literature at the time. These texts find that the interpretive difficulties of action demand a non-systematic and hermeneutic approach to interpreting a self through the genre of narrative. Rousseau’s narrative in particular informs William Godwin’s realist novels of distempered subjects. Departing from his mechanistic philosophy of mind and action, Godwin develops the technique of free indirect discourse in his third novel Fleetwood (1805) as a means of evoking the ironies and self-deceptions in how we talk about willing.

Romantic poetry employs the literary trope of weakness of will primarily through the problem of regretted inaction – a problem which I argue motivates the major poetic innovations of William Wordsworth and John Keats. While Samuel Taylor Coleridge sought to characterize his weakness of will in philosophical writing, Wordsworth turns to poetry with The Prelude (1805), revealing poetry itself to be a self-deceiving and disappointing form of procrastination. More explicitly than Wordsworth, John Keats identifies indolence as the prime symbol and basis of what he calls “negative capability.” In his letters and poems such as “On Seeing the Elgin Marbles” (1817) and “Ode on Indolence” (1819), Keats reveals how the irreducibly contradictory qualities of human agency speak to the particular privilege of “disinterested aesthetics” – a genre fitted for the modern era for its ability to disclose contradictions without seeking to resolve or explain them in terms of component parts.

Table 2: Water stable isotope results and sampling site information of samples taken between 2003 and 2009 on the island of Corsica (western Mediterranean)

The Mediterranean is regarded as a region of intense climate change. To better understand future climate change, this area has been the target of several palaeoclimate studies which also studied stable isotope proxies that are directly linked to the stable isotope composition of water, such as tree rings, tooth enamel or speleothems. For such work, it is also essential to establish an isotope hydrology framework of the region of interest. Surface waters from streams and lakes as well as groundwater from springs on the island of Corsica were sampled between 2003 and 2009 for their oxygen and hydrogen isotope compositions. Isotope values from lake waters were enriched in heavier isotopes and define a local evaporation line (LEL). On the other hand, stream and spring waters reflect the isotope composition of local precipitation in the catchment. The intersection of the LEL and the linear fit of the spring and stream waters reflect the mean isotope composition of the annual precipitation (dP) with values of -8.6(±0.2) per mil for d18O and -58(±2) per mil for d2H. This value is also a good indicator of the average isotope composition of the local groundwater in the island. Surface water samples reflect the altitude isotope effect with a value of -0.17(±0.02) per mil per 100 m elevation for oxygen isotopes. At Vizzavona Pass in central Corsica, water samples from two catchments within a lateral distance of only a few hundred metres showed unexpected but systematic differences in their stable isotope composition. At this specific location, the direction of exposure seems to be an important factor. The differences were likely caused by isotopic enrichment during recharge in warm weather conditions in south-exposed valley flanks compared to the opposite, north-exposed valley flanks.

(Table 1) Age comparison between the GPTS and ODP Site 181-1123 age model for each chron base within the Middle Miocene section

Today the deep western boundary current (DWBC) east of New Zealand is the most important route for deep water entering the Pacific Ocean. Large-scale changes in deep water circulation patterns are thought to have been associated with the development of the East Antarctic Ice Sheet (EAIS) close to the main source of bottom water for the DWBC. Here we reconstruct the changing speed of the southwest Pacific DWBC during the middle Miocene from ~15.5-12.5 Ma, a period of significant global ice accumulation associated with EAIS growth. Sortable silt mean grain sizes from Ocean Drilling Program Site 1123 reveal variability in the speed of the Pacific inflow on the timescale of the 41 kyr orbital obliquity cycle. Similar orbital period flow changes have recently been demonstrated for the Pleistocene epoch. Collectively, these observations suggest that a strong coupling between changes in the speed of the deep Pacific inflow and high-latitude climate forcing may have been a persistent feature of the global thermohaline circulation system for at least the past 15 Myr. Furthermore, long-term changes in flow speed suggest an intensification of the DWBC under an inferred increase in Southern Component Water production. This occurred at the same time as decreasing Tethyan outflow and major EAIS growth between ~15.5 and 13.5 Ma. These results provide evidence that a major component of the deep thermohaline circulation was associated with the middle Miocene growth of the EAIS and support the view that this time interval represents an important step in the development of the Neogene icehouse climate.

Childhood Physical Activity Involvement in Active and Inactive Female Adults

Current trends show progressive declines in levels of physical activity from childhood through adolescence and adulthood, most notably for females. The current study examined organized activity involvement in active and inactive females (age 18) using retrospective data. Results indicated that active females participated in significantly more physical activities than inactive females from age 6 to age 18. No significant differences were found between groups for non-physical activities. In addition, parents of active and inactive females were the most influential factor in initiating physical activity. However, parents of active females initiated more physical activity involvement than did parents of inactive females. Results also indicate that certain periods in childhood and adolescence appear to be critical for developing long-term physical activity habits.