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There is evidence that patients with Complex Regional Pain Syndrome (CRPS) have altered central sensorimotor processing. Sensory input can influence motor output either through indirect pathways or through direct connections from the sensory to motor cortex. The purpose of this study was to investigate sensorimotor interaction via direct connections in patients with CRPS and to compare the results with normal subjects'. Direct short-latency sensory-motor interaction was evaluated in eight patients with CRPS1 affecting a hand. Modulation of EMG responses to transcranial magnetic stimulation (TMS) induced by concomitant median nerve stimulation was measured, the so-called, short-latency afferent inhibition (SAI). Results were compared with eight normal subjects who were age and sex matched with the patients. As expected, all the normal subjects' EMG responses to TMS with median nerve stimulation were smaller than responses to TMS alone. In seven of the eight CRPS patients EMG responses to TMS were suppressed when paired with median nerve stimulation. Only one CRPS patient's results showed no suppression of EMG responses. These results suggest that the disease mechanisms of CRPS1 do not typically affect the direct neural circuit between sensory and motor cortex and that normal sensorimotor interaction is occurring via this route.

Best practice for improving strength and power through resistance strength training has been the subject of much research and subsequent conjecture. Much of the conjecture can be attributed to methodological discrepancies. The type of dynamometry used in testing, the training experience of research participants, the specific technique employed in a lift, and the methods of collection and calculation all impact on the final variables of interest. This review examines contraction force specificity by first addressing the methodological issues surrounding our interpretation of the results. Then we address the kinematics and kinetics associated with single and multiple repetitions in relation to the development of strength, power, and functional performance. This discussion provides the delimitations for analysis of subsequent training studies. Finally, recommendations are formulated with the aim of assisting assessment and training practice as well as providing directions for future research. The results of this review suggest that the enhancements in performance resulting from resistance training are context specific in experienced resistance-trained participants. Thus, specific conditioning could be required to achieve improvements in functional performance in this group.

Given the rise of long term conditions, and focus on living independently in the community, we launched a free crowd sourcing community app called 'ifOnly' to encourage people with disabilities to share the problems they encounter in everyday life. The app allows people to record, upload and share videos and audios that demonstrate everyday problems they face at home. These were then shared on the 'ifOnly' website - www.ifonlyitworked.com. Designers, recruited nationally, were asked to come up with innovative design solutions via a competition hosted by the University of Bath. The designs were evaluated for novelty and commercial potential by a panel of stakeholders.

The objective of this study was to review the evidence for selected risk factors of lower extremity overuse injuries in young elite female ballet dancers. An electronic search of key databases from 1969 to July 2013 was conducted using the keywords dancers, ballet dancers, athletes, adolescent, adolescence, young, injury, injuries, risk, overuse, lower limb, lower extremity, lower extremities, growth, maturation, menarche, alignment, and biomechanics. Thirteen published studies were retained for review. Results indicated that there is a high incidence of lower extremity overuse injuries in the target population. Primary risk factors identified included maturation, growth, and poor lower extremity alignment. Strong evidence from well-designed studies indicates that young elite female ballet dancers suffer from delayed onset of growth, maturation, menarche, and menstrual irregularities. However, there is little evidence that this deficit increases the risk of overuse injury, with the exception of stress fractures. Similarly, there is minimal evidence linking poor lower extremity alignment to increased risk of overuse injury. It is concluded that further prospective, longitudinal studies are required to clarify the relationship between growth, maturation, menarche, and lower extremity alignment, and the risk of lower extremity overuse injury in young elite female ballet dancers.

Objectives. We investigated changes in life expectancy (LE) and cause-specific mortality over time, directly comparing African-descent populations in the United States and the Caribbean. Methods. We compared LE at birth and cause-specific mortality in 6 disease groups between Caribbean countries with a majority (> 90%) African-descent population and US African Americans. Results. The LE improvement among African Americans exceeded that of Afro-Caribbeans so that the LE gap, which favored the Caribbean population by 1.5 years in 1990, had been reversed by 2009. This relative improvement among African Americans was mainly the result of the improving mortality experience of African American men. Between 2000 and 2009, Caribbean mortality rates in 5 of the 6 disease groups increased relative to those of African Americans. By 2009, mortality from cerebrovascular diseases, cancers, and diabetes was higher in Afro-Caribbeans relative to African Americans, with a diabetes mortality rate twice that of African Americans and 4 times that of White Americans. Conclusions. The Caribbean community made important mortality reductions between 2000 and 2009, but this progress fell short of African American health improvements in the same period, especially among men.

Background Cardiovascular diseases (CVD) are the predominant cause of death globally. The large health disparities in the distribution of the burden of disease seen in developed and developing countries are of growing concern. Central to this concern is the poor outcome which is seen disproportionately in socially disadvantaged groups and racial/ethnic minorities. The aim of the study was to conduct a systematic literature review to investigate the nature of cardiovascular disease health disparities among Afro-Caribbean origin populations and identify current knowledge gaps. Methods A systematic literature review including a detailed search strategy was developed to search MEDLINE and other research databases. Using an a priori protocol peer-reviewed publications and grey literature articles were retrieved and screened and relevant data extracted by two independent review authors. Thematic analysis was done according to CVD outcomes and measures of disparity including age, sex, ethnicity and socioeconomic status. Results The search retrieved 665 articles of which 22 met the inclusion criteria. Most studies were conducted in the United Kingdom and centered on the prevalence of CVD by ethnicity, age and sex. An important sub-theme identified was the disparities in health service utilization/hospital admission. Coronary Heart Disease (CHD) and Peripheral Arterial Disease (PAD) were less prevalent among Afro-Caribbeans compared to Caucasian and South East Asian ethnic groups. The prevalence of CHD ranged from 0–7 % in Afro-Caribbean to 2–22 % in Caucasians. Strokes were more common among Afro-Caribbeans. There are inadequate data on morbidity and mortality from CVD, particularly across the socio-economic gradient, in Afro-Caribbean populations. Conclusions There are important differences in morbidity and mortality from CVD across ethnic groups. Important knowledge gaps remain in understanding the social determinants of these disparities in CVD. More research exploring these gaps by varying disparity indicators needs to be undertaken. Electronic supplementary material The online version of this article (doi:10.1186/s12889-015-2166-7) contains supplementary material, which is available to authorized users.

We review new and published analyses of river waters, bedloads and their constituent minerals from the Dhauli Ganga and Alaknanda, headwaters of the Ganges in Garhwal, and the Marsyandi in Nepal and their tributaries. These data are used to discriminate between the inputs of major cations and Sr from silicate and carbonate sources. Methods of estimating the proportion of the carbonate and silicate inputs to river waters using mixing arrays in Sr-Ca-Mg-Na-K 87Sr/86Sr space are shown\ud to suffer from systematic correlations between the magnitude of the precipitation of secondary calcite and the fraction of the silicate component. This results in factor-of two overestimates of the fractions of silicate-derived Ca, Mg and Sr. To correct for this the magnitude of secondary calcite precipitated and relative fractions of silicate and carbonate-derived cations are instead calculated by modeling the displacement of water compositions from the compositions of the carbonate and silicate components of the bedload in subsets of Sr-Ca-Mg-Na-K 87Sr/86Sr space. The compositions of the carbonate and silicate end-members in the bedload are determined by sequential leaching. The results of this modeling are compared with modeling of the modal mineral inputs to waters where mineral compositions are derived from electronmicroprobe analyses of the minerals in the bedload. In the upper Marsyandi catchment, which drains low-grade Tethyan Sedimentary Series formations, a set of mainstem samples collected over a two-year period define tight correlations in Sr-Ca-Mg-Na-K- 87Sr/86Sr space. Modeling of the magnitude of secondary carbonate precipitation and fractions of silicate-derived Ca, Mg and Sr in Sr-Ca-Mg 87Sr/86Sr space gives selfconsistent results that are compatible with both the calculations of mineral modes and published Mg-isotopic compositions, if the ratio of chlorite to biotite weathering is high or if there is another silicate source of Mg. These calculations imply that between 12 and 31 percent of the Sr and 44 and 72 percent of the Mg is derived from silicate minerals where the range reflects the seasonal change in the ratio of silicate-derived to carbonate-derived cations. Modeling in Sr-Ca-Na and/or K space is inconsistent with the Sr-isotopic and Mg-isotopic constraints and we conclude that in this catchment dissolution of Na and K are incongruent relative to Sr-Ca-Mg. Potassium is preferentially retained in micas whereas the controls on Na are unclear. Modeling of the catchments underlain by High Himalayan Crystalline and Lesser Himalayan Series in Garhwal is complicated by the presence of dolomite as well as calcite in the carbonate and the results imply that dolomite dissolves faster in the acetic acid leaches than in nature. Up to 60 percent of the Sr in the catchment on High Himalayan Crystalline Series and 20 to 30 percent of Sr in the catchments on Lesser Himalayan Series are estimated to be derived from silicates. However it should be noted that the element budgets are not all self-consistent and the use of bedrock-element ratios to model the sources of chemical inputs to river waters remains subject to uncertainties.

ObjectiveWe describe trends in life expectancy at birth (LE) and between-country LE disparities since 1965, in Latin America and the Caribbean.Methods & findingsLE trends since 1965 are described for three geographical sub-regions: the Caribbean, Central America, and South America. LE disparities are explored using a suite of absolute and relative disparity metrics, with measurement consensus providing confidence to observed differences. LE has increased throughout Latin America and the Caribbean. Compared to the Caribbean, LE has increased by an additional 6.6 years in Central America and 4.1 years in South America. Since 1965, average reductions in between-country LE disparities were 14% (absolute disparity) and 23% (relative disparity) in the Caribbean, 55% and 51% in Central America, 55% and 52% in South America.ConclusionsLE in Latin America and the Caribbean is exceeding 'minimum standard' international targets, and is improving relative to the world region with the highest human longevity. The Caribbean, which had the highest LE and the lowest between-country LE disparities in Latin America and the Caribbean in 1965-70, had the lowest LE and the highest LE disparities by 2005-10. Caribbean Governments have championed a collaborative solution to the growing burden of non-communicable disease, with 15 territories signing on to the Declaration of Port of Spain, signalling regional commitment to a coordinated public-health response. The persistent LE inequity between Caribbean countries suggests that public health interventions should be tailored to individual countries to be most effective. Between- and within-country disparity monitoring for a range of health metrics should be a priority, first to guide country-level policy initiatives, then to contribute to the assessment of policy success.

Quantitative constraints on the rates of tectonic processes underpin our understanding of the mechanisms that form mountains. In the Sikkim Himalaya, late structural doming has revealed time-transgressive evidence of metamorphism and thrusting that permit calculation of the minimum rate of movement on a major ductile fault zone, the Main Central Thrust (MCT), by a novel methodology. U-Th-Pb monazite ages, compositions, and metamorphic pressure-temperature determinations from rocks directly beneath the MCT reveal that samples from ~50 km along the transport direction of the thrust experienced similar prograde, peak, and retrograde metamorphic conditions at different times. In the southern, frontal edge of the thrust zone, the rocks were buried to conditions of ~550°C and 0.8 GPa between ~21 and 18 Ma along the prograde path. Peak metamorphic conditions of ~650°C and 0.8–1.0 GPa were subsequently reached as this footwall material was underplated to the hanging wall at ~17–14 Ma. This same process occurred at analogous metamorphic conditions between ~18–16 Ma and 14.5–13 Ma in the midsection of the thrust zone and between ~13 Ma and 12 Ma in the northern, rear edge of the thrust zone. Northward younging muscovite 40Ar/39Ar ages are consistently ~4 Ma younger than the youngest monazite ages for equivalent samples. By combining the geochronological data with the >50 km minimum distance separating samples along the transport axis, a minimum average thrusting rate of 10 ± 3 mm yr−1 can be calculated. This provides a minimum constraint on the amount of Miocene India-Asia convergence that was accommodated along the MCT.

OBJECTIVE—The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have recently reported a significant reduction in spinal cord cross-sectional area at the stage of clinically detectable DPN. In this study, we investigated whether spinal cord atrophy occurs in early (subclinical) DPN. RESEARCH DESIGN AND METHODS—Eighty-one male type 1 diabetic subjects, 24 nondiabetic control subjects, and 8 subjects with hereditary sensory motor neuropathy (HSMN) type 1A underwent detailed clinical and neurophysiological assessments. Diabetic subjects were subsequently divided into three groups based on neuropathy severity (19 with no DPN, 23 with subclinical DPN, and 39 with clinically detectable DPN). All subjects underwent magnetic resonance imaging of the cervical spine and cord area measurements at disc level C2/C3. RESULTS—Mean corrected spinal cord area index (SCAI) (corrected for age, height, and weight) was 67.5 mm [95% CI 64.1–70.9] in diabetic subjects without DPN. Those with subclinical (62.4 mm [59.5–65.3]) and clinically detectable DPN (57.2 mm [54.9–59.6]) had lower mean SCAIs compared with subjects with no DPN (P = 0.03 and P < 0.001, respectively). No significant difference was found between diabetic subjects without DPN and nondiabetic control subjects (69.2 mm [66.3–72.0], P = 0.47). Mean SCAIs in subjects with HSMN type 1A (71.07 mm [65.3–76.9]) were not significantly different from those for nondiabetic control subjects and diabetic subjects without DPN. Among diabetic subjects, SCAI was significantly related to sural sensory conduction velocities and the Neuropathy Composite and Symptom Scores. CONCLUSIONS—Spinal cord involvement occurs early in DPN. There is also a significant relation between reduction in SCAI and neurophysiological assessments of DPN.

The determination of the evolving palaeoaltitude of the Tibetan Plateau since the India–Eurasia collision underpins our understanding of how orography in central Asia affects the intensity of the monsoon and hence global climate change. Palaeoaltitudes, however, cannot be measured directly and need to be inferred from proxy observations that are usually model-dependent. Differing tectonic models for the behaviour of the lithosphere during continental collision have contrasting implications for the elevation of the plateau. However, two techniques recently employed for determining palaeo-elevation are independent of tectonic models, the first involving the variation with altitude of oxygen isotopes in precipitation and the second involving the change of leaf morphology with moist static energy of the atmosphere. Elevation studies have focused on southern Tibet, largely due to the relative ease of access to the region. There is a remarkable unanimity amongst the diverse techniques applied that the altitude of the southern plateau has not significantly changed since at least the mid Miocene ( ca. 15 Ma) arguing for an onset of the monsoon system during or before the early Miocene. A range of tectonic studies suggest that the northern and eastern parts of the plateau are younger geomorphological features, but there are few quantitative constraints of the timing of elevation from these regions of Tibet. Since both the elevation and the surface area of the plateau impact on atmospheric circulation, palaeoaltitude studies need to be extended to chart the increasing areas of elevated land surface through time.

The age of pseudotachylite formation in the crustal-scale Cauvery Shear Zone system of the Precambrian Southern Granulite Terrain (South India) has been analyzed by laser-probe Ar-40-Ar-39 dating. Laser spot analyses from a pseudotachylite from the Salem-Attur shear zone have yielded ages ranging from 1214 to 904 Ma. Some evidence for the presence of excess Ar is indicated by the scatter of ages from this locality. The host gneiss preserves Palaeoproterozoic Rb-Sr whole rock-biotite ages (2350 +/- 11 to 2241 +/- 11 Ma). A mylonite in the Koorg shear, ca. 200 km to the north, yielded an age of 895 17 Ma the consistency of the age distribution from spot analyses precludes the presence of significant excess Ar. Despite published evidence for the growth of high-grade minerals within some components of the Cauvery Shear Zone during the Pan-African event (700-550 Ma), the pseudotachylites in this study provide no evidence for Pan-African formation. Instead they document the first evidence for Mesoproterozoic tectonism in the Cauvery Shear Zone system, thus prompting a review of the correlation between the Cauvery Shear Zone system and the large-scale shear zones located elsewhere in eastern Gondwana. (c) 2006 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

The Longshan–Tianshui area is located in the southeast corner of the Qilian orogenic belt. Three intrusions (the Yanjiadian diorite, the Caochuanpu and the Guanshan granites) in this area provide insights into regional tectono-magmatic events, petrogenesis and tectonic evolution. Based on U–Pb zircon SHRIMP dating, the magma emplacement ages of the Yanjiadian diorite, the Caochuanpu and the Guanshan granites are 441±10, 434±10 and 229±7 Ma, respectively. The Yanjiadian diorites have geochemical characteristics similar to island-arc-type rocks, but their formation resulted from northward subduction of the Huluhe (Erlanping) back-arc basin. The Caochuanpu granites with K2O/Na2O

Line capacity in metro and high-frequency suburban railways is as much determined by station stop times as by factors such as line speed or train acceleration. This paper applies the method developed by London Underground to estimate the time that trains spend at stations, as a function of the physical characteristics of the situation (e.g. train door width) and the numbers of passengers involved. Analysis was carried out on a number of alternative designs for refurbishment of South West Trains' Class 455 inner-suburban rolling stock. Whilst there is indeed an interaction between boarding and alighting passengers, this paper demonstrates that the LUL relationship breaks down at the highest passenger loads. Moreover, results indicate that passenger flow is not equal between different parts of the same group of boarders or alighters.

The Songpan-Garze fold belt, located in the eastern part of the Tibetan Plateau, covers a huge triangular area bounded by the Yangtze (South China), the North China and the Tibetan Plateau blocks. In the northeastern part of the Songpan-Garze fold belt, the Yanggon and Maoergai granitoids provide insights into regional tectono-magmatic events, basement nature and tectonic evolution. U-Pb zircon SHRIMP dating shows that the Yanggon and Maoergai granitoids have mag- matic crystallization ages of 221 ± 3.8 Ma and 216 ± 5.7 Ma, respectively. Both the granitoids display adakitic geochemical signatures, suggesting that their magma was derived from partial melting of thickened lower crust. Pb-Sr-Nd isotopic compositions for granitoids reveal that there is an unexposed Proterozoic basement in the Songpan-Garze belt, which has an affinity with the Yangtze block. During development of the Paleo-Tethys ocean, the basement of the Songpan- Garze belt would be a peninsula approaching the Paleo-Tethys ocean from the Yangtze block.

Assistive technology is a term used to describe any device ranging from simple equipment to complex technologies that can assist a person with a disability. The term is now applied to new technological devices to facilitate active rehabilitation as well as to equipment to enable a person to live with their condition. Current developments such as technology for stroke rehabilitation are rarely brought to the attention of health and social care practitioners, even though frontline staff will be at the forefront of implementation, and their views of the nature of devices and their appropriateness is pivotal. This paper describes some of the technologies being developed to assist the process and delivery of stroke rehabilitation, their potential benefits in practice and stakeholder perceptions of these new technologies.

A new data fusion-based tracking algorithm is proposed, based on two wearable inertial sensors that are placed around the wrist and elbow joints, respectively. Assuming that the lengths of two segments of an upper limb are known, measurements of gyro turning rates can be used to locate the wrist and elbow joints via an established kinematic model. To determine the position of a translated and rotated shoulder joint, an equality-constrained optimisation technique is then proposed to seek an optimal solution, incorporating measurements from the tri-axial accelerometers. Experimental results demonstrate that the algorithm is capable of providing consistent motion tracking of human arms without drifts in 45 s, where each standard deviation is less than half of the corresponding mean value of the Euclidean distance between the estimated joint position and the origin of the world coordinate system.

This paper describes the development and home testing of the inTouch system, a video link designed specifically for people with dementia to use. Iterative, user centered design of four user interaction models was carried out at a day centre. A touchscreen with a telephone handset model was chosen as the most usable interface for a range of people with dementia. This model was developed into a fully working prototype and tested in two home trials, linking two households together over domestic broadband connections. The recruitment of participants for home testing proved to be a significant challenge with no single reason being given for declining or not continuing. Two in-home evaluations of the system were carried out; the system was perceived as easy to use and participants could see the potential benefits, such as being reassured about each other's wellbeing, and enjoyed engaging visually. The poor reliability of existing broadband connections in the homes was a significant limitation to gathering data within the trials. We have successfully applied user centered design principles to the development of a home video link for people living with dementia and their carers. Developers need to consider practical issues around recruitment and broadband infrastructure when carrying out real world evaluations of ICT systems.

This paper presents the first systematic survey of lithium and its isotopes in the dissolved load and suspended and bed sediments of tributaries of the Ganges, both before and after the monsoon. Locations were chosen in order to cover catchments draining both silicates and carbonates, at high (2000–4000 m) and low (550–1300 m) altitudes. Modelling of the dissolved composition shows that the Li / Ca ratio of the silicate endmember in Himalayan rivers is at least an order-of-magnitude higher than that of the carbonate endmember. Most of the dissolved Li (> 90%) is derived from silicates even in carbonate-dominated catchments. While the Sr-isotope composition of the dissolved load reflects that of the bedrock, the main control on its Li-isotope composition is fractionation during weathering. Fractionation between the dissolved and suspended load in silicate-dominated catchments is greatest at high altitude and lower at low altitude where weathering is more intense. Tributaries draining silicates have lower dissolved δ7Li values (by 2.3‰ to 4.2‰) following the monsoon when weathering is more intense because of higher runoff and elevated temperatures. Our data suggest that riverine Li fluxes largely reflect silicate weathering rates, while riverine δ7Li varies with weathering intensity. As rivers presently contribute ∼50% of the Li input to the oceans, seawater Li concentrations and δ7Li show potential as proxies for global silicate weathering processes.

We report the first geochemical traverse to integrate U–Pb ages and Hf data on single detrital zircons with bulk-rock Sm– Nd–Rb–Sr isotopic measurements across the breadth of the Himalayan orogen, in northwest India. Our dataset, from key tectonostratigraphic units in the Sutlej valley, provides detailed insights into both the provenance of the sedimentary formations, and their tectonic history. Whole-rock Nd data provide information on the mean age of source areas contributing detritus to the sedimentary units in the mountain belt, regardless of their current metamorphic grade. U–Pb ages of detrital zircons from the same units identify the age of melt formation in the source rocks, while Lu–Hf isotope data from zircons resolve discrete crust formation ages in the multiple eroding terrains. Complex whole-rock Sr systematics hint at the extent of pre-Himalayan thermal events. Our data confirm the geochemical distinction between the older Lesser Himalayan Formations and those of the depositionally younger units (including the High Himalayan Crystalline Series) that has been recorded along the strike of the Himalaya from the western syntaxis to Nepal. Palaeoproterozoic metasediments of the Jutogh Group and Rampur Formation yield eNd(500) values below 17, whereas Neoproterozoic and younger metasediments yield eNd(500) above 13. The latter group encompasses the Vaikrita Group gneisses of the High Himalayan crystallines and the overlying Haimanta Group, but also includes a number of units in thrust sheets north of the Main Boundary Thrust in the Lesser Himalayan Zone (designated the dOuter Lesser HimalayaT to distinguish them from the Palaeoproterozoic dInner Lesser HimalayaT). Zircon populations from the Inner Lesser Himalaya are characterised by Palaeoproterozoic–Late Archaean ages (2.6–1.8 Ga), whereas the depositionally younger units contain populations both of this age, and a younger period (Meso- to Neo-Proterozoic; 1.1–0.8 Ga). Detrital zircon ages are younger than their respective Hf-isotope derived crustal formation ages by 0.7–2.1 Ga, indicating that the source regions of the detrital zircons consisted of older terranes with considerable amounts of reworking and renewed magmatism. The

Rheumatic diseases are expressed in all ethnic populations, but differ in prevalence, genetic associations, clinical features, and responses to interventions. Most data describing these differences do so in reference to and comparisons with white populations. These are sparse data that evaluate differences within minority populations where there is more homogeneity of external factors, such as social, cultural, and behavioral attitudes. This article reviews the features that are unique to various rheumatic diseases within minority populations.

The first aCL test was developed in 1983 and subsequently standardized. Although in the last 6 to 7 years, new and more specific tests have become available, the aCL ELISA and the LA tests are still the first choice to be used in diagnosis of APS. While there is now doubt that the anticardiolipin test is useful in the diagnosis of APS, limitations of the assay have caused uncertainty and misinterpretation of the value of the test. Utilization of validated ELISA kits with well-tested calibrators and an "in-house standard" may enable more reproducible measurements. Reporting results semiquantitatively preserves the clinical utilize of the test without the misinterpretation of a quantitative result that may lack precision. The development of newer tests such as the beta2GPI ELISA and the APhL ELISA Kit, utilizing the phospholipid mixture, give promise to a more specific and reliable diagnosis of APS, while retaining good sensitivity. Other tests such as ELISA for prothrombin antibodies and annexin V antibodies are still under development and will require standardization and extensive evaluation. The aCL test should continue to be done and included in the Sapporo criteria. The aCL test is not as specific as the anti-beta2GPI test, but it is very sensitive and together with the LA test should capture the majority of the APS patients. IgA aCL and anti-beta2GPI positivity alone is rare but occasionally found and shown to be associated with major clinical manifestations of APS. Therefore, it is now recommended to include both tests, IgA aCL and IgG, IgM and IgA anti-beta2GPI to confirm diagnosis of APS.

Exhumation of the Himalayan-Tibetan orogen is implicated in the marked rise in seawater 87Sr/86Sr ratios since 40 Ma. However both silicate and carbonate rocks in the Himalaya have elevated 87Sr/86Sr ratios and there is disagreement as to how much of the 87Sr flux is derived from silicate weathering. Most previous studies have used element ratios from bedrock to constrain the proportions of silicate- and carbonate-derived Sr in river waters. Here we use arrays of water compositions sampled from the head waters of the Ganges in the Indian and Nepalese Himalaya to constrain the end-member element ratios. The compositions of tributaries draining catchments restricted to a limited range of geological units can be described by two-component mixing of silicate and carbonate-derived components and lie on a plane in multicomponent composition space. Key elemental ratios of the carbonate and silicate components are determined by the intersection of the tributary mixing plane with the planes Na = 0 for carbonate and constant Ca/Na for silicate. The fractions of Sr derived from silicate and carbonate sources are then calculated by mass-balance in Sr-Ca-Mg-Na composition space. Comparison of end-member compositions with bedrock implies that secondary calcite deposition may be important in some catchments and that dissolution of low-Mg trace calcite in silicate rocks may explain discrepancies in Sr-Ca-Na-Mg covariation. Alternatively, composition-dependent precipitation or incongruent dissolution reactions may rotate mixing trends on cation-ratio diagrams. However the calculations are not sensitive to transformations of the compositions by incongruent dissolution or precipitation processes provided that the transformed silicate and carbonate component vectors are constrained. Silicates are calculated to provide ∼50% of the dissolved Sr flux from the head waters of the Ganges assuming that discrepancies between Ca-Mg-Na covariation and the silicate rock compositions arise from addition of trace calcite. If the Ca-Mg-Na mixing plane is rotated by composition-dependent secondary calcite deposition, this estimate would be increased. Moreover, when 87Sr/86Sr ratios of the Sr inputs are considered, silicate Sr is responsible for 70 ± 16% (1σ) of the 87Sr flux forcing changes in seawater Sr-isotopic composition. Since earlier studies predict that silicate weathering generates as little as 20% of the total Sr flux in Himalayan river systems, this study demonstrates that the significance of silicate weathering can be greatly underestimated if the processes that decouple the water cation ratios from those of the source rocks are not properly evaluated.

Gneiss domes exposed by the North Himalayan antiform in southern Tibet provide evidence for protracted melting of the mid-crust during convergent tectonics. Anatexis was initiated during underthrusting and recurred during the southwards extrusion of a low-viscosity crustal sheet. Sr–Nd isotope systematics establish that the cores of the domes, dominated by Cambrian gneiss, form a window of the High Himalayan Crystalline Series (HHCS; Indian Plate). Combined trace-element and isotopic analyses from 4 two-mica granites that intrude both core and the metasedimentary mantle of the domes indicate an origin from melting of the High Himalayan Crystalline Series by the incongruent breakdown of muscovite and, to a lesser extent, biotite, at temperatures from 680 to 760 °C. U–Pb dating of accessory phases extends the known period of granite magmatism from the Late Oligocene to Mid-Miocene. A Ca-rich, garnet-bearing leucogranite of Oligocene age (27.5 Ma) provides a rare insight into the pre-Miocene history of the underthrust Indian plate, reflecting prograde melting at greater depths during a period of crustal thickening. The origin of the Miocene granites (15–10 Ma) can be modeled from the exhumation of an extruding channel at a rate of ca. 1 mm/year, constrained by Ar-isotope data. Melting over a protracted time scale along the leading edge of the Indian Plate, less than 50 km from the suture, accelerated horizontal shortening within the collision zone and provided a positive-feedback mechanism between magmagenesis and deformation.

Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and sudden death. This results from both sympatho-adrenal activation and a lowered serum potassium. It has been suggested that cardiac autonomic neuropathy (CAN) might indicate those who are at particular risk. We tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic control subjects. After standard tests of autonomic function and baroreflex sensitivity (BRS) measurement, diabetic participants were divided into three groups: 1) CAN- with normal BRS (BRS+; n = 10), 2) CAN- with impaired BRS (BRS-; n = 9), and 3) CAN+ (n = 9). QTc was then measured during controlled hypoglycemia (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (+/-SE) QTc lengthened from 377 +/- 9 ms (baseline) to a maximum during hypoglycemia of 439 +/- 13 ms in BRS+ subjects and from 378 +/- 5 to 439 +/- 10 ms in control subjects. Peak QTc tended to be lower in CAN+ (baseline, 383 +/- 6; maximum, 408 +/- 10) and BRS- groups (baseline, 380 +/- 8; maximum, 421 +/- 11; F = 1.7, P = 0.18). Peak epinephrine concentrations (nmol/l) were 3.1 +/- 0.8 (BRS+), 2.6 +/- 0.5 (BRS-), 1.4 +/- 0.3 (CAN+), and 5.7 +/- 0.8 (control subjects). These data do not indicate that those with CAN are at particular risk for abnormal cardiac repolarization during hypoglycemia. Indeed, they suggest that such patients may be relatively protected, perhaps as a result of attenuated sympatho-adrenal responses.

Objective: The factors causing production of antiphospholipid (aPL) antibodies remain unidentified. Recently, studies have shown that aPL and anti- β 2 Glycoprotein I (anti- β 2 GPI) antibodies with pathogenic properties can be generated with peptides from bacterial and viral origin, that mimic regions of β 2 GPI. These data suggest a molecular mimicry between bacterial/viral antigens and self-proteins. In this study we examined the ability of a synthetic peptide (named peptide A, NTLKTPRVGGC) that shares similarity with common bacterial antigens, to reverse aPL-mediated thrombosis in mice in vivo. Peptide A is also found in region I/II of β 2 GPI. A scrambled form of peptide A (named scA, GTKGCPNVRLT) was used as a control. Methods and Results: Sera from 29 patients with APS bound to peptide A but not to peptide scA by ELISA in a dose-dependent fashion. Cardiolipin (CL) liposomes inhibited the binding of IgG–APS by ELISA to peptide A by 35% and to CL by 56%. The inhibition of binding to cardiolipin and to peptide A was enhanced by addition of β 2 GPI to the liposomes. CL/peptide A liposomes but not peptide A alone inhibited the binding of IgG–APS to peptide A. β 2 GPI alone did not inhibit binding of IgG–APS to peptide A, to β 2 GPI or to CL. For the in vivo experiments, CD1 mice in groups of 20 were injected with affinity purified aPL antibodies or with control IgG–NHS twice intraperitoneally. Seventy hours after the first injection, and 30 min before the surgical procedure (induction of experimental thrombus) mice were infused i.v. in each group with either peptide A or with peptide scA. The femoral vein of the anesthetized mice were dissected to examine the dynamics of an induced thrombus in treated and control mice. The mean aCL titer of mice injected with aPL was 60 GPL units. Mice treated with aPL and infused with peptide scA produced significantly larger thrombi when compared to mice treated with IgG–NHS and peptide scA (2466±462 μm 2 vs 772.5±626.4 μm 2 ). Treatment with peptide A significantly decreased thrombus size in mice injected with aPL antibodies (1063±890 μm 2 compared to 2466±462 μm 2 ). Conclusion: The data indicates that a synthetic peptide that shares similarity with common bacterial antigens and with regions of β 2 GPI is capable to inhibit thrombogenic properties of aPL in mice. This may have important implications in designing new modalities of prevention and/or treatment of thrombosis in APS.

A great deal of investment is currently going into the railway industry across Europe, including into new lines. The British Channel Tunnel Rail Link is under construction, and a number of other high-speed lines in Britain have been discussed. This paper considers whether high-speed lines are the best solution in the British context. It challenges those involved in decision-making to determine more clearly the reasons for such high-speed lines, where capacity increases are often more important than achieving end-to-end journey time reductions. A number of other strategies for railway investment are also discussed, with the paper concluding that (after operational improvements), a targeted investment in bottlenecks in the existing system may be the most cost-effective solution in general. However, this response is made more difficult by the performance regime on Britain's privatised railway.

A combined metamorphic and isotopic study of lit-par-lit migmatites exposed in the hanging wall of the Main Central Thrust (MCT) from Sikkim has provided a unique insight into the pressure-temperature- time path of the High Himalayan Crystalline Series of the eastern Himalaya. The petrology and geochemistry of one such migmatite indicates that the leucosome comprises a crystallized peraluminous granite coexisting with sillimanite and alkali feldspar. Large garnet crystals (2-3 mm across) are strongly zoned and grew initially within the kyanite stability field. The melanosome is a biotite-garnet pelitic gneiss, with fibrolitic sillimanite resulting from polymorphic inversion of kyanite. By combining garnet zoning profiles with the NaCaMnKFMASHTO pseudosection appropriate to the bulk composition of a migmatite retrieved from c. 1 km above the thrust zone, it has been established that early garnet formed at pressures of 10-12 kbar, and that subsequent decompression caused the rock to enter the melt field at c. 8 kbar and c. 750 � C, generating peritectic sillimanite and alkali feldspar by the incongruent melting of muscovite. Continuing exhumation resulted in resorption of garnet. Sm-Nd growth ages of garnet cores and rim, indicate pre-decompression garnet growth at 23 ± 3 Ma and near-peak temperatures during melting at 16 ± 2 Ma. This provides a decompression rate of 2 ± 1 mm yr )1 that is consistent with exhumation rates inferred from mineral cooling ages from the eastern Himalaya. Simple 1D thermal modelling confirms that exhumation at this rate would result in a near-isothermal decompres- sion path, a result that is supported by the phase relations in both the melanosome and leucosome components of the migmatite. Results from this study suggest that anatexis of Miocene granite protoliths from the Himalaya was a consequence of rapid decompression, probably in response to movement on the MCT and on the South Tibetan detachment to the north.

Neogene potassic lavas in northern and southern Tibet have different isotopic (eNd(i) north, −5·5 to −10·3; south −8·8 to −18·1) and major element signatures suggesting derivation from separate sub-continental lithospheric mantle (SCLM) sources. Inverse trace-element modelling shows that the southern Tibet magmas were derived by 1–2% partial melting of a phlogopite and amphibole peridotite, and that the northern samples were derived by 3–4% partial melting of a phlogopite peridotite. In both cases, melting is inferred to take place in the spinel stability field. Both sources show large ion lithophile element (LILE) enrichment relative to the high field strength elements (HFSE), and heavy rare earth element (HREE) depletion relative to primitive mantle. LILE/HFSE enrichment suggests subduction-related metasomatism; HREE depletion is indicative of prior melt extraction. Extension postdates the earliest magmatism in southern and north–central Tibet by 7 Myr and 5 Myr, respectively, which, in combination with the shallow depths of melting inferred for the Tibetan samples, supports geodynamic models invoking thinning of the SCLM. The northern Tibetan magmatism and extension can be explained by convective removal of the lower SCLM; the older ages and arcuate distribution of the southern magmas are most consistent with the SCLM erosion following slab break-off.

The cosmogenic 10Be exposure histories of in situ bedrock surfaces from the Tibetan Plateau indicate low erosion rates of

Objective Antiphospholipid antibodies (aPL) have thrombogenic properties in vivo, through their interactions with soluble coagulation factors and their ability to modulate the functions of cells involved in coagulation homeostasis. These antibodies have also been shown to enhance the adhesion of leukocytes to endothelial cells (ECs) in vivo. New lipophilic statins such as fluvastatin have antiinflammatory and antithrombogenic effects. This study uses an in vivo mouse model to investigate whether fluvastatin has an effect on decreasing both the adhesion of leukocytes to ECs and the thrombus formation induced by aPL. Methods Two groups of CD-1 male mice, each comprising ∼18 mice, were fed either normal saline solution or 15 mg/kg fluvastatin for 15 days. Each of the 2 groups was further subdivided to receive either purified IgG from patients with the antiphospholipid syndrome (IgG-APS) or normal IgG from healthy subjects. Analysis of thrombus dynamics was performed in treated and control mice, using a standardized thrombogenic injury procedure, and the area (size) of the thrombus was measured. Adhesion of leukocytes to ECs was analyzed with a microcirculation model of exposed cremaster muscle. Baseline and posttreatment soluble intercellular adhesion molecule 1 (sICAM-1) levels were determined by enzyme-linked immunosorbent assay. Results IgG-APS mice treated with fluvastatin showed significantly smaller thrombi, a reduced number of adherent leukocytes, and decreased levels of sICAM-1 compared with IgG-APS animals treated with placebo. Conclusion These findings indicate that fluvastatin significantly diminishes aPL-mediated thrombosis and EC activation in vivo. These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS.

This study establishes that carbonate weathering dominates the supply of Sr with elevated 87Sr/86Sr ratios in the Bhote Kosi–Sun Kosi river system, central Nepal, a major Himalayan tributary to the Ganges. The dissolved load of the Bhote Kosi–Sun Kosi displays a rapid increase in the 87Sr/86Sr ratio in its lower section, downstream of the Main Central Thrust, a feature common to other Himalayan tributaries of the Ganges. Mass balance analysis of the contributing sources to the dissolved load identifies the weathering of Palaeoproterozoic impure carbonates (comprised largely of dolomite and mica) from the Lesser Himalaya as the most significant lithological control upon elevated 87Sr/86Sr ratios. In situ laser ablation analysis of the dolomite component yields 87Sr/86Sr ratios of 0.93 to 1.11, indistinguishable from bulk rock. This confirms the presence of a highly soluble source of radiogenic strontium and suggests that diffusive exchange during a protracted metamorphic history has homogenised Sr isotopes between silicate and carbonate phases within the assemblage. Weathering of the carbonate component of such rocks has yielded unusually high 87Sr/86Sr at significant Sr fluxes in the dissolved load. Approximately 60% of the impact of the Bhote Kosi–Sun Kosi on the marine 87Sr/86Sr ratio can be traced to weathering of this carbonate. Since similar lithologies outcrop within the catchments of most Himalayan tributaries that feed the Ganges and Brahmaputra rivers, the presence of such radiogenic carbonates undermines the inference that the impact of these rivers on Sr isotopes in seawater is indicative of high silicate weathering rates that result from the uplift of Tibet and the Himalaya.

The Ranomandry Complex is a Neoproterozoic, nested intrusion from central Madagascar composed of a gabbroic core within a coeval peraluminous granite ring intruding pelitic metasediments. Although xenocryst entrainment and magma mixing have both contributed to marginal phases of the granite, the primary melt is characterised by steep LREE/HREE ratios and negligible, or slightly positive, Eu anomalies. Both isotopic and trace element systematics preclude an origin from either partial melting of the metapelitic country rock or from fractional crystallisation of the gabbroic magma. However, trace-element modelling suggests an origin from the dehydration melting of a plagioclase-poor, garnet-bearing metagreywacke at temperatures of 850–900 °C and at lower crustal pressures (>10 kbar). Melting of an enriched subcontinental mantle generated gabbroic magmas that caused advective heating and anatexis at the base of thickened continental crust during their ascent. Transport of the resulting granite magma was facilitated by the pre-existing plumbing system that overcame thermal and mechanical problems associated with both diapirism and self-propagating dykes as mechanisms for long-distance transport of granite magmas. The nested geometry of the intrusions is an indication of a structurally homogeneous lower crust that contains no pre-existing shear zones or fault systems.

Symmetry is a remarkably constant clinical feature of chronic inflammatory disease. Rheumatoid arthritis is almost by definition symmetrical [1]. Osteoarthritis, psoriasis and some of its associated arthritides are also symmetrical [2–4]. Pulmonary fibrosis, glomerulonephritis and sympathetic ophthalmia are also symmetrical inflammatory conditions. Whilst the pathophysiology behind this symmetry is unexplained, we and others have speculated that it is likely to be mediated via neurological mechanisms crossing through the spinal cord [5, 6]. The two sides of the spinal column have largely been thought to function independently of each other. There are three lines of evidence to suggest that this is not true. Careful anatomical studies of the spinal cord show transmedian fibres decussating posteriorly at all levels of the spinal cord to synapse in the laminae on the contralateral dorsal horn. These neuronal connections have been seen in many different species, including several primates (Fig. 1). Szentagothai [7], using Golgi analysis on young cats and dogs, showed that neurons with their cell bodies in the substantia gelatinosa send contralateral axons that appear to synapse in the contralateral substantia gelatinosa. Perl and Light [8] corroborated these findings after they had applied horseradish peroxidase to rat, cat and monkey dorsal rootlets. They found projections into the contralateral substantia gelatinosa as well as the ventral portion of the nucleus propius. Culberson et al. [9], using cresyl violet acetate (Fink-Heimer method), identified crossed afferent projections throughout the spinal cord, originating and terminating in laminae III–IV, in four mammalian species. These anatomical studies provide evidence that the opportunity exists for crosstalk between the left and the right sides of the spinal column. Functional studies of decerebrate rats demonstrate that such cross-communication can produce contralateral responses. Electrical stimulation of contralateral peripheral nerves is known to inhibit flexor reflex pathways in the spinal cord [10] as well as the long latency of C-fibre-evoked activity in dorsal horn cells [11, 12]. Contralateral dorsal horn cells are inhibited in response to noxious stimuli applied to the limb or tails of rats [13, 14]. Further electrophysiological studies confirm the presence of neurons in the dorsal horn that have bilateral receptive fields. Of relevance to this article is that the number of these neurons with bilateral receptive fields increases in the presence of unilateral inflammation [15, 16]. Grubb et al. [17] also showed that some of the fields on the contralateral side can become excitatory rather than inhibitory. At what level are these contralateral responses mediated? Woolf [16] documented the persistent reduction in flexor reflex thresholds contralaterally after noxious thermal stimuli had been applied to decerebrate rats with an intact brainstem. Fitzgerald [18], using a decerebrate, spinalized rat model, showed that a contralateral effect on dorsal horn fibres need not involve such higher pathways. Although direct contralateral spinal pathways exist in experimental conditions, there are likely to be significant supraspinal influences in vivo. This is suggested by several studies detailing an attenuation of central sensitization and secondary hyperalgesia following spinalization or inactivation of the rostral ventral medulla in a review of rat models of acute pain [19].

Himalayan weathering is recognized as an important agent in modifying sea water chemistry, but there are significant uncertainties in our understanding of Himalayan riverine fluxes. This paper examines causes of the variability, including that of the seasons, by analysis of downstream variations in Sr, 87Sr, and major ions in the mainstream, in relation to the composition of tributary streams from subcatchments with differing geologic substrates. Water samples were collected over four periods spanning the premonsoon, monsoon, and postmonsoon seasons. Uncertainties in the relative fluxes have been estimated, using Monte Carlo techniques, from the short-term variability of mainstream chemistry and the scatter of tributary compositions. The results show marked seasonal variations in the relative inputs related to high monsoon rainfall in the High and Lesser Himalaya, contrasting with the major contribution from glacial melt waters from the Tibetan Sedimentary Series (TSS) at times of low rainfall. Much of the spread in previously published estimates of the sources of Sr in Himalayan rivers may result from these seasonal variations in Sr fluxes. The annual fluxes of Sr into the headwaters of the Ganges are derived from the three main tectonic units in the proportions 35 ± 1% from the TSS, 27 ± 3% from the High Himalayan Crystalline Series (HHCS), and 38 ± 8% from the Lesser Himalaya. The particularly elevated 87Sr/86Sr ratios characteristic of the HHCS and the Lesser Himalaya enhance their influence on seawater Sr-isotope composition. The TSS contributes 13 ± 1%, the HHCS 30 ± 3%, and the Lesser Himalaya 57 ± 11% of the 87Sr flux in excess of the seawater 87Sr/86Sr ratio of 0.709.

Prolonged cardiac repolarization causes fatal cardiac arrhythmias. There is evidence that these contribute to sudden death associated with nocturnal hypoglycemia in young people with diabetes. We measured cardiac repolarization (QT interval [QTc] and QT dispersion [QTd]) during experimental hypoglycemia with and without β-blockade and potassium infusion to establish possible mechanisms. Two groups of 10 nondiabetic men (study 1 and study 2) each underwent four hyperinsulinemic clamps: two euglycemic (5 mmol/l) and two hypoglycemic (5 mmol/l and 2.5 mmol/l for 60 min each). Study 1 was performed with and without potassium infusion to maintain normal concentrations and study 2 with and without β-blockade (atenolol, 100 mg/day for 7 days). QTd was unchanged during euglycemia but increased during hypoglycemia (55 ms, P < 0.0001 vs. baseline), which was prevented by potassium (6 ms, P = 0.78). QTc increased significantly during hypoglycemia alone (67 ms, P < 0.0001) and during potassium replacement (46 ms, P = 0.02). In study 2, the increase in QTd during hypoglycemia (68 ms, P < 0.0001) was prevented by β-blockade (3 ms, P = 0.88). The increase in QTc during hypoglycemia (55 ms, P < 0.0001) was prevented by β-blockade (1 ms, P = 0.98). Our data indicate that hypoglycemia causes an acquired long QT syndrome. Sympathoadrenal stimulation is the main cause, through mechanisms that involve but are not limited to catecholamine-mediated hypokalemia. These abnormalities are prevented by selective β-blockade.

Background Hypoglycaemia alters cardiac repolarization acutely, with increases in rate-corrected QT (QTc) interval and QT dispersion (QTd) on the electrocardiogram (ECG); such changes are related to the counterregulatory sympatho-adrenal response. Adrenaline produces both QTc lengthening and a fall in plasma potassium (K+) when infused into healthy volunteers. Hypokalaemia prolongs cardiac repolarization independently however, and therefore our aim was to determine whether adrenaline-induced repolarization changes are mediated directly or through lowered plasma K+. Materials and methods Ten healthy males were studied on two occasions. At both visits they received similar l-adrenaline infusions but on one occasion potassium was also administered; infusion rates were adjusted to maintain circulating K+ at baseline. The QTc interval, QTd, peripheral physiological responses and plasma adrenaline and potassium concentrations were measured during both visits. Results The QTc interval and QTd increased both with and without potassium clamping. Without K+ replacement, mean (SE) QTc lengthened from 378 (5) ms to a final maximum value of 433 (10) ms, and QTd increased from 36 (5) ms to 69 (8) ms (both P

In this debate, Nigel Harris and David Coleman discuss the pros and cons of migration. Taking the case of Britain, they address issues such as the desirability or otherwise of migration controls, gains and losses from migration, the ‘optimum’ size and composition of the country’s workforce, and the demographic, social and political consequences of migration.

Background The confirmation of diagnosis of the Antiphospholipid Syndrome (APS) relies on laboratory tests. Current classification criteria for definite APS mandate the use of three “standardized” laboratory assays to detect antiphospholipid antibodies (aPL) [viz: anticardiolipin (aCL) IgG and IgM, anti-β2glycoprotein I (anti-β2GPI) antibodies IgG and IgM and/or a lupus anticoagulant (LAC)], when at least one of the two major clinical manifestations (thrombosis or pregnancy losses) are present. Several attempts have been made to standardize the aCL and anti-β2GPI tests, though, a considerable degree of inconsistencies still exist, limiting the clinical and diagnostic value of aPL tests. Among the areas of concern are the type and source of calibrant material, the lack of proper validated reference material and of universal units of measurement, particularly for anti-β2GPI antibodies. Content A Task Force of scientists and leaders in the field from different countries — discussed and analyzed those critical questions in an evidence-based manner and further discussed and made recommendations at a workshop that was conducted during 13th International Congress on Antiphospholipid Antibodies (APLA 2010, April 13–16, 2010, Galveston, TX). Summary This concise report summarizes the findings, conclusions and recommendations of the task force and preconference workshop. The group recommended to ensure the availability of properly prepared and validated polyclonal and monoclonal antibody reference materials for both assays, to continue reporting the aCL assay in GPL/MPL units and to establish consensus international units of measurement for anti-β2GPI antibodies.

Garnet-whole rock Sm-Nd data are presented for several samples from the Indian plate in the NW Himalaya. These dates, when combined with the P-T evolution of the Indian plate rocks, allow a thorough reconstruction of the prograde thermal evolution of this region (including the Nanga Parbat Haramosh Massif) during the early Cenozoic. Combining these data with Rb-Sr mineral separate ages, enables us to constrain the post-peak cooling history of this region of the Himalaya. The data presented here indicate that the upper structural levels of the cover rocks of the Nanga Parbat Haramosh Massif, and similar rocks in the Kaghan Valley to the south-west, were buried to pressures of c. 10 kbar and heated to temperatures of c. 650 °C at 46–41 Ma. The burial of the lower structural levels of the cover rocks of the Nanga Parbat Haramosh Massif, to similar depths but at higher temperatures of c. 700 °C, occurred slightly later at 40–36 Ma, synchronous with the imbrication and exhumation of the amphibolite- and eclogite-grade rocks of the Kaghan Valley. In contrast, the cover rocks of the Nanga Parbat Haramosh Massif were not imbricated or exhumed at this time, remaining buried beneath the Kohistan-Ladakh Island Arc until the syntaxis-forming event that occurred in the last 10 Myr. The timing of tectonic events in the north-western Himalaya differs from that experienced by the rocks of the Central Himalaya in that the earliest stage of burial in the NW Himalaya predates that of the Central Himalaya by c. 6 Myr. This difference may result from the diachronous nature of the Indo-Asian collision or may simply be a reflection of differing timing at different structural levels.

Since the appearance of his Princeton dissertation in 1991 (on the Nürnberger Prosa-Äsop), Aaron E. Wright has established himself, thanks to a string of articles and a critical edition of the fable collection of the Anonymus Neveleti, as a major authority in the field of fable studies. This new monograph, which is innovative, thoroughly documented and outstandingly well written, can only enhance his reputation.

“Black swan in the kidney”: Renal involvement in the antiphospholipid antibody syndrome. The antiphosphospholipid antibody syndrome (APS) describes a clinical entity with recurrent thrombosis, fetal loss, thrombocytopenia in the presence of lupus anticoagulant and/or antibodies to cardiolipin. These antibodies may be associated with connective tissue diseases such as systemic lupus erythematosus (secondary APS) or be found in isolation (primary APS). Renal syndromes increasingly being reported in association with these antibodies include thrombotic microangiopathy, renal vein thrombosis, renal infarction, renal artery stenosis and/or malignant hypertension, increased allograft vascular thrombosis, and reduced survival of renal allografts. Although much has been understood concerning the biology of these antibodies and the pathogenesis of thrombosis, the optimal therapy remains to be elucidated. This article presents a historical review of the renal involvement in the antiphospholipid syndrome and discusses therapeutic options. Further research is needed.