Eight years experience from a skeletal dysplasia referral center in a tertiary hospital in Southern India: A model for the diagnosis and treatment of rare diseases in a developing country.

We report on a series of 514 consecutive diagnoses of skeletal dysplasia made over an 8-year period at a tertiary hospital in Kerala, India. The most common diagnostic groups were dysostosis multiplex group (n = 73) followed by FGFR3 (n = 49) and osteogenesis imperfecta and decreased bone density group (n = 41). Molecular confirmation was obtained in 109 cases. Clinical and radiographic evaluation was obtained in close diagnostic collaboration with expert groups abroad through Internet communication for difficult cases. This has allowed for targeted biochemical and molecular studies leading to the correct identification of rare or novel conditions, which has not only helped affected families by allowing for improved genetic counseling and prenatal diagnosis but also resulted in several scientific contributions. We conclude that (1) the spectrum of genetic bone disease in Kerala, India, is similar to that of other parts of the world, but recessive entities may be more frequent because of widespread consanguinity; (2) prenatal detection of skeletal dysplasias remains relatively rare because of limited access to expert prenatal ultrasound facilities; (3) because of the low accessibility to molecular tests, precise clinical-radiographic phenotyping remains the mainstay of diagnosis and counseling and of gatekeeping to efficient laboratory testing; (4) good phenotyping allows, a significant contribution to the recognition and characterization of novel entities. We suggest that the tight collaboration between a local reference center with dedicated personnel and expert diagnostic networks may be a proficient model to bring current diagnostics to developing countries. © 2014 Wiley Periodicals, Inc.

Looking for orders of magnitude : five essays in trade and the environment and economic geography

General Summary Although the chapters of this thesis address a variety of issues, the principal aim is common: test economic ideas in an international economic context. The intention has been to supply empirical findings using the largest suitable data sets and making use of the most appropriate empirical techniques. This thesis can roughly be divided into two parts: the first one, corresponding to the first two chapters, investigates the link between trade and the environment, the second one, the last three chapters, is related to economic geography issues. Environmental problems are omnipresent in the daily press nowadays and one of the arguments put forward is that globalisation causes severe environmental problems through the reallocation of investments and production to countries with less stringent environmental regulations. A measure of the amplitude of this undesirable effect is provided in the first part. The third and the fourth chapters explore the productivity effects of agglomeration. The computed spillover effects between different sectors indicate how cluster-formation might be productivity enhancing. The last chapter is not about how to better understand the world but how to measure it and it was just a great pleasure to work on it. "The Economist" writes every week about the impressive population and economic growth observed in China and India, and everybody agrees that the world's center of gravity has shifted. But by how much and how fast did it shift? An answer is given in the last part, which proposes a global measure for the location of world production and allows to visualize our results in Google Earth. A short summary of each of the five chapters is provided below. The first chapter, entitled "Unraveling the World-Wide Pollution-Haven Effect" investigates the relative strength of the pollution haven effect (PH, comparative advantage in dirty products due to differences in environmental regulation) and the factor endowment effect (FE, comparative advantage in dirty, capital intensive products due to differences in endowments). We compute the pollution content of imports using the IPPS coefficients (for three pollutants, namely biological oxygen demand, sulphur dioxide and toxic pollution intensity for all manufacturing sectors) provided by the World Bank and use a gravity-type framework to isolate the two above mentioned effects. Our study covers 48 countries that can be classified into 29 Southern and 19 Northern countries and uses the lead content of gasoline as proxy for environmental stringency. For North-South trade we find significant PH and FE effects going in the expected, opposite directions and being of similar magnitude. However, when looking at world trade, the effects become very small because of the high North-North trade share, where we have no a priori expectations about the signs of these effects. Therefore popular fears about the trade effects of differences in environmental regulations might by exaggerated. The second chapter is entitled "Is trade bad for the Environment? Decomposing worldwide SO2 emissions, 1990-2000". First we construct a novel and large database containing reasonable estimates of SO2 emission intensities per unit labor that vary across countries, periods and manufacturing sectors. Then we use these original data (covering 31 developed and 31 developing countries) to decompose the worldwide SO2 emissions into the three well known dynamic effects (scale, technique and composition effect). We find that the positive scale (+9,5%) and the negative technique (-12.5%) effect are the main driving forces of emission changes. Composition effects between countries and sectors are smaller, both negative and of similar magnitude (-3.5% each). Given that trade matters via the composition effects this means that trade reduces total emissions. We next construct, in a first experiment, a hypothetical world where no trade happens, i.e. each country produces its imports at home and does no longer produce its exports. The difference between the actual and this no-trade world allows us (under the omission of price effects) to compute a static first-order trade effect. The latter now increases total world emissions because it allows, on average, dirty countries to specialize in dirty products. However, this effect is smaller (3.5%) in 2000 than in 1990 (10%), in line with the negative dynamic composition effect identified in the previous exercise. We then propose a second experiment, comparing effective emissions with the maximum or minimum possible level of SO2 emissions. These hypothetical levels of emissions are obtained by reallocating labour accordingly across sectors within each country (under the country-employment and the world industry-production constraints). Using linear programming techniques, we show that emissions are reduced by 90% with respect to the worst case, but that they could still be reduced further by another 80% if emissions were to be minimized. The findings from this chapter go together with those from chapter one in the sense that trade-induced composition effect do not seem to be the main source of pollution, at least in the recent past. Going now to the economic geography part of this thesis, the third chapter, entitled "A Dynamic Model with Sectoral Agglomeration Effects" consists of a short note that derives the theoretical model estimated in the fourth chapter. The derivation is directly based on the multi-regional framework by Ciccone (2002) but extends it in order to include sectoral disaggregation and a temporal dimension. This allows us formally to write present productivity as a function of past productivity and other contemporaneous and past control variables. The fourth chapter entitled "Sectoral Agglomeration Effects in a Panel of European Regions" takes the final equation derived in chapter three to the data. We investigate the empirical link between density and labour productivity based on regional data (245 NUTS-2 regions over the period 1980-2003). Using dynamic panel techniques allows us to control for the possible endogeneity of density and for region specific effects. We find a positive long run elasticity of density with respect to labour productivity of about 13%. When using data at the sectoral level it seems that positive cross-sector and negative own-sector externalities are present in manufacturing while financial services display strong positive own-sector effects. The fifth and last chapter entitled "Is the World's Economic Center of Gravity Already in Asia?" computes the world economic, demographic and geographic center of gravity for 1975-2004 and compares them. Based on data for the largest cities in the world and using the physical concept of center of mass, we find that the world's economic center of gravity is still located in Europe, even though there is a clear shift towards Asia. To sum up, this thesis makes three main contributions. First, it provides new estimates of orders of magnitudes for the role of trade in the globalisation and environment debate. Second, it computes reliable and disaggregated elasticities for the effect of density on labour productivity in European regions. Third, it allows us, in a geometrically rigorous way, to track the path of the world's economic center of gravity.

Modelling the influence of change in fire regime on the local distribution of a Mediterranean pyrophytic plant species (Cistus salviifolius) at its northern range limit

Aims: To assess the potential distribution of an obligate seeder and active pyrophyte, Cistus salviifolius, a vulnerable species in the Swiss Red List; to derive scenarios by changing the fire return interval; and to discuss the results from a conservation perspective. A more general aim is to assess the impact of fire as a natural factor influencing the vegetation of the southern slopes of the Alps. Locations: Alps, southern Switzerland. Methods: Presence-absence data to fit the model were obtained from the most recent field mapping of C. salviifolius. The quantitative environmental predictors used in this study include topographic, climatic and disturbance (fire) predictors. Models were fitted by logistic regression and evaluated by jackknife and bootstrap approaches. Changes in fire regime were simulated by increasing the time-return interval of fire (simulating longer periods without fire). Two scenarios were considered: no fire in the past 15 years; or in the past 35 years. Results: Rock cover, slope, topographic position, potential evapotranspiration and time elapsed since the last fire were selected in the final model. The Nagelkerke R-2 of the model for C. salviifolius was 0.57 and the Jackknife area under the curve evaluation was 0.89. The bootstrap evaluation revealed model robustness. By increasing the return interval of fire by either up to 15 years, or 35 years, the modelled C. salviifolius population declined by 30-40%, respectively. Main conclusions: Although fire plays a significant role, topography and rock cover appear to be the most important predictors, suggesting that the distribution of C. salviifolius in the southern Swiss Alps is closely related to the availability of supposedly competition-free sites, such as emerging bedrock, ridge locations or steep slopes. Fire is more likely to play a secondary role in allowing C. salviifolius to extend its occurrence temporarily, by increasing germination rates and reducing the competition from surrounding vegetation. To maintain a viable dormant seed bank for C. salviifolius, conservation managers should consider carrying out vegetation clearing and managing wild fire propagation to reduce competition and ensure sufficient recruitment for this species.

Upper Triassic to Cretaceous radiolaria from Nicaragua and northern Costa Rica - The Mesquito composite oceanic terrane

We propose a new terrane subdivision of Nicaragua and Northern Costa Rica, based on Upper Triassic to Upper Cretaceous radiolarian biochronology of ribbon radiolarites, the newly studied Siuna Serpentinite Mélange, and published 40Ar/39Ar dating and geochemistry of mafic and ultramafic igneous rock units of the area. The new Mesquito Composite Oceanic Terrane (MCOT) comprises the southern half of the Chortis Block, that was assumed to be a continental fragment of N-America. The MCOT is defined by 4 corner localities characterized by ultramafic and mafic oceanic rocks and radiolarites of Late Triassic, Jurassic and Early Cretaceous age: 1. The Siuna Serpentinite Mélange (NE-Nicaragua), 2. The El Castillo Mélange (Nicaragua/Costa Rica border), 3.The Santa Elena Ultramafics (N-Costa Rica) and, 4. DSDP Legs 67/84. 1. The Siuna Serpentinite Mélange contains, high pressure metamorphic mafics and Middle Jurassic (Bajocian-Bathonian) radiolarites in original, sedimentary contact with arc-metandesites. The Siuna Mélange also contains Upper Jurassic black detrital chert formed in a marginal (fore-arc?) basin shortly before subduction. A phengite 40Ar/39Ar -cooling age dates the exhumation of the high pressure rocks as 139 Ma (earliest Cretaceous). 2. The El Castillo Mélange comprises a radiolarite block tectonically embedded in serpentinite that yielded a diverse Rhaetian (latest Triassic) radiolarian assemblage, the oldest fossils recovered so far from S-Central America. 3. The Santa Elena Ultramafics of N-Costa Rica together with the serpentinite outcrops near El Castillo (2) in Southern Nicaragua, are the southernmost outcrops of the MCOT. The Santa Elena Unit (3) itself is still undated, but it is thrust onto the middle Cretaceous Santa Rosa Accretionary Complex (SRAC), that contains Lower to Upper Jurassic, highly deformed radiolarite blocks, probably reworked from the MCOT, which was the upper plate with respect to the SRAC. 4. Serpentinites, metagabbros and basalts have long been known from DSDP Leg 67/84 (3), drilled off Guatemala in the Nicaragua-Guatemala forearc basement. They have been restudied and reveal 40Ar/39Ar dated Upper Triassic to middle Cretaceous enriched Ocean Island Basalts and Jurassic to Lower Cretaceous depleted Island arc rocks of probable Pacific origin. The area between localities 1-4 is largely covered by Tertiary to Recent arcs, but we suspect that its basement is made of oceanic/accreted terranes. Earthquake seismic studies indicate an ill-defined, shallow Moho in this area. The MCOT covers most of Nicaragua and could extend to Guatemala to the W and form the Lower (southern) Nicaragua Rise to the NE. Some basement complexes of Jamaica, Hispaniola and Puerto Rico may also belong to the MCOT. The Nicoya Complex s. str. has been regarded as an example of Caribbean crust and the Caribbean Large Igneous Province (CLIP). However, 40Ar/39Ar - dates on basalts and intrusives indicate ages as old as Early Cretaceous. Highly deformed Jurassic and Lower Cretaceous radiolarites occur as blocks within younger intrusives and basalts. Our interpretation is that radiolarites became first accreted to the MCOT, then became reworked into the Nicoya Plateau in Late Cretaceous times. This implies that the Nicoya Plateau formed along the Pacific edge of the MCOT, independent form the CLIP and most probably unrelated with he Galapagos hotspot. No Jurassic radiolarite, no older sediment age than Coniacian-Santonian, and no older 40Ar/39Ar age than 95 Ma is known from S-Central America between SE of Nicoya and Colombia. For us this area represents the trailing edge of the CLIP s. str.

What drives invasibility? A multi-model inference test and spatial modelling of alien plant species richness patterns in northern Portugal

Understanding and anticipating biological invasions can focus either on traits that favour species invasiveness or on features of the receiving communities, habitats or landscapes that promote their invasibility. Here, we address invasibility at the regional scale, testing whether some habitats and landscapes are more invasible than others by fitting models that relate alien plant species richness to various environmental predictors. We use a multi-model information-theoretic approach to assess invasibility by modelling spatial and ecological patterns of alien invasion in landscape mosaics and testing competing hypotheses of environmental factors that may control invasibility. Because invasibility may be mediated by particular characteristics of invasiveness, we classified alien species according to their C-S-R plant strategies. We illustrate this approach with a set of 86 alien species in Northern Portugal. We first focus on predictors influencing species richness and expressing invasibility and then evaluate whether distinct plant strategies respond to the same or different groups of environmental predictors. We confirmed climate as a primary determinant of alien invasions and as a primary environmental gradient determining landscape invasibility. The effects of secondary gradients were detected only when the area was sub-sampled according to predictions based on the primary gradient. Then, multiple predictor types influenced patterns of alien species richness, with some types (landscape composition, topography and fire regime) prevailing over others. Alien species richness responded most strongly to extreme land management regimes, suggesting that intermediate disturbance induces biotic resistance by favouring native species richness. Land-use intensification facilitated alien invasion, whereas conservation areas hosted few invaders, highlighting the importance of ecosystem stability in preventing invasions. Plants with different strategies exhibited different responses to environmental gradients, particularly when the variations of the primary gradient were narrowed by sub-sampling. Such differential responses of plant strategies suggest using distinct control and eradication approaches for different areas and alien plant groups.

Juxtaposition of melt impregnation and high-temperature shear zones in the upper mantle; field and petrological constraints from the Lanzo peridotite (Northern Italy)

Results of a field and microstructural study between the northern and the central bodies of the Lanzo plagioclase peridotite massif (NW Italy) indicate that the spatial distribution of deformation is asymmetric across kilometre-scale mantle shear zones. The southwestern part of the shear zone (footwall) shows a gradually increasing degree of deformation from porphyroclastic peridotites to mylonite, whereas the northeastern part (hanging wall) quickly grades into weakly deformed peridotites. Discordant gabbroic and basaltic dykes are asymmetrically distributed and far more abundant in the footwall of the shear zone. The porphyroclastic peridotite displays porphyroclastic zones and domains of igneous crystallization whereas mylonites are characterized by elongated porphyroclasts, embedded between fine-grained, polycrystalline bands of olivine, plagioclase, clinopyroxene, orthopyroxene, spinel, rare titanian pargasite, and domains of recrystallized olivine. Two types of melt impregnation textures have been found: (1) clinopyroxene porphyroclasts incongruently reacted with migrating melt to form orthopyroxene plagioclase; (2) olivine porphyroclasts are partially replaced by interstitial orthopyroxene. The meltrock reaction textures tend to disappear in the mylonites, indicating that deformation in the mylonite continued under subsolidus conditions. The pyroxene chemistry is correlated with grain size. High-Al pyroxene cores indicate high temperatures (11001030C), whereas low-Al neoblasts display lower final equilibration temperatures (860C). The spinel Cr-number [molar Cr/(Cr Al)] and TiO2 concentrations show extreme variability covering almost the entire range known from abyssal peridotites. The spinel compositions of porphyroclastic peridotites from the central body are more variable than spinel from mylonite, mylonite with ultra-mylonite bands, and porphyroclastic rocks of the northern body. The spinel compositions probably indicate disequilibrium and would favour rapid cooling, and a faster exhumation of the central peridotite body, relative to the northern one. Our results indicate that melt migration and high-temperature deformation are juxtaposed both in time and space. Meltrock reaction may have caused grain-size reduction, which in turn led to localization of deformation. It is likely that melt-lubricated, actively deforming peridotites acted as melt focusing zones, with permeabilities higher than the surrounding, less deformed peridotites. Later, under subsolidus conditions, pinning in polycrystalline bands in the mylonites inhibited substantial grain growth and led to permanent weak zones in the upper mantle peridotite, with a permeability that is lower than in the weakly deformed peridotites. Such an inversion in permeability might explain why actively deforming, fine-grained peridotite mylonite acted as a permeability barrier and why ascending mafic melts might terminate and crystallize as gabbros along actively deforming shear zones. Melt-lubricated mantle shear zones provide a mechanism for explaining the discontinuous distribution of gabbros in oceancontinent transition zones, oceanic core complexes and ultraslow-spreading ridges.

Inverse metamorphic zonation in very low-grade Tibetan zone series of SE Zanskar and its tectonic consequences (NW India, Himalaya)

The metamorphism of the carbonate rocks of the SE Zanskar Tibetan zone has been studied by `'illite crystallinity'' and calcite-dolomite thermometry. The epizonal Zangla unit overlies the anchizonal Chumik unit. This discontinuous inverse zonation demonstrates a late to post-metamorphic thrust of the first unit over the second. The studied area underwent a complex tectonic history: - The tectonic units were stacked from the NE to the SW, generating recumbent folds, NE dipping thrusts and the regional metamorphism. The compressive movements were active under lower temperature conditions, resulting in late thrusts that disturbed the metamorphic zonation. The discontinuous inverse metamorphic zonation dates from this phase. - A NE vergent backfolding phase occurred at lower temperature conditions. It caused the uplift of more metamorphic levels. - A late extensional phase is revealed by the presence of NE dipping low angle normal faults, and a major high angle fault, the Sarchu fault. The low angle normal faults locally run along earlier thrusts (composite tectonic contacts). Their throw has been sufficient to reset a normal stratigraphic superposition (young layers overlying old ones), but insufficient to erase the inverse metamorphic relationship. However, the combined action of backfolding and normal faulting can locally lessen, or even cancel, the inverse metamorphic superposition. After deduction of the normal fault translation, the vertical component of the original thrust displacement through stratigraphy is 400 m, which is a value far too low to explain the temperature difference between the two units. The horizontal component of displacement is therefore far more important than the vertical one. The regional distribution of metamorphism within the Zangla unit points out to an anchizonal front and an epizonal inner part. This fact is in agreement with nappe tectonics.

Late Triassic phaeodarian Radiolaria from the Northern Chichibu Belt, Shikoku, Japan

A new genus (Triassiphaeodina gen. nov.) and two new species (Medusetta japonica sp. nov. and Triassiphaeodina niyodoensis sp. nov.) of Late Triassic (Rhaetian) phaeodarian Radiolaria are described from a phosphatic nodule found in melange rocks of the Northern Chichibu Belt, Shikoku, Japan. The Rhaetian age of the nodule and of the phaeodarian new taxa is based on co-occurring Polycystina Radiolaria, including Bipedis acrostylus Bragin, Livarella densiporata Kozur and Mostler, Fontinella primitiva Carter, and Ferresium sp. A of Carter (1993). This finding shows that phaeodarian Radiolaria were already represented in Late Triassic oceans, with morphologies similar to those known in the Late Cretaceous and Cenozoic, from which they have previously been reported. The new taxa described herein represent the oldest known phaeodarian fossils.

Paleohydrological Reconstruction from Late Holocene Records in Interdune Lakes (N'Guigmi, Northern Bank of the Lake Chad, Niger)

An old erg covers the northern part of the Lake Chad basin. This dune landform allowed the formation of many inter- dune ponds of various sizes. Still present in certain zones where the groundwater level is high (e.g. Kanem, southern Manga), these ponds formed in the past a vast network of lacustrine microsystems, as shown by the nature and the dis- tribution of their deposits. In the Manga, these interdune deposits represent the main sedimentary records of the Holo- cene environmental succession. Their paleobiological (pollens, diatoms, ostracods) and geochemical (δ18O, δ13C, Sr/ Ca) contents are often the basis for paleoenvironmental reconstruction. On the other hand, their sedimentological char- acters are rarely exploited. This study of palustro-lacustrine deposits of the Holocene N'Guigmi lake (northern bank of the Lake Chad; Niger) is based on the relationships between the sedimentological features and the climato-hydrological fluctuations. The mineralogical parameters (e.g. calcium carbonate content, clay mineralogy) and the nature of autoch- thonous mineralization (i.e. amorphous silica, clays, calcium carbonates) can be interpreted using a straightforward hy- dro-sedimentary model. Established to explain the geochemical dynamics of Lake Chad, this model is based on a bio- geochemical cycle of the main elements (i.e. silicium, calcium) directly controlled by the local hydrological balance (i.e. rainfall/evaporation ratio). All these results show that a detailed study of sedimentological features can provide impor- tant paleohydrological informations about the regional aridification since ca 6500 14C BP.

Connecting India: The rise of standards in service offshoring

This paper explores the role of international standards in the globalisation of the service economy. Various strands of economic analyses consider that core attributes of services affect their ability to be reliably delocalised, industrialised and standardised. In contrast, international political economy (IPE) approaches draw attention to power configurations supporting conflicting use of standards across industries and nations. The paper examines the case of the Indian service industry in business process outsourcing to probe these opposing views. Our findings suggest that standards matter in types of services conventionally identified as unlikely to be standardised, and that their use raise little conflict. An IPE perspective on service standardisation highlights, however, the importance of potential power issues likely to be included in more progressive forms of standardisation

Genetic differentiation and zoogeography of Asian Suncus murinus (Mammalia: Soricidae)

Protein electrophoresis was used to assess the phylogenetic relationships of populations of the phenotypically variable Asian house shrew Suncus murinus. These populations represent a sample of both commensal and wild forms. They were compared to another taxon, S. montanus, which was formerly considered conspecific with S. murinus. Suncus dayi was used as an outgroup in all phylogenetic reconstructions. Within the S. murinus lineage, the allozyme data show very low levels of genetic differentiation among both wild and commensal Southeast Asian and Japanese samples when compared to the Indian populations. This pattern is consistent with the classical hypothesis of a recent introduction by man in Eastern Asia. The higher genetic diversity found within S. murinus from India, as well as previous mitochondrial and karyological results suggest that this area is the probable centre of origin for the species. Although the lack of gene flow between S. murinus and S. montanus is clearly established in an area of sympatry in Southern India, one Asian house shrew sampled in Nepal was more closely related to S. montanus. This could either reflect the retention of an ancestral polymorphism, or result from a hybridization episode between S. murinus and S. montanus. Similar conclusions were also suggested in mitochondrial DNA studies dealing with animals sampled in the Northern parts of the Indian subcontinent. Clearly, further data on Suncus from this area are needed in order to assess these hypotheses. (C) 1995 The Linnean Society of London