Use of cumulative incidence of novel influenza A/H1N1 in foreign travelers to estimate lower bounds on cumulative incidence in Mexico

Background: An accurate estimate of the total number of cases and severity of illness of an emerging infectious disease is required both to define the burden of the epidemic and to determine the severity of disease. When a novel pathogen first appears, affected individuals with severe symptoms are more likely to be diagnosed. Accordingly, the total number of cases will be underestimated and disease severity overestimated. This problem is manifest in the current epidemic of novel influenza A/H1N1. Methods and Results: We used a simple approach to leverage measures of incident influenza A/H1N1 among a relatively small and well observed group of US, UK, Spanish and Canadian travelers who had visited Mexico to estimate the incidence among a much larger and less well surveyed population of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009. Such an estimate serves as a lower bound because it does not account for underreporting of cases in travelers or for nonrandom mixing between Mexican residents and visitors, which together could increase the estimates by more than an order of magnitude. Conclusions: We find that the number of cases in Mexican residents may exceed the number of confirmed cases by two to three orders of magnitude. While the extent of disease spread is greater than previously appreciated, our estimate suggests that severe disease is uncommon since the total number of cases is likely to be much larger than those of confirmed cases

A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.

Clues to Alzheimer disease (AD) pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP) and its processing has emerged and considerable interest has been directed at the hypothesis that Aβ peptides induce changes central to pathogenesis. Accordingly, molecules that reduce the levels of Aβ peptides have been discovered such as γ-secretase inhibitors (GSIs) and modulators (GSMs). GSIs and GSMs reduce Aβ levels through very different mechanisms. However, GSIs, but not GSMs, markedly increase the levels of APP CTFs that are increasingly viewed as disrupting neuronal function. Here, we evaluated the effects of GSIs and GSMs on a number of neuronal phenotypes possibly relevant to their use in treatment of AD. We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF), suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with respect to anti-amyloid treatments, even an APP-specific GSI may have deleterious effects and GSMs may serve as a better alternative

Rapid changes in meridional advection of Southern Ocean intermediate waters to the tropical Pacific during the last 30 kyr

The Southern Ocean is increasingly recognized as a key player in the general ocean thermohaline circulation and the global climate system during glacial–interglacial transitions. In particular, the advection of Southern Ocean intermediate waters (SOIW), like Antarctic Intermediate Water and Sub-Antarctic Mode Water, to the Eastern Equatorial Pacific (EEP), through a so-called “oceanic tunnelling” mechanism, is an important means for rapid transfer of climatic signals (such as heat, fresh water, salt, and chemical species) from high-to-low latitudes. However, information on how intermediate water advection rates changed in the past, and particularly during deglaciations, is fragmentary. We present new results for Nd isotopes (εNd) in cleaned foraminifera shells (Neogloboquadrina dutertrei) for the last 30 kyr at ODP Site 1240 in the EEP. N. dutertrei preferentially dwells in the lower thermocline, at the core of the Equatorial Undercurrent (EUC), and the εNd variability over time provides a record of the changes in the εNd of the EUC. Through mixing models we show that the EUC record is primarily controlled by changes in the volume transport of intermediate waters and not by Southern Ocean εNd changes. Southern Ocean signals in the EUC are stronger during colder intervals (Younger Dryas, last glacial maximum and Heinrich stadials 1 and 2), in agreement with tropical Atlantic intermediate water records. In addition, covariations between N. dutertrei δ13C, molecular biomarkers, and diatom productivity at Site 1240 confirm the intermediate water route as an important mechanism for the transfer of climate signals from high-to-low latitudes. Changes in the SOIW chemistry during the deglaciation are likely linked to the upwelling of ‘old’ deep waters in the Southern Ocean and subsequent export as intermediate waters, which are coeval with the atmospheric CO2 rise. Moreover, a comparison of multiple proxy records for the last 30 kyr indicates a latitudinal shift and/or a change in the convection depth of intermediate waters in the Southern Ocean prior to the onset of the deglaciation

Elastomeric Osteoconductive Synthetic Scaffolds with Acquired Osteoinductivity Expedite the Repair of Critical Femoral Defects in Rats

Regenerative medicine aspires to reduce reliance on or overcome limitations associated with donor tissue-mediated repair. Structural bone allografts are commonly used in orthopedic surgery, with a high percentage of graft failure due to poor tissue integration. This problem is aggravated among elderly, those suffering from metabolic conditions, or those undergoing cancer therapies that compromise graft healing. Toward this end, we developed a synthetic graft named FlexBone, in which nanocrystalline hydroxyapatite (50-wt%) was structurally integrated with crosslinked poly(hydroxyethyl methacrylate) hydrogel, which provides dimensional stability and elasticity. It recapitulates the essential role of nanocrystalline hydroxyapatite in defining the osteoconductivity and biochemical microenvironment of bone because of its affinity for biomolecules. Here, we demonstrate that FlexBone effectively absorbed endogenously secreted signaling molecules associated with the inflammation/graft healing cascade upon being press-fit into a 5-mm rat femoral segmental defect. Further, when preabsorbed with a single dose of 400-ng recombinant human (rh) bone morphogenetic protein-2/7 heterodimer, it enabled the functional repair of the critical-sized defect by 8-12 weeks. FlexBone was stably encapsulated by the bridging bony callus and the FlexBone-callus interface was continuously remodeled. In summary, FlexBone combines the dimensional stability and osteoconductivity of structural bone allografts with desirable surgical compressibility and acquired osteoinductivity in an easy-to-fabricate and scalable synthetic biomaterial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90480/1/ten-2Etea-2E2010-2E0274.pd

Presenting the AfriArch Isotopic Database

AfriArch is an archaeological and paleoenvironmental data community designed to integrate datasets related to human-environmental interactions in Holocene Africa. Here we present a dataset of bioarchaeological stable isotope (C/N/O) and radiocarbon measurements from African archaeological sites spanning the Holocene. Modern measurements, when reported together with archaeological data in original publications, are also included. The dataset consists of 5568 entries and covers the entirety of Africa, though most isotopic research has been concentrated in southern Africa. The AfriArch isotopic dataset can be used in paleodietary, paleodemography, paleoclimatic, and paleoenvironmental studies. It can also be employed to highlight data gaps across space and time and set future research agendas

On the use of MODIS EVI to assess gross primary productivity of North American ecosystems

[1] Carbon flux models based on light use efficiency (LUE), such as the MOD17 algorithm, have proved difficult to parameterize because of uncertainties in the LUE term, which is usually estimated from meteorological variables available only at large spatial scales. In search of simpler models based entirely on remote‐sensing data, we examined direct relationships between the enhanced vegetation index (EVI) and gross primary productivity (GPP) measured at nine eddy covariance flux tower sites across North America. When data from the winter period of inactive photosynthesis were excluded, the overall relationship between EVI and tower GPP was better than that between MOD17 GPP and tower GPP. However, the EVI/GPP relationships vary between sites. Correlations between EVI and GPP were generally greater for deciduous than for evergreen sites. However, this correlation declined substantially only for sites with the smallest seasonal variation in EVI, suggesting that this relationship can be used for all but the most evergreen sites. Within sites dominated by either evergreen or deciduous species, seasonal variation in EVI was best explained by the severity of summer drought. Our results demonstrate that EVI alone can provide estimates of GPP that are as good as, if not better than, current versions of the MOD17 algorithm for many sites during the active period of photosynthesis. Preliminary data suggest that inclusion of other remote‐sensing products in addition to EVI, such as the MODIS land surface temperature (LST), may result in more robust models of carbon balance based entirely on remote‐sensing data