Assessing Ozone-Related Health Impacts under a Changing Climate

Climate change may increase the frequency and intensity of ozone episodes in future summers in the United States. However, only recently have models become available that can assess the impact of climate change on O(3) concentrations and health effects at regional and local scales that are relevant to adaptive planning. We developed and applied an integrated modeling framework to assess potential O(3)-related health impacts in future decades under a changing climate. The National Aeronautics and Space Administration–Goddard Institute for Space Studies global climate model at 4° × 5° resolution was linked to the Penn State/National Center for Atmospheric Research Mesoscale Model 5 and the Community Multiscale Air Quality atmospheric chemistry model at 36 km horizontal grid resolution to simulate hourly regional meteorology and O(3) in five summers of the 2050s decade across the 31-county New York metropolitan region. We assessed changes in O(3)-related impacts on summer mortality resulting from climate change alone and with climate change superimposed on changes in O(3) precursor emissions and population growth. Considering climate change alone, there was a median 4.5% increase in O(3)-related acute mortality across the 31 counties. Incorporating O(3) precursor emission increases along with climate change yielded similar results. When population growth was factored into the projections, absolute impacts increased substantially. Counties with the highest percent increases in projected O(3) mortality spread beyond the urban core into less densely populated suburban counties. This modeling framework provides a potentially useful new tool for assessing the health risks of climate change

First Fruits of the Spitzer Space Telescope: Galactic and Solar System Studies

This article provides a brief overview of the Spitzer Space Telescope and discusses its initial scientific results on galactic and solar system science.Comment: Review article to appear in slightly different format in Vol.44 of Annual Reviews of Astronomy and Astrophysics, 200

The Involutive Quantaloid of Completely Distributive Lattices

Let L be a complete lattice and let Q(L) be the unital quantale of join-continuous endo-functions of L. We prove the following result: Q(L) is an involutive (that is, non-commutative cyclic ⋆-autonomous) quantale if and only if L is a completely distributive lattice. If this is the case, then the dual tensor operation corresponds, via Raney's transforms, to composition in the (dual) quantale of meet-continuous endo-functions of L. Let sLatt be the category of sup-lattices and join-continuous functions and let cdLatt be the full subcategory of sLatt whose objects are the completely distributive lattices. We argue that (i) cdLatt is itself an involutive quantaloid, and therefore it is the largest full-subcategory of sLatt with this property; (ii) cdLatt is closed under the monoidal operations of sLatt and, consequently, if Q(L) is involutive, then Q(L) is completely distributive as well

Biological evaluation of hydroxynaphthoquinones as anti-malarials

Abstract\ud \ud \ud \ud Background\ud The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone®, an important drug for the treatment and prevention of malaria.\ud \ud \ud \ud Methods\ud Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation. Potential cytotoxicity in HEK293T cells was assessed using the MTT assay. Changes in mitochondrial membrane potential of Plasmodium were measured using the fluorescent dye Mitrotracker Red CMXROS.\ud \ud \ud \ud Results\ud Four compounds demonstrated IC50s in the mid-micromolar range, and the most active compound, N3, had an IC50 of 443 nM. N3 disrupted mitochondrial membrane potential, and after 1 hour presented an IC50ΔΨmit of 16 μM. In an in vitro cytotoxicity assay using HEK 293T cells N3 demonstrated no cytotoxicity at concentrations up to 16 μM.\ud \ud \ud \ud Conclusions\ud N3 was a potent inhibitor of mitochondrial electron transport, had nanomolar activity against cultured Plasmodium falciparum and showed minimal cytotoxicity. N3 may serve as a starting point for the design of new hydroxynaphthoquinone anti-malarials.This work was supported by FAPESP (Fundação de Amparo a Pesquisa de São Paulo) (07/52924-0), by Malaria Pronex, and by a INCT-INBqMed (Instituto Nacional de Ciência e Tecnologia- Instituto Nacional de Ciência e Tecnologia de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosa) grant. C.R.S. Garcia and V. Ferreira are CNPQ (Conselho Nacional de Pesquisa) fellows. D.S. received a CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) Fellowship. D.R. da Rocha thanks FAPERJ (Fundação de Amparo a Pesquisa do Rio De Janeiro) for their doctoral fellowship. LNC and MM received a FAPESP Fellowship. Thanks are due to the CNPQ, CAPES and FAPERJ for funding this work.This work was supported by FAPESP (Fundação de Amparo a Pesquisa de São Paulo) (07/529240), by Malaria Pronex, and by a INCTINBqMed (Instituto Nacional de Ciência e Tecnologia Instituto Nacional de Ciência e Tecnologia de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosa) grant. C.R.S. Garcia and V. Ferreira are CNPQ (Conselho Nacional de Pesquisa) fellows. D.S. received a CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) Fellowship. D.R. da Rocha thanks FAPERJ (Fundação de Amparo a Pesquisa do Rio De Janeiro) for their doctoral fellowship. LNC and MM received a FAPESP Fellowship. Thanks are due to the CNPQ, CAPES and FAPERJ for funding this work

Urban Heat Island and Vulnerable Population. The Case of Madrid

The Urban Heat Island effect shows the differences among temperatures in urban areas and the surrounding rural ones. Previous studies have demonstrated that temperature differences could be up to 8 °C during the hottest periods of summer in Madrid , and that it varies according to the urban structure. Associated to this effect, the impact of temperature increase over dwelling indoor thermal comfort seems to double cooling energy demand . In Madrid, fuel poor households already suffering from inadequate indoor temperatures can face important overheating problems and, as a consequence, relevant health problems could become more frequent and stronger. This poses an increment in mortality rates in risk groups that should be evaluated. This research is aimed at establishing the geospatial connection between the urban heat island and the most vulnerable population living in the city of Madrid. Hence, those areas most in need for an urban intervention can be detected and prioritized

Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Although an increasing number of genetic factors have been connected to this debilitating condition, the proportion of cases that can be attributed to distinct genetic defects is unknown. To provide a comprehensive analysis of the frequency and spectrum of pathogenic missense mutations and coding risk variants in nine genes previously implicated in DLB, we performed exome sequencing in 111 pathologically confirmed DLB patients. All patients were Caucasian individuals from North America. Allele frequencies of identified missense mutations were compared to 222 control exomes. Remarkably, ~ 25% of cases were found to carry a pathogenic mutation or risk variant in APP, GBA or PSEN1, highlighting that genetic defects play a central role in the pathogenesis of this common neurodegenerative disorder. In total, 13% of our cohort carried a pathogenic mutation in GBA, 10% of cases carried a risk variant or mutation in PSEN1, and 2% were found to carry an APP mutation. The APOE ε4 risk allele was significantly overrepresented in DLB patients (p-value < 0.001). Our results conclusively show that mutations in GBA, PSEN1, and APP are common in DLB and consideration should be given to offer genetic testing to patients diagnosed with Lewy body dementia

Access and utilisation of primary health care services comparing urban and rural areas of Riyadh Providence, Kingdom of Saudi Arabia

The Kingdom of Saudi Arabia (KSA) has seen an increase in chronic diseases. International evidence suggests that early intervention is the best approach to reduce the burden of chronic disease. However, the limited research available suggests that health care access remains unequal, with rural populations having the poorest access to and utilisation of primary health care centres and, consequently, the poorest health outcomes. This study aimed to examine the factors influencing the access to and utilisation of primary health care centres in urban and rural areas of Riyadh province of the KSA