Allergies, body mass, and hospitalization due to arbovirus infection: A prospective surveillance study in Machala, Ecuador.

Dengue, chikungunya, and Zika are arboviruses that cause 390 million infections annually. Risk factors for hospitalization are poorly understood. Communities affected by these diseases have an escalating prevalence of allergies and obesity, which are linked to immune dysfunction. We assessed the association of allergies or body mass with hospitalization for an arbovirus infection. From 2014 to 2017, we recruited participants with a clinical diagnosis of arbovirus infection. Arbovirus infections were laboratory-confirmed and allergies were self-reported. Mid-upper arm circumference (MUAC), weight, and height were measured. We used two logistic regression models to assess the relationships between hospitalization and allergies and between hospitalization and body mass (MUAC for participants <20 years old and body mass index (BMI) for adults ≥20 years old). Models were stratified by age group and adjusted for confounders. For allergies, 41 of 265 were hospitalized. There was no association between allergies and hospitalization. For body mass, 34 of 251 were hospitalized. There was a 43% decrease in hospitalization odds for each additional centimetre MUAC among children (aOR 0.566, 95% CI 0.252-1.019) and a 12% decrease in hospitalization odds for each additional BMI unit among adults (aOR 0.877, 95% CI 0.752-0.998). Our work encourages the exploration of the underlying mechanisms.

Pond Sediments Reveal the Increasing Importance of Road Runoff as a Source of Metal Contamination in Industrialized Urban Environments Downwind of Pittsburgh, Pennsylvania (USA).

Toxic levels of trace metals from human activities accumulate in natural environments, yet these metal mixtures are rarely characterized or quantified. Metal mixtures accumulate in historically industrial urban areas and change as economies shift. Previous research has often focused on the sources and fate of a specific element, which limits our understanding of metal contaminant interactions in our environment. Here, we reconstruct the history of metal contamination in a small pond downstream of an interstate highway and downwind of fossil fuel and metallurgical industries that have been active since the middle of the nineteenth century. Metal contamination histories were reconstructed from the sediment record using metal ratio mixing analysis to attribute the relative contributions of contamination sources. Cadmium, copper, and zinc concentrations in sediments accumulated since the construction of major road arteries in the 1930s and 40s are, respectively, 3.9, 2.4, and 6.6 times more concentrated than those during industry-dominated time periods. Shifts in elemental ratios suggest these changes in metal concentrations coincide with increased contributions from road and parking lot traffic, and to a lesser extent, from airborne sources. The metal mixture analysis demonstrates that in near-road environments, contributions from modern surface water pathways can obscure historical atmospheric industrial inputs.

Interhemispheric antiphasing of neotropical precipitation during the past millennium.

Uncertainty about the influence of anthropogenic radiative forcing on the position and strength of convective rainfall in the Intertropical Convergence Zone (ITCZ) inhibits our ability to project future tropical hydroclimate change in a warmer world. Paleoclimatic and modeling data inform on the timescales and mechanisms of ITCZ variability; yet a comprehensive, long-term perspective remains elusive. Here, we quantify the evolution of neotropical hydroclimate over the preindustrial past millennium (850 to 1850 CE) using a synthesis of 48 paleo-records, accounting for uncertainties in paleo-archive age models. We show that an interhemispheric pattern of precipitation antiphasing occurred on multicentury timescales in response to changes in natural radiative forcing. The conventionally defined "Little Ice Age" (1450 to 1850 CE) was marked by a clear shift toward wetter conditions in the southern neotropics and a less distinct and spatiotemporally complex transition toward drier conditions in the northern neotropics. This pattern of hydroclimatic change is consistent with results from climate model simulations indicating that a relative cooling of the Northern Hemisphere caused a southward shift in the thermal equator across the Atlantic basin and a southerly displacement of the ITCZ in the tropical Americas, with volcanic forcing as the principal driver. These findings are at odds with proxy-based reconstructions of ITCZ behavior in the western Pacific basin, where changes in ITCZ width and intensity, rather than mean position, appear to have driven hydroclimate transitions over the last millennium. This reinforces the idea that ITCZ responses to external forcing are region specific, complicating projections of the tropical precipitation response to global warming.

Metal ratio mixing models clarify metal contamination sources to lake sediments in Yunnan, China.

Contaminated legacy sediments contribute to modern pollution loadings, particularly trace metals. These contributions are challenging to quantify as metal histories reconstructed from sediment records cannot be easily divided into legacy and concurrent contamination. In particular, the contribution from re-mobilization and delivery of legacy metals stored in catchment soil, colluvial, and fluvial environments are rarely considered or quantified when interpreting sediment records. Here, extended records of metals accumulation for a set of three lakes in Yunnan, China are compared with endmember chemistries using Monte Carlo-Markov Chain mixing models to help identify source contributions to the sediments. This approach allows attribution of metals transported by atmospheric and fluvial mechanisms in a region with a history of mining and metallurgy spanning millennia. These analyses reveal distinct source mixtures and demonstrate the sensitivity of lake records to basin sediment dynamics. In particular, substantial proportions of elevated metal concentrations in these lake systems seem to arise from soil contributions more than from atmospheric deposition of smelting emissions. The largest soil contributions seem to be in Erhai, a lake with erosion prone soils closely "connected" to the lake. Moreover, these invesigations illustrate the potential for mixing approaches to accommodate and clarify uncertainties in metal source and extraction as differences in extraction efficiency can be incorporated into source uncertainty estimates. Ultimately, these approaches emphasize the need to account for fluvial metal transport in interpretation of sediment histories.

Severe Little Ice Age drought in the midcontinental United States during the Mississippian abandonment of Cahokia.

Drought has long been suspected as playing an important role in the abandonment of pre-Columbian Native American settlements across the midcontinental United States between 1350 and 1450 CE. However, high-resolution paleoclimatic reconstructions reflecting local effective moisture (the ratio of precipitation to evaporation) that are located in proximity to Mississippi period (1050-1450 CE) population centers are lacking. Here, we present a 1600-year-long decadally resolved oxygen isotope (δ18O) record from Horseshoe Lake (Collinsville, IL), an evaporatively influenced oxbow lake that is centrally located within the largest and mostly densely populated series of Mississippian settlements known as Greater Cahokia. A shift to higher δ18O in the Horseshoe Lake sediment record from 1200 to 1400 CE indicates that strongly evaporative conditions (i.e., low effective moisture) were persistent during the leadup to Cahokia's abandonment. These results support the hypothesis that climate, and drought specifically, strongly impacted agriculturally based pre-Columbian Native American cultures in the midcontinental US and highlights the susceptibility of this region, presently a global food production center, to hydroclimate extremes.

Contrasting ecosystem responses to climatic events and human activity revealed by a sedimentary record from Lake Yilong, southwestern China.

Global climate change and human activities have significantly impacted lake ecosystems at an accelerating rate in recent decades, but the differences between the responses of lake ecosystems to these two stressors remain unclear. Thus an improved understanding of the long-term influences of climatic and anthropogenic disturbances is necessary for the management of lake ecosystems. In order to address these issues, a sedimentary record was obtained from Lake Yilong in Yunnan Province in southwestern China, where the climate and natural environment are dominated by the Indian Summer Monsoon and there is a long history of human occupation and intensive human activity. The chronology is based on AMS 14C dates from 13 samples of plant macrofossils and charcoal, which show that the record spans the last ~12,000 yr. Geochemical indices were used to reconstruct hydro-climatic variations and lake ecosystem responses. The results indicate that a cold and humid climate prevailed from the late Pleistocene to the beginning of the Holocene, which was interrupted by an abrupt decrease in precipitation during 9.7-8.7 ka (1 ka = 1000 cal yr BP, corresponding to the 9.3 ka event). A persistent drying trend occurred during the middle and late Holocene, and there was an increase in the intensity of human activity during the past 1500 years. A comparison of the effects of a natural climatic event and human disturbance reveals contrasting lake ecosystem responses. The lake ecosystem was resilient to the 9.3 ka event and subsequently recovered; however, long-term human activity in the watershed, including deforestation and cultivation, reduced the stability of the lake ecosystem and positive feedback effects were strengthened, leading to the deviation of the system far from its previous stable state. It is concluded that, compared to climate change, human activities have had a much more serious impact on lake ecosystem.

Exploring the utility of social-ecological and entomological risk factors for dengue infection as surveillance indicators in the dengue hyper-endemic city of Machala, Ecuador.

The management of mosquito-borne diseases is a challenge in southern coastal Ecuador, where dengue is hyper-endemic and co-circulates with other arboviral diseases. Prior work in the region has explored social-ecological factors, dengue case data, and entomological indices. In this study, we bring together entomological and epidemiological data to describe links between social-ecological factors associated with risk of dengue transmission at the household level in Machala, Ecuador. Households surveys were conducted from 2014-2017 to assess the presence of adult Aedes aegypti (collected via aspiration) and to enumerate housing conditions, demographics, and mosquito prevention behaviors. Household-level dengue infection status was determined by laboratory diagnostics in 2014-2015. Bivariate analyses and multivariate logistic regression models were used to identify social-ecological variables associated with household presence of female Ae. aegypti and household dengue infection status, respectively. Aedes aegypti presence was associated with interruptions in water service and weekly trash collection, and household air conditioning was protective against mosquito presence. Presence of female Ae. aegypti was not associated with household dengue infections. We identified shaded patios and head of household employment status as risk factors for household-level dengue infection, while window screening in good condition was identified as protective against dengue infection. These findings add to our understanding of the systems of mosquito-borne disease transmission in Machala, and in the larger region of southern Ecuador, aiding in the development of improved vector surveillance efforts, and targeted interventions.

A Phase 1, Open-Label Assessment of a Dengue Virus-1 Live Virus Human Challenge Strain.

BACKGROUND: Dengue human infection models (DHIM) have been used as a safe means to test the viability of prophylaxis and therapeutics. METHODS: A phase 1 study of 12 healthy adult volunteers using a challenge virus, DENV-1-LVHC strain 45AZ5, was performed. A dose escalating design was used to determine the safety and performance profile of the challenge virus. Subjects were evaluated extensively until 28 days and then out to 6 months. RESULTS: Twelve subjects received the challenge virus: 6 with 0.5 mL of 6.5 × 103 plaque-forming units (PFU)/mL (low-dose group) and 6 with 0.5 mL of 6.5 × 104 PFU/mL (mid-dose group). All except 1 in the low-dose group developed detectable viremia. For all subjects the mean incubation period was 5.9 days (range 5-9 days) and mean time of viremia was 6.8 days (range 3-9 days). Mean peak for all subjects was 1.6 × 107 genome equivalents (GE)/mL (range 4.6 × 103 to 5 × 107 GE/mL). There were no serious adverse events or long-term safety signals noted. CONCLUSIONS: We conclude that DENV-1-LVHC was well-tolerated, resulted in an uncomplicated dengue illness, and may be a suitable DHIM for therapeutic and prophylactic product testing. CLINICAL TRIALS REGISTRATION: NCT02372175.

A simplified design for the C. elegans lifespan machine.

Caenorhabditis elegans (C. elegans) lifespan assays constitute a broadly used approach for investigating the fundamental biology of longevity. Traditional C. elegans lifespan assays require labor-intensive microscopic monitoring of individual animals to evaluate life/death over a period of weeks, making large-scale high throughput studies impractical. The lifespan machine developed by Stroustrup et al. (2013) adapted flatbed scanner technologies to contribute a major technical advance in the efficiency of C. elegans survival assays. Introducing a platform in which large portions of a lifespan assay are automated enabled longevity studies of a scope not possible with previous exclusively manual assays and facilitated novel discovery. Still, as initially described, constructing and operating scanner-based lifespan machines requires considerable effort and expertise. Here we report on design modifications that simplify construction, decrease cost, eliminate certain mechanical failures, and decrease assay workload requirements. The modifications we document should make the lifespan machine more accessible to interested laboratories.

Annually resolved Atlantic sea surface temperature variability over the past 2,900 y.

Global warming due to anthropogenic factors can be amplified or dampened by natural climate oscillations, especially those involving sea surface temperatures (SSTs) in the North Atlantic which vary on a multidecadal scale (Atlantic multidecadal variability, AMV). Because the instrumental record of AMV is short, long-term behavior of AMV is unknown, but climatic teleconnections to regions beyond the North Atlantic offer the prospect of reconstructing AMV from high-resolution records elsewhere. Annually resolved titanium from an annually laminated sedimentary record from Ellesmere Island, Canada, shows that the record is strongly influenced by AMV via atmospheric circulation anomalies. Significant correlations between this High-Arctic proxy and other highly resolved Atlantic SST proxies demonstrate that it shares the multidecadal variability seen in the Atlantic. Our record provides a reconstruction of AMV for the past ∼3 millennia at an unprecedented time resolution, indicating North Atlantic SSTs were coldest from ∼1400-1800 CE, while current SSTs are the warmest in the past ∼2,900 y.

Andean drought and glacial retreat tied to Greenland warming during the last glacial period.

Abrupt warming events recorded in Greenland ice cores known as Dansgaard-Oeschger (DO) interstadials are linked to changes in tropical circulation during the last glacial cycle. Corresponding variations in South American summer monsoon (SASM) strength are documented, most commonly, in isotopic records from speleothems, but less is known about how these changes affected precipitation and Andean glacier mass balance. Here we present a sediment record spanning the last ~50 ka from Lake Junín (Peru) in the tropical Andes that has sufficient chronologic precision to document abrupt climatic events on a centennial-millennial time scale. DO events involved the near-complete disappearance of glaciers below 4700 masl in the eastern Andean cordillera and major reductions in the level of Peru's second largest lake. Our results reveal the magnitude of the hydroclimatic disruptions in the highest reaches of the Amazon Basin that were caused by a weakening of the SASM during abrupt arctic warming. Accentuated warming in the Arctic could lead to significant reductions in the precipitation-evaporation balance of the southern tropical Andes with deleterious effects on this densely populated region of South America.

A fluoroscopic analysis of the length changes of the capsulo-osseous layer of the distal iliotibial band.

PURPOSE: Previous studies have implicated the iliotibial band and its deeper capsulo-osseous layer as key restraints against internal rotation. However, the kinematic properties of the capsulo-osseous layer, throughout knee range of motion, are not currently known. Therefore, the purpose of this research was to quantify the length changes of this structure through various degrees of knee flexion. METHODS: Ten cadaveric knee specimens were dissected to expose the capsulo-osseous layer of the iliotibial band. Radiopaque beads were embedded, at standardized increments, into the tissue and fluoroscopic images were taken from 0° to 105° of knee flexion in 15° increments. The positions of the beads were identified in each image and the length, width, and area changes of the capsulo-osseous layer were calculated. The data were analyzed as a percent change from 0° and compared across flexion angles using a repeated-measures analysis of variance (α = 0.05). RESULTS: There was a significant increase in the length of the capsulo-osseous layer at flexion angles greater than 30°, with changes occurring primarily at the level of the femoral insertion. Meanwhile, non-homogenous decreases in width and area were found with increasing flexion angle. The distance between the capsulo-osseous layer insertion on the distal femur and proximal tibia significantly increased from 60° to 105°; maximal changes occurred at 105° [9.64 (4.12) %, p = 0.003]. CONCLUSIONS: The capsulo-osseous layer of the iliotibial band behaves in a non-isometric fashion and this work suggests that tensioning and fixation should occur between 75° and 105° of flexion, if repair or reconstruction is indicated.

The Effects of Japanese Encephalitis Vaccine and Accelerated Dosing Scheduling on the Immunogenicity of the Chimeric Yellow Fever Derived Tetravalent Dengue Vaccine: A Phase II, Randomized, Open-Label, Single-Center Trial in Adults Aged 18 to 45 Years in the United States.

BACKGROUND: Dengue is a global health problem requiring an effective, safe dengue vaccine. METHODS: We report the results of a phase II, randomized, open-label, single-center trial in adults aged 18 to 45 years in the United States designed to explore the effects of the Chimeric Yellow Fever Derived Tetravalent Dengue Vaccine (CYD-TDV, Dengvaxia) when administered on its designated schedule (months 0, 6, and 12) or on an accelerated dosing schedule (months 0, 2, and 6) and/or given before, or concomitantly with, a vaccine against Japanese encephalitis (JE). RESULTS: Based on dengue virus serotype-specific neutralizing antibody (NAb), the accelerated dosing schedule was comparable to the 0, 6, and 12-month schedule. Giving JE vaccine concurrently with CYD-TDV did not result in an increase in overall NAb titers. Immunophenotyping of peripheral blood mononuclear cells revealed an increase in activated CD8+ T cells after CYD-TDV vaccination, a phenomenon that was greatest for the JE vaccine primed. CONCLUSIONS: We conclude that an accelerated dosing schedule of CYD-TDV results in essentially equivalent dengue serotype-specific NAb titers as the currently used schedule, and there may be an early benefit in antibody titers and activated CD8+ T cells by the administration of the JE vaccine before CYD-TDV vaccination.

Effect of Antimalarial Drugs on the Immune Response to Intramuscular Rabies Vaccination Using a Postexposure Prophylaxis Regimen.

BACKGROUND: Chloroquine can impair the immune responses to intradermal rabies vaccination. Current guidelines recommend an extra intramuscular dose be given for postexposure prophylaxis in previously unvaccinated persons taking any antimalarial drug. METHODS: We conducted a randomized, open-label, single-site study in 103 previously unvaccinated healthy adults age ≥18 to ≤60 years old to evaluate the effects of chloroquine, atovaquone/proguanil (Malarone), and doxycycline on the antibody response to a purified chick embryo cell vaccine, given on a postexposure prophylaxis schedule. All treatment groups received antimalarials 14 days prior to and during vaccination. RESULTS: All subjects achieved accepted neutralizing antibody titers of ≥0.5 IU/mL following the second rabies vaccination dose and maintained this protection through the duration of the study. We observed a reduction in rabies antibody geometric mean titer in the chloroquine versus control groups 28 days after vaccination: 2.3 versus 6.87 IU/mL, respectively (P < .001, t test). A significant difference was not observed for those taking Malarone or doxycycline. CONCLUSIONS: We conclude that there is no reduction of rabies antibody response in subjects taking Malarone or doxycycline, but a significant reduction in those taking chloroquine; however, accepted antibody levels were achieved for all 3 antimalarials. CLINICAL TRIALS REGISTRATION: NCT02564471.

Serologic Response of 2 Versus 3 Doses and Intradermal Versus Intramuscular Administration of a Licensed Rabies Vaccine for Preexposure Prophylaxis.

BACKGROUND: The World Health Organization recommends intradermal (ID) administration of rabies vaccine for preexposure prophylaxis. METHODS: In a randomized trial in adults assigned to 1 of 6 treatment groups (ID vs intramuscular [IM], 2 vs 3 doses, and controls), rabies neutralizing antibody titers were measured to 1 year postvaccination. RESULTS: ID vaccination produced acceptable antibody levels in all subjects (2- and 3-dose groups). At day 365, acceptable levels were 40% for IM and 50% for ID 2-dose schedule, and 70% for IM and 60% for ID 3-dose schedule. CONCLUSIONS: ID rabies vaccination induces acceptable antibody titers at a fraction of the dose. CLINICAL TRIALS REGISTRATION: NCT02374814.

Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions.

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays. With an interest in increasing throughput, we explored automation with flatbed scanner-based Automated Lifespan Machines (ALMs). We used ALMs to measure survivorship of 22 Caenorhabditis strains spanning three species. Additionally, we tested five chemicals that we previously found extended lifespan in manual assays. Overall, we found similar sources of variation among trials for the ALM and our previous manual assays, verifying reproducibility of outcome. Survival assessment was generally consistent between the manual and the ALM assays, although we did observe radically contrasting results for certain compound interventions. We found that particular lifespan outcome differences could be attributed to protocol elements such as enhanced light exposure of specific compounds in the ALM, underscoring that differences in technical details can influence outcomes and therefore interpretation. Overall, we demonstrate that the ALMs effectively reproduce a large, conventionally scored dataset from a diverse test set, independently validating ALMs as a robust and reproducible approach toward aging-intervention screening.

Climate, Fire, and Vegetation Mediate Mercury Delivery to Midlatitude Lakes over the Holocene.

The rise in mercury concentrations in lake sediment deposited over the last ∼150 years is widely recognized to have resulted from human activity. However, few studies in the Great Lakes region have used lake sediment to reconstruct atmospheric mercury deposition on millennial time scales. Here we present a 9000-year mercury record from sediment in Copper Falls; a small closed-basin lake on the Keweenaw Peninsula. Prior to abrupt increases in the 19th and 20th centuries, mercury remains at relatively low concentrations for the last 9000 years. Higher mercury fluxes in the early Holocene (3.4 ± 1.1 µg m-2 yr-1) are attributed to drier conditions and greater forest fire occurrence. The gradual decline in mercury flux over the middle to late Holocene (1.9 ± 0.2 µg m-2 yr-1) is interpreted to reflect a transition to wetter conditions, which reduced forest fires, and promoted the development of soil organic matter and deciduous forests that sequestered natural sources of mercury. The Copper Falls Lake record highlights the sensitivity of watersheds to changes in mercury inputs from both human and natural forcings, and provides millennial-scale context for recent mercury contamination that will aid in establishing baseline values for restoration efforts.

The Donora Smog Revisited: 70 Years After the Event That Inspired the Clean Air Act.

At a storefront museum approximately 25 miles southeast of Pittsburgh, Pennsylvania, a sign reads, "Clean Air Started Here." This is not hyperbole. At the end of October 1948, the communities of Donora and Webster in Pennsylvania were visited by a smog that changed the face of environmental protection in the United States. Conservative estimates showed that 20 individuals died, while an additional 5900-43% of the population of Donora-were affected by the smog. This event led to the first large-scale epidemiological investigation of an environmental health disaster in the United States. Questions remain about the long-term effects of the smog, because higher rates of cardiovascular disease and cancer than were expected were observed in the region in the decade following the smog. Recent work has suggested that environmental contaminants from a bygone era in Donora might have an impact even today. In addition, reports regarding air pollution have indicated that levels of pollutants similar to those estimated to have occurred in Donora are currently present in some rapidly industrializing regions of China and India. Seventy years after the smog, this event still resonates.

The Burden of Dengue Fever and Chikungunya in Southern Coastal Ecuador: Epidemiology, Clinical Presentation, and Phylogenetics from the First Two Years of a Prospective Study.

Here, we report the findings from the first 2 years (2014-2015) of an arbovirus surveillance study conducted in Machala, Ecuador, a dengue-endemic region. Patients with suspected dengue virus (DENV) infections (index cases, N = 324) were referred from five Ministry of Health clinical sites. A subset of DENV-positive index cases (N = 44) were selected, and individuals from the index household and four neighboring homes within 200 m were recruited (N = 400). Individuals who entered the study, other than the index cases, are referred to as associates. In 2014, 70.9% of index cases and 35.6% of associates had acute or recent DENV infections. In 2015, 28.3% of index cases and 12.8% of associates had acute or recent DENV infections. For every DENV infection captured by passive surveillance, we detected an additional three acute or recent DENV infections in associates. Of associates with acute DENV infections, 68% reported dengue-like symptoms, with the highest prevalence of symptomatic acute infections in children aged less than 10 years. The first chikungunya virus (CHIKV) infections were detected on epidemiological week 12 in 2015; 43.1% of index cases and 3.5% of associates had acute CHIKV infections. No Zika virus infections were detected. Phylogenetic analyses of isolates of DENV from 2014 revealed genetic relatedness and shared ancestry of DENV1, DENV2, and DENV4 genomes from Ecuador with those from Venezuela and Colombia, indicating the presence of viral flow between Ecuador and surrounding countries. Enhanced surveillance studies, such as this, provide high-resolution data on symptomatic and inapparent infections across the population.