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.

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.

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.

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.

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.

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.

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 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.

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.

Reconstructing Early Industrial Contributions to Legacy Trace Metal Contamination in Southwestern Pennsylvania.

Early industrial trace metal loadings are poorly characterized but potentially substantial sources of trace metals to the landscape. The magnitude of legacy contamination in southwestern Pennsylvania, the cradle of North American fossil fuel industrialization, is reconstructed from trace metal concentrations in a sediment core with proxies including major and trace metal chemistry, bulk density, and magnetic susceptibility. Trace metal chemistry in this sediment record reflects 19th and 20th century land use and industry. In particular, early 19th century arsenic loadings to the lake are elevated from pesticides used by early European settlers at a lakeside tannery. Later, sediment barium concentrations rise, likely reflecting the onset of acidic mine drainage from coal operations. Twentieth century zinc, cadmium, and lead concentrations are dominated by emissions from the nearby, infamous Donora Zinc Works yet record both the opening of a nearby coal-fired power plant and amendments to the Clean Air Act. The impact of early industry is substantial and rivals more recent metal fluxes, resulting in a significant potential source of contaminated sediments. Thus, modern assessments of trace metal contamination cannot ignore early industrial inputs, as the potential remobilization of legacy contamination would impact ecosystem and human health.

Synchronous interhemispheric Holocene climate trends in the tropical Andes.

Holocene variations of tropical moisture balance have been ascribed to orbitally forced changes in solar insolation. If this model is correct, millennial-scale climate evolution should be antiphased between the northern and southern hemispheres, producing humid intervals in one hemisphere matched to aridity in the other. Here we show that Holocene climate trends were largely synchronous and in the same direction in the northern and southern hemisphere outer-tropical Andes, providing little support for the dominant role of insolation forcing in these regions. Today, sea-surface temperatures in the equatorial Pacific Ocean modulate rainfall variability in the outer tropical Andes of both hemispheres, and we suggest that this mechanism was pervasive throughout the Holocene. Our findings imply that oceanic forcing plays a larger role in regional South American climate than previously suspected, and that Pacific sea-surface temperatures have the capacity to induce abrupt and sustained shifts in Andean climate.

Environmental legacy of copper metallurgy and Mongol silver smelting recorded in Yunnan Lake sediments.

Geochemical measurements on well-dated sediment cores from Lake Er (Erhai) are used to determine the timing of changes in metal concentrations over 4500 years in Yunnan, a borderland region in southwestern China noted for rich mineral deposits but with inadequately documented metallurgical history. Our findings add new insight into the impacts and environmental legacy of human exploitation of metal resources in Yunnan history. We observe an increase in copper at 1500 BC resulting from atmospheric emissions associated with metallurgy. These data clarify the chronological issues related to links between the onset of Yunnan metallurgy and the advent of bronze technology in adjacent Southeast Asia, subjects that have been debated for nearly half a century. We also observe an increase from 1100 to 1300 AD in a number of heavy metals including lead, silver, zinc, and cadmium from atmospheric emissions associated with silver smelting. Culminating during the rule of the Mongols, known as the Yuan Dynasty (1271-1368 AD), these metal concentrations approach levels three to four times higher than those from industrialized mining activity occurring within the catchment today. Notably, the concentrations of lead approach levels at which harmful effects may be observed in aquatic organisms. The persistence of this lead pollution over time created an environmental legacy that likely contributes to known issues in modern day sediment quality. We demonstrate that historic metallurgical production in Yunnan can cause substantial impacts on the sediment quality of lake systems, similar to other paleolimnological findings around the globe.

1,500 year quantitative reconstruction of winter precipitation in the Pacific Northwest.

Multiple paleoclimate proxies are required for robust assessment of past hydroclimatic conditions. Currently, estimates of drought variability over the past several thousand years are based largely on tree-ring records. We produced a 1,500-y record of winter precipitation in the Pacific Northwest using a physical model-based analysis of lake sediment oxygen isotope data. Our results indicate that during the Medieval Climate Anomaly (MCA) (900-1300 AD) the Pacific Northwest experienced exceptional wetness in winter and that during the Little Ice Age (LIA) (1450-1850 AD) conditions were drier, contrasting with hydroclimatic anomalies in the desert Southwest and consistent with climate dynamics related to the El Niño Southern Oscillation (ENSO) and the Pacific Decadal Oscillation (PDO). These findings are somewhat discordant with drought records from tree rings, suggesting that differences in seasonal sensitivity between the two proxies allow a more compete understanding of the climate system and likely explain disparities in inferred climate trends over centennial timescales.

A 2,300-year-long annually resolved record of the South American summer monsoon from the Peruvian Andes.

Decadal and centennial mean state changes in South American summer monsoon (SASM) precipitation during the last 2,300 years are detailed using an annually resolved authigenic calcite record of precipitation δ(18)O from a varved lake in the Central Peruvian Andes. This unique sediment record shows that δ(18)O peaked during the Medieval Climate Anomaly (MCA) from A.D. 900 to 1100, providing evidence that the SASM weakened considerably during this period. Minimum δ(18)O values occurred during the Little Ice Age (LIA) between A.D. 1400 and 1820, reflecting a prolonged intensification of the SASM that was regionally synchronous. After the LIA, δ(18)O increased rapidly, particularly during the current warm period (CWP; A.D. 1900 to present), indicating a return to reduced SASM precipitation that was more abrupt and sustained than the onset of the MCA. Diminished SASM precipitation during the MCA and CWP tracks reconstructed Northern Hemisphere and North Atlantic warming and a northward displacement of the Intertropical Convergence Zone (ITCZ) over the Atlantic, and likely the Pacific. Intensified SASM precipitation during the LIA follows reconstructed Northern Hemisphere and North Atlantic cooling, El Niño-like warming in the Pacific, and a southward displacement of the ITCZ over both oceans. These results suggest that SASM mean state changes are sensitive to ITCZ variability as mediated by Western Hemisphere tropical sea surface temperatures, particularly in the Atlantic. Continued Northern Hemisphere and North Atlantic warming may therefore help perpetuate the recent reductions in SASM precipitation that characterize the last 100 years, which would negatively impact Andean water resources.

Drought variability in the Pacific Northwest from a 6,000-yr lake sediment record.

We present a 6,000-yr record of changing water balance in the Pacific Northwest inferred from measurements of carbonate δ(18)O and grayscale on a sediment core collected from Castor Lake, Washington. This subdecadally resolved drought record tracks the 1,500-yr tree-ring-based Palmer Drought Severity Index reconstructions of Cook et al. [Cook ER, Woodhouse CA, Eakin CM, Meko DM, Stahle DW (2004) Science 306:1015-1018] in the Pacific Northwest and extends our knowledge back to 6,000 yr B.P. The results demonstrate that low-frequency drought/pluvial cycles, with occasional long-duration, multidecadal events, are a persistent feature of regional climate. Furthermore, the average duration of multidecadal wet/dry cycles has increased since the middle Holocene, which has acted to increase the amplitude and impact of these events. This is especially apparent during the last 1,000 yr. We suggest these transitions were driven by changes in the tropical and extratropical Pacific and are related to apparent intensification of the El Niño Southern Oscillation over this interval and its related effects on the Pacific Decadal Oscillation. The Castor Lake record also corroborates the notion that the 20th century, prior to recent aridity, was a relatively wet period compared to the last 6,000 yr. Our findings suggest that the hydroclimate response in the Pacific Northwest to future warming will be intimately tied to the impact of warming on the El Niño Southern Oscillation.

Lake sediments record prehistoric lead pollution related to early copper production in North America.

The mining and use of copper by prehistoric people on Michigan's Keweenaw Peninsula is one of the oldest examples of metalworking. We analyzed the concentration of lead, titanium, magnesium, iron, and organic matter in sediment cores recovered from three lakes located near mine pits to investigate the timing, location, and magnitude of ancient copper mining pollution. Lead concentrations were normalized to lithogenic metals and organic matter to account for processes that can influence natural (or background) lead delivery. Nearly simultaneous lead enrichments occurred at Lake Manganese and Copper Falls Lake ∼8000 and 7000 years before present (yr BP), indicating that copper extraction occurred concurrently in at least two locations on the peninsula. The poor temporal coherence among the lead enrichments from ∼6300 to 5000 yr BP at each lake suggests that the focus of copper mining and annealing shifted through time. In sediment younger than ∼5000 yr BP, lead concentrations remain at background levels at all three lakes, excluding historic lead increases starting ∼150 yr BP. Our work demonstrates that lead emissions associated with both the historic and Old Copper Complex tradition are detectable and can be used to determine the temporal and geographic pattern of metal pollution.

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.

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.