Serum macrophage migration inhibitory factor levels predict brain atrophy in people with primary progressive multiple sclerosis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine linked to multiple sclerosis (MS) progression that is thought to be inhibited by ibudilast. SPRINT-MS was a phase 2 placebo-controlled trial of ibudilast in progressive multiple sclerosis (PMS). OBJECTIVE: To determine whether baseline MIF levels predict imaging outcomes and assess the effects of ibudilast on serum and cerebrospinal fluid (CSF) MIF levels in people with PMS treated with ibudilast. METHODS: Participants in the SPRINT-MS trial were treated with either ibudilast or placebo and underwent brain magnetic resonance imaging (MRI) every 24 weeks over a duration of 96 weeks. MIF was measured in serum and CSF. RESULTS: MIF levels were compared with imaging outcomes in 223 participants from the SPRINT-MS study. In the primary progressive multiple sclerosis (PPMS) cohort, males had higher serum (p < 0.001) and CSF (p = 0.01) MIF levels, as compared with females. Higher baseline serum MIF levels in PPMS were associated with faster brain atrophy (beta = -0.113%, 95% confidence interval (CI): -0.204% to -0.021%; p = 0.016). These findings were not observed in secondary progressive multiple sclerosis (SPMS). Ibudilast did not affect either serum or CSF MIF levels. CONCLUSIONS: Serum MIF levels were associated with male sex and predicted brain atrophy in PPMS, but not SPMS. Ibudilast did not demonstrate an effect on MIF levels, as compared with placebo, although we cannot exclude a functional effect.

Biotransformation of PFAA Precursors by Oxygenase-Expressing Bacteria in AFFF-Impacted Groundwater and in Pure-Compound Studies with 6:2 FTS and EtFOSE.

Numerous US drinking water aquifers have been contaminated with per- and polyfluoroalkyl substances (PFAS) from fire-fighting and fire-training activities using aqueous film-forming foam (AFFF). These sites often contain other organic compounds, such as fuel hydrocarbons and methane, which may serve as primary substrates for cometabolic (i.e., nongrowth-linked) biotransformation reactions. This work investigates the abilities of AFFF site relevant bacteria (methanotrophs, propanotrophs, octane, pentane, isobutane, toluene, and ammonia oxidizers), known to express oxygenase enzymes when degrading their primary substrates, to biotransform perfluoroalkyl acid (PFAA) precursors to terminal PFAAs. Microcosms containing AFFF-impacted groundwater, 6:2 fluorotelomer sulfonate (6:2 FTS), or N-ethylperfluorooctane sulfonamidoethanol (EtFOSE) were inoculated with the aerobic cultures above and incubated for 4 and 8 weeks at 22 °C. Bottles were sacrificed, extracted, and subjected to target, nontarget, and suspect screening for PFAS. The PFAA precursors 6:2 FTS, N-sulfopropyldimethyl ammoniopropyl perfluorohexane sulfonamide (SPrAmPr-FHxSA), and EtFOSE transformed up to 99, 71, and 93%, respectively, and relevant daughter products, such as the 6:1 fluorotelomer ketone sulfonate (6:1 FTKS), were identified in quantities previously not observed, implicating oxygenase enzymes. This is the first report of a suite of site relevant PFAA precursors being transformed in AFFF-impacted groundwater by bacteria grown on substrates known to induce specific oxygenase enzymes. The data provide crucial insights into the microbial transformation of these compounds in the subsurface.

Food security status and cardiometabolic health by sex/gender and race/ethnicity among adults in the United States.

BACKGROUND: Minoritized racial/ethnic groups and women in the United States (US) are disproportionately burdened by food insecurity, which likely contributes to disparities in cardiovascular health (CVH). Disparities are projected to widen due to the worsening climate crisis that is straining the agricultural system including food supplies. Nonetheless, studies have not investigated the relationship between food security status and 'ideal' CVH in a large, nationally-representative and racially/ethnically diverse US sample. METHODS AND RESULTS: We investigated household food security status in relation to 'ideal' CVH among US adults (N = 157,001) using 2014-2018/2020 National Health Interview Survey data. Food security status was defined as very low, low, marginal, or high. A summed score of 4 health behaviors and 3 clinical factors totaling 7 different measures was dichotomized (yes/no) to assess modified 'ideal' CVH (mICVH). Using Poisson regression with robust variance, we estimated prevalence ratios (PRs) and 95% CIs of mICVH by household food security status. We stratified models by sex/gender and race/ethnicity. Very low food security prevalence was higher among non-Hispanic (NH)-Black (8.0%) compared to Hispanic/Latinx (5.1%), NH-White (3.1%) and NH-Asian (1.7%) adults. The association between very low versus high food security and mICVH was stronger among women (PR = 0.23 [95% CI: 0.17-0.31]) than men (PR = 0.48 [95% CI: 0.35-0.66]). Compared to NH-White adults with high food security, racially/ethnically minoritized groups with very low to high food security were generally less likely (range: [PRvery low = 0.25[95% CI: 0.14-0.44] - [PRhigh = 0.88 [95% CI: 0.79-0.97]) to meet mICVH criteria. CONCLUSIONS: Food insecurity was associated with lower mICVH prevalence and racially/ethnically minoritized groups were disproportionately burdened.

Perceived neighborhood social cohesion and type 2 diabetes mellitus by age, sex/gender, and race/ethnicity in the United States.

In prior research, perceived low neighborhood social cohesion (nSC) has been associated with prevalence of type 2 diabetes mellitus (T2DM); however, few studies have investigated the nSC-T2DM relationship among a large, racially/ethnically diverse, and nationally representative sample of the U.S. population. We used National Health Interview Survey (2013-2018) data to determine overall, age-, sex/gender-, and racial/ethnic-specific associations between nSC and T2DM among 170,432 adults. Self-reported nSC was categorized as low, medium, and high. T2DM was determined by participants being told they had diabetes by a health professional. We used Poisson regression with robust variance to estimate prevalence ratios (PRs) and 95% confidence intervals (CI) while adjusting for confounders. Mean age was 47.4 ±â€¯0.1 years, 52% were women, and 69% self-identified as Non-Hispanic (NH)-White. Low vs. high nSC was associated with a higher prevalence of T2DM (PR = 1.22 [95% CI: 1.16-1.27]), after adjustment. A higher prevalence of T2DM was observed among participants 31-49 years old who perceived low vs. high nSC (PR = 1.36 [95% CI: 1.20-1.54]) and among participants ≥50 years old (PR = 1.18 [95% CI: 1.13-1.24]). Hispanic/Latinx women 18-30 years old in neighborhoods with low vs. high social cohesion had a higher prevalence of T2DM (PR = 3.70 [95% CI: 1.40-9.80]), whereas NH-Black women 18-30 years old in neighborhoods with medium vs. high social cohesion had a lower prevalence of T2DM (PR = 0.35 [95% CI: 0.14-0.89]). Our findings support the literature by demonstrating an association between neighborhood environment and T2DM as well as extend it by identifying determinants for intervention for T2DM.

QuantumScents: Quantum-Mechanical Properties for 3.5k Olfactory Molecules.

Quantitative structure-odor relationships are critically important for studies related to the function of olfaction. Current literature data sets contain expert-labeled molecules but lack feature data. This paper introduces QuantumScents, a quantum mechanics augmented derivative of the Leffingwell data set. QuantumScents contains 3.5k structurally and chemically diverse molecules ranging from 2 to 30 heavy atoms (CNOS) and their corresponding 3D coordinates, total PBE0 energy, molecular dipole moment, and per-atom Hirshfeld charges, dipoles, and ratios. The authors demonstrate that Hirshfeld charges and ratios contain sufficient information to perform molecular classification by training a Message Passing Neural Network with chemprop (Heid, E.; et al. ChemRxiv, 2023, DOI: 10.26434/chemrxiv-2023-3zcfl) to predict scent labels. The QuantumScents data set is freely available on Zenodo along with the authors' code, example models, and data set generation workflow (https://zenodo.org/doi/10.5281/zenodo.8239853).

Prediction of Aqueous Reduction Potentials of X•, ChH•, and XO• Radicals with X = Halogen and Ch = Chalcogen.

The aqueous electron affinity and aqueous reduction potentials for F•, Cl•, Br•, I•, OH•, SH•, SeH•, TeH•, ClO•, BrO•, and IO• were calculated using electronic structure methods for explicit cluster models coupled with a self-consistent reaction field (SMD) to treat the aqueous solvent. Calculations were conducted using MP2 and correlated molecular orbital theory up to the CCSD(T)-F12b level for water tetramer clusters and MP2 for octamer cluster. Inclusion of explicit waters was found to be important for accurately predicting the redox potentials in a number of cases. The calculated reduction potentials for X• and ChH• were predicted to within ∼0.1 V of the reported literature values. Fluorine is anomalous due to abstraction of a hydrogen from one of the surrounding water molecules to form a hydroxyl radical and hydrogen fluoride, so its redox potential was calculated using only an implicit model. Larger deviations from experiment were predicted for ClO• and BrO•. These deviations are due to the free energy of solvation of the anion being too negative, as found in the pKa calculations, and that for the neutral being too positive with the current approach.

NHC Carbene-Metal Complex Ligand Binding Energies.

The ligand binding energies (LBEs) of N-heterocyclic carbenes (NHCs) and CH2 and CF2 adducts with group 1, 2, 10, and 11 metals and complexes with metals from these groups are predicted at the coupled cluster CCSD(T) level of theory by using density functional theory optimized geometries. The differences in LBEs as a function of the metal and the types of bonding interactions as well as the type of carbene are described. The bonding between the alkali cations and alkaline earth dications is predominantly ionic with a linear correlation between the LBEs and the cation hardness. In contrast, the bonding behaviors of the group 10 and 11 metals and metal complexes have only a weak, indirect correlation between the LBEs and the metal hardness. The difference in bonding behavior between the groups of metals arises due to the accessibility of electron donation between the ligand and the metal in the transition metal complexes, which results in more covalent-like bonding behavior. The presence of the methyl groups on the NHC nitrogen results in only slightly more delocalized charge from the metal onto the ring, but there is significant redistribution of the charge on the ring. Saturation of the NHC ring had a much smaller effect on how the charge was distributed on the ring. The analysis of the bonding behavior of NHCs with various metal groups enables improved understanding of carbene-metal interactions to inform rational design of NHC-based systems.

Fine particulate matter and incident coronary heart disease events up to 10 years of follow-up among Deepwater Horizon oil spill workers.

BACKGROUND: During the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM2.5). Exposure to PM2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. OBJECTIVES: To investigate the association between estimated PM2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. METHODS: We included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM2.5 exposures were estimated using a job-exposure matrix that linked modelled PM2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. RESULTS: We observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 µg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 µg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). CONCLUSIONS: Among oil spill workers, exposure to PM2.5 from flaring/burning of oil/gas was associated with increased risk of CHD.

Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors.

Introduction: Positron emission tomography (PET) imaging with prostate-specific membrane antigen- (PSMA-) binding tracers has been found incidentally to demonstrate uptake in CNS tumors. Following the encouraging findings of several such case reports, there is a growing interest in the potential application of PSMA-targeted PET imaging for diagnostics, theranostics, and monitoring of CNS tumors. This is a systematic literature review on PSMA-binding tracers in CNS tumors. Methods: A PubMed search was conducted, including preclinical and clinical reports. One hundred and twelve records were identified, and after screening, 56 were included in the final report. Results: Tissue studies demonstrated PSMA expression in tumor vascular endothelial cells, without expression in normal brain tissue, though the extent and intensity of staining varied by anti-PSMA antibody and methodology. Most included studies reported on gliomas, which showed strong PSMA ligand uptake and more favorable tumor to background ratios than other PET tracers. There are also case reports demonstrating PSMA ligand uptake in prostate cancer brain metastases, nonprostate cancer brain metastases, and meningiomas. We also review the properties of the various PSMA-binding radiotracers available. Therapeutic and theranostic applications of PSMA-binding tracers have been studied, including labeled alpha- and beta-ray emitting isotopes, as well as PSMA targeting in directing MRI-guided focused ultrasound. Conclusions: There is a potential application for PSMA-targeted PET in neuro-oncology as a combination of diagnostic and therapeutic use, as a theranostic modality for managing CNS tumors. Further research is needed regarding the mechanism(s) of PSMA expression in CNS tumors and its differential performance by tumor type.

Why are 'suboptimal' temperatures preferred in a tropical intertidal ectotherm?

In thermally extreme environments, it is challenging for organisms to maximize performance due to risks associated with stochastic variation in temperature and, subsequently, over evolutionary time minimizing the exposure to risk can serve as one of the mechanisms that result in organisms preferring suboptimal temperatures. We tested this hypothesis in a slow-moving intertidal snail on tropical rocky shores, where temperature variability increases with time from 30 min to 20 hr when recorded at 30 min intervals (due to short-term environmental autocorrelation where temperatures closer in time are more similar as compared to temperatures over a long period of time). Failure to accommodate temporal variation in thermal stress by selecting cool habitats can result in mortality. Thermal performance curves for different traits (heart rate and locomotion) were measured and compared to the snail's thermal preferences in both the field and laboratory. Predicted performances of the snails were simulated based on thermal performance curves for different traits over multiple time-scales and simulated carryover effects. A strong mismatch was found between physiological and behavioural thermal maxima of the snails (physiological thermal maximum being higher by ~7°C), but the snails avoided these maxima and sought temperatures 7-14°C cooler. Such a risk-averse strategy can be explained by their predicted performances where the snails should make decisions about preferred temperatures based on time periods ≥5 hr to avoid underestimating the temporal variation in body temperature. In extreme and stochastic environments, where the temporal variation in environmental conditions can lead to substantial divergence between instantaneous and time-averaged thermal performances, 'cooler is better' and 'suboptimal' body temperatures are preferred as they provide sufficient buffer to reduce mortality risk from heat stress.

Neighborhood social cohesion and serious psychological distress among Asian, Black, Hispanic/Latinx, and White adults in the United States: a cross-sectional study.

BACKGROUND: Serious psychological distress (SPD) is common and more prevalent in women, older adults, and individuals with a low-income. Prior studies have highlighted the role of low neighborhood social cohesion (nSC) in potentially contributing to SPD; however, few have investigated this association in a large, nationally representative sample of the United States. Therefore, our objective was to investigate the overall and racial/ethnic-, sex/gender-, self-rated health status-, age-, and household income-specific relationships between nSC and SPD. METHODS: We used data from survey years 2013 to 2018 of the National Health Interview Survey to investigate nSC and SPD among Asian, Non-Hispanic (NH)-Black, Hispanic/Latinx, and NH-White men as well as women in the United States (N = 168,573) and to determine modification by race/ethnicity, sex/gender, self-rated health status, age, and annual household income. nSC was measured by asking participants four questions related to the trustworthiness and dependability of their neighbors. nSC scores were trichotomized into low (< 12), medium (12-14), and high (15-16). SPD was measured using the Kessler 6 psychological distress scale with scores ≥ 13 indicating SPD. After adjusting for sociodemographic, health behavior, and clinical confounders, we used Poisson regression with robust variance to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Among 168,573 participants, most were Non-Hispanic (NH)-White (69%), and mean age was 47 ± 0.01 years. After adjustment, low vs. high nSC was associated with a 75% higher prevalence of SPD overall (PR = 1.75 [1.59-1.92]), 4 times the prevalence of SPD among Asian men (PR = 4.06 [1.57-10.50]), 2 times the prevalence of SPD among participants in at least good health (PR = 2.02 [95% CI: 1.74-2.35]), 92% higher prevalence of SPD among participants ≥ 50 years old (PR = 1.92 [1.70-2.18]), and approximately 3 times the prevalence of SPD among Hispanic/Latinx participants with household incomes ≥ $75,000 (PR = 2.97 [1.45-6.08]). CONCLUSIONS: Low nSC was associated with higher SPD in the overall population and the magnitude of the association was higher in Asian men, participants who reported good health, older participants, and Hispanic/Latinx adults with higher household incomes. Future research should continue to examine how neighborhood contexts can affect health across various sociodemographic groups, especially among groups with multiple marginalized social identities.

Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer's disease (MCI and dementia) in primary care: a review and synthesis.

The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker-defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.

Does the preferred walk-run transition speed on steep inclines minimize energetic cost, heart rate or neither?

As walking speed increases, humans choose to transition to a running gait at their preferred transition speed (PTS). Near that speed, it becomes metabolically cheaper to run rather than to walk and that defines the energetically optimal transition speed (EOTS). Our goals were to determine: (1) how PTS and EOTS compare across a wide range of inclines and (2) whether the EOTS can be predicted by the heart rate optimal transition speed (HROTS). Ten healthy, high-caliber, male trail/mountain runners participated. On day 1, subjects completed 0 and 15 deg trials and on day 2, they completed 5 and 10 deg trials. We calculated PTS as the average of the walk-to-run transition speed (WRTS) and the run-to-walk transition speed (RWTS) determined with an incremental protocol. We calculated EOTS and HROTS from energetic cost and heart rate data for walking and running near the expected EOTS for each incline. The intersection of the walking and running linear regression equations defined EOTS and HROTS. We found that PTS, EOTS and HROTS all were slower on steeper inclines. PTS was slower than EOTS at 0, 5 and 10 deg, but the two converged at 15 deg. Across all inclines, PTS and EOTS were only moderately correlated. Although EOTS correlated with HROTS, EOTS was not predicted accurately by heart rate on an individual basis.

The association between blood metals and hypertension in the GuLF study.

BACKGROUND: Both essential and non-essential metals come from natural and anthropogenic sources. Metals can bioaccumulate in humans and may impact human health, including hypertension. METHODS: Blood metal (cadmium, lead, mercury, manganese, and selenium) concentrations were measured at baseline for a sample of participants in the Gulf Long-Term Follow-up (GuLF) Study. The GuLF Study is a prospective cohort study focused on potential health effects following the 2010 Deepwater Horizon oil spill. Hypertension was defined as high systolic (≥140 mm Hg) or diastolic (≥90 mm Hg) blood pressure or taking anti-hypertensive medications. A total of 957 participants who had blood measurement for at least one metal, baseline blood pressure measurements, information on any anti-hypertensive medication use, and relevant covariates were included in this cross-sectional analysis. We used Poisson regression to explore the association between individual blood metal levels and hypertension. Quantile-based g-computation was used to investigate the association between the metal mixture and hypertension. We also explored the association between individual blood metal levels and continuous blood pressure measurements using general linear regression. RESULTS: Comparing the highest quartile of blood metals with the lowest (Q4vs1), the hypertension prevalence ratio (PR) was 0.92 (95 % confidence interval (CI) = 0.73,1.15) for cadmium, 0.86 (95%CI = 0.66,1.12) for lead, 0.89 (95%CI = 0.71,1.12) for mercury, 1.00 (95%CI = 0.80,1.26) for selenium, and 1.22 (95%CI = 0.95,1.57) for manganese. We observed some qualitative differences across race and BMI strata although none of these differences were statistically significant. In stratified analyses, the PR (Q4vs1) for mercury was 0.69 (95%CI = 0.53, 0.91) in White participants and 1.29 (95%CI = 0.86,1.92) in Black participants (p for interaction = 0.5). The PR (Q4vs1) for manganese was relatively higher in Black participants (PR = 1.37, 95%CI = 0.92,2.05) than in White participants (PR = 1.15, 95%CI = 0.83,1.60, p for interaction = 0.5), with a suggestive dose-response among Blacks. After stratifying by obesity (BMI ≥30 and < 30), positive associations of of hypertension with cadmium (PR [Q4vs1] = 1.19, 95%CI = 0.91,1.56, p for interaction = 0.5), lead (PR [Q4vs1] = 1.14, 95%CI = 0.84,1.55, p for interaction = 1.0) and manganese (PR = 1.25, 95%CI = 0.93,1.68, p for interaction = 0.8) were observed in participants with BMI≥30, but not in participants with BMI<30. The joint effect of the metal mixture was 0.96 (95%CI = 0.73,1.27). We did not observe clear associations between blood metal levels and continuous blood pressure measurements. CONCLUSION: We did not find overall cross-sectional associations between blood cadmium, lead, mercury, selenium levels and hypertension or blood pressure. We found some evidence suggesting that manganese might be positively associated with risk of hypertension. Associations varied somewhat by race and BMI.

Lung function in oil spill responders 4-6 years after the Deepwater Horizon disaster.

Oil spill response and clean-up (OSRC) workers were exposed to hazardous airborne chemicals following the 2010 Deepwater Horizon disaster. The aim of this study was to evaluate lung function in workers 4-6 years following the disaster using a prospective cohort. Participants who completed two spirometry test sessions 1-3 years, and 4-6 years after the spill (N = 1,838) were included and forced expiratory volume in 1 s (FEV1; ml), forced vital capacity (FVC; ml), and ratio (FEV1/FVC; %) determined. Linear mixed models were utilized to estimate relationships between OSRC exposures and lung function 4-6 years after the spill and changes since the prior measurement. Despite suggestive reduced lung function at 1-3 years, at the  4-6-year exam workers with total hydrocarbon (THC) exposure 1-2.99 ppm and ≥3 ppm compared to those with ≤0.29 ppm exhibited higher FEV1 (ß: 108 ml, 95% CI: 17, 198) and (ß: 118 ml, 95% CI: 5, 232), respectively. Compared with support workers, those in higher exposed jobs displayed greater improvement in FEV1 between visits: cleanup on water (ß: 143 ml, 95% CI: 35, 250), operations (ß: 132 ml, 95% CI: 30, 234) and response (ß: 149 ml, 95% CI: 43, 256). Greater FEV1 improvement was also associated with higher versus the lowest level THC exposure: 1-2.99 ppm (ß: 134 ml, 95% CI: 57, 210) and ≥3 ppm (ß: 205 ml, 95% CI: 109, 301). Lung function decrements seen shortly after the spill were no longer apparent 4-6 years later, with the greatest improvement among those with the highest exposures.

Steep (30°) uphill walking vs. running: COM movements, stride kinematics, and leg muscle excitations.

PURPOSE: We sought to biomechanically distinguish steep uphill running from steep uphill walking and explore why athletes alternate between walking and running on steep inclines. METHODS: We quantified vertical center of mass (COM) accelerations and basic stride parameters for both walking and running at a treadmill speed of 1.0 m/s on the level and up a 30° incline. We also investigated how electromyography (EMG) of the gluteus maximus (GMAX), vastus medialis (VM), medial gastrocnemius (MG), and soleus (SOL) muscles differ between gaits when ascending steep hills. RESULTS: The vertical COM accelerations for steep uphill walking exhibited two peaks per step of magnitude 1.47 ± 0.23 g and 0.79 ± 0.10 g. In contrast, steep running exhibited a single peak per step pattern with a magnitude of 1.81 ± 0.15 g. Steep uphill running exhibited no aerial phase, 40% faster stride frequency, and 40% shorter foot-ground contact time compared to steep uphill walking but similar leg swing times. SOL showed 36% less iEMG per stride during steep uphill running versus steep uphill walking, but all other EMG comparisons between steep running and walking were not significantly different. CONCLUSIONS: Multiple biomechanical variables clearly indicate that steep uphill running is a distinctly different gait from steep uphill walking and is more similar to level running. The competing desires to minimize the energetic cost of locomotion and to avoid exhaustion of the SOL may be a possible explanation for gait alternation on steep inclines.

An hypoxia-tolerant flatfish: consequences of sustained stress on the slender sole Lyopsetta exilis (Pleuronectidae) in the context of a changing ocean.

Slender sole Lyopsetta exilis is an abundant groundfish on the continental shelf and inner waters of British Columbia, Canada, where it reaches a maximum standard length of 44 cm. Benthic image surveys coupled with oxygen measurements in Saanich Inlet document a dense population in bottom conditions near anoxia (0.03 ml l-1 oxygen) where diel migrating zooplankton intersect the bottom; we confirm this species is a planktivore, which limits its depth range to the base of the migration layer. In a comparison with slender sole from a nearby well-oxygenated habitat, several probable effects of living in severe hypoxia emerge: both sexes are significantly smaller in Saanich and the sex ratio is male-skewed. Otoliths from the Saanich fish were difficult to read due to many checks, but both sexes were smaller at age with the largest female (20 cm) from the hypoxia zone registering 17 years. Hypoxia appears to have a direct consequence on growth despite good food supply in this productive basin. Hyperventilation, a low metabolic rate and a very low critical oxygen tension help this fish regulate oxygen uptake in severely hypoxic conditions; it will be particularly resilient as the incidence of hypoxia increases on the continental shelf. Data from small-mesh bottom-trawl surveys over four decades reveal an increase in mean annual catch per unit effort in southern regions of the province, including the outer shelf and the Strait of Georgia. The California Cooperative Oceanic Fisheries Investigations (CalCOFI) ichthyoplankton database records a general decline in fish larvae on the Oregon-California shelf since 1990, but slender sole larvae are increasing there, as they are in the Strait of Georgia. We project that the slender sole will gain relative benefits in the future warming, deoxygenated northeast Pacific Ocean.

Lung Function in Oil Spill Response Workers 1-3 Years After the Deepwater Horizon Disaster.

BACKGROUND: Little is known about the effects of inhalation exposures on lung function among workers involved in the mitigation of oil spills. Our objective was to determine the relationship between oil spill response work and lung function 1-3 years after the Deepwater Horizon (DWH) disaster. METHODS: We evaluated spirometry for 7,775 adults living in the Gulf states who either participated in DWH response efforts (workers) or received safety training but were not hired (nonworkers). At an enrollment interview, we collected detailed work histories including information on potential exposure to dispersants and burning oil/gas. We assessed forced expiratory volume in 1 second (FEV1; mL), forced vital capacity (FVC; mL), and the ratio (FEV1/FVC%) for differences by broad job classes and exposure to dispersants or burning oil/gas using multivariable linear and modified Poisson regression. RESULTS: We found no differences between workers and nonworkers. Among workers, we observed a small decrement in FEV1 (Beta, -71 mL; 95% confidence interval [CI], -127 to -14) in decontamination workers compared with support workers. Workers with high potential exposure to burning oil/gas had reduced lung function compared with unexposed workers: FEV1 (Beta, -183 mL; 95% CI, -316 to -49) and FEV1/FVC (Beta, -1.93%; 95% CI, -3.50 to -0.36), and an elevated risk of having a FEV1/FVC in the lowest tertile (prevalence ratio, 1.38; 95% CI, 0.99 to 1.92). CONCLUSIONS: While no differences in lung function were found between workers and nonworkers, lung function was reduced among decontamination workers and workers with high exposure to burning oil/gas compared with unexposed workers.

Stable isotope ecology of black rhinos (Diceros bicornis) in Kenya.

Stable isotope and elemental ratios in hair are influenced by the environment, including both climate and geology. Stable carbon isotopes can be used to give estimates of the C4/CAM fraction of diets of herbivorous mammals; stable nitrogen isotopes are related to the local water deficit; strontium isotopes are determined by the local geology. We studied hair from rhinos in Kenya to determine spatial patterns in δ13C, δ15N, and 87Sr/86Sr ratios. The samples of rhino hair were collected during Kenya Wildlife Service translocation or veterinary activities. δ13C values showed diets dominated by C3 foods, but in some regions the diet, at least seasonally, contained significant quantities (i.e., > ca. 20%) of C4/CAM foods. δ15N values were related to water deficit, with higher δ15N values in regions with high water deficit. 87Sr/86Sr isotope ratios were found to be related to the local geological substrate suggesting that 87Sr/86Sr isotope ratios are provisionally useful for determining the origins of illegal wildlife materials in Kenya and elsewhere in Africa.

Cross-Metathesis Approach to the Tricyclic Marine Alkaloids (-)-Fasicularin and (-)-Lepadiformine A.

A cross-metathesis protocol has been developed to provide facile access to highly hindered trisubstituted α-branched olefins, which when coupled with a cationic azaspirocyclization reaction, generates the marine alkaloids (-)-fasicularin 2 and a pro-forma synthesis of (-)-lepadiformine A 1.