Passive sampling methods for contaminated sediments: scientific rationale supporting use of freely dissolved concentrations.

Passive sampling methods (PSMs) allow the quantification of the freely dissolved concentration (Cfree ) of an organic contaminant even in complex matrices such as sediments. Cfree is directly related to a contaminant\u27s chemical activity, which drives spontaneous processes including diffusive uptake into benthic organisms and exchange with the overlying water column. Consequently, Cfree provides a more relevant dose metric than total sediment concentration. Recent developments in PSMs have significantly improved our ability to reliably measure even very low levels of Cfree . Application of PSMs in sediments is preferably conducted in the equilibrium regime, where freely dissolved concentrations in the sediment are well-linked to the measured concentration in the sampler via analyte-specific partition ratios. The equilibrium condition can then be assured by measuring a time series or a single time point using passive samplers with different surface to volume ratios. Sampling in the kinetic regime is also possible and generally involves the application of performance reference compounds for the calibration. Based on previous research on hydrophobic organic contaminants, it is concluded that Cfree allows a direct assessment of 1) contaminant exchange and equilibrium status between sediment and overlying water, 2) benthic bioaccumulation, and 3) potential toxicity to benthic organisms. Thus, the use of PSMs to measure Cfree provides an improved basis for the mechanistic understanding of fate and transport processes in sediments and has the potential to significantly improve risk assessment and management of contaminated sediments

Sediment-water exchange of polycyclic aromatic hydrocarbons in the lower Hudson Estuary

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2000.Includes bibliographical references.Polyethylene devices (PEDs), which rely on the partitioning of hydrophobic organic contaminants (HOCs) between water and polyethylene, were shown to be useful for the measurement of dissolved HOCs like polycyclic aromatic hydrocarbons (PAHs) in natural waters. These PEDs allow for the measurement of the fugacity or "fleeing tendency" of such chemicals in water. These dissolved concentrations are of ecotoxicological concern as they reflect the HOC fraction that is driving uptake by the surrounding organisms. Because PEDs require on the order of days to equilibrate in the field, their use provides time-averaged measurements. Laboratory-measured polyethylene-water partition coefficients for two PAHs were: 17,000 ±1000 (mol/LPE)/(mol/Lw) for phenanthrene and 89,000 ± 6000 (mol/LPE)/(mol/Lw) for pyrene. These organic polymer-water partition coefficients were found to be comparable to other organic solvent-water partitioning coefficients. These large coefficients allowed for the measurement of dissolved concentrations as low as 1 pg/L for benzo(a)pyrene and 400 pg/L for phenanthrene in the lower Hudson Estuary. Sampling performed in the lower Hudson Estuary during neap and spring tides revealed increased concentrations of dissolved pyrene and benzo(a)pyrene, but not phenanthrene, during increased sediment resuspension. These data suggest that resuspension events mostly influence the bed-to-water exchange of PAHs with greater hydrophobicities. PAH water concentrations predicted assuming dissolved and sorbed concentrations related via the product, fomKom, where fom is the fraction of organic matter in the suspended sediments and Kom is the organic-matter-normalized solid-water partition coefficient for the PAH of concern, were far from observed concentrations. Adding the influence of soot to the partition model via Kd = fomKom + fse,4Ke, where fse. is the weight fraction of soot carbon in the solid phase and Ke is the soot carbon-water partition coefficient estimated form activated carbon data, yielded predicted concentrations that were much closer to the observed values when PAH partitioning to soot was included in the partitioning model. This finding suggests that soot plays an important role in controlling the cycling of PAHs in the aquatic environment. However, even when the soot partitioning of PAHs was included in the model, the predicted dissolved values were still larger than the measured values. This suggests that the time of particle resuspension is too short to allow for particle-water sorptive equilibrium. Using ratios of source indicative PAHs, it was estimated that 90% of the dissolved PAH fraction was derived from petrogenic sources. In contrast, the same source ratios for the total (dissolved and sorbed) PAH concentrations indicated that only 55% of the total were petrogenically-derived. The observations in this work suggest that efforts to regulate and remediate PAH-contaminated sediments must consider the potential impacts of soot associations of the PAHs.by Rachel G. Adams.S.M

Polyethylene devices and the effects of sediment resuspension on the cycling of PAHs and PCBs in the lower Hudson Estuary

Thesis (Ph. D .)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2003.Includes bibliographical references (p. 149-154).In order to examine the importance of sediment resuspension on the sediment bed-to-water column transport of hydrophobic organic contaminants (HOCs) in the lower Hudson Estuary, the following areas of research were pursued: 1) a passive, in situ sampler, a polyethylene device (PED), for measuring HOCs in the aquatic environment was developed; 2) the desorption rate of pyrene, a polycyclic aromatic hydrocarbon (PAH), from native Hudson River sediments was measured, and 3) pyrene and 2,2',5,5'-tetrachlorobiphenyl (PCB #52), a polychlorinated biphenyl (PCB), concentrations were measured in the lower Hudson Estuary so that the input of these chemicals as a result of sediment resuspension could be compared to modeling expectations and the contribution of sediment resuspension to these chemicals' cycling could be quantified. The use of a new passive, in situ sampler, a polyethylene device (PED), for measuring hydrophobic organic contaminants (HOCs) in the aquatic environment was demonstrated. Like semipermeable membrane devices (SPMDs) and solid-phase microextraction (SPME), PEDs passively measure the concentration of chemical present in the dissolved phase. PEDs provide for in situ, time-averaged measurements with fast equilibration times (on the order of days) and simple laboratory extraction. Polyethylene-water equilibrium partitioning constants (KpEws) and polyethylene diffusivity coefficients (DPEs) were measured in the laboratory so that dissolved concentrations could be calculated subsequent to PED extraction.(cont.) KPEWs for eleven PAHs and PCBs were found to correlate closely with octanol-water equilibrium partitioning constants (Kows; log KPEW = 1.1 log Kow-0.45, R2 = 0.85). Temperature and salinity dependence of KPEW for the chemical of interest can be predicted with that chemical's excess enthalpy of solution and Setschenow constant, respectively. DpEs for several HOCs were measured in the laboratory so that the time for equilibrium uptake in the field could be predicted. PEDs allowed for quick, in situ, time-averaged measurements of phenanthrene and pyrene at pM concentrations and PCB #52 at fM concentrations in Boston Harbor seawater. Observations of disequilibrium between sorbed HOCs (e.g., PAHs & PCBs) and the surrounding environmental waters indicate that the times for desorption are important for understanding the fate of HOCs. Settling and resuspended particles can play a significant role in the cycling of HOCs. For PAHs, like pyrene, these chemicals' strong affinity for black carbon in the environment makes the rate of desorption less certain. The desorption rate for pyrene from native Hudson River sediment was measured in the laboratory and a diffusion rate constant (effective diffusivity/particle radius2) ranging from 1.OE-7 to 5.6E-7 s-1 was measured. The results were in good agreement with a physically- and chemically-based model for estimating effective diffusivity and the rate of desorption.by Rachel G. Adams.Ph.D

Preclinical Analysis of JAA-F11, a Specific Anti-Thomsen-Friedenreich Antibody via Immunohistochemistry and In Vivo Imaging.

The tumor specificity of JAA-F11, a novel monoclonal antibody specific for the Thomsen-Friedenreich cancer antigen (TF-Ag-alpha linked), has been comprehensively studied by in vitro immunohistochemical (IHC) staining of human tumor and normal tissue microarrays and in vivo biodistribution and imaging by micro-positron emission tomography imaging in breast and lung tumor models in mice. The IHC analysis detailed herein is the comprehensive biological analysis of the tumor specificity of JAA-F11 antibody performed as JAA-F11 is progressing towards preclinical safety testing and clinical trials. Wide tumor reactivity of JAA-F11, relative to the matched mouse IgG3 (control), was observed in 85% of 1269 cases of breast, lung, prostate, colon, bladder, and ovarian cancer. Staining on tissues from breast cancer cases was similar regardless of hormonal or Her2 status, and this is particularly important in finding a target on the currently untargetable triple-negative breast cancer subtype. Humanization of JAA-F11 was recently carried out as explained in a companion paper "Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis" (Neoplasia 19: 716-733, 2017), and it was confirmed that humanization did not affect chemical specificity. IHC studies with humanized JAA-F11 showed similar binding to human breast tumor tissues. In vivo imaging and biodistribution studies in a mouse syngeneic breast cancer model and in a mouse-human xenograft lung cancer model with humanized 124I- JAA-F11 construct confirmed in vitro tumor reactivity and specificity. In conclusion, the tumor reactivity of JAA-F11 supports the continued development of JAA-F11 as a targeted cancer therapeutic for multiple cancers, including those with unmet need

Contestable adulthood: variability and disparity in markers for negotiating the transition to adulthood

Recent research has identified a discreet set of subjective markers that are seen as characterizing the transition to adulthood. The current study challenges this coherence by examining the disparity and variability in young people’s selection of such criteria. Four sentence-completion cues corresponding to four differentcontexts in which adult status might be contested were given to 156 British 16- to 17-year-olds. Their qualitative responses were analyzed to explore patterns whilst capturing some of their richness and diversity. An astonishing amount of variability emerged, both within and between cued contexts.The implications of this variability for how the transition to adulthood is experienced are explored. The argument is made that markers of the transition to adulthood are not merely reflective of the bio–psycho–social development of young people. Rather, adulthood here is seen as an essentially contested concept,located within the discursive interactional environment in which young people participate

Children and young adults who received tracheostomies or were initiated on long-term ventilation in PICUs

Objectives: To characterize patients who received tracheostomies for airway compromise or were initiated on long-term ventilation for chronic respiratory failure in pediatric intensive care units (PICU), and to examine variation in the incidence of initiation, patient characteristics, and modalities across sites. Design: Retrospective cross-sectional analysis. Settings: Seventy three North American PICUs that participated in the Virtual Pediatric Intensive Care Unit Performance System. Patients: PICU patients admitted between 2009 and 2011. Interventions: None. Measurements and Main Results: Among 115,437 PICU patients, 1.8% received a tracheostomy or were initiated on long-term ventilation; 1034 received a tracheostomy only, 717 were initiated on invasive ventilation (IV), and 381 were initiated on noninvasive ventilation (NIV). Ninety percent had substantial chronic conditions and comorbidities, including more than 50% with moderate or worse cerebral disability upon discharge. Seven percent were initiated after a catastrophic injury/event. Across sites, there was variation in incidence of tracheotomy and initiation of long-term ventilation, ranging 0–4.6%. There also was variation in patient characteristics, time to tracheotomy, number of extubations prior to tracheostomy, and the use of IV versus NIV. Conclusions: While the PICU incidence of initiation of tracheostomies and long-term ventilation was relatively uncommon, it suggests that thousands of children and young adults receive these interventions each year in North American PICUs. The majority of them have conditions and comorbidities that impose on-going care needs, beyond those required by artificial airways and long-term ventilation themselves

Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery

Purpose The delivery of post-mastectomy radiation therapy (PMRT) can be challenging for patients with left sided breast cancer that have undergone mastectomy. This study investigates the use of protons for PMRT in selected patients with unfavorable cardiac anatomy. We also report the first clinical application of protons for these patients. Methods and materials Eleven patients were planned with protons, partially wide tangent photon fields (PWTF), and photon/electron (P/E) fields. Plans were generated with the goal of achieving 95% coverage of target volumes while maximally sparing cardiac and pulmonary structures. In addition, we report on two patients with unfavorable cardiac anatomy and IMN involvement that were treated with a mix of proton and standard radiation. Results: PWTF, P/E, and proton plans were generated and compared. Reasonable target volume coverage was achieved with PWTF and P/E fields, but proton therapy achieved superior coverage with a more homogeneous plan. Substantial cardiac and pulmonary sparing was achieved with proton therapy as compared to PWTF and P/E. In the two clinical cases, the delivery of proton radiation with a 7.2 to 9 Gy photon and electron component was feasible and well tolerated. Akimbo positioning was necessary for gantry clearance for one patient; the other was treated on a breast board with standard positioning (arms above her head). LAO field arrangement was used for both patients. Erythema and fatigue were the only noted side effects. Conclusions: Proton RT enables delivery of radiation to the chest wall and regional lymphatics, including the IMN, without compromise of coverage and with improved sparing of surrounding normal structures. This treatment is feasible, however, optimal patient set up may vary and field size is limited without multiple fields/matching

Motor development in infancy and spine shape in early old age: findings from a British birth cohort study

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from DXA scans in 1327 individuals (688 female) at 60‐64y in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two‐line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient 0.023, 95%CI 0.000‐0.047, p=0.05) and direct angle measurement. Modest associations between walking age and less variation in anterior‐posterior vertebral size caudally (SSM6) were also observed (0.021, 95%CI ‐0.002‐0.044, p=0.07). Sex interactions showed that later walking was associated with larger relative vertebral anterior‐posterior dimensions in men (SSM3; ‐0.043, 95%CI ‐0.075‐0.01, p=0.01) but not women (0.018, 95%CI ‐0.0007‐0.043, p=0.17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on features of spine morphology with clinical significance

Age at onset of walking in infancy is associated with hip shape in early old age

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements, and, accordingly, earlier walking is associated with greater bone strength. However, associations between early life loading and joint shape have not been explored. We therefore examined associations between walking age and hip shape at age 60-64y in 1423 individuals (740 women) from the MRC National Survey of Health and Development, a nationally-representative British birth cohort. Walking age in months was obtained from maternal interview at age 2y. Ten modes of variation in hip shape (HM1-HM10), described by statistical shape models, were ascertained from dual-energy X-ray absorptiometry (DXA) images. In sex-adjusted analyses, earlier walking age was associated with higher HM1 and HM7 scores; these associations were maintained after further adjustment for height, body composition and socioeconomic position. Earlier walking was also associated with lower HM2 scores in women only, and lower HM4 scores in men only. Taken together, this suggests that earlier walkers have proportionately larger (HM4) and flatter (HM1,4) femoral heads, wider (HM1,4,7) and flatter (HM1, 7) femoral necks, smaller neck-shaft angle (HM1,4), anteversion (HM2,7) and development of osteophytes (HM1). These results suggest that age at onset of walking in infancy is associated with variations in hip shape in older age. Early walkers have a larger femoral head and neck and smaller neck-shaft angle; these features are associated with reduced hip fracture risk, but also represent an osteoarthritic-like phenotype. Unlike results of previous studies of walking age and bone mass, associations in this study were not affected by adjustment for lean mass suggesting that associations may relate directly to skeletal loading in early life when joint shape changes rapidly. This article is protected by copyright. All rights reserved.</p

The ethical challenges of diversifying genomic data: a qualitative evidence synthesis

This article aims to explore the ethical issues arising from attempts to diversify genomic data and include individuals from underserved groups in studies exploring the relationship between genomics and health. We employed a qualitative synthesis design, combining data from three sources: 1) a rapid review of empirical articles published between 2000 and 2022 with a primary or secondary focus on diversifying genomic data, or the inclusion of underserved groups and ethical issues arising from this, 2) an expert workshop and 3) a narrative review. Using these three sources we found that ethical issues are interconnected across structural factors and research practices. Structural issues include failing to engage with the politics of knowledge production, existing inequities, and their effects on how harms and benefits of genomics are distributed. Issues related to research practices include a lack of reflexivity, exploitative dynamics and the failure to prioritise meaningful co-production. Ethical issues arise from both the structure and the practice of research, which can inhibit researcher and participant opportunities to diversify data in an ethical way. Diverse data are not ethical in and of themselves, and without being attentive to the social, historical and political contexts that shape the lives of potential participants, endeavours to diversify genomic data run the risk of worsening existing inequities. Efforts to construct more representative genomic datasets need to develop ethical approaches that are situated within wider attempts to make the enterprise of genomics more equitable