Cooperative Stereoinduction in Asymmetric Photocatalysis.

Stereoinduction in complex organic reactions often involves the influence of multiple stereocontrol elements. The interaction among these can often result in the observation of significant cooperative effects that afford different rates and selectivities between the matched and mismatched sets of stereodifferentiating chiral elements. The elucidation of matched/mismatched effects in ground-state chemical reactions was a critically important theme in the maturation of modern stereocontrolled synthesis. The development of robust methods for the control of photochemical reactions, however, is a relatively recent development, and similar cooperative stereocontrolling effects in excited-state enantioselective photoreactions have not previously been documented. Herein, we describe a tandem chiral photocatalyst/Brønsted acid strategy for highly enantioselective [2 + 2] photocycloadditions of vinylpyridines. Importantly, the matched and mismatched chiral catalyst pairs exhibit different reaction rates and enantioselectivities across a range of coupling partners. We observe no evidence of ground-state interactions between the catalysts and conclude that these effects arise from their cooperative behavior in a transient excited-state assembly. These results suggest that similar matched/mismatched effects might be important in other classes of enantioselective dual-catalytic photochemical reactions.

Asymmetric Photochemical [2 + 2]-Cycloaddition of Acyclic Vinylpyridines through Ternary Complex Formation and an Uncontrolled Sensitization Mechanism.

Stereochemical control of photochemical reactions that occur via triplet energy transfer remains a challenge. Suppressing off-catalyst stereorandom reactivity is difficult for highly reactive open-shell intermediates. Strategies for suppressing racemate-producing, off-catalyst pathways have long focused on formation of ground state, substrate-catalyst chiral complexes that are primed for triplet energy transfer via a photocatalyst in contrast to their off-catalyst counterparts. Herein, we describe a strategy where both a chiral catalyst-associated vinylpyridine and a nonassociated, free vinylpyridine substrate can be sensitized by an Ir(III) photocatalyst, yet high levels of diastereo- and enantioselectivity in a [2 + 2] photocycloaddition are achieved through a preferred, highly organized transition state. This mechanistic paradigm is distinct from, yet complementary to current approaches for achieving high levels of stereocontrol in photochemical transformations.

Variable Temperature LED-NMR: Rapid Insights into a Photocatalytic Mechanism from Reaction Progress Kinetic Analysis.

A multitude of techniques are available to obtain a useful understanding of photocatalytic mechanisms. The combination of LED illumination with nuclear magnetic resonance spectroscopy (LED-NMR) provides a rapid, convenient means to directly monitor a photocatalytic reaction in situ. Herein, we describe a study of the mechanism of an enantioselective intermolecular [2 + 2] photocycloaddition catalyzed by a chiral Ir photocatalyst using LED-NMR. The data-rich output of this experiment is suitable for same-excess and variable time normalization analyses (VTNA). Together, these identified an unexpected change in mechanism between reactions conducted at ambient and cryogenic temperatures. At -78 °C, the kinetic data are consistent with the triplet rebound mechanism we previously proposed for this reaction, involving sensitization of maleimide and rapid reaction with a hydrogen-bound quinoline within the solvent cage. At room temperature, the cycloaddition instead proceeds through intracomplex energy transfer to the hydrogen-bound quinolone. These results highlight the potential sensitivity of photocatalytic reaction mechanisms to the precise reaction conditions and the further utility of LED-NMR as a fast, data-rich tool for their interrogation that compares favorably to conventional ex situ kinetic analyses.

Discovery and Elucidation of Counteranion Dependence in Photoredox Catalysis.

Over the past decade, there has been a renewed interest in the use of transition metal polypyridyl complexes as photoredox catalysts for a variety of innovative synthetic applications. Many derivatives of these complexes are known, and the effect of ligand modifications on their efficacy as photoredox catalysts has been the subject of extensive, systematic investigation. However, the influence of the photocatalyst counteranion has received little attention, despite the fact that these complexes are generally cationic in nature. Herein, we demonstrate that counteranion effects exert a surprising, dramatic impact on the rate of a representative photocatalytic radical cation Diels-Alder reaction. A detailed analysis reveals that counteranion identity impacts multiple aspects of the reaction mechanism. Most notably, photocatalysts with more noncoordinating counteranions yield a more powerful triplet excited state oxidant and longer radical cation chain length. It is proposed that this counteranion effect arises from Coulombic ion-pairing interactions between the counteranion and both the cationic photoredox catalyst and the radical cation intermediate, respectively. The comparatively slower rate of reaction with coordinating counteranions can be rescued by using hydrogen-bonding anion binders that attenuate deleterious ion-pairing interactions. These results demonstrate the importance of counteranion identity as a variable in the design and optimization of photoredox transformations and suggest a novel strategy for the optimization of organic reactions using this class of transition metal photocatalysts.

Identification of Degradation Pathways of Chlorohydrocarbons in Saturated Low-Permeability Sediments Using Compound-Specific Isotope Analysis.

This study aims to investigate whether compound-specific carbon isotope analysis (CSIA) can be used to differentiate the degradation pathways of chlorohydrocarbons in saturated low-permeability sediments. For that purpose, a site was selected, where a complex mixture of chlorohydrocarbons contaminated an aquifer-aquitard system. Almost 50 years after contaminant releases, high-resolution concentration, CSIA, and microbial profiles were determined. The CSIA profiles showed that in the aquitard cis-dichloroethene (cDCE), first considered as a degradation product of trichloroethene (TCE), is produced by the dichloroelimination of 1,1,2,2-tetrachloroethane (TeCA). In contrast, TeCA degrades to TCE via dehydrohalogenation in the aquifer, indicating that the aquifer-aquitard interface separates two different degradation pathways for TeCA. Moreover, the CSIA profiles showed that chloroform (CF) is degraded to dichloromethane (DCM) via hydrogenolysis in the aquitard and, to a minor degree, produced by the degradation of carbon tetrachloride (CT). Several microorganisms capable of degrading chlorohydrocarbons were detected in the aquitard, suggesting that aquitard degradation is microbially mediated. Furthermore, numerical simulations reproduced the aquitard concentration and CSIA profiles well, which allowed the determination of degradation rates for each transformation pathway. This improves the prediction of contaminant fate in the aquitard and potential magnitude of impacts on the adjacent aquifer due to back-diffusion.

Gas6 protein induces invasion and reduces inflammatory cytokines in oral squamous cell carcinoma.

BACKGROUND: Gas6 protein is involved in the progression of cancers and has been demonstrated to have a role in inflammation. Oral squamous cell carcinoma is a common form of oral cancer, and it commonly expresses Gas6. Our objective was to determine the effects of Gas6 on oral squamous cell carcinoma invasion and identify signaling molecules and cytokines associated with Gas6-mediated invasion. METHODS: Ca9-22 cells were cultured in the presence or absence of Gas6. Real-time cell invasion was evaluated, and cultured cells were lysed for Western blot analysis. Cell medium was collected and assayed for cytokine elaboration. RESULTS: Treatment of cells with Gas6 resulted in: (i) increased invasion, (ii) increased expression of Gas6 and AXL receptor, (iii) reduced invasion when AXL was inhibited, (iv) decreased ERK activation, (v) increased AKT activation, and (vi) decreased secretion of G-CSF, IL-2, IL-6, and IL-8. CONCLUSIONS: Gas6 increases invasion of oral squamous cell carcinoma, and the invasion correlates with the increased AKT and the downregulation of pro-inflammatory cytokines. These results may prove useful in providing avenues that explain the role of Gas6 in the development and progression of oral squamous cell carcinoma.

Cigarette smoke extract induces oral squamous cell carcinoma cell invasion in a receptor for advanced glycation end-products-dependent manner.

Oral squamous cell carcinoma (OSCC) affects approximately 30,000 people and is associated with tobacco use. Little is known about the mechanistic effects of second-hand smoke in the development of OSSC. The receptor for advanced glycation end-products (RAGE) is a surface receptor that is upregulated by second-hand smoke and inhibited by semi-synthetic glycosaminoglycan ethers (SAGEs). Our objective was to determine the role of RAGE during cigarette smoke extract-induced cellular responses and to use SAGEs as a modulating factor of Ca9-22 OSCC cell invasion. Ca9-22 cells were cultured in the presence or absence of cigarette smoke extract and SAGEs. Cell invasion was determined and cells were lysed for western blot analysis. Ras and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) activation were determined. Treatment of cells with cigarette smoke extract resulted in: (i) increased invasion of OSCC; (ii) increased RAGE expression; (iii) inhibition of cigarette smoke extract-induced OSCC cell invasion by SAGEs; (iv) increased Ras, increased AKT and NF-κB activation, and downregulation by SAGEs; and (v) increased expression of matrix metalloproteinases (MMPs) 2, 9, and 14, and downregulation by SAGEs. We conclude that cigarette smoke extract increases invasion of OSCC cells in a RAGE-dependent manner. Inhibition of RAGE decreases the levels of its signaling molecules, which results in blocking the cigarette smoke extract-induced invasion.

Determination of Cr(III) solids formed by reduction of Cr(VI) in a contaminated fractured bedrock aquifer: Evidence for natural attenuation of Cr(VI).

Hexavalent chromium Cr(VI) is toxic and can be highly mobile in many aquifer systems. Redox reactions with naturally occurring minerals and organic compounds can reduce Cr(VI) to Cr(III), forming labile Cr(III) oxyhydroxide precipitates, which is a natural attenuation process. In fractured bedrock aquifers, reduction of Cr(VI) in the rock matrix can enhance attenuation beyond that from matrix diffusion only, and potentially reduce back diffusion if concentrations in fractures decline following source reduction via natural processes or engineered remediation. In this study, we develop an extraction method for labile Cr(III) precipitates from Cr(VI) reduction using 5% hydrogen peroxide (H2O2). Combining Cr(III) extractions with an established sodium hydroxide (NaOH) method for determination of Cr(VI) concentrations in rock porewater, a measure of the labile Cr(III) and Cr(VI) fractions in geologic samples is achieved. The methods were applied to cores from a contaminated groundwater system in fractured porous bedrock in order to assess the effectiveness of natural attenuation and whether Cr(VI) mass that diffused into the bedrock matrix was undergoing reduction. Detailed vertical distributions display two depth intervals with corresponding elevated concentrations of Cr(VI) in the porewater and extractable total Cr. The correspondence of Cr(VI) and labile Cr(III) provides evidence for reduction of Cr(VI) contamination in the bedrock matrix. Mineralogical analysis suggests that Fe(II)-bearing minerals, chlorite and biotite are the most likely candidates for natural reductants. This study provides evidence for the natural attenuation of anthropogenic Cr(VI) contamination in the porewater of a fractured bedrock aquifer, and it outlines a quantitative method for evaluating the effectiveness of natural attenuation in groundwater systems.

Addressing substance misuse in adolescents: a review of the literature on the screening, brief intervention, and referral to treatment model.

PURPOSE OF REVIEW: Adolescent substance use is a major public health concern in the United States. Pediatricians are in a unique position via the medical home to address this issue. Screening, brief intervention, and referral to treatment (SBIRT) is a comprehensive approach that aims to prevent, identify, and reduce substance use. SBIRT has been heavily studied in adults, but research with adolescents is still ongoing. This review examines the SBIRT model and highlights recent applicable research. RECENT FINDINGS: This research indicates that alcohol and drug use has a negative impact on the developing brain. In 2011, the American Academy of Pediatrics (AAP) released a policy statement recommending the use of SBIRT. An adolescent SBIRT algorithm can be used clinically. Recent studies focus on individual components of SBIRT; however, there have been no studies that examine all three components together in adolescents. Nevertheless, research indicates that SBIRT is an important tool to assess and intervene regarding adolescent substance use. SUMMARY: SBIRT is recommended by the AAP as a way to address adolescent substance use. Pediatricians should be screening adolescents for substance use at every well exam, and acute care visits when possible, with a validated tool. Although more research is needed, SBIRT is an effective method to address adolescent substance use.

Quantification of Degradation of Chlorinated Hydrocarbons in Saturated Low Permeability Sediments Using Compound-Specific Isotope Analysis.

This field and modeling study aims to reveal if degradation of chlorinated hydrocarbons in low permeability sediments can be quantified using compound-specific isotope analysis (CSIA). For that purpose, the well-characterized Borden research site was selected, where an aquifer-aquitard system was artificially contaminated by a three component chlorinated solvent mixture (tetrachloroethene (PCE) 45 vol %, trichloroethene (TCE) 45 vol %, and chloroform (TCM) 10 vol %). Nearly 15 years after the contaminant release, several high-resolution concentration and CSIA profiles were determined for the chlorinated hydrocarbons that had diffused into the clayey aquitard. The CSIA profiles showed large shifts of carbon isotope ratios with depth (up to 24‰) suggesting that degradation occurs in the aquitard despite the small pore sizes. Simulated scenarios without or with uniform degradation failed to reproduce the isotope data, while a scenario with decreasing degradation with depth fit the data well. This suggests that nutrients had diffused into the aquitard favoring stronger degradation close to the aquifer-aquitard interface than with increasing depth. Moreover, the different simulation scenarios showed that CSIA profiles are more sensitive to different degradation conditions compared to concentration profiles highlighting the power of CSIA to constrain degradation activities in aquitards.

Tailoring Dynamic Hydrogels by Controlling Associative Exchange Rates.

Dithioalkylidenes are a newly-developed class of conjugate acceptors that undergo thiol exchange via an associative mechanism, enabling decoupling of key material properties for sustainability, biomedical, and sensing applications. Here, we show that the exchange rate is highly sensitive to the structure of the acceptor and tunable over four orders of magnitude in aqueous environments. Cyclic acceptors exchange rapidly, from 0.95 to 15.6 M-1s-1, while acyclic acceptors exchange between 3.77x10-3 and 2.17x10-2 M-1s-1. Computational, spectroscopic, and structural data suggest that cyclic acceptors are more reactive than their acyclic counterparts because of resonance stabilization of the tetrahedral exchange intermediate. We parametrize molecular reactivity with respect to computed descriptors of the electrophilic site and leverage this insight to design a compound with intermediate characteristics. Lastly, we incorporate this dynamic bond into hydrogels and demonstrate that the characteristic stress relaxation time (τ) is directly proportional to molecular kex.

Academic Careers in Advocacy: Aligning Institutional Values Through Use of an Advocacy Portfolio.

Academic children's hospitals must embrace advocacy as a central component of their missions to discover new knowledge and improve the health of the communities and patients they serve. To do so, they must ensure faculty have both the tools and the opportunities to develop and articulate the work of advocacy as an academic endeavor. This can be accomplished by integrating the work of advocacy at the community and policy-change levels into the traditional value systems of academic medicine, especially the promotions process, to establish its legitimacy. Academic pediatric institutions can support this transformation through robust training and professional development programs and establishing opportunities, resources, and leadership positions in advocacy. The adoption of an advocacy portfolio can be used to align these activities and accomplishments to institutional values and promotion. This alignment is crucial to supporting the advocacy work of pediatricians at a time in which community engagement and systems and policy change must be added to professional activities to ensure optimal outcomes for all children.

The ACTwatch project: methods to describe anti-malarial markets in seven countries.

BACKGROUND: Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. METHODS: The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012.ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. DISCUSSION: The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision-making. CONCLUSIONS: ACTwatch is a unique multi-country research project that threads together anti-malarial supply and consumer behaviour to provide an evidence base to policy makers that can help determine where interventions may positively impact access to and use of quality-assured ACT and RDTs. Because of its ability to detect change over time, it is well suited to monitor the effects of policy or intervention developments in a country.

Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. METHODS: Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. RESULTS: 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (< 25%). In the public/not-for-profit sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector, but often comprised non-artemisinin therapies, and in the DRC and Nigeria, oral artemisinin monotherapies. Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector. CONCLUSIONS: These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.

Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries.

BACKGROUND: Access to artemisinin-based combination therapy (ACT) remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged. This paper presents new evidence on household treatment-seeking behaviour in six African countries. These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm). METHODS: Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010. Caregivers responded to questions about management of recent fevers in children under five. Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests. Logistic regression was used to test for association between socioeconomic status and 1) malaria blood testing, and 2) ACT treatment. RESULTS: Fever treatment with an ACT is low in Benin (10%), the DRC (5%), Madagascar (3%) and Nigeria (5%), but higher in Uganda (21%) and Zambia (21%). The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42); the DRC (OR = 2.18, 95% CI = 1.12-4.24); Madagascar (OR = 5.37, 95% CI = 1.58-18.24); and Nigeria (OR = 6.59, 95% CI = 2.73-15.89). Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia). However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar). Nonetheless, levels of testing and ACT treatment in the public sector are low. Few caregivers name the national first-line drug as most effective for treating malaria in Madagascar (2%), the DRC (2%), Nigeria (4%) and Benin (10%). Awareness is higher in Zambia (49%) and Uganda (33%). CONCLUSIONS: Levels of effective fever treatment are low and inequitable in many contexts. The private sector is frequently accessed however case management practices are relatively poor in comparison with the public sector. Supporting interventions to inform caregiver demand for ACT and to improve provider behaviour in both the public and private sectors are needed to achieve maximum gains in the context of improved access to effective treatment.

Field, Laboratory and Modeling Evidence for Strong Attenuation of a Cr(VI) Plume in a Mudstone Aquifer Due to Matrix Diffusion and Reaction Processes.

This study uses a combination of conventional and high resolution field and laboratory methods to investigate processes causing attenuation of a hexavalent chromium (Cr(VI)) plume in sedimentary bedrock at a former industrial facility. Groundwater plume Cr(VI) concentrations decline by more than three orders of magnitude over a 900 m distance down gradient from the site. Internal plume concentrations generally exhibit stable to declining trends due to diffusive and reactive transport in the low permeability matrix as fluxes from the contamination source dissipate due to natural depletion processes and active remediation efforts. The strong attenuation is attributed to diffusion from mobile groundwater in fractures to immobile porewater in the rock matrix, and reactions causing transformation of aqueous Cr(VI) to low-solubility Cr(III) precipitates, confirmed by high spatial resolution rock matrix contaminant concentrations and comparisons with groundwater concentrations from multi-level sampling within the plume. Field characterization data for the fracture network and matrix properties were used to inform 2-D discrete-fracture matrix (DFM) numerical model simulations that quantify attenuation due to diffusion and reaction processes, which show consistency with field datasets, and provide insights regarding future plume conditions. The combination of field, laboratory and modeling evidence demonstrates effects of matrix diffusion and reaction processes causing strong attenuation of a Cr(VI) plume in a sedimentary bedrock aquifer. This approach has important implications for characterization of sites with Cr(VI) contamination for improved site conceptual models and remediation decision-making.

Quantifying groundwater flow variability in a poorly cemented fractured sandstone aquifer to inform in situ remediation.

This study applies innovative methods to characterize and quantify the magnitude of groundwater flow in a fractured and variably cemented sandstone aquifer to inform an in-situ remediation strategy for trichloroethene (TCE) contamination. A modified active-distributed temperature sensing (A-DTS) approach in which fiber optic cables were permanently grouted in the borehole was used to quantify groundwater flow rates. Two additional tracer tests were conducted: 1) fluorescein tracer injection followed by rock coring and sampling for visual mapping and porewater analysis, and 2) deployment of passive flux meters in conventional monitoring wells to evaluate groundwater velocity and mass flux distributions. Forced gradient injection of fluorescein tracer suggests a dual porosity flow system wherein higher rates of groundwater flow occur within discrete features including highly permeable bedding planes and fractures, with slower flow occurring within the rock matrix. Tracer was observed and detected in the unfractured matrix porewater >1.5 m away from the injection well. Beyond this distance, >6 m radially away from the injection hole, tracer was primarily detected within and adjacent to high transmissivity fractures serving as preferential flow paths. The Darcy flux calculated using active distributed temperature sensing (A-DTS) shows depth-discrete values ranging from 7 to 60 cm/day, with average and median values of 23 and 17 cm/day, respectively. Passive Flux Meters (PFMs) deployed in three conventional monitoring wells with slotted screens and sand filter packs showed groundwater flux values ranging from 2 to 11 cm/day, with an overall average of 4 cm/day and are likely biased low due to spreading in the sand pack. The study results were used to inform an in-situ remediation system design including the proposed injection well spacing and the amendment delivery approach. In addition, the results were used to build confidence in the viability of delivering an oxidant to the rock matrix via advective processes. This is important because 1) the matrix is where the majority of the TCE mass occurs, and 2) it provides insights on processes that directly affect remedial performance expectations given advective delivery to preferential pathways and the matrix overcomes diffusion only conditions.

Workshop on Implementation Science and Digital Therapeutics for Behavioral Health.

Digital therapeutics can overcome many of the barriers to translation of evidence-based treatment for substance use, mental health, and other behavioral health conditions. Delivered via nearly ubiquitous platforms such as the web, smartphone applications, text messaging, and videoconferencing, digital therapeutics can transcend the time and geographic boundaries of traditional clinical settings so that individuals can access care when and where they need it. There is strong empirical support for digital therapeutic approaches for behavioral health, yet implementation science with regard to scaling use of digital therapeutics for behavioral health is still in its early stages. In this paper, we summarize the proceedings of a day-long workshop, "Implementation Science and Digital Therapeutics," sponsored and hosted by the Center for Technology and Behavioral Health at Dartmouth College. The Center for Technology and Behavioral Health is an interdisciplinary P30 Center of Excellence funded by the National Institute on Drug Abuse, with the mission of promoting state-of-the-technology and state-of-the-science for the development, evaluation, and sustainable implementation of digital therapeutic approaches for substance use and related conditions. Workshop presentations were grounded in current models of implementation science. Directions and opportunities for collaborative implementation science research to promote broad adoption of digital therapeutics for behavioral health are offered.

Assessing aquitard integrity in a complex aquifer - aquitard system contaminated by chlorinated hydrocarbons.

This study investigates for the first time the integrity of multiple stacked aquitards with different degrees of contaminant degradation. Aquitard integrity was assessed in a contaminated, multi-layered, alluvial aquifer-aquitard system (Ferrara, northern Italy). The system was contaminated by mixed organic contaminants of industrial origin (mostly chlorinated ethenes) that were illegally disposed in an urban dump four to five decades ago. High spatial resolution profiles of hydraulic head, geochemistry and chlorinated hydrocarbon concentrations were determined through the multi-layered system via discrete interval sampling of continuous cores and multilevel groundwater sampling, at three locations aligned along a transect adjacent to the buried waste to a maximum depth of 53 m below the water table. The profiles revealed that the two shallow aquitards had low integrity with respect to impeding downward migration of dense non-aqueous phase liquid (DNAPL), and provided little protection to the underlying aquifers against DNAPL contamination due to preferential pathways through imperceptible fractures and/or permeable micro-beds. However, both aquitards inhibited downward DNAPL migration to some extent due to DNAPL retention along its flow paths and accumulation at lower permeability interfaces, with decreasing peak concentrations at the top of successively deeper aquitard units. Moreover, both aquitards enhanced contaminant biodegradation due to the occurrence of organic rich sub-layers, influencing the contaminant plume composition, mobility and fate in the underlying and overlying aquifers. The deepest aquitard showed evidence of DNAPL accumulation at the top and slow diffusion-dominated transport consistent with 40 years of transport, suggesting higher integrity compared to the two shallower aquitards. However, the occurrence of micro-fractures and/or discontinuities in the aquitard upgradient under the dump (source) is the most likely explanation for contamination of the deepest aquifer. Analytical 1-D simulations of the diffusion profiles in the deepest aquitard revealed that DNAPL contamination down to the top of this aquitard occurred with minimal delay after DNAPL waste disposal began. The results highlight the necessity of high-resolution vertical profiling for assessing the presence of imperceptible features relevant to DNAPL migration and integrity of individual aquitards affecting organic contaminant source zone mass and phase distributions over decades.

Enhancing Empathy in Medical Students: Family-Faculty Members Facilitate Patient-Centered Reflection.

Parents of children with medical complexity can serve as family-faculty in undergraduate medical education. Medical students can learn about family-centered care through structured interviews, reflective writing, and classroom discussions with family-faculty.