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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

DFN-M field characterization of sandstone for a process-based site conceptual model and numerical simulations of TCE transport with degradation.

Plumes of trichloroethene (TCE) with degradation products occur at a large industrial site in California where TCE as a dense non-aqueous phase liquid (DNAPL) entered the fractured sandstone bedrock at many locations beginning in the late 1940s. Groundwater flows rapidly in closely spaced fractures but plume fronts are strongly retarded relative to groundwater flow velocities owing largely to matrix diffusion in early decades and degradation processes in later decades and going forward. Multiple data types show field evidence for both biotic and abiotic dechlorination of TCE and its degradation products, resulting in non-chlorinated compounds. Analyses were conducted on groundwater samples from hundreds of monitoring wells and on thousands of rock samples from continuous core over depths ranging from 6 to 426 metres below ground surface. Nearly all of the present-day mass of TCE and degradation products resides in the water-saturated, low-permeability rock matrix blocks. Although groundwater and DNAPL flow primarily occur in the fractures, DNAPL dissolution followed by diffusion and sorption readily transfers contaminant mass into the rock matrix. The presence of non-chlorinated degradation products (ethene, ethane, acetylene) and compound specific isotope analysis (CSIA) of TCE and cis-1,2-dichloroethene (cDCE) indicate at least some complete dechlorination by both biotic and abiotic pathways, consistent with the observed mineralogy and hydrogeochemistry and with published results from crushed rock microcosms. The rock matrix contains abundant iron-bearing minerals and solid-phase organic carbon with large surface areas and long contact times, suggesting degradation processes are occurring in the rock matrix. Multiple, high-resolution datasets provide strong evidence for spatially heterogeneous distributions of TCE and degradation products with varying degrees of degradation observed only when using new methods that achieve better detection of dissolved gases (i.e., Snap Sampler™) and contaminant mass stored in the low permeability rock matrix (i.e., CORE-DFN™). Simulations using a discrete fracture-matrix (DFN-M) numerical model capable of rigorously simulating flow and transport in both the fractures and matrix, including interactions, show that even slow, first-order degradation rates (i.e., 5- to 20-year half-lives) informed by site-derived parameters can contribute strongly to natural attenuation, resulting in TCE plumes that become stationary in space and might even retreat after 50 to 100 years, if the DNAPL sources become depleted due to the combination of diffusion and degradation processes.

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.

The Community Pediatrics Training Initiative Project Planning Tool: A Practical Approach to Community-Based Advocacy.

Introduction: To impact social determinants of health, physicians require knowledge, skills, and attitudes to work with communities beyond the clinical milieu. The American Academy of Pediatrics (AAP) Community Pediatrics Training Initiative (CPTI) project planning tool can guide health care professionals and trainees to identify and define issues, build coalitions, assess interventions, and ensure sustainability of successful programs. The Accreditation Council for Graduate Medical Education guidelines for pediatric training require experiences in community health. To date, there have been no widely available tools to ensure both robust learning and validated assessment for pediatric residents in community pediatrics and advocacy training. Methods: The AAP CPTI project planning tool engages learners with a step-by-step process involving investigation, guided reflection, and structured assessment. Learners practice the skills necessary to plan, implement, and evaluate a community pediatrics/child health advocacy proposal focused upon a learner-defined area of interest. An assessment rubric maps to milestones. Results: This project planning tool has been used in a number of programs with learners at multiple levels, including undergraduate education, graduate education, and practicing health care providers. It can be employed to design and implement a community advocacy intervention or as a thought exercise and can be incorporated in a single block rotation or as a longitudinal experience. It can be used with individual learners or as a group exercise. Discussion: The project planning tool can be used by residency programs to demonstrate resident competence in community health and advocacy, either as a learning exercise or to guide actual implemented projects.

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.

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.

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.

An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population.

OBJECTIVE: Analyze the economic value of replacing conventional fetal aneuploidy screening approaches with non-invasive prenatal testing (NIPT) in the general pregnancy population. METHODS: Using decision-analysis modeling, we compared conventional screening to NIPT with cell-free DNA (cfDNA) analysis in the annual US pregnancy population. Sensitivity and specificity for fetal aneuploidies, trisomy 21, trisomy 18, trisomy 13, and monosomy X, were estimated using published data and modeling of both first- and second trimester screening. Costs were assigned for each prenatal test component and for an affected birth. The overall cost to the healthcare system considered screening costs, the number of aneuploid cases detected, invasive procedures performed, procedure-related euploid losses, and affected pregnancies averted. Sensitivity analyses evaluated the effect of variation in parameters. Costs were reported in 2014 US Dollars. RESULTS: Replacing conventional screening with NIPT would reduce healthcare costs if it can be provided for $744 or less in the general pregnancy population. The most influential variables were timing of screening entry, screening costs, and pregnancy termination rates. Of the 13,176 affected pregnancies undergoing screening, NIPT detected 96.5% (12,717/13,176) of cases, compared with 85.9% (11,314/13,176) by conventional approaches. NIPT reduced invasive procedures by 60.0%, with NIPT and conventional methods resulting in 24,596 and 61,430 invasive procedures, respectively. The number of procedure-related euploid fetal losses was reduced by 73.5% (194/264) in the general screening population. CONCLUSION: Based on our analysis, universal application of NIPT would increase fetal aneuploidy detection rates and can be economically justified. Offering this testing to all pregnant women is associated with substantial prenatal healthcare benefits.