Search

Adolescents and young adults with inflammatory bowel disease (IBD) are in vulnerable positions for lapses in care as they transition from pediatric to adult practices. As biologic agents become a mainstay of treatment for these patients, it is important to ensure that responsibility for tasks related to scheduling, remembering, and transporting to infusion appointments for intravenous biologics are mastered prior to transition. This ensures preservation of therapy and disease control.We surveyed 236 adolescents and young adults with IBD aged 13-22 years receiving infusion- based biologic therapy at outpatient infusion visits at Boston Children's Hospital from February to May 2021. The questionnaire asked the ideal and actual ages that patients take responsibility for scheduling their infusion appointments, remembering their infusion appointments, and transporting to their infusion appointments.We received 168 completed survey questionnaires. The ideal reported mean age for independence was 17.9 ± 1.7 years across all three tasks. Among 80 patients 18 years and older, 44 (55%) were independently scheduling their appointments, 63 (79%) were keeping track of their appointments, and 43 (54%) were getting to their appointments independently.Adolescent and young adult patients with IBD ideally would independently manage biologic infusion related tasks prior to the age of 18 years, as this is the natural age that many move away from the homes of their parents/guardians. Our study demonstrates that just over half of patients 18 years or older independently manage their infusion appointments. This is an educational opportunity that has implications for health outcomes of patients with IBD.

Purpose:Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment.Patients and Methods:Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS).Results:Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS.Conclusions:With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.

59 probesets from an analysis of blood These are probesets for which the null hypothesis was rejected and the change over time averaged over treatment groups was {greater than or equal to}1.2-fold.

Supplementary Figure 2

CONSORT diagram.

Genes from an analysis of tumor biopsies with {greater than or equal to}1.3-fold differences between treatment groups over time. Thirty-seven probesets identified from gene expression analysis.

Supplementary Information

Supplementary Tables

Scatter-plot matrix of change from baseline (CFB) of CD3+, CD4+, and CD8+ cell percentages among the 36 patients. The diagonal panels give kernel density estimates and histograms summarizing the univariate distributions for the individual cell-type percentages.

Genes from whole blood analysis with {greater than or equal to}1.2-fold differences between treatment groups over time. Twenty-four probesets identified from gene expression analysis.

Change from baseline PD-L1 expression. Data included are for patients with matched fresh tumor biopsies at baseline and cycle 2, day 8 (C2D8) of nivolumab treatment. Each solid line represents a patient. The horizontal dotted line represents 5% PD-L1 expression.

108 probesets from an analysis of tumor biopsies These are probesets for which the null hypothesis was rejected and the change over time averaged over treatment groups was {greater than or equal to}1.3-fold.

Supplementary Figure 1

Triplet kynurenic acid in anionic form reacts with tyrosine or tryptophan with H or H+ transfer, respectively, to the oxygen of keto- or oxo-quinolinate tautomeric forms but not to the nitrogen of the enol form.

Kynurenic acid (KNA) in the triplet state reacts with tryptophan (Trp) at neutral pH

Purpose Research involving adolescent risk behaviors must balance data confidentiality with participant safety when risky behaviors are revealed. This report details a safety protocol and reports the experience of two contemporaneous studies that used it with variant safety thresholds. Methods We developed a safety protocol for research with adolescent patients and used it in two concurrent studies of adolescent patients, aged 14–18 years. Study “PC” recruited participants from a primary care adolescent medical clinic (N = 490), and Study “SP” recruited participants from subspecialty pediatric clinics (N = 434); both studies involved a similar self-administered assessment of health behaviors. The protocol sets thresholds for clinical intervention (positive safety flags) for past 3-month heavy alcohol consumption (Study PC: 10 or more drinks and Study SP: “binge-”level drinking), illicit drug use other than marijuana and alcohol in combination with a substance other than marijuana, and sets a positive screen for depression. We examined the rates of positive safety flags in both protocol settings, used significance testing to describe demographic differences between participants with and without positive flags in both studies, and described clinician experiences with protocol implementation. Results In studies PC/SP, .6%/8.8% of participants were flagged for heavy alcohol consumption, respectively; .2%/0% for illicit drug use, 2.2%/.7% for combination substance use, and 14.9%/4.8% for depression. Some clinicians found managing positive flags challenging, although both studies completed recruitment on time and without serious adverse events. Conclusions The protocol was feasible in clinical settings. The findings and experiences documented in this report could be useful for future protocols.

Flavin adenine dinucleotide (FAD) is an important cofactor in many light-sensitive enzymes. The role of the adenine moiety of FAD in light-induced electron transfer was obscured, because it involves an adenine radical, which is short-lived with a weak chromophore. However, an intramolecular electron transfer from adenine to flavin was revealed several years ago by Robert Kaptein by using chemically induced dynamic nuclear polarization (CIDNP). The question of whether one or two types of biradicals of FAD in aqueous solution are formed stays unresolved so far. In the present work, we revisited the CIDNP study of FAD using a robust mechanical sample shuttling setup covering a wide magnetic field range with sample illumination by a light-emitting diode. Also, a cost efficient fast field cycling apparatus with high spectral resolution detection up to 16.4 T for nuclear magnetic relaxation dispersion studies was built based on a 700 MHz NMR spectrometer. Site-specific proton relaxation dispersion data for FAD show a strong restriction of the relative motion of its isoalloxazine and adenine rings with coincident correlation times for adenine, flavin, and their ribityl phosphate linker. This finding is consistent with the assumption that the molecular structure of FAD is rigid and compact. The structure with close proximity of the isoalloxazine and purine moieties is favorable for reversible light-induced intramolecular electron transfer from adenine to triplet excited flavin with formation of a transient spin-correlated triplet biradical F⚫−-A⚫+. Spin-selective recombination of the biradical leads to the formation of CIDNP with a common emissive maximum at 4.0 mT detected for adenine and flavin protons. Careful correction of the CIDNP data for relaxation losses during sample shuttling shows that only a single maximum of CIDNP is formed in the magnetic field range from 0.1 mT to 9 T; thus, only one type of FAD biradical is detectable. Modeling of the CIDNP field dependence provides good agreement with the experimental data for a normal distance distribution between the two radical centers around 0.89 nm and an effective electron exchange interaction of −2.0 mT.

Objective: To examine the relationship between perceived effect of inflammatory bowel diseases (IBD) on high school academics and college planning on college adjustment. Participants: Participants ...

Chemically induced dynamic nuclear polarization (CIDNP) has emerged as a highly informative method to study spin-dependent radical reactions by analyzing enhanced NMR (nuclear magnetic resonance) signals of their diamagnetic reaction products. In this way, one can probe the structure of elusive radical intermediates and determine their magnetic parameters. A careful examination of experimental CIDNP data at variable magnetic fields shows that formation of hyperpolarized molecules in a coherent state is a ubiquitous though rarely discussed phenomenon. The presence of nuclear spin coherences commonly leads to subsequent polarization transfer among coupled spins in the diamagnetic products of radical recombination reaction that must be taken into account when analyzing the results of CIDNP experiments at low magnetic field. Moreover, such coherent polarization transfer can be efficiently exploited to polarize spins, which do not acquire CIDNP directly. Here we explain under what conditions such coherences can be generated, focusing on the key role of level anti-crossings in coherent polarization transfer, and provide experimental approaches to probing nuclear spin coherences and their time evolution. We illustrate the theoretical consideration of the outlined coherent spin phenomena in CIDNP by examples, obtained for the dipeptide tryptophan–tryptophan.

BACKGROUND Social media is used by young adult patients for social connection and self-identification. OBJECTIVE This study aims to compare the social media habits of young adults with inflammatory bowel disease (IBD) and type 1 diabetes (T1D). METHODS This is a cross-sectional study of subjects from Boston Children’s Hospital outpatient IBD and diabetes clinics. Patients above 18 years of age were invited to complete a brief anonymous survey, which asked about the various ways they use several social media platforms. RESULTS Responses were received from 108 patients (92.5% response rate), evenly split across disease type. We found that 83% of participants spent at least 30 minutes per day on social media, most commonly on Instagram and Facebook. Although the content varied based on the platform, patients with IBD posted or shared content related to their disease significantly less than those with T1D (23% vs 38%, P=.02). Among Instagram users, patients with IBD were less likely to engage with support groups (22% vs 56%, P=.04). Among Twitter users, patients with IBD were less likely to seek disease information (77% vs 29%, P=.005). Among Facebook users, patients with IBD were less likely to post about research and clinical trials (31% vs 65%, P=.04) or for information seeking (49% vs 87%, P=.003). Patients with IBD were also less likely to share their diagnosis with friends or family in person. CONCLUSIONS Young adults with IBD were less willing to share their diagnosis and post about or explore the disease on social media compared to those with T1D. This could lead to a sense of isolation and should be further explored.

Background:Models of social anxiety suggest that intrusive images/memories are common in social anxiety and contribute to the maintenance of social anxiety.Aims:We examined the context and phenomenological features of intrusive social images using quantitative and qualitative measures across various levels of social anxiety.Method:Undergraduate students (n = 191) completed measures of social anxiety (i.e. Social Interaction Anxiety Scale and Social Phobia Scale) and wrote a description of an intrusive social image. Individuals who reported an intrusive social image (n = 77) rated the frequency, interference and phenomenological (e.g. vividness, emotional intensity) characteristics of the image. A content analysis of the intrusive image narratives was completed by independent raters.Results:High social anxiety (HSA) increased the likelihood and frequency of experiencing intrusive images, and to some extent the interference caused by these images. However, the characteristics of these images with regard to their content and quality were similar across levels of social anxiety. Among participants who provided narratives, HSA individuals (n = 34) did not differ from low socially anxious (LSA) individuals (n = 28) in themes that reflect concerns about their own thoughts, actions and behaviours. However, HSA individuals reported greater concerns about how other individuals would react, and their intrusive images were often from an observer perspective when compared with LSA individuals.Conclusions:These results are interpreted in relation to cognitive models of emotion, memory and cognitive behavioural models of social anxiety.

Flavin adenine dinucleotide (FAD) is an important cofactor in many light-sensitive enzymes. The role of the adenine moiety of FAD in light induced electron transfer was obscured because it involves an adenine radical, short-lived with a weak chromophore. However, an intramolecular electron transfer from adenine to flavin was revealed several years ago by R. Kaptein by using chemically induced dynamic nuclear polarization (CIDNP). The question whether one or two types of biradicals of FAD in aqueous solution are formed stays unresolved so far. In the present work, we revisited the CIDNP study of FAD using a robust mechanical sample shuttling setup covering a wide magnetic field range with sample illumination by a light emitting diode. Also, a cost efficient fast field cycling apparatus with high spectral resolution detection up to 16.4 T for nuclear magnetic relaxation dispersion studies was built based on a 700 MHz NMR spectrometer. Site-specific proton relaxation dispersion data for FAD show a strong restriction of the relative motion of its isoalloxazine and adenine rings with coincident correlation times for adenine, flavin and their ribityl-phosphate linker. This finding is consistent with the assumption that the molecular structure of FAD is rigid and compact. The structure with close proximity of the isoalloxazine and purine moieties is favorable for reversible light induced intramolecular electron transfer from adenine to triplet excited flavin with formation of a transient spin-correlated triplet biradical F•−-A•+. Spin selective recombination of the biradical leads to the formation of CIDNP with a common emissive maximum at 4.0 mT detected for adenine and flavin protons. Careful correction of the CIDNP data for relaxation losses during sample shuttling shows that only a single maximum of CIDNP is formed in the magnetic field range from 0.1 mT to 9 T; thus, only one type of FAD biradical is detectable. Modeling of the CIDNP field dependence provides good agreement with the experimental data for a normal distance distribution between the two radical centers around 0.89 nm and an effective electron exchange interaction of −2.0 mT.

Background and Purpose: Cognitive impairment after stroke, especially executive and attention dysfunction, is common, negatively affects daily functioning, and has limited treatment options. A single-blind, parallel-design, randomized controlled trial was used to examine the impact of goal setting on poststroke cognitive performance. Methods: Stroke survivors (n=72; mean age, 68.38 [SD=11.84] years; 69.4% men) in the chronic phase (≥3 months) after stroke from an academic stroke prevention clinic were randomly assigned to receive goal-setting instructions (n=36) or standard instructions (n=36) after completing baseline cognitive measures of executive function (primary outcome), attention/working memory, verbal learning, and verbal recall. Results: A one-way mixed multivariate analysis of covariance (MANCOVA) found a group by instructional manipulation interaction effect for executive function (Wilks λ=0.66; F [3,66]=11.30; P ≤0.001; η 2 p =0.34), after adjusting for age and years of education. After similar adjustment, attention/working memory (Wilks λ=0.86; F [5,63]=2.10; P =0.043; η 2 p =0.16) and verbal learning ( F [1,60]=5.81; P =0.019; η 2 p =0.09) also showed improvement after instruction but not verbal recall (Wilks λ=0.95; F [1,56]=2.82; P =0.099; η 2 p =0.05). There were no adverse events. Conclusions: Goal setting improved executive function, attention/working memory, and learning in a heterogeneous sample in the chronic phase after stroke. This suggests that >3 months after stroke, vascular cognitive impairment is not a fixed deficit; there is a motivational contributor. Brief treatments targeting goal-oriented behavior and motivation may serve as a novel approach or adjunct treatment to improve cognitive outcomes after stroke. Future research should investigate the use of goal setting on functional outcomes (eg, instrumental activities of daily living and vocational function) in this population, highlighting new potential avenues for treatment for vascular cognitive impairment. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03511300.

Purpose The aim of this study was to establish content validity of a developmentally based assessment tool of readiness for medical independence for specialty providers. Design and methods The validation process used expert panel evaluation to assess the items believed to measure the desired content in the nine age-based scales within the RAISE (Readiness Assessment of Independence for Specialty Encounters) tool. Experts in child development and transition rated items on relevance, clarity and developmental appropriateness via electronic survey. Statistical analyses included calculation of interrater agreement (IRA), content validity indices (CVIs), and factorial validity indices (FVI). Results A total of 135 items were rated by 36 experts. Mean I-CVIs for 123 items across nine developmental scales met criteria for retention, ranging from 0.76 (threshold) to 1.00 (excellent). Mean I-CVIs for all 25 items across the five psychosocial stressor scales met criteria for retention, ranging from 0.92 to 1.00 (excellent). Conclusions Findings from the current content validation study suggest that items on the revised RAISE tool are relevant, clear, and developmentally-appropriate as rated by experts in the fields of child development and transition. The tool, consisting of age based scales (ages birth-2, 3–4, 5–6, 7–8, 9–11, 12–13, 14–15, 16–17, 18–21), is shown to have content validity of the retained items meeting criteria. Practice implications With content validity of the RAISE tool established by experts, this developmentally based assessment tool can be integrated into practice to assist providers in educating patients around skills of medical independence which could improve transition outcomes.

Background Social media is used by young adult patients for social connection and self-identification. Objective This study aims to compare the social media habits of young adults with inflammatory bowel disease (IBD) and type 1 diabetes (T1D). Methods This is a cross-sectional study of subjects from Boston Children’s Hospital outpatient IBD and diabetes clinics. Patients above 18 years of age were invited to complete a brief anonymous survey, which asked about the various ways they use several social media platforms. Results Responses were received from 108 patients (92.5% response rate), evenly split across disease type. We found that 83% of participants spent at least 30 minutes per day on social media, most commonly on Instagram and Facebook. Although the content varied based on the platform, patients with IBD posted or shared content related to their disease significantly less than those with T1D (23% vs 38%, P=.02). Among Instagram users, patients with IBD were less likely to engage with support groups (22% vs 56%, P=.04). Among Twitter users, patients with IBD were less likely to seek disease information (77% vs 29%, P=.005). Among Facebook users, patients with IBD were less likely to post about research and clinical trials (31% vs 65%, P=.04) or for information seeking (49% vs 87%, P=.003). Patients with IBD were also less likely to share their diagnosis with friends or family in person. Conclusions Young adults with IBD were less willing to share their diagnosis and post about or explore the disease on social media compared to those with T1D. This could lead to a sense of isolation and should be further explored.

We report a multifrequency NMR study of heterospin complexes [Eu(SQ)3Ln], where SQ is 3,6-di(tert-butyl)-1,2-semiquinone, L is THF, Py or Dipy and n is the number of diamagnetic ligands. Multifrequency NMR experiments allowed us to determine the effective paramagnetic shifts of the ligands (L = THF or Py) and the chemical equilibrium constant for [Eu(SQ)3(THF)2]. In addition, we have found a strong magnetic field effect on the NMR line broadening, giving rise to very broad NMR lines at high magnetic field. We attribute this effect to broadening under fast exchange conditions when the NMR spectrum represents a homogeneously broadened line with a width proportional to the square of NMR frequency difference of the free and bound forms of L. Consequently, the linewidth strongly increases with the magnetic field. This broadening effect allows one to determine relevant kinetic parameters, i.e., the effective exchange time. The strong broadening effect allows one to exploit the [Eu(SQ)3(THF)2] complex as an effi...

This paper reviews the prevalence and usage of the concept of “ecosystem services” in American and other common law legal systems. Our review suggests that this concept is rarely relied upon by courts and other adjudicatory bodies. We have identified 113 cases in seven common law countries, including a handful in the United States, the majority of which discuss ecosystem services and related concepts in only a peripheral manner, indicating that adjudicating bodies are hearing cases that consider ecosystem services in broad strokes rather than as central issues. Where ecosystem services are considered substantively, the cases view those services through the lens of interpreting and applying existing environmental laws and regulations, including laws that require environmental valuations. We identify several recurring trends in cases discussing ecosystem services and recommend courses of action for environmental agencies and litigants interested in furthering ecosystem services protection through the court systems of common law countries.

Time-resolved chemically induced dynamic nuclear polarization (TR-CIDNP) is applied to follow transformation of the short-lived neutral guanine radical into a secondary guanine radical by its protonation, presumably at position N7. In the initial step the photoreaction of guanosine-5'-monophosphate (GMP) with triplet excited 3,3',4,4'-tetracarboxy benzophenone (TCBP) leads to formation of the neutral radical G(-H). . The evidence of the radical conversion is based on the inversion of CIDNP sign for TCBP and GMP protons on the microsecond timescale as a result of the change in magnetic resonance parameters in the pairs of TCBP and GMP radicals due to structural changes of the GMP radical. Acceleration of the CIDNP sign change upon addition of phosphate (proton donor) confirms that the radical transformation responsible for the observed CIDNP kinetics is protonation of the neutral guanine radical with formation of the newly characterized cation radical, (G.+ )'. From the full analysis of the pH-dependent CIDNP kinetics, the protonation and deprotonation behaviour is quantitatively characterized, giving pKa =8.0±0.2 of the cation radical (G.+ )'.

Objectives Transition planning for children with chronic disease includes the development of independence in many self-management tasks. Conditions that depend on diet have distinct skill sets not well assessed by the traditional transition-readiness tools. There has been literature that describes age-appropriate skill acquisition for diabetes and food allergy patients. There are, however, no age-appropriate benchmarks established for celiac disease (CD). Methods CD experts (including physician, nurse, dietician, social worker, patient, and parent) created a list of celiac-related tasks, which formed the basis of the survey. Patients with CD, and their parents, were recruited from outpatient celiac clinic and support groups, and invited to report the age each task was mastered. Results Respondents included 204 patients and 155 parents. Mean age was 12 years (standard deviation 4.6) with average of 4 years since diagnosis. The earliest tasks were mastered by a median age of 8 years, such as recognizing GF as gluten-free, eating safely in a shared space and recognizing basic unsafe foods. Describing the effects of eating gluten or explaining CD to a friend or stranger occurred around age 10. Asking about gluten-free preparation in a restaurant, and identifying gluten-free medications or vitamins was mastered around age 12, whereas tasks involved with safe domestic travel or assessing risk in a job environment occurred between 14 and 16. The interquartile range was about 4 years for each question. No significant difference seen between patient and parent reports. Conclusions This novel patient-centered celiac skill list may improve anticipatory guidance and accelerate self-management skills.

BACKGROUND: We seek to determine how youth with chronic medical conditions experience alcohol screening and counseling. METHOD: Adolescents with type 1 diabetes, juvenile idiopathic arthritis, moderate persistent asthma, cystic fibrosis, attention deficit hyperactivity disorder, or inflammatory bowel disease were surveyed. Descriptive statistics and regression analysis quantified rates of asking and counseling about alcohol. RESULTS: Of 390 participants (75.1% white/non-Hispanic, 51.8% female, average age 16.4 years), 70% reported being asked about their alcohol use by a healthcare provider and 76% reported receiving at least one message regarding alcohol and health. Of past year drinkers 54% disclosed use to their provider. Only 2.0% of youth reported receiving the message “I should not drink”. CONCLUSION: Most youth with chronic medical conditions were asked and counseled about alcohol use though few heard unambiguous recommendations to avoid alcohol consumption. IMPLICATIONS AND CONTRIBUTION: Youth with medical conditions are commonly asked and counseled about alcohol. Asking about alcohol use seems to increase the likelihood of counseling. Improving screening implementation and delivering unambiguous advice not to use alcohol may increase the effectiveness of this practice.

A detailed experimental study on reversible photo-induced intramolecular charge separation is presented based on NMR detection of Chemically Induced Dynamic Nuclear Polarization (CIDNP). From variation of such polarization with the external magnetic field the coupling constants of isotropic and anisotropic hyperfine interaction at individual 13C sites are measured in the short-lived charge separated state of dyad molecules composed of donor-bridge-acceptor parts. The objects of study were rigid donor-bridge- acceptor dyads, consisting of triarylamine as a donor, naphthalene diimide (NDI) as an acceptor, and a meta-conjugated diethynyl benzene fragment as a bridge. By systematic variation of side groups in the bridging moiety their influence on the electron withdrawing strength is traced. In combination with similar data for the 1H positions obtained previously for the same compounds (I. Zhukov, et al J. Chem. Phys 2020, 152, 014203) our results provide a reliable basis for determination of the spin density distribution in the charge separated state of such dyads.

As mental health navigation services continue to be implemented, the need for valid and reliable tools to assess the quality of these services increases. While case managers target individuals with severe mental illness and aim to reduce burden and cost, and increase independence, navigation services target all individuals with a range of mental health and/or substance use issues, with the aim of reducing barriers to treatment and coordinating individualized care. The current study evaluated satisfaction with a navigation service using a new 22-item questionnaire, the Navigation Satisfaction Tool (NAVSAT). Forty clients completed a web-based version of the NAVSAT to evaluate satisfaction with a family mental health navigation service in Toronto, Canada. Descriptive statistics on the sample and range of treatments/services are provided. The NAVSAT has excellent reliability (Cronbach's alpha = 0.96) and face validity. Satisfaction with the following navigation-level factors were the best predictors of overall satisfaction with navigation; the navigator's ability to recommend the appropriate treatment (β = 0.116, p = .05), intake procedures (β = 0.364, p = .005), and the principal contact's satisfaction with his/her frequency of contact with the navigator (β = 0.602, p = .001). Satisfaction with the following provider-level factors were the best predictors of overall satisfaction with the referred service; the referred service's ability to improve the youth's well being (β = 0.684, p

The Lower Mississippian upper shale member of the Bakken Formation in the Williston Basin, North Dakota, consists of organic-rich, black, siliciclastic mudstones deposited offshore on a low-gradient shelf; 12 fine-grained facies are recognized and grouped into 5 facies associations (FAs). Very fine-grained, massive to faintly laminated mudstone (FA1) records deposition in the deepest, calmest parts of the basin, whereas well-laminated mudstones (FA2a); well-laminated, clay-clast–bearing mudstones (FA2b); burrow-mottled mudstone with shells (FA3); and interlaminated siltstone and mudstone (FA4) suggest deposition in the shallower, less calm, and more proximal offshore environment. These proximal-offshore mudstones (FA2a, FA2b, FA3, and FA4) reflect (1) variation in bottom-water oxygen levels and (2) lateral changes in the input of silt and clay clasts. Ubiquitous Phycosiphon fecal strings, patches of shells, burrows, and rare agglutinated foraminifera indicate dysoxic to suboxic basinal deposition and not a persistently anoxic environment. In all FAs, storm-event laminae are sparse to ubiquitous. Repeated stacking of FAs defines up to 10 coarsening-upward parasequences mostly 0.15–0.60 m (0.49–1.97 ft) thick. Individual parasequences can be correlated for 300 km (180 mi) through the basin. The lower half of the succession (interval 1) represents a transgressive systems tract and shows high radiolarian productivity with minor silt input. The upper half of the succession (interval 2) represents the base of a highstand systems tract. In contrast to interval 1, interval 2 mudstones are characterized by high clay content, low radiolarian productivity, and intermittent colonization of the sea floor during higher-order sea-level lowstands.

This study examined the relationship between apathy and cognition in patients with cerebrovascular disease. Apathy may result from damage to frontal subcortical circuits causing dysexecutive syndromes, but apathy is also related to depression. We assessed the ability of apathy to predict phonemic fluency and semantic fluency performance after controlling for depressive symptoms in 282 individuals with stroke and/or transient ischemic attack.Participants (N = 282) completed the Phonemic Fluency Test, Semantic Fluency Test, Center for Epidemiologic Studies Depression Scale, and Apathy Evaluation Scale. A cross-sectional correlational design was utilized.Using hierarchical linear regressions, apathy scores significantly predicted semantic fluency performance (β = -.159, p = .020), but not phonemic fluency performance (β = -.112, p = .129) after scaling scores by age and years of education and controlling for depressive symptoms. Depressive symptoms entered into the first step of both hierarchical linear regressions did not predict semantic fluency (β = -.035, p = .554) or phonemic fluency (β = -.081, p = .173). Apathy and depressive symptoms were moderately correlated, r(280) = .58, p .001.The results of this study are consistent with research supporting a differentiation between phonemic and semantic fluency tasks, whereby phonemic fluency tasks primarily involve frontal regions, and semantic fluency tasks involve recruitment of more extended networks. The results also highlight a distinction between apathy and depressive symptoms and suggest that apathy may be a more reliable predictor of cognitive deficits than measures of mood in individuals with cerebrovascular disease. Apathy may also be more related to cognition due to overlapping motivational and cognitive frontal subcortical circuitry. Future research should explore whether treatments for apathy could be a novel target for improving cognitive outcomes after stroke.

Transition is the long process of developing independent self-management skills whereas transfer is the actual move from pediatric to adult-centered provider. Structured anticipated transition works best with timelines of tasks to master and discussion of the stylistic differences between pediatric and adult practices. Disease-specific issues need to be addressed, such as earlier timelines for diet-based therapies, parental support for critical illnesses, and differences in therapeutic strategies.

In order to model the involvement of histidine radicals in the electron transfer reactions in proteins, we investigated the kinetics of the reduction of hisitidine radicals in the reactions with aromatic amino acid residues by means of chemically induced dynamic nuclear polarization with microsecond time resolution. Histidine radicals were generated in photochemical reaction with triplet-excited 3,3’,4,4’-benzophenone tetracarboxylic acid. The intermolecular electron transfer from N-acetyl derivatives of tyrosine and tryptophan to the radical of N-acetyl histidine was studied in neutral and basic aqueous solutions. It was found that the rate constant of reduction of short-lived histidine radical in the reactions with tyrosine anion is k r = (1.9±0.5)•108 L mol–1 s–1, which is more than two orders of magnitude higher than that of reduction of histidine radical with neutral tyrosine (k r = (1.2±0.4)•106 L mol–1 s–1). In the reduction of histidine radical with N-acetyl tryptophan, the protonated states of reagents do not change, when pH of aqueous solution varies from neutral to basic and the reaction rate coefficient remains constant being k r = (1.3±0.4)•106 L mol–1 s–1.

Background Inflammatory bowel disease (IBD) may limit physical activity due to intestinal or extraintestinal manifestations, fatigue, or exercise perception. We sought to evaluate the influence of IBD diagnosis on exercise and sports participation in a pediatric population. We compared patient-reported and parent-reported perspectives. Aim To evaluate the influence of IBD diagnosis on exercise and sports participation in a pediatric population. Methods Consecutive IBD outpatients (aged 10-18 years) and their parents completed parallel voluntary surveys. A validated, patient-reported functional activity scale, the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) was used to assess children's activity levels. Results There were 149 completed surveys (75% response rate) with mean participant age of 16.5 years [standard deviation (SD) = 4.0] and mean age at IBD diagnosis of 11.8 years (SD = 3.4). Most patients (77%) were diagnosed within 12 mo of symptom onset. Current athletic participation was reported in 65% across 65 sports. Participation was greatest before (40%) rather than after (32%) IBD diagnosis, with no reported change in 28%. IBD negatively impacted play/performance in 45% but did not change play/performance in 44%. IBD treatment improved patients' desire to exercise (70%) and subjective capacity for aerobic exercise (72%). Patients and parents agreed that IBD subjects demonstrate normal capacity for aerobic exercise (0.40, 95%CI: 0.22-0.58) and that treatment improved both participatory desire (0.33, 95%CI: 0.12-0.54) and capacity for aerobic exercise (0.52, 95%CI: 0.31-0.71). Almost all (99%) viewed exercise as healthy, and most encouraged its practice. IBD patients demonstrated normal mean HSS Pedi-FABS scores. Conclusion After pediatric IBD diagnosis, most patients continue exercise and sports, with mean activity levels comparable to American youth. Treatment positively impacts participatory desire and aerobic capacity. Patients favor the role of exercise in IBD.

Introduction In a flipped classroom, students learn basic concepts before class, allowing them time during class to apply newly gained knowledge to problem sets and cases. Harvard Medical School (HMS) has introduced a form of flipped classroom, called case-based collaborative learning (CBCL), during preclinical curricula. Finding few published resources, the HMS Academy's Peer Observation of Teaching Interest Group developed a guide for observations and feedback to CBCL facilitators. Methods After conducting an extensive literature search, speaking to flipped classroom methodology experts, and observing 14 facilitators using CBCL methods, the interest group identified specific teaching behaviors that optimize student interaction and knowledge application. The group next engaged in several rounds of the modified Delphi method to develop the CBCL peer observation worksheet and compendium and then tested these materials' effectiveness in capturing CBCL teaching behaviors and providing feedback to CBCL faculty facilitators. Results Seventy-three percent of faculty rated the worksheet and compendium as extremely helpful or helpful in identifying new teaching techniques. Moreover, 90% found the CBCL peer observation and debriefing to be extremely helpful or helpful, and 90% were extremely likely or likely to incorporate peer suggestions in future teaching sessions. Discussion Medical schools have begun to embrace flipped classroom methods to eliminate passive, lecture-style instruction during the preclinical years of the MD curriculum. This tool identifies specific in-classroom approaches that engage students in active learning, guides peer observers in offering targeted feedback to faculty on teaching strategies, and presents consensus-based resources for use during CBCL faculty development and training.

Objective:Transition readiness assessment has focused attention on adolescent knowledge and skills, but data-driven benchmarks have not been established.Methods:Patients with inflammatory bowel disease (IBD), ages 25 to 50 years, attending an outpatient gastroenterology clinic, were recruite

Objectives Transition and transfer to adult-oriented health care is an important yet challenging task for adolescents and young adults with chronic medical conditions. Transition practices vary widely, but a paucity of data makes determination of best practices difficult. We described North American pediatric gastroenterologists' preferences and present transition practice patterns and explored whether experience affected providers' perspectives. Methods An online survey was distributed via e-mail to members of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition. Participation was voluntary and answers were anonymous. Quantitative and qualitative analysis was performed. Results Almost three quarters of the 175 respondents describe providing transition or self-care management education, but only 23% use structured readiness assessments. Most respondents (88%) report having age cutoffs above which they no longer accept new referrals, with the most common age being 18 years (57%). One third report the ability to provide age-appropriate care to patients older than 21 years. Only 6% indicate that their practice or institution should provide care for individuals older than 25 years. Many (63%) indicate that their practice or institution has a policy regarding age of transfer, but most (79%) are flexible. Provider preferences for triggers to transfer to adult care diverge widely between age, milestones, and comorbidities. Overall, parent (81%) and patient (74%) attachment to pediatric health care providers are cited as the most common barriers to transition. Conclusions Preferences and practices surrounding transition preparation and transfer to adult care vary widely, reflecting continued uncertainty regarding optimal transition strategies.

BACKGROUND Surgical specialties are underrepresented in the discussions regarding transition and transfer of patients to adult care. We sought the pediatric orthopaedic perspective on types of patients seen into adulthood, age cut-offs, triggers for transfer, and barriers to transition. We examined provider demographic factors that may influence perspectives. METHODS An internet-based survey was sent to all members of the Pediatric Orthopaedic Society of North America and the Pediatric Orthopaedic Practitioner Society. Responses were voluntary and anonymous. RESULTS Response rates were 27% for the Pediatric Orthopaedic Society of North America and 24% for the Pediatric Orthopaedic Practitioner Society. Most respondents (70%) care for patients over the age of 25 years and many (35%) for patients over the age of 40. The most common conditions cared for were neuromuscular and congenital disorders. Respondents who worked in a fully salaried model reported caring for fewer of these adult patients compared with those working in other types of payment structure (P

As a model of chemical DNA repair, intramolecular electron transfer from tryptophan to the radical of the purine base guanosine combined into a conjugate by a flexible linker was studied by time-resolved chemically induced dynamic nuclear polarization (CIDNP). The guanosyl radicals were photochemically generated in the quenching reaction of the triplet excited dye 2,2′-dipyridyl. The CIDNP kinetics was obtained by detection of NMR spectra containing anomalously enhanced signals of diamagnetic products that are formed during a variable period after excitation by a laser pulse. The kinetic data obtained for the protons located on the guanosyl and tryptophanyl moieties of the conjugate were compared to those obtained in photoreactions of the molecules containing the same linker, but with only one of the two reactive moieties of the conjugate – tryptophanyl or guanosyl. Strong differences between the CIDNP kinetics of different conjugates were revealed and explained by a rapid intramolecular electron transfer from tryptophan to the guanosyl radical in the conjugate. Model simulations of the CIDNP kinetics allowed for determination of the rate constant of intramolecular electron transfer at (1.0±0.5)×106 s–1 indicating a high potential of chemical repair of the guanosyl radical by means of electron transfer from the tryptophanyl moiety in a surrounding protein pool that can provide rather efficient protection of oxidized DNA bases from pathological damage on a submicrosecond time scale.

Self-management, including medication adherence, is associated with improved health and outcomes for patients with inflammatory bowel disease. The concept of self-management is complex, but can be divided into those aspects that involve the individual patient, those that involve the provider-patient relationship, and those that encompass the social environment. At the individual level, enhancing problem-solving skills and self-efficacy have both been shown to improve self-management tasks, particularly adherence to treatment. However, it is critical to consider these domains from a lifespan perspective because these processes by which self-management can be improved are distinct for children, adolescents, young adults, and adults. A particular emphasis is placed on strategies to improve self-management of older adolescents and young adults as they transition from pediatric to adult providers. The review concludes with recommendations for providers, including rationale and techniques for assessing and promoting patient self-efficacy, encouraging the development of problem-solving skills, improving the patient-provider relationship, and enhancing social support. Providers are encouraged to utilize elements of problem-solving skills training, engage in collaborative relationships with their patients, and offer their patients recommendations for how to increase the quality of their social support networks as ways of increasing overall self-management.

Although fatigue is a common problem for men with prostate cancer undergoing androgen deprivation therapy (ADT), there has been little systematic research on this issue. The present study examined changes in fatigue among prostate cancer patients receiving ADT compared to controls and predictors of heightened fatigue in ADT patients.Prostate cancer patients treated with ADT (ADT+ group, n = 60) completed assessments of fatigue prior to or just after ADT initiation (baseline) and 6 and 12 months later. Prostate cancer patients treated with prostatectomy only (ADT- group, n = 85) and men without cancer (CA- group, n = 86) matched on age and education completed assessments at similar intervals.Group-by-time interactions for fatigue severity, interference, and duration were observed when comparing the ADT+ group to the controls. Groups did not differ at baseline; however, the ADT+ group reported worse fatigue at 6 and 12 months. The same pattern was observed for changes in the prevalence of clinically meaningful fatigue and the extent of clinically meaningful change in fatigue. Within the ADT+ group, higher baseline comorbidity scores were associated with greater increases in fatigue interference, and higher baseline Gleason scores were associated with greater increases in fatigue duration.Prostate cancer patients receiving ADT demonstrate a trajectory of worsened fatigue during the first 12 months following treatment initiation relative to the controls. Greater comorbidities and higher Gleason scores at baseline appear to be risk factors for heightened fatigue during the first year following ADT initiation. Results highlight important time points for implementation of interventions aimed at fatigue reduction.

Background & Aims Studies are needed to determine the mechanisms of mucosal dysregulation in patients with inflammatory bowel diseases (IBDs) and differences in inflammatory responses of patients with ulcerative colitis (UC) vs Crohn’s disease (CD). We used mass cytometry (CyTOF) to characterize and compare immune cell populations in the mucosa and blood from patients with IBD and without IBD (controls) at single-cell resolution. Methods We performed CyTOF analysis of colonic mucosa samples (n = 87) and peripheral blood mononuclear cells (n = 85) from patients with active or inactive UC or CD and controls. We also performed single-cell RNA sequencing, flow cytometry, and RNA in situ hybridization analyses to validate key findings. We used random forest modeling to identify differences in signatures across subject groups. Results Compared with controls, colonic mucosa samples from patients with IBD had increased abundances of HLA-DR+CD38+ T cells, including T-regulatory cells that produce inflammatory cytokines; CXCR3+ plasmablasts; and IL1B+ macrophages and monocytes. Colonic mucosa samples from patients with UC were characterized by expansion of IL17A+ CD161+ effector memory T cells and IL17A+ T-regulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reductions in type 3 innate lymphoid cells. Mucosal samples from patients with active CD were characterized by IL1B+HLA-DR+CD38+ T cells, IL1B+TNF+IFNG+ naive B cells, IL1B+ dendritic cells (DCs), and IL1B+ plasmacytoid DCs. Peripheral blood mononuclear cells from patients with active CD differed from those of active UC in that the peripheral blood mononuclear cells from patients with CD had increased IL1B+ T-regulatory cells, IL1B+ DCs and IL1B+ plasmacytoid DCs, IL1B+ monocytes, and fewer group 1 innate lymphoid cells. Random forest modeling differentiated active UC from active CD in colonic mucosa and blood samples; top discriminating features included many of the cellular populations identified above. Conclusions We used single-cell technologies to identify immune cell populations specific to mucosa and blood samples from patients with active or inactive CD and UC and controls. This information might be used to develop therapies that target specific cell populations in patients with different types of IBD.