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The R2 Library is an electronic book product designed by Rittenhouse Book Distributors for medicine, nursing, and allied health professionals. This article describes the contents and features of the Library, as well as appraises the navigation and searching functions. This article also notes special features of the R2 Library, such as an institutional administration module and an individual user section called My R2. [ABSTRACT FROM AUTHOR]

Introduction: It is well documented that librarian involvement in systematic reviews generally increases quality of reporting and the review overall. We used bibliometric analysis methods to analyze the level of librarian involvement in systematic reviews conducted at the University of Alberta (U of A)., Methods: Using Web of Science (WoS), we searched for systematic reviews completed in the years 2016-2020 with a U of A co-author. Systematic reviews identified through WoS were screened in two phases: ( i ) exclusion of duplicates, protocols, other types of reviews, and systematic review methodology literature to leave true systematic review publications, and ( ii ) screening for level of librarian involvement (acknowledgement, co-author, or no involvement)., Results: 640 reviews were analyzed for the following categories: ( i ) librarian named as a coauthor; ( ii ) librarian named in the acknowledgements section; ( iii ) librarian mentioned in the body of the manuscript; ( iv ) no librarian involvement. We identified 152 reviews who named a librarian as a co-author on the paper, 125 reviews named a librarian in the acknowledgements section, and 67 reviews mentioned a librarian in the body of the review without naming them as a co-author or in an acknowledgement. WoS Research Areas were used to identify disciplines that used librarian support and those that did not. A keyword network analysis revealed research areas that were very active in producing systematic reviews, while also providing information on the areas publishing systematic reviews without librarian support., Conclusion: There is a great deal of variation in how the work of librarians is reflected in systematic reviews. This was particularly apparent in reviews where a librarian was mentioned in the body of the review but they were not named as an author or formally acknowledged. Continuing to educate researchers about the work of librarians is crucial to fully represent the value librarians bring to systematic reviews. Bibliometric analysis provides useful insights on service gaps for specific disciplines or research areas that are currently not using librarian support in systematic review publications, which can help inform service planning., Competing Interests: The authors declare no conflicts of interest., (© Kennedy and Kung.)

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs) 1 , sources of high-frequency gravitational waves (GWs) 2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process) 3 . Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers 4-6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs.  7-12 ). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe., (© 2023. The Author(s).)

Background: Certain communities are underserved by research, resulting in lower inclusion rates, under researched health issues and a lack of attention to how different communities respond to health interventions. Minoritised ethnic groups are often underserved by research and services. They experience health inequalities and face significant barriers to accessing health services. It is recognised that new approaches are needed to reach underserved communities and make research more relevant. The purpose of this work was to utilise World Cafés, a participatory method, to explore research agendas with diverse communities., Methods: Two World Cafés were conducted as research agenda setting activities with individuals from minoritised ethnic communities in Bristol, UK. World Café 1 explored Black and Asian women's perspectives about supporting mental health. World Café 2 with men from the Somali community, focused on prostate cancer. Community members co-developed the focus and questions of each World Café and were also instrumental in recruiting individuals to the sessions and facilitating discussions, including translation. Audio and written records were made of the discussions and from these key issues about each topic were identified, and a visual representation of the discussion was also generated. These were shared with participants to check for accuracy., Results: Community members identified a range of issues that are important to them in relation to mental health and prostate cancer, including barriers to help seeking and accessing primary and secondary care, ideas for service improvements and a need for health information that is accessible and culturally relevant., Conclusions: World Cafés are a flexible method that can be successfully adapted for research agenda setting with individuals from minoritised ethnic communities. The role of community members in co-developing the focus of sessions, recruiting community members and co-facilitating sessions is crucial to this success. The discussions at both World Cafés provided a rich insight into the experiences of participants in relation to the topics mental health and prostate cancer and identified issues that are important to these communities that will be followed-up with communities, researchers and clinicians to co-develop research and service improvement strategies., (© 2023. The Author(s).)

The presence and distribution of preserved organic matter on the surface of Mars can provide key information about the Martian carbon cycle and the potential of the planet to host life throughout its history. Several types of organic molecules have been previously detected in Martian meteorites 1 and at Gale crater, Mars 2-4 . Evaluating the diversity and detectability of organic matter elsewhere on Mars is important for understanding the extent and diversity of Martian surface processes and the potential availability of carbon sources 1,5,6 . Here we report the detection of Raman and fluorescence spectra consistent with several species of aromatic organic molecules in the Máaz and Séítah formations within the Crater Floor sequences of Jezero crater, Mars. We report specific fluorescence-mineral associations consistent with many classes of organic molecules occurring in different spatial patterns within these compositionally distinct formations, potentially indicating different fates of carbon across environments. Our findings suggest there may be a diversity of aromatic molecules prevalent on the Martian surface, and these materials persist despite exposure to surface conditions. These potential organic molecules are largely found within minerals linked to aqueous processes, indicating that these processes may have had a key role in organic synthesis, transport or preservation., (© 2023. The Author(s).)

Behavioural coding is time-intensive and laborious. Thin slice sampling provides an alternative approach, aiming to alleviate the coding burden. However, little is understood about whether different behaviours coded over thin slices are comparable to those same behaviours over entire interactions. To provide quantitative evidence for the value of thin slice sampling for a variety of behaviours. We used data from three populations of parent-infant interactions: mother-infant dyads from the Grown in Wales (GiW) cohort ( n  = 31), mother-infant dyads from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort ( n  = 14), and father-infant dyads from the ALSPAC cohort ( n  = 11). Mean infant ages were 13.8, 6.8, and 7.1 months, respectively. Interactions were coded using a comprehensive coding scheme comprised of 11-14 behavioural groups, with each group comprised of 3-13 mutually exclusive behaviours. We calculated frequencies of verbal and non-verbal behaviours, transition matrices (probability of transitioning between behaviours, e.g., from looking at the infant to looking at a distraction) and stationary distributions (long-term proportion of time spent within behavioural states) for 15 thin slices of full, 5-min interactions. Measures drawn from the full sessions were compared to those from 1-, 2-, 3- and 4-min slices. We identified many instances where thin slice sampling (i.e., < 5 min) was an appropriate coding method, although we observed significant variation across different behaviours. We thereby used this information to provide detailed guidance to researchers regarding how long to code for each behaviour depending on their objectives., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s) 2023.)

Reliable neutron star mass measurements are key to determining the equation of state of cold nuclear matter, but such measurements are rare. Black widows and redbacks are compact binaries consisting of millisecond pulsars and semi-degenerate companion stars. Spectroscopy of the optically bright companions can determine their radial velocities, providing inclination-dependent pulsar mass estimates. Although inclinations can be inferred from subtle features in optical light curves, such estimates may be systematically biased due to incomplete heating models and poorly understood variability. Using data from the Fermi Large Area Telescope, we have searched for gamma-ray eclipses from 49 spider systems, discovering significant eclipses in 7 systems, including the prototypical black widow PSR B1957+20. Gamma-ray eclipses require direct occultation of the pulsar by the companion, and so the detection, or significant exclusion, of a gamma-ray eclipse strictly limits the binary inclination angle, providing new robust, model-independent pulsar mass constraints. For PSR B1957+20, the eclipse implies a much lighter pulsar (1.81 ± 0.07 solar masses) than inferred from optical light curve modelling., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

The Perseverance rover landed in Jezero crater, Mars, in February 2021. We used the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument to perform deep-ultraviolet Raman and fluorescence spectroscopy of three rocks within the crater. We identify evidence for two distinct ancient aqueous environments at different times. Reactions with liquid water formed carbonates in an olivine-rich igneous rock. A sulfate-perchlorate mixture is present in the rocks, which probably formed by later modifications of the rocks by brine. Fluorescence signatures consistent with aromatic organic compounds occur throughout these rocks and are preserved in minerals related to both aqueous environments.

Background: Ubiquitous, smart technology has the potential to assist humans in numerous ways, including with health and social care. COVID-19 has notably hastened the move to remotely delivering many health services. A variety of stakeholders are involved in the process of developing technology. Where stakeholders are research participants, this poses practical and ethical challenges, particularly if the research is conducted in people's homes. Researchers must observe prima facie ethical obligations linked to participants' interests in having their autonomy and privacy respected., Objective: This study aims to explore the ethical considerations around consent, privacy, anonymization, and data sharing with participants involved in SPHERE (Sensor Platform for Healthcare in a Residential Environment), a project for developing smart technology for monitoring health behaviors at home. Participants' unique insights from being part of this unusual experiment offer valuable perspectives on how to properly approach informed consent for similar smart home research in the future., Methods: Semistructured qualitative interviews were conducted with 7 households (16 individual participants) recruited from SPHERE. Purposive sampling was used to invite participants from a range of household types and ages. Interviews were conducted in participants' homes or on-site at the University of Bristol. Interviews were digitally recorded, transcribed verbatim, and analyzed using an inductive thematic approach., Results: Four themes were identified-motivation for participating; transparency, understanding, and consent; privacy, anonymity, and data use; and trust in research. Motivations to participate in SPHERE stemmed from an altruistic desire to support research directed toward the public good. Participants were satisfied with the consent process despite reporting some difficulties-recalling and understanding the information received, the timing and amount of information provision, and sometimes finding the information to be abstract. Participants were satisfied that privacy was assured and judged that the goals of the research compensated for threats to privacy. Participants trusted SPHERE. The factors that were relevant to developing and maintaining this trust were the trustworthiness of the research team, the provision of necessary information, participants' control over their participation, and positive prior experiences of research involvement., Conclusions: This study offers valuable insights into the perspectives of participants in smart home research on important ethical considerations around consent and privacy. The findings may have practical implications for future research regarding the types of information researchers should convey, the extent to which anonymity can be assured, and the long-term duty of care owed to the participants who place trust in researchers not only on the basis of this information but also because of their institutional affiliation. This study highlights important ethical implications. Although autonomy matters, trust appears to matter the most. Therefore, researchers should be alert to the need to foster and maintain trust, particularly as failing to do so might have deleterious effects on future research., (©Mari-Rose Kennedy, Richard Huxtable, Giles Birchley, Jonathan Ives, Ian Craddock. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 26.11.2021.)

Background: During the arrival of the COVID-19 pandemic, various professional ethical guidance was issued to (and for) health and social care professionals in England and Wales. Guidance can help to inform and support such professionals and their patients, clients and service users, but a plethora of guidance risked information overload, confusion, and inconsistency., Methods: During the early months of the pandemic, we undertook a rapid review, asking: what are the principles adopted by professional ethical guidance in England and Wales for dealing with COVID-19? We undertook thematic content analysis of the 29 documents that met our inclusion criteria., Results: The 29 documents captured 13 overlapping principles: respect, fairness, minimising harm, reciprocity, proportionality, flexibility, working together, inclusiveness, communication, transparency, reasonableness, responsibility, and accountability., Conclusions: We intend this attempt to collate and outline the prominent principles to be helpful, particularly, for healthcare practice during the COVID-19 pandemic and, hopefully, for future pandemic planning. We also offer some reflections on the guidance and the principles therein. After describing the principles, we reflect on some of the similarities and differences in the guidance, and the challenges associated not only with the specific guidance reviewed, but also with the nature and import of "professional ethical guidance".

A strategy to conformationally restrain a series of GlyT1 inhibitors identified potent analogs that exhibited slowly interconverting rotational isomers. Further studies to address this concern led to a series of azetidine-based inhibitors. Compound 26 was able to elevate CSF glycine levels in vivo and demonstrated potency comparable to Bitopertin in an in vivo rat receptor occupancy study. Compound 26 was subsequently shown to enhance memory in a Novel Object Recognition (NOR) behavioral study after a single dose of 0.03 mg/kg, and in a contextual fear conditioning (cFC) study after four QD doses of 0.01-0.03 mg/kg., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We report here the identification and optimization of a novel series of potent GlyT1 inhibitors. A ligand design campaign that utilized known GlyT1 inhibitors as starting points led to the identification of a novel series of pyrrolo[3,4- c]pyrazoles amides (21-50) with good in vitro potency. Subsequent optimization of physicochemical and in vitro ADME properties produced several compounds with promising pharmacokinetic profiles. In vivo inhibition of GlyT1 was demonstrated for select compounds within this series by measuring the elevation of glycine in the cerebrospinal fluid (CSF) of rats after a single oral dose of 10 mg/kg. Ultimately, an optimized lead, compound 46, demonstrated in vivo efficacy in a rat novel object recognition (NOR) assay after oral dosing at 0.1, 1, and 3 mg/kg.

Purpose: The clinical utility of next-generation sequencing (NGS) in breast cancer has not been demonstrated. We hypothesized that we could perform NGS of a new biopsy from patients with metastatic triple-negative breast cancer (TNBC) in a clinically actionable timeframe., Experimental Design: We planned to enroll 40 patients onto a prospective study, Individualized Molecular Analyses Guide Efforts (IMAGE), to evaluate the feasibility of obtaining a new biopsy of a metastatic site, perform NGS (FoundationOne), and convene a molecular tumor board to formulate treatment recommendations within 28 days. We collected blood at baseline and at time of restaging to assess cell-free circulating plasma tumor DNA (ptDNA)., Results: We enrolled 26 women with metastatic TNBC who had received ≥1 line of prior chemotherapy, and 20 (77%) underwent NGS of a metastatic site biopsy. Twelve (60%) evaluable patients received treatment recommendations within 28 days of consent. The study closed after 20 patients underwent NGS, based on protocol-specified interim futility analysis. Three patients went on to receive genomically directed therapies. Twenty-four of 26 patients had genetic alterations successfully detected in ptDNA. Among 5 patients, 4 mutations found in tumor tissues were not identified in blood, and 4 mutations found in blood were not found in corresponding tumors. In 9 patients, NGS of follow-up blood samples showed 100% concordance with baseline blood samples., Conclusions: This study demonstrates challenges of performing NGS on prospective tissue biopsies in patients with metastatic TNBC within 28 days, while also highlighting the potential use of blood as a more time-efficient and less invasive method of mutational assessment. Clin Cancer Res; 23(2); 379-86. ©2016 AACR., (©2016 American Association for Cancer Research.)

Objective: To complete a systematic review of internal memory strategy use with people who have brain injury and provide practitioners with information that will impact their clinical work., Methods: A systematic literature search to identify published intervention studies that evaluated an internal memory strategy or technique to improve memory function of individuals with brain injury. Relevant data from reviewed articles were coded using 4 clinical questions targeting participants, interventions, research methods, and outcomes., Results: A comprehensive search identified 130 study citations and abstracts. Forty-six met inclusion/exclusion criteria and were systematically reviewed. Visual imagery was most frequently studied, in isolation or in combination with other internal strategies. Despite significant variability in research methods and outcomes across studies, the evidence provides impetus for use of internal memory strategies with individuals following brain injury., Conclusions: Individuals with traumatic brain injury may benefit from internal memory strategy use, and clinicians should consider internal memory strategy instruction as part of intervention plans. Further research needs to better delineate influences on intervention candidacy and outcomes.

Density functional theory (DFT) has been applied to the proposed rate-limiting step of the hydrolytic kinetic resolution (HKR) of terminal epoxides as catalyzed by Co-salen-X (X = counterion) in order to resolve questions surrounding the mechanism. The present results indicate that the bimetallic mechanism proposed by Jacobsen shows nonadditive, cooperative catalysis with a larger reduction in barrier height than the sum of the barrier height reductions from the two monometallic reaction pathways. We computed barrier heights for the reaction using several counterions (chloride, acetate, tosylate, and hydroxide). For the three counterions that are experimentally active (chloride, acetate, and tosylate) the barrier heights are 35, 38, and 34 kJ mol(-1), respectively, while for hydroxide it is 48 kJ mol(-1). The similarity of the barrier heights for chloride, acetate, and tosylate is in agreement with their similar peak reaction rates. The finding that Co-salen-X with these counterions leads to rather different overall reaction profiles suggests that they have quite different rates of reaction with epoxide to form the activated Co-salen-OH required for the bimetallic mechanism. Co-salen-OH is inactive as the sole catalyst for HKR, and this inactivity is ascribed to its larger barrier height for the ring-opening step, rather than to any inability to activate epoxide. Barrier heights were also computed using propylene oxide, 1-hexene oxide, and epichlorohydrin; propylene oxide and 1-hexene oxide have similar barrier heights, 35.5 and 33.2 kJ mol(-1), respectively, and epichlorohydrin has a significantly lower barrier height of 18.8 kJ mol(-1), which is qualitatively consistent with experiments showing faster reactions for epicholorohydrin than propylene oxide when catalyzed by Co-salen-OAc.

Diatoms are single-celled eukaryotic microalgae that are ubiquitously found in almost all aquatic ecosystems, and are characterized by their intricately structured SiO2 (silica)-based cell walls. Diatoms with a benthic life style are capable of attaching to any natural or man-made submerged surface, thus contributing substantially to both microbial biofilm communities and economic losses through biofouling. Surface attachment of diatoms is mediated by a carbohydrate- and protein- based glue, yet no protein involved in diatom underwater adhesion has been identified so far. In the present work, we have generated a normalized transcriptome database from the model adhesion diatom Amphora coffeaeformis. Using an unconventional bioinformatics analysis we have identified five proteins that exhibit unique amino acid sequences resembling the amino acid composition of the tyrosine-rich adhesion proteins from mussel footpads. Establishing the first method for the molecular genetic transformation of A. coffeaeformis has enabled investigations into the function of one of these proteins, AC3362, through expression as YFP fusion protein. Biochemical analysis and imaging by fluorescence microscopy revealed that AC3362 is not involved in adhesion, but rather plays a role in biosynthesis and/or structural stability of the cell wall. The methods established in the present study have paved the way for further molecular studies on the mechanisms of underwater adhesion and biological silica formation in the diatom A. coffeaeformis.

Purpose: Prior research has shown that individuals with traumatic brain injury (TBI) may be overconfident in their judgments of learning (JOLs; online measures of self-monitoring of learning and memory). JOLs had been presumed to be driven by explicit processes, but recent research has also revealed implicit memory involvement. Given that implicit learning mechanisms are often intact in those with TBI, the purpose of this study was to investigate whether priming and antipriming of immediate and delayed JOLs in individuals with TBI might affect their overconfidence., Method: A standard 3-field masked priming paradigm was combined with a paired-associate learning task with JOLs and administered to individuals with TBI and matched controls (18 per group). In each trial, a subliminal masked stimulus was immediately followed by supraliminal presentation of a word pair for study; participants also made immediate and delayed JOLs, with cued-recall testing 10 min after study and judgment., Results: Antipriming significantly lowered JOLs and overconfidence for both groups, whereas delaying JOLs significantly improved recall for both groups., Conclusions: The results suggest that JOLs may be influenced by subliminal implicit memory. Clinical implications include the possible use of antipriming to reduce overconfidence after brain injury and delaying JOLs to improve recall.

Coupled-cluster theory including single, double, and perturbative triple excitations [CCSD(T)] has been applied to trimers that appear in crystalline benzene in order to resolve discrepancies in the literature about the magnitude of non-additive three-body contributions to the lattice energy. The present results indicate a non-additive three-body contribution of 0.89 kcal mol(-1), or 7.2% of the revised lattice energy of -12.3 kcal mol(-1). For the trimers for which we were able to compute CCSD(T) energies, we obtain a sizeable difference of 0.63 kcal mol(-1) between the CCSD(T) and MP2 three-body contributions to the lattice energy, confirming that three-body dispersion dominates over three-body induction. Taking this difference as an estimate of three-body dispersion for the closer trimers, and adding an Axilrod-Teller-Muto estimate of 0.13 kcal mol(-1) for long-range contributions yields an overall value of 0.76 kcal mol(-1) for three-body dispersion, a significantly smaller value than in several recent studies.

Purpose: The psychometric properties of the college challenges sub-set from The College Survey for Students with Brain Injury (CSS-BI) were investigated with adults with and without traumatic brain injury (TBI)., Methods: Adults with and without TBI completed the CSS-BI. A sub-set of participants with TBI were interviewed, intentional and convergent validity were investigated, and the internal structure of the college challenges was analysed with exploratory factor analysis/principle component analysis., Results: Respondents with TBI understood the items describing college challenges with evidence of intentional validity. More individuals with TBI than controls endorsed eight of the 13 college challenges. Those who reported more health issues endorsed more college challenges, demonstrating preliminary convergent validity. Cronbach's alphas of >0.85 demonstrated acceptable internal reliability. Factor analysis revealed a four-factor model for those with TBI: studying and learning (Factor 1), time management and organization (Factor 2), social (Factor 3) and nervousness/anxiety (Factor 4). This model explained 72% and 69% of the variance for those with and without TBI, respectively., Conclusion: The college challenges sub-set from the CSS-BI identifies challenges that individuals with TBI face when going to college. Some challenges were related to two factors in the model, demonstrating the inter-connections of these experiences.

Purpose: This preliminary study explored differences between adults with and without traumatic brain injury (TBI) for speech processing accuracy, processing speed and effort in various conditions of interference., Methods: Ten adults with TBI and six adults without TBI participated. Speech processing was studied using sentence repetition in six listening conditions with different types of interference, including noise and two simultaneous talkers. Participants repeated sentences and rated effort. Participants also completed standardized tests of cognition, including working memory and processing speed measures., Results: Sentence repetition accuracy did not differ between groups. However, the TBI group demonstrated slower processing speed than the control group and also reported significantly greater effort in the two-talker condition. Faster processing speed was also correlated with higher accuracy in the two-talker condition., Conclusions: RESULTS of this study show group similarities in repetition accuracy across listening conditions, but group differences in speed and effort. This preliminary finding, as well as the relationship between processing speed and repetition accuracy, suggests that it is only in the most complex listening conditions that the effects of brain injury may be detectable.

Regina Kennedy, an architect and urbanist with a Master's degree in healthcare facility planning and design, who is currently a programme manager at Hamad Medical Corporation (HMC), the state of Qatar's 'premier' non-profit healthcare provider, examines how, during the design process, the right principles can be applied to ensure that hospitals and other healthcare facilities 'work' for all user groups.

Context: A broad analysis of adrenal gland-derived 19-carbon (C19) steroids has not been reported. This is the first study that uses liquid chromatography-tandem mass spectrometry to quantify 9 C19 steroids (androgens and their precursors), estrone, and estradiol in the adrenal vein (AV) of women, before and after ACTH stimulation., Objective: The objective of this study was to define the adrenal androgen metabolome in women before and after ACTH infusion., Design: This was a retrospective study., Patients: Seven women, aged 50.4 ± 5.4 years, with suspected diagnosis of an adrenal aldosterone-producing adenoma were included in the study., Methods: AV and iliac serum samples were collected before and after administration of ACTH (15 minutes). AV samples were analyzed using for concentrations of 9 unconjugated C19 steroids, estrone, and estradiol. Dehydroepiandrosterone sulfate (DHEA-S) was quantified by radioimmunoassay., Results: AV levels of DHEA-S were the highest among the steroids measured. The most abundant unconjugated C19 steroids in AV were 11β-hydroxyandrostenedione (11OHA), dehydroepiandrosterone (DHEA), and androstenedione (A4). ACTH significantly increased the adrenal output of 9 of the 12 steroids that were measured. ACTH increased the mean AV concentration of DHEA-S by 5-fold, DHEA by 21-fold, A4 by 7-fold, and 11OHA by 5-fold. 11β-Hydroxytestosterone and testosterone were found to be potent androgen receptor agonists when tested with an androgen-responsive cell reporter model., Conclusion: The current study indicates that the adrenal gland secretes primarily 3 weak androgens, namely DHEA, 11OHA, and A4. Active androgens, including testosterone and 11β-hydroxytestosterone, are also produced but to a lesser degree.

π-π interactions are integral to many areas of chemistry, biochemistry, and materials science. Here we use electronic structure theory to analyze how π-π interactions change as the π-systems are curved in model complexes based on coronene and corannulene dimers. Curvature redistributes electronic charge in the π-cloud and creates a dipole moment in these systems, leading to enhanced intermolecular electrostatic interactions in the concave-convex (nested) geometries that are the focus of this work. Curvature of both monomers also has a geometric effect on the interaction by decreasing the average C-C distance between monomers and by increasing the magnitude of both favorable London dispersion interactions and unfavorable exchange-repulsion interactions. Overall, increasing curvature in nested π-π interactions leads to more favorable interaction energies regardless of the native state of the monomers, except at short distances where the most highly curved systems are less favorable as exchange repulsion terms begin to dominate the interaction.

Background: Healthcare design is produced by large design teams with vital input from clients and expert consultants. Throughout the design process, choices are made based on evaluations by all parties; however, some of these evaluations cannot be reduced to a common metric. Many complex interactions defy objective evaluation. It is proposed that jointly agreed-on values can be deployed as moderators in subjective evaluations, allowing design teams to work together more harmoniously., Object: Design evidence base for one use-value: sleep. A literature review considers the evidence currently found regarding the value of sleep for hospital inpatients and the actual quality of inpatient sleep. Intrinsic and extrinsic reasons for shortened or poor sleep are reviewed, with an emphasis on environmental considerations. There are many manners in which designers and caregivers are aware that good sleeping conditions can be provided; therefore it is by choice, albeit unwittingly, that poor sleeping conditions have arisen., Conclusion: The value of sleep to hospital inpatients is very high, even in the short term. Inpatients' sleep is currently not as good as it could or should be. Conflicting views, varied constraints, and requirements might be harmonized and give way to successful innovation if design teams and project stakeholders adopt moderating values as a guide for design evaluations.

Context: Although steroid hormones produced by the adrenal gland play critical roles in human physiology, a detailed quantitative analysis of the steroid products has not been reported. The current study uses a single methodology (liquid chromatography-tandem mass spectrometry, LC-MS/MS) to quantify ten corticosteroids in adrenal vein (AV) samples pre- and post-adrenocorticotropic hormone (ACTH) stimulation., Design/methods: Three men and six women with a diagnosis of an adrenal aldosterone-producing adenoma (APA) were included in the study. Serum was collected from the iliac vein (IV) and the AV contralateral to the diseased adrenal. Samples were collected, before and after administration of ACTH. LC-MS/MS was then used to quantify serum concentrations of unconjugated corticosteroids and their precursors., Results: Prior to ACTH stimulation, the four most abundant steroids in AV were cortisol (90%), cortisone (4%), corticosterone (3%) and 11-deoxycortisol (0.8%). Post-ACTH administration, cortisol remained the major adrenal product (79%); however, corticosterone became the second most abundantly produced adrenal steroid (11%) followed by pregnenolone (2.5%) and 17α-hydroxypregnenolone (2%). ACTH significantly increased the absolute adrenal output of all ten corticosteroids measured (P < 0.05). The four largest post-ACTH increases were pregnenolone (300-fold), progesterone (199-fold), 17α-hydroxypregnenolone (187-fold) and deoxycorticosterone (82-fold)., Conclusion: Using LC-MS/MS, we successfully measured 10 corticosteroids in peripheral and AV serum samples under pre- and post-ACTH stimulation. This study demonstrates the primary adrenal steroid products and their response to ACTH., (© 2012 Blackwell Publishing Ltd.)

Androst-5-ene-3β,7β,17β-triol (βAET) is an anti-inflammatory metabolite of DHEA that is found naturally in humans, but in rodents only after exogenous DHEA administration. Unlike DHEA, C-7-oxidized DHEA metabolites cannot be metabolized into potent androgens or estrogens, and are not peroxisome proliferators in rodents. The objective of our current studies was to characterize the pharmacology of βAET to enable clinical trials in humans. The pharmacology of βAET was characterized by pharmacokinetics, drug metabolism, nuclear hormone receptor interactions, androgenicity, estrogenicity, and systemic toxicity studies. βAET's acute anti-inflammatory activity and immune modulating characteristics were measured in vitro in RAW264.7 cells and in vivo in murine models with parenteral administration. βAET was rapidly metabolized and cleared from circulation in mice and monkeys. βAET was weakly androgenic and estrogenic in immature rodents, but not bound by androgen, estrogen, progesterone, or glucocorticoid nuclear hormone receptors. βAET did not induce peroxisome proliferation, nor was it systemically toxic or trophic for sex hormone responsive tissues in mature rats and monkeys. βAET significantly attenuated acute inflammation both in vitro and in vivo, augmented immune responses in adult mice, and reversed immune senescence in aged mice. βAET may contribute to the anti-inflammatory activity in rodents attributed to DHEA. Unlike DHEA, βAET's anti-inflammatory activity cannot be ascribed to activation of PPARs, androgen, or estrogen nuclear hormone receptors. Exogenous βAET is unlikely to produce untoward toxicity or hormonal perturbations in humans., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To describe a program that integrates self-regulated learning theory with supported education for college students with traumatic brain injury using a dynamic coaching model; to demonstrate the feasibility of developing and implementing such a program; and to identify individualized outcomes., Design: Case study comparisons., Setting: University setting., Participants: Two severely injured students with cognitive impairments., Interventions: A dynamic coaching model of supported education which incorporated self-regulated learning was provided for students with traumatic brain injury while attending college., Outcomes: Outcomes were both short and long term including decontextualized standardized test scores, self-reported academic challenges, number and specificity of reported strategies, grades on assignments, number of credits completed versus attempted, and changes in academic status and campus life., Results: Students improved on graded assignments after strategy instruction and reported using more strategies by the end of the year. Students completed most of the credits they attempted, were in good academic standing, and made positive academic decisions. Performance on decontextualized tests pre- and postintervention was variable., Conclusions: It is feasible to deliver a hybrid supported education program that is dynamically responsive to individual students' needs and learning styles. Reasons for including both functional and standardized test outcomes are discussed.

The objectives of this study were to determine the prevalence of and factors associated with prenatal HIV screening and the availability of HIV test results in medical records in Pittsburgh, PA, USA. Three hundred postpartum women were surveyed about demographics and prenatal care provider(s) and practice setting and were asked to recall prenatal HIV screening and reasons for accepting or declining a HIV test. Medical records were reviewed for documentation of HIV results. Overall, 65% of women reported screening. White race, higher annual household income and fewer lifetime sexual partners were independently associated with decreased likelihood of prenatal HIV screening. Provider presentation of screening as standard practice and provider encouragement were associated with prenatal HIV screening. Only 38% of medical records contained HIV results at the time of labour. Universal and routine offering of prenatal HIV screening as standard practice, in conjunction with encouragement from health-care providers, may increase patient acceptability and the uptake of prenatal HIV screening.

A largely unsolved problem in computational biochemistry is the accurate prediction of binding affinities of small ligands to protein receptors. We present a detailed analysis of the systematic and random errors present in computational methods through the use of error probability density functions, specifically for computed interaction energies between chemical fragments comprising a protein-ligand complex. An HIV-II protease crystal structure with a bound ligand (indinavir) was chosen as a model protein-ligand complex. The complex was decomposed into twenty-one (21) interacting fragment pairs, which were studied using a number of computational methods. The chemically accurate complete basis set coupled cluster theory (CCSD(T)/CBS) interaction energies were used as reference values to generate our error estimates. In our analysis we observed significant systematic and random errors in most methods, which was surprising especially for parameterized classical and semiempirical quantum mechanical calculations. After propagating these fragment-based error estimates over the entire protein-ligand complex, our total error estimates for many methods are large compared to the experimentally determined free energy of binding. Thus, we conclude that statistical error analysis is a necessary addition to any scoring function attempting to produce reliable binding affinity predictions.

17α-Ethynyl-androst-5ene-3β, 7β, 17β-triol (HE3286) is an orally bioavailable analogue of androst-5-ene-3β,7β,17β-triol, a non-glucocorticoid anti-inflammatory metabolite of the adrenal steroid, dehydroepiandrosterone. The pharmacology of HE3286 was characterized in preparation for clinical trials in type 2 diabetes mellitus and other diseases of inflammation. Interactions with nuclear hormone receptors and P450 enzymes were measured in vitro. Drug metabolism was studied preclinically in mice, rats, dogs, and monkeys. Neurological and cardiopulmonary safety and dose-ranging and chronic toxicity studies were conducted in rats and dogs in accordance with FDA guidelines. Pharmacokinetics and metabolites were measured in Phase I clinical trials. HE3286 was differentially metabolized between species. HE3286 and metabolites did not bind or transactivate steroid binding nuclear hormone receptors or inhibit P450 enzymes. There were no adverse effects in safety pharmacology and canine toxicology studies. Although HE3286 did not elicit systemic toxicity in rats, mild estrogenic effects were observed, but without apparent association to hormonal changes. Safety margins were greater than 20-fold in rats and dogs with respect to the most commonly used clinical dose of 10 mg/day. The terminal half-life in humans was 8 hours in males and 5.5 hours in females. HE3286 is the first derivative of the DHEA metabolome to undergo a comprehensive pharmacological and safety evaluation. The results of these investigations have shown that HE3286 has a low potential for toxicity and possesses pharmacological properties generally suitable for use in human medicine. The favorable profile of HE3286 warrants further exploration of this new class of anti-inflammatory agents.

Two natural 5-androstene steroid tetrols, androst-5-ene-3β,7β,16α,17β-tetrol (HE3177) and androst-5-ene-3α,7β,16α,17β-tetrol (HE3413), were discovered in human plasma and urine. These compounds had significant aqueous solubility, did not bind or transactivate steroid-binding nuclear hormone receptors, and were not immunosuppressive in murine mixed-lymphocyte studies. Both compounds appear to be metabolic end products, as they were resistant to primary and secondary metabolism. Both were orally bioavailable, and were very well tolerated in a two-week dose-intensive toxicity study in mice. Anti-inflammatory properties were found with exogenous administration of these compounds in rodent disease models of multiple sclerosis, lung injury, chronic prostatitis, and colitis., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Primary Objective: This study explored whether adults with and without traumatic brain injury (TBI) adjust their judgements of learning (JOLs) over the course of a verbal learning task., Research Design: Regression analyses were performed of JOLs and recall over time, for both group means and individual performance., Procedures: Twenty adults with TBI and 16 healthy controls studied lists of noun-pairs, making Likert scale JOLs for each item during the study phase. Half of the JOLs were made immediately following item study; the other half after several minutes delay. Recall was tested for each list after all JOLs were complete., Outcomes: Analyses revealed significant differences between participants with TBI and controls in how JOLs changed over time. As a group, TBI survivors increased JOLs over the course of the learning experiment in the delayed condition, whereas the control group decreased JOL predictions in the immediate condition., Conclusions: These results support previous work showing that metamemory abilities of adults with TBI are heterogeneous, but show some differences from those of healthy adults. Possible explanations are derived from Koriat's findings that, with practice, individuals tend to shift toward basing metamemory predictions on mnemonic cues rather than cues intrinsic to task items.

New impact craters at five sites in the martian mid-latitudes excavated material from depths of decimeters that has a brightness and color indicative of water ice. Near-infrared spectra of the largest example confirm this composition, and repeated imaging showed fading over several months, as expected for sublimating ice. Thermal models of one site show that millimeters of sublimation occurred during this fading period, indicating clean ice rather than ice in soil pores. Our derived ice-table depths are consistent with models using higher long-term average atmospheric water vapor content than present values. Craters at most of these sites may have excavated completely through this clean ice, probing the ice table to previously unsampled depths of meters and revealing substantial heterogeneity in the vertical distribution of the ice itself.

Context: The human adrenal gland produces small amounts of testosterone that are increased under pathological conditions. However, the mechanisms through which the adrenal gland produces testosterone are poorly defined., Objective: Our objective was to define the role of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) in human adrenal production of testosterone., Design and Methods: Adrenal vein sampling was used to confirm ACTH stimulation of adrenal testosterone production. Adrenal expression of AKR1C3 was studied using microarray, quantitative real-time RT-PCR, and immunohistochemical analyses. AKR1C3 knockdown was accomplished in cultured adrenal cells (H295R) using small interfering RNA, followed by measurement of testosterone production., Results: Acute ACTH administration significantly increased adrenal vein testosterone levels. Examination of the enzymes required for the conversion of androstenedione to testosterone using microarray analysis, quantitative real-time RT-PCR, and immunohistochemistry demonstrated that AKR1C3 was present in the adrenal gland and predominantly expressed in the zona reticularis. Decreasing adrenal cell expression of AKR1C3 mRNA and protein inhibited testosterone production in the H295R adrenal cell line., Conclusions: The human adrenal gland directly secretes small, but significant, amounts of testosterone that increases in diseases of androgen excess. AKR1C3 is expressed in the human adrenal gland, with higher levels in the zona reticularis than in the zona fasciculata. AKR1C3, through its ability to convert androstenedione to testosterone, is likely responsible for adrenal testosterone production.

Objectives: In a previous investigation, we observed altered expression of sepiapterin reductase (SPR) in cultured neural cells chronically exposed to paroxetine. SPR is an enzyme, which catalyzes the final step in the synthesis of tetrahydrobiopterin (BH4). BH4 is an essential cofactor for synthesis of many neurotransmitters including serotonin. Given the pivotal role of SPR in neurotransmitter production, we sought to test the hypothesis that SPR would influence susceptibility to mood disorders and patient response to antidepressants., Methods: We tested for association of SPR promoter polymorphisms with antidepressant response in a well-characterized triad cohort of mood disorders. We evaluated the functional effect of these variants using the Dual-Luciferase Reporter Gene Assay System in two independent cell lines., Results: Two promoter single nucleotide polymorphisms (rs1876487 and rs2421095) in SPR were identified that occurred in three distinct haplotypes. We found a statistically significant association of haplotype pair 2,3 with bipolar I disorder [odds ratio: 5.47; 95% confidence interval: (1.68-17.88); P<0.005] and the personality measure self-transcendence (P = 0.020). Moreover, we found preliminary evidence that individuals with haplotype pair 2,3 responded better to the treatment with selective serotonin reuptake inhibitors. Reporter gene assays revealed a 1.4-fold to 1.6-fold decrease in the transcription rate of the two less common haplotypes (2 and 3) compared with haplotype 1, in the two cell lines investigated., Conclusion: This reduced transcription rate for SPR promoter haplotypes 2 and 3 may impact on BH4-mediated neurotransmitter production, thus suggesting a biological process through which SPR gene variants might influence antidepressant response and susceptibility to bipolar disorder.

Background: Serologic assays that identify herpes simplex type 2 (HSV-2) type-specific antibodies have been commercially available for more than a decade. Greater acceptance of these tests is hindered by uncertainty regarding their performance in real-world clinical settings., Objectives: The primary objective was to compare the test characteristics of the Focus HerpeSelect Express Assay (EA) versus the Focus HerpeSelect enzyme linked immunoassay (ELISA) for detection of HSV-2 type-specific antibodies among pregnant women enrolled from 3 geographic sites with varying prevalences of HSV-2 infection. A second objective was to evaluate the performance of a HSV-2 testing strategy in which EA screens and ELISA confirms HSV-2 serodiagnosis., Study Design: We enrolled 399 pregnant women from Atlanta, GA, Moorestown, NJ, and Pittsburgh, PA into this cross-sectional investigation. Capillary whole blood was obtained from study participants, and evaluated for the presence of type-specific HSV-2 antibodies using the EA. Serum samples were also obtained from all study participants for subsequent identification of HSV-2 type-specific antibodies using both ELISA and the Focus Immunoblot assays., Results: We observed 96.2% agreement between results obtained with EA and ELISA. Overall, when compared to ELISA results, the sensitivity of EA for detection of HSV-2 type-specific antibodies was 94.2% and the specificity was 97.1%. Using Immunoblot results as our standard for performance calculations, the positive predictive value (PPV) of HSV-2 serodiagnosis increased from 91.7% to 98.2% when ELISA was used to confirm EA testing., Conclusions: EA provides similar results to ELISA for the identification of HSV-2 type-specific antibodies among pregnant women. As use of the point-of-care (POC) EA in conjunction with confirmatory ELISA testing improves the PPV of HSV-2 serodiagnosis compared to the use of EA or ELISA testing alone, validation of this diagnostic algorithm in other at-risk populations may be warranted.

Diffusion tensor imaging was used to investigate white matter (WM) integrity in adults with traumatic brain injury (TBI) and healthy adults as controls. Adults with TBI had sustained severe vehicular injuries on the average of 7 years earlier. A multivariate analysis of covariance with verbal IQ as the covariate revealed that adults with TBI had lower fractional anisotropy and higher mean diffusivity than controls, specifically in the three regions of interest (ROIs), the centrum semiovale (CS), the superior frontal (SPF), and the inferior frontal (INF). Adults with TBI averaged in the normal range in motor speed and two of three executive functions and were below average in delayed verbal recall and inhibition, whereas controls were above average. Time since injury, but not age, was associated with WM changes in the SPF ROI, whereas age, but not time since injury, was associated with WM changes in the INF ROI, suggesting that the effects of WM on time since injury may interact with age. To understand the utility of WM changes in chronic recovery, larger sample sizes are needed to investigate associations between cognition and WM integrity of severely injured individuals who have substantial cognitive impairment compared to severely injured individuals with little cognitive impairment. (JINS, 2009, 15, 130-136.).

A systematic review of studies that focused on the executive functions of problem solving, planning, organising and multitasking by adults with traumatic brain injury (TBI) was performed through 2004. Qualitative and quantitative methods were used to evaluate the 15 studies that met inclusion criteria. Demographic variables, design and intervention features, and impairment and activity/participation outcomes (ICF) (World Health Organization, 2001) were documented. Five randomised control treatment (RCT) studies used step-by-step, metacognitive strategy instruction (MSI) and outcomes were evaluated in a meta-analysis. Effect sizes (ESs) from immediate impairment outcomes after MSI and "control" intervention were similar to each other, and both were significantly larger than chance. ESs from immediate activity/participation outcomes after MSI were significantly larger than the ESs from control intervention, and both were significantly larger than chance. These results, along with positive outcomes from the other group, single-subject design and single case studies, provided sufficient evidence to make the clinical recommendation that MSI should be used with young to middle-aged adults with TBI, when improvement in everyday, functional problems is the goal (Level A) (American Academy of Neurology, 2004). Although maintenance effects were generally positive, there was insufficient data quantitatively to evaluate this. Furthermore, there was insufficient evidence to make clinical recommendations for children or older adults. Intervention that trained verbal reasoning and multi-tasking was promising, although the evidence is insufficient to make clinical recommendations at this time. Additional research needs were highlighted.

For many with traumatic brain injury (TBI), going to college is a realistic goal; however there is little documentation of the challenges faced by those with TBI who attend college. The primary purposes of this study were to document the academic challenges (studying, in-class experiences, time management, psychosocial aspects) reported by adults with TBI, and to investigate relationships between these challenges and the physical, cognitive and psychosocial consequences of TBI. An electronic anonymous survey was distributed. Of the 35 respondents with TBI, nearly all reported the need to review material more and a majority reported that others do not understand their problems. In-class experiences of being nervous before tests, forgetting what is said in class, and getting overwhelmed in class were also reported by a majority. Those who reported more physical, cognitive and psychosocial consequences of their injury also identified more academic challenges as well, although cognitive consequences alone predicted academic challenges better than all of the consequences combined. Psychosocial aspects also predicted academic challenges to a lesser extent. In spite of these findings, nearly half of the respondents had not heard of or had never accessed campus disability services. To develop effective on-campus service delivery models, additional research is needed to understand why students do or do not make use of existing services.