Hybrid RPA:DFT Approach for Adsorption on Transition Metal Surfaces: Methane and Ethane on Platinum (111).

The hybrid QM:QM approach is extended to adsorption on transition metal surfaces. The random phase approximation (RPA) as the high-level method is applied to cluster models and, using the subtractive scheme, embedded in periodic models which are treated with density functional theory (DFT) that is the low-level method. The PBE functional, both without dispersion and augmented with the many-body dispersion (MBD), is employed. Adsorption of methane and ethane on the Pt(111) surface is studied. For methane in a 2 × 2 surface cell, the hybrid RPA:PBE and RPA:PBE+MBD results, -14.3 and -16.0 kJ mol-1, respectively, are in close agreement with the periodic RPA value of -13.8 kJ mol-1 at significantly reduced computational cost (factor of ∼50). For methane and ethane, the RPA:PBE results (-14.3 and -17.8 kJ mol-1, respectively) indicate underbinding relative to energies derived from experimental desorption barriers for relevant loadings (-15.6 ± 1.6 and -27.2 ± 2.9 kJ mol-1, respectively), whereas the hybrid RPA:PBE+MBD results (-16.0 and -24.9 kJ mol-1, respectively) agree with the experiment well within experimental uncertainty limits (deviation of -0.4 ± 1.5 and +2.3 ± 2.9 kJ mol-1, respectively). Finding a cluster that adequately and robustly represents the adsorbate at the bulk surface is important for the success of the RPA-based QM:QM scheme for metals.

Adsorption of CH4 on the Pt(111) surface: Random phase approximation compared to density functional theory.

We investigate the adsorption of CH4 on the Pt(111) surface for two adsorption modes, hcp (hexagonal closed packed) hollow tripod and top monopod in a (√3 × âˆš3)R30° surface cell that corresponds to experimental surface coverage. Surface structures are optimized with density functional theory using the Perdew-Burke-Ernzerhof (PBE) functional augmented with the many-body dispersion scheme of Tkatchenko (PBE+MBD). Whereas the Random Phase Approximation (RPA) predicts a clear preference of about 5 kJ mol-1 for the hcp tripod compared to the top monopod structure, in agreement with vibrational spectra, PBE+MBD predicts about equal stability for the two adsorption structures. For the hcp tripod, RPA yields an adsorption energy of -14.5 kJ mol-1, which is converged to within 1.0 ± 0.5 kJ mol-1 with respect to the plane wave energy cutoff (500 eV), the k-point mesh (4 × 4 × 1), the vacuum layer (about 10.3 Å, with extrapolation to infinite distance), and the number of Pt layers (3). Increments for increasing the number of Pt layers to 4 (+1.6 kJ mol-1) and the k-point mesh to 6 × 6 × 1 (-0.6 kJ mol-1) yield a final estimate of -13.5 ± 2.1 kJ mol-1, which agrees to within 2.2 ± 2.1 kJ mol-1 with experiment (-15.7 ± 1.6), well within the chemical accuracy range.

Culture-independent multilocus sequence typing of Pseudomonas aeruginosa for cross-infection screening.

The genotyping of pathogens within cystic fibrosis cohorts is an important process, enabling the detection of transmissible and clinically-important strains. Traditionally this has been via culture-dependent processes. However, culture-independent investigation of respiratory samples is becoming more common, with such approaches highlighting the limitations of culture-based methods. In this study we describe the culture-independent application of multilocus sequence typing (MLST) for Pseudomonas aeruginosa, performed on DNA extracted from the sputa of cystic fibrosis patients. We compare the output to conventional culture-dependent MLST applied to the same samples and demonstrate high concordance. Culture-independent MLST enabled genotyping of culture-negative samples in patients from whom P. aeruginosa was intermittently isolated, and revealed the hidden presence of transmissible strains. Culture-independent MLST is also capable of highlighting samples containing multiple strains, albeit inconsistently. We conclude that culture-independent MLST can be a useful genotyping tool for screening cohorts and identifying patients that warrant further detailed investigation.

The feasibility of online video calling to engage patients with cystic fibrosis in exercise training.

INTRODUCTION: Physical activity, including structured exercise, is an essential component in the management of cystic fibrosis. The use of telehealth such as video-calling may be a useful method for the delivery of exercise and physical activity interventions, though the feasibility of this remains unknown. METHODS: Nine patients with cystic fibrosis (three female, six male, 30.9 ± 8.7 years) volunteered to participate. Participants completed an eight-week exercise training intervention conducted via Skype, using personalised exercises, with all sessions supervised by an exercise therapist. Feasibility was assessed by demand, implementation, practicality and acceptability. Changes in anthropometric, pulmonary, physical activity and quality of life variables were also assessed. RESULTS: Two male participants withdrew from the study, citing lack of available time. The remaining participants found use of Skype useful, with a mean satisfaction rating of 9/10, and three participants requesting to continue the sessions beyond the duration of the study. Mean compliance with sessions was 68%, with mean duration of sessions being 20 min. A total of 25% of calls suffered from technical issues such as video or audio lags. Anthropometric, pulmonary, physical activity and quality of life variables remained unchanged over the course of the study period. DISCUSSION: The use of Skype to deliver an exercise intervention to patients withcystic fibrosis was found to be technologically feasible, and acceptable among participants. Findings have implications for clinical practice and could allow care teams to engage patients remotely in exercise. Further research is required to assess the efficacy of this modality on increasing physical activity and associated health outcomes.

Molecular epidemiology of Pseudomonas aeruginosa in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort.

While Pseudomonas aeruginosa (PA) cross-infection is well documented among patients with cystic fibrosis (CF), the equivalent risk among patients with non-CF bronchiectasis (NCFB) is unclear, particularly those managed alongside patients with CF. We performed analysis of PA within a single centre that manages an unsegregated NCFB cohort alongside a segregated CF cohort. We found no evidence of cross-infection between the two cohorts or within the segregated CF cohort. However, within the unsegregated NCFB cohort, evidence of cross-infection was found between three (of 46) patients. While we do not presently advocate any change in the management of our NCFB cohort, longitudinal surveillance is clearly warranted.

Identification, optimization, and pharmacology of acylurea GHS-R1a inverse agonists.

Ghrelin plays a major physiological role in the control of food intake, and inverse agonists of the ghrelin receptor (GHS-R1a) are widely considered to offer utility as antiobesity agents by lowering the set-point for hunger between meals. We identified an acylurea series of ghrelin modulators from high throughput screening and optimized binding affinity through structure-activity relationship studies. Furthermore, we identified specific substructural changes, which switched partial agonist activity to inverse agonist activity, and optimized physicochemical and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS penetrant inverse agonist 38 (AZ-GHS-38). Free feeding efficacy experiments showed that CNS exposure was necessary to obtain reduced food intake in mice, and it was demonstrated using GHS-R1a null and wild-type mice that this effect operates through a mechanism involving GHS-R1a.

Adolescent depression: an update and guide to clinical decision making.

Depression in adolescence and adulthood is common, afflicting up to 20 percent of these populations. It represents a significant public health concern and is associated with considerable suffering and functional impairment. Adolescent-onset depression tends to be a particularly malignant and recalcitrant condition, increasing the likelihood of recurrence and chronicity in adulthood. Clinical presentations for various medical and psychiatric conditions, as well as reactions to psychosocial stressors, can mimic or confound the picture of depression in adolescents. Therefore, careful assessment and differential diagnosis is essential. Effective treatments, both pharmacological and psychosocial in nature, exist, and so early detection and intervention is paramount. This article presents an overview of optimal prevention, assessment, and clinical decision-making strategies for managing depression in adolescents.

Zinc therapy for night blindness in cystic fibrosis.

This is the first report of a supplemented CF patient presenting with clinical vitamin A deficiency to be successfully treated with zinc therapy alone. Therefore in addition to retinol supplementation, normalizing serum zinc levels may be important in maintaining the vitamin A status of CF patients. The interactions and synergistic effects between the two micronutrients are discussed.

Nonsuicidal Self injury in Adolescents.

Nonsuicidal self injury (NSSI) is more common in adolescent and young adult populations than previously thought. Although it is important to assess the associated risk of suicidal behavior, NSSI is generally used to cope with distressing negative affective states, especially anger and depression, and mixed emotional states. Although previously believed to be a characteristic of severe psychopathology, it now appears that NSSI is associated with a wide variety of externalizing and internalizing conditions. Effective treatment is grounded in a collaborative understanding of the function of the NSSI for the adolescent. Affective, psychosocial, biological and cognitive factors are addressed through psychotherapeutic, psychopharmacological and skill-building strategies appropriate for each individual.

Treating persistent adolescent aggression.

Adolescent aggressive behavior is a frequently encountered problem for clinicians and society as a whole. Better understanding of biological, social, and familial risk factors for maladaptive aggressive behavior may lead to more effective interventions. The social information processing problems characteristic of this group interfere with treatment and outcome. Although further studies are needed, evidence for the effectiveness of psychopharmacologic treatments is increasing. There is also evidence for several effective psychotherapeutic interventions, especially for those with affective/impulsive aggression. Knowledge of risk factors, psychosocial strategies, and psychopharmacologic treatments can enhance the clinician's ability to intervene with this difficult group.

Understanding cystic-fibrosis-related diabetes: best thought of as insulin deficiency?

The limited available evidence supports the use of insulin treatment in CFRD. This fits with the dominant problem in CFRD being insulin deficiency and progressive beta cell dysfunction, making tablets that stimulate the beta cell unlikely to be a successful strategy. It is possible that patients with IGT or CFRD with moderate hyperglycaemia (e.g. relative preservation of fasting glucose) may initially respond to beta cell secretagogues. A large randomized prospective trial in the USA should answer this point in the next few years.

Lung volume reduction surgery in a ventilator-dependent patient.

In recent years lung volume reduction surgery (LVRS) has been advocated in a selected group of severe chronic obstructive pulmonary disease (COPD) patients. There are few reports of successful surgical intervention on ventilator-dependent patients. We present our own experience with a 53-year-old male who suffered an acute exacerbation of COPD and who could not be weaned off ventilation after 22 days. He underwent bilateral LVRS after which he was successfully weaned from ventilation. He is alive 4 years later with a satisfactory quality of life.