Structure of a Model Dye/Titania Interface: Geometry of Benzoate on Rutile-TiO2 (110)(1 x 1)

Scanned-energy mode photoelectron diffraction (PhD) and ab initio density functional theory calculations have been employed to investigate the adsorption geometry of benzoate ([C6H5COO]−) on rutile-TiO2(110)(1 × 1). PhD data indicate that the benzoate moiety binds to the surface through both of its oxygen atoms to two adjacent fivefold surface titanium atoms in an essentially upright geometry. Moreover, its phenyl (C6H5−) and carboxylate ([−COO]−) groups are determined to be coplanar, being aligned along the [001] azimuth. This experimental result is consistent with the benzoate geometry emerging from DFT calculations conducted for laterally rather well-separated adsorbates. At shorter interadsorbate distances, the theoretical modeling predicts a more tilted and twisted adsorption geometry, where the phenyl and carboxylate groups are no longer coplanar; i.e., interadsorbate interactions influence the configuration of adsorbed benzoate

Temporal evolution of sweet oilfield corrosion scale: Phases, morphologies, habits, and protection

Electrochemical measurements and substrate analysis have been employed to study the corrosion of iron in sweet solution (pH = 6.8, T = 80 °C) over a period of 288 h. Correlated with decreasing corrosion rate, diffraction, microscopy, and spectroscopy data reveal the evolution of adhered sweet corrosion scale. Initially, it is comprised of two phases, siderite and chukanovite, with the latter affording little substrate protection. Subsequently, as the scale becomes highly protective, siderite is the sole component. Notably, siderite crystals are concluded to display a somewhat unexpected habit, which may be a trigger for local breakdown of protective sweet scales

Protective Efficacy of Menthol Propylene Glycol Carbonate Compared to N, N-diethyl-Methylbenzamide Against Mosquito Bites in Northern Tanzania.

The reduction of malaria parasite transmission by preventing human-vector contact is critical in lowering disease transmission and its outcomes. This underscores the need for effective and long lasting arthropod/insect repellents. Despite the reduction in malaria transmission and outcomes in Tanzania, personal protection against mosquito bites is still not well investigated. This study sought to determine the efficacy of menthol propylene glycol carbonate (MR08), Ocimum suave as compared to the gold standard repellent N, N-diethyl-methylbenzamide (DEET), either as a single dose or in combination (blend), both in the laboratory and in the field against Anopheles gambiae s.l and Culex quinquefasciatus. In the laboratory evaluations, repellents were applied on one arm while the other arm of the same individual was treated with a base cream. Each arm was separately exposed in cages with unfed female mosquitoes. Repellents were evaluated either as a single dose or as a blend. Efficacy of each repellent was determined by the number of mosquitoes that landed and fed on treated arms as compared to the control or among them. In the field, evaluations were performed by human landing catches at hourly intervals from 18:00  hr to 01:00  hr. A total of 2,442 mosquitoes were collected during field evaluations, of which 2,376 (97.30%) were An. gambiae s.l while 66 (2.70%) were Cx. quinquefaciatus. MR08 and DEET had comparatively similar protective efficacy ranging from 92% to 100 for both single compound and blends. These findings indicate that MR08 has a similar protective efficacy as DEET for personal protection outside bed nets when used singly and in blends. Because of the personal protection provided by MR08, DEET and blends as topical applicants in laboratory and field situations, these findings suggest that, these repellents could be used efficiently in the community to complement existing tools. Overall, Cx. quinquefasciatus were significantly prevented from blood feeding compared to An. gambiae s.l. The incorporation of these topical repellents for protection against insect bites can be of additional value in the absence or presence of IRS and ITNs coverage. However, a combination of both the physical (bed nets) and the repellent should be used in an integrated manner for maximum protection, especially before going to bed. Additional research is needed to develop repellents with longer duration of protection

Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration : A Novel Regression Analysis to Capture the Bilateral Nature of the Disease

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited

Lessons from SARS: A retrospective study of outpatient care during an infectious disease outbreak

<p>Abstract</p> <p>Background</p> <p>During severe acute respiratory syndrome (SARS) outbreak in Toronto, outpatient clinics at SickKids Hospital were closed to prevent further disease transmission. In response, a decision was made by the neonatal neuro-developmental follow up (NNFU) clinic staff to select patients with scheduled appointments to have a mail/telephone assessment using Ages and Stages Questionnaire (ASQ) or to postpone/skip their visit. The objective of this study was to compare the developmental assessment and its outcome in two groups of NNFU clinic patients, SARS versus non-SARS, over three standard clinic appointments.</p> <p>Methods</p> <p>We compared the diagnostic accuracy (identification of developmental delay), and patient management (referral for therapy or communication of a new diagnosis) of the strategies used during SARS, April/May 2003, to the standard assessment methods used for patients seen in April/May 2005 (non-SARS). In all cases data were obtained for 3 patient visits: before, during and after these 2 months and were compared using descriptive statistics.</p> <p>Results</p> <p>There were 95 patients in the SARS group and 99 non-SARS patients. The gestational age, sex, entry diagnosis and age at the clinic visit was not different between the groups. The NNFU clinic staff mailed ASQ to 27 families during SARS, 17 (63%) were returned, and 8 of the 17 were then contacted by telephone. Criteria used to identify infants at risk selected for either mailed ASQ or phone interviews were not clearly defined in the patients' charts. There was a significant under identification of developmental delay during SARS (18% versus 45%). Of those who responded to the mailed questionnaire, referrals for therapy rates were similar to non-SARS group. The lost to follow up rate was 24% for the SARS group compared with 7% for non-SARS. There was no difference in the overall rate of developmental delay in the two groups as identified at the 'after' visit.</p> <p>Conclusions</p> <p>Poor advanced planning led to a haphazard assessment of patients during this infectious disease outbreak. Future pandemic plans should consider planning for outpatient care as well as in hospital management of patients.</p

Reduction in Fracture Rate and Back Pain and Increased Quality of Life in Postmenopausal Women Treated with Teriparatide: 18-Month Data from the European Forsteo Observational Study (EFOS)

The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and health-related quality of life (HRQoL, EQ-5D) were assessed. Spontaneous reports of adverse events were collected. All 1,648 enrolled women were teriparatide treatment-naive, 91.0% of them had previously received other anti-osteoporosis drugs, and 72.8% completed the 18-month study. A total of 168 incident clinical fractures were sustained by 138 (8.8%) women (821 fractures/10,000 patient-years). A 47% decrease in the odds of fracture in the last 6-month period compared to the first 6-month period was observed (P < 0.005). Mean back pain VAS was reduced by 25.8 mm at end point (P < 0.001). Mean change from baseline in EQ-VAS was 13 mm by 18 months. The largest improvements were reported in the EQ-5D subdomains of usual activities and pain/discomfort. There were 365 adverse events spontaneously reported, of which 48.0% were considered related to teriparatide; adverse events were the reason for discontinuation for 79 (5.8%) patients. In conclusion, postmenopausal women with severe osteoporosis who were prescribed teriparatide in standard clinical practice had a significant reduction in the incidence of fragility fractures and a reduction in back pain over an 18-month treatment period. This was associated with a clinically significant improvement in HRQoL. Safety was consistent with current prescribing information. These results should be interpreted in the context of the open-label, noncontrolled design of the study

Evaluation of a student-run smoking cessation clinic for a medically underserved population

<p>Abstract</p> <p>Background</p> <p>Smoking is common among medically underserved populations. Accessible resources to encourage and support smoking cessation among these patients are limited. Volunteer medical student-run free smoking cessation clinics may provide an effective option to help these individuals achieve smoking abstinence. In order to demonstrate the feasibility and cost-effectiveness of a student-run clinic, we analyzed a case series of patients receiving care in a medical student-run Smoking Cessation Clinic (SCC) at the Rochester, Minnesota Salvation Army Good Samaritan Health Clinic (GSHC).</p> <p>Findings</p> <p>Between January 2005 and March 2009, 282 cigarette smokers seeking care at the SCC were analyzed. Student providers at the SCC conducted 1652 weekly individual counseling sessions averaging 18 minutes per encounter. Patients were offered a choice of pharmacotherapies including nicotine replacement therapy (NRT), bupropion, and varenicline for up to 12 weeks. Smoking abstinence was confirmed with exhaled carbon monoxide (CO). Thirty-two patients completed the entire 12-week program (11.3%). At last contact, 94 patients (33.3%) abstained from smoking for ≥ 7 days and 39 patients (13.8%) were continuously abstinent for ≥ 4 weeks. The 7-day point prevalence abstinence rates at last contact were 58.6% for varenicline, 41.2% for bupropion, 33.9% for NRT, and 23.5% for bupropion and NRT. Analyzing missing patients as smoking, the 7-day point prevalence abstinence rates were 7.1%, 8.9%, and 8.2%, at 1 month, 2 months, and 3 months after program enrollment, respectively. No serious adverse drug reactions were recorded.</p> <p>Conclusions</p> <p>Our medical student-run smoking cessation clinic provided an effective and safe experience for medically underserved patients who might not otherwise have access to conventional smoking cessation programs because of high cost, lack of insurance, or other disparities. Similar medical student initiatives focusing on healthy lifestyles may be feasible and beneficial for individuals with limited access to healthcare resources.</p

Regulation of Adipocyte 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) by CCAAT/Enhancer-Binding Protein (C/EBP) β Isoforms, LIP and LAP

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses intracellular regeneration of active glucocorticoids, notably in liver and adipose tissue. 11β-HSD1 is increased selectively in adipose tissue in human obesity, a change implicated in the pathogenesis of metabolic syndrome. With high fat (HF)-feeding, adipose tissue 11β-HSD1 is down-regulated in mice, plausibly to counteract metabolic disease. Transcription of 11β-HSD1 is directly regulated by members of the CCAAT/enhancer binding protein (C/EBP) family. Here we show that while total C/EBPβ in adipose tissue is unaltered by HF diet, the ratio of the C/EBPβ isoforms liver-enriched inhibitor protein (LIP) and liver-enriched activator protein (LAP) (C/EBPβ-LIP:LAP) is increased in subcutaneous adipose. This may cause changes in 11β-HSD1 expression since genetically modified C/EBPβ(+/L) mice, with increased C/EBPβ-LIP:LAP ratio, have decreased subcutaneous adipose 11β-HSD1 mRNA levels, whereas C/EBPβΔuORF mice, with decreased C/EBPβ-LIP:LAP ratio, show increased subcutaneous adipose 11β-HSD1. C/EBPβ-LIP:LAP ratio is regulated by endoplasmic reticulum (ER) stress and mTOR signalling, both of which are altered in obesity. In 3T3-L1 adipocytes, 11β-HSD1 mRNA levels were down-regulated following induction of ER stress by tunicamycin but were up-regulated following inhibition of mTOR by rapamycin. These data point to a central role for C/EBPβ and its processing to LIP and LAP in transcriptional regulation of 11β-HSD1 in adipose tissue. Down-regulation of 11β-HSD1 by increased C/EBPβ-LIP:LAP in adipocytes may be part of a nutrient-sensing mechanism counteracting nutritional stress generated by HF diet