1,1ʹ-Bis(ortho-carborane) : ruthenium chelates, phosphines and tether derivatives

Chapter one provides a brief exposition on the history and importance of boron and carboranes and introduces 1,1ʹ-bis(o-carborane). It also provides literature examples of 1,1ʹ-bis(o-carborane) chelates, 1,1ʹ-bis(o-carboranyl)phosphines and tethered 1,1ʹ-bis(o carboranes). Chapter two discusses the reaction between dilithiated 1,1ʹ-bis(o-carborane) and di halogenated ruthenium compounds to afford several new compounds of the formula [Ru(κ2/3-2,2ʹ(3ʹ)-{1-(1ʹ-1ʹ,2ʹ-closo-C2B10H10)-1,2-closo-C2B10H10})(L)]. The first compound prepared, whereby L = p-cymene, reacts with either PPh3 or dppe and shows unusual displacement of the p-cymene ligand and a change in the bonding mode of 1,1ʹ bis(o-carborane). The fully saturated (MeCN or CO) derivatives of these compounds are also synthesised and studied, some of which are excellent examples of illustrating the structural trans effect. The initial {Ru(p-cymene)} was tested as a catalyst and displayed good Lewis acid catalytic activity of a Diels-Alder cycloaddition. Chapter three explores two carboranylphosphines [µ-2,2ʹ-PR-{1-(1ʹ-1ʹ,2ʹ-closo C2B10H10)-1,2-closo-C2B10H10}], where R = Et or Ph. Two-dimensional NMR spectroscopy and DFT calculations are used to explain an unusual lack of observed 2JPH coupling in the 1H NMR spectrum of the ethyl derivative. Their subsequent reactions with {AuCl} and {Se} are also discussed as they provide a route to identifying the steric bulk and electronic properties of these carboranylphosphines. Chapter four discusses one new tethered 1,1ʹ-bis(o-carborane) and its comparison with non-carborane analogues. A known tethered carborane is also synthesised and its single decapitation and metalation with {Ru(p-cymene)} explored producing the desired 12 vertex ruthenacarborane/12-vertex carborane but also an unusual 13-vertex diruthenacarborane/12-vertex carborane. Chapter five gives all the synthetic and analytical details for the compounds discussed. Appendix one provides crystallographic tables and appendix two provides all the crystallographic information on a CD. Appendix three includes copies of all published work related to this thesis (to date)

Knowledge, attitudes, and reported practices among obstetrician-gynecologists in the USA regarding antibiotic prescribing for upper respiratory tract infections.

BACKGROUND: Knowledge, attitudes, and practices regarding antibiotic prescribing for upper respiratory tract infections (URIs) have not been well described among obstetrician-gynecologists (OB/GYNs). This information is useful for determining whether an OB/GYN-specific program promoting appropriate antibiotic use would significantly contribute to the efforts to decrease inappropriate antibiotic use among primary care providers. METHODS: An anonymous questionnaire asking about the treatment of URIs was sent to 1031 obstetrician-gynecologists. RESULTS: The overall response rate was 46%. The majority of respondents (92%) were aware of the relationship between antibiotic use and antibiotic resistance, and respondents estimated that 5% of their patients had URI symptoms at their office visits. Overall, 56% of respondents reported that they would prescribe an antibiotic for uncomplicated bronchitis and 43% for the common cold. OB/GYNs with the fewest years of experience were less likely than those with the most years of experience to report prescribing for uncomplicated bronchitis (Odds ratio (OR) 0.46, 95% confidence interval (CI) 0.23 to 0.91) or the common cold (OR 0.44, CI 0.22 to 0.89). The majority of respondents (60%) believed that most patients wanted an antibiotic for URI symptoms, with male OB/GYNs being more likely than female OB/GYNs (OR 2.1, CI 1.2 to 3.8) to hold this belief. Both male OB/GYNs (OR 1.9, CI 1.1 to 3.4) and rural practitioners (OR 2.1, CI 1.1 to 4.0) were more likely to believe that it was hard to withhold antibiotics for URI symptoms because other physicians prescribe antibiotics for these symptoms. OB/GYNs who believed that postgraduate training prepared them well for primary care management were more likely than those who did not (OR 2.1, CI 1.1 to 4.2) to believe that they could reduce antibiotic prescribing without reducing patient satisfaction. CONCLUSION: Multiple demographic factors affect attitudes and reported practices regarding antibiotic prescribing. However, in view of the low proportion of office visits for URIs, an OB/GYN-specific program is not warranted

Opportunities to reduce overuse of antibiotics for perinatal group B streptococcal disease prevention and management of preterm premature rupture of membranes.

OBJECTIVE: To identify opportunities to reduce overuse of antibiotics for prevention of perinatal group B streptococcal (GBS) disease and management of preterm premature rupture of membranes (pPROM). METHODS: An anonymous written questionnaire was sent to each of 1031 Fellows of the American College of Obstetricians and Gynecologists, and the responses were subjected to statistical analysis. RESULTS: Among those of the 404 respondents who saw obstetric patients in 2001, most (84%) screened for GBS colonization, and 22% of these prescribed prenatal antibiotics to try to eradicate GBS colonization. Of the 382 respondents (95%) who prescribed antibiotics for pPROM, 36% continued antibiotics for more than 7 days despite negative results from GBS cultures collected before initiation of treatment. Having more years of clinical experience (adjusted odds ratio (OR) 3.0, 95% confidence interval (CI) 1.5 to 6.2), working in a non-academic setting (adjusted OR 2.7, 95% CI 1.0 to 6.9), and prescribing antibiotics prenatally for GBS colonization (adjusted OR 2.0, 95% CI 1.1 to 3.4) were associated with prescribing prolonged antibiotics for pPROM. CONCLUSION: Prenatal antibiotic treatment for GBS colonization and prolonged antibiotic treatment for pPROM contribute to overuse of antibiotics in obstetrics

Provider Knowledge, Attitudes, and Practices regarding Obstetric and Postsurgical Gynecologic Infections Due to Group A Streptococcus and Other Infectious Agents

Background. Knowledge, attitudes, and practices of obstetricians and gynecologists regarding the Centers for Disease Control and Prevention (CDC) recommendations for prevention of healthcare-associated group A streptococcal (GAS) infections as well as general management of pregnancy-related and postpartum infections are unknown. Methods. Questionnaires were sent to 1300 members of the American College of Obstetricians and Gynecologists. Results. Overall, 53% of providers responded. Postpartum and postsurgical infections occurred in 3% and 7% of patients, respectively. Only 14% of clinicians routinely obtain diagnostic specimens for postpartum infections; providers collecting specimens determined the microbial etiology in 28%. Microbiologic diagnoses were confirmed in 20% of postsurgical cases. Approximately 13% and 15% of postpartum and postsurgical infections for which diagnoses were confirmed were attributed to GAS, respectively. Over 70% of clinicians were unaware of CDC recommendations. Conclusions. Postpartum and postsurgical infections are common. Providing empiric treatment without attaining diagnostic cultures represents a missed opportunity for potential prevention of diseases such as severe GAS infections

Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect mRNA expression of hundreds of putative myokines that may underlie the endocrine functions of skeletal muscle. We identify candidate genes that may drive tissue specialization, including Smarca4, Vegfa, and Myostatin. By demonstrating the intrinsic diversity of skeletal muscles, these data provide a resource for studying the mechanisms of tissue specialization

Evaluation of clinical prediction models (part 2):how to undertake an external validation study

External validation studies are an important but often neglected part of prediction model research. In this article, the second in a series on model evaluation, Riley and colleagues explain what an external validation study entails and describe the key steps involved, from establishing a high quality dataset to evaluating a model’s predictive performance and clinical usefulness.</p

External validation of clinical prediction models:simulation-based sample size calculations were more reliable than rules-of-thumb

INTRODUCTION: Sample size "rules-of-thumb" for external validation of clinical prediction models suggest at least 100 events and 100 non-events. Such blanket guidance is imprecise, and not specific to the model or validation setting. We investigate factors affecting precision of model performance estimates upon external validation, and propose a more tailored sample size approach.METHODS: Simulation of logistic regression prediction models to investigate factors associated with precision of performance estimates. Then, explanation and illustration of a simulation-based approach to calculate the minimum sample size required to precisely estimate a model's calibration, discrimination and clinical utility.RESULTS: Precision is affected by the model's linear predictor (LP) distribution, in addition to number of events and total sample size. Sample sizes of 100 (or even 200) events and non-events can give imprecise estimates, especially for calibration. The simulation-based calculation accounts for the LP distribution and (mis)calibration in the validation sample. Application identifies 2430 required participants (531 events) for external validation of a deep vein thrombosis diagnostic model.CONCLUSION: Where researchers can anticipate the distribution of the model's LP (eg, based on development sample, or a pilot study), a simulation-based approach for calculating sample size for external validation offers more flexibility and reliability than rules-of-thumb.</p

Physiological consequences of rising water salinity for a declining freshwater turtle.

Sea-level rise, drought and water diversion can all lead to rapid salinization of freshwater habitats, especially in coastal areas. Increased water salinities can in turn alter the geographic distribution and ecology of freshwater species including turtles. The physiological consequences of salinization for freshwater turtles, however, are poorly known. Here, we compared the osmoregulatory response of two geographically separate populations of the freshwater Western Pond Turtle (Actinemys marmorata)-a species declining across its range in western North America-to three constant salinities: 0.4 ppt, 10 ppt and 15 ppt over 2 weeks. We found that turtles from a coastal estuarine marsh population regulated their plasma osmolality at lower levels than their conspecifics from an inland freshwater creek population 45 km away. Plasma osmolalities were consistently lower in estuarine marsh turtles than the freshwater creek turtles over the entire 2-week exposure to 10 ppt and 15 ppt water. Furthermore, estuarine marsh turtles maintained plasma osmolalities within 1 SD of their mean field osmolalities over the 2-week exposure, whereas freshwater creek turtles exceeded their field values within the first few days after exposure to elevated salinities. However, individuals from both populations exhibited body mass loss in 15 ppt water, with significantly greater loss in estuarine turtles. We speculate that the greater ability to osmoregulate by the estuarine marsh turtles may be explained by their reduced feeding and drinking in elevated salinities that was not exhibited by the freshwater creek population. However, due to mass loss in both populations, physiological and behavioural responses exhibited by estuarine marsh turtles may only be effective adaptations for short-term exposures to elevated salinities, such as those from tides and when traversing saline habitats, and are unlikely to be effective for long-term exposure to elevated salinity as is expected under sea-level rise

Glass Ceramic Waste Forms for Combined CS+LN+TM Fission Products Waste Streams

In this study, glass ceramics were explored as an alternative waste form for glass, the current baseline, to be used for immobilizing alkaline/alkaline earth + lanthanide (CS+LN) or CS+LN+transition metal (TM) fission-product waste streams generated by a uranium extraction (UREX+) aqueous separations type process. Results from past work on a glass waste form for the combined CS+LN waste streams showed that as waste loading increased, large fractions of crystalline phases precipitated upon slow cooling.[1] The crystalline phases had no noticeable impact on the waste form performance by the 7-day product consistency test (PCT). These results point towards the development of a glass ceramic waste form for treating CS+LN or CS+LN+TM combined waste streams. Three main benefits for exploring glass ceramics are: (1) Glass ceramics offer increased solubility of troublesome components in crystalline phases as compared to glass, leading to increased waste loading; (2) The crystalline network formed in the glass ceramic results in higher heat tolerance than glass; and (3) These glass ceramics are designed to be processed by the same melter technology as the current baseline glass waste form. It will only require adding controlled canister cooling for crystallization into a glass ceramic waste form. Highly annealed waste form (essentially crack free) with up to 50X lower surface area than a typical High-Level Waste (HLW) glass canister. Lower surface area translates directly into increased durability. This was the first full year of exploring glass ceramics for the Option 1 and 2 combined waste stream options. This work has shown that dramatic increases in waste loading are achievable by designing a glass ceramic waste form as an alternative to glass. Table S1 shows the upper limits for heat, waste loading (based on solubility), and the decay time needed before treatment can occur for glass and glass ceramic waste forms. The improvements are significant for both combined waste stream options in terms of waste loading and/or decay time required before treatment. For Option 1, glass ceramics show an increase in waste loading of 15 mass % and reduction in decay time of 24 years. Decay times of {approx}50 years or longer are close to the expected age of the fuel that will be reprocessed when the modified open or closed fuel cycle is expected to be put into action. Option 2 shows a 2x to 2.5x increase in waste loading with decay times of only 45 years. Note that for Option 2 glass, the required decay time before treatment is only 35 years because of the waste loading limits related to the solubility of MoO{sub 3} in glass. If glass was evaluated for similar waste loadings as those achieved in Option 2 glass ceramics, the decay time would be significantly longer than 45 years. These glass ceramics are not optimized, but already they show the potential to dramatically reduce the amount of waste generated while still utilizing the proven processing technology used for glass production

Addressing Obesity in Pregnancy: What Do Obstetric Providers Recommend?

Maternal obesity is associated with adverse pregnancy outcomes. To improve outcomes, obstetric providers must effectively evaluate and manage their obese pregnant patients. We sought to determine the knowledge, attitudes, and practice patterns of obstetric providers regarding obesity in pregnancy