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\"Looking for the perfect mix of smart, sexy, and sassy? Mai Tai'd Up continues USA TODAY bestselling author Alice Clayton's Cocktail series, which began with Wallbanger and continued with Rusty Nailed and Screwdrivered. Eligible bachelor Lucas Campbell is very available, but very picky. A veterinarian in Monterey, California, his life is perfect: he works, he sails, he loves the ocean and the mountains--so why rock the boat? Then Miss Chloe Patterson comes along. Chloe has the body of a supermodel, the mouth of a sailor, and the fashion sense of teenage guy in 1990s Seattle. A former Miss California, she walked away from a cushy life, bought an old ranch outside Monterey, and turned it into Our Gang, a sanctuary for rescued and abandoned pit bulls. A woman who's clearly not afraid of dog poop, she enjoys rehabilitating her \"warrior angels.\" Local gossip reports that she ditched her fiance; the night before their wedding (true), and that she moved up north to start a new life (also true). She didn't want to be tied down (true), but she wouldn't mind being tied up--especially by that hot vet she's seen around town a few times (true, true, and have-you-seen-his-butt?-true). But is Chloe ready to date again? And is Lucas ready to take on not only Chloe, but forty pit bulls? One moonlit sail, two bottles of wine, and a few sailor knots might just do the trick\"-- Provided by publisher.

Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings will be utilized as a resource for the broader scientific community.

Avery Bardot steps off the plane in Rome, looking for a fresh start. She's left behind a soon-to-be ex-husband in Boston and plans to spend the summer with her best friend Daisy, licking her wounds--and perhaps a gelato or two. But when her American-expat friend throws her a welcome party on her first night, Avery's thrown for a loop when she sees a man she never thought she'd see again: Italian architect Marcello Bianchi.

Introduction: A positive patient experience is a key component of good quality of care. Post-pandemic healthcare systems face the challenge of addressing burnout among healthcare staff, who are directly involved in the delivery of healthcare, which has implications for the patient experience. There is an established association between staff and patient experience; exploring the experience of staff may give insights into factors that negatively impact the patient experience. Experience-based design (EBD) is a quality improvement approach that uses the experience of service users to derive improvements. The purpose of this study is to design, validate, and test an EBD tool that may be used to capture the staff experience. Methods: A focus group of clinical and nonclinical staff (identified through the NHS Elect networks) and the development team coproduced an EBD survey based on nine “touch-points” of a typical working day. Once the survey questionnaire was tested and agreed with it was distributed to 1300 members of NHS networks. Results: A total of 377 NHS staff responded to the questionnaire. Analysis revealed effective teamwork had a positive psychological impact on staff. However, increased workload, missed meal breaks, and an increased administrative/IT burden were associated with the greatest negative responses by clinical and nonclinical staff. Conclusion: Overall, factors impacting staff well-being are multifaceted and varied between trusts. However, leaders in healthcare can use EBD to identify targeted improvements for the day-to-day experiences of staff.

The United Kingdom Office of National Statistics population estimates that 10 million people are aged 65 years and older, of which some would be considered frail. This is conceptualized as a complex progressive loss of physiological and social function. In order to establish and evaluate appropriate services, feedback tools designed for this patient group have begun to take greater importance, which the Acute Frailty Network has been developing using experience-based design. These tools focus on the experience of frail patients in the settings of accident and emergency and the acute medical unit. An analysis of data from 12 hospitals was used to look at the common emotions and comments expressed at the key touchpoints. A total of 609 respondents were used in the analysis, revealing that patients expressed mostly positive experiences. The areas with the most negative emotions and comments were in the domains “being admitted,” “first assessment,” and “preparing to leave hospital.” We would recommend that future quality improvement projects focus in improving the communication standards around the admission and discharge process.

A microdeletion on human chromosome 16p11.2 is one of the most common copy number variants associated with autism spectrum disorder and other neurodevelopmental disabilities. Arbaclofen, a GABA(B) receptor agonist, is a component of racemic baclofen, which is FDA-approved for treating spasticity, and has been shown to alleviate behavioral phenotypes, including recognition memory deficits, in animal models of 16p11.2 deletion. Given the lack of reproducibility sometimes observed in mouse behavioral studies, we brought together a consortium of four laboratories to study the effects of arbaclofen on behavior in three different mouse lines with deletions in the mouse region syntenic to human 16p11.2 to test the robustness of these findings. Arbaclofen rescued cognitive deficits seen in two 16p11.2 deletion mouse lines in traditional recognition memory paradigms. Using an unsupervised machine-learning approach to analyze behavior, one lab found that arbaclofen also rescued differences in exploratory behavior in the open field in 16p11.2 deletion mice. Arbaclofen was not sedating and had modest off-target behavioral effects at the doses tested. Our studies show that arbaclofen consistently rescues behavioral phenotypes in 16p11.2 deletion mice, providing support for clinical trials of arbaclofen in humans with this deletion.A microdeletion on human chromosome 16p11.2 is one of the most common copy number variants associated with autism spectrum disorder and other neurodevelopmental disabilities. Arbaclofen, a GABA(B) receptor agonist, is a component of racemic baclofen, which is FDA-approved for treating spasticity, and has been shown to alleviate behavioral phenotypes, including recognition memory deficits, in animal models of 16p11.2 deletion. Given the lack of reproducibility sometimes observed in mouse behavioral studies, we brought together a consortium of four laboratories to study the effects of arbaclofen on behavior in three different mouse lines with deletions in the mouse region syntenic to human 16p11.2 to test the robustness of these findings. Arbaclofen rescued cognitive deficits seen in two 16p11.2 deletion mouse lines in traditional recognition memory paradigms. Using an unsupervised machine-learning approach to analyze behavior, one lab found that arbaclofen also rescued differences in exploratory behavior in the open field in 16p11.2 deletion mice. Arbaclofen was not sedating and had modest off-target behavioral effects at the doses tested. Our studies show that arbaclofen consistently rescues behavioral phenotypes in 16p11.2 deletion mice, providing support for clinical trials of arbaclofen in humans with this deletion.

The Diels-Alder reaction is a highly valuable reaction via which a [4+2] cycloaddition occurs to form a cyclohexene ring. Several biosynthetic enzymes, termed Diels-Alderases, have previously been shown to stereoselectively catalyse this reaction in the biosynthesis of the spirotetronate class of natural products. This spiro forming Diels-Alder reaction can have one of four stereochemical outcomes, and there are examples of all four stereochemistries in known spirotetronates. This stereocontrol is important to understand if the Diels-Alderases are to be exploited as biocatalysts that mediate stereocontrolled Diels-Alder reactions. [Figure i Generic structures of the four stereoisomeric products of the spiro forming Diels-Alder reaction in spirotetronate biosynthesis. Open circles indicate si faces, and closed circles indicate re faces involved in the overlap of the diene (blue) and the dienophile (red).] Ent-abyssomicin is a novel class I spirotetronate natural product from Streptomyces incarnatus NRRL 8089. It has been shown to be enantiomeric to the spirotetronate antibiotic abyssomicin C, resulting from an enantiodivergent Diels-Alder reaction. The structure of ent-abyssomicin was elucidated by MS, NMR, CD spectroscopy, and X-ray crystallography. The function of the Diels-Alderase involved in the biosynthesis of ent-abyssomicin has been demonstrated in vitro and the molecular basis for catalysis and stereocontrol has been investigated computationally. Also reported here is the discovery of a second biosynthetic gene cluster that produces the known class II spirotetronate MM46115. The pathway to its biosynthesis has been proposed and the compound was reisolated and structurally characterised. A DH-like domain that is proposed to install the diene required for the spiro forming Diels-Alder reaction by catalysing two consecutive dehydration reactions was studied.

This thesis explores the attitudes, beliefs and opinions of members of the cultural elite in Wales. This term is used to mean people who hold prominent, high profile and prestigious positions within the culture sector in Wales, specifically located around the capital city of Cardiff. Through the analysis of data collected from in-depth semi-structured interviews with twenty key informants I examine how they construct their biographies and make sense of the social world which they inhabit. I address two main research questions, firstly whether they see themselves as belonging to a closed, restricted and self-referencing network. Secondly, how do they try to justify their positions of power and privilege in society? Using themes from the literature I also consider to what extent the different sectors (culture, business and political) overlap, how the network is constructed in terms of a core and a periphery, what purpose this serves, and how the network is at once generally cohesive but also not without some internal divisions. This is all done in a specifically Welsh context and I argue that their national identity has a very important role to play in how they define and experience culture, and that this directly impacts on how they explain their reasons and motivations for their involvement. I use Bourdieu’s notions of cultural and social capital and demonstrate how these are exchangeable commodities. While members of the cultural elite are in possession of large amounts of cultural capital, success in the network depends on them being able to demonstrate this, and this in turn increases their social capital. The act of networking is fundamental for sustaining the network and this is a performance on their part. How the interviewees performed for me, the interviewer, lies at the heart of the discussion.

To expand, analyze and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng s Shank3tm2Gfng model, hereafter Shank3/F, Jiang s Shank3tm1Yhj model, hereafter Shank3/J, and the Cacna1c deletion model. The Shank3/F and Shank3/J models mimick gene mutations associated with Phelan-Mcdermid syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. The current study utilizes both standard and novel, computer-vision based behavioral tests, the same methdology used in our previously published companion report on the Cntnap2 null and 16p11.2 deletion models. Overall, some but not all behaviors replicated published findings. Those that replicated, such as social behavior and overgrooming in Shank3 models, also tended to be milder than previous reports. The Shank3/F model, and to a much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a general anxiety-like behavior triggered by external stimuli which pervaded social interactions. We did not detect deficits in a cognitive procedural learning test nor did we observe perseverative behavior in these models. We did, however, find differences in exploratory patterns of Cacna1c mutant mice suggestive of a behavioral effect in a social setting. In addition, Shank3/F but not Shank3/J KO or Cacna1c HET showed differences in sensory-gating. Discrepancies in our current results from previous reports may be dependent on subtle differences in testing conditions, housing enrichment, or background strain. Both positive and negative results from this study will be useful in identifying the most robust and replicable behavioral signatures within and across mouse models of autism. Understanding these phenotypes may shed light of which features to study when screening compounds for potential therapeutic interventions.

This study examines the relationship between a woman's perception of her chance of conceiving and her consistency of contraceptive use, using a convenience sample of 22 women seeking first trimester abortion. Subjects were between the ages of 19 and 37 and completed self-report questionnaires at the time of their abortions. The data show a negative correlation between a woman's perception of her chance of conceiving and her consistency of birth control use. Older women reported more consistent use of birth control even though they did not perceive a higher pregnancy risk. The study concludes that the decision whether or not to use contraceptives is complex and still not well understood.