The development and application of new methods for the synthesis of organozinc carbenoids

This thesis concerns the generation of organozinc carbenoids and their subsequent reactions, particularly with alkenes to generate cyclopropanes. The thesis is divided into three major sections. The first section comprises a review of the current methods available for the direct cyclopropanation of alkenes. The review focuses on the more controlled methods, and in particular on the different classes of precursor suitable for cyclopropanation. The second chapter opens with an overview of the development of the generation of organozinc carbenoid via the reductive deoxygenation of carbonyl compounds. The generation of zinc carbenoids from a range of precursors is subsequently discussed in detail. The results are arranged to allow the reader to observe the chronological development of the chemistry. New observations on the formation of organozinc carbenoids from aldehydes and ketones are discussed first. The generation of organozinc carbenoids from acetals is then studied, and a series of new results presented. The generation of a novel class of α-alkoxyzinc carbenoids from simple orthoformates is then reported. A study into the generation of methylene organozinc carbenoids run concurrently with the aforementioned work is discussed and the chapter finishes with a brief insight into some attempts to generate other organozinc carbenoids and the range of unsuccessful precursors studied so far. A concluding chapter summarises the results of the work described above, and full experimental details together with appropriate references are appended

Excess maternal salt or fructose intake programmes sex-specific, stress- and fructose-sensitive hypertension in the offspring

The Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (±4 % salt) and water (±10 % fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypotensive (10 mmHg MAP) above and below controls, respectively. Sex differences were unrelated to endothelial nitric oxide activity in vivo, but isolation-induced anxiety revealed a significantly steeper coupling between blood pressure and heart rate in salt-exposed male offspring but not in female offspring. MAP of all offspring was refractory to salt loading but sensitive to subsequent dietary fructose, an effect exacerbated in female offspring from fructose-fed dams. Circadian analyses of pressure in all offspring revealed higher mean set-point for heart rate and relative non-dipping of nocturnal pressure. In conclusion, increased salt and fructose in the maternal diet has lasting effects on offspring cardiovascular function that is sex-dependent and related to the offspring’s stress–response axis

Increasing outdoor host-seeking in Anopheles gambiae over 6 years of vector control on Bioko Island.

BACKGROUND: Vector control through indoor residual spraying (IRS) has been employed on Bioko Island, Equatorial Guinea, under the Bioko Island Malaria Control Project (BIMCP) since 2004. This study analyses the change in mosquito abundance, species composition and outdoor host-seeking proportions from 2009 to 2014, after 11 years of vector control on Bioko Island. METHODS: All-night indoor and outdoor human landing catches were performed monthly in the Bioko Island villages of Mongola, Arena Blanca, Biabia and Balboa from 2009 to 2014. Collected mosquitoes were morphologically identified and a subset of Anopheles gambiae sensu lato (s.l.) were later identified molecularly to their sibling species. Mosquito collection rates, species composition and indoor/outdoor host-seeking sites were analysed using generalized linear mixed models to assess changes in mosquito abundance and behaviour. RESULTS: The overall mosquito collection rate declined in each of the four Bioko Island villages. Anopheles coluzzii and Anopheles melas comprised the An. gambiae s.l. mosquito vector population, with a range of species proportions across the four villages. The proportion of outdoor host-seeking An. gambiae s.l. mosquitoes increased significantly in all four villages with an average increase of 58.8 % [57.9, 59.64 %] in 2009 to 70.0 % [67.8, 72.0 %] in 2014. Outdoor host-seeking rates did not increase in the month after an IRS spray round compared to the month before, suggesting that insecticide repellency has little impact on host-seeking behaviour. CONCLUSION: While vector control on Bioko Island has succeeded in substantial reduction in overall vector biting rates, populations of An. coluzzii and An. melas persist. Host-seeking behaviour has changed in these An. gambiae s.l. populations, with a shift towards outdoor host-seeking. During this study period, the proportion of host-seeking An. gambiae s.l. caught outdoors observed on Bioko Island increased to high levels, exceeding 80 % in some locations. It is possible that there may be a genetic basis underlying this large shift in host-seeking behaviour, in which case outdoor feeding could pose a serious threat to current vector control programmes. Currently, the BIMCP is preparing for this potential challenge by testing source reduction as a complementary control effort that also targets outdoor transmission

Systematic Assessment of the Quality and Comprehensibility of YouTube Content on Ulnar Collateral Ligament Injury and Management

Background: Ulnar collateral ligament (UCL) reconstruction has received a unique level of attention in the press and social media. There has also been an increasing use of the internet by patients to seek medical information. Concern exists regarding the quality and comprehensibility of online information when used for patient education. Purpose: To evaluate the quality and comprehensibility of the most-viewed YouTube videos related to the diagnosis and management of UCL injuries. Based on our new evidence-based scoring rubrics, we hypothesized that the quality and comprehensibility of these videos would be poor. Study Design: Cross-sectional study. Methods: The YouTube platform was searched on September 7, 2021, with the terms “UCL injury,” “ulnar collateral ligament injury,” “UCL surgery,” “ulnar collateral ligament surgery,” and “Tommy John surgery,” and the 50 most-viewed videos from each search were compiled, yielding 250 videos. After removal of duplicates and application of exclusion criteria, the 100 most-viewed videos remained. Basic attributes, including duration of video and number of views, were recorded. Each video was then analyzed by 2 independent reviewers and evaluated for 4 key parameters (quality of diagnostic content [QAR-D], quality of treatment content [QAR-T], presence of inaccurate information, and comprehensibility) and graded on a novel scale from 1 to 4 (4 being the most appropriate for patient education). Results: The mean QAR-D was 4.83 ± 3.41 (fair quality), and the mean QAR-T was 2.76 ± 3.26 (poor quality). Physician-led educational videos had both the highest mean QAR-D (6.37) and the highest mean QAR-T (4.34). No correlation was observed between video quality and views/likes. A total of 12 videos included ≥1 inaccuracy. The mean comprehensibility score was 2.66 ± 1.12, with 39 videos falling below the acceptable comprehensibility threshold (score \u3c3). Conclusion: The overall quality of UCL injury–related YouTube content was low. In addition, the absence of correlation between video quality and views/likes suggests that patients are not preferentially utilizing the limited high-quality content that does exist on the YouTube platform. In addition, inaccurate videos were prevalent (12%), and almost half of all videos were deemed inappropriate for patient education in terms of comprehensibility, as defined by our comprehensibility parameter

A morphometric system to distinguish sheep and goat postcranial bones.

Distinguishing between the bones of sheep and goat is a notorious challenge in zooarchaeology. Several methodological contributions have been published at different times and by various people to facilitate this task, largely relying on a macro-morphological approach. This is now routinely adopted by zooarchaeologists but, although it certainly has its value, has also been shown to have limitations. Morphological discriminant criteria can vary in different populations and correct identification is highly dependent upon a researcher's experience, availability of appropriate reference collections, and many other factors that are difficult to quantify. There is therefore a need to establish a more objective system, susceptible to scrutiny. In order to fulfil such a requirement, this paper offers a comprehensive morphometric method for the identification of sheep and goat postcranial bones, using a sample of more than 150 modern skeletons as a basis, and building on previous pioneering work. The proposed method is based on measurements-some newly created, others previously published-and its use is recommended in combination with the more traditional morphological approach. Measurement ratios, used to translate morphological traits into biometrical attributes, are demonstrated to have substantial diagnostic potential, with the vast majority of specimens correctly assigned to species. The efficacy of the new method is also tested with Discriminant Analysis, which provides a successful verification of the biometrical indices, a statistical means to select the most promising measurements, and an additional line of analysis to be used in conjunction with the others

A morphometric system to distinguish sheep and goat postcranial bones.

Distinguishing between the bones of sheep and goat is a notorious challenge in zooarchaeology. Several methodological contributions have been published at different times and by various people to facilitate this task, largely relying on a macro-morphological approach. This is now routinely adopted by zooarchaeologists but, although it certainly has its value, has also been shown to have limitations. Morphological discriminant criteria can vary in different populations and correct identification is highly dependent upon a researcher's experience, availability of appropriate reference collections, and many other factors that are difficult to quantify. There is therefore a need to establish a more objective system, susceptible to scrutiny. In order to fulfil such a requirement, this paper offers a comprehensive morphometric method for the identification of sheep and goat postcranial bones, using a sample of more than 150 modern skeletons as a basis, and building on previous pioneering work. The proposed method is based on measurements-some newly created, others previously published-and its use is recommended in combination with the more traditional morphological approach. Measurement ratios, used to translate morphological traits into biometrical attributes, are demonstrated to have substantial diagnostic potential, with the vast majority of specimens correctly assigned to species. The efficacy of the new method is also tested with Discriminant Analysis, which provides a successful verification of the biometrical indices, a statistical means to select the most promising measurements, and an additional line of analysis to be used in conjunction with the others

Obesity and male breast cancer: Provocative parallels?

While rare compared to female breast cancer the incidence of male breast cancer (MBC) has increased in the last few decades. Without comprehensive epidemiological studies, the explanation for the increased incidence of MBC can only be speculated. Nevertheless, one of the most worrying global public health issues is the exponential rise in the number of overweight and obese people, especially in the developed world. Although obesity is not considered an established risk factor for MBC, studies have shown increased incidence among obese individuals. With this observation in mind, this article highlights the correlation between the increased incidence of MBC and the current trends in obesity as a growing problem in the 21st century, including how this may impact treatment. With MBC becoming more prominent we put forward the notion that, not only is obesity a risk factor for MBC, but that increasing obesity trends are a contributing factor to its increased incidence