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In 2017, the World Health Organization published new nomenclature for preimplantation genetic diagnosis (PGD). They renamed the procedure preimplantation genetic testing (PGT), with PGT-M for monogenic diseases and PGT-SR for structural rearrangements. Preimplantation genetic screening (PGS) was renamed PGT-A (aneuploidy). In this chapter, PGT-M and PGT-SR will be referred to as PGT.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
A new protocol has been devised for determining elastic properties of natural biocomposites in the form of bivalve shells under wet and dry conditions. Four-point bending on shell slices of Mytilus edulis, Ensis siliqua, and Pecten maximus give generally lower and more reliable values of Young’s modulus, E, than those in the literature from three-point bending, due to the more even distribution of strain. Finite element analysis of the prismatic microstructure of Pinna nobilis, obtained by X-ray tomography, shows that values of E ≈ 20 GPa can be understood in terms of the real microstructure containing a small proportion of organic matrix phase with E ≈ 1 GPa and a dominant proportion of calcite with E ≈ 90 GPa. Higher values of E obtained by nanoindentation give results which are biased toward the properties of the carbonate phase rather than of the biocomposite as a whole.
Inequality and changing responses to food scarcity may create a stigmatization complex around certain foods. Here, we conduct a literature search to develop a working definition of “famine foods” in the Maya lowlands, centering qualities such as hardiness, productivity, nutrition, preparation, and stigmatization complexes. An analysis of the nutritional characteristics that might make up such a food yields the idea that famine foods are likely members of a time- and place-specific arsenal of plant resources. We compare the results of the literature search to botanical data from a rejollada survey from Xuenkal and a solar (house garden) survey conducted in Yaxunah. Examining the data through the lens of a history of manipulation of food access, shifting relations of power, and modern responses to food insecurity illuminates cultural plasticity and resilience in diet and agricultural strategies in the Maya lowlands. We conceptualize solares and rejolladas as food-related resilience strategies.
Lowering dietary protein concentration is known to decrease urinary nitrogen (N) losses and increase milk N efficiency in dairy cows, but it may negatively affect animal productivity. Plant-derived essential oils (EO) may alleviate these negative effects by improving the efficiency of rumen fermentation in cows fed reduced feed protein diets. The experiment was conducted to investigate the effects of lowering crude protein (CP) supply alone or in a combination with an EO product on feed intake, milk production and composition, rumen fermentation, total tract digestibility and N utilization in dairy cows. Twenty-one Holstein cows were used in a replicated 3 × 3 Latin square design experiment. Each period consisted of 14 days for adaptation and 14 days for data collection and sampling. Cows were randomly assigned to one of three experimental diets: a 165 g/kg CP diet (control), a 155 g/kg CP diet (LCP) and LCP supplemented with 35 g/day per cow EO (LCPEO). The dry matter (DM) intake was decreased by LCP and LCPEO compared with the control; there was no effect of EO on DM intake. Milk yield and composition and feed efficiency were similar among treatments. Ruminal pH, lactate, ammonia and volatile fatty acids concentrations were not affected by treatment, except increased valerate concentration by LCPEO compared with LCP. The supplementation of EO tended to decrease protozoal counts. The LCP and LCPEO increased total tract digestibility of DM and organic matter and decreased CP digestibility compared with the control. Supplementation with EO did not affect total tract digestibility of dietary nutrients compared with the control or LCP. The LCP and LCPEO decreased urinary and fecal N excretions and increased milk N efficiency; nitrogen losses were not affected by EO. In this study, lowering dietary CP by 10 g/kg decreased urinary and fecal N excretion without affecting productivity. The supplementation of EO to LCP had only minor effects on rumen fermentation and did not affect productivity, digestibility and N excretion in lactating dairy cows.
Labour emigrants in the nineteenth century had ever-increasing access to a global employment market. Many of those who left Great Britain looked beyond Europe, to the British Empire and the United States. They took advantage of improvements in transportation, and followed a wide variety of occupations. Decisions to emigrate were often shaped by their involvement in trade unions and were based on concerns about living standards and working conditions. This study considers a selection of globetrotting British settlers and sojourners who went to Canada, the United States and Australia between 1815 and the 1880s. The article analyses the historiography of labour migration; carries out an empirical study constructed around four pieces of analytical scaffolding; and closes by identifying recurring threads in the multi-hued tapestry of labour emigration, highlighting how concerns and traditions about recruitment, wages and working conditions, which had emerged in the nineteenth century, created legacies that persisted into the period after the First World War.
In this article, James Harper of LexisNexis UK outlines the company's bi-centenary, and its contribution to the ‘rule of law’. The article will describe the fascinating development of UK law during this period, focusing on key milestones in arguably the largest and most exponential increase in the quantity of English language law the world has seen. It will also outline the range of legal industry innovations which LexisNexis and its companies have spearheaded over the years.
This article reviews a recent wave of literature on the resurgence of vinyl records, examining what it has claimed about vinyl's capacity for tangibility and the contrast to digital media, associated with intangibility. These claims are explained with reference to other literatures on touch, and it is suggested that vinyl's haptics mediates and embodies the emotionally rewarding production of a sense of self. The apparent contrast of vinyl aesthetics with classical music aesthetics is also discussed, and the presence of contemporary classical music within the vinyl resurgence is considered.
This was the fourteenth year of Music We'd Like To Hear, the summer series of concerts organised by composers John Lely and Tim Parkinson. The atmosphere at these Friday evening concerts is informal and convivial – the audience is routinely invited to join the musicians down at the pub on the corner afterwards – but the underlying purpose is entirely serious about music. As always, each programme focuses on new music and significant works that have been rarely, or never, played in this country. The concerts wouldn't look out of place at Huddersfield, but the rationale here is less academic than personal.
Lebanon has a need for innovative approaches to increase access to mental health care to meet the country's current high demand. E-mental health has been included in its national mental health strategy while in parallel the World Health Organization has produced an online intervention called ‘Step-by-Step’ to treat symptoms of depression that is being tested in Lebanon over the coming years.
The primary aim of this study is to conduct bottom-up, community-driven qualitative cognitive interviewing from a multi-stakeholder perspective to inform the cultural adaptation of an Internet-delivered mental health intervention based on behavioural activation in Lebanon.
National Mental Health Programme staff conducted a total of 11 key informant interviews with three mental health professionals, six front-line workers in primary health care centres (PHCCs) and two community members. Also, eight focus group discussions, one with seven front-line workers and seven others with a total of 66 community members (Lebanese, Syrians and Palestinians) were conducted in several PHCCs to inform the adaptation of Step-by-Step. Results were transcribed and analysed thematically by the project coordinator and two research assistants.
Feedback generated from the cognitive interviewing mainly revolved around amending the story, illustrations and the delivery methods to ensure relevance and sensitivity to the local context. The results obtained have informed major edits to the content of Step-by-Step and also to the model of provision. Notably, the intervention was made approximately 30% shorter; it includes additional videos of content alongside the originally proposed comic book-style delivery; there is less emphasis on total inactivity as a symptom of low mood and more focus on enjoyable activities to lift mood; the story and ways to contact participants to provide support were updated in line with local gender norms; and many of the suggested or featured activities have been revised in line with suggestions from community members.
These findings promote and advocate the use of community-driven adaptation of evidence-based psychological interventions. Some of the phenomena recorded mirror findings from other research about barriers to care seeking in the region and so changes made to the intervention should be useful in improving utility and uptake of ‘Step-by-Step’.
Halász’s theorem gives an upper bound for the mean value of a multiplicative function
. The bound is sharp for general such
, and, in particular, it implies that a multiplicative function with
has either mean value
, or is ‘close to’
for some fixed
. The proofs in the current literature have certain features that are difficult to motivate and which are not particularly flexible. In this article we supply a different, more flexible, proof, which indicates how one might obtain asymptotics, and can be modified to treat short intervals and arithmetic progressions. We use these results to obtain new, arguably simpler, proofs that there are always primes in short intervals (Hoheisel’s theorem), and that there are always primes near to the start of an arithmetic progression (Linnik’s theorem).