Sudden infant death syndrome and the central nervous system: a review of the triple-risk theory

Sudden infant death syndrome (SIDS) is the devastating condition in which an infant suddenly and unexplainably passes away over the course of sleeping. This is an unfortunate situation that many new parents dread every night as they lay their newborns to rest. SIDS is the leading cause of death in infants aged from one month to one year, and the medical world still does not fully understand what causes it. However, the triple-risk theory is a new model that sets out to explain the pathology of this syndrome through the combination of genetic vulnerabilities, a critical time period, and external stressors. This thesis summarizes the current research in the realm of the central nervous system (specifically the cerebellum and brainstem) as a means of evaluating the validity of this new model. The analyzed literature concentrated on a few important topics, such as proven risk factors, evidence of homeostatic abnormalities, and significant associations with the occurrence of SIDS. It was found that there was central nervous system dysfunction on most levels, including: damaged Purkinje cells in the cerebellum, malformations of the human choroid plexus, decreased neuropeptide signaling (both orexin and brain-derived neurotrophic factors), malformations of the amino acid neurotransmitters (both excitatory glutamate and inhibitory GABA), and finally significant reductions in the receptor density and activity of the serotonin system. These irregularities were associated, in most studies, with either the prone sleeping position or known maternal nicotine use during pregnancy. In conclusion, the triple-risk model is currently the most accurate description of SIDS, given its reasonable three criteria and present-day research. This is because the studies, and real-life victims, were all concentrated within the critical time period of transition from intra-uterine to extra-uterine life, satisfying the first element of timing. The list of central nervous system dysfunctions found in SIDS cases was compelling enough to fulfill the second factor of inherent vulnerability. Finally, the associations between low oxygen rebreathing and the prone sleep position, or over-heating and tight swaddling displayed a strong relationship with the occurrence of SIDS and satisfied the third and final event, which was the induction of an exogenous stressor. These three factors of the triple-risk model allow for the variations in victim pathology, but still offers a compelling and coherent understanding of the sudden infant death syndrome

Process issues in redox biocatalysis: Cyclohexanone monooxygenase catalysed chiral lactone syntheses

This thesis investigates the Baeyer-Villiger oxidation of cyclic ketones to optically enriched lactones by the enzyme cyclohexanone monooxygenase (CHMO), cloned into Escherichia coli JM107 pQR210. Two model substrates were selected (2-hexyl cyclopentanone and 4-methyl cyclohexanone) to conduct investigations with. A major constraint found was that whole cell catalysis produced low reaction rates and poor enzyme stability. Isolated enzyme was stabilised effectively by using elevated levels of the cofactor NADPH. Recycle of the expensive NADPH was investigated by detailed studies of thermostable glucose and alcohol dehydrogenases. These were characterised by marked product inhibition. Alcohol dehydrogenase from Thermoanaerobacter brockii (TBADH) was chosen for the ease of removal of the acetone product from the system and the high affinity for NADPH. The interaction between CHMO and TBADH was modeled by simultaneous numerical integration of their rate equations leading to an understanding of the effect of different enzyme ratios on system performance. This model also predicts the conditions necessary to maximise cofactor stability and re-usability. Quantification of a range of processing strategies was performed, fed-batch operation was found to be 2.5 times more productive than batch. Multi-gram syntheses of lactones were performed at 2L scale with both free and immobilised enzymes. NADPH recycle was effective at producing over 700 reaction cycles. Immobilised CHMO was found to be significantly more stable than free enzyme under process conditions, a catalyst with retained activity of 12% and specific activity of 1.2Ug-1 was produced. TBADH produced 42% retained and 13.6Ug-1 specific activity. Co-immobilisation of both enzymes on the same support produced a catalyst with an activity of 0.6Ug-1

Military Retention Incentives: Evidence from the Air Force Selective Reenlistment Bonus

The limited lateral entry and rigid pay structure for U.S. military personnel present challenges in retaining skilled individuals who have attractive options in the civilian labor market. One tool the services use to address this challenge is the Selective Reenlistment Bonus (SRB), which offers eligible personnel with particular skills a substantial cash bonus upon reenlistment. However, the sequential nature of the bonus offer and reenlistment process limits the ability to adjust manpower quickly, raising interest in research that estimates the effect of the SRB on retention. While this literature has acknowledged challenges including potential endogeneity of bonus levels, attrition, and reenlistment eligibility, many studies do not address these concerns adequately. This paper uses a comprehensive panel data set on Air Force enlisted personnel to estimate the effect of the SRB on retention rates. We exploit variation in bonus levels within skill groups, control for civilian labor market conditions, and model reenlistment eligibility to avoid common assumptions that lead to biased impact estimates. We find substantial heterogeneity in the effect of the bonus, with the largest effects on first-term service members and those whose skills have not historically received a substantial bonus. We also find evidence that the bonus affects the timing of reenlistment decisions in addition to their frequency

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation

The British Army, information management and the First World War revolution in military affairs

Information Management (IM) – the systematic ordering, processing and channelling of information within organisations – forms a critical component of modern military command and control systems. As a subject of scholarly enquiry, however, the history of military IM has been relatively poorly served. Employing new and under-utilised archival sources, this article takes the British Expeditionary Force (BEF) of the First World War as its case study and assesses the extent to which its IM system contributed to the emergence of the modern battlefield in 1918. It argues that the demands of fighting a modern war resulted in a general, but not universal, improvement in the BEF’s IM techniques, which in turn laid the groundwork, albeit in embryonic form, for the IM systems of modern armies. KEY WORDS: British Army, Information Management, First World War, Revolution in Military Affairs, Adaptatio

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.Peer reviewe