Study protocol - A systematic review and meta-analysis of hypothermia in experimental traumatic brain injury: Why have promising animal studies not been replicated in pragmatic clinical trials?

Traumatic brain injury (TBI) is a major cause of death and permanent disability. Systemic hypothermia, a treatment used in TBI for many decades, has recently been found to be associated with neutral or unfavourable clinical outcomes despite apparently promising preclinical research. Systematic review and meta‐analysis is a tool to summarize literature and observe trends in experimental design and quality that underpin its general conclusions. Here we aim to use these techniques to describe the use of hypothermia in animal TBI models, collating data relating to outcome and both study design and quality. From here we intend to observe correlations between features and attempt to explain any discrepancies found between animal and clinical data. This protocol describes the relevant methodology in detail

An Association between Head Circumference and Alzheimer's Disease in a Population-Based Study of Aging and Dementia

We investigated the association between head circumference (HC) and Alzheimer's disease (AD) in a cross-sectional population-based study of aging in North Manhattan. Six hundred forty-nine subjects underwent neurologic, neuropsychological, and anthropometric evaluations; apolipoprotein E (apoE) genotype was available for a subsample of 300 individuals. Logistic regression analyses were performed with AD the outcome of interest to evaluate any association between HC and AD. In these analyses, HC evaluated as a continuous variable was associated with AD (OR 0.8, 95% CI 0.7-0.9) after adjusting for age, education, and ethnicity, gender, and height. Analyses suggested that increased risk resided mainly in those with smallest HC. Thus, women whose HC was within the lowest quintile of HC for women were 2.9 (95% CI 1.4-6.1) times more likely to have AD, after adjusting for age, education, and ethnicity; and men in the lowest quintile of HC (for men) were 2.3 times more likely to have AD (95% CI 0.6-9.8). There was no confounding by height, weight, or apoE genotype. The results are consistent with previous studies that suggest that premorbid brain size may influence the age-specific risk for AD. Future epidemiologic studies seeking environmental risk factors for AD may benefit by making HC measurements on all subjects to decrease the variance associated with other potential risk factors

Project Gatekeeper:An entrance control system embedded radiation detection capability for security applications

Threat assessments continue to conclude that terrorist groups and individuals as well as those wanting to cause harm to society have the ambition and increasing means to acquire unconventional weapons such as improvised nuclear explosive devices and radiological disposal devices. Such assessments are given credence by public statements of intent by such groups/persons, by reports of attempts to acquire radioactive material and by law enforcement actions which have interdicted, apprehended or prevented attempts to acquire such material. As a mechanism through which to identify radioactive materials being transported on an individual’s person, this work sought to develop a detection system that is of lower-cost, reduced form-factor and more covert than existing infrastructure, while maintaining adequate sensitivity and being retrofittable into an industry standard and widely utilised Gunnebo Speed Gate system. The system developed comprised an array of six off-set Geiger–Muller detectors positioned around the gate, alongside a single scintillator detector for spectroscopy, triggered by the systems inbuilt existing IR proximity sensor. This configuration served to not only reduce the cost for such a system but also allowed for source localisation and identification to be performed. Utilising the current setup, it was possible to detect a 1 µSv/h source carried into the Speed Gate in all test scenarios, alongside locating and spectrally analysing the material in a significant number

Bed-load Transport of Mixed-size Sediment: Fractional Transport Rates, Bed Forms, and the Development of a Coarse Bed-surface Layer

Fractional transport rates, bed surface texture, and bed configuration were measured after a mixed size sediment had reached an equilibrium transport state for seven different flow strengths in a recirculating laboratory flume. Fractional transport rates were also measured at the beginning of each run when the bed was well mixed and planar. The start-up observations allow us to describe the variation of fractional transport rates with bed shear stress for a constant bed surface texture and bed configuration. The start-up and equilibrium observations together allow, for the first time, an unambiguous description of the mutual adjustment among the transport, the bed configuration, and the bed surface, as the transport system moves toward equilibrium. We find that a substantial interaction exists among the transport, bed surface, and bed configuration. Bed forms and a coarse surface layer coexist over a range of bed shear stress. Under some flow conditions the size and shape of the bed forms are controlled by the presence of the coarse surface layer. At higher flows the coarse surface layer is eliminated by scour in the lee of the bed forms. If the bed surface is defined as that over which the bed forms move, a coherent relation between the bed surface texture and the transport grain size distribution may be defined. At equilibrium the transport rates of all fractions were not equally mobile, defined as identical transport and bed grain size distributions, although equal mobility was approached for runs in which the bed shear stress was more than twice that for initial motion of the mixture. Under some flow conditions the transport was observed to adjust away from equal mobility as the bed adjusted from a well-mixed start-up condition to an equilibrium state. Development of a partial static armor, wherein some individual grains become essentially immobile even though other grains in the same fraction remain in transport, is suggested to explain these adjustments between the transport and bed surface grain size distributions. Constraints on equilibrium mixed size sediment transport are defined. The special conditions for which equal mobility must hold and the relevance to natural conditions of flume results and the equal mobility concept are discussed

Saw-tooth cardiomyopathy

We present an unusual case of cardiomyopathy in a two month old male infant with a grade-I systolic murmur. Echocardiographic examination disclosed left ventricular (LV), dysplasia with saw-tooth like inwards myocardial projections extending from the lateral walls towards the LV cavity. There was mild LV systolic dysfunction with apical hypokinesia. Cardiovascular magnetic resonance demonstrated in detail these cross bridging muscular projections originating from the inferior interventricular septum and lateral LV wall, along with areas of hypokinesis at the LV septum and apex in a noncoronary distribution, without any late gadolinium enhancement. We have termed this condition saw-tooth cardiomyopathy because of the very characteristic appearance

David Quentin Bowen: A memorial

The Quaternary community lost a giant and a leader on October 5, 2020, when David Quentin Bowen, known to many as “DQ” and founding editor of Quaternary Science Reviews, passed away in Cardiff. Born on February 14, 1938 in Llanelli, SouthWales, he received his PhD at University College London. David’s 50 years of contributions to our science cannot be adequately summarized in a brief memorial but past, present, and future generations of Quaternary scientists will long remember his landmark achievements in publishing, his scientific contributions, and his personal and professional class in all his endeavors

PTF11iqb: Cool supergiant mass loss that bridges the gap between Type IIn and normal supernovae

PTF11iqb was initially classified as a TypeIIn event caught very early after explosion. It showed narrow Wolf-Rayet (WR) spectral features on day 2, but the narrow emission weakened quickly and the spectrum morphed to resemble those of Types II-L and II-P. At late times, Halpha emission exhibited a complex, multipeaked profile reminiscent of SN1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN~1998S, although with weaker interaction with circumstellar material (CSM) at early times, and stronger CSM interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for weak CSM interaction added to the light curve of a normal SN~II-P. This plateau requires that the progenitor had an extended H envelope like a red supergiant, consistent with the slow progenitor wind speed indicated by narrow emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum --- meaning that the presence of such WR features in an early SN spectrum does not necessarily indicate a WR-like progenitor. [abridged] Overall, PTF11iqb bridges SNe~IIn with weaker pre-SN mass loss seen in SNe II-L and II-P, implying a continuum between these types.Comment: 21 pages, 12 figures, submitted to MNRA

Linear modeling of possible mechanisms for parkinson tremor generation

The power of Parkinson tremor is expressed in terms of possibly changed frequency response functions between relevant variables in the neuromuscular system. The derivation starts out from a linear loopless equivalent model of mechanisms for general tremor generation. Hypothetical changes in this model from the substrate of the disease are indicated, and possible ones are inferred from literature about experiments on patients. The result indicates that in these patients tremor appears to have been generated in loops, which did not include the brain area which in surgery usually is inactivated. For some patients in the literature, these loops could involve muscle length receptors, the static sensitivity of which may have been enlarged by pathological brain activity

Modest changes in Spi1 dosage reveal the potential for altered microglial function as seen in Alzheimer's disease

Genetic association studies have identified multiple variants at the SPI1 locus that modify risk and age of onset for Alzheimer’s Disease (AD). Reports linking risk variants to gene expression suggest that variants denoting higher SPI1 expression are likely to have an earlier AD onset, and several other AD risk genes contain PU.1 binding sites in the promoter region. Overall, this suggests the level of SPI1 may alter microglial phenotype potentially impacting AD. This study determined how the microglial transcriptome was altered following modest changes to Spi1 expression in primary mouse microglia. RNA-sequencing was performed on microglia with reduced or increased Spi1/PU.1 expression to provide an unbiased approach to determine transcriptomic changes affected by Spi1. In summary, a reduction in microglial Spi1 resulted in the dysregulation of transcripts encoding proteins involved in DNA replication pathways while an increased Spi1 results in an upregulation of genes associated with immune response pathways. Additionally, a subset of 194 Spi1 dose-sensitive genes was identified and pathway analysis suggests that several innate immune and interferon response pathways are impacted by the concentration of Spi1. Together these results suggest Spi1 levels can alter the microglial transcriptome and suggests interferon pathways may be altered in individuals with AD related Spi1 risk SNPs