Publications by authors named "Geddes S"

Pioneering road markings for motorcyclists, designed as Perceptual Rider Information for Maximising Expertise and Enjoyment (PRIMEs) were installed on approach to demanding bends at 22 trial sites and two comparison sites across the West Highlands of Scotland. The markings provided a series of 'gateways' to encourage safer riding. With 32,213 motorcyclists observed, the following statistically significant results were observed: speed reductions at 10 trial sites; positive changes in lateral position at the final PRIME gateway marking at 15 trial sites and positive changes in lateral position at the apex of the bend at 13 trial sites; reductions in braking at nine trial sites; increases use of PRIME road markings across 18 of the 22 trial sites.

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Introduction: Systems science methodologies have been used in attempts to address the complex and dynamic causes of childhood obesity with varied results. This paper presents a protocol for the Reflexive Evidence and Systems interventions to Prevention Obesity and Non-communicable Disease (RESPOND) trial. RESPOND represents a significant advance on previous approaches by identifying and operationalising a clear systems methodology and building skills and knowledge in the design and implementation of this approach among community stakeholders.

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Ecosystem restoration is a critical component of land management, countering the loss of native biodiversity. Restoration efforts are enhanced by reintroducing naturally occurring ecosystem processes, including disturbances that may impact species characteristics such as niche position or niche size. In grasslands, grazing and fire affect plant diversity and habitat complexity, which potentially influence insect dietary behaviors and thus their contributions to functions like seed and arthropod predation.

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  • Selective serotonin reuptake inhibitors (SSRIs) are common antidepressants that take weeks to become effective, but chronic use can cause changes in serotonin neurotransmission due to 5-HT1A autoreceptor desensitization.
  • Research on mice lacking 5-HT1A autoreceptors showed that while SSRIs like fluoxetine can enhance serotonin levels, they also led to increased anxiety responses, especially in certain behavioral tests.
  • The findings suggest that a lack of 5-HT1A autoreceptors may cause an unusual increase in anxiety when using SSRIs, indicating that monitoring these receptors could help predict adverse reactions to SSRI treatment.
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PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-.

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Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 , we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons (). In mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe.

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Background: Fine-needle aspiration (FNA) biopsy of lung lesions is a highly accurate method for diagnosing and staging of lung cancers, particularly in patients with advanced cancer. Although, the majority of FNA cases of non-small cell lung carcinoma (NSCLC) can be subclassified by hematoxylin and eosin (H&E) sections, immunohistochemical (IHC) markers are usually necessary for difficult cases. Our previous study has shown that both P40 and P63 demonstrate differential sensitivity and specificity in the subclassification of squamous cell carcinoma (SqCC) using tumor tissue microarrays (TMA).

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  • The C (-1019) G rs6295 polymorphism in the serotonin-1A receptor gene has mixed associations with major depression, indicating potential compensatory mechanisms that foster resilience.
  • The study examined Deaf1-/- mice, which lack the Deaf1 repressor, revealing increased 5-HT1A autoreceptor expression but unchanged receptor function, suggesting adaptations occur over generations.
  • Male Deaf1-/- mice showed anxiety-like behavior in certain tests, while females only exhibited increased anxiety in specific situations, highlighting the sex-dependent effects of Deaf1 on anxiety and its possible implications for depression sensitivity.
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Serotonin (5-HT) neurons located in the raphe nuclei modulate a wide range of behaviors by means of an expansive innervation pattern. In turn, the raphe receives a vast array of synaptic inputs, and a remaining challenge lies in understanding how these individual inputs are organized, processed, and modulated in this nucleus to contribute ultimately to the core coding features of 5-HT neurons. The details of the long-range, top-down control exerted by the medial prefrontal cortex (mPFC) in the dorsal raphe nucleus (DRN) are of particular interest, in part, because of its purported role in stress processing and mood regulation.

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Personalized treatment of lung cancer requires an accurate subclassification of non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and other subtypes. In poorly differentiated tumors especially on small fine-needle aspirate specimens, the subclassification could be difficult in certain cases. Our previous study using resected tumor tissue has shown that the combination of commonly used individual markers (thyroid transcription factor 1 [TTF-1], P40, and Napsin A) into a novel triple marker has high sensitivity and specificity in subclassification of NSCLC and also the advantage of using minimal tumor tissue.

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Background: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and amplification are detected in 1% of primary lung adenocarcinomas (ADCs) and in 38% of primary lung squamous cell carcinomas. Alterations of PIK3CA in metastatic non-small cell lung carcinoma (NSCLC), however, are still not fully understood. This study investigated PIK3CA alterations in metastatic ADCs and correlated the findings with those for other commonly tested molecular abnormalities via fine-needle aspiration (FNA) and small-core biopsy materials.

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A description of a letter bought at auction and the subsequent research of the 18th century dentist.

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Background: Fine needle aspiration (FNA) biopsy plays a critical role in the diagnosis and staging of lung primary and metastatic lung carcinoma. Accurate subclassification of adenocarcinoma (ADC) and/or squamous cell carcinoma (SqCC) is crucial for the targeted therapy. However, the distinction between ADC and SqCC may be difficult in small FNA specimens.

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Article Synopsis
  • SSRIs, like citalopram, enhance serotonin transmission over time rather than immediately, which explains the delayed therapeutic effects of these medications.
  • Short-term treatment with citalopram can initially weaken the strength of glutamate synapses onto serotonin-producing neurons in the brain, which is opposite to the desired effect of increasing serotonin.
  • Understanding how SSRIs dynamically modulate synaptic activity can help clarify both their delayed antidepressant effects and potential early increases in suicide risk during treatment.
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Background: SALL4 and OCT4 are transcription factors and play essential roles in stem cell development and oncogenesis. However, the expression of these transcription factors has not been well studied in lung cancers. In this study, we evaluated the expression of SALL4 and OCT4 in non-small cell lung carcinomas (NSCLC) by immunochemistry.

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Objectives: Endorectal endoscopic ultrasound (ERUS) allows highly detailed assessment of the rectal wall layers and visualization of the extraluminal structures. Herein, we study the utility of ERUS fine-needle aspiration (FNA) to evaluate perirectal lesions.

Study Design: Forty-nine ERUS-FNAs were retrieved from the cytopathology archives of The Johns Hopkins Hospital.

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Organic molecules are a significant and highly varied component of atmospheric aerosols. Measurement of aerosol composition and improvements in our understanding of the complex chemistry involved in their formation and aging are being aided by innovations in soft ionization aerosol MS. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.

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A new method, near-infrared laser desorption/ionization aerosol mass spectrometry (NIR-LDI-AMS), is described for the real time analysis of organic aerosols at atmospherically relevant mass loadings. Use of a single NIR laser pulse to vaporize and ionize particle components deposited on an aluminum probe results in minimal fragmentation to produce exclusively intact pseudomolecular anions at [M-H](-). Limits of detection (total particulate mass sampled) for oxidized compounds of relevance to atmospheric primary and secondary organic aerosol range from 89 fg for pinic acid to 8.

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Mutations in the protein dysferlin, a member of the ferlin family, lead to limb girdle muscular dystrophy type 2B and Myoshi myopathy. The ferlins are large proteins characterised by multiple C2 domains and a single C-terminal membrane-spanning helix. However, there is sequence conservation in some of the ferlin family in regions outside the C2 domains.

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UvrB is the damage recognition element of the highly conserved UvrABC pathway that functions in the removal of bulky DNA adducts. Pivotal to this is the formation of a damage detection complex that relies on the ability of UvrB to locate and sequester diverse lesions. Whilst structures of UvrB bound to DNA have recently been reported, none address the issue of lesion recognition.

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Background: This study was designed to optimize a liquid-based Papanicolaou (Pap) test by using common cytopathology laboratory equipment and resulted in an inexpensive test that was equivalent at least diagnostically to the conventional Papanicolaou (Pap) smear.

Methods: Adult women (n = 482) were consented, enrolled, and included in this Institutional Review Board-approved study. After conventional Pap smear slides were obtained, clinicians placed the collection device with residual cells from the uterine cervix in a preservative fluid.

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The UvrABC pathway is a ubiquitously occurring mechanism targeted towards the repair of bulky base damage. Key to this process is UvrB, a DNA-dependent limited helicase that acts as a lesion recognition element whilst part of a tracking complex involving UvrA, and as a DNA-binding platform required for the presentation of damage to UvrC for subsequent processing. We have been able to determine the structure of a ternary complex involving UvrB* (a C-terminal truncation of full-length UvrB), a polythymine trinucleotide and ADP.

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An understanding of genetic variation and structure of pest populations has the potential to improve the efficiency of measures to control them. Genetic analysis was undertaken at five microsatellite loci in four native Australian and 14 introduced New Zealand populations of the common brushtail possum Trichosurus vulpecula in order to document these parameters. Genetic variation in New Zealand populations, and phylogenetic relationships among Australian and New Zealand populations, were largely predicted by the recorded introduction history.

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