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Large-scale food fortification of vegetable oils with vitamin A has been implemented successfully for decades in numerous African and Asian countries, contributing demonstrably to reductions in vitamin A deficiency. For these programmes, reliable and validated analytical data are essential to demonstrate compliance with legal standards and fortification levels. Commonly, many analytical laboratories use a saponification method for the quantitative analysis of retinyl palmitate (the mostly used form of vitamin A for fortification) in fortified oils, which implies a multiple-step procedure with long analysis times and the potential risk of analyte loss. The aim of the present study was to develop and validate a direct High-performance Liquid Chromatography (HPLC) method that reduces these sample preparation steps, leading to the cost- and time-efficient quantification of retinyl palmitate in fortified oils. Oil samples are dissolved into the HPLC solvents, then injected directly into a common C

Background: Aging is considered the most important risk factor for Alzheimer’s disease (AD). Recent research supports the theory that immunotherapy targeting the “oligomeric” forms of amyloid-β (Aβ) may halt the progression of AD. However, previous clinical trial of the vaccine against Aβ, called AN1792, was suspended due to cases of meningoencephalitis in patients. Objective: To develop a peptide sensitized dendritic cells (DCs) vaccine that would target oligomer Aβ and prevent an autoimmune response. Methods: Double transgenic APPswe/PS1ΔE9 (Tg) and C57BL/6J control mice were used in this study. Cytokine expression profile detection, characterization of antisera, brain GSK-3β, LC3 expression, and spatial working memory testing before and post-vaccination were obtained. Results: Epitope prediction indicated that E22W42 could generate 13 new T cell epitopes which can strengthen immunity in aged subjects and silence several T cell epitopes of the wild type Aβ. The silenced T cell epitope could help avoid the autoimmune response that was seen in some patients of the AN-1792 vaccine. The E22W42 not only helped sensitize bone marrow-derived DCs for the development of an oligomeric Aβ-specific antibody, but also delayed memory impairment in the APP/PS1 mouse model. Most importantly, this E22W42 peptide will not alter the DC’s natural immunomodulatory properties. Conclusion: The E22W42 vaccine is possibly safer for patients with impaired immune systems. Since there is increasing evidence that oligomeric form of Aβ are the toxic species to neurons, the E22W42 antibody’s specificity for these “oligomeric” Aβ species could provide the opportunity to produce some clinical benefits in AD subjects.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

This study investigated the role of cathode conditions and microbial fuel cell (MFC) connection modes of a 30 L pilot-scale constructed wetlands-microbial fuel cell (CW-MFC) in the performance of wastewater treatment and power generation. A MFC with four anodes and one cathode was integrated into constructed wetland (CW) to form a CW-MFC. Ten cathode working conditions of different connections, aeration and local effluent recirculation were tested and interpreted. The results demonstrated that activated cathode to guarantee cathode reaction is vital for CW-MFC. Higher power output of MFC was achieved with larger activated cathode area and wetting cathode environment. Parallel connection (each anode connected to cathode with separated resistor) of MFC was much better than combined connection (all anodes connected to cathode through one resistor only). The best wastewater treatment efficiency (91.7% of COD, 97.3% of ammonia-N) of the CW-MFC was reached with the highest power output (7.99 mW/m2) of MFC.

This article investigates the applicability of certain aspects of Lacanian psychoanalytic theory to the study of visual satire and/or caricature. Lacan’s treatment of the phenomenon of visual anamorphosis can provide a fruitful new way of thinking about the art of caricature. The visual exaggerations and distortions central to the art of caricature function as they do, as works of social or political satire, by virtue of the extent to which they expose the psychological emptiness or hollowness (castration) which inheres in all human social or symbolic activity. This argument is then applied to the political circumstances prevailing in late Georgian England: in particular, the visual satirical treatment devoted to the nature and status of the monarchy during this period is examined in the light of foregoing arguments.

Introduction: This paper describes the funding rates established in Ontario to reflect best practices in hospital-based care delivery for these endoscopic procedures: colonoscopy, colonoscopy biopsy, gastroscopy, gastroscopy biopsy, and colonoscopy combined with gastroscopy. Methods: The funding rates are based on direct costs and were established using a micro-costing approach after receipt of inputs from 3 working groups and a review of the administrative data and literature, where applicable. The first group advised on nursing activities, time, and staffing ratios along the patient pathway for each of the procedures. The second group provided recommendations about the duration for each procedure, and the third group provided information about supplies and equipment, their use, and costs. Results: The resulting funding rates are $161.18 for colonoscopy and $151.08 for gastroscopy (without accompanying interventions), $16.06 for colonoscopy biopsy and $8.22 for gastroscopy biopsy (added to the respective procedures), and $207.26 for combined colonoscopy and gastroscopy. Detailed costs for each component embedded in the rates are also provided. Conclusions: The rates came into effect in April 2018. The process and outcomes described here allowed for a transparent pricing mechanism in which funding follows the patient, clinical expert consensus is the basis for practice, and providers and payers both understand the components.

We use more than 10years of the Martian topside ionospheric data measured by the Mars Advanced Radar for Subsurface and Ionosphere Sounding radar sounder on board the Mars Express spacecraft to der ...

BACKGROUND AND GOALS The role of early proactive therapeutic drug level monitoring for anti-tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes. MATERIALS AND METHODS This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR. RESULTS Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P=0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P=0.11). CONCLUSIONS Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.

Considerable evidence has accumulated implicating a role for immune mechanisms in moderating the pathology in Alzheimer's disease dementia. However, the appropriate therapeutic target, the appropriate direction of manipulation, and the stage of disease at which to begin treatment remain unanswered questions. Part of the challenge derives from the absence of any selective pressure to develop a coordinated beneficial immune response to severe neural injury in adults. Thus, immune responses to the prevailing stimuli are likely to contain both beneficial and detrimental components. Knowledge gaps include: (1) how a biomarker change relates to the underlying biology, (2) the degree to which pathological stage group differences reflect a response to pathology versus trait differences among individuals regulating risk of developing pathology, (3) the degree to which biomarker levels are predictive of subsequent changes in pathology and/or cognition, and (4) experimental manipulations in model systems to determine whether differences in immune biomarkers are causally related to pathology.

Although the phenomenon of termite fishing by chimpanzees (Pan troglodytes) has historical and theoretical importance for primatology, we still have a limited understanding of how chimpanzees accomplish this activity, and in particular, about details of skilled actions and the nature of individual variation in fishing techniques. We examined movements, hand positions, grips, and other details from remote video footage of seven adult and subadult female chimpanzees using plant probes to extract Macrotermes muelleri termites from epigeal nests. Six chimpanzees used exclusively one hand (left or right) to grip the probe during termite fishing. All chimpanzees used the same repertoire of actions to insert, adjust, and withdraw the probe but differed in the frequency of use of particular actions. Chimpanzees have been described as eating termites in two ways—directly from the probe or by sweeping them from the probe with one hand. We describe a third technique: sliding the probe between the digits of one stationary hand as the probe is extracted from the nest. The sliding technique requires complementary bimanual coordination (extracting with one hand and grasping lightly with the other, at the same time). We highlight the importance of actions with two hands—one gripping, one assisting—in termite fishing and discuss how probing techniques are correlated with performance. Additional research on digital function and on environmental, organismic, and task constraints will further reveal manual dexterity in termite fishing., chimpanzee fishing termites using the sliding technique., Research Highlights ‐Using remote video footage from camera traps in Goualougo Triangle, Republic of Congo, we describe chimpanzees' manual actions, postures, and positions, and movements of the probe while they fished for termites in epigeal termite nests. ‐Chimpanzees used diverse grips, with and without the thumb, and two hands—one gripping, one assisting—to handle the probe delicately and to move it precisely. ‐We describe a new technique for recovering termites: sliding the probe between the digits of one stationary hand as the probe is extracted from the nest with the other hand, and a new action: oscillatory movements of the probe while it was inserted in the nest.

This article presents a new interpretation of the relationship between technology and warfare at sea before and during the First World War. It challenges existing accounts which view technological innovations as the primary driver of naval strategy during this period, and argues for a more contingent, incremental and contextualised approach to the relationship between technology and strategy. It illustrates these points with a specific example: the highly controversial topic of the Royal Navy’s so-called ‘Battle Cruisers’, three of which suffered catastrophic explosions at the Battle of Jutland in 1916. In doing so it forwards a new interpretation of British naval policy between 1890 and 1918, the Anglo-German naval arms race, and elements of the First World War at sea.

Background Circulating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer’s disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone variant macroH2A1 in the cerebral cortex, and loss of plaque/tangle pathology. Conversely, adult females display less severe autoimmunity and retain their AD-like phenotype. This study examines the link between immunity and other traits of the current 3xTg-AD model. Methods Young 3xTg-AD and wild-type mice drank a sucrose-laced 0.4 mg/ml solution of the immunosuppressant cyclophosphamide on weekends for 5 months. After behavioral phenotyping at 2 and 6 months of age, we assessed organ mass, serologic markers of autoimmunity, molecular markers of early AD pathology, and expression of genes associated with neurodegeneration. Results Chronic immunosuppression prevented hematocrit drop and reduced soluble Aβ in 3xTg-AD males while normalizing the expression of histone variant macroH2A1 in 3xTg-AD females. This treatment also reduced hepatosplenomegaly, lowered autoantibody levels, and increased the effector T cell population while decreasing the proportion of regulatory T cells in both sexes. Exposure to cyclophosphamide, however, neither prevented reduced brain mass and BDNF expression nor normalized increased tau and anxiety-related behaviors. Conclusion The results suggest that systemic autoimmunity increases soluble Aβ production and affects transcriptional regulation of macroH2A1 in a sex-related manner. Despite the complexity of multisystem interactions, 3xTg-AD mice can be a useful in vivo model for exploring the regulatory role of autoimmunity in the etiology of AD-like neurodegenerative disorders.

Scholars can interpret images as historical artifacts that perform enchantment. I will define enchantment as the action that images perform as part of a network of other things such as people, other images, and places. To this group of agents, we may add other actors such as lore, ritual, and the physical setting in which people encounter images. Taken together, these components form the ecology of vision. An image does not operate alone, but as part of an extended network or assemblage that engages viewers. One of the primary ways in which the assemblage is engaged is as a system of exchange, or intercession. Devotion to the Veil of Veronica will serve as a case study to show all of this at work.

Infants are more likely to develop lethal disseminated forms of tuberculosis compared with older children and adults. The reasons for this are currently unknown. In this study we test the hypothesis that antimycobacterial function is impaired in infant alveolar macrophages (AMfs) compared with those of adults. We develop a method of obtaining AMfs from healthy infants using rigid bronchoscopy and incubate the AMfs with live virulent Mycobacterium tuberculosis (Mtb). Infant AMfs are less able to restrict Mtb replication compared with adult AMfs, despite having similar phagocytic capacity and immunophenotype. RNA-Seq showed that infant AMfs exhibit lower expression of genes involved in mycobactericidal activity and IFNγ-induction pathways. Infant AMfs also exhibit lower expression of genes encoding mononuclear cell chemokines such as CXCL9. Our data indicates that failure of AMfs to contain Mtb and recruit additional mononuclear cells to the site of infection helps to explain the more fulminant course of tuberculosis in early life.

BACKGROUND: Non-lesional skin in atopic dermatitis (AD) is abnormal, but the pathobiology of lesional and non-lesional skin and the definition of endotypes are poorly understood. OBJECTIVE: To define lesional and non-lesional endotypes of AD by building the first US-based early life prospective cohort of children with AD, the Mechanisms of Progression from AD to Asthma in Children (MPAACH) cohort. METHODS: We assessed lesional and non-lesional skin TEWL, filaggrin (FLG) and alarmin (S100A8, S100A9) expression, staphylococcal colonization, and patterns of aeroallergen and food sensitization to define non-lesional and lesional phenotypes and endotypes. RESULTS: Pathophysiologic changes were present in lesional and non-lesional skin and were associated with SCORAD. Non-lesional skin had features characteristic of diseased skin including low FLG and high alarmin expression, and increased colonization with S. aureus. In a multivariate model, non-lesional, but not lesional, FLG expression was associated with the development of co-sensitization and moderate-severe AD. Lesional skin was characterized by further deficits in FLG expression (p

Introduction The quest to identify an effective therapeutic strategy for neurodegenerative diseases, such as mild congitive impairment (MCI) and Alzheimer's disease (AD), suffers from the lack of good human‐based models. Animals represent the most common models used in basic research and drug discovery studies. However, safe and effective compounds identified in animal studies often translate poorly to humans, yielding unsuccessful clinical trials. Methods A functional in vitro assay based on long‐term potentiation (LTP) was used to demonstrate that exposure to amyloid beta (Aβ42) and tau oligomers, or brain extracts from AD transgenic mice led to prominent changes in human induced pluripotent stem cells (hiPSC)‐derived cortical neurons, notably, without cell death. Results Impaired information processing was demonstrated by treatment of neuron‐MEA (microelectrode array) systems with the oligomers and brain extracts by reducing the effects of LTP induction. These data confirm the neurotoxicity of molecules linked to AD pathology and indicate the utility of this human‐based system to model aspects of AD in vitro and study LTP deficits without loss of viability; a phenotype that more closely models the preclinical or early stage of AD. Discussion In this study, by combining multiple relevant and important molecular and technical aspects of neuroscience research, we generated a new, fully human in vitro system to model and study AD at the preclinical stage. This system can serve as a novel drug discovery platform to identify compounds that rescue or alleviate the initial neuronal deficits caused by Aβ42 and/or tau oligomers, a main focus of clinical trials.

In recent years, there has been an increasing interest in the application of Artificial Intelligence - and especially Machine Learning - to the field of Sustainable Development (SD). However, until now, NLP has not been applied in this context. In this research paper, we show the high potential of NLP applications to enhance the sustainability of projects. In particular, we focus on the case of community profiling in developing countries, where, in contrast to the developed world, a notable data gap exists. In this context, NLP could help to address the cost and time barrier of structuring qualitative data that prohibits its widespread use and associated benefits. We propose the new task of Automatic UPV classification, which is an extreme multi-class multi-label classification problem. We release Stories2Insights, an expert-annotated dataset, provide a detailed corpus analysis, and implement a number of strong neural baselines to address the task. Experimental results show that the problem is challenging, and leave plenty of room for future research at the intersection of NLP and SD., Comment: 18 pages, 9 figures. Accepted at EMNLP 2020

Author(s): Albrecht, Courtney; Hicks, Amelia; Hornbaker, Victoria; Khalid, Sara; Kumagai, Lucita; Morgan, David; Okasaki, Keith | Abstract: This document sets forth the California Department of Food and Agriculture (CDFA), Citrus Pest and Disease Prevention Division (CPDPD) statewide Action Plan for Asian citrus psyllid (ACP) and Huanglongbing (HLB). This document details the program implemented by CPDPD to sustain and protect California’s commercial citrus production, residential citrus plantings, and natural resources.

Aims Our goals were to compare the effect of adding fentanyl to midazolam in a double-blinded, randomized, placebo-controlled trial and determine if fentanyl enhances sedation, increases adverse events or effects time of the procedure or discharge. Methods Patients 18 to 65 years scheduled for outpatient upper endoscopy were eligible for the study. Patients were randomized to receive either 100 mcg/2 mL of Fentanyl or 2 mL of placebo IV with a double-blinded protocol. All patients received 2 mg of intravenous midazolam initially. Additional midazolam could be given to achieve adequate sedation. Results There were 68 patients randomized to the Fentanyl group and 69 patients to the placebo group. The mean dose of midazolam was 4.0 mg for the Fentanyl group and 5.2 mg for placebo group (P=0.003). Both endoscopist and nurse independently rated sedation to be better in the fentanyl group (P=0001). The patient did not perceive any difference in sedation (P=0.4). Procedure time was significantly shorter in the Fentanyl group (8.5 versus 11.1 minutes, P=0.001), with no difference in the discharge time. There was significantly less retching observed in patients in the fentanyl group (P

Unnecessary investigations, inappropriate treatment, worsening disease, and frustration for both patients and health care professionals are the hallmarks of hidradenitis suppurativa (HS) management. In light of a new treatment algorithm and biologic therapies made available to patients, an HS model of care is outlined in this article. The recommendations and management strategy presented here have been developed to help address the currently unmet needs of this patient population. The patient-centred model of care and disease management strategies were developed through the guidance and recommendations of HS medical experts in Newfoundland and Labrador. This article lays the foundation for the resources and steps required to change the status of this orphan disease and firmly embed patients with HS within a coordinated and integrative system of care.

Beginning with a definition of the sacred as a two-fold process of making things special, which consists of accentuation and affiliation, this essay proceeds to argue that things are made sacred in devotional piety and in fine art in parallel ways that configure images within webs of agents. The two kinds of imagery perform in practices of sacralization that move toward different ends. The production of aura is at work in each case, but operates with distinct aims. The essay then presents a historical account of fine art as a modern development tied to the rise of the nation-state, in which secularization extended to making art independent of religious institutions and patrons, allowing it to develop in a way that should be distinguished from devotional imagery. This does not mean that religion withers in the modern era, but that art developed its own mode of sacralization.

Background and Objective Major depressive disorder is a multidimensional disease, in which demonstrating the efficacy of treatments is difficult. The Hamilton Rating Scale for Depression (HRSD) and the Montgomery–Asberg Depression Rating Scale (MADRS) cover different domains but are used interchangeably as primary measures of the outcome in trials and—with standardized measures—in meta-analyses. We aimed at understanding (i) whether the choice of the outcome measurement tool can influence the outcome of a trial, and if so, (ii) whether one systematically outperforms the other, and (iii) whether using standardized measures of the effect in meta-analysis is justified. Methods Short-term randomized trials in patients with major depressive disorder that used both the scales were systematically searched and the results were collected. To quantify the differences in the results—both in terms of the standardized mean difference (SMD) and odds ratio (OR) for response—and their range, data were analyzed and plotted with the Bland–Altman method. Results 161 comparisons from 80 studies were included, involving a total of 18,189 patients. Neither of the two scales appears systematically more sensitive to the treatment effect than the other in terms of SMDs (P-value = 0.06, 95% CI −0.044 to 0.001) or ORs (P-value = 0.15, 95% CI −0.25 to 0.04). However, the variability of differences between the HRSD and MADRS largely depends on the number of patients included in the comparison. Conclusion No systematic differences between the two scales were found supporting the use of standardized measures in meta-analyses. However, the same trial may give very different results with either scale, especially in small trials. Further research is needed to understand the causes of this variability.

Whatever the actual status of marriage and the family as institutions there can be little doubt that talk about these topics remains a popular activity. The talk, of course, varies considerably in terms of level of abstraction and degree of formality ranging from the speech at a party political conference or the scholarly paper to everyday talk about particular weddings, baptisms or funerals and the complex and shifting nexus of relationships and obligations that come to the fore on such occasions. The differences between these two sets of practices might be characterised as approximating to the differences between a speech and a conversation. In both cases words are uttered but in the case of the conversation these words are exchanged and conducted with all the interplays between verbal and non-verbal cues, modifications and qualifications and hesitations that characterise interpersonal encounters generally. Exchange is not absent in the former case, of course, although it may be conducted more formally, through question and answer mediated through a chair or through verbal and written exchanges through the mass media, exchanges that do not require the direct co-presence of the other.

Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) radar sounder on board the Mars Express spacecraft revealed oblique reflections coming systematically from apparently stable dens ...

Study Objectives To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (Aβ42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) elderly. Methods Longitudinal study with mean follow-up time of 2.52 ± 0.51 years. Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF Aβ42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA. Results In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B = .06, 95% CI = .02, .11 and B = .08, 95% CI = .05, .12, respectively) and decrease in CSF Aβ42 levels (B = −2.71, 95% CI = −3.11, −2.35 and B = −2.62, 95% CI = −3.23, −2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA− participants. No significant variations in the biomarker changes over time were seen in the AD group. Conclusions In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.

Study Objectives: To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (A beta 42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer's disease (AD) elderly. Methods: Longitudinal study with mean follow-up time of 2.52 +/- 0.51 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF A beta 42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA. Results: In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B =.06, 95% CI =.02,.11 and B =.08, 95% CI =.05, .12, respectively) and decrease in CSF A beta 42 levels (B = -2.71, 95% CI = -3.11, -2.35 and B = -2.62, 95% CI = -3.23, -2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA- participants. No significant variations in the biomarker changes over time were seen in the AD group. Conclusions: In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.

Objectives:Stereotactic radiotherapy (SBRT) is gaining popularity although its use in head and neck cancer (HNC) is not well defined. The primary objective was to review the published evidence regarding the use of stereotactic radiotherapy in HNC.Methods:A literature search was performed by using MEDLINE and EMBASE databases for eligible studies from 2000 to 2019 and 26 relevant studies were identified.Results:Literature demonstrates a heterogeneous use of this technique with regards to patient population, primary or salvage treatment, dose fractionation regimens, outcomes and follow-up protocols. Carotid blow out syndrome is a risk as with other forms of reirradiation but alternative treatment regimens may reduce this risk.Conclusion:At present there is a lack of evidence regarding SBRT as a primary treatment option for HNC and definitive answers regarding efficacy and tolerability cannot be provided but there is growing evidence that SBRT reirradiation regimens are safe and effective. In lieu of evidence from large Phase III trials, we define appropriate organ at risk constraints and prescription doses, with accurate plan summation approaches. Prospective randomised trials are warranted to validate improved treatment outcomes and acceptable treatment morbidity.Advances in knowledge:This article provides a comprehensive review of evidence of use of stereotactic radiotherapy in HNC site (either as a primary treatment or as reirradiation). We also provide an evidence–based approach to the implementation and practical consideration of stereotactic radiotherapy in HNC.

SummaryBackground Clinicians are advised to refer patients with lower gastrointestinal (GI) alarm features for urgent colonoscopy to exclude colorectal cancer (CRC). However, the utility of alarm features is debated. Aims To assess whether performance of alarm features is improved by using a symptom frequency threshold to trigger referral, or by combining them into composite variables, including minimum age thresholds, as recommended by the National Institute for Health and Care Excellence (NICE). Methods We collected data prospectively from 1981 consecutive adults with lower GI symptoms. Assessors were blinded to symptom status. The reference standard to define CRC was histopathological confirmation of adenocarcinoma in biopsy specimens from a malignant-looking colorectal lesion. Controls were patients without CRC. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values were calculated for individual alarm features, as well as combinations of these. Results In identifying 47 (2.4%) patients with CRC, individual alarm features had sensitivities ranging from 11.1% (family history of CRC) to 66.0% (loose stools), and specificities from 30.5% (loose stools) to 75.6% (family history of CRC). Using higher symptom frequency thresholds improved specificity, but to the detriment of sensitivity. NICE referral criteria also had higher specificities and lower sensitivity, with PPVs above 4.8%. More than 80% of those with CRC met at least one of the NICE referral criteria. Conclusions Using higher symptom frequency thresholds for alarm features improved specificity, but sensitivity was low. NICE referral criteria had PPVs above 4.8%, but sensitivities ranged from 2.2% to 32.6%, meaning many cancers would be missed.

After vestibular labyrinth injury, behavioral measures of vestibular performance recover to variable degrees (vestibular compensation). Central neuronal responses after unilateral labyrinthectomy (UL), which eliminates both afferent resting activity and sensitivity to movement, have been well-studied. However, unilateral semicircular canal plugging (UCP), which attenuates angular-velocity detection while leaving afferent resting activity intact, has not been extensively studied. The current study reports response properties of yaw-sensitive non-eye-movement rhesus macaque vestibular neurons after compensation from UCP. The responses at a series of frequencies (0.1–2 Hz) and peak velocities (15–210°/s) were compared between neurons recorded before and at least 6 wk after UCP. The gain (sp/s/°/s) of central type I neurons (responding to ipsilateral yaw rotation) on the side of UCP was reduced relative to normal controls at 0.5 Hz, ±60°/s [0.48 ± 0.30 (SD) normal, 0.32 ± 0.15 ipsilesion; 0.44 ± 0.2 contralesion]. Type II neurons (responding to contralateral yaw rotation) after UCP have reduced gain (0.40 ± 0.27 normal, 0.35 ± 0.25 ipsilesion; 0.25 ± 0.18 contralesion). The difference between responses after UCP and after UL is primarily the distribution of type I and type II neurons in the vestibular nuclei (type I neurons comprise 66% in vestibular nuclei normally; 51% ipsilesion UCP; 59% contralesion UCP; 38% ipsilesion UL; 65% contralesion UL) and the magnitude of the responses of type II neurons ipsilateral to the lesion. These differences suggest that the need to compensate for unilateral loss of resting vestibular nerve activity after UL necessitates a different strategy for recovery of dynamic vestibular responses compared to after UCP.

Although the Parmenidean poem (late 6th-early 5th centuries BCE) is in epic meter and teems with vivid imagery, it has been translated into the domain of philosophy since its earliest reception. Within this domain it has traditionally been interpreted as the first "explicit and self-conscious argumentation" of western philosophy (Gallop 1984, 3). Yet, the poem aims at persuasion and affect rather than logical demonstration (Smith 2003, 269-75).Working primarily with a sense of translation as critical reception, this paper articulates the history of a translational protocol that excises conceptual matter from linguistic form (Cassin 2010, 19; Batchelor 2010, 49-50), reducing the semantic range of the Parmenidean poem. Beginning with Zeno and Melissus (early 5th c BCE), a series of translations reduces the Parmenidean poem into a vehicle for a separable and fully translatable doctrine, stabilizing and homogenizing a thinking that otherwise persists as polyvalent and heterogeneous.

This chapter contends that believing and making-believe are not strongly isolated from one another—indeed, often they intermingle. The magic of images often consists in their ability to make belief from the fiction of make-believe. A close analysis of a famous painting of Pygmalion and Galatea, drawn from Ovid’s ancient verse, forms the central discussion about the power of images to make belief from make-believe. In making this comparison, the author establishes that enchantment is an instrument for representation of interior dynamics that lead to healthy psychological development; the imaginative condition for artistic enjoyment and creative thinking; the ascription of agency to things that are not animate; and the assignment of intentionality or will to events that might otherwise be attributed to random occurrence.

BACKGROUND: Bowel preparation is essential as a quality measure of colonoscopy. Many studies have reported factors associate with a good bowel preparation but few have evaluated the effect of baseline bowel habit as a predictor. AIMS: We aimed to identify factors associated with a good bowel preparation. Specifically, we wanted to determine if baseline bowel habit predicted response to bowel preparation and how accurate patient perception of their bowel preparation was compared to a standard bowel prep score. METHODS: Prospective data was collected from out-patients undergoing colonoscopy in the form of a survey in the waiting room of the endoscopy unit. Data included baseline patient and endoscopy factors, and was compared to endoscopist reported Ottawa Bowel Preparation Score (OBPS) to look for correlation in a statistical analysis. RESULTS: Data were available for 243 patients; mean age 57 years, 46% male, 51% had more than a high school education. PEG-Lyte solution (4L) was used for bowel preparation by 48 (19.8%) and sodium picosulfate by 190 (80.2%). The mean OBPS was 3.48 +/- 2.47 SD. The baseline Bristol Stool Form Score (BSFS) was 1–2 in 13%, 3–5 in 74%, and 6–7 in 13% of patients, but BSFS did not predict a better OBPS (p=0.82). The mean times from the patients’ last fluids and last solids food to colonoscopy was 5.47 +/- 5.0 and 27.8 +/- 4.8 hours respectively, but neither was a significant predictor of better bowel prep. More procedures were in the afternoon (78%) but there was no difference in the OBPS in the morning and afternoon (Mann-Whitney test, p=0.47). Self-assessment of the quality of bowel preparation was not correlated with OBPS (Spearman rho 0.03, p=0.63), but a patients’ level of concern with not having a clean enough preparation was correlated with a worse OBPS (Spearman rho -0.175, p=0.012). The only significant predictor in a univariate analysis was bowel preparation type with sodium picosulfate being significantly better (Mann Whitney test, p

Government-led regeneration schemes and policies encouraging the use of brownfield land present a challenge, particularly in coalfield areas. Coalfields have typically experienced multiple phases of development and can be susceptible to a suite of problematic ground conditions that may be rooted in the near-surface geology or result from anthropogenic activity. Such problems, related to the nature of void backfill, undermined and unstable ground and the presence of contaminated land in the near-surface, may deter investment in the very areas earmarked for redevelopment. An understanding of previous developments within coalfields is required to identify potential geological hazards, so that regeneration proposals include measures that address these issues. Public records of landfill and site investigations, and minerals exploration including opencast mine plans can reveal the distribution, thickness and high-level descriptions of fill materials, although the coverage of data typically precludes a comprehensive analysis of entire cities. The best way to show the spatial distribution of fill materials is currently as a two dimensional national/regional scale dataset. Depending on the distribution of data points, however, 3D modelling can be possible, which is much more detailed and accurate. Focusing on the heavily urbanised county of West Yorkshire in northern England, the assessment of opencast coal mining on the landscape and benefits of quantifying the impact are discussed. We demonstrate how certain types of publicly available data allow a greater understanding of the interaction between human activity and natural superficial and bedrock geology. If successful, this approach can help lessen the impact of delays and increased financial costs caused by unforeseen ground conditions.

There are few data concerning the utility of symptoms and signs at first presentation in predicting a diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). We conducted a study to examine this issue in secondary care.We collected complete symptom, colonoscopy, and histology data prospectively from 1,981 consecutive adult patients with lower gastrointestinal symptoms at two hospitals in Hamilton, Ontario. Assessors were blinded to symptom status. The reference standard used to define the presence of UC or CD was according to accepted histological criteria. Patients without UC or CD served as controls. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for individual items from the clinical history, as well as combinations of these.In identifying 302 patients with inflammatory bowel diseases (IBD), positive LRs for individual items ranged from 1.18 (incomplete emptying) to 2.30 (passage of stools more than four times per day at least most of the time) and negative LRs from 0.70 (bloody stools) to 0.96 (incomplete emptying). Combinations of items had a high specificity, but at the expense of sensitivity. Items that were independent predictors of IBD after logistic regression analysis were family history of IBD, younger age, passage of stools more than four times per day ≥75% of the time, urgency most of the time, and anemia.Individual items from the clinical history are not helpful in predicting a diagnosis of UC or CD. However, this may be because some items lacked sufficient detail. Combinations of symptoms and computer models had a high specificity, but overall were only modestly useful diagnostically. Future studies should evaluate biological markers in combination with symptoms to improve accuracy.

This paper discusses the approaches to characterizing and monitoring two very similar sites in proximity. It explores the paucity of scientific evidence for understanding conditions of preservation, and techniques for monitoring it, that presently exist for sites that lie in superficial unconsolidated sediments within which a capillary fringe has developed above a groundwater table, rather than for a more conventional water-logged site. Challenge and review by peers is essential for a robust approach to ensuring management measures are appropriate, rather than relying on the knowledge and experience of a single individual or team. Since 2007, a monitoring programme for the internationally important timber platform at Hanson's Must Farm clay extraction site has been developed and enhanced, whilst excavations within the footprint of the quarry have revealed outstanding preservation of organic remains. The 3000 year inundation and sedimentary sequence, and the 100 years recent development in this landscape, are described along with the unusual preservation processes which have contributed to exceptional survival of archaeological remains. The results from Must Farm are contrasted to the paucity of monitoring data from Flag Fen, and the separate trajectories between a developer-funded project and a nationally protected monument are discussed.

SummaryBackground Psychological factors may influence persistence and perceived severity of symptoms in irritable bowel syndrome (IBS). Literature suggests that somatisation is associated with IBS. However, the relationship between IBS subtype, symptoms of IBS and somatisation is unclear. Aim To examine this issue in a large cohort of secondary care patients. Methods Demographic and gastrointestinal (GI) symptom data were collected from 4224 adult patients via the Rome III questionnaire. Somatisation data were collected using the patient health questionnaire-12. Mean somatisation score and number of somatic symptoms were compared between IBS patients and controls with minimal GI symptoms, and between IBS subtypes using analysis of variance. Effect of level of somatisation on symptom frequency was compared according to IBS subtype using a χ2 test. Results 840 patients met Rome III criteria for IBS, controls were 2137 patients with GI symptoms without IBS. Mean somatisation scores and number of somatic symptoms were higher in IBS vs. controls (P

Item does not contain fulltext BACKGROUND: Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. METHODS: Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033. FINDINGS: Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p

Collecting is a particular kind of activity that should not be confused with other forms of accumulation. For instance, hunting and gathering food, rounding up stray cattle, or calling in school ch...

Gastrocolic fistulas are observed in association with several conditions. Traditionally, peptic ulcer disease was commonly implicated in the formation of gastrocolic fistulas; however, this is now a rare etiology. Here, we present a case of gastrocolic fistula secondary to peptic ulcer disease alone, in addition to reviewing the literature and providing options for diagnosis and treatment.

Objectives: The objective of this systematic review was to identify and appraise the existing evidence of role of palliative radiotherapy for locally advanced non-metastatic head and neck cancer. Methods: A systematic search of the literature was conducted using Medline, Embase and Cochrane databases and relevant references were included. Results: Literature search revealed a wide variation in dose fractionation regimens. Reported outcomes showed high efficacy and low rate of significant side effects, except in studies utilising higher doses of radiotherapy where higher grade toxicities were seen. Reported median overall survival was in the range of 33-17 months, but most studies reported median survival of around 6 months. Conclusions: The choice of palliative radiotherapy varies significantly. This is in contrast to regimens of curative radiotherapy for locally advanced head and neck cancer, which are well standardised. Given the reported relatively short overall survival of this patient group, an ideal treatment should be of the shortest possible duration whilst ensuring effective palliation and minimal side effects. Future well designed trials are needed to evaluate quality of life and duration of side effects in addition to survival and severity of toxicities in this group of patients. Crown Copyright (C) 2017 Published by Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 126 (2018) 558-567

Considerable effort has gone into generating mathematical models for use in the assessment of risk of specific foodborne pathogens present in various foodstuffs. The usefulness of such models, especially to the food industry and regulators, is subject to generalizations made and assumptions used, by modellers. In particular, accuracy of these models is highly dependent on the human dose response data incorporated. For many pathogens, these data are sparse and (when available) are widely accepted as often inaccurate. The sweeping assumption made in all such models, that all strains of the same pathogen species are equally virulent and able to cause disease in humans, is incorrect. In this review, we speculate that some of the major bacterial foodborne pathogens (e.g., Salmonella, Campylobacter and Shiga toxin-producing Escherichia coli) substantially vary between strains, in their ability to (1) survive in and respond to the environment from the point of detection of the pathogen load in food, (2) colonize the human gut and (3) generate a disease outcome which will be observed as a dose response. There is increasing evidence for these speculations, and we propose that this variation could have a major impact on the dose response curves currently used for microbiological risk assessments. We discuss the importance of mechanisms that facilitate the survival of pathogens as they transit from farm-to-fork and then into the host. We also comment on the impact of genetic polymorphisms and how they impact the widely differing infectious doses observed with many pathogens. In conclusion, we suggest that mathematical models should be modified to incorporate more realistic dose response data, based on known knowledge of strain variation in environmental survival, colonization and clinical impact. Such modification would more accurately inform the food industry and regulators.

Over the last century there has been a significant increase in the number and size of oil spills to the marine environment due to the global proliferation of oil and gas extraction as well as the number of tankers and other maritime transport infrastructure associated with increased production. Efforts have traditionally been focussed on containment and deflection of oil rather than responding to wildlife. The present study examines total oiled wildlife effort in response to maritime spills for 286 recorded globally. Between 1910 and 1961 there was an average of 1.23 ± 0.43 incidents per year, spilling an average of 114,062 ± 352,512 tonnes of oil per year. These averages increased to 3.83 ± 2.65 events with 123,277 ± 166,735 tonnes of oil spilt per year from 1962 to 1990, and again, from 1991 to 2012 to 6.50 ± 5.17 events with 164,299 ± 290,655 tonnes of oil spilt per year. Offshore platform and tanker spills have accounted for 37% and 27% of this total, respectively. Of the 104 recorded instances where wildlife interactions occurred (40%), spill volume was not related to the total number of animals caught, oiled or pre-emptively; however, it was related to the number of carcasses collected. A lack of planning for Oiled Wildlife Response (OWR) was identified as a contributing factor exacerbating the impact of a spill on wildlife and for resourcing a response. Inadequacies within operator and government contingency planning, to prepare for and sustain a wildlife response for extended periods, can be overcome by using a mobilisation model that integrates wildlife carer networks, government regulatory agencies and operator resourcing via an independent coordinating organisation consisting of a small group of personnel highly experienced and trained in maritime operations and marine science with access to a network of persons with experience in responding to wildlife and their handling, treatment and rehabilitation.