Eye-tracking while reading passives: An event structure account of difficulty

Among existing accounts of passivisation difficulty, some argue it depends on the predicate semantics (i.e. passives are more difficult with subject-experiencer than agent-patient verbs). Inconsistent with the accounts that predict passive difficulty, Paolazzi et al. (2019) found that passives were read faster than actives at the verb and object by-phrase in a series of self-paced reading experiments, with no modulation of verb type. However, self-paced reading provides limited direct measurement of late revision/interpretive processing. We used modified stimuli from Paolazzi et al. (2019) to re-examine this issue in two eye-tracking while reading experiments. We found that in late measures, passives with subject-experiencer verbs had longer fixation durations than actives at the verb and two subsequent regions but no difference was observed across agent-patient verbs. Subject-experiencer verbs provide a state, but the passive structure requires an event. Thus, the required eventive interpretation is coerced with subject-experiencers (if possible) and induces difficulty

Poverty-Centred Rural Road Funds Sharing in Sub-Saharan Africa

Poverty-centred allocation of funds for rural roads and their systematic prioritisation are important to enhance sustainability, provide equality of transport opportunities and mitigate poverty. The aim of this work was to investigate and develop new approaches with specific emphasis on sub-Saharan Africa, given that the existing decision systems do not appropriately consider social impacts and poverty. An understanding of rural road funds allocation and road scheme prioritisation to alleviate poverty is important as road transport is by far the most predominant form of transport in Africa. This study developed new allocation and prioritisation processes for rural roads based on expert opinion surveys and empirical evidence, which were then applied to analyse allocation and road scheme selection processes used in Uganda and Ghana. The study found that the multi-dimensional poverty index is the most highly prioritised factor in rural road scheme selection and, for regional rural road funds sharing, poverty is equally weighted with the rural accessibility index. A goal programming model, based on expert opinion weightings, is recommended for poverty alleviation

Mouse Model of Mutated in Colorectal Cancer Gene Deletion Reveals Novel Pathways in Inflammation and Cancer

© 2019 The Authors Background & Aims: The early events by which inflammation promotes cancer are still not fully defined. The MCC gene is silenced by promoter methylation in colitis-associated and sporadic colon tumors, but its functional significance in precancerous lesions or polyps is not known. Here, we aimed to determine the impact of Mcc deletion on the cellular pathways and carcinogenesis associated with inflammation in the mouse proximal colon. Methods: We generated knockout mice with deletion of Mcc in the colonic/intestinal epithelial cells (MccΔIEC) or in the whole body (MccΔ/Δ). Drug-induced lesions were analyzed by transcriptome profiling (at 10 weeks) and histopathology (at 20 weeks). Cell-cycle phases and DNA damage proteins were analyzed by flow cytometry and Western blot of hydrogen peroxide–treated mouse embryo fibroblasts. Results: Transcriptome profiling of the lesions showed a strong response to colon barrier destruction, such as up-regulation of key inflammation and cancer-associated genes as well as 28 interferon γ–induced guanosine triphosphatase genes, including the homologs of Crohn's disease susceptibility gene IRGM. These features were shared by both Mcc-expressing and Mcc-deficient mice and many of the altered gene expression pathways were similar to the mesenchymal colorectal cancer subtype known as consensus molecular subtype 4 (CMS4). However, Mcc deletion was required for increased carcinogenesis in the lesions, with adenocarcinoma in 59% of MccΔIEC compared with 19% of Mcc-expressing mice (P =.002). This was not accompanied by hyperactivation of β-catenin, but Mcc deletion caused down-regulation of DNA repair genes and a disruption of DNA damage signaling. Conclusions: Loss of Mcc may promote cancer through a failure to repair inflammation-induced DNA damage. We provide a comprehensive transcriptome data set of early colorectal lesions and evidence for the in vivo significance of MCC silencing in colorectal cancer

Nanolitre real-time PCR detection of bacterial, parasitic, and viral agents from patients with diarrhoea in Nunavut, Canada

Background. Little is known about the microbiology of diarrhoeal disease in Canada's Arctic regions. There are a number of limitations of conventional microbiology testing techniques for diarrhoeal pathogens, and these may be further compromised in the Arctic, given the often long distances for specimen transport. Objective. To develop a novel multiple-target nanolitre real-time reverse transcriptase (RT)-PCR platform to simultaneously test diarrhoeal specimens collected from residents of the Qikiqtani (Baffin Island) Region of Nunavut, Canada, for a wide range of bacterial, parasitic and viral agents. Study design/methods. Diarrhoeal stool samples submitted for bacterial culture to Qikiqtani General Hospital in Nunavut over an 18-month period were tested with a multiple-target nanolitre real-time PCR panel for major diarrhoeal pathogens including 8 bacterial, 6 viral and 2 parasitic targets. Results. Among 86 stool specimens tested by PCR, a total of 50 pathogens were detected with 1 or more pathogens found in 40 (46.5%) stool specimens. The organisms detected comprised 17 Cryptosporidium spp., 5 Clostridium difficile with toxin B, 6 Campylobacter spp., 6 Salmonella spp., 4 astroviruses, 3 noroviruses, 1 rotavirus, 1 Shigella spp. and 1 Giardia spp. The frequency of detection by PCR and bacterial culture was similar for Salmonella spp., but discrepant for Campylobacter spp., as Campylobacter was detected by culture from only 1/86 specimens. Similarly, Cryptosporidium spp. was detected in multiple samples by PCR but was not detected by microscopy or enzyme immunoassay. Conclusions. Cryptosporidium spp., Campylobacter spp. and Clostridium difficile may be relatively common but possibly under-recognised pathogens in this region. Further study is needed to determine the regional epidemiology and clinical significance of these organisms. This method appears to be a useful tool for gastrointestinal pathogen research and may also be helpful for clinical diagnostics and outbreak investigation in remote regions where the yield of routine testing may be compromised

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

A rapid and sensitive system for recovery of nucleic acids from Mycobacteria sp. on archived glass slides

The field of diagnostics continues to advance rapidly with a variety of novel approaches, mainly dependent upon high technology platforms. Nonetheless much diagnosis, particularly in developing countries, still relies upon traditional methods such as microscopy. Biological material, particularly nucleic acids, on archived glass slides is a potential source of useful information both for diagnostic and epidemiological purposes. There are significant challenges faced when examining archived samples in order that an adequate amount of amplifiable DNA can be obtained. Herein, we describe a model system to detect low numbers of bacterial cells isolated from glass slides using (laser capture microscopy) LCM coupled with PCR amplification of a suitable target. Mycobacterium smegmatis was used as a model organism to provide a proof of principle for a method to recover bacteria from a stained sample on a glass slide using a laser capture system. Ziehl-Neelsen (ZN) stained cells were excised and catapulted into tubes. Recovered cells were subjected to DNA extraction and pre-amplified with multiple displacement amplification (MDA). This system allowed a minimum of 30 catapulted cells to be detected following a nested real-time PCR assay, using rpoB specific primers. The combination of MDA and nested real-time PCR resulted in a 30-fold increase in sensitivity for the detection of low numbers of cells isolated using LCM. This study highlights the potential of LCM coupled with MDA as a tool to improve the recovery of amplifiable nucleic acids from archived glass slides. The inclusion of the MDA step was essential to enable downstream amplification. This platform should be broadly applicable to a variety of diagnostic applications and we have used it as a proof of principle with a Mycobacterium sp. model system

Understanding adaptation to first episode psychosis through the creation of images

This article aims to understand and explore the meaning of adaptation to First Episode Psychosis (FEP). An innovative method of data collection was used with ten participants who experienced FEP which integrated drawings of their lived experience within semi-structured interviews. The data were analysed through Interpretative Phenomenological Analysis and hermeneutic-phenomenological image analysis. Participants’ experience was captured in four superordinate themes which identified that adaptation to FEP entailed: ‘Finding out how psychosis fits into my story’, ‘Breaking free from psychosis’, ‘Fighting my way through psychosis’, and ‘Finding a new way of being ‘me’’. The participants’ path of adaptation to FEP was an interplay of pains, challenges, and gains, and there was resonance with posttraumatic growth in their accounts. This article illustrates that creating images may offer a powerful way of conveying the multifaceted aspects of adaptation to FEP and could help individuals in communicating and processing their experience

Combined Point-of-Care Nucleic Acid and Antibody Testing for SARS-CoV-2 following Emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in the hospital is essential, although this is complicated by 30%–50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant dominates the pandemic and it is unclear how serological tests designed to detect anti-spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild-type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95% CI 57.8–92.9) by rapid NAAT alone. The combined point of care antibody test and rapid NAAT is not affected by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity