Assessing behavioural changes in ALS: cross-validation of ALS-specific measures

Objective: The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Methods: 60 ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity and overall accuracy of the BBI, when compared to the ALS-FTD-Q, were obtained. Results: The mean score of the whole sample on the BBI was 11.45±13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6±14.64, 9.62±11.38; p<.0001). A significant large positive correlation between the BBI and the ALS-FTD-Q was observed (r=.807, p<.0001), and no significant correlations between the BBI and other clinical/demographic characteristics, indicating good convergent and discriminant validity, respectively. 72% of overall concordance was observed. Precision, sensitivity and specificity for the classification of severely impaired patients were adequate. However, lower concordance in the classification of mild behavioural changes was observed, with higher sensitivity using the BBI, most likely secondary to BBI items which endorsed behavioural aspects not measured by the ALS-FTD-Q. Discussion: Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition

‘It was all my fault’: negative interpretation bias in depressed adolescents

The extent to which cognitive models of development and maintenance of depression apply to adolescents is largely untested, despite the widespread application of Cognitive Behavior Therapy (CBT) for depressed adolescents. Cognitive models suggest that negative cognitions, including interpretation bias, play a role in etiology and maintenance of depression. Given that cognitive development is incomplete by the teenage years and that CBT is not superior to non-cognitive treatments in the treatment of adolescent depression, it is important to test the underlying model. The primary aim of this study was to test the hypothesis that interpretation biases are exhibited by depressed adolescents. Four groups of adolescents were recruited: clinically-referred depressed (n = 27), clinically-referred non-depressed (n = 24), community with elevated depression symptoms (n = 42) and healthy community (n = 150). Participants completed a 20 item ambiguous scenarios questionnaire. Clinically-referred depressed adolescents made significantly more negative interpretations and rated scenarios as less pleasant than all other groups. The results suggest that this element of the cognitive model of depression is applicable to adolescents. Other aspects of the model should be tested so that cognitive treatment can be modified or adapted if necessary

“Excellence R Us”: university research and the fetishisation of excellence

The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Propulsion in cubomedusae : mechanisms and utility

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 8 (2013): e56393, doi:10.1371/journal.pone.0056393.Evolutionary constraints which limit the forces produced during bell contractions of medusae affect the overall medusan morphospace such that jet propulsion is limited to only small medusae. Cubomedusae, which often possess large prolate bells and are thought to swim via jet propulsion, appear to violate the theoretical constraints which determine the medusan morphospace. To examine propulsion by cubomedusae, we quantified size related changes in wake dynamics, bell shape, swimming and turning kinematics of two species of cubomedusae, Chironex fleckeri and Chiropsella bronzie. During growth, these cubomedusae transitioned from using jet propulsion at smaller sizes to a rowing-jetting hybrid mode of propulsion at larger sizes. Simple modifications in the flexibility and kinematics of their velarium appeared to be sufficient to alter their propulsive mode. Turning occurs during both bell contraction and expansion and is achieved by generating asymmetric vortex structures during both stages of the swimming cycle. Swimming characteristics were considered in conjunction with the unique foraging strategy used by cubomedusae.This work was supported by an ONR MURI award (N000140810654) and National Science Foundation grant OCE 0623508 to JHC, SPC, JOD. And the work was supported by the Roger Williams University Foundation to Promote Scholarship

Internal and external cooling methods and their effect on body temperature, thermal perception and dexterity

© 2018 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0191416© 2018 Maley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective The present study aimed to compare a range of cooling methods possibly utilised by occupational workers, focusing on their effect on body temperature, perception and manual dexterity. Methods Ten male participants completed eight trials involving 30 min of seated rest followed by 30 min of cooling or control of no cooling (CON) (34C, 58% relative humidity). The cooling methods utilised were: ice cooling vest (CV0), phase change cooling vest melting at 14C (CV14), evaporative cooling vest (CVEV), arm immersion in 10C water (AI), portable water-perfused suit (WPS), heliox inhalation (HE) and ice slushy ingestion (SL). Immediately before and after cooling, participants were assessed for fine (Purdue pegboard task) and gross (grip and pinch strength) manual dexterity. Rectal and skin temperature, as well as thermal sensation and comfort, were monitored throughout. Results Compared with CON, SL was the only method to reduce rectal temperature (P = 0.012). All externally applied cooling methods reduced skin temperature (P0.05). Conclusion The present study observed that ice ingestion or ice applied to the skin produced the greatest effect on rectal and skin temperature, respectively. AI should not be utilised if workers require subsequent fine manual dexterity. These results will help inform future studies investigating appropriate pre-cooling methods for the occupational worker.This project is financially supported by the US Government through the Technical Support Working Group within the Combating Terrorism Technical Support Office.Published versio

Extensive Anti-CoA Immunostaining in Alzheimer’s Disease and Covalent Modification of Tau by a Key Cellular Metabolite Coenzyme A

Alzheimer’s disease (AD) is a neurodegenerative disorder, accounting for at least two-thirds of dementia cases. A combination of genetic, epigenetic and environmental triggers is widely accepted to be responsible for the onset and development of AD. Accumulating evidence shows that oxidative stress and dysregulation of energy metabolism play an important role in AD pathogenesis, leading to neuronal dysfunction and death. Redox-induced protein modifications have been reported in the brain of AD patients, indicating excessive oxidative damage. Coenzyme A (CoA) is essential for diverse metabolic pathways, regulation of gene expression and biosynthesis of neurotransmitters. Dysregulation of CoA biosynthesis in animal models and inborn mutations in human genes involved in the CoA biosynthetic pathway have been associated with neurodegeneration. Recent studies have uncovered the antioxidant function of CoA, involving covalent protein modification by this cofactor (CoAlation) in cellular response to oxidative or metabolic stress. Protein CoAlation has been shown to both modulate the activity of modified proteins and protect cysteine residues from irreversible overoxidation. In this study, immunohistochemistry analysis with highly specific anti-CoA monoclonal antibody was used to reveal protein CoAlation across numerous neurodegenerative diseases, which appeared particularly frequent in AD. Furthermore, protein CoAlation consistently co-localized with tau-positive neurofibrillary tangles, underpinning one of the key pathological hallmarks of AD. Double immunihistochemical staining with tau and CoA antibodies in AD brain tissue revealed co-localization of the two immunoreactive signals. Further, recombinant 2N3R and 2N4R tau isoforms were found to be CoAlated in vitro and the site of CoAlation mapped by mass spectrometry to conserved cysteine 322, located in the microtubule binding region. We also report the reversible H_{2}O_{2}-induced dimerization of recombinant 2N3R, which is inhibited by CoAlation. Moreover, CoAlation of transiently expressed 2N4R tau was observed in diamide-treated HEK293/Pank1β cells. Taken together, this study demonstrates for the first time extensive anti-CoA immunoreactivity in AD brain samples, which occurs in structures resembling neurofibrillary tangles and neuropil threads. Covalent modification of recombinant tau at cysteine 322 suggests that CoAlation may play an important role in protecting redox-sensitive tau cysteine from irreversible overoxidation and may modulate its acetyltransferase activity and functional interactions

Control of Mycobacterium bovis infection in two sika deer herds in Ireland

In a number of countries, tuberculosis (due to infection with Mycobacterium bovis) is a significant health problem of captive deer. This paper describes outbreaks of bovine tuberculosis in sika deer (Cervus nippon) on two farms in Ireland and the methods used to control the disease. On Farm A, infection was first detected during 1993. The infection was eradicated using a programme of test and removal, in association with segregation of young animals. A second outbreak (also due to infection with M. bovis, but a different RFLP profile) was detected in 2002. In the latter outbreak, infection was particularly prevalent in two groups of young deer. M. bovis with the same RFLP profile was also isolated in a badger found dead on the farm. Control was achieved by test and removal in association with herd management changes. In Herd B, infection was first detected in 1995, and subsequently eradicated using test and removal alone. In Herd A, re-infection remains an ongoing risk. Control rather than eradication of infection may more realistic in the short-to medium-term

Molecular Detection of Invasive Species in Heterogeneous Mixtures Using a Microfluidic Carbon Nanotube Platform

Screening methods to prevent introductions of invasive species are critical for the protection of environmental and economic benefits provided by native species and uninvaded ecosystems. Coastal ecosystems worldwide remain vulnerable to damage from aquatic species introductions, particularly via ballast water discharge from ships. Because current ballast management practices are not completely effective, rapid and sensitive screening methods are needed for on-site testing of ships in transit. Here, we describe a detection technology based on a microfluidic chip containing DNA oligonucleotide functionalized carbon nanotubes. We demonstrate the efficacy of the chip using three ballast-transported species either established (Dreissena bugensis) or of potential threat (Eriocheir sinensis and Limnoperna fortuneii) to the Laurentian Great Lakes. With further refinement for on-board application, the technology could lead to real-time ballast water screening to improve ship-specific management and control decisions

A case study of bovine tuberculosis in an area of County Donegal, Ireland

A descriptive analysis, to investigate the potential risk factors that might have contributed to the increased incidence of bovine tuberculosis (BTB) herd-breakdowns in the reference area of Co. Donegal during the fifth year of the four-area project (FAP), was performed. Seventy two different herds were restricted for BTB during the FAP; 10 of these herds were restricted twice, resulting in a total of 82 BTB breakdowns. During the first four years of the FAP, the number of BTB herd breakdowns in the area varied from a lowest of nine to a maximum of 18 per year, and were geographically dispersed. In the fifth year of the study a considerable increase in the number of BTB breakdowns (n = 32) was observed, and there was a spatial 'cluster' of infected herds in the eastern part of the study area. The increased number of BTB breakdowns during the fifth year most likely occurred because of the recrudescence of infection, herd-to-herd transmission and, to a lesser extent, purchase of infected cattle. Infected badgers remain as a possible but less likely source of infection, especially as an explanation for the cluster of infected herds. The analysis supports the hypothesis that BTB in herds is a problem that cannot be addressed successfully by dedicating our efforts to the elimination of single risk factors. Neither is it a problem that needs to be investigated only at the herd level, but rather at the area level, including groups of contiguous herds