Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
461
result(s) for
"Sutton, Daniel"
Sort by:
Business continuity in a cyber world : surviving cyberattackes
\"Until recently, if it has been considered at all in the context of business continuity, cyber security may have been thought of in terms of disaster recovery and little else. Recent events have shown that cyberattacks are now an everyday occurrence, and it is becoming clear that the impact of these can have devastating effects on organizations whether large or small, public or private sector. Cybersecurity is one aspect of information security, since the impacts or consequences of a cyberattack will inevitably damage one or more of the three pillars of information security: the confidentiality, integrity or availability of an organization's information assets. The main difference between information security and cyber security is that while information security deals with all types of information assets, cyber security deals purely with those which are accessible by means of interconnected electronic net- works, including the Internet. Many responsible organizations now have robust information security, business continuity and disaster recovery programs in place, and it is not the intention of this book to re-write those, but to inform organizations about the kind of precautions they should take to stave off successful cyberattacks and how they should deal with them when they arise in order to protect the day-to-day businesses.\"--Publisher website.
Book
Comparative exploration of mammalian deafness gene homologues in the Drosophila auditory organ shows genetic correlation between insect and vertebrate hearing
Johnston’s organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness. We used bioinformatic comparisons to screen previously reported human and mouse deafness genes and found that 156 of them have orthologues in Drosophila melanogaster . We used fluorescent imaging of T2A-GAL4 gene trap and GFP or YFP fluorescent protein trap lines for 54 of the Drosophila genes and found 38 to be expressed in different cell types in Johnston’s organ. We phenotypically characterized the function of strong loss-of-function mutants in three genes expressed in Johnston’s organ ( Cad99C , Msp-300 , and Koi ) using a courtship assay and electrophysiological recordings of sound-evoked potentials. Cad99C and Koi were found to have significant courtship defects. However, when we tested these genes for electrophysiological defects in hearing response, we did not see a significant difference suggesting the courtship defects were not caused by hearing deficiencies. Furthermore, we used a UAS/RNAi approach to test the function of seven genes and found two additional genes, CG5921 and Myo10a , that gave a statistically significant delay in courtship but not in sound-evoked potentials. Our results suggest that many mammalian deafness genes have Drosophila homologues expressed in the Johnston’s organ, but that their requirement for hearing may not necessarily be the same as in mammals.
Journal Article
Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing
Assembly of actin-based stereocilia is critical for cochlear hair cells to detect sound. To tune their mechanosensivity, stereocilia form bundles composed of graded rows of ascending height, necessitating the precise control of actin polymerization. Myosin 15 (MYO15A) drives hair bundle development by delivering critical proteins to growing stereocilia that regulate actin polymerization via an unknown mechanism. Here, we show that MYO15A is itself an actin nucleation-promoting factor. Moreover, a deafness-causing mutation in the MYO15A actin-binding interface inhibits nucleation activity but still preserves some movement on filaments in vitro and partial trafficking on stereocilia in vivo. Stereocilia fail to elongate correctly in this mutant mouse, providing evidence that MYO15A-driven actin nucleation contributes to hair bundle biogenesis. Our work shows that in addition to generating force and motility, the ATPase domain of MYO15A can directly regulate actin polymerization and that disrupting this activity can promote cytoskeletal disease, such as hearing loss.
Actin filament polymerization is crucial for building sound-sensitive stereocilia in the cochlea. Here, the authors show that a myosin motor can nucleate actin filaments, revealing a mechanism for stereocilia growth and hereditary hearing loss.
Journal Article
Implementation of a sensory modulation intervention in mental health outpatient services: a process evaluation study
Background
Mental health service users often experience difficulties interpreting and regulating sensory stimuli resulting in increased anxiety, decreased abilities to engage in activities and a hampered recovery process. However, there are limited studies on the implementation of such recovery-oriented interventions targeting sensory difficulties via sensory modulation techniques. Therefore, the aim of this study was to investigate staff and manager views on the implementation process of a group-based sensory modulation intervention in mental health outpatient services in Southern Sweden.
Methods
This mixed method implementation process evaluation included eight outpatient units, which were also study sites for a Randomized Controlled Trial (RCT) (NCT06432114), evaluating the effectiveness of the sensory modulation intervention. Quantitative data were analysed using descriptive statistics and qualitative data were analysed using deductive and inductive content analysis.
Results
The results indicated that the intervention was highly accepted by the mental health staff. The dose delivered and received were high and the intervention in general met the needs of the target group. Managers and staff reflections indicated that following the intervention service users seemed to feel better prepared to handle anxiety in daily life due to the acquisition of new sensory coping strategies. Staff expressed that they benefitted from acquiring a different perspective or “new sensory glasses” to apply in their clinical practice. However, managers’ and staff reflections also highlighted the need for an adapted manual for people with cognitive issues and more education for staff.
Conclusions
This study contributed to new knowledge of implementing a recovery-oriented sensory modulation intervention in mental health outpatient services. The implementation was generally carried out as intended. Nonetheless, certain challenges emerged during the implementation process, both within the contextual environment and during the delivery of the intervention.
Trial registration
Retrospectively registered 20,240,529, in ClinicalTrials.gov NCT06432114.
Journal Article
Neutralisation of Interleukin-13 in Mice Prevents Airway Pathology Caused by Chronic Exposure to House Dust Mite
Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM).
Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (R(L)) and dynamic compliance (C(dyn)). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05) the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05) the increase in baseline R(L) and the decrease in baseline C(dyn) caused by chronic exposure to inhaled HDM.
These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.
Journal Article
A Phenomenological Study of Occupational Engagement in Recovery from Mental Illness
Background. Recovery from mental illness has been described as a process involving personal growth and a search for meaning. Occupation is a primary medium for human development as well as the creation of life meaning, suggesting the exploration of recovery from an occupational perspective is warranted.
Purpose. To explore the experience and meaning of occupation for 13 people who self-identified as being in recovery from mental illness.
Methods. Recovery narratives were collected from participants in conversational interviews that were recorded and transcribed. The transcripts were analysed using hermeneutic phenomenology.
Findings. A range of experiences were evident in the recovery narratives, from complete disengagement to full engagement in occupations. Insights into the experience and meaning of different states of occupation were revealed.
Implications. All forms of occupational engagement, including disengagement, can be meaningful in the recovery process. Increased understanding of different modes of occupational engagement will assist therapists to support recovery more effectively.
Journal Article
Multi-modal molecular imaging maps the correlation between tumor microenvironments and nanomedicine distribution
Gaining insight into the heterogeneity of nanoparticle drug distribution within tumors would improve both design and clinical translation of nanomedicines. There is little data showing the spatio-temporal behavior of nanomedicines in tissues as current methods are not able to provide a comprehensive view of the nanomedicine distribution, released drug or its effects in the context of a complex tissue microenvironment.
A new experimental approach which integrates the molecular imaging and bioanalytical technologies MSI and IMC was developed to determine the biodistribution of total drug and drug metabolite delivered via PLA-PEG nanoparticles and to overlay this with imaging of the nanomedicine in the context of detailed tumor microenvironment markers. This was used to assess the nanomedicine AZD2811 in animals bearing three different pre-clinical PDX tumors.
This new approach delivered new insights into the nanoparticle/drug biodistribution. Mass spectrometry imaging was able to differentiate the tumor distribution of co-dosed deuterated non-nanoparticle-formulated free drug alongside the nanoparticle-formulated drug by directly visualizing both delivery approaches within the same animal or tissue. While the IV delivered free drug was uniformly distributed, the nanomedicine delivered drug was heterogeneous. By staining for multiple biomarkers of the tumor microenvironment on the same tumor sections using imaging mass cytometry, co-registering and integrating data from both imaging modalities it was possible to determine the features in regions with highest nanomedicine distribution. Nanomedicine delivered drug was associated with regions higher in macrophages, as well as more stromal regions of the tumor. Such a comparison of complementary molecular data allows delineation of drug abundance in individual cell types and in stroma.
This multi-modal imaging solution offers researchers a better understanding of drug and nanocarrier distribution in complex tissues and enables data-driven drug carrier design.
Journal Article
AMPK activation protects against diet-induced obesity through Ucp1-independent thermogenesis in subcutaneous white adipose tissue
Obesity results from a chronic imbalance between energy intake and energy output but remains difficult to prevent or treat in humans. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an important regulator of energy homeostasis
1
–
3
and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity
4
,
5
. Here we show that mice expressing a gain-of-function AMPK mutant
6
display a change in morphology of subcutaneous white adipocytes that is reminiscent of browning. However, despite a dramatic increase in mitochondrial content, Ucp1 expression is undetectable in these adipocytes. In response to a high-fat diet (HFD), expression of skeletal muscle–associated genes is induced in subcutaneous white adipocytes from the gain-of-function AMPK mutant mice. Chronic genetic AMPK activation results in protection against diet-induced obesity due to an increase in whole-body energy expenditure, most probably because of a substantial increase in the oxygen consumption rate of white adipose tissue. These results suggest that AMPK activation enriches, or leads to the emergence of, a population of subcutaneous white adipocytes that produce heat via Ucp1-independent uncoupling of adenosine triphosphate (ATP) production on a HFD. Our findings indicate that AMPK activation specifically in adipose tissue may have therapeutic potential for the treatment of obesity.
AMPK is a master regulator of cellular metabolism. Here the authors show that a constitutively active AMPK mutation protects mice fed a high-fat diet from obesity by increasing energy expenditure in subcutaneous white adipocytes, possibly as a result of the emergence of a hitherto-unknown type of adipocyte.
Journal Article
Using organisational case study methodology in practice
This paper illustrates the application of case study methodology using the example of exploratory case studies of sensory modulation implementation. In Aotearoa New Zealand, a sensory modulation approach has been introduced as a less coercive approach than other practices such as seclusion and restraint. However, there is limited research exploring the implementation of sensory modulation at an organisational level. To address this gap, organisational case studies were conducted in two inpatient mental health services where a sensory modulation programme was introduced. Learnings are described and considerations for future application of this methodology in health services are offered.
Journal Article
A comprehensive welfare scoring system for graft versus host disease clinical assessment in humanised mouse models used for pharmaceutical research
Immuno-oncology drug discovery increasingly relies on humanised mouse models of cancer due to limitations of murine surrogate tools and differences between mouse and human immune systems. Graft-versus-Host Disease (GvHD) is a significant complication following xenogeneic transplantation of human immune cells into mice, limiting their lifespan and impacting the utility of these studies. Existing GvHD scoring systems inadequately capture the disease’s complexity, hampering optimal welfare management and clinical progression monitoring. We propose a comprehensive, practical scoring system for monitoring clinical signs of GvHD in humanised mice. It evaluates seven clinical signs reflecting disease complexity, sums the scores, and categorises overall GvHD severity into four stages, each with specific welfare actions. This refined tool reduces animal suffering through early detection and timely interventions, enabling mice to remain on studies where possible to maximise scientific impact. Our scoring system correlates with histological scores of GvHD-induced tissue damage across multiple organs, with liver and kidney histopathology ranking highly, unlike lung pathology. The system is reproducible among independent experimenters and versatile, effectively applied across multiple types of humanised mouse models and strains. It identifies common clinical signs including weight loss, swelling/reddening of extremities, fur condition, and posture changes, aiding users in distinguishing relevant signs. This system refines and standardises welfare decision-making, supporting the responsibility to minimise suffering when working with humanised mice.
Journal Article