Imaging microscopic distribution of antifungal agents in dandruff treatments with stimulated Raman scattering microscopy

This is the final version of the article. Available from SPIE via the DOI in this record.Treatment of dandruff condition usually involves use of antidandruff shampoos containing antifungal agents. Different antifungal agents show variable clinical efficacy based on their cutaneous distribution and bioavailability. Using stimulated Raman scattering (SRS), we mapped the distribution of unlabeled low-molecular weight antifungal compounds zinc pyrithione (ZnPT) and climbazole (CBZ) on the surface of intact porcine skin with cellular precision. SRS has sufficient chemical selectivity and sensitivity to detect the agents on the skin surface based on their unique chemical motifs that do not occur naturally in biological tissues. Moreover, SRS is able to correlate the distribution of the agents with the morphological features of the skin using the CH2CH2 stretch mode, which is abundant in skin lipids. This is a significant strength of the technique since it allows the microscopic accumulation of the agents to be correlated with physiological features and their chemical environment without the use of counter stains. Our findings show that due to its lower solubility, ZnPT coats the surface of the skin with a sparse layer of crystals in the size range of 1 to 4  μm4  μm. This is consistent with the current understanding of the mode of action of ZnPT. In contrast, CBZ being more soluble and hydrophobic resulted in diffuse homogeneous distribution. It predominantly resided in microscopic lipid-rich crevasses and penetrated up to 60  μm60  μm into the infundibular spaces surrounding the hair shaft. The ability of the SRS to selectively map the distribution of agents on the skin’s surface has the potential to provide insight into the mechanisms underpinning the topical application of antifungal or skin-active agents that could lead to the rational engineering of enhanced formulations.The authors would like to acknowledge financial support from Unilever to undertake all research reported in this manuscript

Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Plasma REST: A novel candidate biomarker of Alzheimer\u27s disease is modified by psychological intervention in an at-risk population

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain’s stress response. It is reduced in conditions of stress and Alzheimer’s disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention—mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Measuring Accuracy of Automated Parsing and Categorization Tools and Processes in Digital Investigations

This work presents a method for the measurement of the accuracy of evidential artifact extraction and categorization tasks in digital forensic investigations. Instead of focusing on the measurement of accuracy and errors in the functions of digital forensic tools, this work proposes the application of information retrieval measurement techniques that allow the incorporation of errors introduced by tools and analysis processes. This method uses a `gold standard' that is the collection of evidential objects determined by a digital investigator from suspect data with an unknown ground truth. This work proposes that the accuracy of tools and investigation processes can be evaluated compared to the derived gold standard using common precision and recall values. Two example case studies are presented showing the measurement of the accuracy of automated analysis tools as compared to an in-depth analysis by an expert. It is shown that such measurement can allow investigators to determine changes in accuracy of their processes over time, and determine if such a change is caused by their tools or knowledge.Comment: 17 pages, 2 appendices, 1 figure, 5th International Conference on Digital Forensics and Cyber Crime; Digital Forensics and Cyber Crime, pp. 147-169, 201

A survey evaluation comparing pain curriculum taught in Australian exercise physiology degrees to graduate perceptions of their preparedness and competency to treat people with chronic pain

Background and Aims: This cross-sectional study evaluated the nature of pain curriculum being taught in accredited exercise physiology degrees across Australian universities and its perceived usefulness for preparing exercise physiologists to treat people with chronic pain. Materials & Methods: Universities and graduates were asked about the nature and sufficiency of pain curriculum taught, with particular emphasis on competencies for physical therapists as outlined by the International Association for the Study of Pain. Results: Ten universities and 101 graduates responded. Median (interquartile range) instruction time on pain curriculum was 12 (7.25–18.75) hours. Few universities (30%) were aware of the guidelines for physical therapy pain curricula, although most (70%) agreed their degrees contained adequate instruction on pain assessment and management. In contrast, 74% of graduates felt their degree did not adequately prepare them to treat people with chronic pain. Half the graduates (51%) were not aware of the guidelines for physical therapy pain curricula. Discussion & Conclusion: There is a disconnect between perceptions of Australian universities and their graduates regarding the sufficiency of pain curriculum taught to student exercise physiologists. Benchmarking pain curriculum in Australian university programs against relevant international recommendations may enhance the suitability of pain curricula taught to exercise physiologists, thereby better preparing new graduates to treat people with pain

Acidification in the Cairngorms and Lochnagar: a palaeoecological assessment

Sensitive lakes in areas of the United Kingdom with moderate to high sulphur deposition have been acidified since the middle of the nineteenth century- (Battarbee et al. 1988). Regions such as Galloway, south west Scotland (eg. Flower and Battarbee 1983, Flower et al. 1987), Wales (eg. Battarbee et al. 1988, Fritz et aL 1990), Cumbria (eg. Battarbee et al 1988, Atkinson and Haworth 1990), and Rannoch Moor in the central Scottish Highlands (eg. Flower et al 1988) have been affected. This study extends the geographical survey of lake acidification to the Caimgorm and Lochnagar regions of north east Scotland (Figure 1). The Caimgorms and Lochnagar are areas of considerable conservation value, forming the largest single area of land over 1000 m in the UK. The Caimgorm mountain plateau is a National Nature Reserve, noted for its alpine flora and fauna, whilst the Lochnagar range is a Scottish Wildlife Trust reserve. A secondary- aim of the study was to evaluate the 11land-use 11 hypothesis (eg. Rosenqvist 1977, 1978, 1981) as a mechanism for lake acidification by examining high altitude sites with no active land-management. Sites selected are all remote, lie above the tree line and have undisturbed catchments. Lochnagar and the Caimgorms are situated on sensitive granite geology (Kinniburgh and Edmunds 1986, Wells et al. 1986) in an area of moderate acid deposition (c. 0.95 g S yr-1 ). It can be predicted that sensitive lakes in this area (those having Ca2 + values of <60 μeq i-1 ) will have acidified (Battarbee 1989)

High-resolution complementary chemical imaging of bio-elements in Caenorhabditis elegans

© 2016 The Royal Society of Chemistry. Here, we present a sub-μm multimodal approach to image essential elements in Caenorhabditis elegans. A combination of chemical imaging technologies reveals total metal concentration, chemical state and the protein to which an element is associated. This application of distinct yet complementary chemical imaging techniques provided unique insight into essential and trace elements at the subcellular level

Towards cot-side mapping of the sensorimotor cortex in preterm and term infants with wearable high-density diffuse optical tomography

We are translating wearable HD-DOT to the neonatal clinic to investigate healthy and brain-injured infants and establish a model of the developmental trajectory of the infant sensorimotor system

Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study

The measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44–0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80–1.00). Peri‐operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre‐empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies

"I am in favour of organ donation, but I feel you should opt-in"—qualitative analysis of the #options 2020 survey free-text responses from NHS staff toward opt-out organ donation legislation in England

\ua9 The Author(s) 2024. Background: In May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey. Methods: The #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed. Results: The #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes. Conclusions: The overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings. Trial registration: National Institute of Health Research (NIHR) [IRAS 275992]