The Advanced Data Acquisition Model (Adam): A Process Model for Digital Forensic Practice

As with other types of evidence, the courts make no presumption that digital evidence is reliable without some evidence of empirical testing in relation to the theories and techniques associated with its production. The issue of reliability means that courts pay close attention to the manner in which electronic evidence has been obtained and in particular the process in which the data is captured and stored. Previous process models have tended to focus on one particular area of digital forensic practice, such as law enforcement, and have not incorporated a formal description. We contend that this approach has prevented the establishment of generally-accepted standards and processes that are urgently needed in the domain of digital forensics. This paper presents a generic process model as a step towards developing such a generally-accepted standard for a fundamental digital forensic activity–the acquisition of digital evidence

Investigation of Cellular Uptake Mechanism of Functionalised Gold Nanoparticles into Breast Cancer Using SERS

Gold nanoparticles (AuNPs) are widely used in various applications such as cancer imaging and drug delivery. The functionalisation of AuNPs has been shown to affect their cellular internalisation, accumulation and targeting efficiency. The mechanism of cellular uptake of functionalised AuNPs by different cancer cells is not well understood. Therefore, a detailed understanding of the molecular processes is necessary to improve AuNPs for their selective uptake and fate in specific cellular systems. This knowledge can greatly help in designing nanotags with higher cellular uptake for more selective and specific targeting capabilities with less off-target effects. Here, we demonstrate for the first time a straightforward and non-destructive 3D surface enhanced Raman spectroscopy (SERS) imaging approach to track the cellular uptake and localisation of AuNPs functionalised with an anti-ERα (estrogen receptor alpha) antibody in MCF-7 ERα-positive human breast cancer cells under different conditions including temperature and dynamin inhibition. 3D SERS enabled information rich monitoring of the intracellular internalisation of the SERS nanotags. It was found that ERα-AuNPs were internalised by MCF-7 cells in a temperature-dependent manner suggesting an active endocytosis-dependent mechanism. 3D SERS cell mapping also indicated that the nanotags entered MCF-7 cells using dynamin dependent endocytosis, since dynamin inhibition resulted in the SERS signal being obtained from, or close to, the cell surface rather than inside the cells. Finally, ERα-AuNPs were found to enter MCF-7 cells using an ERα receptor-mediated endocytosis process. This study addresses the role of functionalisation of SERS nanotags in biological environments and highlights the benefits of using 3D SERS for the investigation of cellular uptake processes

Longitudinal Evaluation of the Impact of Placement Development Teams on Student Support in Clinical Practice

AIMS: To investigate the impact of a new structure for supporting healthcare students and mentors in practice placements (Placement Development Teams). INTRODUCTION: The English Model National Partnership Agreement for healthcare education required Strategic Health Authorities, Higher Education Institutions and National Health Service Trusts to redesign strategies for student support. Placement Development Teams are one English University's response to this. MATERIALS AND METHODOLOGY: This study was phase 2 of a longitudinal qualitative evaluation of Placement Development Teams. Data were collected after establishment of Placement Development Teams, and compared and contrasted with those collected prior to their implementation. Telephone interviews were conducted with key educational stakeholders in Trusts and Strategic Health Authorities. Focus groups were conducted with third year non-medical healthcare students and first year paramedics working in 16 NHS Trusts in the south west peninsula of England. RESULTS: Pre-Placement Development Teams, themes from the students' data were: Supportive and unsupportive behaviour of staff; Mentor allocation; Placement allocation; Benefits of students to the placement area and Perceived control over the learning experience. Post-Placement Development Teams, the themes were Communication; Supportive and unsupportive behaviour of staff; The effect of peers on the placement experience; Knowledge and perceptions of the work of the PDTs. Form the staff data, pre-Placement Development Teams the themes were: Vision for improving student support. Post-Placement Development Teams themes from the staff data were how they provided a central point of contact for student and mentor support; and how they supported students and mentors. CONCLUSION: Support of students and mentors is particularly important following the introduction of The English Model National Partnership Agreement for healthcare education. Placement Development Teams can facilitate partnership working between higher education institutions and placement providers for student support

Physiological Responses to Prolonged Aquatic Hypoxia in the Queensland Lungfish Neoceratodus forsteri

The effects of moderate and severe hypoxia on air breathing frequency and respiratory properties of the blood of the Queensland (Australian) lungfish Neoceratodus forsteri were measured in fish exposed to these conditions for 14-22 days at 20 degrees C. Haemoglobin oxygen affinity increased after exposure to moderate hypoxia (PwO2 = 60 mmHg), but did not increase further after exposure to severe hypoxia (PwO2 =40 mmHg). The P50 of whole blood (20 degrees C, PCO2 =16.0 mmHg) fell from 22.0 +/- 1.5 mmHg in normoxic conditions to 19.0 +/- 1.0 mmHg in hypoxic conditions. Under both moderate and severe hypoxia, haematocrit, haemoglobin, blood lactate, and erythrocyte phosphate concentrations did not differ from normoxic values. The observed increase in haemoglobin oxygen affinity in response to aquatic hypoxia is typical of compensatory responses seen in obligate water breathers, but smaller. This suggests that the capacity of lungfish to respond to hypoxia by breathing air removes the necessity for further left-shifting of the oxygen equilibrium curve

Rapid on-site identification of hazardous organic compounds at fire scenes using person-portable gas chromatography-mass spectrometry (GC-MS). Part 2: Water sampling and analysis

Building and factory fires pose a great risk to human and environmental health, due to the release of hazardous by-products of combustion. These hazardous compounds can dissipate into the environment through fire water run-off, and the impact can be immediate or chronic. Current laboratory-based methods do not report hazardous compounds released from a fire scene at the time and location of the event. Reporting of results is often delayed due to the complexities and logistics of laboratory-based sampling and analysis. These delays pose a risk to the health and wellbeing of the environment and exposed community. Recent developments in person-portable instrumentation have the potential to provide rapid analysis of samples in the field. A portable gas chromatograph-mass spectrometer (GC-MS) was evaluated for the on-site analysis of water samples for the identification of hazardous organic compounds at fire scenes. The portable GC-MS was capable of detecting and identifying a range of volatile and semi-volatile organic compounds in fire water run-off, and can be used in conjunction with conventional laboratory analysis methods for a comprehensive understanding of hazardous organics released at fire scenes. Deployment of this portable instrumentation provides first responders with a rapid, on-site screening tool to appropriately manage the run-off water from firefighting activities. This ensures that environmental and human health is proactively protected

Rapid on-site identification of hazardous organic compounds at fire scenes using person-portable gas chromatography-mass spectrometry (GC-MS). Part 1: Air sampling and analysis

Recent advancements in person-portable instrumentation have resulted in the potential to provide contemporaneous results through rapid in-field analyses. These technologies can be utilised in emergency response scenarios to aid first responders in appropriate site risk assessment and management. Large metropolitan fires can pose great risk to human and environmental health due to the rapid release of hazardous compounds into the atmosphere. Understanding the release of these hazardous organics is critical in understanding their associated risks. Person-portable gas chromatography-mass spectrometry (GC-MS) was evaluated for its potential to provide rapid on-site analysis for real-time monitoring of hazardous organic compounds at fire scenes. Air sampling and analysis methods were developed for scenes of this nature. Controlled field testing demonstrated that the portable GC-MS was able to provide preliminary analytical results on the volatile organic compounds present in air samples collected from both active and extinguished fires. In-field results were confirmed using conventional laboratory-based air sampling and analysis procedures. The deployment of portable instrumentation could provide first responders with a rapid on-site assessment tool for the appropriate management of scenes, thereby ensuring environmental and human health is proactively protected and scientifically informed decisions are made for the provision of timely advice to stakeholders

Computer-aided design of multi-target ligands at A1R, A2AR and PDE10A, key proteins in neurodegenerative diseases.

Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required to produce a clinical effect. In particular, suitable compounds may be useful in treating neurodegenerative diseases by promoting neuronal survival in a synergistic manner via their multi-target activity at the adenosine A1 and A2A receptors (A1R and A2AR) and phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, in this work we describe a computational method for the design of synthetically feasible ligands that bind to A1 and A2A receptors and inhibit phosphodiesterase 10A (PDE10A), involving a retrosynthetic approach employing in silico target prediction and docking, which may be generally applicable to multi-target compound design at several target classes. This approach has identified 2-aminopyridine-3-carbonitriles as the first multi-target ligands at A1R, A2AR and PDE10A, by showing agreement between the ligand and structure based predictions at these targets. The series were synthesized via an efficient one-pot scheme and validated pharmacologically as A1R/A2AR–PDE10A ligands, with IC50 values of 2.4–10.0 μM at PDE10A and Ki values of 34–294 nM at A1R and/or A2AR. Furthermore, selectivity profiling of the synthesized 2-amino-pyridin-3-carbonitriles against other subtypes of both protein families showed that the multi-target ligand 8 exhibited a minimum of twofold selectivity over all tested off-targets. In addition, both compounds 8 and 16 exhibited the desired multi-target profile, which could be considered for further functional efficacy assessment, analog modification for the improvement of selectivity towards A1R, A2AR and PDE10A collectively, and evaluation of their potential synergy in modulating cAMP levels

A 21-year record of vertically migrating subepilimnetic populations of Cryptomonas spp.

The vertical distribution and diel migration of Cryptomonas spp. were monitored continuously for 21 years in mesotrophic Cross Reservoir, northeast Kansas, USA. The movements of these motile algae were tracked on multiple dates during July–October of each year using in situ fluorometry and optical microscopy of Lugol’s iodine-preserved samples. Episodes of subepilimnetic diel vertical migration by Cryptomonas were detected and recorded on 221 different days between 1994 and 2014, with just 2 of these years (1998 and 2013) lacking any sampling events with deep peaks sufficiently large enough to track. Whenever a subepilimnetic layer of Cryptomonas was detectable, it was generally observed to ascend toward the bottom of the epilimnion beginning approximately at sunrise; to descend toward the lake bottom during the late afternoon and evening; and to remain as a deep-dwelling population until dawn of the following day. Moreover, there was high day-to-day consistency in the absolute water column depths at which the migrating algal cells would cease their ascending or descending movement. We believe this unique and remarkable dataset comprises the most detailed record of diel migratory behavior for any planktonic freshwater alga reported for a single freshwater lake

National trends and local delivery in old age mental health services: towards an evidence base: a mixed-methodology study of the balance of care approach, community mental health teams and specialist mental health outreach to care homes

Background The rising number of older people with mental health problems makes the effective use of mental health resources imperative. Little is known about the clinical effectiveness and/or cost-effectiveness of different service models. Aims The programme aimed to (1) refine and apply an existing planning tool [‘balance of care’ (BoC)] to this client group; (2) identify whether, how and at what cost the mix of institutional and community services could be improved; (3) enable decision-makers to apply the BoC framework independently; (4) identify variation in the structure, organisation and processes of community mental health teams for older people (CMHTsOP); (5) examine whether or not different community mental health teams (CMHTs) models are associated with different costs/outcomes; (6) identify variation in mental health outreach services for older care home residents; (7) scope the evidence on the association between different outreach models and resident outcomes; and (8) disseminate the research findings to multiple stakeholder groups. Methods The programme employed a mixed-methods approach including three systematic literature reviews; a BoC study, which used a systematic framework for choosing between alternative patterns of support by identifying people whose needs could be met in more than one setting and comparing their costs/outcomes; a national survey of CMHTs’ organisation, structure and processes; a multiple case study of CMHTs exhibiting different levels of integration encompassing staff interviews, an observational study of user outcomes and a staff survey; national surveys of CMHTs’ outreach activities and care homes. A planned randomised trial of depression management in care homes was removed at the review stage by the National Institute for Health Research (NIHR) prior to funding award. Results BoC: Past studies exhibited several methodological limitations, and just two related to older people with mental health problems. The current study suggested that if enhanced community services were available, a substantial proportion of care home and inpatient admissions could be diverted, although only the latter would release significant monies. CMHTsOP: 60% of teams were considered multidisciplinary. Most were colocated, had a single point of access (SPA) and standardised assessment documentation. Evidence of the impact of particular CMHT features was limited. Although staff spoke positively about integration, no evidence was found that more integrated teams produced better user outcomes. Working in high-integration teams was associated with poor job outcomes, but other factors negated the statistical significance of this. Care home outreach: Typical services in the literature undertook some combination of screening (less common), assessment, medication review, behaviour management and training, and evidence suggested intervention can benefit depressed residents. Care home staff were perceived to lack necessary skills, but relatively few CMHTs provided formal training. Limitations Limitations include a necessary reliance on observational rather than experimental methods, which were not feasible given the nature of the services explored. Conclusions BoC: Shifting care towards the community would require the growth of support services; clarification of extra care housing’s (ECH) role; timely responses to people at risk of psychiatric admission; and improved hospital discharge planning. However, the promotion of care at home will not necessarily reduce public expenditure. CMHTsOP: Although practitioners favoured integration, its goals need clarification. Occupational therapists (OTs) and social workers faced difficulties identifying optimal roles, and support workers’ career structures needed delineating. Care home outreach: Further CMHT input to build care home staff skills and screen for depression may be beneficial. Priority areas for further study include the costs and benefits for older people of age inclusive mental healt