Naresuan University Journal
Not a member yet
39887 research outputs found
Sort by
Non-symmetrical furan-amidines as novel leads for the treatment of cancer and malaria
No full textNRH:quinone oxidoreductase 2 enzyme (NQO2) is a potential therapeutic target in cancer and neurodegenerative diseases, with roles in either chemoprevention or chemotherapy. Here we report the design, synthesis and evaluation of non-symmetrical furan-amidines and their analogues as novel selective NQO2 inhibitors with reduced adverse off-target effects, such as binding to DNA. A pathway for the synthesis of the non-symmetrical furan-amidines was established from the corresponding 1,4-diketones. The synthesized non-symmetrical furan-amidines and their analogues showed potent NQO2 inhibition activity with nano-molar IC50 values. The most active compounds were non-symmetrical furan-amidines with meta- and para-nitro substitution on the aromatic ring, with IC50 values of 15 nM. In contrast to the symmetric furan-amidines, which showed potent intercalation in the minor grooves of DNA, the synthesized non-symmetrical furan-amidines showed no affinity towards DNA, as demonstrated by DNA melting temperature experiments. In addition, Plasmodium parasites, which possess their own quinone oxidoreductase PfNDH2, were inhibited by the non-symmetrical furan-amidines, the most active possessing a para-fluoro substituent (IC50 9.6 nM). The high NQO2 inhibition activity and nanomolar antimalarial effect of some of these analogues suggest the lead compounds are worthy of further development and optimization as potential drugs for novel anti-cancer and antimalarial strategies.</p
STEM-EDX tomography of bimetallic nanoparticles:A methodological investigation
No full textThis paper presents an investigation of the limitations and optimisation of energy dispersive X-ray (EDX) tomography within the scanning transmission electron microscope, focussing on application of the technique to characterising the 3D elemental distribution of bimetallic AgAu nanoparticles. The detector collection efficiency when using a standard tomography holder is characterised using a tomographic data set from a single nanoparticle and compared to a standard low background double tilt holder. Optical depth profiling is used to investigate the angles and origin of detector shadowing as a function of specimen field of view. A novel time-varied acquisition scheme is described to compensate for variations in the intensity of spectrum images at each sample tilt. Finally, the ability of EDX spectrum images to satisfy the projection requirement for nanoparticle samples is discussed, with consideration of the effect of absorption and shadowing variations.</p
Scaling in natural and laboratory earthquakes
No full textLaboratory experiments reproducing seismic slip conditions show extreme frictional weakening due to the activation of lubrication processes. Due to a substantial variability in the details of the weakening transient, generalization of experimental results and comparison to seismic observations have not been possible so far. Here we show that during the weakening, shear stress � is generally well matched by a power law of slip u in the form � � u−� (with 0.3
Clinical management following self-harm in a UK-wide primary care cohort
No full textBackground: Little is known about the clinical management of patients in primary care following self-harm.Methods: A descriptive cohort study using data from 684 UK general practices that contributed to the Clinical Practice Research Datalink (CPRD) during 2001-2013. We identified 49,970 patients with a self-harm episode, 41,500 of whom had one complete year of follow-up. Results: Among those with complete follow-up, 26,065 (62.8%, 62.3-63.3) were prescribed psychotropic medication and 6,318 (15.2%, 14.9-15.6) were referred to mental health services; 4,105 (9.9%, CI 9.6-10.2) were medicated without an antecedent psychiatric diagnosis or referral, and 4,506 (10.9%, CI 10.6-11.2) had a diagnosis but were not subsequently medicated or referred. Patients registered at practices in the most deprived localities were 27.1% (CI 21.5-32.2) less likely to be referred than those in the least deprived. Despite a specifically flagged NICE ‘Do not do’ recommendation in 2011 against prescribing tricyclic antidepressants following self-harm because of their potentially lethal toxicity in overdose, 8.8% (CI 7.8-9.8) of individuals were issued a prescription in the subsequent year. The percentage prescribed Citalopram, an SSRI antidepressant with higher toxicity in overdose, fell sharply during 2012/2013 in the aftermath of a Medicines and Healthcare products Regulatory Agency (MHRA) safety alert issued in 2011. Conclusions: A relatively small percentage of these vulnerable patients are referred to mental health services, and reduced likelihood of referral in more deprived localities reflects a marked health inequality. National clinical guidelines have not yet been effective in reducing rates of tricyclic antidepressant prescribing for this high-risk group. <br/
The Take Control Course::Conceptual rationale for the development of a transdiagnostic group for common mental health problems
No full textOccupational therapy roles and responsibilities: Evidence from a pilot study of time use in an integrated health and social care trust
No full textIntroduction: Occupational therapists undertake a broad spectrum of activities, yet no mechanism exists to record how working time is distributed across them. This is a hindrance to research, evaluation and evidence-based practice. Method: A new diary schedule was piloted by 151 qualified and assistant-grade practitioners working in multiple adult health and social care settings in an integrated NHS and social care trust in England. Time use relating to 37 occupational therapy tasks was recorded in 30 minute intervals for one week. Results: Almost 5000 hours of activity were recorded. For the average working week, 39% of time was spent in direct care with clients, 31% involved undertaking indirect casework such as liaison and administration, whilst a further 22% was in team/service activity. Only modest differences were observed between qualified and assistant-grade respondents, whilst occupational therapists in traditional social care roles spent significantly longer in liaison and administrative duties. Individual tasks capturing ‘therapeutic activity’ accounted for just 10% of practitioner time. Conclusion: The new diary tool is a viable data collection instrument to evaluate practice and the impact of service redesign. However, further work is needed to evaluate its measurement properties in more detai
Baby Steps - an online program promoting the wellbeing of new mothers and fathers: a study protocol
No full textBackground: Parental well-being can be seriously impacted during the challenging perinatal period. Most research and support services focus on perinatal psychopathology, leaving a need for programs that recognize and enhance the strengths and well-being of parents. Furthermore, fathers have received minimal attention and support relative to mothers, despite experiencing perinatal distress. New parents have limited time and energy to invest in program attendance, and web-based programs provide an ideal platform for delivering perinatal well-being programs. Such programs are globally accessible, available at any time, and can be accessed anywhere with an Internet connection.Objective: This paper describes the protocol of a randomized controlled trial investigating the effects on first-time parents’ perinatal well-being, comparing two versions of the online program Baby Steps.Methods: The clinical trial will randomize 240 primiparous mother-father couples to either (1) Babycare, an online information-only program providing tips on selected childcare issues, or (2) Well-being, an online interactive program including all content from the Babycare program, plus parental well-being-focused content with tools for goal-setting and problem solving. Both programs will be supported by short message service (SMS) texts at two, four, seven, and ten weeks to encourage continued use of the program. Primary outcomes will be measures of perinatal distress and quality of life. Secondary outcomes will be couple relationship satisfaction, parent self-efficacy, and social support. Cost-effectiveness will also be measured for each Baby Steps program.Results: Participant recruitment commenced March, 2015 and continued until October, 2015. Follow-up data collection has commenced and will be completed May, 2016 with results expected in July, 2016.Conclusions: Perinatal distress has substantial impacts on parents and their infants, with potential to affect later childhood adjustment, relationships, and development. This study aims to test the impact of a highly accessible online program to support parental coping, and maximize the well-being of both parents. By including fathers in the program, Baby Steps has the potential to engage and support this often neglected group who can make a substantial contribution to familial well-being
Construct, Merge, Solve & Adapt A new general algorithm for combinatorial optimization
No full textThis paper describes a general hybrid metaheuristic for combinatorial optimization labelled Construct, Merge, Solve & Adapt. The proposed algorithm is a specific instantiation of a framework known from the literature as Generate-And-Solve, which is based on the following general idea. First, generate a reduced sub-instance of the original problem instance, in a way such that a solution to the sub-instance is also a solution to the original problem instance. Second, apply an exact solver to the reduced sub-instance in order to obtain a (possibly) high quality solution to the original problem instance. And third, make use of the results of the exact solver as feedback for the next algorithm iteration. The minimum common string partition problem and the minimum covering arborescence problem are chosen as test cases in order to demonstrate the application of the proposed algorithm. The obtained results show that the algorithm is competitive with the exact solver for small to medium size problem instances, while it significantly outperforms the exact solver for larger problem instances
Playing with Exclusionary Logics: Alternative Spatio-Temporal Understandings
No full textAn alternative spatio-temporal imagery is an ‘invitation to become lost in the world’. Everyday experiences drive the need to rethink our understanding in and of IR
Encouraging use of subordination in children’s narratives: a classroom-based priming study
No full textThis study investigated the long-term effect of classroom-based input manipulation on children’s use of subordination in a story re-telling task; it also explored the role of receptive vocabulary skills and expressive grammatical abilities in predicting the likelihood of priming.During a two-week priming phase, 47 monolingual English-speaking five-year-olds heard 10 stories, one a day, that either contained a high proportion of subordinate clauses (subordination condition) or a high proportion of coordinate clauses (coordination condition). Post-intervention, there was a significant group difference in likelihood of subordinate use which persisted ten weeks after the priming. Neither expressive grammatical nor receptive vocabulary skills were positively correlated with the likelihood of subordinate use.These findings show that input manipulation can have a facilitative effect on the use of complex syntax over several weeks in a realistic communicative task