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Pain associated with bleeding disorders has been demonstrated to have an impact on patients’ and families’ quality of life. Both acute and chronic pain are common experiences and require attention by professionals working in haemophilia treatment centres (HTCs). The benefits of psychological pain management strategies such as cognitive behaviour therapy and self-management skills training are well documented; however, it is not well understood how Canadian social workers involved in haemophilia care perceive and provide pain management support to patients.

1 The kinetics of primaquine have been studied in twenty volunteers after single and multiple dose regimes. 2 The kinetic parameters were similar in glucose-6-phosphate dehydrogenase (G6PD) normal Thais, G6PD deficient Thais and in Caucasians. 3 The Caucasian subjects showed about 1% of the dose was excreted in the urine. 4 The kinetic parameters obtained from multiple dose studies in Thais were very similar to those obtained from single dose studies in Thais. [ABSTRACT FROM AUTHOR]

1 Red cell methaemoglobin levels were found to be significantly raised in healthy subjects given a 14-day course of primaquine with chloroquine on the first 3 days. 2 The methaemoglobin levels were not related to the quantity of primaquine excreted. 3 No primaquine could be detected in the plasma at 24 h following the last three daily doses. [ABSTRACT FROM AUTHOR]

Abstract Background DNA polymerase zeta (Polζ) is a specialized DNA polymerase that, unlike classical replicative polymerases, is capable of replicating past DNA lesions, i.e. of performing translesion synthesis (TLS). The catalytic subunit of hPolζ, hRev3, has been shown to play a critical role in DNA damage-induced mutagenesis in human cells, but less is known about the role of hRev7, the accessory subunit of hPolζ, in such mutagenesis. To address this question, we recently generated human fibroblasts with very significantly reduced levels of hRev7 protein and demonstrated that hRev7 is required to protect cells from ultraviolet(254 nm) (UV) radiation-induced cytotoxicity and mutagenesis (McNally et al., DNA Repair 7 (2008) 597-604). The goal of the present study was to determine whether hRev7 is similarly involved in the tolerance of DNA damage induced by benzo[a]pyrene diol epoxide (BPDE), the reactive form of the widespread environmental carcinogen benzo[a]pyrene. Methods To determine whether hRev7 also plays a role in protecting human cells from the cytotoxicity and mutagenesis induced by benzo[a]pyrene diol epoxide (BPDE), cell strains with reduced hRev7 were compared to their parental strain and a vector control strain for the effect of BPDE on cell survival, induction of mutations, and the ability to progress through the cell cycle. Results The results show that cell strains with reduced hRev7 are more sensitive to the cytotoxic effect of BPDE than the control strains, and progress through S-phase at a slower rate than the control cells following BPDE treatment, indicating that hRev7, and likely hPolζ, is required for efficient bypass of BPDE-induced DNA lesions. However, neither the frequency nor kinds of mutations induced by BPDE in cells with reduced hRev7 differ significantly from those induced in the control strains, suggesting that hPolζ is not essential for inserting nucleotides opposite BPDE-induced DNA damage. Conclusions Taken together, our results which show that hRev7 is required for TLS past BPDE-induced DNA lesions but that it is not essential for inserting nucleotides opposite such lesions suggest a role for hPolζ in the extension step of translesion synthesis.

Abstract Background Obesity rates in adults continue to rise and effective treatment programs with a broad reach are urgently required. This paper describes the study protocol for a web-based randomized controlled trial (RCT) of a commercially available program for overweight and obese adult males and females. The aim of this RCT was to determine and compare the efficacy of two web-based interventions for weight loss and maintenance of lost weight. Methods/Design Overweight and obese adult males and females were stratified by gender and BMI and randomly assigned to one of three groups for 12-weeks: waitlist control, or basic or enhanced online weight-loss. Control participants were re-randomized to the two weight loss groups at the end of the 12-week period. The basic and enhanced group participants had an option to continue or repeat the 12-week program. If the weight loss goal was achieved at the end of 12, otherwise on completion of 24 weeks of weight loss, participants were re-randomized to one of two online maintenance programs (maintenance basic or maintenance enhanced), until 18 months from commencing the weight loss program. Assessments took place at baseline, three, six, and 18 months after commencing the initial weight loss intervention with control participants repeating the initial assessment after three month of waiting. The primary outcome is body mass index (BMI). Other outcomes include weight, waist circumference, blood pressure, plasma markers of cardiovascular disease risk, dietary intake, eating behaviours, physical activity and quality of life. Both the weight loss and maintenance of lost weight programs were based on social cognitive theory with participants advised to set goals, self-monitor weight, dietary intake and physical activity levels. The enhanced weight loss and maintenance programs provided additional personalized, system-generated feedback on progress and use of the program. Details of the methodological aspects of recruitment, inclusion criteria, randomization, intervention programs, assessments and statistical analyses are described. Discussion Importantly, this paper describes how an RCT of a currently available commercial online program in Australia addresses some of the short falls in the current literature pertaining to the efficacy of web-based weight loss programs. Australian New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12610000197033

Abstract Background Blood pressure (BP) lowering in people who have had a stroke or transient ischaemic attack (TIA) leads to reduced risk of further stroke. However, it is not clear what the target BP should be, since intensification of therapy may lead to additional adverse effects. PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting, and whether more intensive therapy is associated with adverse effects on quality of life. Methods/Design This is a randomised controlled trial (RCT) in patients with a past history of stroke or TIA. Patients will be randomised to two groups and will either have their blood pressure (BP) lowered intensively to a target of 130 mmHg systolic, (or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg) compared to a standard group where the BP will be reduced to a target of 140 mmHg systolic. Patients will be managed by their practice at 1-3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months. 610 patients will be recruited from approximately 50 general practices. The following exclusion criteria will be applied: systolic BP The primary outcome will be change in systolic BP over twelve months. Secondary outcomes include quality of life, adverse events and cardiovascular events. In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals understanding and views of BP management. Discussion The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care, and help determine whether or not further research is required before recommending such targets for this population. Trial Registration ISRCTN29062286

Abstract Background Atrial fibrillation (AF) is an important independent risk factor for stroke. Randomised controlled trials have shown that this risk can be reduced substantially by treatment with warfarin or more modestly by treatment with aspirin. Existing trial data for the effectiveness of warfarin are drawn largely from studies in selected secondary care populations that under-represent the elderly. The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study will provide evidence of the risks and benefits of warfarin versus aspirin for the prevention of stroke for older people with AF in a primary care setting. Study design A randomised controlled trial where older patients with AF are randomised to receive adjusted dose warfarin or aspirin. Patients will be followed up at three months post-randomisation, then at six monthly intervals there after for an average of three years by their general practitioner. Patients will also receive an annual health questionnaire. 1240 patients will be recruited from over 200 practices in England. Patients must be aged 75 years or over and have AF. Patients will be excluded if they have a history of any of the following conditions: rheumatic heart disease; major non-traumatic haemorrhage; intra-cranial haemorrhage; oesophageal varices; active endoscopically proven peptic ulcer disease; allergic hypersensitivity to warfarin or aspirin; or terminal illness. Patients will also be excluded if the GP considers that there are clinical reasons to treat a patient with warfarin in preference to aspirin (or vice versa). The primary end-point is fatal or non-fatal disabling stroke (ischaemic or haemorrhagic) or significant arterial embolism. Secondary outcomes include major extra-cranial haemorrhage, death (all cause, vascular), hospital admissions (all cause, vascular), cognition, quality of life, disability and compliance with study medication.

There is limited research into horse slaughter, particularly ante mortem welfare, and the effectiveness of captive-bolt gun (CBG) stunning, despite this being a widely used method worldwide. To address this evidence gap and explore associations between ante and post mortem factors, the welfare of 62 horses was assessed at a commercial Italian abattoir. Animal-based measures were used to identify stress-related behaviours and stunning effectiveness. A sub-sample (44%; 27/62) of heads were assessed for gross brain pathology. All animals in the study showed stress-related behaviours at all stages of the slaughter process. Additionally, 53% (33/62) of horses slipped in the stunning box, with poor floor surface condition and use of force associated with this. At least one sign of an ineffective stun was observed in 22% (14/62) of animals. Six animals were shot twice, with the application of a second shot significantly associated with a higher stress behaviour index score in the stunning box. Damage to critical brainstem structures was found in 85% (23/27) of heads that were assessed with gross pathology. An absence of damage to critical brainstem structures meant that animals were ten times more likely to show signs of ineffective stunning. These results highlight the risks to equine welfare throughout the slaughter process and suggest that mitigating ante mortem stress could improve stunning effectiveness, whilst CBG usage should be refined to ensure that critical brainstem structures are targeted., Competing Interests: None., (© The Author(s) 2025.)

Current legislation in the United Kingdom stipulates that horses should not be slaughtered within sight of one another. However, abattoir personnel anecdotally report that, for semi-feral horses unused to restraint, co-slaughtering alongside a conspecific could reduce distress through social buffering and improve safety, but there is a lack of evidence to support this. CCTV footage from an English abattoir was assessed retrospectively with welfare indicators from when horses entered the kill pen until they were killed. Of 256 horses analysed, 12% (32/256) were co-slaughtered (alongside a conspecific) and 88% (224/256) individually. Co-slaughtered horses moved more in the pen, but individually slaughtered horses showed more agitated behaviour, required more encouragement to enter the kill pen, and experienced more slips or falls. Unrestrained horses (40%; 102/256) showed increased agitation, movement, and agonistic behaviour towards the operator and resisted entry to the kill pen compared to restrained horses (60%; 154/256). Positive interactions between conspecifics were seen in 94% (30/32) of co-slaughtered horses, and only 6% (1/16) showed a startled response to the first horse being shot, with a median time of 15 s between shots. This study highlights the impact that both conspecific and human interactions can have on equine welfare at slaughter. Semi-feral or unrestrained horses appear to experience increased distress compared to horses more familiar with human handling, and the presence of a conspecific at slaughter mitigated this.

Background: Nurses have a rich history in performing their duty both domestically and internationally in response to a disaster. Comprising the largest proportion of the healthcare workforce, nurses possess a unique opportunity to inform disaster planning and management. With the ongoing threat from COVID-19 and continuing conflict, humanitarian aid needs, epidemics and natural disasters; the capacity of nurses to continue to respond in times of global need is unparalleled., Aims: The aim of this paper is to explore the developments in the field of disaster nursing. Mapping key changes in policy, practice and outcomes., Methods: A qualitative interpretive historical review was conducted to examine core developments in the history of disaster nursing, examining key organisations (e.g. World Health Organization, International Council of Nurses), national and international policies and historical accounts., Results: 29 articles were analysed, and politics, strategic perspectives and nursing identity ('sense of duty' and roles) emerged from the literature. The influence of professionalisation and public health/health promotion emerged next. A total of 10 articles refer to disaster nursing specifically, of which 4 of these are reports/policy., Conclusions: Nurses have spent centuries building the trust and legitimacy of the profession. Disaster nursing goes beyond the expectations of a registered nurse. The responsibilities of a disaster nurse encompass wider community health promotion, critical decision-making beyond the individual patient, resilience and ethical challenges. Whilst significant advancements have emerged in the last 30 years, further research, and representation of the profession at a strategic and political level could enhance the effectiveness of nurses' roles in the 4 phases of disaster response: mitigation, preparation, response and recovery., Competing Interests: Declaration of conflicting interests: The author(s) received no financial support for the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objective We sought to define and measure four types of perceived interruptions and to examine their relationships with stress outcomes. Background Interruptions have been defined and measured in a variety of inconsistent ways. No study has simultaneously examined the subjective experience of all types of interruptions. Method First, we provide a synthesized definition and model of interruptions that aligns interruptions along two qualities: origin and degree of multitasking. Second, we create and validate a self-report measure of these four types of perceived interruptions within two samples (working undergraduate students and working engineers). Last, we correlate this measure with self-reported psychological and physical stress outcomes. Results Our results support the four-factor model of interruptions. Results further support the link between each of the four types of interruptions (intrusions, breaks, distractions, and a specific type of ruminations, discrepancies) and stress outcomes. Specifically, results suggest that distractions explain a unique portion of variance in stress outcomes above and beyond the shared variance explained by intrusions, breaks, and discrepancies. Conclusion The synthesized four-factor model of interruptions is an adequate representation of the overall construct of interruptions. Further, perceived interruptions can be measured and are significantly related to stress outcomes. Application Measuring interruptions by observation can be intrusive and resource intensive. Additionally, some types of interruptions may be internal and therefore unobservable. Our survey measure offers a practical alternative method for practitioners and researchers interested in the outcomes of interruptions, especially stress outcomes.

Solubilization environment afforded by several of the novel allyl glycidyl ether-modified methylhydrosiloxane polymers are investigated using a common polycyclic aromatic hydrocarbon fluorescence probe, pyrene. The backbone of the polymer has been modified by the addition of an alkyl chain of varying length (either C8, C12, or C18) and to differing degrees of substitution. The nomenclature adopted for the purposes of these studies is as follows: "AGENT" represents the backbone polymer with no alkyl substitution, and "OAGENT", "DAGENT", and "SAGENT" are substituted with n-octyl, n-dodecyl, and n-octadecyl, respectively. The percentage of alkyl substitution is designated as 10, 15, and 20%. The pyrene polarity scale (defined as the ratio of the intensity of peak I to peak III) was used to determine the relative dipolarity of the cybotactic region provided by approximately 1 w/w% aqueous polymer solutions compared to 10 mM sodium dodecylsulfate (SDS) micellar solution. Results indicate that 10-15% DAGENT afforded the most hydrophobic solubilization site, followed by 15% OAGENT and 15% SAGENT. In addition, as the degree of alkyl substitution of DAGENT increased from 10 to 20%, the cybotactic region appeared to become more hydrophobic. Furthermore, a deeper investigation into the relative size of the solubilization site revealed that all alkyl-substituted polymers promoted excimer formation at relatively low pyrene concentrations, indicating the possibility of localized concentration enhancement within the solvation pockets and/or compartmentalization of the solute molecules. The pyrene fluorescence excitation data strongly indicates ground-state heterogeneity that is most prominent in AGENT and decreases as the alkyl chain length is increased. This provides a relative sense of the size and shape of the solvation pockets afforded by each polymer solution. An overall analysis of the collected data indicated that these alkyl-substituted polymers may provide a more selective and efficient pseudostationary phase in electrokinetic chromatography with better solvation capacity for hydrophobic compounds compared to SDS.

Modifications to the method for estimating aryl hydrocarbon hydroxylase (AHH) activity in cultured human lymphocytes are described. Despite the improvements to the technique it was not possible to show significant 'repeatability' of values for AHH induction over a period of 2 weeks or more. Significant repeatability could be seen when a blood sample from each subject was split into duplicates. However, this level of repeatability was low when considered for quantitative genetics purposes. Possible reasons for the poor repeatability have been discussed.

A sensitive and specific assay for primaquine in plasma and urine using gas chromatography/mass spectrometry has been developed and used to study the plasma kinetics of primaquine. Preliminary studies on the effects of single and multiple oral doses have been carried out. In both cases the drug was completely, or almost completely, removed from the plasma in 24 h. The concentration of primaquine in the plasma usually reached a peak 1-2 hours after oral administration. The plasma elimination half-life was about 4 h. Less than 1% of the dose was detected in the urine collected over a 24-h period following drug ingestion. When Caucasian volunteers were given primaquine and chloroquine concurrently, some of them developed significant methaemoglobinaemia. Primaquine was not detectable in the plasma of any of the volunteers, 24 h after each daily dose.