Reclaiming Agency in Care Decisions and Barriers From the Perspectives of Individuals With Acquired Brain Injury and Their Family Members.

BACKGROUND: The ability to self-advocate or have a say in one's care is integral to personalised care after acquired brain injury (ABI). This study aimed to understand what constitutes self-advocacy and associated barriers and facilitators throughout hospital transitions and into the community. METHOD: Qualitative methodology was employed with semistructured interviews conducted with 12 people with ABI and 13 family members. Interviews were conducted at predischarge (in-person or via telephone) and 4 months postdischarge (via telephone) from the brain injury rehabilitation unit of a tertiary hospital. Data were thematically analysed using a hybrid deductive-inductive approach. RESULTS: Self-advocacy reflects the process of reclaiming agency or people's efforts to exert influence over care decisions after ABI. Agency varies along a continuum, often beginning with impaired processing of the self or environment (loss of agency) before individuals start to understand and question their care (emerging agency) and ultimately plan and direct their ongoing and future care (striving for agency). This process may vary across individuals and contexts. Barriers to self-advocacy for individuals with ABI include neurocognitive deficits that limit capacity and desire for control over decisions, unfamiliar and highly structured environments and lack of family support. Facilitators include neurocognitive recovery, growing desire to self-advocate and scaffolded support from family and clinicians. CONCLUSION: Self-advocacy after ABI entails a process of reclaiming agency whereby individuals seek to understand, question and direct their ongoing care. This is facilitated by neurocognitive recovery, growing capacity and desire and scaffolded supports. Research evaluating approaches for embedding self-advocacy skills early in brain injury rehabilitation is recommended. PATIENT OR PUBLIC CONTRIBUTION: Two caregivers with lived experience of supporting a family member with ABI were involved in the design and conduct of this study and contributed to and provided feedback on the manuscript.

Effect of a novel pharmacist-led reporting system on appropriate use of direct-acting oral anticoagulants (DOACs) in a patient-centered medical home.

Recent analyses demonstrate roughly 16-24% of patients taking direct-acting oral anticoagulants (DOACs) are prescribed an inappropriate dose, exposing patients to increased risk of thrombosis or bleeding. The use of reporting systems in the outpatient setting can efficiently identify potential medication errors and safety concerns. The purpose of this study was to evaluate the effect of a novel pharmacist-driven reporting system on appropriate prescribing of DOACs in the outpatient setting. This single-center qualitative study was conducted within a patient-centered medical home (PCMH). Reports were generated monthly to include all new DOAC prescriptions. Branching logic and filters were utilized within a secure web application to make the reporting process more efficient and identify regimens needing an intervention. Pharmacists reviewed the regimens populated by filters and made recommendations to prescribers as appropriate. The number of interventions proposed was captured as the primary outcome. Secondary outcomes include the nature of drug therapy problems identified and number of interventions accepted by prescribers. A total of 107 patients were analyzed for appropriateness from November 2017 to February 2019. Of the regimens included for review, 15 regimens were identified as potentially inappropriate. The nature of drug therapy problems identified include under dosing (4.25%), overdosing (2.13%), correction of documentation (2.13%), clarification of indication (3.19%), and ordering laboratory studies (3.19%). Of the interventions recommended, fourteen (93%) were accepted. Pharmacists integrated in a PCMH are well positioned to monitor and resolve DOAC drug therapy problems using local clinical reports.

Archaeosine Modification of Archaeal tRNA: Role in Structural Stabilization.

Archaeosine (G+) is a structurally complex modified nucleoside found quasi-universally in the tRNA of Archaea and located at position 15 in the dihydrouridine loop, a site not modified in any tRNA outside the Archaea G+ is characterized by an unusual 7-deazaguanosine core structure with a formamidine group at the 7-position. The location of G+ at position 15, coupled with its novel molecular structure, led to a hypothesis that G+ stabilizes tRNA tertiary structure through several distinct mechanisms. To test whether G+ contributes to tRNA stability and define the biological role of G+, we investigated the consequences of introducing targeted mutations that disrupt the biosynthesis of G+ into the genome of the hyperthermophilic archaeon Thermococcus kodakarensis and the mesophilic archaeon Methanosarcina mazei, resulting in modification of the tRNA with the G+ precursor 7-cyano-7-deazaguansine (preQ0) (deletion of arcS) or no modification at position 15 (deletion of tgtA). Assays of tRNA stability from in vitro-prepared and enzymatically modified tRNA transcripts, as well as tRNA isolated from the T. kodakarensis mutant strains, demonstrate that G+ at position 15 imparts stability to tRNAs that varies depending on the overall modification state of the tRNA and the concentration of magnesium chloride and that when absent results in profound deficiencies in the thermophily of T. kodakarensisIMPORTANCE Archaeosine is ubiquitous in archaeal tRNA, where it is located at position 15. Based on its molecular structure, it was proposed to stabilize tRNA, and we show that loss of archaeosine in Thermococcus kodakarensis results in a strong temperature-sensitive phenotype, while there is no detectable phenotype when it is lost in Methanosarcina mazei Measurements of tRNA stability show that archaeosine stabilizes the tRNA structure but that this effect is much greater when it is present in otherwise unmodified tRNA transcripts than in the context of fully modified tRNA, suggesting that it may be especially important during the early stages of tRNA processing and maturation in thermophiles. Our results demonstrate how small changes in the stability of structural RNAs can be manifested in significant biological-fitness changes.

Early onset cerebral amyloid angiopathy following childhood exposure to cadaveric dura.

Amyloid-ß transmission has been described in patients both with and without iatrogenic Creutzfeldt-Jakob disease; however, there is little information regarding the clinical impact of this acquired amyloid-ß pathology during life. Here, for the first time, we describe in detail the clinical and neuroimaging findings in 3 patients with early onset symptomatic amyloid-ß cerebral amyloid angiopathy following childhood exposure to cadaveric dura (by neurosurgical grafting in 2 patients and tumor embolization in a third). Our observations provide further in vivo evidence that cerebral amyloid angiopathy might be caused by transmission of amyloid-ß seeds (prions) present in cadaveric dura and have diagnostic relevance for younger patients presenting with suspected cerebral amyloid angiopathy. Ann Neurol 2019; 1-7 ANN NEUROL 2019;85:284-290.

Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis.

BACKGROUND: It was recently reported that, using Western blotting, some multiple sclerosis (MS) patients in the United States had antibodies against epsilon toxin (Etx) from Clostridium perfringens, suggesting that the toxin may play a role in the disease. OBJECTIVE: We investigated for serum antibodies against Etx in UK patients with clinically definite multiple sclerosis (CDMS) or presenting with clinically isolated syndrome (CIS) or optic neuritis (ON) and in age- and gender-matched controls. METHODS: We tested sera from CDMS, CIS or ON patients or controls by Western blotting. We also tested CDMS sera for reactivity with linear overlapping peptides spanning the amino acid sequence (Pepscan) of Etx. RESULTS: Using Western blotting, 24% of sera in the combined CDMS, CIS and ON groups ( n = 125) reacted with Etx. In the control group ( n = 125), 10% of the samples reacted. Using Pepscan, 33% of sera tested reacted with at least one peptide, whereas in the control group only 16% of sera reacted. Out of 61 samples, 21 (43%) were positive to one or other testing methodology. Three samples were positive by Western blotting and Pepscan. CONCLUSION: Our results broadly support the previous findings and the role of Etx in the aetiology of MS warrants further investigation.

Higher Hepatitis C Cure Rates in a Patient-Centered Medical Home Compared to Specialist Care.

PURPOSE: The new era of direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) has led many primary care clinicians to begin treating HCV. Nevertheless, many patients are referred to specialists due to comorbidities, care complexities, and knowledge gaps of the primary care provider. We compared clinical outcomes for patients treated within a Family Medicine Residency Program (FMRP) affiliated patient-centered medical home (PCMH) with those referred to a specialist. METHODS: Following didactic education and development of practice resources we conducted a single-center quasi-experimental study of adults with HCV referred for treatment either internally or externally to a specialist between January 2019 and December 2020. The primary outcome was the number of patients with a sustained virologic response at 12 weeks after treatment (SVR12), utilizing an intention-to-treat analysis. RESULTS: During the study period 107 patients were assessed by the PCMH, of whom 24 were deemed not a good candidate for treatment. Of the 83 patients referred for treatment, 36 patients were referred externally and 47 were treated internally. While the rate of SVR12 was 100% for both groups when analyzed per protocol (ie, only patients who completed treatment and attended all follow-ups), the rate of SVR12 was 31% for patients referred externally and 62% for patients treated internally when analyzed by intention to treat (relative risk [RR] 2.02, 95% CI 1.18-3.47, P = .01). This difference was entirely attributable to differences in lost to follow-up rates. CONCLUSIONS: Following education and creation of practice resources, achievement of SVR12 among patients with HCV treated by an internal interdisciplinary family medicine team was superior to those who were externally referred. This was primarily attributable to differences in follow-up rates.

Normalising interdisciplinary role-based goal setting in inpatient brain injury rehabilitation: reflections and recommendations of clinicians.

PURPOSE: Person-centred goal setting with people with brain injury, by interdisciplinary teams has benefits including improved communication between patients, families and clinicians, person-centred care, and improved engagement in rehabilitation. Exploring the experiences of team members who have adopted interdisciplinary, person-centred goal setting may assist in understanding what is needed to implement this complex, core component of rehabilitation practice. This study explored experiences of clinicians working in an extended inpatient brain injury rehabilitation unit about implementing a role-based goal planning approach within an interdisciplinary team. MATERIALS AND METHODS: Semi-structured interviews with 13 clinicians working at the rehabilitation unit explored their experiences about the cognitive participation and collective actions required to carry out the practice, with data analysed using inductive content analysis guided by Normalisation Process Theory. RESULTS: Three primary themes were identified: putting the person at the centre, accepting the mind-shift to participation focused goals and working collaboratively. CONCLUSIONS: This study has elucidated some key processes that occurred and were necessary to carry out goal setting. A mind-shift towards holistic, participation-focussed goal setting was described as "unlearning" discipline-specific goal setting. Development and ownership by the team, acceptance of team members and willingness to share, and structured processes and resources were necessary.IMPLICATIONS FOR REHABILITATIONNormalising interdisciplinary role-based goal setting in multi-professional teams requires a mind-shift away from traditional, discipline-specific goal setting.Implementation of interdisciplinary, collaborative team goal setting within health service settings requires collective actions including collaborative working by team members, structured processes including organised time for collaborative team and family meetings, practical resources and training to support processes.Clinicians perceived the goal setting approach to put the person at the centre resulting in a deep understanding of the person, shared understanding, and motivation for rehabilitation.

Meta-analysis of lytic catheter-based intervention for acute proximal deep vein thrombosis in the reduction of post-thrombotic syndrome.

OBJECTIVE: Post-thrombotic syndrome (PTS) is a common complication of deep vein thrombosis (DVT) that can result in significant morbidity for the patient with detrimental impact on their quality of life. Evidence supporting lytic catheter-based interventions (LCBI) undertaken for early thrombus reduction in acute proximal DVT for the prevention of PTS is conflicting. Despite this, rates of LCBIs are increasing. To summaries the existing evidence and pool treatment effects, a meta-analysis of randomized controlled trials assessing the efficacy of LCBIs in proximal acute DVT for the prevention of PTS was undertaken. METHODS: This meta-analysis was undertaken aligning with PRISMA guidelines following a protocol pre-registered on PROSPERO. Online searches of Medline and Embase databases, as well as the gray literature, were performed up to December 2022. Included articles were randomized controlled trials that studied the use of LCBIs with additional anticoagulation vs anticoagulation alone and had determined follow-up periods. Outcomes of interest were PTS development, moderate to severe PTS, major bleeding episodes, and quality-of-life measures. Subgroup analyses were performed for DVTs involving the iliac vein and/r common femoral vein. Meta-analysis was performed using a fixed effects model. Quality assessment was performed using the Cochrane Risk of Bias and GRADE assessment tools. RESULTS: Three trials were included in the final meta-analysis, the Post-thrombotic Syndrome after Catheter-directed Thrombolysis for Deep Vein Thrombosis (CaVenT), Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT), and Ultrasound-accelerated Catheter-directed Thrombolysis Versus Anticoagulation for the Prevention of Post-thrombotic Syndrome (CAVA) trials, comprising 987 patients. Patients undergoing LCBIs had a reduced risk of PTS (relative risk [RR], 0.84; 95% confidence interval [CI], 0.74-0.95; P = .006) and a lower risk of developing moderate to severe PTS (RR, 0.75; 95% CI, 0.58-0.97; P = .03). LBCIs increased the risk of having a major bleed (RR, 2.03; 95% CI, 1.08-3.82; P = .03). In the iliofemoral DVT subgroup analysis, there was a trend toward decreasing the risk of developing PTS and moderate to severe PTS (P = .12 and P = .05, respectively). There was no significant difference in quality-of-life score (as measured by the Venous Insufficiency Epidemiological and Economic Study - Quality of Life/Symptoms) between the two groups (P = .51). CONCLUSIONS: Pooling of current best evidence suggests that LCBIs in acute proximal DVT decreases the rate of PTS and moderate to severe PTS with a number needed to treat of 12 and 18, respectively. However, this is complicated by a significantly higher rate of major bleeding with a number needed to treat of 37. This evidence supports the use of LCBIs in selected patients, including those who are at low risk of major bleeding.

Knee Osteoarthritis in Patients With High BMI: The Role of an Orthopaedic Surgeon.

Obesity and lower limb osteoarthritis (OA) are amongst the commonest conditions worldwide, with increasing burden on health systems. The relationship between the two is complex. Obesity is thought to be a risk factor for OA, and OA can hinder efforts to reduce weight. Total knee replacement (TKR) is a widely used and effective management for knee OA. However, high body mass index (BMI) can complicate the surgery, which leads to some surgeons denying this operation to patients above a certain BMI. Orthopaedic surgeons have an important part in helping patients lose weight in the process of preparing for their TKR. We review the effect of high BMI on developing symptomatic knee OA, the complication rate with high BMI and TKR and the obstacles to losing weight in the presence of OA and point to areas where the orthopaedic surgeon can find support for their patients during their journey to losing weight. We review the evidence to see whether denying patients a TKR based on their BMI is justified and look into the most effective way to engage high BMI patients to improve their chance of a complication-free TKR.

Predictive Factors for Magnetic Resonance Imaging Changes Suggestive of Demyelination in Adult Patients with Uveitis Scanned Prior to Commencing Adalimumab Therapy.

PURPOSE: To report the predictive clinical factors for abnormal magnetic resonance imaging (MRI) scans suggestive of demyelination by analysis of MRI's performed for adult non-infectious uveitic patients prior to commencing adalimumab therapy. METHODS: Retrospective case review of 240 patients was conducted in a single tertiary institution between November 2017 and March 2020. Aetiology of underlying disease, clinical characteristics, and MRI outcomes were analysed. RESULTS: The presence of bilateral idiopathic intermediate uveitis (IIU) (p = .0048) and neurological symptoms (p = .028) were highly predictive of an abnormal MRI strongly suggestive of demyelination (MRSSD); 5 out of 64 scans (7.8%) with these clinical characteristics had MRSSD. CONCLUSIONS: Tumor necrosis factor antagonist-induced demyelination is a concern in adalimumab use. We propose an MRI screening protocol to identify those at high risk of demyelination; positive results can be maximised by screening all patients with IIU and those with neurological symptoms.

Using framework analysis to understand multiple stakeholders' views of vocational rehabilitation following acquired brain injury.

PURPOSE: To explore how vocational rehabilitation (VR) is currently delivered for individuals with acquired brain injury (ABI) across multiple stakeholder groups and identify areas for improvement in service delivery using the Consolidated Framework for Implementation Research (CFIR). METHODS: Seven focus groups were conducted with rehabilitation clinicians; outreach providers, insurers/regulators, VR providers and disability employment service providers (n = 44) experienced in VR of individuals with ABI. All groups were audio-recorded and transcribed verbatim. Data analysis was guided by the CFIR constructs. RESULTS: All stakeholder groups believed they offered quality VR interventions given available resources and legislation, but many clients fell through the 'cracks'. Themes that were identified included: a) number and complexity of systems supporting VR; b) fractured communication across systems, c) lack of knowledge by both stakeholders and clients in navigating systems, d) lack of expertise in supporting the vocational needs of clients with ABI and e) perceived limited awareness of ABI by employers. CONCLUSION: Stakeholders and clients need support to navigate Australia's complex VR pathways. Limited specialist ABI clinicians, VR providers and disability employment services were identified as barriers for effective VR. Domains of the CFIR were appropriate for organising and understanding how VR is delivered.

Exploring the lived return-to-work experience of individuals with acquired brain injury: use of vocational services and environmental, personal and injury-related influences.

PURPOSE: To explore work outcomes, vocational services, barriers and facilitators for returning to work in individuals with acquired brain injury (ABI) in Queensland, Australia and to identify areas for improvement. DESIGN AND METHODS: Ten semi-structured interviews were conducted with individuals with ABI (stroke, traumatic brain injury, tumour). Interviews were analysed using a realist thematic analysis approach. RESULTS: Participants either returned to the same work, different work, did not maintain work or did not have any work since their injury. Use of vocational services depended on participants' needs and insurance. Facilitators for return to work (RTW) were a supportive workplace and family, vocational rehabilitation that met the individual's needs, insurance coverage and self-motivation. Workplaces that were not understanding of brain injury, employment service providers who were unable to find work for participants, and physical and cognitive deficits were barriers to RTW. Workplaces, employment service providers and individuals require more information about the deficits associated with brain injury. CONCLUSIONS: The use and effectiveness of vocational services were variable across participants and depended on insurance coverage and needs. Barriers and facilitators for RTW were affected by both the environment and the individual. Implications for vocational rehabilitation were identified.Implications for RehabilitationA supportive workplace and family, and access to appropriate vocational rehabilitation are important environmental facilitators for RTW in individuals with ABI.Workplaces with a poor understanding of ABI and employment service providers unable to find work for individuals with ABI are environmental barriers to RTW.Workplaces, employment service providers and individuals with ABI require more information about the physical and cognitive deficits associated with ABI.Employment service providers need more training to develop comprehensive strategies to help individuals with ABI find new employment.

Perioperative Care of Children with Severe Neurological Impairment and Neuromuscular Scoliosis-A Practical Pathway to Optimize Peri-Operative Health and Guide Decision Making.

Neuromuscular scoliosis is a common feature in children with severe neurological impairment (SNI), including those with severe cerebral palsy. Surgical correction of scoliosis is the mainstay of treatment. This group of patients also have associated medical complexity. The complication rates post-surgery are high, although, for many, they are worth the risk. There are currently no published practice guidelines or care pathways for children with SNI who are undergoing scoliosis corrective surgery. In response to the high uptake of this surgery, coupled with the expected complication rates, our hospital established a perioperative clinic. The purpose of this paper is to describe our perioperative approach. This clinic has developed into a service beyond perioperative care and, with the collaborative meeting, enables shared decision-making to identify the right candidate for surgery. The process involves surgical expertise, understanding the family and child at the centre, and optimisation of medical care pre- and post-surgery. In this paper, we describe the process in a step-by-step manner. We provide clinical vignettes, as well as the proformas that we use, and we highlight the benefits of the team-based process.

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series.

OBJECTIVE: To examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. METHODS: This was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined. RESULTS: The cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6-85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure. CONCLUSIONS: Efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher. CLASSIFICATION OF EVIDENCE: This study is rated Class IV because of the uncontrolled, open-label design.

Systematic approach needed to establish cause of vertigo.

Vertigo can be defined as an illusion or hallucination of movement. The control of balance is complicated. Vertigo can be caused by many different pathologies, some of which are potentially life threatening. An important differentiation is whether the symptoms of vertigo originate from a central or peripheral origin. Clues to a central origin are other brainstem symptoms or signs of acute onset such as headache, deafness and other neurological findings. These patients warrant urgent referral and investigation. Red flags in patients with vertigo include: headache; neurological symptoms; and neurological signs. It is useful to categorise vertigo into acute and chronic. The former usually has a single mechanism whereas chronic dizziness is often multifactorial. History is usually the most important part of the assessment. Key questions should be asked and it is vital to establish if the patient is suffering from vertigo or some other complaint such as anxiety or syncope. A neurological and otological examination should be performed, appropriate to the history. Assessment of gait and posture is crucial. If the patient has positional vertigo then a Hallpike test should be performed. Visual acuity should be checked as vision is a vital part of the balance system. The cranial nerves should be tested in particular eye movements for any ophthalmoplegia pointing to focal cranial nerve pathology and for nystagmus. The rest of the neurological examination should exclude evidence of central disease, in particular cerebellar disease, and neuropathy. If syncope is suspected it is wise to perform an extensive systemic examination in particular lying and standing BP, and cardiovascular and respiratory system assessments.

ß-lactam dosing strategies: Think before you push.

OBJECTIVES: There has been interest in administering cefepime, a ß-lactam antibiotic, via intravenous push (IVP) as a means to improve time to first-dose antibiotic and reduce cost; however, the downstream impacts on antibiotic exposure and pharmacodynamic efficacy need to be further evaluated. METHODS: This study used a population pharmacokinetic model for cefepime and simulated exposures to predict the pharmacodynamic (PD) effect for cefepime regimens administered via IVP or 30-minute intermittent infusion in adults with different renal functions. FDA-approved adult dosages of 1-2 g every 8 or 12 hours were compared. This study aimed to compare the absolute difference in pharmacodynamic probability of target attainment (PTA) between IVP and intermittent infusion, defined as free cefepime concentrations above organism MIC for ≥ 70% of the time. RESULTS: At MICs of 0.25-0.5 mg/L, absolute differences in PTA were observed, with a reduction as great as 2.3% (89% to 86.7% for 30-minute intermittent infusion and IVP, respectively). At MICs of 1-4 mg/L, 30-minute intermittent infusion and IVP exhibited PTA differences as great as 5.4%, from 89.4% to 84%, respectively. At MICs of ≥8 mg/L, similar absolute differences existed; however, no regimen achieved a PTA >70%. Across renal function strata of 60, 100 and 140 mL/minute (within the same dosing group and MICs), better renal function lowered PTAs. CONCLUSIONS: Simulations demonstrated that IVP cefepime resulted in lower PTAs than traditional intermittent infusion among a subset of elevated MICs. Clinicians should exercise caution in IVP strategy, as unintended clinical consequences are possible.

Assessing emotional status following acquired brain injury: the clinical potential of the depression, anxiety and stress scales.

PRIMARY OBJECTIVE: To investigate the clinical potential of the Depression, Anxiety and Stress Scales (DASS 42) and its shorter version (DASS 21) for assessing emotional status following acquired brain injury. METHODS AND PROCEDURES: Participants included 23 individuals with traumatic brain injury (TBI), 25 individuals with brain tumour and 29 non-clinical controls. Investigations of internal consistency, test-re-test reliability, theory-consistent differences, sensitivity to change and concurrent validity were conducted. MAIN OUTCOMES AND RESULTS: Internal consistency of the DASS was generally acceptable (r > 0.70), with the exception of the anxiety scale for the TBI sample. Test-re-test reliability (1-3 weeks) was sound for the depression scale (r > 0.75) and significant but comparatively lower for other scales (r = 0.60-0.73, p < 0.01). Theory-consistent differences were only evident between the brain tumour sample and non-clinical control sample on the anxiety scale (p < 0.01). Sensitivity to change of the DASS in the context of hospital discharge was demonstrated for depression and stress (p < 0.01), but not for anxiety (p > 0.05). Concurrent validity with the Hospital Anxiety and Depression Scale was significant for all scales of the DASS (p < 0.05). CONCLUSIONS: While the results generally support the clinical application of the DASS following ABI, further research examining the factor structure of existing and modified versions of the DASS is recommended.

QueF-Like, a Non-Homologous Archaeosine Synthase from the Crenarchaeota.

Archaeosine (G⁺) is a structurally complex modified nucleoside ubiquitous to the Archaea, where it is found in the D-loop of virtually all archaeal transfer RNA (tRNA). Its unique structure, which includes a formamidine group that carries a formal positive charge, and location in the tRNA, led to the proposal that it serves a key role in stabilizing tRNA structure. Although G⁺ is limited to the Archaea, it is structurally related to the bacterial modified nucleoside queuosine, and the two share homologous enzymes for the early steps of their biosynthesis. In the Euryarchaeota, the last step of the archaeosine biosynthetic pathway involves the amidation of a nitrile group on an archaeosine precursor to give formamidine, a reaction catalyzed by the enzyme Archaeosine Synthase (ArcS). Most Crenarchaeota lack ArcS, but possess two proteins that inversely distribute with ArcS and each other, and are implicated in G⁺ biosynthesis. Here, we describe biochemical studies of one of these, the protein QueF-like (QueF-L) from Pyrobaculum calidifontis, that demonstrate the catalytic activity of QueF-L, establish where in the pathway QueF-L acts, and identify the source of ammonia in the reaction.