The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates.

Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to be developed. Our previous study showed the synthetic TLR2/TLR6 ligand fibroblast stimulating lipopeptide (FSL-1) prolonged survival and provided MyD88-dependent mitigation of hematopoietic acute radiation syndrome (H-ARS) in mice. Although mice and humans differ in TLR number, expression, and function, nonhuman primate (NHP) TLRs are like those of humans; therefore, studying both animal models is critical for drug development. The objectives of this study were to determine the efficacy of FSL-1 on hematopoietic recovery in small and large animal models subjected to sublethal total body irradiation and investigate its mechanism of action. In mice, we demonstrate a lack of adverse effects, an easy route of delivery (subcutaneous) and efficacy in promoting hematopoietic progenitor cell proliferation by FSL-1. NHP given radiation, followed a day later with a single subcutaneous administration of FSL-1, displayed no adversity but showed elevated hematopoietic cells. Our analyses revealed that FSL-1 promoted red blood cell development and induced soluble effectors following radiation exposure. Cytologic analysis of bone marrow aspirates revealed a striking enhancement of mononuclear progenitor cells in FSL-1-treated NHP. Combining the efficacy of FSL-1 in promoting hematopoietic cell recovery with the lack of adverse effects induced by a single administration supports the application of FSL-1 as a viable countermeasure against H-ARS.

Establishing Mental Health Friendly Pharmacies to Assist in THe Early Identification and Support of OldEr Adults at Risk of Depression: the EMPATHISE pilot study.

BACKGROUND: Late-life depression (LLD) often goes underdiagnosed and undertreated. Community pharmacists are one of the most accessible and trusted healthcare professionals (HCPs) and may play a significant role in LLD screening. OBJECTIVES: This study aimed to develop and pilot a pharmacist-delivered depression screening and referral service for older adults (≥65 years) at risk of depression, within community pharmacy. METHODS: Community pharmacists across New South Wales, Australia, were recruited to participate in a prospective pilot study. Pharmacists/pharmacy staff received specialised training before recruiting and screening patients aged ≥65 years using the Geriatric Depression Scale-15 (GDS-15). Patients scoring ≥6 were referred to another HCP, e.g., general practitioner, and followed-up by the pharmacist one-week post-screening. Patients were also followed-up by a research team member 6-weeks post-screening to explore outcomes of the screening. Semi-structured interviews with pharmacists and patients were undertaken following completion of the pilot study to explore their experiences delivering/receiving the screening service. A thematic inductive analysis approach was used to analyse interview data. RESULTS: A total of 39 community pharmacies participated in this study. In total, 113 participants attended the training sessions. Pharmacists screened 15 patients from 8 pharmacies, of which 67% were female. Two thirds of patients (67%) received a GDS-15 score of ≥6, indicating possible depression and requiring referral. Pharmacists referred 80% of patients to another HCP. One patient was diagnosed with depression and commenced antidepressant therapy. Five patients and six pharmacists participated in semi-structured interviews. Barriers to screening included lack of time and mental illness stigma. Facilitators included pharmacist-patient relationships and training. CONCLUSION: Pharmacist-delivered LLD screening was found to be acceptable by both pharmacists and patients, with pharmacists reporting training improved their comfort and confidence with depression screening. These pilot study findings may inform future work into service delivery models to support early identification and treatment of LLD.

Bullying Victimization, Future Orientation, and Suicidal Ideation of African American Youth in an Under-Resourced Community: A Moderated-Mediation Approach.

African American youth living in low-resourced communities are at high risk for bullying victimization which is positively associated with suicidal ideation. This study explored whether positive future orientation mediated the relationship between bullying victimization and suicidal ideation. This study engaged 627 African American adolescents and measured bullying victimization, internalizing problems, suicidal ideation, future orientation, and several covariates. Major findings indicated that controlling for gender, socioeconomic status, school motivation, and perceived teacher support, internalizing problems mediated the relationship between bullying victimization and suicidal ideation. Furthermore, both the effect of bullying victimization on suicidal ideation and the mediating effect of internalizing problems were moderated by future orientation. The effects were weakened when the level of future orientation increased. The implications for future research and supporting resiliency are discussed based on these findings.

Technological Advances in Cognitive-Behavioral Therapy and Clinical Practice: Challenges in an Evolving Field.

Technological innovations in cognitive-behavioral therapy (CBT) provide excellent opportunities for mental health clinicians to expand access to mental health treatment among culturally diverse and marginalized populations. This brief report highlights challenges that mental health clinicians encounter as they integrate technological innovations in CBT into their work with diverse clients and provides recommendations for addressing them. The authors identify five key challenges of using technology-driven CBT: development of the therapeutic alliance; potential fit for clients from culturally diverse backgrounds and marginalized groups; geographic and economic access; ethical and legal concerns; and competency in CBT practice, training, and supervision. Technological advances in CBT allow clinicians to treat more individuals from underserved communities. Existing challenges compel clinicians across disciplines to ensure that their practice is congruent with CBT practice values and ethics, policy, and research and that the best available CBT intervention can be integrated into all aspects of mental health practice.

Technology-Assisted, Group-Based CBT for Rural Adults' Depression: Open Pilot Trial Results.

Purpose: This pilot study assesses the association of Raising Our Spirits Together (ROST), a technology-assisted, group-based cognitive behavioral therapy for depression, with rural adults' depressive symptoms and anxiety. Method: Nine adults from rural Michigan participated in an open pilot of ROST. Clergy facilitated pilot groups. The pilot began in February 2020 in-person. Due to COVID-19, the pilot was completed virtually. Results: Mean depressive symptom scores, based on the PHQ-9, significantly decreased from pre-treatment (M = 14.4) to post-treatment (M = 6.33; t (8) = 6.79; P < .001). Symptom reduction was maintained at 3-month follow-up (M = 8.00), with a significant pattern of difference in depressive symptoms over time (F(2) = 17.7; P < .001; eta-squared = .689). Similar patterns occurred for anxiety based on the GAD-7. Participants attended an average of 7.33 of 8 sessions. Fidelity ratings were excellent. Discussion: ROST is a potentially feasible intervention for rural adults' depressive symptoms. ROST offers a promising model for increasing treatment access and building capacity in rural areas.

Impact of the Goal-directed Medication Review Electronic Decision Support System on Drug Burden Index: A cluster-randomised clinical trial in primary care.

AIMS: The Goal-directed Medication Review Electronic Decision Support System (G-MEDSS) assesses and reports a patient's goals, attitudes to deprescribing and Drug Burden Index (DBI) score, a measure of cumulative exposure to anticholinergic and sedative medications. This study evaluated the effect of implementing G-MEDSS in home medicines reviews (HMRs) on DBI exposure and clinical outcomes. METHODS: A cluster-randomised clinical trial was performed across Australia. Accredited clinical pharmacists were randomised into intervention (G-MEDSS with usual care HMR) or comparison groups (usual care HMR alone). Patients were recruited by pharmacists from those routinely referred by general practitioners for HMR. The primary outcome was the proportion of patients with any reduction in DBI at 3-months follow-up. Secondary outcomes included change in DBI continuous score at 3-months, HMR recommendations to change DBI and clinical outcomes. RESULTS: There were 201 patient participants at baseline (n = 88 intervention, n = 113 comparison), with 159 followed-up at 3-months (n = 63 intervention, n = 96 comparison). The proportion of patients with a reduction in DBI was not significantly different at 3-months (intervention 17%, comparison 11%; adjusted odds ratio 1.44, 95% confidence interval 0.56-3.80). Regarding secondary outcomes, there was no difference in change in DBI score at 3-months. However, the HMR report made recommendations to reduce DBI for a significantly greater proportion of patients in the intervention than in the comparison group (intervention 37%, comparison 14%; adjusted odds ratio 3.20, 95% confidence interval 1.50-6.90). No changes were observed in clinical outcomes. CONCLUSION: Implementation of G-MEDSS within HMR did not reduce patients' DBI at 3 months compared with usual care HMR.

Development and dissemination of the national strategic action plan for reducing inappropriate polypharmacy in older Australians.

A cohesive, national approach is needed to address inappropriate polypharmacy in older adults and promote deprescribing. We describe the dissemination of the Quality Use of Medicines to Optimise Ageing in Older Australians: Recommendations for a National Strategic Action Plan to Reduce Inappropriate Polypharmacy, and the initiatives taken to date that align with, and assist in operationalising this plan.

Implementation of the Goal-directed Medication review Electronic Decision Support System (G-MEDSS)© into home medicines review: a protocol for a cluster-randomised clinical trial in older adults.

BACKGROUND: Older people living in the community have a high prevalence of polypharmacy and are vulnerable to adverse drug events. Home Medicines Review (HMR) is a collaborative medication review service involving general practitioners (GPs), accredited clinical pharmacists (ACPs) and patients, which aims to prevent medication-related problems. This study aims to evaluate the implementation of a Computerised Clinical Decision Support System (CCDSS) called G-MEDSS© (Goal-directed Medication Review Electronic Decision Support System) in HMRs to deprescribe anticholinergic and sedative medications, and to assess the effect of deprescribing on clinical outcomes. METHODS: This study consists of 2 stages: Stage I - a two-arm parallel-group cluster-randomised clinical trial, and Stage II - process evaluation of the CCDSS intervention in HMR. Community-dwelling older adults living with and without dementia who are referred for HMR by their GP and recruited by ACPs will be included in this study. G-MEDSS is a CCDSS designed to provide clinical decision support for healthcare practitioners when completing a medication review, to tailor care to meet the patients' goals and preferences. The G-MEDSS contains three tools: The Goals of Care Management Tool, The Drug Burden Index (DBI) Calculator©, and The revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. The G-MEDSS produces patient-specific deprescribing reports, to be included as part of the ACPs communication with the patient's GP, and patient-specific reports for the patient (or carer). ACPs randomised to the intervention arm of the study will use G-MEDSS to create deprescribing reports for the referring GP and for their patient (or carer) when submitting the HMR report. ACPs in the comparison arm will provide the usual care HMR service (without the G-MEDSS). OUTCOMES: The primary outcome is reduction in DBI exposure 3 months after HMR ± G-MEDSS intervention between comparison and intervention groups. The secondary outcomes include changes in clinical outcomes (physical and cognitive function, falls, institutionalisation, GP visits, medication adherence and mortality) 3-months after HMR. DISCUSSION: This study is expected to add to the evidence that the combination of CCDSS supporting medication review can improve prescribing and clinical outcomes in older adults. TRIAL REGISTRATION: The trial was registered on the Australian New Zealand Clinical Trials Registry ACTRN12617000895381 on 19th June 2017.

Correction to: Implementation of the goal-directed medication review electronic decision support system (G-MEDSS)© into home medicines review: a protocol for a clusterrandomised clinical trial in older adults.

An amendment to this paper has been published and can be accessed via the original article.

Patient Empowerment Using Electronic Telemonitoring With Telephone Support in the Transition to Insulin Therapy in Adults With Type 2 Diabetes: Observational, Pre-Post, Mixed Methods Study.

BACKGROUND: Initiation of insulin therapy for the management of type 2 diabetes can be an unwelcome and distressful development for patients. Current evidence suggests that telemonitoring can help improve glycemic control in type 2 diabetes and can support empowerment to self-manage diabetes. This telemonitoring intervention was underpinned by an empowerment approach. OBJECTIVE: This study aimed to evaluate the clinical effectiveness and feasibility and the patients' and health care providers' experiences of a 12-week telemonitoring intervention with telephone support for patients commencing insulin therapy. This paper focuses on the impact on patient empowerment. METHODS: An observational, pre-post, multimethod, and triangulation design was employed to study a 12-week automated electronic telemonitoring intervention with telephone support from a diabetes clinical nurse specialist (CNS). Forty patients were recruited from the clinic as they were about to commence insulin therapy. In the quantitative arm, biometric data (hemoglobin A1c [HbA1c] and weight) and psychosocial data (diabetes empowerment scale [DES] scores and diabetes distress scale [DDS] scores) were gathered by the research team at baseline (T1), the end of the intervention (T2), and 3 months postintervention (T3). Data on hospital admission and general practitioner (GP) visits were collected for the duration of the study. In the qualitative arm, separate focus group interviews were conducted with the CNS team supporting the intervention (n=2) and patients (n=16). RESULTS: Of 39 patients who completed the intervention, 23 (59%) were male. The mean age of the sample was 62.4 years (range 37-80 years). The mean HbA1c (mmol/mol) decreased significantly between T1 and T2 (mean difference [MD] -17.13; P<.001) and T1 and T3 (MD -18.16; P<.001), with no significant impact on weight. In the focus groups, patients reported an increased awareness to self-manage diabetes and feelings of safety and comfort. There were 13% (5/39) of patients who had hypoglycemia on two or more occasions. A significant increase in the mean DES score occurred between T1 and T2 (MD 0.62; P=.001) and T1 and T3 (MD 0.72; P<.001). The mean DDS score decreased between T1 and T2 (MD -0.64; P=.002) and T1 and T3 (MD -0.6; P=.002). The mean patient satisfaction with the intervention was above 4 out of possible 5 on all items on the Telemedicine Satisfaction and Usefulness Questionnaire. We observed a reduction in diabetes clinic attendances and GP visits. A significant increase in workload was reported by the CNS team. CONCLUSIONS: This intervention had an empowering effect for patients in the self-management of type 2 diabetes and has the potential to meet the need for safer and more effective care in insulin initiation in the community setting. We observed a significant increase in workload for health care staff. Telemonitoring needs to be streamlined with health care delivery and accompanied by adequate support services.

A Randomized Comparison of Two Psychosocial Interventions on Family Functioning in Adolescents with Bipolar Disorder.

Impairments in family functioning are associated with more severe depressive and manic symptoms, earlier recurrences, and more suicidal behaviors in early-onset bipolar disorder. This study examined whether family-focused treatment for adolescents (FFT-A) with BD I or II disorder led to greater increases in family cohesion and adaptability and decreases in conflict over 2 years compared to a briefer psychoeducational treatment (enhanced care, EC). Participants were 144 adolescents (mean age: 15.6 ± 1.4 years) with BD I or II with a mood episode in the previous 3 months. Adolescents and parents were randomized to either FFT-A (21 sessions) or EC (three sessions). Patients received guideline-based pharmacotherapy throughout the 2-year study. Trajectories of adolescent- and parent-rated family cohesion, adaptability, and conflict were analyzed over 2 years. FFT-A had greater effects on adolescent-rated family cohesion compared to EC over 2 years. Participants in FFT-A and EC reported similar improvements in family conflict across the 2 years. In the FFT-A group, low-conflict families had greater adolescent-rated family cohesion throughout the study compared to high-conflict families. High-conflict families in both treatment groups tended to show larger reductions in conflict over 2 years than low-conflict families. Family psychoeducation and skills training may improve family cohesion in the early stages of BD. Measuring levels of family conflict at the start of treatment may inform treatment responsiveness among those receiving FFT-A.

Los problemas en el funcionamiento familiar están asociados con síntomas depresivos y maníacos más graves, recidivas en periodos más breves y más conductas suicidas en el trastorno bipolar de inicio precoz. Este estudio analizó si el "Tratamiento centrado en la familia para adolescentes" (Family-Focused Treatment for Adolescents, FFT-A) con trastorno bipolar tipo I y tipo II condujo a mayores aumentos en la cohesión familiar y en la adaptabilidad y a disminuciones en el conflicto durante dos años en comparación con un tratamiento psicoeducativo más breve (atención optimizada; Enhanced Care: EC). Los participantes fueron 144 adolescentes (edad promedio: 15.6±1.4 años) con trastorno bipolar tipo I o tipo II con un episodio de alteración del humor en los tres meses previos. Los adolescentes y los padres fueron asignados aleatoriamente al FFT-A (21 sesiones) o a la EC (3 sesiones). Los pacientes recibieron farmacoterapia pautada durante todo el estudio de dos años. Las trayectorias de la cohesión familiar evaluada por los adolescentes y los padres, la adaptabilidad y el conflicto se analizaron durante dos años. El FFT-A tuvo mayores efectos en la cohesión familiar evaluada por los adolescentes en comparación con la EC durante dos años. Los participantes del FFT-A y de la EC informaron mejoras similares en el conflicto familiar durante los dos años. Las familias con un alto nivel de conflicto en el FFT-A tuvieron una menor cohesión evaluada por los adolescentes y una menor adaptabilidad durante dos años en comparación con las familias con un bajo nivel de conflicto en el FFT-A. Las familias con un alto nivel de conflicto en ambos grupos de tratamiento tendieron a mostrar reducciones más grandes en el conflicto durante dos años que las familias con un bajo nivel de conflicto. La psicoeducación familiar y la capacitación en habilidades pueden mejorar la cohesión familiar en las etapas iniciales del trastorno bipolar. La medición de los niveles de conflicto familiar al comienzo del tratamiento puede respaldar la capacidad de respuesta al tratamiento entre aquellos que reciben el FFT-A.

Self-reported affective biases, but not all affective performance biases, are present in depression remission.

OBJECTIVE: Individuals with active major depressive disorder (MDD) have shown affective biases in cognitive flexibility and memory, particularly for negatively valenced stimuli. We evaluated whether impairments in affective flexibility would remain even during remission (rMDD), potentially representing trait- or scar-like effects of illness. METHOD: Participants completed the Emotion Card Sort Test (ECST), a measure of cognitive flexibility containing emotionally valenced stimuli, and the Emotion Word Stimulus Test (EWST), a measure of affective biases in delayed recall and recognition memory, and several self-report measures. RESULTS: Healthy controls (HCs; n = 35) and individuals with rMDD (n = 93) did not differ on performance for any of the three word types on the ECST or EWT. However, individuals with rMDD demonstrated greater negative bias on EWT recognition trials relative to HCs (d = .36). On self-report measures, individuals with rMDD exhibited greater levels of neuroticism, problems with attentional control, pessimistic attributional style, and negative automatic thoughts compared to HCs. CONCLUSIONS: These results provide initial evidence that some performance, but not self-reported, indices of affective bias may improve during remission from MDD. Results of this study could suggest that some components of affective bias may represent state feature of illness and others trait-like risk or scar features. PRACTITIONER POINTS: This study suggests that self-reported affective biases may persist in remission of major depressive disorder (rMDD). Affective attentional biases and affective memory biases were not demonstrated in individuals with rMDD, with the exception of a bias for recognizing negatively versus neutrally valenced stimuli. CAUTIONS OR LIMITATIONS: A limitation of this study was its cross-sectional design. Under ideal conditions, the same individuals would be studied in both the active and remitted phases of illness. Another limitation of this study was the smaller number of healthy controls relative to individuals with rMDD.

Psychotropic medications in older people in residential care facilities and associations with quality of life: a cross-sectional study.

BACKGROUND: Psychotropic medications have been associated with many adverse outcomes in older people living in residential care. Home-like models of residential care may be preferable to traditional models of care and we hypothesized that this model may impact on the prevalence of psychotropic medications. The objectives were to: 1) examine associations between psychotropic medications and quality of life in older adults living in residential care facilities with a high prevalence of cognitive impairment and dementia and 2) determine if there was a difference in prevalence of psychotropic medications in facilities which provide a small group home-like model of residential care compared to a 'standard model' of care. METHODS: Participants included 541 residents from 17 residential aged care facilities in the Investigating Services Provided in the Residential Environment for Dementia (INSPIRED) study. Cross-sectional analyses were completed to examine the above objectives. Quality of life was measured with the dementia quality of life questionnaire (DEMQOL) and the EQ-5D-5L completed by the resident or a proxy. RESULTS: Overall, 70.8% (n = 380) of the population had been prescribed/dispensed at least one psychotropic medication in the 100 days prior to recruitment. An increased number of psychotropic medications was associated with lower quality of life according to DEMQOL-Proxy-Utility scores (ß (SE): - 0.012 (0.006), p = 0.04) and EQ-5D-5L scores (- 0.024 (0.011), p = 0.03) after adjustment for resident-level and facility-level characteristics. Analysis of the individual classes of psychotropic medications showed antipsychotics were associated with lower DEMQOL-Proxy-Utility scores (- 0.030 (0.014), p = 0.03) and benzodiazepines were associated with lower EQ-5D-5L scores (- 0.059 (0.024), p = 0.01). Participants residing in facilities which had a home-like model of residential care were less likely to be prescribed psychotropic medications (OR (95% CI): 0.24 (0.12, 0.46), p < 0.001). CONCLUSIONS: An increased number of psychotropic medications were associated with lower quality of life scores. These medications have many associated adverse effects and the use of these medications should be re-examined when investigating approaches to improve quality of life for older people in residential care. Home-like models of residential care may help to reduce the need for psychotropic medications, but further research is needed to validate these findings.

A Preliminary Study of Central Nervous System Arousal and Sleep Quality in Bipolar Disorder.

Sleep disturbances are commonly reported in patients with bipolar I disorder (BPI) and are risk factors for mood episodes. In other populations, central nervous system (CNS) hyperarousal is associated with sleep initiation and maintenance problems, and CNS hypoarousal is associated with increased sleep drive. However, it is unclear whether CNS arousal levels are a useful index of sleep disruption in BPI. This study aimed to investigate daytime CNS arousal levels in relation to perceived sleep quality in BPI. Resting EEG, mood state, and self-reported sleep quality data were collected from 34 individuals with BPI. CNS hyperarousal was associated with pervasive poor subjective sleep quality including increased sleep disturbances, increased sleep latency, and reduced global sleep quality. CNS hypoarousal was associated with greater daytime sleepiness, indicating reduced arousal. These preliminary findings suggest that CNS arousal may be a useful index for identifying individuals at high risk for relapse into a mood episode. A limitation of this study is the use of self-report instruments for sleep quality assessment. Future research should investigate the temporal relationship of CNS arousal to sleep disturbances using objective measurements of sleep quality such as polysomnography. If these findings are replicated, measures of CNS arousals may allow for identification of high-risk patients with BPI.

Altered N170 and mood symptoms in bipolar disorder: An electrophysiological study of configural face processing.

OBJECTIVES: Altered social behavior during mood episodes in bipolar disorder often has detrimental and long-lasting interpersonal consequences. Abnormal face processing may play a role in linking brain functions to clinical symptoms and behavior. This study aimed to understand configural face processing in bipolar disorder as a function of basic communicative attributes of the face and mood symptoms using event-related brain potentials (ERPs). METHODS: Forty-two participants with bipolar I disorder (BP) and 43 healthy controls (HC) viewed face stimuli varying in emotion (neutral or fearful), head orientation (forward or deviated), and gaze direction (direct or averted) while ERPs were recorded. Configural face processing was indexed by the N170 wave. RESULTS: BP participants had comparable overall N170 amplitude and peak latency to HC, although timing was more variable in the BP group. Abnormal N170 modulations by communicative face attributes were observed in BP: exaggerated sensitivity to emotion (fearful > neutral) in the left hemisphere, and reduced sensitivity to gaze-head incongruency (where N170 is normally larger in response to faces with incongruent than congruent gaze and head direction) in the right hemisphere. The former was not associated with mood symptoms, suggesting a heightened trait-like sensitivity to negative emotions. The latter was correlated with greater manic symptoms, indicating that an impaired perceptual sensitivity to faces with features signaling incongruent social attention may underlie social deficits observed during mania. CONCLUSIONS: These findings suggest a pathophysiological role of altered configural face processing in the phenomenology of bipolar disorder, and call for further investigations to evaluate its potential as a biomarker and treatment target.

Assessment of Multiplate platelet aggregometry using citrate, heparin or hirudin in Rhesus macaques.

Electrical impedance aggregometry (EIA) has gained popularity in clinical and research applications. Nonhuman primates are used to study disease and drug-related mechanisms that affect hemostasis, therefore establishing normal EIA parameters are necessary. The anticoagulants sodium heparin, hirudin and sodium citrate and three agonists, ADP, ASPI, and collagen were evaluated. Whole blood from 12 adult male rhesus macaques was collected to evaluate anticoagulants, sodium heparin, hirudin and sodium citrate using three agonists (ADP, ASPI and collagen), on the Multiplate® 5.0 Analyzer. Platelet function was reported for three parameters: Area under the curve (AUC), aggregation, and aggregation velocity. There was a significant difference in mean AUC between citrate and heparin samples, and citrate and hirudin samples regardless of the agonist used. There was no difference in AUC between heparin and hirudin. ADP-activated samples showed an increase in impedance with hirudin samples compared to citrate. Furthermore, heparin and hirudin out-perform citrate as the anticoagulant for EIA in the macaque. Finally, this study demonstrates the utility of the Multiplate® system in this model and provides important insight into anticoagulant choice when using EIA.