The emotional face of anorexia nervosa: The neural correlates of emotional processing.

Social-emotional processing difficulties have been reported in Anorexia Nervosa (AN), yet the neural correlates remain unclear. Previous neuroimaging work is sparse and has not used functional connectivity paradigms to more fully explore the neural correlates of emotional difficulties. Fifty-seven acutely unwell AN (AAN) women, 60 weight-recovered AN (WR) women and 69 healthy control (HC) women categorised the gender of a series of emotional faces while undergoing Functional Magnetic Resonance Imaging. The mean age of the AAN group was 19.40 (2.83), WR 18.37 (3.59) and HC 19.37 (3.36). A whole brain and psychophysical interaction connectivity approach was used. Parameter estimates from significant clusters were extracted and correlated with clinical symptoms. Whilst no group level differences in whole brain activation were demonstrated, significant group level functional connectivity differences emerged. WR participants showed increased connectivity between the bilateral occipital face area and the cingulate, precentral gyri, superior, middle, medial and inferior frontal gyri compared to AAN and HC when viewing happy valenced faces. Eating disorder symptoms and parameter estimates were positively correlated. Our findings characterise the neural basis of social-emotional processing in a large sample of individuals with AN.

Evaluating the impact of COVID-19 on supportive care needs, psychological distress and quality of life in UK cancer survivors and their support network.

OBJECTIVES: The COVID-19 pandemic is having considerable impact on cancer care, including restricted access to hospital-based care, treatment and psychosocial support. We investigated the impact on unmet needs and psychosocial well-being. METHODS: One hundred and forty four participants (77% female), including people with cancer and their support networks, were recruited. The most prevalent diagnosis was breast cancer. Forty-one participants recruited pre-pandemic were compared with 103 participants recruited during the COVID-19 pandemic. We measured participants' unmet supportive care needs, psychological distress and quality of life. RESULTS: Half of our patient respondents reported unexpected changes to treatment following pandemic onset, with widespread confusion about their longer-term consequences. Although overall need levels have not increased, specific needs have changed in prominence. People with cancer reported significantly reduced anxiety (p = 0.049) and improved quality of life (p = 0.032) following pandemic onset, but support network participants reported reduced quality of life (p = 0.009), and non-significantly elevated anxiety, stress and depression. CONCLUSION: Psychological well-being of people with cancer has not been detrimentally affected by pandemic onset. Reliance on home-based support to compensate for the lost availability of structured healthcare pathways may, however, explain significant and detrimental effects on the well-being and quality of life of people in their support and informal care networks.

A novel approach for autism spectrum condition patients with eating disorders: Analysis of treatment cost-savings.

OBJECTIVE: In the current economic context, it is critical to ensure that eating disorder (ED) treatments are both effective and cost-effective. We describe the impact of a novel clinical pathway developed to better meet the needs of autistic patients with EDs on the length and cost of hospital admissions. METHOD: The pathway was based on the Institute for Healthcare's Model of Improvement methodology, using an iterative Plan, Do, Study, Act format to introduce change and to co-produce the work with people with lived experience and with healthcare professionals. We explored the change in length and cost of admissions before and after the pathway was introduced. RESULTS: Preliminary results suggest that the treatment innovations associated with this pathway have led to reduced lengths of admission for patients with the comorbidity, which were not seen for patients without the comorbidity. Estimated cost-savings were approximately £22,837 per patient and approximately £275,000 per year for the service as a whole. CONCLUSION: Going forward, our aim is to continue to evaluate the effectiveness and cost-effectiveness of investment in the pathway to determine whether the pathway improves the quality of care for patients with a comorbid ED and autism and is good value for money.

The neural correlates of a central coherence task in young women with anorexia nervosa.

OBJECTIVE: Heightened detail-processing and low levels of central coherence are common in individuals with anorexia nervosa (AN) and predict poorer prognosis. However, it is unclear whether these processing styles predate the disorder or, rather, emerge during later stages of AN. The current study aimed to address this question by investigating central coherence, and the neural correlates of central coherence, in a sample of young women with AN with shorter duration of illness than previous studies recruiting adult samples. METHODS: We recruited 186 participants, including: 73 young women with AN, 45 young women weight-recovered from AN, and 68 age-matched controls. Participants completed the Embedded Figures Task during an fMRI scan. RESULTS: There were no significant differences between the participant groups in performance accuracy or reaction time. There were no other between-groups differences in neural response to the Embedded Figures Task. CONCLUSIONS: These findings contrast with evidence from older adults demonstrating differences in the neural underpinning of central coherence amongst participants with AN versus control participants. The current study adds to an increasing literature base demonstrating the resilience of neuropsychological traits and associated brain systems in the early stages of AN.

The use of a positive mood induction video-clip to target eating behaviour in people with bulimia nervosa or binge eating disorder: An experimental study.

Recent theoretical models and empirical research have indicated that momentary negative affect increases the likelihood of binge eating episodes for individuals with bulimia nervosa and binge eating disorder. However, relatively little research has explored the potential for positive mood to serve a protective effect in reducing the likelihood of overeating behaviour in bulimia nervosa and binge eating disorder. The current study included 30 women with bulimia nervosa or binge eating disorder in a within-subjects crossover design. Following exposure to a video designed to induce food craving, we found that a positive mood vodcast was associated with significantly lower levels of negative mood and food consumption in a taste test meal, when compared to a neutral vodcast (p = 0.002). These findings support a role for decreasing negative mood in reducing the likelihood of binge eating behaviour in women with bulimia nervosa and binge eating disorder.

Testing the addictive appetite model of binge eating: The importance of craving, coping, and reward enhancement.

In the current study, we examine components of the "addictive appetite" model of recurrent binge eating. Specifically, we tested the influence of addictive processes and the influence of emotional regulation processes on recurrent binge eating behaviour. We recruited 79 women in total for the current study: 22 with bulimia nervosa, 26 weight-matched lean comparison women, 15 women with binge eating disorder, and 16 weight-matched overweight/obese comparison women. Participants completed questionnaire assessments of food craving and motivations for eating. Compared with weight-matched comparison women, women with binge-type eating disorders endorse significantly greater levels of food craving, eating for purposes of coping, and eating for purposes of reward enhancement. A cluster analysis revealed that these three traits distinguish women with binge-type eating disorders from weight-matched comparison women. These findings provide support for the addictive appetite model of binge eating behaviour and highlight addictive and emotional regulation processes as potential targets for treatment.

Are trans diagnostic models of eating disorders fit for purpose? A consideration of the evidence for food addiction.

Explanatory models for eating disorders have changed over time to account for changing clinical presentations. The transdiagnostic model evolved from the maintenance model, which provided the framework for cognitive behavioural therapy for bulimia nervosa. However, for many individuals (especially those at the extreme ends of the weight spectrum), this account does not fully fit. New evidence generated from research framed within the food addiction hypothesis is synthesized here into a model that can explain recurrent binge eating behaviour. New interventions that target core maintenance elements identified within the model may be useful additions to a complex model of treatment for eating disorders.

Web-Based Psychological Interventions for People Living With and Beyond Cancer: Meta-Review of What Works and What Does Not for Maximizing Recruitment, Engagement, and Efficacy.

BACKGROUND: Despite high levels of psychological distress experienced by many patients with cancer, previous research has identified several barriers to accessing traditional face-to-face psychological support. Web-based psychosocial interventions have emerged as a promising alternative. OBJECTIVE: This meta-review aimed to synthesize evidence on recruitment challenges and enablers, factors that promote engagement and adherence to web-based intervention content, and factors that promote the efficacy of web-based psychosocial interventions for patients with cancer and cancer survivors. METHODS: We conducted a systematic search of previous reviews that investigated the recruitment, engagement, and efficacy of web-based and app-based psychosocial interventions in adult patients with cancer and cancer survivors. We searched PubMed, CINAHL, PsycINFO, and the Cochrane Library database for relevant literature. The search terms focused on a combination of topics pertaining to neoplasms and telemedicine. Two independent authors conducted abstract screening, full text screening, and data extraction for each identified article. RESULTS: A total of 20 articles met eligibility criteria. There was inconsistency in the reporting of uptake and engagement data; however, anxiety about technology and perceived time burden were identified as 2 key barriers. Web-based psychosocial oncology interventions demonstrated efficacy in reducing depression and stress but reported weak to mixed findings for distress, anxiety, quality of life, and well-being. Although no factors consistently moderated intervention efficacy, preliminary evidence indicated that multicomponent interventions and greater communication with a health care professional were preferred by participants and were associated with superior effects. CONCLUSIONS: Several consistently cited barriers to intervention uptake and recruitment have emerged, which we recommend future intervention studies address. Preliminary evidence also supports the superior efficacy of multicomponent interventions and interventions that facilitate communication with a health care professional. However, a greater number of appropriately powered clinical trials, including randomized trials with head-to-head comparisons, are needed to enable more confident conclusions regarding which web-based psychosocial oncology interventions work best and for whom. TRIAL REGISTRATION: PROSPERO CRD42020202633; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=202633.

The Finding My Way UK Clinical Trial: Adaptation Report and Protocol for a Replication Randomized Controlled Efficacy Trial of a Web-Based Psychological Program to Support Cancer Survivors.

BACKGROUND: Cancer survivors frequently report a range of unmet psychological and supportive care needs; these often continue after treatment has finished and are predictive of psychological distress and poor health-related quality of life. Web-based interventions demonstrate good efficacy in addressing these concerns and are more accessible than face-to-face interventions. Finding My Way (FMW) is a web-based, psycho-educational, and cognitive behavioral therapy intervention for cancer survivors developed in Australia. Previous trials have demonstrated that FMW is acceptable, highly adhered to, and effective in reducing the impact of distress on quality of life while leading to cost savings through health resource use reduction. OBJECTIVE: This study aims to adapt the Australian FMW website for a UK cancer care context and then undertake a single-blinded, randomized controlled trial of FMW UK against a treatment-as-usual waitlist control. METHODS: To an extent, our trial design replicates the existing Australian randomized controlled trial of FMW. Following a comprehensive adaptation of the web resource, we will recruit 294 participants (147 per study arm) from across clinical sites in North West England and North Wales. Participants will have been diagnosed with cancer of any type in the last 6 months, have received anticancer treatment with curative intent, be aged ≥16 years, be proficient in English, and have access to the internet and an active email address. Participants will be identified and recruited through the National Institute for Health Research clinical research network. Measures of distress, quality of life, and health economic outcomes will be collected using a self-report web-based questionnaire at baseline, midtreatment, posttreatment, and both 3- and 6-month follow-up. Quantitative data will be analyzed using intention-to-treat mixed model repeated measures analysis. Embedded semistructured qualitative interviews will probe engagement with, and experiences of using, FMW UK and suggestions for future improvements. RESULTS: The website adaptation work was completed in January 2021. A panel of cancer survivors and health care professionals provided feedback on the test version of FMW UK. Feedback was positive overall, although minor updates were made to website navigation, inclusivity, terminology, and the wording of the Improving Communication and Sexuality and Intimacy content. Recruitment for the clinical trial commenced in April 2021. We aim to report on findings from mid-2023. CONCLUSIONS: Replication studies are an important aspect of the scientific process, particularly in psychological and clinical trial literature, especially in different geographical settings. Before replicating the FMW trial in the UK setting, content updating was required. If FMW UK now replicates Australian findings, we will have identified a novel and cost-effective method of psychosocial care delivery for cancer survivors in the United Kingdom. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 14317248; https://www.isrctn.com/ISRCTN14317248. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31976.

A pilot study investigating the influence of oxytocin on attentional bias to food images in women with bulimia nervosa or binge eating disorder.

BACKGROUND: Previous research has found that exogenous oxytocin administration has the potential to modulate attentional biases in women with anorexia nervosa. Recent work has indicated that attentional biases to food may reinforce the recurrent binge eating behaviour characterising bulimia nervosa and binge eating disorder. To date, however, no study has yet investigated the effect of oxytocin on attentional biases to palatable food in women with bulimia nervosa and binge eating disorder. METHODS: The present study employed a single-session cross-over design to test the hypothesis that a divided dose of 64 IU of intranasal oxytocin, administered as one intranasal dose of 40 IU of oxytocin followed by a top-up of 24 IU of oxytocin 80 minutes later, vs placebo administration administered in the same dosing schedule would reduce attentional biases towards food images in a dot probe task. We hypothesised that oxytocin administration would reduce vigilance towards food to a greater degree in women with bulimia nervosa or binge eating disorder vs healthy comparison women. Twenty-five women with bulimia nervosa or binge eating disorder and 27 comparison women without history of an eating disorder were recruited to take part in the study. RESULTS: In contrast to our hypothesis, there was no main effect of diagnosis on attentional bias to food (fixed effect = 5.70, P = 0.363), nor a significant interaction between diagnosis and drug condition (fixed effect =-14.80, P = 0.645). There was a main effect of drug condition, such that oxytocin increased vigilance towards food vs neutral images in the dot probe task (fixed effect = 10.42, P = 0.044). A correlation analysis revealed that this effect was moderated by attentional bias in the placebo condition, such that greater avoidance of food stimuli in the placebo condition was associated with a greater increase in vigilance induced by oxytocin. CONCLUSIONS: The findings of the present study add to a mixed body of literature investigating the therapeutic effects of oxytocin in women. Future research would benefit from dose-response studies investigating the optimal dose of oxytocin for modulating the attentional processing of palatable food in populations with eating disorders.

Investigating resting brain perfusion abnormalities and disease target-engagement by intranasal oxytocin in women with bulimia nervosa and binge-eating disorder and healthy controls.

Advances in the treatment of bulimia nervosa and binge-eating disorder (BN/BED) have been marred by our limited understanding of the underpinning neurobiology. Here we measured regional cerebral blood flow (rCBF) to map resting perfusion abnormalities in women with BN/BED compared with healthy controls and investigate whether intranasal oxytocin (OT), proposed as a potential treatment, can restore perfusion in disorder-related brain circuits. Twenty-four women with BN/BED and 23 healthy women participated in a randomized, double-blind, crossover, placebo-controlled study. We used arterial spin labelling MRI to measure rCBF and the effects of an acute dose of intranasal OT (40 IU) or placebo over 18-26 min post dosing, as we have previously shown robust OT-induced changes in resting rCBF in men in a similar time-window (15-36 min post dosing). We tested for effects of treatment, diagnosis and their interaction on extracted rCBF values in anatomical regions-of-interest previously implicated in BN/BED by other neuroimaging modalities, and conducted exploratory whole-brain analyses to investigate previously unidentified brain regions. We demonstrated that women with BN/BED presented increased resting rCBF in the medial prefrontal and orbitofrontal cortices, anterior cingulate gyrus, posterior insula and middle/inferior temporal gyri bilaterally. Hyperperfusion in these areas specifically correlated with eating symptoms severity in patients. Our data did not support a normalizing effect of intranasal OT on perfusion abnormalities in these patients, at least for the specific dose (40 IU) and post-dosing interval (18-26 min) examined. Our findings enhance our understanding of resting brain abnormalities in BN/BED and identify resting rCBF as a non-invasive potential biomarker for disease-related changes and treatment monitoring. They also highlight the need for a comprehensive investigation of intranasal OT pharmacodynamics in women before we can fully ascertain its therapeutic value in disorders affecting predominantly this gender, such as BN/BED.

Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa.

People with anorexia nervosa (AN) commonly exhibit social difficulties, which may be related to problems with understanding the perspectives of others, commonly known as Theory of Mind (ToM) processing. However, there is a dearth of literature investigating the neural basis of these differences in ToM and at what age they emerge. This study aimed to test for differences in the neural correlates of ToM processes in young women with AN, and young women weight-restored (WR) from AN, as compared to healthy control participants (HC). Based on previous findings in AN, we hypothesized that young women with current or prior AN, as compared to HCs, would exhibit a reduced neural response in the medial prefrontal cortex (mPFC), the inferior frontal gyrus, and the temporo-parietal junction (TPJ) whilst completing a ToM task. We recruited 73 young women with AN, 45 WR young women, and 70 young women without a history of AN to take part in the current study. Whilst undergoing a functional magnetic resonance imaging (fMRI) scan, participants completed the Frith-Happé task, which is a commonly used measure of ToM with demonstrated reliability and validity in adult populations. In this task, participants viewed the movements of triangles, which depicted either action movements, simple interactions, or complex social interactions. Viewing trials with more complex social interactions in the Frith-Happé task was associated with increased brain activation in regions including the right TPJ, the bilateral mPFC, the cerebellum, and the dorsolateral prefrontal cortex. There were no group differences in neural activation in response to the ToM contrast. Overall, these results suggest that the neural basis of spontaneous mentalizing is preserved in most young women with AN.

Corrigendum: Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa.

[This corrects the article DOI: 10.3389/fpsyg.2020.568073.].

The influence of oxytocin on eating behaviours and stress in women with bulimia nervosa and binge eating disorder.

The current study aimed to test the influence of oxytocin on palatable food intake, 24-h caloric consumption, and stress in women with bulimia nervosa and binge eating disorder. We recruited 25 women with DSM-5 bulimia nervosa or binge eating disorder, and 27 weight-matched comparison women without history of an eating disorder. We employed a double-blind, placebo-controlled crossover design in which each participant attended the lab for two experimental sessions, receiving a divided dose of 64IU intranasal oxytocin in one session and equivalent volume of placebo nasal spray in the opposite session. The order of administration was pseudo-randomised across participants. We hypothesised that a divided dose of 64IU intranasal oxytocin administration would reduce subjective hunger, the immediate consumption of palatable food, 24-h calorie consumption, and the incidence of binge eating when compared to placebo. We also hypothesised that oxytocin administration would be associated with lower levels of stress and salivary cortisol, and that there would be an interaction with participant group such that oxytocin would reduce eating behaviour and stress to a greater degree in women with bulimia nervosa or binge eating disorder, compared to women without history of an eating disorder. We did not find a significant effect of oxytocin on any of the measurements of eating behaviour, subjective stress, or salivary cortisol. We recommend that future studies test the dose-response effect of oxytocin on eating behaviours and stress in human populations with eating disorders to further clarify the moderating factors for oxytocin's effect on eating.

The influence of oxytocin on risk-taking in the balloon analogue risk task among women with bulimia nervosa and binge eating disorder.

Previous theoretical models of bulimia nervosa (BN) and binge eating disorder (BED) have implicated cross-domain risk-taking behaviour as a significant maintenance factor in both disorders. The present study aimed to test this hypothesis by administering the Balloon Analogue Risk Task (BART) to 25 women with BN or BED and 27 healthy comparison women without a history of an eating disorder. Furthermore, we tested the effect of a divided dose of 64 IU of oxytocin on risk-taking behaviour in the BART. Contrary to our hypothesis, women with BN or BED did not exhibit baseline differences in performance on the BART in the placebo condition (t = 1.42, df = 50, P = 0.161, d = 0.39). Oxytocin did not have a main effect on performance in the BART (F = 0.01, df = 1, P = .907, η2partial  < 0.001); however, there was an interaction, such that participants in the BN/BED participant group, compared to the healthy comparison group, demonstrated safer behaviour on the BART in the oxytocin condition, but not in the placebo condition (F = 4.29, df = 1, P = 0.044, η2partial  = 0.082). These findings cast doubt on the common assumption that individuals with BN and BED exhibit greater risk-taking behaviour in all domains and add to the evidence that oxytocin plays a functional role in modulating behaviours that entail trade-offs between reward approach and risk in humans. We recommend that future dose-response studies investigate the effect of oxytocin on reward approach behaviour further in women with recurrent binge eating behaviour, as well as the clinical significance of this effect.

A Systematic Review and Quantitative Meta-Analysis of Oxytocin's Effects on Feeding.

PURPOSE: Oxytocin's anorexigenic effects have been widely documented and accepted; however, no paper has yet used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to compile previous findings in a single systematic review and quantitative meta-analysis. The current paper aimed to identify published and unpublished studies examining the effects of oxytocin on energy intake in animals and humans, and the factors that moderate this effect. METHODS: Web of Science, Pub Med, and Ovid were searched for published and unpublished studies reporting the effects of oxytocin on energy intake in wild-type animals and in humans, when administered in the absence of other active drugs or surgery. RESULTS: 2049 articles were identified through the original systematic literature search, from which 54 articles were identified as relevant for inclusion in this review. An additional 3 relevant articles were identified in a later update of the literature search. Overall, a single-dose of oxytocin was found to reduce feeding in animals. Despite several individual studies which found that this effect persists to the end of the third week of chronic administration in rodent models, overall, this anorexigenic effect did not hold in the meta-analyses testing the effects of chronic administration. There was no overall effect of oxytocin on energy intake in humans, although a trend was identified for oxytocin to reduce consumption of solid foods. CONCLUSIONS: Oxytocin reduces energy intake when administered as a single dose. Oxytocin can inhibit feeding over two- to three-week periods in rodent models. These effects typically do not persist beyond the third week of treatment. The anorexigenic effect of oxytocin is moderated by pregnant status, dose, method of administration, and diet composition. This article is protected by copyright. All rights reserved.

Effects of intranasal oxytocin on the attentional bias to emotional stimuli in patients with bulimia nervosa.

BACKGROUND: Bulimia nervosa (BN) is characterized by binge eating and emotional dysregulation including increased negative affectivity (anger, anxiety). The aim of this study was to examine the effect of oxytocin on attentional processes towards anger in patients with BN. METHOD: The study design consisted of a double-blind, placebo-controlled within-subject crossover, single dose experiment. Sixty-four women (31 patients with BN and 33 healthy comparisons) completed self-reported measures to evaluate emotional difficulties and were administered a single dose of intranasal oxytocin (40IU) or placebo followed by a visual probe detection task to examine attentional orienting to angry or happy faces. RESULTS: Patients with BN reported higher emotional dysregulation and more difficulties in controlling anger compared to the healthy comparison group. Patients with BN and the healthy women exhibited similar attentional bias to angry faces in the placebo condition. Intranasal oxytocin reduced the attentional bias towards angry faces in both the BN patients and the healthy women. CONCLUSIONS: We found that a single dose of oxytocin reduced vigilance towards angry faces in patients with BN as well as healthy women. The results showed that patients with BN are not different from healthy women in terms of vigilance towards threat.

Eating Disorders Impact on Vigilance and Decision Making of a Community Sample of Treatment Naive Attention-Deficit/Hyperactivity Disorder Young Adults.

Although impulsivity is suggested as a possible link to explain the association of Attention-Deficit/Hyperactivity Disorder (ADHD) with an Eating Disorder (ED), there is little research on how clinical and cognitive/neuropsychological functioning might change when this comorbidity occurs. ADHD individuals are at a higher of developing ED and also obesity. Some research has described the impact of ADHD in clinical treatment-seeking samples of ED patients. Consequently, we investigated how ED impacted on clinical and cognitive variables of a community sample of treatment-naive ADHD individuals. Ninety college students arranged in three groups (ADHD+ED, ADHD only and Controls) were analyzed using semi-structured interviews for ADHD (K-SADS), the Iowa Gambling Task, the Conner's Continuous Performance Test, Digit and Visual span, as well as rating scales for anxiety (STAI), depression (BDI) and impulsivity (BIS-11), and binge eating (BES). We found that ADHD+ED individuals significantly differed from both groups, presenting with a higher body mass index; more hyperactivity-impulsivity symptoms; higher binge eating scores; more omission errors on the Continuous Performance Test; disadvantageous choices on the Iowa Gambling Task. Also, we demonstrated through a moderation/mediation analysis that a greater level of binge eating mediated the increases in body mass index on our sample. There were no significant paths to explain binge-eating severity through changes on any of the neuropsychological tests used. The presence of an ED in normal weight in a community sample of ADHD individuals is associated with higher body mass index and a worse cognitive functioning.

Patterns and risk factors of birth defects in rural areas of south-eastern Gabon.

Within the context of high neonatal mortality in sub-Saharan Africa, a retrospective study was conducted on the prevalence of congenital malformations and the association between maternal risk factors and birth defects in rural populations of south-eastern Gabon. Two populations were studied: a group of 3500 births recorded in rural area (Koula-Moutou) and a second group of 4212 births in a semi-rural area (Franceville) in Gabon. Our data showed an increasing prevalence in congenital anomalies from rural to urban areas (P < 0.001). Maternal risk factors such as age > 35 years, multiparity and employment status were significantly associated with the levels of stillbirth. Together with abortions and stillbirths, congenital malformations require strong monitoring in rural and urban areas of sub-Saharan Africa.