Accelerating ethics, empathy, and equity in geographic information science.

Science has traditionally been driven by curiosity and followed one goal: the pursuit of truth and the advancement of knowledge. Recently, ethics, empathy, and equity, which we term "the 3Es," are emerging as new drivers of research and disrupting established practices. Drawing on our own field of GIScience (geographic information science), our goal is to use the geographic approach to accelerate the response to the 3Es by identifying priority issues and research needs that, if addressed, will advance ethical, empathic, and equitable GIScience. We also aim to stimulate similar responses in other disciplines. Organized around the 3Es we discuss ethical issues arising from locational privacy and cartographic integrity, how our ability to build knowledge that will lead to empathy can be curbed by data that lack representativeness and by inadvertent inferential error, and how GIScientists can lead toward equity by supporting social justice efforts and democratizing access to spatial science and its tools. We conclude with a call to action and invite all scientists to join in a fundamentally different science that responds to the 3Es and mobilizes for change by engaging in humility, broadening measures of excellences and success, diversifying our networks, and creating pathways to inclusive education. Science united around the 3Es is the right response to this unique moment where society and the planet are facing a vast array of challenges that require knowledge, truth, and action.

Evaluation of a training programme for Pharmacist Independent Prescribers in a care home medicine management intervention.

BACKGROUND: The provision of independent prescribing rights for United Kingdom (UK) pharmacists has enabled them to prescribe within their area of competence. The aim of this study was to evaluate an evidence-based training programme designed to prepare Pharmacist Independent Prescribers (PIPs) to safely and effectively assume responsibility for pharmaceutical care of older people in care homes in the UK, within a randomised controlled trial. METHODS: The training and competency assessment process included two training days, professional development planning against a bespoke competency framework, mentor support, and a viva with an independent General Practitioner (GP). Data on the PIPs' perceptions of the training were collected through evaluation forms immediately after the training days and through online questionnaires and interviews after delivery of the 6-month intervention. Using a mixed method approach each data set was analysed separately then triangulated providing a detailed evaluation of the process. Kaufman's Model of Learning Evaluation guided interpretations. RESULTS: All 25 PIPs who received the training completed an evaluation form (N = 25). Post-intervention questionnaires were completed by 16 PIPs and 14 PIPs took part in interviews. PIPs reported the training days and mentorship enabled them to develop a personalised portfolio of competence in preparation for discussion during a viva with an independent GP. Contact with the mentor reduced as PIPs gained confidence in their role. PIPs applied their new learning throughout the delivery of the intervention leading to perceived improvements in residents' quality of life and medicines management. A few PIPs reported that developing a portfolio of competence was time intensive, and that further training on leadership skills would have been beneficial. CONCLUSIONS: The bespoke training programme was fit for purpose. Mentorship and competency assessment were resource intensive but appropriate. An additional benefit was that many PIPs reported professional growth beyond the requirement of the study. TRIAL REGISTRATION: The definitive RCT was registered with the ISRCTN registry (registration number ISRCTN 17,847,169 ).

Novel genetic factors involved in resistance to Bacillus thuringiensis in Plutella xylostella.

The widespread and sustainable exploitation of the entomopathogen Bacillus thuringiensis (Bt) in pest control is threatened by the evolution of resistance. Although resistance is often associated with loss of binding of the Bt toxins to the insect midgut cells, other factors have been implicated. Here we used suppressive subtractive hybridization and gene expression suppression to identify additional molecular components involved in Bt-resistance in Plutella xylostella. We isolated transcripts from genes that were differentially expressed in the midgut of larvae from a resistant population, following ingestion of a Bt kurstaki HD1 strain-based commercial formulation (DiPel), and compared with a genetically similar susceptible population. Quantitative real-time polymerase-chain reaction (RT-PCR) analysis confirmed the differential basal expression of a subset of these genes. Gene expression suppression of three of these genes (P. xylostella cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1, stromal cell-derived factor 2-like 1 and hatching enzyme-like 1) significantly increased the pathogenicity of HD1 to the resistant population. In an attempt to link the multitude of factors reportedly influencing resistance to Bt with the well-characterized loss of toxin binding, we also considered Bt-resistance models in P. xylostella and other insects.

The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention.

BACKGROUND AND OBJECTIVES: Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation-induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation-induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown. MATERIALS AND METHODS: 'Strategies To Reduce Iron Deficiency' (STRIDE) was a two-year, randomized, placebo-controlled study in blood donors. 692 donors were randomized into one of two educational groups or one of three interventional groups. Donors randomized to educational groups either received letters thanking them for donating, or, suggesting iron supplements or delayed donation if they had low ferritin. Donors randomized to interventional groups either received placebo, 19-mg or 38-mg iron pills. RESULTS: Iron deficient erythropoiesis was present in 52·7% of males and 74·6% of females at enrolment. Adverse events within 60 days of enrolment were primarily mild gastrointestinal symptoms (64%). The incidence of de-enrolment within 60 days was more common in the interventional groups than in the educational groups (P = 0·002), but not more common in those receiving iron than placebo (P = 0·68). CONCLUSION: The prevalence of iron deficient erythropoiesis in donors enrolled in the STRIDE study is comparable to previously described cohorts of regular blood donors. De-enrolment within 60 days was higher for donors receiving tablets, although no more common in donors receiving iron than placebo.

Knowledge of HIV testing and attitudes towards blood donation at three blood centres in Brazil.

BACKGROUND: Reducing risk of HIV window period transmission requires understanding of donor knowledge and attitudes related to HIV and risk factors. STUDY DESIGN AND METHODS: We conducted a survey of 7635 presenting blood donors at three Brazilian blood centres from 15 October through 20 November 2009. Participants completed a questionnaire on HIV knowledge and attitudes about blood donation. Six questions about blood testing and HIV were evaluated using maximum likelihood chi-square and logistic regression. Test seeking was classified in non-overlapping categories according to answers to one direct and two indirect questions. RESULTS: Overall, respondents were male (64%) repeat donors (67%) between 18 and 49 years old (91%). Nearly 60% believed blood centres use better HIV tests than other places; however, 42% were unaware of the HIV window period. Approximately 50% believed it was appropriate to donate to be tested for HIV, but 67% said it was not acceptable to donate with risk factors even if blood is tested. Logistic regression found that less education, Hemope-Recife blood centre, replacement, potential and self-disclosed test-seeking were associated with less HIV knowledge. CONCLUSION: HIV knowledge related to blood safety remains low among Brazilian blood donors. A subset finds it appropriate to be tested at blood centres and may be unaware of the HIV window period. These donations may impose a significant risk to the safety of the blood supply. Decreasing test-seeking and changing beliefs about the appropriateness of individuals with behavioural risk factors donating blood could reduce the risk of transfusing an infectious unit.

Patient's and Consultant's Views and Perceptions on Switching from an Originator Biologic to Biosimilar Medication: A Qualitative Study.

The aim of this study was to describe the opinions of patients undergoing treatment with originator biologics and medical consultants managing their conditions and identify the barriers and enablers to transitioning from originator biologics to equivalent biosimilars. This study was undertaken prior to biosimilar switching at a large teaching hospital in the United Kingdom. Five gastroenterology, rheumatology, and dermatology consultants were interviewed. Two focus groups were conducted with patients prescribed infliximab (n = 2) and etanercept originators (n = 7). Four main themes emerged, as follows: (1) 'Benefit to the NHS'; (2) 'Evidence for efficacy and safety'; (3) 'Team roles'; and (4) 'Effective communication during switching', with sub-themes such as (4a) 'What patients want to know' and (4b) 'How it should be communicated'. Recognition of the ability to save NHS money was an enabler for both patients and consultants, with patients wanting to be reassured that the money saved would be used to benefit other patients. Consultants did not always believe that biosimilars had similar efficacy as the originators or that the manufacturing standards were the same. Effective interventions to address these concerns are required. Offering patients the opportunity to revert back to their originator if necessary was seen as an enabler, as was the provision of readily available mechanisms for reporting suspected adverse events resulting from switching. The role of pharmacy in the process of switching from originator biologics to biosimilars can range from educating consultants regarding the safety and efficacy of biosimilars, explaining the rationale for switching patients, and providing a route for reporting adverse events.

Reducing Grip Uncertainty During Initial Prosthetic Hand Use Improves Eye-Hand Coordination and Lowers Mental Workload.

The reliance on vision to control a myoelectric prosthesis is cognitively burdensome and contributes to device abandonment. The feeling of uncertainty when gripping an object is thought to be the cause of this overreliance on vision in hand-related actions. We explored if experimentally reducing grip uncertainty alters the visuomotor control and mental workload experienced during initial prosthesis use. In a repeated measures design, twenty-one able-bodied participants took part in a pouring task across three conditions: (a) using their anatomical hand, (b) using a myoelectric prosthetic hand simulator, and (c) using a myoelectric prosthetic hand simulator with Velcro attached to reduce grip uncertainty. Performance, gaze behaviour (using mobile eye-tracking) and self-reported mental workload, was measured. Results showed that using a prosthesis (with or without Velcro) slowed task performance, impaired typical eye-hand coordination and increased mental workload compared to anatomic hand control. However, when using the prosthesis with Velcro, participants displayed better prosthesis control, more effective eye-hand coordination and reduced mental workload compared to when using the prosthesis without Velcro. These positive results indicate that reducing grip uncertainty could be a useful tool for encouraging more effective prosthesis control strategies in the early stages of prosthetic hand learning.

Risk factors for human immunodeficiency virus infection among Brazilian blood donors: a multicentre case-control study using audio computer-assisted structured interviews.

BACKGROUND: Although risk factors for HIV infection are known, it is important for blood centres to understand local epidemiology and disease transmission patterns. Current risk factors for HIV infection in blood donors in Brazil were assessed. METHODS: A case-control study was conducted at large public blood centres located in four major cities between April 2009 and March 2011. Cases were persons whose donations were confirmed positive by enzyme immunoassays followed by Western blot confirmation. Audio computer-assisted structured interviews (ACASI) were completed by all cases and controls. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and associated 95% confidence intervals (CIs). RESULTS: There were 341 cases, including 47 with recently acquired infection, and 791 controls. Disclosed risk factors for both females and males were sex with an HIV-positive person AOR 11.3, 95% CI (4.1, 31.7) and being an IVDU or sexual partner of an IVDU [AOR 4.65 (1.8, 11.7)]. For female blood donors, additional risk factors were having male sex partners who also are MSM [AOR 13.5 (3.1, 59.8)] and having unprotected sex with multiple sexual partners [AOR 5.19 (2.1, 12.9)]. The primary risk factor for male blood donors was MSM activity [AOR 21.6 (8.8, 52.9)]. Behaviours associated with recently acquired HIV were being a MSM or sex partner of MSM [13.82, (4.7, 40.3)] and IVDU [11.47, (3.0, 43.2)]. CONCLUSION: Risk factors in blood donors parallel those in the general population in Brazil. Identified risk factors suggest that donor compliance with selection procedures at the participating blood centres is inadequate.

First-time donors responding to a national disaster may be an untapped resource for the blood centre.

BACKGROUND: On 12 May 2008, a severe earthquake struck Sichuan in China. Many people donated blood for the first time, leading us to question whether these donors might become repeat donors in the future. The return pattern of post-earthquake first-time donors (PEFTD) was compared with that of first-time donors (FTD) in a comparable period. METHODS: Demographic characteristics, transfusion-transmissible infection rates and 1-year return rates were compared between 5147 PEFTD (5/13-5/19, 2008) and 3176 FTD (5/13-5/19, 2009) from five Chinese blood centres using chi-squared tests. Adjusted logistic regression was used to detect earthquake effect on donor return. RESULTS: Post-earthquake first-time donors were more frequently between 26 and 45 years, men, and better educated compared with the control group. Slightly higher but not statistically significant increased rates of hepatitis B virus surface antigen (HBsAg) (0·87% vs. 0·50%, P=0·054), hepatitis C virus (HCV) (0·70% vs. 0·63%, P=0·414), syphilis (0·9% vs. 0·7%, P=0·489) and lower rates of human immunodeficiency virus (HIV) (0·31% vs. 0·60%, P=0·078) reactivity were detected for PEFTD. The 1-year return rate for PEFTD was significantly lower than that of the controls (8·0% vs. 13·0%, P<0·001). After adjusting for demographic factors, donation volume and sites, the PEFTD were less likely to return in 1 year than the controls (OR: 0·520; 95% CI: 0·442, 0·611). CONCLUSION: Post-earthquake first-time donors may be less likely to donate again without continuing motivation strategies. Further studies on PEFTD's lack of motivation to return for donation are needed to design recruitment strategies to convert PEFTD to become repeat donors to continuously replenish the blood supply.

Should I stay or should I go? An exploration of the decision-making behavior of acute cardiac patients during the COVID-19 pandemic.

BACKGROUND: During the SARS-COV-2 (COVID-19) pandemic efforts to reduce virus transmission resulted in non-emergency patients being deterred from seeking help. The number of patients presenting with acute cardiac conditions reduced, significantly OBJECTIVES: To explore the decision-making process, and influential factors in that process, of patients and their family during an acute cardiac event. METHODS: A qualitative research design was employed using purposive sampling of patients who experienced an acute cardiac event during the social containment mandates. Semi-structured interviews were conducted, with thematic analysis of interview transcripts. RESULTS: Twenty-five participants were recruited from three UK hospitals. Themes identified were reliance on informal support network, lack of awareness of cardiac symptoms leading to delayed help-seeking, and an indirect COVID-19 effect (e.g. avoiding treatment). CONCLUSIONS: These results highlight the need for informed public health messages, targeting patients and their support networks, that allow those in need of treatment to access care.

Effects of host plant and genetic background on the fitness costs of resistance to Bacillus thuringiensis.

Novel resistance to pathogens and pesticides is commonly associated with a fitness cost. However, measurements of the fitness costs of insecticide resistance have used diverse methods to control for genetic background and rarely assess the effects of environmental variation. Here, we explored how genetic background interacts with resource quality to affect the expression of the fitness costs associated with resistance. We used a serially backcrossed line of the diamondback moth, Plutella xylostella, resistant to the biopesticide Bacillus thuringiensis, to estimate the costs of resistance for insects feeding on two Brassica species. We found that fitness costs increased on the better-defended Brassica oleracea cultivars. These data were included in two meta-analyses of fitness cost experiments that used standardized protocols (and a common resistant insect stock) but which varied in the methodology used to control for the effects of genetic background. The meta-analysis confirmed that fitness costs were higher on the low-quality host (B. oleracea); and experimental methodology did not influence estimates of fitness costs on that plant species. In contrast, fitness costs were heterogeneous in the Brassica pekinensis studies: fitness costs in genetically homogenized lines were significantly higher than in studies using revertant insects. We hypothesize that fitness modifiers can moderate fitness costs on high-quality plants but may not affect fitness when resource quality is low.

Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever.

Massive release of tumor necrosis factor is responsible for the potentially fatal larisch-Herxheimer reaction that follows antibiotic treatment of relapsing fever due to Borrelia recurrentis. We have undertaken the quantitative purification of the components of B. recurrentis that stimulate human monocytes to produce tumor necrosis factor. We show that the predominant factor inducing tumor necrosis factor is a variable lipoprotein homologous to the variable major protein of B. hermsii. We found antibodies to different forms of variable major protein in two patients with louse-borne relapsing fever. The three purified variable major proteins studied here differ in their ability to induce tumor necrosis factor production, which may partly explain the variable clinical severity of borrelial infection. These results may be of considerable relevance for the pathogenesis of Lyme disease and other forms of human borreliosis.

Variations in Eastern bongo (Tragelaphus eurycerus isaaci) feeding practices in UK zoological collections.

The feeding strategy of the Eastern bongo in the wild is unusual, poorly understood, and few captive feeding recommendations are currently available to zoos. To assess the current state of nutritional husbandry of this rare antelope, eight UK zoos were surveyed. A nutritional husbandry questionnaire was completed and bongos at each zoo were visually assessed by body condition scoring (BCS). Representative samples of the forage and browse consumed by bongos at each zoo were analyzed for nutrient composition using standard agricultural techniques. Significant differences in bongo body condition were found, indicating that zoo husbandry practices are sufficiently varied to have identifiable impacts on the physical condition of the animals. The results highlight a disparity in feeding regimes and diet quality, with significant differences found in forage and browse nutrient compositions and in vitro digestibility. Most forage samples were of a low nutritional quality. Browse provision was found to be largely opportunistic and limited in most zoos. The provision of energy-rich produce was also found to be unnecessary in maintaining a bongo herd at an ideal mean BCS. This survey provides baseline data which may be useful in establishing "good practice" standards for Eastern bongo captive nutrition and highlights several areas requiring further research.

Validation of a novel patient reported tool to assess the impact of treatment in erythropoietic protoporphyria: the EPP-QoL.

BACKGROUND: A novel treatment has been developed for erythropoietic protoporphyria (EPP) (a rare condition that leaves patients highly sensitive to light). To fully understand the burden of EPP and the benefit of treatment, a novel patient reported outcome (PRO) measure was developed called the EPP-QoL. This report describes work to support the validation of this measure. METHODS: Secondary analysis of trial data was undertaken. These analyses explored the underlying factor structure of the measure. This supported the deletion of some items. Further work then explored the reliability of these factors, their construct validity and estimates of meaningful change. RESULTS: The factor analyses indicated that the items could be summarised in terms of two factors. One of these was labelled EPP Symptoms and the other EPP Wellbeing, based on the items included in the domain. EPP Symptoms had evidence to support its reliability and validity. EPP Wellbeing had poor psychometric properties. CONCLUSIONS: Based on the analysis it was recommended to drop the EPP Wellbeing domain (and associated items). EPP Symptoms, despite limitations in the development of items, showed evidence of validity. This work is consistent with the recommendations of a task force that provided recommendations regarding the development, modification and use of PROs in rare diseases.

Combined action observation and motor imagery facilitates visuomotor adaptation in children with developmental coordination disorder.

The internal modelling deficit (IMD) hypothesis suggests that motor control issues associated with Developmental Coordination Disorder (DCD) are the result of impaired predictive motor control. In this study, we examined the benefits of a combined action observation and motor imagery (AO + MI) intervention designed to alleviate deficits in internal modelling and improve eye-hand coordination during a visuomotor rotation task. Twenty children with DCD were randomly assigned to either an AO + MI group (who watched a video of a performer completing the task whilst simultaneously imagining the kinaesthetic sensations associated with action execution) or a control group (who watched unrelated videos involving no motor content). Each group then attempted to learn a 90° visuomotor rotation while measurements of completion time, eye-movement behaviour and movement kinematics were recorded. As predicted, after training, the AO + MI group exhibited quicker completion times, more target-focused eye-movement behaviour and smoother movement kinematics compared to the control group. No significant after-effects were present. These results offer further support for the IMD hypothesis and suggest that AO + MI interventions may help to alleviate such deficits and improve motor performance in children with DCD.

Complementary roles of simple variables, NYHA and N-BNP, in indicating aerobic capacity and severity of heart failure.

AIMS: The extent of exercise intolerance in patients with chronic heart failure (CHF) is dependent on and representative of the severity of heart failure. However, few primary care physicians have direct access to facilities for formal exercise testing. We have therefore explored whether information readily obtainable in the community can reliably predict the functional capacity of patients. METHODS AND RESULTS: Ninety-six subjects with a wide range of cardiac function (10 healthy controls and 86 CHF patients with NYHA classes I-IV, LVEF 36.9+/-15.2%) were recruited into the study and had resting plasma N-BNP and cardiopulmonary exercise testing to measure peak oxygen consumption (VO2). Significantly higher N-BNP levels were found in the CHF group (299.3 [704.8] fmol/ml, median [IQR]) compared with the healthy control group (7.2 [51.2] fmol/ml), p<0.0001. There were significant correlations between peak VO2 and N-BNP levels (R=0.64, P<0.001), peak VO2 and NYHA class (R=0.76, P=0.001), but no significant correlation was seen between peak VO2 and LVEF (R=0.0788, P=0.33). Multivariate analysis identified plasma N-BNP (P<0.0001) and NYHA class (P<0.0001) as significant independent predictors of peak VO2. Logistic modelling with NYHA class and log N-BNP to predict peak VO2<20 ml/kg/min showed that the area under the curve of receiver-operating-characteristic (ROC) curve was 0.906 (95% CI 0.844-0.968). A nomogram based on the data has been constructed to allow clinicians to estimate the likelihood of peak VO2 to be <20 ml/kg/min for given values of plasma N-BNP and NYHA class. CONCLUSIONS: By combining information from a simple objective blood test (N-BNP) and a simple scoring of functional status (NYHA), a clinician can deduce the aerobic exercise capacity and indirectly the extent of cardiac dysfunction of patients with CHF.

Increased incidence of infectious diseases during prospective follow-up of human T-lymphotropic virus type II- and I-infected blood donors. Retrovirus Epidemiology Donor Study.

BACKGROUND: To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities. METHODS: Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use. RESULTS: Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years). CONCLUSIONS: These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.

Expression of myosin heavy chain isoforms during development of domestic pigeon pectoralis muscle.

The pectoralis muscle of birds provides virtually all the power for the downstroke of the wing during flight. In adults it consists almost entirely of FOG (fast-twitch oxidative-glycolytic) and/or FG (fast-twitch glycolytic) fiber types. The aims of this study are to contrast MyHC (myosin heavy chain) transitions occurring within avian FG and FOG fibers during development, and to test the hypothesis that the pectoralis matures before the acquisition of flight. Pectoralis was obtained from pigeons (Columba livia) aged from 13 days in ovo to adult. Monoclonal antibodies generated against chicken MyHC isoforms were used with Western blots and immunocytochemistry. FG and FOG fibers were differentiated using a histochemical method demonstrating NADH (nicotinamide adenine dinucleotide), and "lesser fiber diameters" were quantified. Western blots confirm that the antibodies label pigeon MyHCs. A small number of the fibers are slow type in ovo, but these are quickly restricted in distribution and lost after hatching. In ovo fast-twitch fibers contain a ventricular isoform, and at least two embryonic-neonatal forms (designated E-N103 and E-N165). One week after hatching, fast-twitch fibers can be distinguished by NADH as FG or FOG. At fledging, four weeks after hatching, FG and FOG fibers are smaller than in older birds and E-N103 and E-N165 persist in both fibertypes. E-N103 wanes in all fibers shortly after fledging. E-N165 gradually disappears from FG fibers. Thus, despite pigeons being at adult body mass at fledging, their pectoralis is not fully mature.

The influence of the HPG axis on stress response and depressive-like behaviour in a transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant, neurodegenerative disease caused by a CAG tandem repeat mutation encoding a polyglutamine tract expansion in the huntingtin protein. Depression is among the most common affective symptoms in HD but the pathophysiology is unclear. We have previously discovered sexually dimorphic depressive-like behaviours in the R6/1 transgenic mouse model of HD at a pre-motor symptomatic age. Interestingly, only female R6/1 mice display this phenotype. Sexual dimorphism has not been explored in the human HD population despite the well-established knowledge that the clinical depression rate in females is almost twice that of males. Female susceptibility suggests a role of sex hormones, which have been shown to modulate stress response. There is evidence suggesting that the gonads are adversely affected in HD patients, which could alter sex hormone levels. The present study examined the role sex hormones play on stress response in the R6/1 mouse model of HD, in particular, its modulatory effect on the hypothalamic-pituitary-adrenal (HPA) axis and depression-like behaviour. We found that the gonads of female R6/1 mice show atrophy at an early age. Expression levels of gonadotropin-releasing hormone (GnRH) were decreased in the hypothalamus of female HD mice, relative to wild-type female littermates, as were serum testosterone levels. Female serum estradiol levels were not significantly changed. Gonadectomy surgery reduced HPA-axis activity in female mice but had no effect on behavioural phenotypes. Furthermore, expression of the oestrogen receptor (ER) α gene was found to be higher in the adrenal cells of female HD mice. Finally, administration of an ERß agonist diarylpropionitrile (DPN) rescued depressive-like behaviour in the female HD mice. Our findings provide new insight into the pathogenesis of sexually dimorphic neuroendocrine, physiological and behavioural endophenotypes in HD, and suggest a new avenue for therapeutic intervention.