The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial.

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation. CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial.

BACKGROUND: The optimal time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer is unknown and has traditionally been 4-6 weeks in clinical practice. Observational studies have suggested better outcomes, especially in terms of histological response, after prolonged delay of up to 3 months after nCRT. The NeoRes II trial is the first randomised trial to compare standard to prolonged TTS after nCRT for oesophageal cancer. PATIENTS AND METHODS: Patients with resectable, locally advanced oesophageal cancer were randomly assigned to standard delay of surgery of 4-6 weeks or prolonged delay of 10-12 weeks after nCRT. The primary endpoint was complete histological response of the primary tumour in patients with adenocarcinoma (AC). Secondary endpoints included histological tumour response, resection margins, overall and progression-free survival in all patients and stratified by histologic type. RESULTS: Between February 2015 and March 2019, 249 patients from 10 participating centres in Sweden, Norway and Germany were randomised: 125 to standard and 124 to prolonged TTS. There was no significant difference in complete histological response between AC patients allocated to standard (21%) compared to prolonged (26%) TTS (P = 0.429). Tumour regression, resection margins and number of resected lymph nodes, total and metastatic, did not differ between the allocated interventions. The first quartile overall survival in patients allocated to standard TTS was 26.5 months compared to 14.2 months after prolonged TTS (P = 0.003) and the overall risk of death during follow-up was 35% higher after prolonged delay (hazard ratio 1.35, 95% confidence interval 0.94-1.95, P = 0.107). CONCLUSION: Prolonged TTS did not improve histological complete response or other pathological endpoints, while there was a strong trend towards worse survival, suggesting caution in routinely delaying surgery for >6 weeks after nCRT.

Ultrafast photoinduced dynamics in Prussian blue analogues.

New magnetic materials and methods for controlling them are needed to improve data storage technologies. Recent progress has enabled optical detection and manipulation of spins in molecule-based magnets on the femtosecond timescale, which is promising for both increasing the read/write speed but also the data storage density. Experimental developments in femtosecond X-ray free-electron lasers (XFELs) and magneto-optics, in combination with theory advances, have opened up several new avenues to investigate molecule-based magnets. This review discusses the literature concerning ultrafast photoinduced dynamics in Prussian blue analogues (PBAs), which are molecule-based magnets. In PBAs spin-flips and lattice distortions can happen on the 100 fs timescale, which in some analogues lead to photoinduced changes in the long-range magnetic order. The literature and themes covered in this review are of relevance for ultrafast optical control of new multifunctional materials.

A strong ultraviolet pulse from a newborn type Ia supernova.

Type Ia supernovae are destructive explosions of carbon-oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious. One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations with the Swift Space Telescope of strong but declining ultraviolet emission from a type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some type Ia supernovae arise from the single degenerate channel.

Recombinant BRICHOS chaperone domains delivered to mouse brain parenchyma by focused ultrasound and microbubbles are internalized by hippocampal and cortical neurons.

The BRICHOS domain is found in human precursor proteins associated with cancer, dementia (Bri2) and amyloid lung disease (proSP-C). Recombinant human (rh) proSP-C and Bri2 BRICHOS domains delay amyloid-ß peptide (Aß) fibril formation and reduce associated toxicity in vitro and their overexpression reduces Aß neurotoxicity in animal models of Alzheimer's disease. After intravenous administration in wild-type mice, rh Bri2, but not proSP-C, BRICHOS was detected in the brain parenchyma, suggesting that Bri2 BRICHOS selectively bypasses the blood-brain barrier (BBB). Here, our objective was to increase the brain delivery of rh proSP-C (trimer of 18 kDa subunits) and Bri2 BRICHOS (monomer to oligomer of 15 kDa subunits) using focused ultrasound combined with intravenous microbubbles (FUS + MB), which enables targeted and transient opening of the BBB. FUS + MB was targeted to one hemisphere of wild type mice and BBB opening in the hippocampal region was confirmed by magnetic resonance imaging. Two hours after FUS + MB brain histology showed no signs of tissue damage and immunohistochemistry showed abundant delivery to the brain parenchyma in 13 out of 16 cases given 10 mg/kg of proSP-C or Bri2 BRICHOS domains. The Bri2, but not proSP-C BRICHOS domain was detected also in the non-targeted hemisphere. ProSP-C and Bri2 BRICHOS domains were taken up by a subset of neurons in the hippocampus and cortex, and were detected to a minor extent in early endosomes. These results indicate that rh Bri2, but not proSP-C, BRICHOS, can be efficiently delivered into the mouse brain parenchyma and that both BRICHOS domains can be internalized by cell-specific mechanisms.

Vision therapy as part of neurorehabilitation after acquired brain injury - a clinical study in an outpatient setting.

Introduction: Oculomotor (OM) functions may be affected by acquired brain injury (ABI). The ability to benefit from rehabilitation or to perform daily activities may be affected by OM dysfunctions and associated symptoms. The purpose of this study was to investigate the effects of vision therapy (VT) as part of neurorehabilitation after ABI.Materials and Methods: The study included two groups of outpatients (median 49.5-52.0 years, range 27-67) admitted to neurorehabilitation due to moderate to severe ABI. One group received VT while the other group served as controls to monitor the course of OM dysfunctions without VT.Results: The intervention group showed significant improvements in convergence (Z = 2.26, p = .02), vergence facility (Z = -2.16, p = .03) and vergence reserves (Z = -2.44, p < .01 and t = -4.47, DF = 15, p < .01) along with a significant reduction in vision-related symptoms (Z = 2.97, p < .01).Discussion: We conclude that OM issues were frequent and that targeted VT, as part of neurorehabilitation, can be an efficient treatment resulting in improved functions and reduced symptoms. Further study will be required to understand how improved functions link to performance and satisfaction with everyday activities.

Geographical differences in cancer treatment and survival for patients with oesophageal and gastro-oesophageal junctional cancers.

BACKGROUND: Only around one-quarter of patients with cancer of the oesophagus and the gastro-oesophageal junction (GOJ) undergo surgical resection. This population-based study investigated the rates of treatment with curative intent and resection, and their association with survival. METHODS: Patients diagnosed with oesophageal and GOJ cancer between 2006 and 2015 in Sweden were identified from the National Register for Oesophageal and Gastric Cancer (NREV). The NREV was cross-linked with several national registries to obtain information on additional exposures. The annual proportion of patients undergoing treatment with curative intent and surgical resection in each county was calculated, and the counties divided into groups with low, intermediate and high rates. Treatment with curative intent was defined as definitive chemoradiation therapy or surgery, with or without neoadjuvant oncological treatment. Overall survival was analysed using a multilevel model based on county of residence at the time of diagnosis. RESULTS: Some 5959 patients were included, of whom 1503 (25·2 per cent) underwent surgery. Median overall survival after diagnosis was 7·7, 8·8 and 11·1 months respectively in counties with low, intermediate and high rates of treatment with curative intent. Corresponding survival times for the surgical resection groups were 7·4, 9·3 and 11·0 months. In the multivariable analysis, a higher rate of treatment with curative intent (time ratio 1·17, 95 per cent c.i. 1·05 to 1·30; P < 0·001) and a higher resection rate (time ratio 1·24, 1·12 to 1·37; P < 0·001) were associated with improved survival after adjustment for relevant confounders. CONCLUSION: Patients diagnosed in counties with higher rates of treatment with curative intent and higher rates of surgery had better survival.

ANTECEDENTES: En los pacientes con cáncer en el esófago y de la unión gastroesofágica (gastroesophageal junction, GOJ), solamente en una cuarta parte se practica una resección quirúrgica. Este estudio de base poblacional analizó las tasas de tratamiento con intención curativa y de resección y su asociación con la supervivencia. MÉTODOS: A partir del Registro Nacional Sueco de Cáncer de Esófago y Estómago (National Register for Oesophageal and Gastric Cancer, NREV), se identificaron los pacientes diagnosticados de cáncer de esófago y de la GOJ entre 2006-2015. El NREV se cruzó con otros registros nacionales para obtener información adicional. Se calculó la proporción anual de pacientes tratados con intención curativa o mediante resección quirúrgica en cada una de las áreas territoriales de los condados y se categorizaron en baja, intermedia y alta. El tratamiento con intención curativa se definió como la quimiorradioterapia definitiva (definitive chemoradiation therapy, dCRT) o la cirugía, con o sin tratamiento oncológico neoadyuvante. Se analizó la supervivencia global con un modelo multinivel basado en el condado de residencia en el momento del diagnóstico. RESULTADOS: Se incluyeron 5.959 pacientes, de los que 1.503 (25,2%) fueron tratados quirúrgicamente. La mediana de supervivencia global después del tratamiento con intención curativa fue de 7,7, 8,8 y 11,1 meses para los condados de volumen bajo, intermedio y alto. Para el grupo de cirugía fue de 7,4, 9,3 y 11,0 meses, respectivamente. En el análisis multivariable, una mayor tasa de tratamiento con intención curativa y una mayor tasa de resección se asociaron con una mejor supervivencia (tiempo ganado 1,17; i.c. del 95% 1,05-1,30, P < 0,001 y tiempo ganado 1,24; i.c. del 95% 1,12-1,37, P < 0,001) después del ajuste para los factores principales de confusión. CONCLUSIÓN: Los pacientes diagnosticados en condados con tasas altas de tratamiento con intención curativa y de cirugía tuvieron una mejor supervivencia.

Improvements in esophageal and gastric cancer care in Sweden-population-based results 2007-2016 from a national quality register.

The Swedish National Register for Esophageal and Gastric cancer was launched in 2006 and contains data with adequate national coverage and of high internal validity on patients diagnosed with these tumors. The aim of this study was to describe the evolution of esophageal and gastric cancer care as reflected in a population-based clinical registry. The study population was 12,242 patients (6,926 with esophageal and gastroesophageal junction (GEJ) cancers and 5,316 with gastric cancers) diagnosed between 2007 and 2016. Treatment strategies, short- and long-term mortality, gender aspects, and centralization were investigated. Neoadjuvant oncological treatment became increasingly prevalent during the study period. Resection rates for both esophageal/GEJ and gastric cancers decreased from 29.4% to 26.0% (P = 0.022) and from 38.8% to 33.3% (P = 0.002), respectively. A marked reduction in the number of hospitals performing esophageal and gastric cancer surgery was noted. In gastric cancer patients, an improvement in 30-day mortality from 4.2% to 1.6% (P = 0.005) was evident. Overall 5-year survival after esophageal resection was 38.9%, being higher among women compared to men (47.5 vs. 36.6%; P < 0.001), whereas no gender difference was seen in gastric cancer. During the recent decade, the analyses based on the Swedish National Register for Esophageal and Gastric cancer database demonstrated significant improvements in several important quality indicators of care for patients with esophagogastric cancers. The Swedish National Register for Esophageal and Gastric cancer offers an instrument not only for the control and endorsement of quality of care but also a unique tool for population-based clinical research.

Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer: a national cohort study.

The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64-1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41-0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21-4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery.

Synthetic surfactants with SP-B and SP-C analogues to enable worldwide treatment of neonatal respiratory distress syndrome and other lung diseases.

Treatment of neonatal respiratory distress syndrome (RDS) using animal-derived lung surfactant preparations has reduced the mortality of handling premature infants with RDS to a 50th of that in the 1960s. The supply of animal-derived lung surfactants is limited and only a part of the preterm babies is treated. Thus, there is a need to develop well-defined synthetic replicas based on key components of natural surfactant. A synthetic product that equals natural-derived surfactants would enable cost-efficient production and could also facilitate the development of the treatments of other lung diseases than neonatal RDS. Recently the first synthetic surfactant that contains analogues of the two hydrophobic surfactant proteins B (SP-B) and SP-C entered clinical trials for the treatment of neonatal RDS. The development of functional synthetic analogues of SP-B and SP-C, however, is considerably more challenging than anticipated 30 years ago when the first structural information of the native proteins became available. For SP-B, a complex three-dimensional dimeric structure stabilized by several disulphides has necessitated the design of miniaturized analogues. The main challenge for SP-C has been the pronounced amyloid aggregation propensity of its transmembrane region. The development of a functional non-aggregating SP-C analogue that can be produced synthetically was achieved by designing the amyloidogenic native sequence so that it spontaneously forms a stable transmembrane α-helix.

Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits.

AIM: In acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS. METHODS: ARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (VT 20 m/kg body weight) until P/F ratio < 26.7 kPa. The animals were treated with two intratracheal boluses of 2.5 mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf®), both surfactants containing 80 mg phospholipids/mL, or air as control. The animals were subsequently ventilated (VT 8-9 m/kg body weight) for an additional 3 h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNFα IL-6 and IL-8 in lung homogenates were evaluated. RESULTS: Both surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1 h, P/F ratio and PaO2 at 1.5 h compared to rSP-C33Leu surfactant. CONCLUSION: This study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

Optical coherence tomography represents a sensitive and reliable tool for routine monitoring of idiopathic intracranial hypertension with and without papilledema.

BACKGROUND AND PURPOSE: We previously reported that certain optical coherence tomography (OCT) measures were sensitive and reliable in identifying idiopathic intracranial hypertension (IIH). This prospective study aimed to define OCT measures that allow differentiation of IIH with and without papilledema, thereby helping clinical decision-making. METHODS: Eight patients with IIH with papilledema, nine without papilledema and 19 with other neurological diseases were included. OCT measures were obtained before lumbar puncture and within 2 h, 1, 3 and 6 months after lumbar puncture with cerebrospinal fluid (CSF) removal. RESULTS: All patients with papilledema had increased retinal nerve fiber layer (RNFL) thickness and elevated CSF pressure. All patients without papilledema had normal RNFL but elevated CSF pressure. After CSF removal, reduced RNFL thickness was registered in all eight patients with IIH with papilledema. No significant change in RNFL thickness after CSF removal was observed in IIH without papilledema or in patients with other neurological diseases, although reduced CSF pressure was documented. RNFL thickness tended to be normal in patients with IIH with papilledema at 3-6 months after CSF removal. All patients with IIH showed increased rim area and rim thickness, but reduced optic cup volume regardless of RNFL thickness or papilledema. CONCLUSIONS: Retinal nerve fiber layer thickness is sensitive for monitoring acute IIH and evaluating treatment effect. Increased rim area and rim thickness and decreased optic cup volume are reliable parameters that indicate persistently increased CSF pressure and risk of relapse. OCT measures are sensitive and reliable for diagnosing subtle IIH even in the absence of papilledema.

Targeting Alzheimer's disease with gene and cell therapies.

Alzheimer's disease (AD) causes dementia in both young and old people affecting more than 40 million people worldwide. The two neuropathological hallmarks of the disease, amyloid beta (Aß) plaques and neurofibrillary tangles consisting of protein tau are considered the major contributors to the disease. However, a more complete picture reveals significant neurodegeneration and decreased cell survival, neuroinflammation, changes in protein and energy homeostasis and alterations in lipid and cholesterol metabolism. In addition, gene and cell therapies for severe neurodegenerative disorders have recently improved technically in terms of safety and efficiency and have translated to the clinic showing encouraging results. Here, we review broadly current data within the field for potential targets that could modify AD through gene and cell therapy strategies. We envision that not only Aß will be targeted in a disease-modifying treatment strategy but rather that a combination of treatments, possibly at different intervention times may prove beneficial in curing this devastating disease. These include decreased tau pathology, neuronal growth factors to support neurons and modulation of neuroinflammation for an appropriate immune response. Furthermore, cell based therapies may represent potential strategies in the future.

Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study.

INTRODUCTION: The highly selective α2-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMRglu) with three commonly used anaesthetic drugs at equi-sedative doses. METHODS: One hundred and sixty healthy male subjects were randomised to EC50 for verbal command of dexmedetomidine (1.5 ng ml-1; n=40), propofol (1.7 µg ml-1; n=40), sevoflurane (0.9% end-tidal; n=40) or S-ketamine (0.75 µg ml-1; n=20) or placebo (n=20). Anaesthetics were administered using target-controlled infusion or vapouriser with end-tidal monitoring. 18F-labelled fluorodeoxyglucose was administered 20 min after commencement of anaesthetic administration, and high-resolution positron emission tomography with arterial blood activity samples was used to quantify absolute CMRglu for whole brain and 15 brain regions. RESULTS: At the time of [F18]fluorodeoxyglucose injection, 55% of dexmedetomidine, 45% of propofol, 85% of sevoflurane, 45% of S-ketamine, and 0% of placebo subjects were unresponsive. Whole brain CMRglu was 63%, 71%, 71%, and 96% of placebo in the dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively (P<0.001 between the groups). The lowest CMRglu was observed in nearly all brain regions with dexmedetomidine (P<0.05 compared with all other groups). With S-ketamine, CMRglu did not differ from placebo. CONCLUSIONS: At equi-sedative doses in humans, potency in reducing CMRglu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia. CLINICAL TRIAL REGISTRATION: NCT02624401.

Ventral striatal dopaminergic defect is associated with hallucinations in Parkinson's disease.

BACKGROUND AND PURPOSE: Visual hallucinations (VHs) are a common complication of Parkinson's disease (PD). The pathogenesis of VHs in PD is still largely unclear. The aim of this study was to investigate the dopaminergic mechanisms of VHs and specifically whether the degree of striatal dopamine transporter (DAT) function or extrastriatal serotonin transporter (SERT) function can predict the appearance of VHs in patients with PD. METHODS: Twenty-two PD patients scanned with [123 I]FP-CIT single photon emission computed tomography at an early stage of their disease who later developed VHs were identified and compared with 48 non-hallucinating PD patients. The groups were matched for age, medication, disease duration and motor symptom severity. Clinical follow-up after the scan was a median (range) of 6.9 (3.8-9.6) years. Imaging analyses were performed with both regions-of-interest-based and voxel-based (Statistical Parametric Mapping) methods for the striatal and extrastriatal regions. RESULTS: The median interval between the scan and the emergence of VHs was 4.8 years. Patients who developed VHs had 18.4% lower DAT binding in the right ventral striatum (P = 0.009), 16.7% lower binding in the left ventral striatum (P = 0.02) and 18.8% lower binding in the right putamen (P = 0.03) compared to patients who did not develop VHs. CONCLUSIONS: Low striatal DAT function may predispose PD patients to VHs, and the regional distribution of the findings suggests a particular role of the ventral striatum. This is in line with non-PD research that has implicated ventral striatal dysfunction in psychosis.