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PurposeAntitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen).Experimental designSerum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels.ResultsIn patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P < 0.01), but not control. IgG responses (≥ 2-fold elevation posttreatment) occurred in ≥ 25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T-treated patients from IMPACT (P ≤ 0.05).ConclusionsSipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. See related commentary by Hellstrom and Hellstrom, p. 3581.

Objectives: Diffusion weighted brain imaging (DWI) is used in acute stroke, and also shows an acute ischaemic lesion in most transient ischamic attack (TIA) patients scanned acutely. However, it may [...]

Study Design: Prospective observational study., Objective: To evaluate pelvic MRI muscle signal changes and their association with early heterotopic ossification (HO) in patients with spinal cord injuries., Setting: National Spinal Injuries Unit, Stoke Mandeville, UK., Methods: Forty patients were imaged with at least two interval magnetic resonance (MR) studies of the pelvis in the first 6 months following a spinal cord injury. Scans were reviewed and scored for heterotopic ossification, muscle signal change and extent of muscle involvement., Results: Muscle signal change was present in 28 (70%) on the initial MRI and 31 (77%) by the second study. Six patients developed MR changes of prodromal or immature heterotopic ossification (15%). No restricted diffusion was demonstrated and no patient developed mature HO. Patients developing MR changes of early HO were more likely to have grade 3 muscle changes., Conclusion: Increased T2 muscle signal is common following cord injury, is frequently progressive in the subacute period and is associated with complete injury and early MR signs of heterotopic ossification.

Introduction: Ganglion impar block (GIB) is a well-recognised treatment for chronic coccydynia. Several side effects have previously been described with this procedure, including transient motor dysfunction, bowel, bladder, and sexual dysfunction, neuritis, rectal perforation, impingement of the sciatic nerve, cauda equina syndrome, and infection., Case Presentation: We describe the first report of imaging-documented conus infarction after an unguided-GIB performed in theatre using particulate steroids for a 17-year-old patient with coccydynia. Immediately post-GIB, patient developed transient neurological deficits in her lower limbs of inability to mobilise her legs that lasted for 24 h. These include back and leg pain, decreased power and movement, increased tone, brisk reflexes, reduced light touch sensation and proprioception of legs up to the T10 level. Urgent MRI spine showed intramedullary hyperintense signal within the conus and mild restricted diffusion on the distal cord and conus, suggestive of an acute conus infarction. On follow-up, the GIB did not result in symptom improvement of coccydynia and there was persistent altered sensation of her legs., Discussion: Various approaches of ganglion impar block have been described and performed in the past with different imaging techniques and injectants. A few cases of unusual neurological complications have been reported with the use of epidural steroid injections and ganglion impar block. Clinicians should be aware of the possible neurological complications following ganglion impar blocks and the risk of inadvertent intravascular injection of particulate steroids can potentially to be minimised by using imaging guidance., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

In order to establish effective conservation strategy, drivers of local and regional patterns of biodiversity need to be understood. The composition of local biodiversity is dependent on a number of factors including evolution and redistribution of lineages through dispersal and environmental heterogeneity. Brazilian canga is characterised by a ferrugineous substrate, found both in the Iron Quadrangle of Minas Gerais and in the Carajás mountains in Amazonia. Canga is one of several specialised habitat types comprising Brazilian campo rupestre, a montane vegetation found within or adjacent to several major Brazilian bioregions, including the Atlantic Forest and Amazonia, with exceptionally high levels of diversity and endemism arising from both history of dispersal and environmental variation. In order to inform biodiversity conservation for canga, and more broadly for campo rupestre, we performed floristic and phylogenetic analyses investigating affinities between 28 sites on different substrates (canga and quartzite) and geographic locations (Carajás, Pará [Amazonia]; Cadeia do Espinhaço, Minas Gerais; Chapada Diamantina, Bahia). Through analysis of 11204 occurrences of 4705 species of angiosperms, we found that Amazonian Carajás canga plant communities formed a cohesive group, distinct from species assemblages found in Eastern Brazil (Minas Gerais, Bahia), either on canga or quartzite. The phylogenetic megatree of species across all sites investigated shows associations between certain clades and Amazonian canga, with few shared species between the Amazonian Carajás and Eastern Brazil sites, while the floristic comparison shows high levels of heterogeneity between sites. The need for reserves for Amazonian Carajás canga has been recognized and addressed by the creation of a national park. However, current sampling does not provide sufficient reassurance that the canga areas now benefitting from full legal protection adequately represent the regional canga flora., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Chiari malformation is characterized by caudal descent of the cerebellar tonsils through the foramen magnum. Acquired Chiari malformations (ACM) have previously been described after a variety of pathologies including lumbar puncture, cerebrospinal fluid (CSF) drainage, lumboperitoneal shunts, and conditions causing craniocephalic disproportion., Case Presentation: We present four cases of ACM following spinal cord injury (SCI), which has not previously been described in the literature., Discussion: ACM is rare and typically associated with abnormalities in CSF pressure or space-occupying lesions. This case series describes the potential association of SCI with ACM. We discuss the imaging findings and clinical management of these patients. Early recognition and intervention may be important to prevent progressive neurology in this vulnerable patient group., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

Study design:Prospective study.Objective:To ascertain the prevalence of posterior circulation stroke in traumatic chronic spinal cord injured (SCI) patients and associated traumatic vertebral artery injuries (VAI).Methods:All adult patients with cervical SCI and American Spinal Injury Association Impairment Scale (AIS) grade A or B referred for follow-up magnetic resonance imaging of their spinal cord were invited to take part in the study between January 2010 and December 2012 at the National Spinal Injury Centre. Two additional sequences were added to the existing imaging protocol to evaluate the brain and vertebral arteries.Results:Ninety-eight patients were recruited. All imaging were analysed independently by three consultant radiologists. Posterior circulation infarcts were noted in seven (7%) patients. Significant VAI was noted in 13 patients (13%) with 10 occlusions and 3 with high-grade stenosis. However, only one patient had co-existent posterior circulation infarct and significant VAI.Conclusion:There is an increased prevalence of posterior circulation infarction in SCI patients. The relationship with associated traumatic VAI requires further investigation. [ABSTRACT FROM AUTHOR]

Study design:Retrospective review study.Objectives:To identify whether it is safe to perform a magnetic resonance imaging (MRI) exam on patients who have a sacral anterior root stimulator (SARS).Setting:Adult patients with spinal cord injury and implanted SARS attending the National Spinal Injuries Centre who have had MRI scans.Methods:Retrospective review between 1989 and 2010. The effect of the MRI scans on the function of the SARS (Finetech-Brindley, UK) was assessed up to 6 months following MRI at 0.2 and 1.5 T.Results:A total of 18 patients with SARS implants had MRI scans at 0.2 and 1.5 T of the cervical, thoracic and lumbar spine, head, shoulder and pelvis. MRI examinations were abandoned on two occasions in one patient due to radiofrequency interference. One patient's stimulator ceased to function 5 months following MRI; both of these patients showing complications had their MRI examinations at 0.2 T. There were no adverse effects at 1.5 T. In one patient the SARS was removed within 6 months after MRI due to an unrelated medical condition. A total of 17 patients showed no symptoms that required terminating the examination. In all the 11 patients with a complete and functioning implant before MRI at 1.5 T, the SARS was functioning appropriately, and no change in bladder function was reported up to 6 months following MRI.Conclusion:It is safe to perform an MRI scan on patients with SARS providing the examination is conducted in a 1.5 T system. [ABSTRACT FROM AUTHOR]

Study design:Pictorial review.Objectives:To illustrate MRI signs of acute and subacute injury with emphasis on evidence-based links to clinical outcome and implications for treatment.Methods:Description of important aspects of MRI techniques and illustration of critical MRI signs important in the assessment of spinal cord injury following trauma, in the acute and subacute stages.Conclusions:Familiarity with cord MRI appearances has an important impact on planning the management of the acutely spinal cord injured patient and also identifying complications in the subacute phase particularly in the presence of neurological deterioration. [ABSTRACT FROM AUTHOR]

Study design:Retrospective Case Review.Objectives:To describe the clinical presentation and course of patients with magnetic resonance imaging (MRI) features of subacute progressive ascending myelopathy (SPAM). A rare complication of spinal cord injury.Setting:National Spinal Injuries Centre, Stoke Mandeville Hospital, UK.Materials and methods:A retrospective review of the case notes and MRI studies of 11 cases with typical MRI features of ascending myelopathy presenting to a tertiary Spinal Injuries centre over a 15-year period.Results:Eleven patients were identified with MRI features typical of SPAM, a median of 13 days (mean 24, range 4–86 days) following cord injury. The median number of cord segments involved above the initial insult was 6 (mean 6.2, range 4–11). MRI appearances include extension four or more segments cephalad to the initial cord injured segment, cord expansion and increased intramedullary T2 signal with a rim of cord sparing peripherally. Cord changes and neurological deficits improved over time but did not return to the initial injured level on MRI. One patient died (mortality 9%).Conclusion:SPAM is a rare cause of neurological deterioration following spinal cord injury but may remain subclinical. SPAM most commonly presents as neurological deterioration but may present with shoulder pain, respiratory deterioration or remain subclinical. There are characteristic MRI appearances. It can be fatal.Spinal Cord (2008) 46, 140–144; doi:10.1038/sj.sc.3102056; published online 3 April 2007 [ABSTRACT FROM AUTHOR]

Aiming at the problems of collapse, deformation, and displacement in the concrete paving of roadway floors, this paper adopts the way of adding alkali-free accelerators to the concrete on both sides, through mechanical analysis, single factor experiment, orthogonal experiment, and polynomial fitting method, and determines the relevant parameters of concrete and accelerators in the sliding form paving of roadway floor from two aspects of paving material and size. The results show that the FSA-AF alkali-free liquid accelerator is more suitable for roadway floor paving than the J85 powder accelerator. When the FSA-AF accelerator dosage reaches 8%, the decreasing trend of initial setting time curve tends to be flat. The deformation resistance of concrete containing accelerator is positively correlated with the dosage of the accelerator. Concrete side pressure is positively correlated with pavement paving height. The FSA-AF accelerator can reduce the compressive strength of concrete; the compressive strength and retention rate of concrete at all ages are the highest when the dosage of FSA-AF is 7%. A water–cement ratio of 0.4 and a 9% dosage of accelerator are the optimal combination to meet the four evaluation indexes. According to the width estimation formula, the width of the side concrete should be set to 14 cm. [ABSTRACT FROM AUTHOR]

Analyzes the nucleo-cytoplasmic male sterility and alternative routes to dioecy. Impact of nucleo-cytoplasmic gynodioecy on the invasion of males and conversion of dioecy in a single cytotype; Rates of evolution; Conditions for male invasion; Restorable sterile cytotypes; Stable breeding systems; Population genetic models.

Study design:Case report.Objective:To describe the clinical benefit of a spinal cordectomy with the aim of limiting neurological deterioration related to the development of a subacute posttraumatic ascending myelopathy (SPAM) supporting previously described mechanism for SPAM formation.Setting:National Spinal Injuries Centre, Stoke Mandeville Hospital, UK.Method and results:A 38-year old patient presented 6 months after spinal cord injury substantial neurological deterioration expanding from the initial T4-injury level through C4. Magnetic resonance imaging revealed intra-medullary haemorrhage at the site of injury and subsequent-ascending cord oedema. A cordectomy was performed leading to neurological stabilisation and complete resolution of SPAM.Conclusion:Cordectomy can be an effective intervention in case of rapid progressive neurological deterioration. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate timeliness of an outpatient urgent access neurovascular clinic in a district general hospital setting through an audit of delay from event to completion of evaluation following transient ischaemic attack (TIA) or minor stroke. Participants included those referred for evaluation of suspected TIA or minor stroke. The median delay from event to completion was 16 days, with 45% seen within two weeks of symptom onset, and 15% within one week of symptom onset. A weekly TIA clinic is not capable of achieving the National Clinical Guidelines for Stroke recommendation for evaluation within one week of symptoms. This audit supports the National Stroke Strategy recommendation for immediate evaluation of patients presenting with a recent TIA or minor stroke.

The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation (EU) 2018/2019 as 'High risk plants, plant products and other objects'. This Scientific Opinion covers plant health risks posed by plants of Betula pendula and B. pubescens imported from the United Kingdom (UK) taking into account the available scientific information, including the technical information provided by the UK. The commodities were grouped in the risk assessment as (a) bundles of 10–20 graftwood/budwood (up to 1‐year‐old), (b) bare root plants which include bundles of 25 or 50 seedlings or transplants (1–2 years‐old), bundles of 5, 10 or 15 whips (1–2 years‐old) and single bare root plants (1–7 years‐old), (c) plants in pots which include bundles of 5 and 10 cell‐grown plants (1–2 years‐old) and rooted plants in pots (1–7 years‐old), and (d) large specimen trees up to 15‐years‐old. All pests associated with the commodities were evaluated against specific criteria for their relevance for this opinion. Two EU quarantine pests i.e. Meloidogyne fallax and Phytophthora ramorum (non‐EU isolates) and two protected zone quarantine pests i.e. Entoleuca mammata and Thaumetopoea processionea fulfilled all relevant criteria and were selected for further evaluation. For the selected pests, the risk mitigation measures described in the technical dossier from the UK were evaluated considering the possible limiting factors. For these pests an expert judgement is given on the likelihood of pest freedom taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. In the assessment of risk, the age of the plants was considered, as larger trees are more likely to be infested mainly due to longer time grown in the field. In addition, larger canopies and root systems are more difficult to inspect, thereby making the detection of pests more challenging on large trees. The likelihood of pest freedom varies among the pests evaluated, with M. fallax being the pest most frequently expected on the imported plants. The Expert Knowledge Elicitation (EKE) indicated with 95% certainty that between 9735 and 10,000 per 10,000 large specimen trees will be free from M. fallax. [ABSTRACT FROM AUTHOR]

A fundamental understanding of the underlying mechanisms involved in biological invasions is crucial to developing effective risk assessment and control measures against invasive species. The fall armyworm (FAW), Spodoptera frugiperda, is a highly invasive pest that has rapidly spread from its native Americas into much of the Eastern Hemisphere, with a highly homogeneous nuclear genetic background. However, the exact mechanism behind its rapid introduction and propagation remains unclear. Here, a systematic investigation is conducted into the population dynamics of FAW in China from 2019 to 2021 and found that FAW individuals carrying "rice" mitochondria (FAW‐mR) are more prevalent (>98%) than that with "corn" mitochondria (FAW‐mC) at the initial stage of the invasion and in newly‐occupied non‐overwintering areas. Further fitness experiments show that the two hybrid‐strains of FAW exhibit different adaptions in the new environment in China, and this may have been facilitated by amino acid changes in mitochondrial‐encoded proteins. FAW‐mR used increases energy metabolism, faster wing‐beat frequencies, and lower wing loadings to drive greater flight performance and subsequent rapid colonization of new habitats. In contrast, FAW‐mC individuals adapt with more relaxed mitochondria and shuttle energetics into maternal investment, observed as faster development rate and higher fecundity. The presence of two different mitochondria types within FAW has the potential to significantly expand the range of damage and enhance competitive advantage. Overall, the study describes a novel invasion mechanism displayed by the FAW population that facilitates its expansion and establishment in new environments. [ABSTRACT FROM AUTHOR]

Carajasia cangae (Rubiaceae) is a narrow endemic species from the canga ecosystems of the Carajás National Forest that is facing extinction due to a limited range and habitat disturbance from hydroclimatological changes and mining activities. This study examines the influence of rhizospheric and endophytic bacteria on C. cangae seed germination to support conservation efforts. Soil samples, both rhizospheric and non-rhizospheric, as well as plant root tissues, were collected. Bacteria from these samples were subsequently isolated, cultured, and identified. DNA sequencing revealed the presence of 16 isolates (9 rhizospheric and 7 endophytic), representing 19 genera and 6 phyla: Proteobacteria, Actinobacteria, Acidobacteria, Firmicutes, Bacteroidetes, and Chloroflexi. The endophytic isolates of Bacillus and the rhizospheric isolates of Planococcus and Lysinibacillus reduced the median germination time and initiation time, while the rhizospheric isolates Serratia and Comamonas increased the germination time and decreased the germination percentage in comparison to the control sample. These findings emphasize the crucial role of endophytic bacteria in the germination of C. cangae and highlight isolates that could have beneficial effects in the following stages of plant growth. Understanding the impact of endophytic and rhizospheric bacterial isolates on seed germination can enhance conservation efforts by shortening the germination period of this species and thereby improving seedling production. Additionally, this knowledge will pave the way for future research on the role of bacteria in the establishment of C. cangae. [ABSTRACT FROM AUTHOR]

Background: This retrospective study aimed to evaluate the characteristics of patients with long COVID syndrome. Methods: This study included 457 adults who had at least one persistent symptom after COVID-19 infection. Results: The median time interval between the last SARS-CoV-2 infection and emergency room presentation was 3 months. Older patients had comorbidities (61.7 vs. 44.9 years, p < 0.0001), moderate or severe forms of COVID-19 (61.2 vs. 50.9 years, p < 0.0001), and respiratory symptoms (56.1 vs. 52.0 years, p = 0.0027). Non-vaccinated patients were older than vaccinated patients (56.0 vs. 51.5 years, p = 0.0008) and had residual lung abnormalities following COVID-19 infection (51.5% vs. 36.8%, p < 0.003). The time interval between the last SARS-CoV-2 infection and the hospital evaluation was shorter for vaccinated patients (3.2 vs. 3.9 months, p < 0.0001) and those with mild forms (3.3 vs. 4.12 months, p = 0.0001) versus non-vaccinated individuals. After the last SARS-CoV-2 infection, 107 patients developed impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus, being patients with already known chronic diseases (p = 0.0002), or hypertension (p = 0.001). Conclusions: Our study pointed out the heterogeneity of symptoms following COVID-19, and they are associated with age, vaccination status, or severity of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]