Lincoln University entomological expedition to Pitt Island

The expedition had two objectives: 1. To search for the Pitt Island longhorn beetle, Xylotoles costatus and determine its distribution, abundance and conservation status. 2. To undertake general entomological survey work, particularly in the orders Coleoptera, Diptera, Lepidoptera and Hymenoptera by using trapping methods not previously used on Pitt Island

Technical Note: Error metrics for estimating the accuracy of needle/instrument placement during transperineal MR/US-guided prostate interventions

Purpose: Image-guided systems that fuse magnetic resonance imaging (MRI) with three-dimensional (3D) ultrasound (US) images for performing targeted prostate needle biopsy and minimally-invasive treatments for prostate cancer are of increasing clinical interest. To date, a wide range of different accuracy estimation procedures and error metrics have been reported, which makes comparing the performance of different systems difficult. Methods: A set of 9 measures are presented to assess the accuracy of MRI-US image registration, needle positioning, needle guidance, and overall system error, with the aim of providing a methodology for estimating the accuracy of instrument placement using a MR/US-guided transperineal approach. Results: Using the SmartTarget fusion system, an MRI-US image alignment error was determined to be 2.0±1.0 mm (mean ± SD), and an overall system instrument targeting error of 3.0±1.2 mm. Three needle deployments for each target phantom lesion was found to result in a 100% lesion hit rate and a median predicted cancer core length of 5.2 mm. Conclusions: The application of a comprehensive, unbiased validation assessment for MR/TRUS guided systems can provide useful information on system performance for quality assurance and system comparison. Furthermore, such an analysis can be helpful in identifying relationships between these errors, providing insight into the technical behaviour of these systems

The SmartTarget BIOPSY trial: A prospective, within-person randomised, blinded trial comparing the accuracy of visual-registration and MRI/ultrasound image-fusion targeted biopsies for prostate cancer risk stratification

Background: Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. Whether visual-registration targeting is sufficient or if augmentation with image-fusion software is needed is unknown. Objective: To assess concordance between the two methods. Design, Setting, and Participants: We conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3 to 5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study. Intervention: The order of performing biopsies using visual-registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias. Outcome Measurements and Statistical Analysis: The proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3+4=7, maximum cancer core length ≥4 mm; secondary outcome: Gleason pattern ≥4+3=7, maximum cancer core length ≥6 mm) detected by each method was compared using McNemar's test of paired proportions. Results and Limitations: The two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy individually detected 80/93 (86%) of these cancers; each strategy detected 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 weeks) was observed. The key limitation was lack of parallel-group randomisation and limit on number of targeted cores. Conclusions: Visual-registration and image-fusion targeting strategies combined had the highest detection rate for clinically significant cancers. Targeted prostate biopsy should be performed using both strategies together. Patient Summary: We compared two prostate cancer biopsy strategies: visual-registration and image-fusion. The combination of the two strategies found the most clinically important cancers and should be used together whenever targeted biopsy is being performed

COVID-19 and maternal and perinatal outcomes - Authors' reply.

Author's reply

More or less likely to offend? Young adults with a history of identified Developmental Language Disorder

Background: There is now substantial literature demonstrating that a disproportionate number of young people who come into contact with youth justice services evidence unidentified language difficulties. These young people, therefore, have received little or no professional input in this area. Conversely, there is a dearth of research pertaining to criminality outcomes among those individuals with identified developmental language disorders who have received such interventions. Aims: The paper examines police-initiated contact and substance use outcomes of young adults with a history of identified developmental language disorders (DLD) versus age matched peers (AMPs). Additionally, self-reported rule breaking behaviours and aggression are considered. We hypothesise that early identification/intervention reduces engagement with risky behaviour such as substance and alcohol use as well as offending-related behaviours. Methods & Procedures: Adversarial police-initiated contacts were examined in 84 young adults with a history of DLD and 88 AMPs. Rule-breaking and aggression were evaluated using the Achenbach Adult Self-Report for ages 18-59. Outcomes & Results: Adults with a history of DLD, who received targeted intervention during their school years, reported less contact with their local police service compared to AMPs at age 24. Comparable proportions of both groups reported current alcohol consumption but group differences were found relating to alcohol use. No group differences in rule breaking behaviours were found but the DLD group was found to have a statistically significant higher raw score on the aggressive behaviour scale. Conclusions & Implications: There is a need for early identification of children with DLD. Early intervention aimed at ameliorating such difficulties could possibly have distal outcomes in relation to offending

Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin

Immune responses to autoantigens are in part controlled by deletion of autoreactive cells through genetically regulated selection mechanisms. We have directly analyzed peripheral CD4+ proinsulin (PI) 76–90 (SLQPLALEGSLQKRG)-specific T cells using soluble fluorescent major histocompatibility complex class II tetramers. Subjects with type I diabetes and healthy controls with high levels of peripheral proinsulin-specific T cells were characterized by the presence of a disease-susceptible polymorphism in the insulin variable number of tandem repeats (INS-VNTR) gene. Conversely, subjects with a ‘protective' polymorphism in the INS-VNTR gene had nearly undetectable levels of proinsulin tetramer-positive T cells. These results strongly imply a direct relationship between genetic control of autoantigen expression and peripheral autoreactivity, in which proinsulin genotype restricts the quantity and quality of the potential T-cell response. Using a modified tetramer to isolate low-avidity proinsulin-specific T cells from subjects with the susceptible genotype, transcript arrays identified several induced pro-apoptotic genes in the control, but not diabetic subjects, likely representing a second peripheral mechanism for maintenance of tolerance to self antigens

Global changes in maternity care provision during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: The COVID-19 pandemic has had a profound impact on healthcare systems globally, with a worrying increase in adverse maternal and foetal outcomes. We aimed to assess the changes in maternity healthcare provision and healthcare-seeking by pregnant women during the COVID-19 pandemic. Methods: We performed a systematic review and meta-analysis of studies of the effects of the pandemic on provision of, access to and attendance at maternity services (CRD42020211753). We searched MEDLINE and Embase in accordance with PRISMA guidelines from January 1st, 2020 to April 17th 2021 for controlled observational studies and research letters reporting primary data comparing maternity healthcare-seeking and healthcare delivery during compared to before the COVID-19 pandemic. Case reports and series, systematic literature reviews, and pre-print studies were excluded. Meta-analysis was performed on comparable outcomes that were reported in two or more studies. Data were combined using random-effects meta-analysis, using risk ratios (RR) or incidence rate ratios (IRR) with 95% confidence intervals (CI). Findings: Of 4743 citations identified, 56 were included in the systematic review, and 21 in the meta-analysis. We identified a significant decrease in the number of antenatal clinic visits (IRR 0614, 95% CI 0486-0776, P<00001, I2=54.6%) and unscheduled care visits (IRR 0741, 95% CI 0602-0911, P = 00046, I2=00%) per week, and an increase in virtual or remote antenatal care (IRR 4656 95% CI 7762-2794, P<00001, I2=90.6%) and hospitalisation of unscheduled attendees (RR 1214, 95% CI 1118-1319, P<00001, I2=00%). There was a decrease in the use of GA for category 1 Caesarean sections (CS) (RR 0529, 95% CI 0407-0690, P<00001, I2=00%). There was no significant change in intrapartum epidural use (P = 00896) or the use of GA for elective CS (P = 079). Interpretation: Reduced maternity healthcare-seeking and healthcare provision during the COVID-19 pandemic has been global, and must be considered as potentially contributing to worsening of pregnancy outcomes observed during the pandemic

Influenza and associated co-infections in critically ill immunosuppressed patients

Background: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P &lt; 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P &lt; 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

“PMA Sounds Fun”: Negotiating Drug Discourses Online

In 2007, a young woman, Annabel Catt, died after consuming a capsule sold as “ecstasy” that contained para-methoxyamphetamine. In this paper, we describe how this death was depicted in online drug-user communities and illustrate how the meanings of drug use are negotiated in online settings. News articles, public online discussions, and online fieldwork formed the data. This paper demonstrates how dominant drug discourses may be resisted by drug users, drawing on theories of health resistance and Kane Race’s concept of counter public health. Online environments may offer ways of engaging people who use drugs that acknowledge both pleasure and safety. The study’s limitations are noted