Vertical Transmission of Trypanosoma Cruzi in a Non-Endemic Country: Histology of the Infected Placenta.

Chagas disease, once confined to rural Latin America is an increasing public health concern in non-endemic countries due to population movements. Here we present an unexpected finding of a placenta infected with T. cruzi from a Brazilian woman residing in Ireland. Histology of the placenta showed a lymphocytic chorioamnionitis with multinucleated giant cells (MNGCs) as well as cord vasculitis and funisitis. Amastigotes of trypanosomiasis were found in both cord and membranes. The placenta parenchyma, however, had no villitis or amastigotes and maturation was appropriate for gestation. To date, there have been few reported cases of vertical transmission in non-endemic countries. We discuss the histological findings and review the literature on potential modes of transmission from mother to fetus.

Urothelial cancer: a narrative review of the role of novel immunotherapeutic agents with particular reference to the management of non-muscle-invasive disease.

AIM: This narrative review describes current guidelines for treating NMIBC, provides an overview of the principle behind immune checkpoint inhibition, and summarizes current evidence for checkpoint inhibitors in urothelial malignancy. Further, we discuss potential strategies for immune checkpoint inhibition in the management of NMIBC. BACKGROUND: Adjuvant intravesical BCG immunotherapy has been the mainstay of treatment for high-risk non-muscle-invasive bladder cancer (NMIBC) for decades but is associated with both a significant side effect profile and failure rate. Recently, a substantial body of trial data has been published demonstrating the successful use of systemic immunotherapy in the treatment of advanced urothelial malignancy and, in particular, a class of drugs known as 'immune checkpoint inhibitors'. This has led to the approval of a number of these drugs by the UK National Institute of Health and Care Excellence and the US Food and Drug Administration, and ongoing trials are examining use in the management of NMIBC. METHODS: To identify relevant published data, using the PubMed/ Medline search engine, an online search of the Pubmed/ Medline archives was conducted using the terms bladder cancer' in combination with 'checkpoint inhibitors', and limited to articles in English published between 1966 and September 2017.To identify ongoing trials of interest but not yet published, a further search of the clinical trials.gov search engine was conducted using the term 'non-muscle-invasive bladder cancer'. CONCLUSION: There has been little advance in available adjuvant therapy for NMIBC treated with TURBT. Current intravesical therapies are associated with a high recurrence rate and significant side effect profile. The impending publication of the wealth of ongoing trials, both into the delivery and efficacy of checkpoint inhibition will direct the future treatment of NMIBC.

Perceptions of risk characteristics of earthquakes compared to other hazards and their impact on risk tolerance.

People tolerate different levels of risk owing to a variety of hazards. Previous research shows that the psychometric properties of hazards predict people's tolerance of them. However, this work has not taken into account events such as earthquakes. The present study tested how earthquakes score vis-à-vis risk properties and risk tolerance as compared to five other familiar hazards. Participants from Wellington, New Zealand (N=139) rated these six hazards using measures of risk characteristics and risk tolerance. Participants demonstrated different levels of risk tolerance for the different hazards and viewed earthquakes as having similar risk features to nuclear power. They also preferred different risk mitigation strategies for earthquakes (more government funding) to the other five hazards (stronger legislation). In addition, earthquake risk tolerance was predicted by different risk characteristics than the other five hazards. These findings will help risk communicators in identifying which risk characteristics to target to influence citizens' risk tolerance.

Intra-familial variability associated with recessive RYR1 mutation diagnosed prenatally by exome sequencing.

OBJECTIVE: To determine the underlying molecular aetiology in a non-consanguineous Irish family who have had three fetal losses because of a primary myopathy characterised by fetal akinesia, arthrogryposis multiplex, bilateral pulmonary hypoplasia and reduced muscle bulk. METHODS: Fetal DNA extracted from amniotic cells was whole genome amplified and subjected to whole exome sequencing. RESULTS: Whole exome sequencing identified compound heterozygous variants in RYR1 as the cause of the lethal myopathy in this family. All three fetuses were compound heterozygous for a paternally inherited missense variant (c.2113G > A; p.Gly705Arg) and a novel maternally inherited truncating frameshift deletion (c.8843delC; p.Ser2948Cysfs*58). This family did not have the classic cores and fibre type disproportion typically associated with RYR1 mutation. The RYR1 exome finding was made during the couple's third pregnancy and enabled prenatal genetic testing to be undertaken. CONCLUSION: We show that recessive RYR1 mutations can be associated with significant intra-familial variability in clinical presentation which can complicate prediction of clinical outcome. RYR1 mutations can also cause diverse muscle pathologies which thwarts diagnosis. This study demonstrates the impact that exome-based diagnoses can have for families with lethal disorders. © 2016 John Wiley & Sons, Ltd.

Systematic review of the efficacy of stereotactic ablative radiotherapy for oligoprogressive disease in metastatic cancer.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) for the treatment of oligometastatic disease can improve survival and delay the requirement for systemic therapy. The benefits of SABR in oligoprogressive disease are less well-defined. Here, we evaluate the available evidence investigating the efficacy of SABR in the treatment of oligoprogressive disease. METHODS: A systematic review was carried out following PRISMA guidelines. Medline and Embase databases were searched using the terms "stereotactic radiotherapy" OR "SABR" OR "Stereotactic Ablative Body Radiotherapy" OR "SBRT" OR "SRT" AND "oligoprogression" in May 2022, June 2023, and February 2024. Studies were excluded where: SABR was used as a radical treatment, a specific oligoprogressive cohort could not be identified, publication was as a conference abstract or where fewer than 10 patients were recruited. Studies treating only brain metastases were also excluded. The site of primary tumour, oligoprogressive sites, rates of overall survival (OS), progression free survival (PFS), local control (LC) and time to next systemic therapy were collected. RESULTS: Thirty-three full text studies were included. These consisted of single centre and multi-institutional observational studies, case series and phase II trials. Twenty-two studies were related to a specific tumour type: 12 urological cancer (9 prostate, 3 renal cancer), 6 non-small cell lung cancer, 2 colorectal cancer, 2 breast cancer and 11 were studies covering multiple tumour sites (5 studies involving SABR to a single organ and 6 studies involving SABR to multi-organ). Median PFS was >6 months in patients with oligoprogressive prostate, non-small cell lung cancer and renal cancer patients. CONCLUSIONS: SABR appears to have clinical benefit in oligoprogresssive prostate, lung, and renal patients. However, the optimal management of patients with oligoprogressive disease is still somewhat uncertain due to lack of prospective data. This will hopefully become clearer in the near future with the publication of further randomised trials.

Splenic vein rupture in pregnancy: A case report and systematic review of the literature.

Splenic vein aneurysm (SVA) rupture is a rare clinical entity, with few case reports detailing its occurrence during pregnancy. We describe a case of a SVA rupture and present a systematic review of the literature in relation to splenic vein rupture, with or without aneurysm. Our case was of a 30-year-old woman, Para 4 at 37 weeks' gestation who presented with significant abdominal pain and subsequent maternal collapse. Massive intra-abdominal hemorrhage was identified, with splenic vessel rupture suspected. A splenectomy and partial pancreatectomy were performed along with massive blood product transfusion. There was both maternal and fetal survival with no long-term sequelae at follow-up. Histological examination of the spleen and its vessels noted a SVA rupture. In a subsequent systematic review of the literature, we identified 10 cases of splenic vein rupture with only two previously documented cases of SVA rupture in pregnancy. Maternal and fetal survival has only been reported in two cases of splenic vein rupture, with ours being a third.

Prognostic value of the Scottish Inflammatory prognostic Score in patients with NSCLC expressing PD-L1 ≥ 50 % progressing on first-line pembrolizumab.

BACKGROUND: Most patients with advanced non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab monotherapy will experience progressive disease (PD). Only a minority will go on to receive subsequent systemic anticancer therapy for which outcomes are guarded. We investigated the prognostic significance of biomarkers of systemic inflammation following failure of first-line pembrolizumab for NSCLC to aid subsequent management decisions. METHODS: Patients with radiological and/or clinical evidence of PD on first-line pembrolizumab for advanced NSCLC at a regional Scottish cancer centre were identified. Inflammatory biomarkers at the time of PD, including serum albumin, neutrophil count and the Scottish Inflammatory Prognostic Score (SIPS; combing albumin and neutrophils), and clinicopathological factors, including age, sex, histology, PDL1 expression and time to PD were recorded. The relationship between these and post-progression overall survival (ppOS) were examined. RESULTS: Data were available for 211 patients. Median ppOS was 2.1 months. Only SIPS was predictive of ppOS on multivariate analysis (HR2.54 (95 %CI 1.81-3.56) (<0.001)), stratifying ppOS from 0.8 months (SIPS2), to 1.8 months (SIPS1), to 8.1 months (SIPS0) (p < 0.001). Thirty (14 %) patients received second-line systemic anticancer therapy with median ppOS 8.7 months. These patients had lower levels of systemic inflammation, as defined by albumin (p < 0.001), neutrophil count (p = 0.002), and SIPS (p = 0.004)), than all other patients. CONCLUSIONS: SIPS, a simple biomarker of systemic inflammation, predicts ppOS after first-line pembrolizumab and may be useful alongside routine assessments of patient fitness to inform individualised discussions about subsequent treatment. We highlight poor outcomes in this patient group and a role for SIPS in signposting transition to best supportive care and early referral to palliative care. It may also help identify a small group of patients most likely to benefit from further lines of therapy.

Deep Learning-Assisted interactive contouring of lung Cancer: Impact on contouring time and consistency.

BACKGROUND AND PURPOSE: To evaluate the impact of a deep learning (DL)-assisted interactive contouring tool on inter-observer variability and the time taken to complete tumour contouring. MATERIALS AND METHODS: Nine clinicians contoured the gross tumour volume (GTV) using the PET-CT scans of 10 non-small cell lung cancer (NSCLC) patients, either using DL-assisted or manual contouring tools. After contouring a case using one contouring method, the same case was contoured one week later using the other method. The contours and time taken were compared. RESULTS: Use of the DL-assisted tool led to a statistically significant decrease in active contouring time of 23 % relative to the standard manual segmentation method (p < 0.01). The mean observation time for all clinicians and cases made up nearly 60 % of interaction time for both contouring approaches. On average the time spent contouring per case was reduced from 22 min to 19 min when using the DL-assisted tool. Additionally, the DL-assisted tool reduced contour variability in the parts of tumour where clinicians tended to disagree the most, while the consensus contour was similar whichever of the two contouring approaches was used. CONCLUSIONS: A DL-assisted interactive contouring approach decreased active contouring time and local inter-observer variability when used to delineate lung cancer GTVs compared to a standard manual method. Integration of this tool into the clinical workflow could assist clinicians in contouring tasks and improve contouring efficiency.

Placental pathology and neonatal encephalopathy.

Neonatal encephalopathy (NE) is an important cause of neonatal morbidity and mortality worldwide; however, there remain gaps in our knowledge about its pathogenesis. The placenta has been implicated in the pathogenesis of this disease but conclusive evidence related to the placental factors that influence it is sparse. This review aims to outline the current knowledge on the role of the placenta with particular attention to its role in NE as a consequence of hypoxia-ischemia. A total of 26 original articles/review papers were used to compile this review. Three themes were identified from these publications: fetal vascular malperfusion including umbilical cord pathology, inflammatory changes in the placenta, and maternal vascular malperfusion including placental weight. These features were identified as being significant in the development of NE. Advancing our understanding of this relationship between placental pathology and NE may facilitate the development of additional antenatal screening to better identify at-risk fetuses. We highlight areas for further research through antenatal screening and placental histology.

COVID-19 vaccine intentions in Aotearoa New Zealand: Behaviour, risk perceptions, and collective versus individual motivations.

The global SARS-CoV-2 (COVID-19) pandemic presents a pressing health challenge for all countries, including Aotearoa New Zealand (NZ). As of early 2022, NZ public health measures have reduced impacts of the pandemic, but ongoing efforts to limit illness and fatalities will be significantly aided by widescale uptake of available vaccines including COVID-19 booster doses. Decades of research have established a broad range of demographic, social, cognitive, and behavioural factors which influence peoples' uptake of vaccinations, including a large amount of research in the last two years focused on COVID-19 vaccination in particular. In this study, we surveyed people in New Zealand (N = 660) in May and June of 2021, at which point the vaccine had been made available to high-risk groups. We explored individual versus collective motivations, finding that people who were hesitant about COVID-19 vaccination scored lower on independent self-construals (how people define themselves) but higher on community identity, weaker but still positive perceived social norms, lower general risk of COVID-19 to New Zealanders and higher vaccine risk for both themselves and others, and lower response-efficacy both for personal and collective benefits. Overall, the findings suggest some benefit of collective over individual appeals, but that generally messaging to encourage vaccination should focus on conveying social norms, risk from COVID-19 broadly, and vaccine safety and efficacy.

Postnatal maternal behaviour expression depends on lambing difficulty in Merino ewes.

Dystocia, a prolonged or non-progressive birth event, is the main contributor to lamb mortality in Australia and across the world. Dystocia can cause neonatal hypoxia, central nervous system (CNS) damage leading to increased risk of starvation, exposure and mismothering, and death. These prolonged birth events can also cause fatigue, injury and death in the ewe. Dystocia may interrupt the expression of maternal behaviour and the strength of the ewe-lamb bond, and consequently lamb survival. This study focused on the effect of dystocia on ewe behaviour in the 2 h post-lambing. A total of 18 ewes were chosen for continuous behaviour annotation and analysis (dystocic (n = 9) and eutocic (n = 9)) based on the quality of video recordings, length of stage 2 parturition and classification by a single experienced observer. Dystocic ewes showed significantly lower expression of maternal behaviours and a significantly greater expression of avoidance behaviours compared to eutocic ewes. Additionally, dystocic ewes performed fewer behaviours in total compared to eutocic ewes. Dystocia can significantly affect the quality and quantity of ewe maternal behaviour expression, leading to increased avoidance of the lamb, increased risk of maternal disinterest, and increased risk of death for the lamb. If dystocic events can be identified quickly and accurately, measures can be taken to ensure the ewe and lamb recover successfully.

Know when to fold 'em: Polycomb complexes in oncogenic 3D genome regulation.

Chromatin is spatially and temporally regulated through a series of orchestrated processes resulting in the formation of 3D chromatin structures such as topologically associating domains (TADs), loops and Polycomb Bodies. These structures are closely linked to transcriptional regulation, with loss of control of these processes a frequent feature of cancer and developmental syndromes. One such oncogenic disruption of the 3D genome is through recurrent dysregulation of Polycomb Group Complex (PcG) functions either through genetic mutations, amplification or deletion of genes that encode for PcG proteins. PcG complexes are evolutionarily conserved epigenetic complexes. They are key for early development and are essential transcriptional repressors. PcG complexes include PRC1, PRC2 and PR-DUB which are responsible for the control of the histone modifications H2AK119ub1 and H3K27me3. The spatial distribution of the complexes within the nuclear environment, and their associated modifications have profound effects on the regulation of gene transcription and the 3D genome. Nevertheless, how PcG complexes regulate 3D chromatin organization is still poorly understood. Here we glean insights into the role of PcG complexes in 3D genome regulation and compaction, how these processes go awry during tumorigenesis and the therapeutic implications that result from our insights into these mechanisms.

Using Pen-Side Measurable Blood Parameters to Predict or Identify Dystocic Lambing Events.

Dystocia is the greatest contributor to neonatal lamb mortality in Australia and poses significant welfare and economic concerns worldwide. In this study, we set out to investigate whether pen-side analysis technology could be employed to detect blood parameters predictive of dystocic labour events in sheep. In a pilot trial, we collected and analysed blood samples in pen-side assays for glucose, lactate, pH, pCO2, pO2, base excess, HCO3, TCO2, sO2, lactate, sodium, potassium, chloride, calcium, urea nitrogen, creatinine, haematocrit, haemoglobin and anion gap. From the pilot data, we identified creatinine, TCO2, chloride and calcium as potentially useful markers. To develop a time course and to establish variability of the selected blood parameters, a time series of samples was collected from 12 ewes, from mid-gestation to 48 h after birth. For the main trial, blood samples were collected at mid- and late gestation for glucose determination and for the full set of blood parameters at three time points before, at and after birth. Possible predictors of lambing difficulty were chloride, haematocrit and haemoglobin, sampled one week before birth; creatinine, sampled at birth; and blood pH and base excess after birth. In conclusion, we found that pen-side analysis of blood markers showed promise in identifying dystocic lambing events.

Grazier perceptions and management practices for liver fluke control in north eastern NSW, Australia.

A survey of livestock producers (graziers) located in north eastern NSW Australia, collected information on perceptions and management practices for liver fluke control in livestock. The total area farmed by the 161 respondents was 195,600 ha (ranging in size from 4 to 10,522 ha) with cattle and sheep being the dominant livestock enterprises. Overall, 80% of graziers relied exclusively on anthelmintics for liver fluke control and few of these graziers (9%) integrated parasite management (IPM) strategies to reduce disease prevalence. Of those relying on anthelmintic control, triclabendazole (TCBZ) was preferentially chosen by 75% of graziers. Fifty five percent of these graziers used TCBZ in combination with oxfendazole (46%), ivermectin (5%) or abamectin (4%) whilst 45% used TCBZ as a single active ingredient. Thirty eight percent of graziers drenched livestock one or more times per year for liver fluke despite claiming they had no liver fluke or confirmed knowledge of infection. Fifty one percent of graziers based anthelmintic dose on the known weight of the heaviest animal in the herd whilst 43% visually guessed livestock bodyweight to calculate anthelmintic dose. Choice of anthelmintic was predominately based on perceived efficacy (45%) despite very few graziers (2%) having conducted post-treatment fluke egg counts. The majority of graziers (76%) were unsure if they had anthelmintic resistance, 21% claimed they had no resistance whilst 3% of graziers had confirmed resistance. Most graziers (97%) also reported farms were cohabited by kangaroos highlighting additional grazing pressures on-farm. This current survey has revealed that graziers rely on anthelmintics as their primary choice for liver fluke control. Reluctance to adopt IPM strategies and a continued heavy reliance on TCBZ, whilst basing anthelmintic decisions on perception rather than measurement and testing, pose threats for the future control of liver fluke in livestock within this endemic area.

Multi-source Multimodal Data and Deep Learning for Disaster Response: A Systematic Review.

Mechanisms for sharing information in a disaster situation have drastically changed due to new technological innovations throughout the world. The use of social media applications and collaborative technologies for information sharing have become increasingly popular. With these advancements, the amount of data collected increases daily in different modalities, such as text, audio, video, and images. However, to date, practical Disaster Response (DR) activities are mostly depended on textual information, such as situation reports and email content, and the benefit of other media is often not realised. Deep Learning (DL) algorithms have recently demonstrated promising results in extracting knowledge from multiple modalities of data, but the use of DL approaches for DR tasks has thus far mostly been pursued in an academic context. This paper conducts a systematic review of 83 articles to identify the successes, current and future challenges, and opportunities in using DL for DR tasks. Our analysis is centred around the components of learning, a set of aspects that govern the application of Machine learning (ML) for a given problem domain. A flowchart and guidance for future research are developed as an outcome of the analysis to ensure the benefits of DL for DR activities are utilized.

Kangaroos and liver fluke: The role played in cross-species transmission and drug resistance.

Australian livestock are challenged by liver fluke (Fasciola hepatica) in grazing regions endemic to the intermediate snail host. Liver fluke infests a wide range of herbivores including free-roaming wildlife such as kangaroos (Macropods). The role played by Macropods in cross-species transmission and as vectors for anthelmintic resistance is largely unknown. In Phase 1 of this study, liver fluke of Eastern grey kangaroo (Macropus giganteus Shaw, 1790) origin (Kangaroo isolate) were artificially infected in sheep to confirm establishment and cross-species transmission. In Phase 2, the efficacy of triclabendazole (TCBZ) was assessed in vivo against the Kangaroo isolate to identify any drug resistance. Forty (40) merino sheep were housed in pens and allocated to one of 4 groups (Groups 1-4). Groups 1 and 2 were artificially infected with a TCBZ resistant liver fluke isolate (Oberon) originating from sheep whilst Groups 3 and 4 were infected with the Kangaroo isolate (Phase 1). At 9 weeks post infection (wpi), sheep in Groups 2 and 4 were treated with 10 mg/kg TCBZ (Phase 2). Sheep were subsequently euthanased at 11 wpi to conduct total fluke counts (TFC) in the liver. Faecal samples were collected fortnightly to measure fluke egg counts and coproantigens. Individual blood samples were collected, concurrently with faecal sampling, to monitor haematocrit and plasma proteins levels. Liver fluke of kangaroo origin established to patent infections in sheep with similar establishment and pathogenicity to the Oberon isolate. TCBZ achieved an 86 % reduction in TFC (99.8 % - adult fluke, 0 % - immature fluke) in sheep with the Kangaroo isolate and a 28 % reduction in the Oberon isolate (37 % - adult, 0 % - immature fluke). An 89 % reduction in faecal coproantigens was observed in sheep with the Kangaroo isolate and no reduction in sheep with Oberon. This study confirmed cross-species transmission of liver fluke from a kangaroo to sheep. When cohabiting the livestock grazing environment, kangaroos may act as reservoirs for liver fluke and vectors for drug resistance within liver fluke endemic areas.

Prevalence and pathology of liver fluke (Fasciola hepatica) in fallow deer (Dama dama).

A survey conducted on fallow deer (n = 79) in northern New South Wales Australia, aimed to ascertain the prevalence and gross pathology of liver fluke. In total, three deer populations were assessed (1 farmed and 2 wild) across 2 sites (site A and B) by conducting total fluke counts in the liver and fluke egg counts in faecal samples. At site A, 16 of 19 farmed deer (84.2 %) and 9 of 20 wild deer (45 %) had active or resolved infections. At site B, 16 of 40 wild deer (40 %) had active or resolved infections. Deer with active infections had low fluke burdens (1-11 fluke) which were in the adult development stage, shedding eggs with faeces (0-121.7 eggs per gram). Liver pathology score did not exceed 3.5 out of 5 with gross pathomorphological lesions predominately confined to the peripheral regions of the left lobe. Farmed deer, confined within a fluky habitat, attained the highest group mean pathology score, with dense fibrosis and concomitant atrophy of the left lobe (site A: farmed - 1.8, wild- 0.6; site B: wild - 0.3). Well-defined fibrotic capsules captured and restricted fluke migration beyond the peripheral region of the left lobe of the liver. The presence of live and dead fluke within the fibrotic capsules confirms the inherent ability of fallow deer to resolve infections. This survey has highlighted the susceptibility of fallow deer to liver fluke within an endemic region. Recurrent exposure, as seen in the farmed deer confined within a fluky habitat, appears to strengthen tissue response in terms of gross pathology and may impede the release of fluke eggs from the liver. Low fluke burdens and limited lesions suggest fallow deer have a strong level of resistance to liver fluke. Nevertheless, within this endemic region, fallow deer are widespread and clearly facilitating the liver fluke life cycle. Further research is warranted to ascertain the impact of fallow deer on disease transmission in livestock production when cohabiting the grazing environment.