It pays to follow the leader: Metabolic cost of flight is lower for trailing birds in small groups.

Many bird species commonly aggregate in flocks for reasons ranging from predator defense to navigation. Available evidence suggests that certain types of flocks-the V and echelon formations of large birds-may provide a benefit that reduces the aerodynamic cost of flight, whereas cluster flocks typical of smaller birds may increase flight costs. However, metabolic flight costs have not been directly measured in any of these group flight contexts [Zhang and Lauder, J. Exp. Biol. 226, jeb245617 (2023)]. Here, we measured the energetic benefits of flight in small groups of two or three birds and the requirements for realizing those benefits, using metabolic energy expenditure and flight position measurements from European Starlings flying in a wind tunnel. The starlings continuously varied their relative position during flights but adopted a V formation motif on average, with a modal spanwise and streamwise spacing of [0.81, 0.91] wingspans. As measured via CO2 production, flight costs for follower birds were significantly reduced compared to their individual solo flight benchmarks. However, followers with more positional variability with respect to leaders did less well, even increasing their costs above solo flight. Thus, we directly demonstrate energetic costs and benefits for group flight followers in an experimental context amenable to further investigation of the underlying aerodynamics, wake interactions, and bird characteristics that produce these metabolic effects.

Transmission dynamics and pathogenesis differ between pheasants and partridges infected with clade 2.3.4.4b H5N8 and H5N1 high-pathogenicity avian influenza viruses.

During the UK 2020-2021 epizootic of H5Nx clade 2.3.4.4b high-pathogenicity avian influenza viruses (HPAIVs), high mortality occurred during incursions in commercially farmed common pheasants (Phasianus colchicus). Two pheasant farms, affected separately by H5N8 and H5N1 subtypes, included adjacently housed red-legged partridges (Alectoris rufa), which appeared to be unaffected. Despite extensive ongoing epizootics, H5Nx HPAIV partridge outbreaks were not reported during 2020-2021 and 2021-2022 in the UK, so it is postulated that partridges are more resistant to HPAIV infection than other gamebirds. To assess this, pathogenesis and both intra- and inter-species transmission of UK pheasant-origin H5N8-2021 and H5N1-2021 HPAIVs were investigated. Onward transmission to chickens was also assessed to better understand the risk of spread from gamebirds to other commercial poultry sectors. A lower infectious dose was required to infect pheasants with H5N8-2021 compared to H5N1-2021. However, HPAIV systemic dissemination to multiple organs within pheasants was more rapid following infection with H5N1-2021 than H5N8-2021, with the former attaining generally higher viral RNA levels in tissues. Intraspecies transmission to contact pheasants was successful for both viruses and associated with viral environmental contamination, while interspecies transmission to a first chicken-contact group was also efficient. However, further onward transmission to additional chicken contacts was only achieved with H5N1-2021. Intra-partridge transmission was only successful when high-dose H5N1-2021 was administered, while partridges inoculated with H5N8-2021 failed to shed and transmit, although extensive tissue tropism was observed for both viruses. Mortalities among infected partridges featured a longer incubation period compared to that in pheasants, for both viruses. Therefore, the susceptibility of different gamebird species and pathogenicity outcomes to the ongoing H5Nx clade 2.3.4.4b HPAIVs varies, but pheasants represent a greater likelihood of H5Nx HPAIV introduction into galliforme poultry settings. Consequently, viral maintenance within gamebird populations and risks to poultry species warrant enhanced investigation.

Utilizing citizen science data to rapidly assess changing associations between wild birds and avian influenza outbreaks in poultry.

High pathogenicity avian influenza virus (HPAIV) is a rapidly evolving virus causing significant economic and environmental harm. Wild birds are a key viral reservoir and an important source of viral incursions into animal populations, including poultry. However, we lack a thorough understanding of which species drive incursions and whether this changes over time. We explored associations between the abundances of 152 avian species and outbreaks of highly pathogenic avian influenza (HPAI) in poultry premises across Great Britain between October 2021 and January 2023. Spatial generalized additive models were used, with species abundance distributions sourced from eBird. Associations were investigated at the species-specific level and across species aggregations. During autumn/winter, associations were generally strongest with waterbirds such as ducks and geese; however, we also found significant associations in groups such as non-native gamebirds and rapid change in species-specific associations over time. Our results demonstrate the value of citizen science to rapidly explore wild species as potential facilitators of disease incursions into well-monitored populations, especially in regions where viral surveillance in wild species is limited. This can be a critical step towards prioritizing targeted surveillance that could inform species-specific biosecurity measures; particularly for HPAIV, which has undergone sudden shifts in host range and continues to rapidly evolve.

Antigenic mapping of the hemagglutinin of the H9 subtype influenza A viruses using sera from Japanese quail (Coturnix c. japonica).

IMPORTANCE: Determining the relevant amino acids involved in antigenic drift on the surface protein hemagglutinin (HA) is critical to understand influenza virus evolution and efficient assessment of vaccine strains relative to current circulating strains. We used antigenic cartography to generate an antigenic map of the H9 hemagglutinin (HA) using sera produced in one of the most relevant minor poultry species, Japanese quail. Key antigenic positions were identified and tested to confirm their impact on the antigenic profile. This work provides a better understanding of the antigenic diversity of the H9 HA as it relates to reactivity to quail sera and will facilitate a rational approach for selecting more efficacious vaccines against poultry-origin H9 influenza viruses in minor poultry species.

Validation of Metallothionein Immunohistochemistry as a Highly Sensitive Screening Test for Wilson Disease.

Wilson disease (WD) is a rare autosomal recessive condition with protean clinical manifestations that result from biallelic ATP7B mutations. However, nondestructive tissue tests to be applied clinically to tissue specimens are not widely available to effectively assess patients for possible WD. Previously, we showed that metallothionein (MTH) immunohistochemistry (IHC) has a high sensitivity and specificity for WD diagnosis and, thus, represents a potentially powerful diagnostic tool that can be used in routine histologic sections. This study aimed to validate this finding in a large cohort of bona fide patients with WD and to correlate metallothionein expression with other histologic features. We identified 91 cases of WD, which included 28 needle biopsies and 64 explants from 14 centers worldwide. Histologic features were evaluated, and a histopathological pattern was assigned to each case. All cases were evaluated with Masson trichrome and MTH IHC (clone UC1MT, Abcam) using a previously published technique. Liver tissues from chronic cholestatic diseases (n = 42) were used as controls. The median age of the cohort was 28.5 years. Of the 91 total cases, 83 were positive for MTH immunostain. In the controls, all 42 cases were negative for MTH immunostain. The sensitivity and specificity of MTH immunostain for WD were 91.20% and 100%, respectively. MTH IHC is a highly sensitive and specific cost-effective screening tool for WD. It can be used for patients across age groups, varied histologic patterns, and fibrosis stages. This marker could prove to be a valuable tool in the evaluation of patients with possible WD.

Genome sequences of haemagglutinin cleavage site predict the pathogenicity phenotype of avian influenza virus: statistically validated data for facilitating rapid declarations and reducing reliance on in vivo testing.

Based on the pathogenicity in chickens, most H1-H16 avian influenza viruses (AIV) cause mild diseases, whereas some of the H5 and H7 AI viruses cause severe, systemic disease. The number of basic amino acids in the haemagglutinin (HA) cleavage site of AIV plays a critical role in pathogenicity. As we gain a greater understanding of the molecular mechanisms of pathogenicity, genome sequencing of the HA0 cleavage site has assumed a greater role in assessment of the potential pathogenicity of H5 and H7 viruses. We validated the use of HA cleavage site motif analysis by comparing molecular pathotyping data against experimental in vivo (intravenous pathogenicity index [IVPI] and lethality) data for determination of both low pathogenicity and high pathogenicity AI virus declaration with the goal of expediting pathotype confirmation and further reducing the reliance on in vivo testing. Our data provide statistical support to the continued use of molecular determination of pathotype for AI viruses based on the HA cleavage site sequence in the absence of an in vivo study determination. This approach not only expedites the declaration process of highly pathogenic AIV (HPAIV) but also reduces the need for experimental in vivo testing of H5 and H7 viruses.

Highly pathogenic avian influenza virus H5N1 infection in skua and gulls in the United Kingdom, 2022.

The reemergence of the highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in the United Kingdom in 2021-2022 has caused unprecedented epizootic events in wild birds and poultry. During the summer of 2022, there was a shift in virus transmission dynamics resulting in increased HPAIV infection in seabirds, and consequently, a profound impact on seabird populations. To understand the pathological impact of HPAIV in seabirds, we evaluated the virus antigen distribution and associated pathological changes in the tissues of great skua (Stercorarius skua, n = 8), long-tailed skua (Stercorarius longicaudus, n = 1), European herring gull (Larus argentatus, n = 5), and black-headed gull (Chroicocephalus ridibundus, n = 4), which succumbed to natural infection of HPAIV during the summer of 2022. Cases were collected from Shetland, including Scatness (mainland), No Ness (mainland), Clumlie (mainland), Hermaness (island), Fair Isle (island), Noss (island), and the West Midlands, South East, and South West of England. Grossly, gizzard ulceration was observed in one great skua and pancreatic necrosis was observed in 4 herring gulls, with intralesional viral antigen detected subsequently. Microscopical analysis revealed neuro-, pneumo-, lymphoid-, and cardiomyotropism of HPAIV H5N1, with the most common virus-associated pathological changes being pancreatic and splenic necrosis. Examination of the reproductive tract of the great skua revealed HPAIV-associated oophoritis and salpingitis, and virus replication within the oviductal epithelium. The emergence of HPAIV in seabirds Stercorariidae and Laridae, particularly during summer 2022, has challenged the dogma of HPAIV dynamics, posing a significant threat to wild bird life with potential implications for the reproductive performance of seabirds of conservation importance.

Neuronal SKN-1B modulates nutritional signalling pathways and mitochondrial networks to control satiety.

The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-ß), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.

A case of swine influenza A(H1N2)v in England, November 2023.

Under International Health Regulations from 2005, a human infection caused by a novel influenza A virus variant is considered an event that has potential for high public health impact and is immediately notifiable to the World Health Organisation. We here describe the clinical, epidemiological and virological features of a confirmed human case of swine influenza A(H1N2)v in England detected through community respiratory virus surveillance. Swabbing and contact tracing helped refine public health risk assessment, following this unusual and unexpected finding.

Interspecies Transmission of Swine Influenza A Viruses and Human Seasonal Vaccine-Mediated Protection Investigated in Ferret Model.

We investigated the infection dynamics of 2 influenza A(H1N1) virus isolates from the swine 1A.3.3.2 (pandemic 2009) and 1C (Eurasian, avian-like) lineages. The 1C-lineage virus, A/Pavia/65/2016, although phylogenetically related to swine-origin viruses, was isolated from a human clinical case. This strain infected ferrets, a human influenza model species, and could be transmitted by direct contact and, less efficiently, by airborne exposure. Infecting ferrets and pigs (the natural host) resulted in mild or inapparent clinical signs comparable to those observed with 1A.3.3.2-lineage swine-origin viruses. Both H1N1 viruses could infect pigs and were transmitted to cohoused ferrets. Ferrets vaccinated with a human 2016-17 seasonal influenza vaccine were protected against infection with the antigenically matched 1A pandemic 2009 virus but not against the swine-lineage 1C virus. Our results reaffirm the need for continuous influenza A virus surveillance in pigs and identification of candidate human vaccine viruses.

Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) from the 2021/22 epizootic is highly duck adapted and poorly adapted to chickens.

The 2021/2022 epizootic of high pathogenicity avian influenza (HPAIV) remains one of the largest ever in the UK, being caused by a clade 2.3.4.4b H5N1 HPAIV. This epizootic affected more than 145 poultry premises, most likely through independent incursion from infected wild birds, supported by more than 1700 individual detections of H5N1 from wild bird mortalities. Here an H5N1 HPAIV, representative of this epizootic (H5N1-21), was used to investigate its virulence, pathogenesis and transmission in layer chickens and Pekin ducks, two species of epidemiological importance. We inoculated both avian species with decreasing H5N1-21 doses. The virus was highly infectious in ducks, with high infection levels and accompanying shedding of viral RNA, even in ducks inoculated with the lowest dose, reflecting the strong waterfowl adaptation of the clade 2.3.4.4 HPAIVs. Duck-to-duck transmission was very efficient, coupled with high environmental contamination. H5N1-21 was frequently detected in water sources, serving as likely sources of infection for ducks, but inhalable dust and aerosols represented low transmission risks. In contrast, chickens inoculated with the highest dose exhibited lower rates of infection compared to ducks. There was no evidence for experimental H5N1-21 transmission to any naive chickens, in two stocking density scenarios, coupled with minimal and infrequent contamination being detected in the chicken environment. Systemic viral dissemination to multiple organs reflected the pathogenesis and high mortalities in both species. In summary, the H5N1-21 virus is highly infectious and transmissible in anseriformes, yet comparatively poorly adapted to galliformes, supporting strong host preferences for wild waterfowl. Key environmental matrices were also identified as being important in the epidemiological spread of this virus during the continuing epizootic.

Cystic lesions of the retrorectal space.

Cysts of the retrorectal space comprise a heterogeneous group of rare lesions. Most develop from embryological remnants and include tailgut cysts, dermoid cysts, rectal duplication cysts, anal canal duplication cysts, sacrococcygeal teratomas and anterior meningocoele. Tailgut cyst is the most common cyst of developmental origin, usually presenting as a multilocular cystic mass with mucoid content and lined by multiple epithelial types. Compared with tailgut cysts, rectal duplication cysts display all layers of the large bowel wall including a well-defined muscularis propria. Retrorectal cysts of non-developmental origin are far less common and represent lesions that either infrequently involve the retrorectal space or undergo extensive cystic change. This review provides an overview of the various histological types of cystic lesions of the retrorectal space, divided into cysts of developmental origin and those of non-developmental origin. A practical pathological and multidisciplinary approach to diagnosing these lesions is presented.

Pathological features associated with metastasis in patients with early invasive (pT1) colorectal carcinoma in colorectal polyps.

AIMS: Colorectal carcinoma (CRC) arising in a colorectal polyp with invasion limited to the submucosa is sufficiently treated by complete endoscopic resection alone in many cases. Histological features of the carcinoma including tumour size, vascular invasion and poor tumour differentiation or evidence of de-differentiation, such as tumour budding, are associated with a higher risk for metastasis such that oncological resection is recommended. However, most malignant polyps with these features do not have lymph node metastases at the time of resection, so there is a need for better refinement of the histological risk features. METHODS AND RESULTS: A total of 437 consecutive colorectal polyps with submucosal invasive carcinoma from a single centre, 57 of which had metastatic disease, were supplemented by 30 cases with known metastatic disease from two additional centres. Clinical and histological features of the polyp cancers were reviewed looking for differences between the 87 cancers with metastatic disease and the remaining cases without metastasis. A subgroup of 204 polyps removed intact was also analysed to ensure maximum histological accuracy. CONCLUSIONS: This study confirmed larger invasive tumour size, vascular invasion and poor tumour differentiation as adverse predictive features. Prominent peritumoral desmoplasia and high cytological grade were additional adverse features. A predictive logistic regression model comprised of (i) presence of any form of vascular invasion; (ii) presence of high tumour budding (BD3); (iii) width of invasive tumour component > 8 mm; (iv) depth of invasive tumour > 1.5 mm; and (v) the finding of prominent expansile desmoplasia located within and beyond the deep invasive edge of the carcinoma, showed excellent performance in predicting metastatic disease.

Implications of the Regulation of Endothelial Glycocalyx Breakdown and Reconstitution in Severe Burn Injury.

INTRODUCTION: Effective initial fluid resuscitation is the cornerstone intervention in the setting of severe burn injury. Critically, few major advances in burn resuscitation have been made since the 1970s, and since that time there has been only modest improvement in overall morbidity and mortality. Recently, investigations regarding the dynamic changes of vascular endothelium, and more specifically the vascular endothelial glycocalyx, in the setting of severe burn injury and resuscitation have offered insight into the possibility of more tightly controlling fluid shifts and understanding the consequences thereof during this critical period. METHODS: We conducted a literature search of the PubMed database using the terms "burn", and "glycocalyx" limited to studies published in the English language over the past 10 y. A total of 31 articles were initially identified. Abstracts and full text were manually reviewed to identify suitable articles. Of the identified articles, 10 were deemed relevant and included within this review, along with additional articles necessary to provide background on glycocalyx structure and function as well as principles of burn injury management. RESULTS: Glycocalyx shedding is a process known to occur early in the setting of severe burn injury and resuscitation. The degree of shedding tends to increase with age and severity of injury. Though the role and regulation of this shedding is incompletely understood, it has direct consequences on vascular unction and permeability and likely coagulation as well. CONCLUSIONS: Here in this research review, we examine what is known regarding the dynamic breakdown and reconstitution of the glycocalyx during burn injury and how it may be impacted by fluid resuscitation strategies. We further explore the need to more completely understand this mechanism and the consequences of its manipulation.

Understanding the disease and economic impact of avirulent avian paramyxovirus type 1 (APMV-1) infection in Great Britain.

Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the 'testing to exclude' scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.

Comparative pathogenesis of two genotype VI.2 avian paramyxovirus type-1 viruses (APMV-1) in pheasants, partridges and chickens.

Newcastle disease (ND) is caused by virulent forms of avian paramyxovirus-1 (APMV-1) and is an economically important disease of poultry world-wide. Pigeon paramyxovirus 1 (PPMV-1), a sub-group of APMV-1 is endemic in Columbiformes and can cause infections of poultry. An outbreak of ND in partridges in Scotland, UK, in 2006 (APMV-1/partridge/UK(Scotland)/7575/06) was identified as a class II, genotype VI.2.1.1.2.1, more commonly associated with PPMV-1. It has been hypothesized that game birds may be a route of transmission into commercial poultry settings due to the semi-feral rearing system, which potentially brings them into contact with both wild-birds and poultry species. Therefore, the pathogenesis and transmission of APMV-1/partridge/UK(Scotland)/7575/06 in game birds and chickens was investigated, and compared to a contemporary PPMV-1 isolate, PPMV-1/pigeon/UK/015874/15. Viral shedding and seroconversion profiles demonstrated that pheasants were susceptible to infection with APMV-1/partridge/UK(Scotland)/7575/06 with limited clinical signs observed although they were able to excrete and transmit virus. In contrast, partridges and pheasants showed limited infection with PPMV-1/pigeon/UK/015874/15, causing mild clinical disease. Chickens, however, were productively infected and were able to transmit virus in the absence of clinical signs. From the data, it can be deduced that whilst game birds may play a role in the transmission and epidemiology of genotype VI.2 APMV-1 viruses, the asymptomatic nature of circulation within these species precludes evaluation of natural infection by clinical surveillance. It therefore remains a possibility that genotype VI.2 APMV-1 infection in game birds has the potential for asymptomatic circulation and remains a potential threat to avian production systems.RESEARCH HIGHLIGHTS Demonstration of infection of game birds with Pigeon paramyxovirus-1 (PPMV-1).There are differing dynamics of infection between different game bird species.Differing dynamics of infection between different PPMV-1 isolates and genotypes in game birds and chickens.

In comparison with polypectomy, colorectal resection is associated with improved survival for patients diagnosed with malignant polyps.

AIM: Patients diagnosed with a malignant polyp generally have favourable overall survival (OS) and cancer-specific survival (CSS). However, it is unclear how choice in management for malignant polyps may affect survival. METHODS: Data from the Queensland Oncology Repository was analysed to derive a population wide assessment of the impact of management strategy on OS and CSS for patients diagnosed with malignant polyps. Log-rank testing, Kaplan-Meier and Cox-regression models were performed. Patients were matched using propensity score and Mahalanobis distance matching. RESULTS: A total of 1,646 patients were included with 240 deaths and 52 colorectal cancer related deaths until censor date. Following propensity score and Mahalanobis distance matching of patients undergoing polypectomy alone versus colorectal resection, there was no significant difference in the age groups (<60 years of age or ≥60 years of age), American Society of Anesthesiology score, comorbidity count or Association of ColoProctology of Great Britain and Ireland risk category. However, of note Log-rank testing demonstrated a significant difference in OS (p < 0.001) and CSS (p = 0.0061) between management strategies. Multivariable Cox-regression models in matched and un-matched patient cohorts demonstrated significantly lower hazards of death for OS with resection (p < 0.001). However, CSS was no longer significantly different between management groups in multivariable Cox-regression analysis (p = 0.073). CONCLUSION: Patients who underwent colorectal resection had significantly improved OS and CSS compared with polypectomy alone. Improved OS was furthermore seen on multivariable analysis, and in matched cohorts. Future research should investigate why this unexpected finding may be the case and whether updates to guidelines should be considered.

Management of high and low risk malignant polyps: a population-wide analysis.

AIM: The management of malignant polyps is a treatment dilemma in selecting between polypectomy and colorectal resection. To assist clinicians, guidelines have been developed by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to provide treatment recommendations. METHODS: This study compared management strategy based on the ACPGBI risk categorization for malignant polyps. Univariable and multivariable statistical analysis was undertaken to assess the factors predicting management strategy. A population-wide analysis was performed of 1646 malignant polyps and the factors that predicted their management strategy, from Queensland, Australia, from 2011 to 2019. RESULTS: Overall, 31.55% of patients with very low or low risk disease proceeded to resection. Of those with high or very high risk disease, 36.69% did not proceed to resection. In very low and low risk polyps, age (P = 0.003) and polyp location (P < 0.001) were significantly different between the colorectal resection group and the polypectomy alone group. In those with very high or high risk polyps age (P < 0.001), type of facility (public or private) for the colonoscopy (P = 0.037), right colonic polyps compared to left colonic polyps (P = 0.015) and rectal polyps (P < 0.001) and mismatch repair mutations present (P = 0.027) were predictive of resection in high risk disease using a multivariable model. CONCLUSION: Over 30% of patients with very low and low risk malignant polyps proceeded to resection, against the advice of guidelines. Furthermore, over 35% of patients with very high or high risk malignant polyps did not proceed to resection. Education strategies may improve management decision choices. Furthermore, improvements in data collation will improve the understanding of management choices in the future.

Crystal Structure of a Transcribing RNA Polymerase II Complex Reveals a Complete Transcription Bubble.

Notwithstanding numerous published structures of RNA Polymerase II (Pol II), structural details of Pol II engaging a complete nucleic acid scaffold have been lacking. Here, we report the structures of TFIIF-stabilized transcribing Pol II complexes, revealing the upstream duplex and full transcription bubble. The upstream duplex lies over a wedge-shaped loop from Rpb2 that engages its minor groove, providing part of the structural framework for DNA tracking during elongation. At the upstream transcription bubble fork, rudder and fork loop 1 residues spatially coordinate strand annealing and the nascent RNA transcript. At the downstream fork, a network of Pol II interactions with the non-template strand forms a rigid domain with the trigger loop (TL), allowing visualization of its open state. Overall, our observations suggest that "open/closed" conformational transitions of the TL may be linked to interactions with the non-template strand, possibly in a synchronized ratcheting manner conducive to polymerase translocation.

High incidence of inflammatory bowel disease in Northern Australia: a prospective community population-based Australian incidence study in the Mackay-Isaac-Whitsunday region.

BACKGROUND AND AIMS: To determine the incidence of inflammatory bowel disease (IBD) in the Mackay-Isaac-Whitsunday region in Northern Queensland (-21.14° S) and to allow a comparison with Southern Australian and New Zealand data (Geelong, Australia -38.14° S; Tasmania -41.43° S and -42.88° S (Launceston and Hobart) and Canterbury, New Zealand -43.46 °S). DESIGN: A prospective observational community population-based IBD study was conducted between 1 June 2017 and 31 May 2018. OUTCOME MEASURES: Primary includes the crude annual incidence rate of IBD, Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease-unclassified (IBDU), while secondary includes disease phenotype and behaviour. RESULTS: Fifty-six new cases of IBD were identified. Twenty-three were CD, 30 were UC and 3 were IBDU. The crude annual incidence rate per 100 000 for IBD, CD, UC and IBDU were 32.2 (95% confidence interval (CI): 24.78-41.84), 13.23 (95% CI: 8.79-19.90), 17.25 (95% CI: 12.06-24.67) and 1.73 (95% CI: 0.56-5.35). When directly age-standardised to the World Health Organisation Standard Population Distribution, the overall CD, UC and IBDU incidence were 13.19, 17.34 and 1.85 per 100 000, with an overall age-standardised IBD incidence of 32.38. CONCLUSIONS: This is the first study to define the incidence of IBD in a Northern Australian cohort and to allow a comparison between North and Southern Australia. The IBD crude is the highest reported in Australia. Like others, we found a high and low incidence of upper gastrointestinal Crohn's disease and complicated disease at diagnosis respectively, likely reflective of the increased availability and early uptake of endoscopic procedures.