War and disaster are forcing a major rethink around mass casualty management.

Mass casualty events (MASCAL) do not follow the same rules as typical major incidents. In the West at least, the latter often occur in stable, networked trauma systems, whereas MASCAL are characterised by overwhelming numbers of patients, compounded by protracted scene and transport times, decompensated response systems and significant disruption to infrastructure, command and control.This paper describes the 8Ds approach being taken by the UK Defence Medical Services and the North Atlantic Treaty Organization Emergency Medicine Panel framework to approach MASCAL. The eight domains were derived from literature about management of casualties in the World Wars, and also from approaches taken by civilian health systems as they struggle to manage increasing demand. They are: distribute; decompress; delay; delegate; deliver faster and deliver better; dynamic levels of care; and de-escalate These domains will allow a structured approach to research and innovate around MASCAL, informing better guidelines for their management.

The current status and outlook for insecticide, acaricide and anthelmintic resistances across the Australian ruminant livestock industries: assessing the threat these resistances pose to the livestock sector.

The Australian ruminant livestock industries are faced with the need to control parasitic infectious diseases that can seriously impact the health of animals. However, increasing levels of resistance to insecticides, anthelmintics and acaricides are substantially reducing the ability to control some of these parasites. Here we review the current situation with regard to chemical resistances in parasites across the various sectors of the Australian ruminant livestock industries and assess the level of threat that these resistances pose to the sustainability of these sectors in the short to long terms. We also look at the extent to which testing for resistance occurs across the various industry sectors, and hence how well-informed these sectors are of the extent of chemical resistance. We examine on-farm management practices, breeding of parasite-resistant animals, and non-chemical therapeutics that may act as short to long term means to reduce the current reliance on chemicals for parasite control. Finally, we look at the balance between the prevalence and magnitude of current resistances and the availability and adoption rates of management, breeding and therapeutic alternatives in order to assess the parasite control outlook for the various industry sectors.

Resonant X-ray photoelectron spectroscopy: identification of atomic contributions to valence states.

Valence electronic structure is crucial for understanding and predicting reactivity. Valence non-resonant X-ray photoelectron spectroscopy (NRXPS) provides a direct method for probing the overall valence electronic structure. However, it is often difficult to separate the varying contributions to NRXPS; for example, contributions of solutes in solvents or functional groups in complex molecules. In this work we show that valence resonant X-ray photoelectron spectroscopy (RXPS) is a vital tool for obtaining atomic contributions to valence states. We combine RXPS with NRXPS and density functional theory calculations to demonstrate the validity of using RXPS to identify atomic contributions for a range of solutes (both neutral and ionic) and solvents (both molecular solvents and ionic liquids). Furthermore, the one-electron picture of RXPS holds for all of the closed shell molecules/ions studied, although the situation for an open-shell metal complex is more complicated. The factors needed to obtain a strong RXPS signal are investigated in order to predict the types of systems RXPS will work best for; a balance of element electronegativity and bonding type is found to be important. Additionally, the dependence of RXPS spectra on both varying solvation environment and varying local-covalent bonding is probed. We find that RXPS is a promising fingerprint method for identifying species in solution, due to the spectral shape having a strong dependence on local-covalency but a weak dependence on the solvation environment.

Racial and ethnic disparities in COVID-19 disease incidence independent of comorbidities, among people with HIV in the US.

OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

Respuesta inmune innata y adaptativa frente al SARS-CoV-2. Diagnóstico: PCR y serología / Innate and adaptive immune response against SARS-CoV-2. Diagnosis: PCR and serology

SARS-CoV-2 infection in the people has been characterized by great variability in the clinical manifestations, ranging from an asymptomatic infection in some individuals to a fatal disease in others. Recently, the importance of human genetics in determining clinical response has been highlighted. Within this context there are patients who don't become infected despite viral exposure and others who, being young without comorbidities, develop a severe disease. On the other hand, it's under constant investigation whether the presence of a concomitant primary or secondary immunodeficiency determines a different clinical course. (AU)

Tratamiento Covid-19 / Covid-19 treatment

The main treatment for patients with severe Covid-19 is to maintain adequate ventilatory support and monitor the possible progression of the disease. Therapeutic strategies such as High Flow Nasal Cannula, awake prone position, antithrombotic prophylaxis and the use of dexamethasone. There have improved the probability of not presenting complications and not requiring invasive mechanical ventilation. The use of convalescent plasma is still under investigation and is currently only recommended in clinical trials. Finding antivirals that allow treating the infection and clinically improving patients has led to mounting studies with different methodologies, and currently there are specific and limited indications for their routine use, as in the case of Remdesivir, which has been approved by the FDA as emergency treatment in severe cases. Immunomodulatory treatments are still under study. An example of this is Tocilizumab and Anakinra, which have shown promising results for the management of seriously ill patients. It should be noted that there are many therapies that are being tested and that every day the information about the results obtained is changing. (AU)

Anemia risk factors among people living with HIV across the United States in the current treatment era: a clinical cohort study.

BACKGROUND: Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking. METHODS: Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site. RESULTS: This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR. CONCLUSION: Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

Imputation of Assay Bioactivity Data Using Deep Learning.

We describe a novel deep learning neural network method and its application to impute assay pIC50 values. Unlike conventional machine learning approaches, this method is trained on sparse bioactivity data as input, typical of that found in public and commercial databases, enabling it to learn directly from correlations between activities measured in different assays. In two case studies on public domain data sets we show that the neural network method outperforms traditional quantitative structure-activity relationship (QSAR) models and other leading approaches. Furthermore, by focusing on only the most confident predictions the accuracy is increased to R2 > 0.9 using our method, as compared to R2 = 0.44 when reporting all predictions.

Inequalities in health? An update on the effect of social deprivation for patients with breast cancer in South East Wales.

BACKGROUND: Breast cancer, historically a disease of more affluent women, has increased in incidence for women from areas of greater social deprivation, yet prognosis is worse for these women. This study identifies differences in presentation, treatment and prognostic factors between the socioeconomic groups. METHODS: Patient data obtained from the prospectively maintained Welsh national Cancer Network Information System Cymru, for an 11-year period, were categorised according to Welsh Index of Multiple Deprivation quintiles. Quintiles were compared for differences in variables relating to patient characteristics, detection of cancer, tumour biology and treatment. RESULTS: 1570 patients were included. Analysis showed that in the more socially deprived quintiles, there are proportionally fewer women being diagnosed through the NHS breast cancer screening programme and as a consequence greater numbers of women from poorer areas being diagnosed outwith the screening age parameters. Screen detection is strongly associated with better prognosis in terms of Nottingham Prognostic Index. Similarly, increasing levels of social deprivation are associated with higher incidence of oestrogen receptor negative and triple negative tumours, both features associated with a shorter disease free and overall survival. Other variables of tumour biology, rates and type of surgical and adjuvant treatment were similar across social deprivation quintiles. CONCLUSION: There is a trend of reduced early detection of breast cancer in South East Wales in those patients living in areas of higher social deprivation. Given that there is equity in access to treatment within NHS, which is free for patients at the point of care, further study is warranted to address this existing disparity. Population cancer surveillance will need to inform both public health and NHS service responses, to continue to achieve improvements. Health trends may yet alter depending on current and future shifts in governmental health policy.

Nursing and medical contribution to Defence Healthcare Engagement: initial experiences of the UK Defence Medical Services.

INTRODUCTION: The WHO Constitution enshrines '…the highest attainable standard of health as a fundamental right of every human being.' Strengthening delivery of health services confers benefits to individuals, families and communities, and can improve national and regional stability and security. In attempting to build international healthcare capability, UK Defence Medical Services (DMS) assets can contribute to the development of healthcare within overseas nations in a process that is known as Defence Healthcare Engagement (DHE). METHODS: In the first bespoke DMS DHE tasking, a team of 12 DMS nurses and doctors deployed to a 1000-bedded urban hospital in a partner nation and worked alongside indigenous healthcare workers (doctors, nurses and paramedical staff) during April and May 2016. The DMS nurses focused on nursing hygiene skills by demonstrations of best practice and DMS care standards, clinical leadership and female empowerment. A Quality Improvement Programme was initiated that centred on hand hygiene (HH) compliance before and after patient contact, and the introduction of peripheral cannula care and surveillance. RESULTS: After a brief induction on the ward, it was apparent that compliance with HH was poor. Peripheral cannulas were secured with adhesive zinc oxide tape and no active surveillance process (such as venous infusion phlebitis (VIP) scoring) was in place. After intensive education and training, initial week-long audits were undertaken and repeated after a further 2 weeks of training and coworking. In the second audit cycle, HH compliance had increased to 69% and VIP scoring compliance to 99%. In the final audit cycle, it was noted that nursing compliance with HH (75/98: 77%) was significantly higher than the doctors' HH compliance (76/200: 38%); p<0.0001. CONCLUSIONS: DHE is a long-term collaborative process based on the establishment and development of comprehensive relationships that can help transform indigenous healthcare services towards patient-centred systems with a focus on safety and quality of care. Short deployments to allow clinical immersion of UK healthcare workers within indigenous teams can have an immediate impact. Coworking is a powerful method of demonstrating standards of care and empowering staff to institute transformative change. A multidisciplinary group of Quality Improvement Champions has been identified and a Hospital Oversight Committee established, which will offer the prospect of longer term sustainability and development.

Simulated Soil Organic Carbon Response to Tillage, Yield, and Climate Change in the Southeastern Coastal Plains.

Intensive tillage, low-residue crops, and a warm, humid climate have contributed to soil organic carbon (SOC) loss in the southeastern Coastal Plains region. Conservation (CnT) tillage and winter cover cropping are current management practices to rebuild SOC; however, there is sparse long-term field data showing how these management practices perform under variable climate conditions. The objectives of this study were to use CQESTR, a process-based C model, to simulate SOC in the top 15 cm of a loamy sand soil (fine-loamy, kaolinitic, thermic Typic Kandiudult) under conventional (CvT) or CnT tillage to elucidate the impact of projected climate change and crop yields on SOC relative to management and recommend the best agriculture management to increase SOC. Conservation tillage was predicted to increase SOC by 0.10 to 0.64 Mg C ha for six of eight crop rotations compared with CvT by 2033. The addition of a winter crop [rye ( L.) or winter wheat ( L.)] to a corn ( L.)-cotton ( L.) or corn-soybean [ (L.) Merr.] rotation increased SOC by 1.47 to 2.55 Mg C ha. A continued increase in crop yields following historical trends could increase SOC by 0.28 Mg C ha, whereas climate change is unlikely to have a significant impact on SOC except in the corn-cotton or corn-soybean rotations where SOC decreased up to 0.15 Mg C ha by 2033. The adoption of CnT and cover crop management with high-residue-producing corn will likely increase SOC accretion in loamy sand soils. Simulation results indicate that soil C saturation may be reached in high-residue rotations, and increasing SOC deeper in the soil profile will be required for long-term SOC accretion beyond 2030.

Who's challenging who training for staff empathy towards adults with challenging behaviour: cluster randomised controlled trial.

BACKGROUND: One in five adults with intellectual disabilities (ID) known to services display challenging behaviours (CBs), and these individuals are at risk for restrictive practices and poor care. Staff attitudes may contribute to the development and/or maintenance of CBs. We investigated the effectiveness of co-produced Who's Challenging Who? training delivered by people with ID to staff. METHOD: This study involved a cluster randomised controlled trial (RCT) of Who's Challenging Who? training with follow-up at six and 20 weeks post-randomisation. PARTICIPANTS: two staff from each of 118 residential care settings for adults with ID at least one of whom displayed aggressive CB. PRIMARY OUTCOME: Self-reported Staff Empathy for people with Challenging Behaviour Questionnaire. ANALYSIS: intention to treat of all randomised settings. ISCRTN registration: ISRCTN53763600. RESULTS: 118 residential settings (including 236 staff) were randomised to either receive training (59 settings) or to receive training after a delay (59 settings). The primary analysis included data from 121 staff in 76 settings (51% of staff, 64% of settings). The adjusted mean difference on the transformed (cubed) Staff Empathy for people with Challenging Behaviour Questionnaire score at the primary end point was 1073.2 (95% CI: -938.1 to 3084.5, P = 0.296) in favour of the intervention group (effect size Cohen's d = .19). CONCLUSIONS: This is the first large-scale RCT of a co-produced training course delivered by people with ID. Findings indicated a small positive (but statistically non-significant) effect on increased staff empathy at 20 weeks, and small to moderate effects for staff reported secondary outcomes in favour of the intervention group.

Performance, egg quality, and liver lipid reserves of free-range laying hens naturally infected with Ascaridia galli.

A study was conducted to determine the performance, egg quality, and liver lipid reserves of laying hens exposed to ranges contaminated with Ascaridia galli. Sixteen-week-old Lohmann Brown laying hens (n = 200) were divided into 4 treatments with 5 replicates containing 10 hens per pen. Hens of treatment 1 [negative control (NC)] ranged on a decontaminated area, and hens of treatments 2 (low infection) and 3 (medium infection) ranged on areas previously contaminated by hens artificially infected with 250 and 1,000 embryonated A. galli eggs, respectively. The hens of treatment 4 [positive control (PC)] ranged on areas previously contaminated by hens artificially infected with 2,500 embryonated A. galli eggs, and in addition these hens were orally inoculated with 1,000 embryonated eggs. Results indicated that hens of the medium infection group had a higher number of intestinal A. galli worms and A. galli eggs in the coprodeum excreta (43.9 ± 4.0 and 3,437 ± 459 eggs/g) compared to hens of the low infection group (23.8 ± 4.0 and 1,820 ± 450 eggs/g) (P < 0.01) and similar worm counts to PC hens (34.4 ± 4.0 and 2,918 ± 474) (P > 0.05). Egg production, egg mass, feed intake, and feed conversion ratio (FCR) were not affected by A. galli infection (P > 0.05). Egg quality parameters (egg weight, shell reflectivity, shell weight, shell thickness, shell percentage, shell breaking strength, deformation, albumen height, Haugh unit, and yolk score) were not affected by A. galli infection (P > 0.05). Highly infected hens had lower liver lipid content (2.72 ± 0.51 g) compared to uninfected hens (4.46 ± 0.58 g, P < 0.01). The results indicate that exposure to ranges contaminated with A. galli resulted in infection of the ranging hens, but this did not affect egg production or egg quality. Infection with A. galli lowered the liver lipid reserves of the host significantly, suggesting infected hens use more energy reserves for maintenance and production.

Temporal and geospatial trends of pediatric cancer incidence in Nebraska over a 24-year period.

BACKGROUND: Data from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009-2013. Further investigation could help understand these patterns. METHODS: This retrospective cohort study investigated pediatric cancer (0-19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990-2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, location-allocation analysis (LAA) was performed to identify a site for the placement of a medical center to best accommodate rural pediatric cancer cases. RESULTS: The AAR of pediatric cancers was 173.3 per 1,000,000 in Nebraska compared to 167.1 per 1,000,000 in SEER. The AAR for lymphoma was significantly higher in Nebraska (28.1 vs. 24.6 per 1,000,000; p = 0.009). For the 15-19 age group, the AAR for the 3 most common pediatric cancers were higher in Nebraska (p < 0.05). Twenty-three counties located >2 h driving distance to care facilities showed at least a 10% higher incidence than the overall state AAR. GIS mapping identified a second potential treatment site that would alleviate this geographic burden. CONCLUSIONS: Regional differences within Nebraska present a challenge for rural populations. Novel use of GIS mapping to highlight regional differences and identify solutions for access to care issues could be used by similar states.

The outcome of patients in traumatic cardiac arrest presenting to deployed military medical treatment facilities: data from the UK Joint Theatre Trauma Registry.

BACKGROUND: The UK military was continuously engaged in armed conflict in Iraq and Afghanistan between 2003 and 2014, resulting in 629 UK fatalities. Traumatic cardiac arrest (TCA) is a precursor to traumatic death, but data on military outcomes are limited. In order to better inform military treatment protocols, the aim of this study was to define the epidemiology of TCA in the military population with a particular focus on survival rates and injury patterns. METHODS: A retrospective database analysis of the UK Joint Theatre Trauma Registry was undertaken. Patients who were transported to a UK deployed hospital between 2003 and 2014 and suffered TCA were included. Those patients injured by asphyxiation, electrocution, burns without other significant trauma and drowning were excluded. Data included mechanism of injury, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) for each body region and survival to deployed (Role 3) field hospital discharge. RESULTS: 424 TCA patients were identified during the study period; median age was 23 years, with a median ISS of 45. The most common mechanism of injury was explosive (55.7%), followed by gunshot wound (38.9%), road traffic collision (3.5%), crush (1.7%) and fall (0.2%). 45 patients (10.6% (95% CI 8.0% to 13.9%)) survived to deployed (Role 3) hospital discharge. The most prevalent body region with a severe to maximum AIS injury was the head, followed by the lower limbs, thorax and abdomen. Haemorrhage secondary to abdominal and lower limb injury was associated with survival; traumatic brain injury was associated with death. CONCLUSIONS: This study has shown that short-term survival from TCA in a military population is 10.6%. With appropriate and aggressive early management, although unlikely, survival is still potentially possible in military patients who suffer traumatic cardiac arrest.

Effect of an artificial Ascaridia galli infection on egg production, immune response, and liver lipid reserve of free-range laying hens.

This study was conducted to determine the effect of Ascaridia galli infection on free-range laying hens. Lohmann Brown laying hens (n = 200) at 17 wk of age were allocated to 4 treatment groups (n = 50 per group), each with 5 replicate pens of 10 hens. Hens in 3 treatment groups were orally inoculated with different doses of embryonated A. galli eggs: low (250 eggs), medium (1,000 eggs), and high (2,500 eggs) levels, whereas hens of the control group were not infected. Infection levels were monitored using excreta egg counts and mature A. galli worm counts in the intestine. Anti A. galli antibody titers (IgY) in the serum were measured prior to infection, and at 6, 11, 15, and 20 wk post infection (PI) and in egg yolk at 11 and 20 wk PI. Parameters evaluated included feed intake, egg production, egg weight, egg mass, FCR, liver weight, liver fat, and intra epithelial immune cell infiltration. The results showed no difference in feed intake, body weight, or FCR among any treatment groups (P > 0.05). Egg production was lower in the low infection group compared to other groups at 20 wk of age (P < 0.01). Serum IgY was higher in the infected groups' hens at 20 wk PI compared to control group hens (P < 0.01). Yolk IgY increased significantly over time and was higher in infected hens compared to hens of the control group at 11 and 20 wk PI (P < 0.001). No differences were observed in liver lipid content or intraepithelial lymphocytes infiltration among treatment groups. Ascaridia galli eggs in the coprodeum content and adult A. galli worm count were higher in infected hens compared to hens of the control group (P < 0.01). In conclusion, the effects of artificial infection with A. galli on the parameters investigated were minor, and egg yolk antibody may be a more reliable indicator of A. galli infection than serum antibody or excreta egg count.

The impact of ionic liquids on the coordination of anions with solvatochromic copper complexes.

Solvatochromic transition metal (TM)-complexes with weakly associating counter-anions are often used to evaluate traditional neutral solvent and anion coordination ability. However, when employed in ionic liquids (IL) many of the common assumptions made are no longer reliable. This study investigates the coordinating ability of weakly coordinating IL anions in traditional solvents and within IL solvents employing a range of solvatochromic copper complexes. Complexes of the form [Cu(acac)(tmen)][X] (acac = acetylacetonate, tmen = tetramethylethylenediamine) where [X]- = [ClO4]-, Cl-, [NO3]-, [SCN]-, [OTf]-, [NTf2]- and [PF6]- have been synthesised and characterised both experimentally and computationally. ILs based on these anions and imidazolium and pyrrolidinium cations, some of which are functionalised with hydroxyl and nitrile groups, have been examined. IL-anion coordination has been investigated and compared to typical weakly coordinating anions. We have found there is potential for competition at the Cu-centre and cases of anions traditionally assigned as weakly associating that demonstrate a stronger than expected level of coordinating ability within ILs. [Cu(acac)(tmen)][PF6] is shown to contain the least coordinating anion and is established as the most sensitive probe studied here. Using this probe, the donor numbers (DNs) of ILs have been determined. Relative donor ability is further confirmed based on the UV-Vis of a neutral complex, [Cu(sacsac)2] (sacsac = dithioacetylacetone), and DNs evaluated via23Na NMR spectroscopy. We demonstrate that ILs can span a wide donor range, similar in breadth to conventional solvents.

Bacteroides are associated with GALT iNKT cell function and reduction of microbial translocation in HIV-1 infection.

Invariant natural killer T (iNKT) cells are innate-like T cells that respond to lipid antigens presented by CD1d. These immunoregulatory cells have the capacity for rapid cytokine release after antigen recognition and are essential for the activation of multiple arms of the immune response. HIV-1 infection is associated with iNKT cell depletion in the peripheral blood; however, their role in the gastrointestinal-associated lymphoid tissue (GALT) is less well studied. Our results show that iNKT cells are found at a higher frequency in GALT compared with blood, particularly in HIV-1 elite controllers. The capacity of iNKT cells to produce interleukin-4 (IL-4) and IL-10 in the GALT was associated with less immune activation and lower markers of microbial translocation, whereas regulatory T cell frequency showed positive associations with immune activation. We hypothesized that the composition of the microbiota would influence iNKT cell frequency and function. We found positive associations between the abundance of several Bacteroides species and iNKT cell frequency and their capacity to produce IL-4 in the GALT but not in the blood. Overall, our results are consistent with the hypothesis that GALT iNKT cells, influenced by certain bacterial species, may have a key role in regulating immune activation in HIV-1 infection.

Pathogenicity, tissue distribution, shedding and environmental detection of two strains of IBDV following infection of chickens at 0 and 14 days of age.

Infectious bursal disease virus (IBDV) is endemic to most poultry-producing countries worldwide. Immunosuppressive classical and variant IBDV strains endemic to Australia are genetically distinct from other international strains. We report the results of infection experiments with Australian classical strain 06/95 and variant strain 02/95 in SPF chickens. We tested the effects of strain and age of infection on bursal atrophy, viral RNA (vRNA) load in bursa of Fabricius (bursa), spleen, thymus, caecal tonsils, faeces, litter and exhaust dust as determined by real-time reverse transcriptase polymerase chain reaction. The two IBDV strains did not differ in the degree of bursal atrophy induced, lymphoid organ distribution and faecal shedding but variant strain 02/95 induced a greater antibody response to the infection than classical strain 06/95 which was associated with a more rapid decline in IBDV vRNA genome copy number (VCN) in lymphoid organs and faeces. Infection at 14 days of age induced greater bursal atrophy and higher vRNA copy number in lymphoid tissues than infection on the day of hatching, indicating true age susceptibility independent of maternal antibody (Mab) status. The direction of the association between rankings for IBDV vRNA load in bursa and relative bursal weight changed from positive at 3 and 6 days post-infection to negative at 28 days post-infection. Intra-tracheal administration of dust collected from chickens infected with IBDV resulted in successful transmission of IBDV. IBDV vRNA was detected successfully at high levels in the environmental litter and dust samples.

Predominance of weakly cytotoxic, T-betLowEomesNeg CD8+ T-cells in human gastrointestinal mucosa: implications for HIV infection.

The gastrointestinal mucosa is an important site of HIV acquisition, viral replication, and pathogenesis. Immune cells in mucosal tissues frequently differ in phenotype and function from their non-mucosal counterparts. Although perforin-mediated cytotoxicity as measured in blood is a recognized correlate of HIV immune control, its role in gastrointestinal tissues is unknown. We sought to elucidate the cytotoxic features of rectal mucosal CD8+ T-cells in HIV infected and uninfected subjects. Perforin expression and lytic capacity were significantly reduced in rectal CD8+ T-cells compared with their blood counterparts, regardless of HIV clinical status; granzyme B (GrzB) was reduced to a lesser extent. Mucosal perforin and GrzB expression were higher in participants not on antiretroviral therapy compared with those on therapy and controls. Reduction in perforin and GrzB was not explained by differences in memory/effector subsets. Expression of T-bet and Eomesodermin was significantly lower in gut CD8+ T-cells compared with blood, and in vitro neutralization of TGF-ß partially restored perforin expression in gut CD8+ T-cells. These findings suggest that rectal CD8+ T-cells are primarily non-cytotoxic, and phenotypically shaped by the tissue microenvironment. Further elucidation of rectal immune responses to HIV will inform the development of vaccines and immunotherapies targeted to mucosal tissues.