HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation.

A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago1,2. The individual-who is known as the 'Berlin patient'-underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin's lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression.

Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study.

BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Exploration into the Needs and Requirements of the Remote Driver When Teleoperating the 5G-Enabled Level 4 Automated Vehicle in the Real World-A Case Study of 5G Connected and Automated Logistics.

Connected and automated vehicles have the potential to deliver significant environmental, safety, economic and social benefits. The key advancement for automated vehicles with higher levels of automation (SAE Level 4 and over) is fail-operational. One possible solution for the failsafe mode of automated vehicles is a 5G-enabled teleoperation system controlled by remote drivers. However, knowledge is missing regarding understanding of the human-machine interaction in teleoperation from the perspective of remote drivers. To address this research gap, this study qualitatively investigated the acceptance, attitudes, needs and requirements of remote drivers when teleoperating a 5G-enabled Level 4 automated vehicle (5G L4 AV) in the real world. The results showed that remote drivers are positive towards the 5G L4 AV. They would like to constantly monitor the driving when they are not controlling the vehicle remotely. Improving their field of vision for driving and enhancing the perception of physical motion feedback are the two key supports required by remote drivers in 5G L4 AVs. The knowledge gained in this study provides new insights into facilitating the design and development of safe, effective and user-friendly teleoperation systems in vehicle automation.

Observational cohort study of rilpivirine (RPV) utilization in Europe.

INTRODUCTION: Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. METHODS: Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann-Whitney U test and Chi-square test. A logistic regression model was used to compare participants' characteristics by treatment group. Kaplan-Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). RESULTS: 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3-5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001). CONCLUSION: Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS).

Qualitative Examination of Cooperative-Intelligent Transportation Systems in Cities to Facilitate Large-Scale Future Deployment.

The rate of urbanization in Europe is increasing rapidly. Traffic congestion has become one of the biggest challenges for cities. Additionally, thousands of people die each year in accidents on European roads. In addition, road transport is one of the biggest reasons for the increase in air pollution and greenhouse gases in Europe. To solve these problems, cooperative intelligent transport systems (C-ITS) have accelerated in Europe, after more than ten years of research and development. The European Commission has carried out significant work in this field in recent years and has prepared a strategy document for the deployment of C-ITS services in Europe. The Commission considers that C-ITS have significant potential in reducing the negative effects of road traffic and expects these systems to deploy rapidly in European cities. However, in order to achieve this, it is imperative to clearly identify the needs of cities in implementing and managing these systems, the extent to which these systems will respond to different mobility problems of the cities, and the important barriers to widespread deployment. This study focused on qualitatively examining the C-ITS deployment from the stakeholder perspective. The knowledge generated is useful to facilitate the large-scale future deployment of C-ITS.

Opposing associations of depression with sexual behaviour: implications for epidemiological investigation among gay, bisexual and other men who have sex with men.

OBJECTIVE: The aim of this report is to investigate the nature of the relationship between depression and condomless sex (CLS) among gay, bisexual and other men who have sex with men (GBMSM). METHODS: Data are from the Antiretrovirals, Sexual Transmission Risk and Attitude (ASTRA) study of people living with HIV and attending one of eight HIV outpatient clinics in England (2011-2012) and the Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study of HIV-negative/unknown status individuals attending one of 20 genitourinary medicine clinics in England (2013-2014). This analysis included GBMSM only. For each study, the prevalence of depressive symptoms (Patient Health Questionnaire-9 score ≥10) was presented according to three categories of sex in the past 3 months (considering anal/vaginal sex with men/women and anal sex with men in separate definitions): (1) no sex, (2) condom-protected sex only and (3) CLS. Multinomial logistic regression with 'condom-protected sex only' as the reference group was used to adjust for age and (for ASTRA participants) time since HIV diagnosis. RESULTS: There were opposing associations of depression with recent sexual behaviour: the prevalence of depression was higher among those who reported no sex and those who reported CLS, compared with those who reported condom-protected sex only. Among the 2170 HIV-positive GBMSM in ASTRA, considering anal/vaginal sex with men/women, the prevalence of depressive symptoms was 32%, 20% and 28%, respectively, among men reporting no sex (n=783), condom-protected sex only (n=551) and CLS (n=836) (global p<0.001). Among the 1477 HIV-negative GBMSM in AURAH, the prevalence of depressive symptoms was 12%, 8% and 13%, respectively, for no sex (n=137), condom-protected sex only (n=487) and CLS (n=853) (global p=0.017). Patterns were similar after adjustment and when only considering anal sex between men. CONCLUSIONS: Depression may be linked both to lack of sexual activity and to sexual risk taking. When investigating associations between depression and CLS, it is important to separate out individuals reporting condom-protected sex only from those reporting no sex.

A Highly Tailored Text and Voice Messaging Intervention to Improve Medication Adherence in Patients With Either or Both Hypertension and Type 2 Diabetes in a UK Primary Care Setting: Feasibility Randomized Controlled Trial of Clinical Effectiveness.

BACKGROUND: The efficacy of a highly tailored digital intervention to support medication adherence and feasibility to support clinical effectiveness as an adjunct to the primary care setting has not been evaluated. OBJECTIVE: This trial aimed to assess the behavioral efficacy of a highly tailored digital intervention to support medication adherence and to evaluate the feasibility of its clinical effectiveness, in patients with either or both hypertension and type 2 diabetes. We also examined quality of life and mechanisms of behavior change. Intervention fidelity, engagement, and satisfaction were also explored. METHODS: This was a multicenter, individually randomized controlled trial of 2 parallel groups: an intervention group that received a highly tailored text message and interactive voice response intervention for 12 weeks, and a control group that received usual care. Medication adherence was measured using self-reports and assessor-blinded practice records of a repeat prescription. Systolic blood pressure and glucose levels were assessed by nurses blinded to group allocation during practice visits at 3 months follow-up. Questionnaires obtained data to assess intervention mechanisms of action and satisfaction and digital log files captured data to evaluate fidelity and engagement. RESULTS: A total of 135 nonadherent patients (62/135, 46% female; 122/135, 90.3%; aged above 50 years) were randomly allocated in the intervention (n=79) or in the control group (n=56); of whom 13% (18/135) were lost at follow-up. Medication adherence was significantly improved in the intervention group compared with the control group (t116=2.27; P=.02, 2-tailed). Systolic blood pressure was 0.6 mmHg (95% CI -7.423 to 6.301), and hemoglobin A1c was 4.5 mmol/mol (95% CI -13.099 to 4.710) lower in the intervention group compared with the control group. Changes in intentional nonadherence and nonintentional nonadherence explained the improvements in medication adherence in the intervention group (beta=.074, SE=0.464; P=.04), but not in the control group (beta=.00, SE 1.35; P=.37). The intervention had 100% fidelity, a median of 12 days of engagement, and 76% overall satisfaction. CONCLUSIONS: Our trial is the first that has been conducted in the United Kingdom and showed that among nonadherent patients with either or both hypertension and type 2 diabetes, a highly tailored digital intervention was effective at improving treatment adherence and feasible to obtain clinically meaningful outcomes. Changes in intentional and nonintentional nonadherence predicted the improvements in medication adherence. The intervention had high fidelity, engagement, and satisfaction. Future research using a rigorous design is needed to evaluate the clinical effectiveness and cost-effectiveness of the intervention in primary care. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 10668149; http://www.controlled-trials.com/ISRCTN10668149.

Review of a medical illustration department's data processing system to confirm general data protection regulation (GDPR) compliance.

This article reviews the clinical photography and video data processing and storage arrangements of the Medical Illustration Department (MID) at the Queen Elizabeth Hospital Birmingham National Health Service (NHS) Foundation Trust (QEHB), part of the University Hospitals Birmingham (UHB) NHS Foundation Trust umbrella group. This review suggests that the department's current workflow and technical processing solution satisfies the requirements of the general data protection regulation (GDPR). At the time of writing, there were no additional financial costs or technical skills required for implementing GDPR regulations but this could change in future data processing systems. There are significant potential costs for non-compliance with GDPR. Brexit is unlikely to have any effect on complying with GDPR requirements. The GDPR gives the public the right to access information and be informed of how and why it is processed. It is recommended that improved administrative processing capability to accommodate this requirement should be included in future data processing designs. At the QEHB informed consent for use of photographs and videos is currently adequate to satisfy the common law of confidence.

Diffuse White Matter Signal Abnormalities on Magnetic Resonance Imaging Are Associated With Human Immunodeficiency Virus Type 1 Viral Escape in the Central Nervous System Among Patients With Neurological Symptoms.

Background: Human immunodeficiency virus type 1 (HIV-1) can replicate independently in extravascular compartments such as the central nervous system, resulting in either cerebrospinal fluid (CSF) discordance (viral load [VL] in CSF 0.5 log10 copies HIV-1 RNA greater than plasma VL) or escape (detection of HIV VL >50 copies/mL in CSF in patients with suppressed plasma VL <50 copies/mL). Both discordance and escape may be associated with neurological symptoms. We explored risk factors for CSF discordance and escape in patients presenting with diverse neurological problems. Methods: HIV-infected adult patients undergoing diagnostic lumbar puncture (LP) at a single center between 2011 and 2015 were included in the analysis. Clinical and neuroimaging variables associated with CSF discordance/escape were identified using multivariate logistic regression. Results: One hundred forty-six patients with a median age of 45.3 (interquartile range [IQR], 39.6-51.5) years underwent 163 LPs. Median CD4 count was 430 (IQR, 190-620) cells/µL. Twenty-four (14.7%) LPs in 22 patients showed CSF discordance, of which 10 (6.1%) LPs in 9 patients represented CSF escape. In multivariate analysis, both CSF discordance and escape were associated with diffuse white matter signal abnormalities (DWMSAs) on cranial magnetic resonance imaging (adjusted odds ratio, 10.3 [95% confidence interval {CI}, 2.3-45.0], P = .007 and 56.9 [95% CI, 4.0-882.8], P = .01, respectively). All 7 patients with CSF escape (10 LPs) had been diagnosed with HIV >7 years prior to LP, and 6 of 6 patients with resistance data had documented evidence of drug-resistant virus in plasma. Conclusions: Among patients presenting with diverse neurological problems, CSF discordance or escape was observed in 15%, with treatment-experienced patients dominating the escape group. DWMSAs in HIV-infected individuals presenting with neurological problems should raise suspicion of possible CSF discordance/escape.

Impact of the National Cervical Screening Programme in New Zealand by age: analysis of cervical cancer trends 1985-2013 in all women and in Maori women.

BACKGROUND: New Zealand is an example of a country with a well-established cytology-based screening program. New Zealand's National Cervical Screening Programme (NCSP) commenced in 1990, and recommends three-yearly cytology-based screening for women aged 20-69 years. In 2018, the NCSP will transition to five-yearly HPV-based screening for women aged 25-69 years. The aim of this study was to assess the impact of the program to date in different groups, to provide a benchmark for the new program. METHODS: Analysis of cervical cancer trends in New Zealand by age and ethnicity over the period 1985-2013, and by morphology over the period 1997-2013, using data from the New Zealand Cancer Registry was conducted. RESULTS: The overall incidence of cervical cancer was 56% (95% CI 51-60%) lower in 2009-2013 than in 1985-1989, and significant reductions were observed in women aged 25-49, 50-69, and 70 + years. Relative reductions in cervical cancer were very similar for Maori and non-Maori women aged 25-49 (50% in Maori; 52% in non-Maori) and 50-69 years (65% in Maori; 69% in non-Maori). In contrast, incidence appeared to increase after around 1996 in women aged 20-24. The increasing trend was significant for women aged 20-24 overall and for non-Maori women (p < 0.01 in both cases). CONCLUSION: There have been substantial reductions in cervical cancer among women aged 25 + years in New Zealand since the inception of the NCSP, and these reductions are similar in Maori and non-Maori women. Cervical cancer incidence among women 20-24 years has not declined since the NCSP began, and appears to be increasing.

Condomless sex in HIV-diagnosed men who have sex with men in the UK: prevalence, correlates, and implications for HIV transmission.

OBJECTIVE: HIV transmission is ongoing among men who have sex with men (MSM) in the UK. Sex without a condom (condomless sex, CLS) is the main risk factor. We investigated the prevalence of and factors associated with types of CLS. METHODS: Cross-sectional questionnaire study in UK HIV clinics in 2011/2012 (ASTRA). MSM diagnosed with HIV for ≥3 months reported on anal and vaginal sex, CLS with HIV-serodifferent partners (CLS-D) and CLS with HIV-seroconcordant (CLS-C) partners in the previous 3 months. Mutually exclusive sexual behaviours were as follows: (1) Higher HIV risk CLS-D (not on antiretroviral therapy (ART) or clinic-recorded viral load(VL) >50 c/mL), (2) Other CLS-D, (3) CLS-C without CLS-D, (4) Condom-protected sex only and (5) No anal or vaginal sex. Associations were examined of sociodemographic, HIV-related, lifestyle, and other sexual measures with the five categories of sexual behaviour. We examined the prevalence of higher HIV risk CLS-D incorporating (in addition to ART and VL) time on ART, ART non-adherence, and recent sexually transmitted infections (STIs). RESULTS: Among 2189 HIV-diagnosed MSM (87% on ART), prevalence of any CLS in the past 3 months was 38.2% (95% CI 36.2% to 40.4%) and that of any CLS-D was 16.3% (14.8%-17.9%). The five-category classification was as follows: (1) Higher HIV risk CLS-D: 4.2% (3.5% to 5.2%), (2) Other CLS-D: 12.1% (10.8% to 13.5%), (3) CLS-C without CLS-D: 21.9% (20.2% to 23.7%), (4) Condom-protected sex only: 25.4% (23.6% to 27.3%) and (5) No anal or vaginal sex: 36.4% (34.3% to 38.4%). Compared with men who reported condom-protected sex only, MSM who reported any CLS in the past 3 months had higher prevalence of STIs, chemsex-associated drug use, group sex, higher partner numbers, and lifetime hepatitis C. Prevalence of higher HIV risk CLS-D ranged from 4.2% to 7.5% according to criteria included. CONCLUSION: CLS was prevalent among HIV-diagnosed MSM, but CLS-D with higher HIV transmission risk was overall low. CLS-D is no longer the most appropriate measure of HIV transmission risk behaviour among people with diagnosed HIV; accounting for VL is important.

Proof-of-Principle for Immune Control of Global HIV-1 Reactivation In Vivo.

BACKGROUND: Emerging data relating to human immunodeficiency virus type 1 (HIV-1) cure suggest that vaccination to stimulate the host immune response, particularly cytotoxic cells, may be critical to clearing of reactivated HIV-1-infected cells. However, evidence for this approach in humans is lacking, and parameters required for a vaccine are unknown because opportunities to study HIV-1 reactivation are rare. METHODS: We present observations from a HIV-1 elite controller, not treated with combination antiretroviral therapy, who experienced viral reactivation following treatment for myeloma with melphalan and autologous stem cell transplantation. Mathematical modeling was performed using a standard viral dynamic model. Enzyme-linked immunospot, intracellular cytokine staining, and tetramer staining were performed on peripheral blood mononuclear cells; in vitro CD8 T-cell-mediated control of virion production by autologous CD4 T cells was quantified; and neutralizing antibody titers were measured. RESULTS: Viral rebound was measured at 28,000 copies/mL on day 13 post-transplant before rapid decay to <50 copies/mL in 2 distinct phases with t1/2 of 0.71 days and 4.1 days. These kinetics were consistent with an expansion of cytotoxic effector cells and killing of productively infected CD4 T cells. Following transplantation, innate immune cells, including natural killer cells, recovered with virus rebound. However, most striking was the expansion of highly functional HIV-1-specific cytotoxic CD8 T cells, at numbers consistent with those applied in modeling, as virus control was regained. CONCLUSIONS: These observations provide evidence that the human immune response is capable of controlling coordinated global HIV-1 reactivation, remarkably with potency equivalent to combination antiretroviral therapy. These data will inform design of vaccines for use in HIV-1 curative interventions.

Genetic analysis reveals diversity and genetic relationship among Trichoderma isolates from potting media, cultivated soil and uncultivated soil.

BACKGROUND: Trichoderma is one of the most common fungi in soil. However, little information is available concerning the diversity of Trichoderma in soil with no previous history of cultivation. This study was conducted to investigate the most common species and the level of genetic relatedness of Trichoderma species from uncultivated soil in relation to cultivated soil and potting media. RESULTS: A total of 24, 15 and 13 Trichoderma isolates were recovered from 84 potting media samples, 45 cultivated soil samples and 65 uncultivated soil samples, respectively. Analysis based on the internal transcribed spacer region of the ribosomal RNA (rRNA) and the translation elongation factor gene (EF1) indicated the presence of 9 Trichoderma species: T. harzianum (16 isolates), T. asperellum (13), T. citrinoviride (9), T. orientalis (3), T. ghanense (3), T. hamatum (3), T. longibrachiatum (2), T. atroviride (2), and T. viride (1). All species were found to occur in potting media samples, while five Trichoderma species were recovered from the cultivated soils and four from the uncultivated soils. AFLP analysis of the 52 Trichoderma isolates produced 52 genotypes and 993 polymorphic loci. Low to moderate levels of genetic diversity were found within populations of Trichoderma species (H = 0.0780 to 0.2208). Analysis of Molecular Variance indicated the presence of very low levels of genetic differentiation (Fst = 0.0002 to 0.0139) among populations of the same Trichoderma species obtained from the potting media, cultivated soil and uncultivated soil. CONCLUSION: The study provides evidence for occurrence of Trichoderma isolates in soil with no previous history of cultivation. The lack of genetic differentiation among Trichoderma populations from potting media, cultivated soil and uncultivated soil suggests that some factors could have been responsible for moving Trichoderma propagules among the three substrates. The study reports for the first time the presence of 4 Trichoderma species in Oman: T. asperellum, T. ghanense, T. longibrachiatum and T. orientalis.

Combining Models is More Likely to Give Better Predictions than Single Models.

In agricultural research, it is often difficult to construct a single "best" predictive model based on data collected under field conditions. We studied the relative prediction performance of combining empirical linear models over the single best model in relation to number of models to be combined, number of variates in the models, magnitude of residual errors, and weighting schemes. Two scenarios were simulated: the modeler did or did not know the relative of performance of the models to be combined. For the former case, model averaging is achieved either through weights based on the Akaike Information Criterion (AIC) statistic or with arithmetic averaging; for the latter case, only the arithmetic averaging is possible (because the relative model predictive performance is not known for a common dataset). In addition to two experimental datasets on oat mycotoxins in relation to environmental variables, two datasets were generated assuming a consistent correlation structure among explanatory variates with two magnitudes of residual errors. For the majority of cases, model averaging resulted in improved prediction performance over the single-model predictions, especially when a modeler does not have the information of relative model performance. The fewer variates in the models to be combined, the greater is improvement of model averaging over the single-model predictions. Combining models led to very little improvement over individual models when there were many variates in individual models. Overall, simple arithmetic averaging resulted in slightly better performance than the AIC-based weighted averaging. The advantage in model averaging is also noticeable for larger residual errors. This study suggests that model averaging generally performs better than single-model predictions, especially when a modeler does not have information on the relative performance of the candidate models.

Tablet and phone applications--A reflection on the experience of development.

Tablet devices are now ubiquitous. Medical illustrators have the skills to produce a wide range of media content. These devices offer the potential of using their creative abilities in new and exciting ways. There is much to explore. The primary difficulty lies in understanding the necessary computer technical skills to realise a vision.

Modeling the effects of environmental conditions on HT2 and T2 toxin accumulation in field oat grains.

Fusarium head blight (FHB) of wheat and barley has been extensively researched worldwide; in contrast, there is limited information on the effects of environmental conditions on Fusarium toxin accumulation in oat grains. More than 300 samples of oat grain from various regions of the United Kingdom from 2006 to 2008 were analyzed for mycotoxin contamination due to infection by Fusarium spp. HT2 and T2 toxins were the two most commonly detected, and their concentrations in individual samples were highly correlated. Hourly weather data were obtained from meteorological recording stations near most of the sampling sites. Statistical modeling was applied to both the original toxin (HT2 plus T2) data and the toxin data adjusted for oat cultivars and number of cereal crops in the previous four seasons. Accumulation of HT2 and T2 toxin was positively correlated with warm and wet conditions during early May and dry conditions thereafter. Using a collection of 51 environmental variables summarized over three lengths (10, 15, and 20 days) of time periods encompassing early May, late May, and early July, all-subsets regression showed that many models, consisting of three to six predictor variables, could be identified with similar explanatory strength for the effect of environmental conditions on toxin accumulation. Most important predictor variables were related to wet conditions during the early-May period, which was before anthesis. These results suggest that the predominant period for Fusarium langsethiae infection of oat is likely to be before rather than during anthesis, as for other head blight pathogens. These empirical models may be further improved by using quantified pathogen biomass within the grains and weather predictor variables summarized in relation to plant growth stages (instead of calendar times).

Trypanosoma cruzi screening in people living with HIV in the UK.

People living with HIV (PLWH) are at higher risk of reactivation of Chagas disease, a neglected tropical disease, caused by Trypanosoma cruzi. There are no data from UK HIV clinics on the prevalence of T. cruzi. We implemented T. cruzi screening at our clinic as part of routine care for PLWH with epidemiological risk factors. Among 86 patients screened, none had positive serology: one seropositive patient was identified due to increased clinician awareness. Implementing T. cruzi screening as part of routine clinical care was feasible, though labour intensive and identified at-risk individuals.

Grass-Endophyte Interactions and Their Associated Alkaloids as a Potential Management Strategy for Plant Parasitic Nematodes.

Claviceptaceous endophytic fungi in the genus Epichloë mostly form a symbiotic relationship with cool-season grasses. Epichloë spp. are capable of producing bioactive alkaloids such as peramines, lolines, ergot alkaloids, and indole-diterpenes, which protect the host plant from herbivory by animals, insects, and nematodes. The host also benefits from enhanced tolerance to abiotic stresses, such as salt, drought, waterlogging, cold, heavy metals, and low nitrogen stress. The bioactive alkaloids produced can have both direct and indirect effects towards plant parasitic nematodes. Direct interaction with nematodes' motile stages can cause paralysis (nematostatic effect) or death (nematicidal effect). Indirectly, the metabolites may induce host immunity which inhibits feeding and subsequent nematode development. This review highlights the different mechanisms through which this interaction and the metabolites produced have been explored in the suppression of plant parasitic nematodes and also how the specific interactions between different grass genotypes and endophyte strains result in variable suppression of different nematode species. An understanding of the different grass-endophyte interactions and their successes and failures in suppressing various nematode species is essential to enable the proper selection of grass-endophyte combinations to identify the alkaloids produced, concentrations required, and determine which nematodes are sensitive to which specific alkaloids.

Application of a portable ion chromatograph for real-time field analysis of nitrite and nitrate in soils and soil pore waters.

Real-time monitoring of nitrite and nitrate is crucial for maintaining soil health and promoting plant growth. In this study, a portable ion-chromatograph (IC, Aquamonitrix) analyser, coupled with a field-applicable ultrasonic-assisted extraction method, was utilised for in-field determination of nitrate and nitrite in soils. This is the first application of this type of analyser to soil nutrients. On-site analysis of soil from a local sports field showed 94.8 ± 4.3 µg g-1 nitrate, with LODs of 32.0 µg g-1 for nitrate and 5.4 µg g-1 for nitrite. The results were in close agreement with those obtained using a conventional lab-based IC. Relative standard deviations (%RSDs) for soil analysis using Aquamonitrix were consistently below 10%. The obtained average recoveries of samples spiked with nitrite were 100% and 104% for the portable IC and conventional IC, respectively. Furthermore, to assess the suitability of portable IC for samples with high organic matter content, various natural organic fertilisers were extracted and analysed. The results showed 16.2 ± 0.7 µg g-1 nitrite and 28.5 ± 5.6 µg g-1 nitrate in sheep manure samples with LODs of 2.0 µg g-1 for nitrite and 12.0 µg g-1 for nitrate. The portable IC system was further demonstrated via real-time on-site analysis of soil pore-water acquired using a portable battery-based ceramic pore-water sampler. A continuous increase in nitrate concentration over time was observed (from 80 to 148 µg mL-1) in the soil pore-water in a vegetable garden four days after heavy rain. Unlike conventionally sampled natural waters, 7-day storage of the studied pore water samples revealed no changes in nitrate concentrations. An average of 558 ± 51 µg mL-1 nitrate was detected in the soil pore-water samples analysed on a spinach farm, immediately after irrigation.

Screening of Fungicides and Comparison of Selective Media for Isolation of Fusarium graminearum from Soil and Plant Material.

The culture media recommended for the isolation and enumeration of the Fusarium spp. lack selectivity for Fusarium graminearum. Five fungicides-Amistar® (250 g·L-1 azoxystrobin), Filan® (500 g·kg-1 boscalid), Comet® 200 (200 g·L-1 pyraclostrobin), Imtrex® (62.5 g·L-1 fluxapyroxad), Poraz® (450 g·L-1 prochloraz)-were investigated for their potential as selective inhibitors in culture media for the isolation of F. graminearum from soil and plant material. Based on the screening, fluxapyroxad was further tested for selective inhibition for the isolation of F. graminearum from soil. Additionally, selective media were compared for the isolation of F. graminearum from plant material. The fungicides tested did not prove to be effective inhibitors for the development of selective media. For the detection of F. graminearum in plant material, Czapek Dox propiconazole dichloran agar was found to be a better medium than Komada's media, as the former resulted in colonies with darker pigmentation over a shorter incubation time and appeared to have a less inhibitory effect on F. graminearum growth.