Profile of reticulated platelets in the early, subacute and late phases after transient ischemic attack or ischemic stroke.

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.

Body Size Influences Stingless Bee (Hymenoptera: Apidae) Communities Across a Range of Deforestation Levels in Rondônia, Brazil.

Developments in understanding bee responses to habitat loss indicate that body size is a trait with important consequences for conservation. Stingless bees (Hymenoptera, Apidae, Meliponini) are a diverse group of eusocial bees providing pollination services in tropical landscapes, exhibiting a large range in body size across species. We tested the effects of deforestation on the body sizes of stingless bee communities by using museum specimens and revisiting a previous effort that sampled stingless bee communities across varying levels of deforestation at 183 sites in Rondônia, Brazil, in 1996-1997. Body size measurements (intertegular distance) from 72 species collected were included as dependent variables in response to forest area, forest edge, and connectivity of forest patches at several spatial scales. We find that stingless bee body size is negatively related to forest cover: mean community body size was larger in areas with greater amounts of deforestation, and smaller in areas with less deforestation. Second, stingless bee species richness was positively associated with forest edge regardless of body size. Lastly, we find that as forest patch isolation increased, the stingless bee community body size also increased. These findings support hypotheses that small stingless bee species might be more negatively affected by deforestation, adding to the growing body of evidence that stingless bees require areas of intact forest in near proximity to other forest patches to conserve these diverse pollinator communities.

Willingness to care for blood-borne virus-infected patients in Thailand.

Background: Although stigma and discrimination by nurses against patients infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) have been reported, potential determinants of nurses' willingness to care for these patients have not been well studied in Thailand. Aims: To identify factors associated with Thai nurses' willingness to care for patients infected with HIV or HCV. Methods: Multivariable logistic regression analysis of data from a questionnaire completed by nurses at a large hospital in Bangkok, Thailand. Results: Of 626 nurses, 546 (87%) nurses participated. Eleven per cent (59) and 6% (34) had previously experienced HIV- or HCV-infected blood contamination incidents, respectively. Forty-four per cent (240) and 38% (208) reported unwillingness to care for HIV- or HCV-infected patients, respectively. Willingness to care was less common [adjusted odds ratios 0.51 (0.34-0.74) for HIV and 0.62 (0.42-0.89) for HCV] in nurses aged ≥ 40 years and in those who feared HCV [0.63 (0.37-0.99)], but not HIV [0.84 (0.5-1.26)] transmission. Nurses who had confidence in protecting themselves against infection with HIV [1.84 (1.52-2.04)] and HCV [1.87 (1.45-2.18)], and accepting attitudes towards HIV-infected co-workers [1.39 (1.08-1.66)] but not HCV-infected co-workers [1.16 (0.83-1.5)], were more willing to care for HIV- and HCV-infected patients. Conclusions: Around 4 in 10 Thai nurses in our sample were unwilling to care for HIV- or HCV-infected patients. Minimizing the risk of nosocomial transmission and improving the public perception of infected individuals may help improve nurses' willingness to care for such patients, in Thailand or elsewhere.

Profiling cancer risk in oral potentially malignant disorders-A patient cohort study.

BACKGROUND: Oral potentially malignant disorders harbour variable and unpredictable risk for squamous carcinoma development. Whilst current management strategies utilise histopathological diagnoses, dysplasia grading and targeted intervention for "high-risk" lesions, clinicians are unable to predict malignant potential. METHODS: Detailed, retrospective clinico-pathological analysis of potentially malignant lesions undergoing malignant transformation, from a 590 patient cohort treated by interventional laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was documented at study census date (31 December 2014). RESULTS: A total of 99 patients (16.8%) developed cancer: 71 (12%) seen "unexpectedly" upon excision and 28 (4.8%) progressing to malignancy at a median of 87.3 months post-surgery. Thirty "unexpected" excisions were micro-invasive (42.3%) arising primarily in severely dysplastic precursors (75%) at ventro-lateral tongue and floor of mouth sites (54.5%); 1 patient (1.4%) had a cancer-related death, whilst 58 (81.7%) were disease free. A total of 19 of 28 "progressive" cancers (67.9%) arose at new sites, with erythroleukoplakia a significant predictor of malignancy (P = .0019). Nine (32.1%) developed at the same precursor site, with 6 (77.7%) on the ventro-lateral tongue and floor of mouth. Three (10.7%) were micro-invasive, 9 patients (32.1%) died from metastatic disease and 12 (42.9%) were disease free (P < .001). CONCLUSION: Squamous carcinoma may arise at the site of a precursor lesion as transformation or new-site development via field cancerisation. Whilst interventional surgery facilitates early diagnosis and treatment of occult disease, thus reducing risk from same-site transformation, new-site cancer is a significant long-term risk for patients with potentially malignant disorder.

Efficacy of oral brush biopsy in potentially malignant disorder management.

BACKGROUND: Oral potentially malignant disorders (PMD) harbour unpredictable risk for squamous cell carcinoma development. Current management requires tissue biopsy for histopathology characterisation, dysplasia grading and targeted intervention to "high-risk" lesions, although evidence-based guidelines are limited and diagnoses subjective. This study investigated the use of adjunctive oral brush biopsy techniques during the management of PMD in a UK hospital population. METHODS: Retrospective review of a 310 PMD patient cohort presenting to Maxillofacial Surgery in Newcastle upon Tyne with new, single-site lesions between December 2009 and May 2014. Patients underwent Orcellex® brush biopsy and liquid-based cytology examination in addition to conventional biopsy techniques, with management proceeding along established care pathways. Patient demographics, cytology data, most significant histopathology diagnoses and clinical outcome were all documented at the study census date (31.12.15). RESULTS: A total of 170 male & 140 female patients (age range 18-91 years), exhibiting primarily leukoplakia (86.5%) at floor of mouth and ventrolateral tongue sites (44.9%), were identified. Management comprised: observation (49.7%), laser surgery (44.9%), antifungal treatment (3.5%) and Head & Neck clinic referral following cancer diagnosis (1.9%). Clinical outcomes were as follows: disease free (51.3%), persistent PMD (42.3%) and malignant transformation (6.4%). Histology and cytology diagnoses strongly correlated (r = .305). Treatment modality, lesion site, histology and cytology diagnoses were the best predictors of clinical outcome. CONCLUSIONS: Orcellex® brush cytology provides reliable diagnoses consistent with conventional histopathology and offers less invasive, adjunctive assessment appropriate for long-term monitoring of patients in specialist clinics.

Treatment resistance in potentially malignant disorders-'Nature' or 'Nurture' ?

BACKGROUND: Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention. METHODS: A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). RESULTS: A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027). CONCLUSION: Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure.

Introducing loupes to clinical practice: dental hygienists experiences and opinions.

OBJECTIVES: Recent literature has identified a number of potential advantages in wearing loupes for dental hygienists, including improved quality of care and ergonomics. The aim of the study was to determine dental hygienists' opinions about wearing loupes. METHODS: A short online survey was distributed to all dental hygienists who had recently participated in a study investigating the efficacy of loupes on musculoskeletal disorders; all had only worn loupes for a 6-month period, and prior to the study had not worn loupes. All of those invited completed the survey (n = 12), achieving a 100% response rate. RESULTS: The majority of respondents noted that the loupes were adaptable to wear; however, only one-quarter of hygienists surveyed were wearing them often following the study. Respondents identified that the biggest advantage to loupes was calculus removal (91.7%), and most indicated that they felt the quality of their work increased when wearing loupes (75%). The biggest disadvantage to wearing loupes was the adjustment period (50%), with limited depth of vision, headache, vertigo and infection control noted by at least one-third of respondents. CONCLUSIONS: This study revealed that hygienists identify both benefits and limitations to wearing loupes, and therefore, ongoing support may be required for hygienists adopting their use in clinical practice.

Impact of ferromanganese alloy plants on household dust manganese levels: implications for childhood exposure.

Adolescents living in communities with ferromanganese alloy plant activity have been shown to exhibit deficits in olfactory and fine motor function. Household dust may serve as an important manganese (Mn) exposure pathway to children, though dust Mn concentrations have not previously been measured to assess household contamination from ferromanganese alloy plant emissions. Here we determined the association between dust concentrations and surface loadings of Mn and other metals (Al, Cd, Cr, Cu, Fe, Pb, and Zn) in indoor and outdoor household dust from three Italian communities that differ by history of ferromanganese alloy plant activity: Bagnolo Mella, with an active ferromanganese alloy plant (n=178 households); Valcamonica, with historically active plants (n=166); and Garda Lake, with no history of ferromanganese plant activity (n=99). We also evaluated Mn levels in other environmental (soil, airborne particulates) and candidate biomarker (blood, hair, saliva, fingernails) samples from children within the households. Household dust Mn concentrations and surface loadings were significantly different between the three sites, with levels highest in Bagnolo Mella (outdoor median Mn concentration=4620, range 487-183,000µg/g), intermediate in Valcamonica (median=876, range 407-8240µg/g), and lowest in Garda Lake (median=407, range 258-7240µg/g). Outdoor dust Mn concentrations in Bagnolo Mella, but not the other communities, were significantly inversely related with distance from the plant (R(2)=0.6630, P<0.0001). Moreover, outdoor dust Mn concentrations and loadings were highly predictive of but significantly higher than indoor dust Mn concentrations and loadings by ~2 to ~7-fold (Mn concentrations) and ~7 to ~20-fold (Mn loadings). Finally, both indoor and outdoor dust Mn concentrations and outdoor dust Mn loading values were highly significantly correlated with both soil and air Mn concentrations, and with children's hair and fingernail Mn concentrations, but weakly or not associated with saliva or blood Mn levels. Given the evidence associating elevated Mn exposure with neurological impairments in children, these data support that dust Mn levels should be reduced in contaminated environments to protect the health of resident children.

Geographic variation in polyandry of the Eastern Honey Bee, Apis cerana, in Thailand.

The repeated evolution of extreme polyandry in advanced social insects is exceptional and its explanation has attracted significant attention. However, most reported estimates of the number of matings are derived from limited sampling. Temporal and geographic variation in mating behavior of social insects has not been sufficiently studied. Worker offspring of 18 Eastern Honey Bee (Apis cerana Fabr.) queens from three populations across Thailand were genotyped at five microsatellite markers to test for population differences of mating behavior across three different ecosystems. The number of matings decreased from a northern, more seasonal environment to a southern tropical population and was lowest in a tropical island population. Our study confirms earlier findings that social insect mating behavior shows biogeographic variation and highlights that data from several populations are needed for reliable species-specific estimates of the number of matings. Detailed studies of populations that show significant differentiation in the number of matings may be able to discriminate effectively among the different hypotheses that have been proposed to explain the evolution of polyandry in honey bees and other advanced social insects.

The effect of wearing loupes on upper extremity musculoskeletal disorders among dental hygienists.

OBJECTIVES: It is well established that musculoskeletal disorders (MSD) are a significant occupational health issue for dentists and hygienists. Despite this, there has been little advancement in the application of ergonomic principles in the dental profession. While the use of loupes is often promoted as an ergonomic solution, there is little published research to robustly support this claim. The aim of the present study was to investigate the effect of the use of loupes on upper extremity MSD among dental hygienists. METHODS: The study was conducted using an exploratory pretest and post-test design, comparing musculoskeletal measures in practising dental hygienists wearing loupes with final-year dental hygiene students who did not wear loupes. Pre- and post-test measures included valid self-reported and objective outcome measures and were measured at baseline and 6 months following the intervention. Statistical analysis was conducted as a series of mixed anovas with time and treatment as the independent variables. RESULTS: The analysis revealed a significant interaction between time and treatment for the Disabilities of the Shoulder, Arm and Hand (DASH) scores (P < 0.04), indicating an improvement in symptoms for the treatment group but a reversed trend for the controls. There was also a significant mean increase in scapular position measures; however, this finding was evident in both groups, indicating that these were not a result of the intervention. CONCLUSIONS: Overall, this study suggests that wearing loupes appears to have both positive and negative effects on upper extremity MSD among dental hygienists. Ongoing research is required to determine the long-term effects of loupes wear, over an extended period of time.

Predicting consequences of COVID-19 control measure de-escalation on nosocomial transmission and mortality: a modelling study in a French rehabilitation hospital.

INTRODUCTION: Infection control measures are effective for nosocomial COVID-19 prevention but bear substantial health-economic costs, motivating their "de-escalation" in settings at low risk of SARS-CoV-2 transmission. Yet consequences of de-escalation are difficult to predict, particularly in light of novel variants and heterogeneous population immunity. AIM: To estimate how infection control measure de-escalation influences nosocomial COVID-19 risk. METHODS: An individual-based transmission model was used to simulate SARS-CoV-2 outbreaks and control measure de-escalation in a French long-term care hospital with multi-modal control measures in place (testing and isolation, universal masking, single-occupant rooms). Estimates of COVID-19 case fatality rates (CFRs) from reported outbreaks were used to quantify excess COVID-19 mortality due to de-escalation. RESULTS: In a population fully susceptible to infection, de-escalating both universal masking and single rooms resulted in hospital-wide outbreaks of 114 (95% CI: 103-125) excess infections, compared with five (three to seven) excess infections when de-escalating only universal masking or 15 (11-18) when de-escalating only single rooms. When de-escalating both measures and applying CFRs from the first wave of COVID-19, excess patient mortality ranged from 1.57 (1.41-1.71) to 9.66 (8.73-10.57) excess deaths/1000 patient-days. By contrast, when applying CFRs from subsequent pandemic waves and assuming susceptibility to infection among 40-60% of individuals, excess mortality ranged from 0 (0-0) to 0.92 (0.77-1.07) excess deaths/1000 patient-days. CONCLUSIONS: The de-escalation of bundled COVID-19 control measures may facilitate widespread nosocomial SARS-CoV-2 transmission. However, excess mortality is probably limited in populations at least moderately immune to infection and given CFRs resembling those estimated during the 'post-vaccine' era.

von Willebrand factor antigen, von Willebrand factor propeptide and ADAMTS13 activity in TIA or ischaemic stroke patients changing antiplatelet therapy.

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays). VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04). Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.

Developmental Manganese Exposure Causes Lasting Attention Deficits Accompanied by Dysregulation of mTOR Signaling and Catecholaminergic Gene Expression in Brain Prefrontal Cortex.

Elevated manganese (Mn) exposure is associated with attentional deficits in children, and is an environmental risk factor for attention deficit hyperactivity disorder (ADHD). We have shown that developmental Mn exposure causes lasting attention and sensorimotor deficits in a rat model of early childhood Mn exposure, and that these deficits are associated with a hypofunctioning catecholaminergic system in the prefrontal cortex (PFC), though the mechanistic basis for these deficits is not well understood. To address this, male Long-Evans rats were exposed orally to Mn (50 mg/kg/d) over PND 1-21 and attentional function was assessed in adulthood using the 5-Choice Serial Reaction Time Task. Targeted catecholaminergic system and epigenetic gene expression, followed by unbiased differential DNA methylation and gene regulation expression transcriptomics in the PFC, were performed in young adult littermates. Results show that developmental Mn exposure causes lasting focused attention deficits that are associated with reduced gene expression of tyrosine hydroxylase, dopamine transporter, and DNA methyltransferase 3a. Further, developmental Mn exposure causes broader lasting methylation and gene expression dysregulation associated with epigenetic regulation, inflammation, cell development, and hypofunctioning catecholaminergic neuronal systems. Pathway enrichment analyses uncovered mTOR and Wnt signaling pathway genes as significant transcriptomic regulators of the Mn altered transcriptome, and Western blot of total, C1 and C2 phospho-mTOR confirmed mTOR pathway dysregulation. Our findings deepen our understanding of the mechanistic basis of how developmental Mn exposure leads to lasting catecholaminergic dysfunction and attention deficits, which may aid future therapeutic interventions of environmental exposure associated disorders. Significance Statement: Attention deficit hyperactivity disorder (ADHD) is associated with environmental risk factors, including exposure to neurotoxic agents. Here we used a rodent model of developmental manganese (Mn) exposure producing lasting attention deficits to show broad epigenetic and gene expression changes in the prefrontal cortex, and to identify disrupted mTOR and Wnt signaling pathways as a novel mechanism for how developmental Mn exposure may induce lasting attention and catecholaminergic system impairments. Importantly, our findings establish early development as a critical period of susceptibility to lasting deficits in attentional function caused by elevated environmental toxicant exposure. Given that environmental health threats disproportionately impact communities of color and low socioeconomic status, our findings can aid future studies to assess therapeutic interventions for vulnerable populations.

How have mathematical models contributed to understanding the transmission and control of SARS-CoV-2 in healthcare settings? A systematic search and review.

Since the onset of the COVID-19 pandemic, mathematical models have been widely used to inform public health recommendations regarding COVID-19 control in healthcare settings. The objective of this study was to systematically review SARS-CoV-2 transmission models in healthcare settings, and to summarize their contributions to understanding nosocomial COVID-19. A systematic search and review of published articles indexed in PubMed was carried out. Modelling studies describing dynamic inter-individual transmission of SARS-CoV-2 in healthcare settings, published by mid-February 2022 were included. Models have mostly focused on acute-care and long-term-care facilities in high-income countries. Models have quantified outbreak risk, showing great variation across settings and pandemic periods. Regarding surveillance, routine testing rather than symptom-based was highlighted as essential for COVID-19 prevention due to high rates of silent transmission. Surveillance impacts depended critically on testing frequency, diagnostic sensitivity, and turn-around time. Healthcare re-organization also proved to have large epidemiological impacts: beyond obvious benefits of isolating cases and limiting inter-individual contact, more complex strategies (staggered staff scheduling, immune-based cohorting) reduced infection risk. Finally, vaccination impact, while highly effective for limiting COVID-19 burden, varied substantially depending on assumed mechanistic impacts on infection acquisition, symptom onset and transmission. Modelling results form an extensive evidence base that may inform control strategies for future waves of SARS-CoV-2 and other viral respiratory pathogens. We propose new avenues for future models of healthcare-associated outbreaks, with the aim of enhancing their efficiency and contributions to decision-making.

Characterization of microsatellite markers in cassava based on microsatellite-AFLP technique.

We developed molecular markers for cassava based on the microsatellite-amplified fragment length polymorphism (M-AFLP) technique. Twenty primer pairs were developed and used for the analysis of 48 samples of Manihot species, consisting of M. esculenta (33), M. esculenta ssp flabellifolia (3), M. chlorosticta (3), M. carthaginensis (3), M. filamentosa (3), and M. tristis (3). Nine microsatellite loci that were polymorphic among these Manihot species were identified, giving 32 polymorphic alleles and from two to seven alleles per locus. Unbiased and direct count heterozygosity varied from 0.0233 to 0.7924 and 0.0000 to 0.7083, respectively. There was significant deviation (P < 0.05) from Hardy-Weinberg equilibrium at five loci. Genotypic data from the Manihot species were subjected to genetic diversity analysis. We found that M. chlorosticta and M. esculenta ssp flabellifolia were the closest populations, while M. filamentosa and M. esculenta ssp flabellifolia were the most divergent. Considering within M. esculenta, the samples from Nigeria and Fiji were the most closely related, while those from Venezuela and of unknown origin were the most divergent. We conclude that the M-AFLP technique is an effective method for generating microsatellite markers that are useful for genetic diversity analysis in Manihot species.

Predictors of work-related musculoskeletal disorders among dental hygienists.

OBJECTIVES: Work-related musculoskeletal disorders (MSD) have been recognized as a considerable problem for the dental hygiene profession, with the majority of professionals reporting musculoskeletal pain. The aim of this study was to investigate which risk factors may help predict MSD among Australian dental hygienists. METHODS: A modified version of the Standardised Nordic questionnaire was distributed to registered hygienists throughout Australia. RESULTS: Logistic regression analysis revealed a variety of work-related and psychosocial factors that correlate with reported MSD, including scaling tasks, type of practice and work interference in home life. Statistical predictors for non-reporting of MSD included wearing loupes, ergonomics education and wage satisfaction. Concerning is the impact on the profession, with an association between MSD and hygienists considering reducing working hours or even alternate careers. CONCLUSIONS: In general, it appears as though the causes of MSD among dental hygienists may be multifactorial, as may be the solutions to this problem. Further research is required to objectively examine whether controllable variables can be implemented as preventive strategies or interventions for MSD.

Rift Valley fever MP-12 vaccine elicits an early protective immune response in mice.

Rift Valley fever virus (RVFV) is an important mosquito-borne pathogen that causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The development of an effective veterinary and human vaccine to protect against Rift Valley fever (RVF) disease remains a high priority. The live attenuated RVFV MP-12 is a promising vaccine candidate for the prevention of RVF in both human and domestic ruminants. The aim of this study was to determine the onset of protective immunity elicted in mice by a single dose of this vaccine. Groups of CD-1 mice were vaccinated intraperitoneally with RVFV MP-12 vaccine and challenged on days 2, 5, 6 and 7 post-vaccination (PV) with a lethal dose of virulent RVFV. The mice were observed once daily for terminal morbidity and blood samples were obtained from the retro-orbital sinus complex on days 23 and 28 PV of surviving mice to determine RVFV neutralizing antibody titers. In one test, 2 of 3 mice challenged on day 2 PV survived and all 3 mice challenged at days 5 and 7 PV also survived. A second test of 10 mice per group was performed, and half (5) of those challenged at day 2 PV survived while all (10) survived challenge at day 4 and 6 PV. All surviving animals develop antibody that ranged from 1:80 to 1:1,280 PV. In a separate experiment, RVFV MP-12 vaccinated CD-1 mice, but not challenged developed a low viremia for the first 3 days PV and neutralzing antibody was detected on days 5 through day 28 PV. These findings demonstrated that the RVFV MP-12 vaccine elicited a rapid protective immune response in mice as early as 2 days PV, thus further supporting the effectiveness of this vaccine candidate for preventing RVF among humans and domestic ruminants.

Conceptual design and performance predictions for 2D beam emission spectroscopy turbulence measurements at Wendelstein 7-X.

A conceptual design for a 2D beam emission spectroscopy diagnostic system to measure ion gyro-scale plasma turbulence at Wendeslstein 7-X is described. The conceptual design identifies field-aligned viewing geometries and ports for cross-field turbulence measurements in the neutral beam volume. A 2D sightline grid covers the outer plasma region, and the grid configuration provides sufficient k-space coverage in radial and poloidal directions for ion temperature gradient and trapped-electron mode turbulence measurements. Emission intensity estimates, optical transmission losses, and detector noise levels indicate that the measurements will be sensitive to plasma density fluctuations as small as δn/n ≈ 0.5% with a bandwidth of 1 MHz. Implementation challenges include a small beam emission Doppler shift due to nearly radial heating beams and reduced optical throughput due to collection aperture limitations.

Pedestal fluctuation measurements with charge exchange imaging at the DIII-D tokamak.

A new high radial resolution 2D multichannel Charge eXchange Imaging (CXI) diagnostic is under development for deployment at DIII-D. The diagnostic system will measure low-to-intermediate radial wavenumber carbon density fluctuations by observing the n = 8 - 7 (λ = 529.06 nm) C-VI emission line, resulting from charge exchange collisions between heating neutral beam atoms and the intrinsic carbon ion density. The new CXI diagnostic will provide measurements with ΔR ∼ 0.4 cm to access higher kr instabilities (kr < 8 cm-1) predicted to arise in the steep-gradient region of the H-mode pedestal. The CXI system will feature 60 fiber bundles in a 12 × 5 arrangement, with each bundle consisting of four 1 mm fibers. A custom optical system has been designed to filter and image incoming signals onto an 8 × 8 avalanche photodiode array. Additionally, a novel electronics suite has been designed and commissioned to amplify and digitize the relatively low-intensity carbon signal at a 2 MHz bandwidth. Forward modeling results of the active C-VI emission suggest sufficient signal to noise ratios to resolve turbulent fluctuations. Prototype measurements demonstrate the ability to perform high frequency pedestal measurements.

Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke.

BACKGROUND: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin. AIMS: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD. METHODS: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin. RESULTS: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR. DISCUSSION: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.