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.

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.

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.

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.

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.

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.

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.

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.

Unexpected difficult tracheal intubation secondary to subglottic stenosis leading to emergency front-of-neck airway.

A 26-year-old woman presenting for an elective day case procedure under general anaesthesia had undiagnosed subglottic stenosis leading to a life threatening airway emergency requiring emergency front-of-neck airway. We outline the case and discuss key anaesthetic considerations in subglottic stenosis, including concerning features of a medical/anaesthetic history and the potential for rapid deterioration of a stenotic airway following manipulation. We also consider the effect of anaesthesia on the calibre of subglottic stenosis and the effects of positive pressure ventilation. Subglottic stenosis is a rare condition with congenital, acquired and idiopathic origins; however, iatrogenic trauma is the most common cause. We are aware of a small number of published case reports of previously undiagnosed subglottic stenosis in adults discovered after induction of anaesthesia; situational deterioration to 'cannot intubate, cannot oxygenate' scenarios appear even rarer.

The Latitudes, Attitudes, and Platitudes of Watershed Phosphorus Management in North America.

Phosphorus (P) plays a crucial role in agriculture as a primary fertilizer nutrient-and as a cause of the eutrophication of surface waters. Despite decades of efforts to keep P on agricultural fields and reduce losses to waterways, frequent algal blooms persist, triggering not only ecological disruption but also economic, social, and political consequences. We investigate historical and persistent factors affecting agricultural P mitigation in a transect of major watersheds across North America: Lake Winnipeg, Lake Erie, the Chesapeake Bay, and Lake Okeechobee/Everglades. These water bodies span 26 degrees of latitude, from the cold climate of central Canada to the subtropics of the southeastern United States. These water bodies and their associated watersheds have tracked trajectories of P mitigation that manifest remarkable similarities, and all have faced challenges in the application of science to agricultural management that continue to this day. An evolution of knowledge and experience in watershed P mitigation calls into question uniform solutions as well as efforts to transfer strategies from other arenas. As a result, there is a need to admit to shortcomings of past approaches, plotting a future for watershed P mitigation that accepts the sometimes two-sided nature of Hennig Brandt's "Devil's Element."

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.

Epidemiology and health-economic burden of urinary-catheter-associated infection in English NHS hospitals: a probabilistic modelling study.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) and bloodstream infection (CABSI) are leading causes of healthcare-associated infection in England's National Health Service (NHS), but health-economic evidence to inform investment in prevention is lacking. AIMS: To quantify the health-economic burden and value of prevention of urinary-catheter-associated infection among adult inpatients admitted to NHS trusts in 2016/17. METHODS: A decision-analytic model was developed to estimate the annual prevalence of CAUTI and CABSI, and their associated excess health burdens [quality-adjusted life-years (QALYs)] and economic costs (£ 2017). Patient-level datasets and literature were synthesized to estimate population structure, model parameters and associated uncertainty. Health and economic benefits of catheter prevention were estimated. Scenario and probabilistic sensitivity analyses were conducted. FINDINGS: The model estimated 52,085 [95% uncertainty interval (UI) 42,967-61,360] CAUTIs and 7529 (UI 6857-8622) CABSIs, of which 38,084 (UI 30,236-46,541) and 2524 (UI 2319-2956) were hospital-onset infections, respectively. Catheter-associated infections incurred 45,717 (UI 18,115-74,662) excess bed-days, 1467 (UI 1337-1707) deaths and 10,471 (UI 4783-13,499) lost QALYs. Total direct hospital costs were estimated at £54.4M (UI £37.3-77.8M), with an additional £209.4M (UI £95.7-270.0M) in economic value of QALYs lost assuming a willingness-to-pay threshold of £20,000/QALY. Respectively, CABSI accounted for 47% (UI 32-67%) and 97% (UI 93-98%) of direct costs and QALYs lost. Every catheter prevented could save £30 (UI £20-44) in direct hospital costs and £112 (UI £52-146) in QALY value. CONCLUSIONS: Hospital catheter prevention is poised to reap substantial health-economic gains, but community-oriented interventions are needed to target the large burden imposed by community-onset infection.

Temporal evaluation of estrogenic endocrine disruption markers in smallmouth bass (Micropterus dolomieu) reveals seasonal variability in intersex.

A reconnaissance project completed in 2009 identified intersex and elevated plasma vitellogenin in male smallmouth bass inhabiting the Missisquoi River, VT. In an attempt to identify the presence and seasonality of putative endocrine disrupting chemicals or other factors associated with these observations, a comprehensive reevaluation was conducted between September 2012 and June 2014. Here, we collected smallmouth bass from three physically partitioned reaches along the river to measure biomarkers of estrogenic endocrine disruption in smallmouth bass. In addition, polar organic chemical integrative samples (POCIS) were deployed to identify specific chemicals associated with biological observations. We did not observe biological differences across reaches indicating the absence of clear point source contributions to the observation of intersex. Interestingly, intersex prevalence and severity decreased in a stepwise manner over the timespan of the project. Intersex decreased from 92.8% to 28.1%. The only significant predictor of intersex prevalence was year of capture, based on logistic regression analysis. The mixed model of fish length and year-of-capture best predicted intersex severity. Intersex severity was also significantly different across late summer and early spring collections indicating seasonal changes in this metric. Plasma vitellogenin and liver vitellogenin Aa transcript abundance in males did not indicate exposure to estrogenic endocrine disrupting chemicals at any of the four sample collections. Analysis of chemicals captured by the POCIS as well as results of screening discrete water samples or POCIS extracts did not indicate the contribution of appreciable estrogenic chemicals. It is possible that unreported changes in land-use activity have ameliorated the problem, and our observations indicate recovery. Regardless, this work clearly emphasizes that single, snap shot sampling for intersex may not yield representative data given that the manifestation of this condition within a population can change dramatically over time.

Extracting the turbulent flow-field from beam emission spectroscopy images using velocimetry.

The 2D turbulent E × B flow-field is inferred from density fluctuation images obtained with the beam emission spectroscopy diagnostic on DIII-D using the orthogonal dynamic programming velocimetry algorithm. A synthetic turbulence model is used to test the algorithm and optimize it for measuring zonal flows. Zonal flow measurements are found to require a signal-to-noise ratio above ∼10 and a zonal flow wavelength longer than ∼2 cm. Comparison between the velocimetry-estimated flow-field and the E × B flow-field using a nonlinear gyrokinetic GENE simulation finds that the flow-fields have identical spatial structure and differ only by the mean turbulence phase velocity, which is spatially uniform in this flux tube simulation.

Cross-sectional study to estimate the prevalence of enterohaemorrhagic Escherichia coli on hides of market beef cows at harvest.

Cattle hides are an important source of enterohaemorrhagic Escherichia coli (EHEC) carcass contamination at slaughter. Seven EHEC serogroups are adulterants in raw, non-intact beef: EHEC O26, O45, O103, O111, O121, O145 and O157. The objective of this study was to estimate the probability for hide contamination with EHEC among US market beef cows at slaughter and to test the effects of season and geographic region on prevalence of hide contamination. Hides (n = 800) of market cows were swabbed at slaughter immediately after exsanguination, prior to hide removal. Cows were sampled from two geographically distinct beef packing plants during four seasons of 2015. Cattle source was categorized by northern or southern region. Samples were tested for EHEC by a molecular screening assay. The effects of region, season and their interaction on the probability of hide contamination by each EHEC serogroup were tested in separate multilevel multivariable logistic regression models, accounting for the random effect of clustering by plant. Statistical significance was set α = .05. Of 800 total samples, at least one EHEC was detected on 630 (79%) hides. Enterohaemorrhagic E. coli O26 was detected on 129 (16%) of all hides sampled, EHEC O45 on 437 (55%), EHEC O103 on 289 (36%), EHEC O111 on 189 (24%), EHEC O121 on 140 (18%), EHEC O145 on 171 (21%) and EHEC O157 on 89 (11%). Detection of EHEC O26 and EHEC O121 was associated with season. Season and region were associated with detecting EHEC O45 and EHEC O157. Season-by-region interactions were associated with the outcome of detecting EHEC O103, EHEC O111 and EHEC O145. Season, region of origin and the interaction of these factors affect hide contamination of market beef cattle at slaughter by EHEC, and each serogroup responds to these factors uniquely.

A four-season longitudinal study of enterohaemorrhagic Escherichia coli in beef cow-calf herds in Mississippi and Nebraska.

Our objective was to describe the probability of detecting seven serogroups of enterohaemorrhagic Escherichia coli (EHEC-7) of public health importance in faecal samples from beef cow-calf herds and to test for factors associated with their detection. Fresh faecal samples (n = 85) from two Mississippi and two Nebraska herds were collected in each of four seasons. Samples were tested for each EHEC-7 serogroup by a molecular screening assay. Separate management groups within herds were sampled, and group-level factors were recorded. To measure the effects of factors on faecal shedding of EHEC-7, separate multivariable logistic regression models were used, accounting for the random effect of clustering by group within farm. Statistical significance was set α = 0.05. Fifty-nine samples (4.3%) were positive for EHEC O26, and Nebraska samples were more likely to be positive than Mississippi samples (OR = 12.4, 95% CI: 1.1, 139.2). Forty-four samples (3.2%) were positive for EHEC O45. Odds for detection were greater in the summer than all other seasons combined (OR = 4.2, 95% CI: 1.3, 14.0), and odds decreased if a precipitation event occurred (OR = 0.07, 95% CI: 0.006, 0.8). EHEC O103 was detected in 66 samples (4.9%) with increased probability to be detected at increased temperature. EHEC O111 was detected in 71 samples (5.2%), and 43 samples (3.2%) were positive for EHEC O145. Both EHEC O111 and O145 were associated separately with season, with greater probability for detection in the summer. Eighteen (1.3%) and 68 (5.0%) samples were positive for EHEC O121 and EHEC O157, respectively. We failed to detect significant explanatory factors associated with probability to detect EHEC O121 or O157. Factors that vary by time and place, such as precipitation, ambient temperature, region and season, are uniquely associated with the probability to detect EHEC-7 in fresh faeces collected from cow-calf herds.

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.

A randomized controlled trial to evaluate the effects of dietary fibre from distillers grains on enterohemorrhagic Escherichia coli detection from the rectoanal mucosa and hides of feedlot steers.

Feeding high levels (≥40% dry matter) of distillers grains may increase the risk for cattle to carry enterohemorrhagic Escherichia coli (EHEC) O157. The mechanism for the increased risk is not known nor whether non-O157 EHEC are similarly affected. Our objective was to test whether the fibre content or other components of modified distillers grains plus solubles (MDGS) affects the probability for cattle to carry EHEC serogroups of public health importance. A 2 × 2 plus 1 factorial treatment arrangement within a randomized block design was utilized. Within each of four blocks, 25 feedlot pens (n = 8 steers/pen) were assigned randomly to (i) corn-based control diet; (ii) 20% dry matter (DM) MDGS; (iii) 40% DM MDGS; (iv) corn bran added to corn-based diet to match fibre of 20% MDGS or (v) 40% MDGS. Rectoanal mucosa swabs (RAMS) were collected on day (d)0, d35, d70 and d105; hide swabs were collected on the last feeding day. Samples were tested for EHEC by a molecular screening assay. The effects of fibre source and fibre level on EHEC carriage were tested using multilevel logistic regression (generalized linear mixed models; α = 0.05). EHEC O45 RAMS detection was associated with fibre level, source and sampling day. EHEC O103 RAMS detection increased by feeding 40% MDGS but not the corresponding corn bran diet. Hide contamination by EHEC O45 or O103 was less likely in cattle fed MDGS compared to corn bran diets. EHEC O111 RAMS detection decreased by feeding 40% MDGS but not by feeding the corresponding corn bran diet. Detection of EHEC O157 or O145 was not associated with dietary factors. Feeding 40% MDGS increased the probability for carriage of some EHEC serogroups but decreased probability of others, which indicated that EHEC serogroups have different risk factors associated with feeding MDGS and little association with dietary fibre.

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.

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.