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Background: There is an unmet need for blood-based biomarkers that can reliably detect MS disease activity. Serum Biomarkers of interest includ Neurofilament-light-chain (NfL), Glial-fibrillary-strocyte-protein(GFAP) and Tau. Bone Marrow Transplantation (BMT) is reserved for aggressive forms of MS and has been shown to halt detectable CNS inflammatory activity for prolonged periods. Significant pre-treatment tissue damage at followed by inflammatory disease abeyance should be reflected longitudinal sera collected from these patients. Methods: Sera were collected from 23 MS patients pre-treatment, and following BMT at 3, 6, 9 and 12-months in addition from 33 non-inflammatory neurological controls. Biomarker quantification was performed with SiMoA. Results: Pre-AHSCT levels of serum NfL and GFAP but not Tau were elevated compared to controls (p=0.0001), and NfL correlated with lesion-based disease activity (6-month-relapse, MRI-T2 and Gadolinium-enhancement). 3-months post-treatment, while NfL levels remained elevated, Tau/GFAP paradoxically increased (p=0.0023/0.0017). These increases at 3m correlated with MRI ‘pseudoatrophy’ at 6-months. NfL/Tau levels dropped to that of controls by 6-months (p=0.0036/0.0159). GFAP levels dropped progressively after 6-months although even at 12-months remained higher than controls (p=0.004). Conclusions: NfL was the closest correlate of MS disease activity and treatment response. Chemotherapy-related toxicity may account for transient increases in NfL, Tau and MRI brain atrophy post-BMT.
Social patterning of infectious diseases is increasingly recognised. Previous studies of social determinants of acute respiratory illness (ARI) have found that highly educated and lower income families experience more illnesses. Subjective social status (SSS) has also been linked to symptomatic ARI, but the association may be confounded by household composition. We examined SSS and ARI in the Household Influenza Vaccine Evaluation (HIVE) Study in 2014–2015. We used SSS as a marker of social disadvantage and created a workplace disadvantage score for working adults. We examined the association between these measures and ARI incidence using mixed-effects Poisson regression models with random intercepts to account for household clustering. In univariate analyses, mean ARI was higher among children <5 years old (P < 0.001), and females (P = 0.004) at the individual level. At the household level, mean ARI was higher for households with at least one child <5 years than for those without (P = 0.002). In adjusted models, individuals in the lowest tertile of SSS had borderline significantly higher rates of ARI than those in the highest tertile (incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 0.98–1.92). Households in the lowest tertile of SSS had significantly higher ARI incidence in household-level models (IRR 1.46, 95% CI 1.05–2.03). We observed no association between workplace disadvantage and ARI. We detected an increase in the incidence of ARI for households with low SSS compared with those with high SSS, suggesting that socio-economic position has a meaningful impact on ARI incidence.
Preemergence herbicides are typically applied by broadcasting to the top of raised beds before laying the plastic mulch in plasticulture production systems. Broadleaf and grass emergence is limited to transplant holes in the mulch. As a result, most herbicides are applied under the mulch in locations where weeds cannot emerge and herbicides are unnecessary. To reduce this excessive off-target application, a precision hole-punch sprayer was developed at the University of Florida for use in plasticulture production systems. The technology facilitates the application of herbicides during the hole-punch operation immediately before transplant. Application of napropamide and S-metolachlor in an application volume of 233 L ha−1 of water using the precision hole-punch applicator had no effect on tomato and bell pepper growth and yield. Equipment accuracy ranged from 55% to 90%. Preemergence herbicide use was reduced by 88% to 92% with no reduction in weed control. The hole-punch applicator is an effective way to reduce PRE herbicide use in transplant vegetables grown using the plasticulture production system.
Weed interference during crop establishment is a serious concern for Florida strawberry [Fragaria×ananassa (Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] producers. In situ remote detection for precision herbicide application reduces both the risk of crop injury and herbicide inputs. Carolina geranium (Geranium carolinianum L.) is a widespread broadleaf weed within Florida strawberry production with sensitivity to clopyralid, the only available POST broadleaf herbicide. Geranium carolinianum leaf structure is distinct from that of the strawberry plant, which makes it an ideal candidate for pattern recognition in digital images via convolutional neural networks (CNNs). The study objective was to assess the precision of three CNNs in detecting G. carolinianum. Images of G. carolinianum growing in competition with strawberry were gathered at four sites in Hillsborough County, FL. Three CNNs were compared, including object detection–based DetectNet, image classification–based VGGNet, and GoogLeNet. Two DetectNet networks were trained to detect either leaves or canopies of G. carolinianum. Image classification using GoogLeNet and VGGNet was largely unsuccessful during validation with whole images (Fscore<0.02). CNN training using cropped images increased G. carolinianum detection during validation for VGGNet (Fscore=0.77) and GoogLeNet (Fscore=0.62). The G. carolinianum leaf–trained DetectNet achieved the highest Fscore (0.94) for plant detection during validation. Leaf-based detection led to more consistent detection of G. carolinianum within the strawberry canopy and reduced recall-related errors encountered in canopy-based training. The smaller target of leaf-based DetectNet did increase false positives, but such errors can be overcome with additional training images for network desensitization training. DetectNet was the most viable CNN tested for image-based remote sensing of G. carolinianum in competition with strawberry. Future research will identify the optimal approach for in situ detection and integrate the detection technology with a precision sprayer.
To explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.
Retrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.
The study included 27 transplant centers in freestanding children’s hospitals.
The primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraftment. Hospital antibiotic utilization rates were reported as days of therapy (DOTs) per 1,000 neutropenic days. Negative binomial regression was used to estimate hospital utilization rates, adjusting for patient covariates including demographics, transplant characteristics, and severity of illness. To better quantify the magnitude of hospital variation and to explore hospital-level drivers in addition to patient-level drivers of variation, mixed-effects negative binomial models were also constructed.
Adjusted hospital rates of antipseudomonal antibiotic use varied from 436 to 1121 DOTs per 1,000 neutropenic days, and rates of broad-spectrum, gram-positive antibiotic use varied from 153 to 728 DOTs per 1,000 neutropenic days. We detected variability by hospital in choice of antipseudomonal agent (ie, cephalosporins, penicillins, and carbapenems), but gram-positive coverage was primarily driven by vancomycin use. Considerable center-level variability remained even after controlling for additional hospital-level factors. Antibiotic use was not strongly associated with days of significant illness or mortality.
Among a homogenous population of children undergoing HCT for acute leukemia, both the quantity and spectrum of antibiotic exposure in the immediate posttransplant period varied widely. Antimicrobial stewardship initiatives can apply these data to optimize the use of antibiotics in transplant patients.
As utilization of CT imaging has risen dramatically, evidence-based decision rules and clinical decision support (CDS) tools have been developed to avoid unnecessary CT use in low risk patients. However, their ability to change physician practice has been limited to date, with a number of barriers cited. The purpose of this study was to identify the barriers and facilitators to CDS adoption following a local CDS implementation. Methods: All emergency physicians at 4 urban EDs and 1 urgent care center were randomized to voluntary evidence-based CT imaging CDS for patients with either mild traumatic brain injury (MTBI) or suspected pulmonary embolism (PE). CDS was integrated into the computerized physician order entry (CPOE) software and triggered whenever a CT scan for an eligible patient was ordered. Physicians in both the MTBI and PE arms were ranked according to their CDS use, and a stratified sampling strategy was used to randomly select 5 physicians from each of the low, medium and high CDS use tertiles in each study arm. Each physician was invited to participate in a 30-minute semi-structured interview to assess the barriers and facilitators to CDS use. Physician responses were reported using a thematic analysis. Results: A total of 202 emergency physicians were randomized to receive CDS for either MTBI or PE, triggering CDS 4561 times, and interacting with the CDS software 1936 times (42.4%). Variation in CDS use ranged from 0% to 88.9% of eligible encounters by physician. Fourteen physicians have participated in interviews to date, and data collection is ongoing. Physicians reported that CDS use was facilitated by their confidence in the evidence supporting the CDS algorithms and that it provided documentation to reduce medico-legal risk. CDS use was not impeded by concerns over missed diagnoses or patient expectations. Reported barriers to CDS use included suboptimal integration into the CPOE such as the inability to auto-populate test results, it disrupted the ordering process and was time consuming. A common concern was that CDS was implemented too late in workflow as most decision making takes place at the bedside. Physicians did not view CDS as infringing on physician autonomy, however they advised that CDS should be a passive educational option and should not automatically trigger for all physicians and eligible encounters. Conclusion: Physicians were generally supportive of CDS integration into practice, and were confident that CDS is an evidence-based way to reduce unnecessary CT studies. However, concerns were raised about the optimal integration of CDS into CPOE and workflow. Physicians also stated a preference to a passive educational approach to CDS rather than an automatic triggering mechanism requiring clinical documentation.
The controls on rapid surface lake drainage on the Greenland ice sheet (GrIS) remain uncertain, making it challenging to incorporate lake drainage into models of GrIS hydrology, and so to determine the ice-dynamic impact of meltwater reaching the ice-sheet bed. Here, we first use a lake area and volume tracking algorithm to identify rapidly draining lakes within West Greenland during summer 2014. Second, we derive hydrological, morphological, glaciological and surface-mass-balance data for various factors that may influence rapid lake drainage. Third, these factors are used within Exploratory Data Analysis to examine existing hypotheses for rapid lake drainage. This involves testing for statistical differences between the rapidly and non-rapidly draining lake types, as well as examining associations between lake size and the potential controlling factors. This study shows that the two lake types are statistically indistinguishable for almost all factors investigated, except lake area. Thus, we are unable to recommend an empirically supported, deterministic alternative to the fracture area threshold parameter for modelling rapid lake drainage within existing surface-hydrology models of the GrIS. However, if improved remotely sensed datasets (e.g. ice-velocity maps, climate model outputs) were included in future research, it may be possible to detect the causes of rapid drainage.
Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any ‘gold standard’. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.
Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed polymerase chain reaction (TP-PCR) for robust detection of expanded FMR1 alleles, in parallel with linked multi-marker haplotype analysis of 13 highly polymorphic microsatellite markers located within 1 Mb of the FMR1 CGG repeat, and the AMELX/Y dimorphism for gender identification. The assay was optimised and validated on single lymphoblasts isolated from fragile X reference cell lines, and applied to a simulated PGD case and a clinical in vitro fertilisation (IVF)-PGD case. In the simulated PGD case, definitive diagnosis of the expected results was achieved for all ‘embryos’. In the clinical IVF-PGD case, delivery of a healthy baby girl was achieved after transfer of an expansion-negative blastocyst. FMR1 TP-PCR reliably detects presence of expansion mutations and obviates reliance on informative normal alleles for determining expansion status in female embryos. Together with multi-marker haplotyping and gender determination, misdiagnosis and diagnostic ambiguity due to allele dropout is minimised, and couple-specific assay customisation can be avoided.
Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.
LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.
Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.
These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.
Supraglacial ponds play a key role in absorbing atmospheric energy and directing it to the ice of debris-covered glaciers, but the spatial and temporal distribution of these features is not well documented. We analyse 172 Landsat TM/ETM+ scenes for the period 1999–2013 to identify thawed supraglacial ponds for the debris-covered tongues of five glaciers in the Langtang Valley of Nepal. We apply an advanced atmospheric correction routine (Landcor/6S) and use band ratio and image morphological techniques to identify ponds and validate our results with 2.5 m Cartosat-1 observations. We then characterize the spatial, seasonal and interannual patterns of ponds. We find high variability in pond incidence between glaciers (May–October means of 0.08–1.69% of debris area), with ponds most frequent in zones of low surface gradient and velocity. The ponds show pronounced seasonality, appearing in the pre-monsoon as snow melts, peaking at the monsoon onset at 2% of debris-covered area, then declining in the post-monsoon as ponds drain or freeze. Ponds are highly recurrent and persistent, with 40.5% of pond locations occurring for multiple years. Rather than a trend in pond cover over the study period, we find high interannual variability for each glacier after controlling for seasonality.
In current practice, children with anatomically normal hearts routinely undergo fluoroscopy-free ablations. Infants and children with congenital heart disease (CHD) represent the most difficult population to perform catheter ablation without fluoroscopy. We report two neonatal patients with CHD in whom cardiac ablations were performed without fluoroscopy. The first infant had pulmonary atresia with intact ventricular septum with refractory supraventricular tachycardia, and the second infant presented with Ebstein’s anomaly of the tricuspid valve along with persistent supraventricular tachycardia. Both patients underwent uncomplicated, successful ablation without recurrence of arrhythmias. These cases suggest that current approaches to minimising fluoroscopy may be useful even in challenging patients such as neonates with CHD.
In order to define the cathodoluminescence (CL) properties of magmatic topaz and its relation with trace-element composition, we studied topaz phenocrysts from the Ary-Bulak ongonite massif, Russia using a wide array of analytical techniques. Scanning electron microscopy CL panchromatic images reveal strong variations, which define micrometre-scale euhedral growth textures. Several truncations of these growth textures occur in single grains implying multiple growth and resorption events. The CL-spectra of both CLbright and -dark domains have a major peak in the near-ultraviolet centred at 393 nm. Cathodoluminescence images taken after several minutes of electron bombardment show decreasing emission intensity. Electron microprobe analyses indicate high F concentrations (average OH/(OH + F) = 0.04 calculated by difference, 100 wt.% – total from electron probe microanalyses), consistent with what has been found previously in topaz-bearing granites, and the OH stretching vibration (∼3653 cm–1) was detected in Raman spectra. Laser ablation inductively-coupled plasma mass spectrometry traverses performed across the CL textures detected trace elements at ppm to thousands of ppm levels, including: Fe, Mn, Li, Be, B, P, Nb, Ta, W, Ti, Ga, light rare-earth elements, Th and U. Lithium, W, Nb and Ta appear to be correlated with CL intensity, suggesting a role for some of these elements in the activation of CL in topaz. In contrast, no clear correlation was found between CL intensity and F contents, despite the fact that the replacement of OH for F is known to affect the cell parameters of topaz.
Antarctica Bedmap2 datasets are used to calculate subglacial hydraulic potential and the area, depth and volume of hydraulic potential sinks. There are over 32 000 contiguous sinks, which can be thought of as predicted lakes. Patterns of subglacial melt are modelled with a balanced ice flux flow model, and water fluxes are cumulated along predicted flow pathways to quantify steady-state fluxes from the main basin outlets and from known subglacial lakes. The total flux from the continent is ~21 km3 a−1. Byrd Glacier has the greatest basin flux of ~2.7 km3 a−1. Fluxes from subglacial lakes range from ~1 × 10−4 to ~1.5 km3 a−1. Lake turnover times are calculated from their volumes and fluxes, and have median values of ~100 a for known ‘active’ lakes and ~500 a for other lakes. Recurrence intervals of a 0.25 km3 flood range from ~2 months to ~2000 a (median ≈130 a) for known ‘active’ lakes and from ~2 to ~2400 a (median ≈ 360 a) for other lakes. Thus, several lakes that have recently been observed to fill and drain may not do so again for many centuries; and several lakes that have not, so far, been observed to fill and drain have the potential to do so, even at annual to decadal timescales.
Glaciers and ice caps around the world are changing quickly, with surge-type behaviour superimposed upon climatic forcing. Here, we study Iceland's second largest ice cap, Langjökull, which has both surge- and non-surge-type outlets. By differencing elevation change with surface mass balance, we estimate the contribution of ice dynamics to elevation change. We use DEMs, in situ stake measurements, regional reanalyses and a mass-balance model to calculate the vertical ice velocity. Thus, we not only compare the geodetic, modelled and glaciological mass balances, but also map spatial variations in glacier dynamics. Maps of emergence and submergence velocity successfully highlight the 1998 surge and subsequent quiescence of one of Langjökull's outlets by visualizing both source and sink areas. In addition to observing the extent of traditional surge behaviour (i.e. mass transfer from the accumulation area to the ablation area followed by recharge of the source area), we see peripheral areas where the surge impinged upon an adjacent ridge and subsequently retreated. While mass balances are largely in good agreement, discrepancies between modelled and geodetic mass balance may be explained by inaccurate estimates of precipitation, saturated adiabatic lapse rate or degree-day factors. Nevertheless, the study was ultimately able to investigate dynamic surge behaviour in the absence of in situ measurements during the surge.
Supraglacial ponds on debris-covered glaciers present a mechanism of atmosphere/glacier energy transfer that is poorly studied, and only conceptually included in mass-balance studies of debris-covered glaciers. This research advances previous efforts to develop a model of mass and energy balance for supraglacial ponds by applying a free-convection approach to account for energy exchanges at the subaqueous bare-ice surfaces. We develop the model using field data from a pond on Lirung Glacier, Nepal, that was monitored during the 2013 and 2014 monsoon periods. Sensitivity testing is performed for several key parameters, and alternative melt algorithms are compared with the model. The pond acts as a significant recipient of energy for the glacier system, and actively participates in the glacier’s hydrologic system during the monsoon. Melt rates are 2-4 cm d-1 (total of 98.5 m3 over the study period) for bare ice in contact with the pond, and <1 mmd-1 (total of 10.6m3) for the saturated debris zone. The majority of absorbed atmospheric energy leaves the pond system through englacial conduits, delivering sufficient energy to melt 2612 m3 additional ice over the study period (38.4 m3 d-1). Such melting might be expected to lead to subsidence of the glacier surface. Supraglacial ponds efficiently convey atmospheric energy to the glacier’s interior and rapidly promote the downwasting process.
Food has a considerable environmental impact. Diets with less meat and dairy reduce environmental impact but may pose nutritional challenges for children. The current modelling study investigates the impact of diets with less or no meat and dairy products on nutrient intakes.
Energy and nutrient intakes were assessed for observed consumption patterns (reference) and two replacement scenarios with data from the Dutch National Food Consumption Survey – Young Children (2005–2006). In the replacement scenarios, 30 % or 100 % of the consumed dairy and meat (in grams) was replaced by plant-derived foods with similar use.
Children (n 1279) aged 2–6 years.
Partial and full replacement of meat and dairy foods by plant-derived foods reduced SFA intake by 9 % and 26 %, respectively, while fibre intake was 8 % and 29 % higher. With partial replacement, micronutrient intakes were similar, except for lower vitamin B12 intake. After full meat and dairy replacement, mean intakes of Ca, Zn and thiamin decreased by 5–13 %, and vitamin B12 intake by 49 %, while total intake of Fe was higher but of lower bioavailability. With full replacement, the proportion of girls aged 4–6 years with intakes below recommendations was 15 % for thiamin, 10 % for vitamin B12 and 6 % for Zn.
Partial replacement of meat and dairy by plant-derived foods is beneficial for children’s health by lowering SFA intake, increasing fibre content and maintaining similar micronutrient intakes. When full replacements are made, attention is recommended to ensure adequate thiamin, vitamin B12 and Zn intakes.
This study investigated the benefits of hot-water spraying (HWS) as a diagnostic test to verify the absence of signs of life (SOL) before scalding in pigs slaughtered with carbon dioxide (CO2) stunning. A total of 37 108 finishing pigs from five German abattoirs (A to E) operating at 55 to 571 pigs per hour were assessed. Suspended pigs were sprayed onto the muzzle, head and front legs (143 to 258 s post sticking for 4 to 10 s, 57°C to 72°C). Any active movements during HWS were rated as positive test outcomes. In comparison, SOL were considered to be absent if a subsequent manual examination was negative and no active movements were observed following HWS. The incidence of pigs with activity during hot-water spraying (PWA) was restricted to two abattoirs (B: 0.25%; D: 0.02%; A, C, E: 0.00%). PWA showed movements of facial muscles (88%), mouth opening (78%), righting reflex (63%), isolated leg movements (35%) and vocalization (4%). The manual examination was positive in 71% of PWA (corneal/dazzle reflex: 67%/53%, nasal septum pinch: 33%), whereas all inactive pigs tested negative (P<0.001). The sensitivity for HWS as a test for SOL was calculated as 100%, dropping to 75% when only obvious and strong movements were taken into account. The specificity was >99.9% in either case. Any positive manual findings as well as any respiratory activity were instantly terminated using a penetrating captive bolt. Active movements triggered by the shot were shown to be an indicator for SOL (P<0.001). Video analyses revealed that spontaneous movements (SM) following sticking were present in 100% of PWA as opposed to 3.1% in pigs without such activity (controls). Results for different categories of SM in PWA v. controls were as follows: 100% v. 2.6% for mouth opening, 16.0% v. 0.1% for righting reflex and 22.0% v. 0.9% for isolated leg movements (all P<0.001). First mouth opening after sticking was observed later in PWA (28±24 v. 10±7 s), but mouth openings were observed for a longer period of time (141±44 v. 27±25 s) (both P<0.001). PWA with shorter mouth-opening intervals showed higher movement intensities during HWS and more positive manual findings (P<0.05). We conclude that HWS is a promising test for SOL. SM and sustained mouth opening in particular are indicators for compromised animal welfare and affected pigs should be shot by captive bolt.