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Staphylococcus aureus nasal carriers were randomized (1:1) to XF-73 or placebo nasal gel, administered 5x over ∼24hrs pre-cardiac surgery. S. aureus burden rapidly decreased after 2 doses (–2.2log10 CFU/mL; placebo –0.01log10 CFU/mL) and was maintained to 6 days post-surgery. Among XF-73 patients, 46.5% received post-operative anti-staphylococcal antibiotics versus 70% in placebo (P = 0.045).
Identifying thrombus formation in Fontan circulation has been highly variable, with reports between 17 and 33%. Initially, thrombus detection was mainly done through echocardiograms. Delayed-enhancement cardiac MRI is emerging as a more effective imaging technique for thrombus identification. This study aims to determine the prevalence of occult cardiac thrombosis in patients undergoing clinically indicated cardiac MRI.
Methods:
A retrospective chart review of children and adults in the Duke University Hospital Fontan registry who underwent delayed-enhancement cardiac MRI. Individuals were excluded if they never received a delayed-enhancement cardiac MRI or had insufficient data. Demographic characteristics, native heart anatomy, cardiac MRI measurements, and thromboembolic events were collected for all patients.
Results:
In total, 119 unique individuals met inclusion criteria with a total of 171 scans. The median age at Fontan procedure was 3 (interquartile range 1, 4) years. The majority of patients had dominant systemic right ventricle. Cardiac function was relatively unchanged from the first cardiac MRI to the third cardiac MRI. While 36.4% had a thrombotic event by history, only 0.5% (1 patient) had an intracardiac thrombus detected by delayed-enhancement cardiac MRI.
Conclusions:
Despite previous echocardiographic reports of high prevalence of occult thrombosis in patients with Fontan circulation, we found very low prevalence using delayed-enhancement cardiac MRI. As more individuals are reaching adulthood after requiring early Fontan procedures in childhood, further work is needed to develop thrombus-screening protocols as a part of anticoagulation management.
Air-dried and high-pressure frozen/freeze-etched samples of clinopyroxene and smectite in a saprolitized clinopyroxenite from Koua Bocca, Ivory Coast, West Africa, were compared to characterize textures developed during natural weathering of chain silicates. Comparison with air-dried material allowed evaluation of high-pressure cryofixation as a technique for preserving textures of hydrated clay minerals. Air-dried pyroxene surfaces appear very smooth. Small, flat lamellae, oriented parallel to the c axis, lend a distinct splintery appearance to pyroxene surfaces in fully hydrated samples. These lamellae often display a combination of straight (110) pyroxene edges and a crinkled border, suggestive of smectite. Narrow lenticular (110) open cleavages occur in both preparations and are not a pressurization artifact. Most often these openings contain no secondary minerals. Spaces between pyroxene denticles, lined with collapsed smectite in air-dried samples, are filled with thin packets of anhedral smectite crystallites oriented face to face when hydrated. Smectite microboxwork preserves original topotactic textures developed during isovolumetric pyroxene transformation, and smaller nanoporosity appears in hydrated cryofixed examples. Occasional regions of edge-to-face ‘house of cards’ texture also occur. Elimination of sample preparation artifacts induced by surface tension during air drying demonstrates that pores actually present during a hydration reaction-driven weathering episode are smaller and more numerous than would be inferred from examining air-dried materials.
For 147 hospital-onset bloodstream infections, we assessed the sensitivity, specificity, positive predictive value, and negative predictive value of the National Healthcare Safety Network surveillance definitions of central-line–associated bloodstream infections against the gold standard of physician review, examining the drivers of discrepancies and related implications for reporting and infection prevention.
Protoporphyrinogen oxidase (PPO)-inhibiting herbicides remain an important and useful chemistry 60 yr after their first introduction. In this review, based on topics introduced at the Weed Science Society of America 2021 symposium titled “A History, Overview, and Plan of Action on PPO Inhibiting Herbicides,” we discuss the current state of PPO-inhibiting herbicides. Renewed interest in the PPO-inhibiting herbicides in recent years, due to increased use and increased cases of resistance, has led to refinements in knowledge regarding the mechanism of action of PPO inhibitors. Herein we discuss the importance of the two isoforms of PPO in plants, compile a current knowledge of target-site resistance mechanisms, examine non–target site resistance cases, and review crop selectivity mechanisms. Consistent and reproducible greenhouse screening and target-site mutation assays are necessary to effectively study and compare PPO-inhibitor resistance cases. To this end, we cover best practices in screening to accurately identify resistance ratios and properly interpret common screens for point mutations. The future of effective and sustainable PPO-inhibitor use relies on development of new chemistries that maintain activity on resistant biotypes and the promotion of responsible stewardship of PPO inhibitors both new and old. We present the biorational design of the new PPO inhibitor trifludimoxazin to highlight the future of PPO-inhibitor development and discuss the elements of sustainable weed control programs using PPO inhibitors, as well as how responsible stewardship can be incentivized. The sustained use of PPO inhibitors in future agriculture relies on the effective and timely communication from mode of action and resistance research to agronomists, Extension workers, and farmers.
Precision Medicine is an approach to disease treatment and prevention taking into account individual genetic, environmental, therapeutic and lifestyle variability for each person. This holistic approach to therapeutics is intended to enhance drug efficacy and safety not only across healthcare systems but for individual patients. While weight and to some extent gestational age have been considered in determining drug dosing in children, historically other factors including genetic variability have not been factored into therapeutic decision making. As our knowledge of the role of ontogeny and genetics in determining drug efficacy and safety has expanded, these insights have provided new opportunities to apply principles of Precision Medicine to the care of infants, children and youth. These opportunities are most likely to be achieved first in select sub-groups of children. While there are many challenges to the successful implementation of Precision Medicine in children including the need to ensure that Precision Medicine enhances rather than reduces equity in children’s health care rather, there are many more opportunities. Research, advocacy, planning and teamwork are required to move Precision Medicine forward in children in pursuit of the common goal of safe and effective drug therapy.
In this survey of 41 hospitals, 18 (72%) of 25 respondents reporting utilization of National Healthcare Safety Network resources demonstrated accurate central-line–associated bloodstream infection reporting compared to 6 (38%) of 16 without utilization (adjusted odds ratio, 5.37; 95% confidence interval, 1.16–24.8). Adherence to standard definitions is essential for consistent reporting across healthcare facilities.
Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC).
Design:
Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC.
Setting:
Participants were recruited from Memory Services in the North East of England.
Participants:
Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC.
Measurements:
Olfaction was assessed using SS-16 and a questionnaire.
Results:
Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62–3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51–5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69–94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them.
Conclusions:
MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.
ABSTRACT IMPACT: A single seismocardiography (SCG) parameter has been shown to accurately classify aortic valve disease (AVD) status in healthy controls and AVD patients. This could support development of SCG as a quick, inexpensive screening tool to better tailor MRI examination to patients’ needs. OBJECTIVES/GOALS: MRI is used commonly for monitoring of aortic valve disease (AVD), but it has high costs. We hypothesize that energy in seismocardiograms (SCG)’‘ signals from chest surface vibrations’‘ is different between healthy controls and AVD patients, and we evaluate potential efficacy of using SCG to recommend MRI only for patients with flow abnormalities. METHODS/STUDY POPULATION: With IRB approval, 45 healthy control subjects (47 ±18years, 18 female) and 9 patients (63 ±16years, 2 female) with aortic valve disease history and known flow abnormalities were recruited. SCG signals were acquired supine, immediately prior to MRI of thoracic aortic blood flow at 1.5T with a time-resolved phase contrast (4D Flow) sequence.
The SCG was processed to calculate late-systole high-frequency (120-240Hz) RMS energy. MR velocity images were analyzed to measure peak velocity and trace pathlines of flow.
Screening efficacy of the SCG energy metric was assessed, with hypothesis testing for differences in energy level distributions between controls and patients, and receiver-operator characteristic (ROC) analysis was used to calculate rates of correct/incorrect classification of disease. RESULTS/ANTICIPATED RESULTS: Healthy subjects had coherent flow pathlines through the aortic arch and mid-ascending aorta peak velocities of 106 ±21cm/s (cohort mean ±standard deviation). All valve disease subjects had flow abnormalities, such as jetting flow near the valve or swirling through the arch, as visualized by pathlines. Patients’ peak mid-ascending aorta velocities were 167 ±69cm/s. The SCG energy for healthy controls was significantly different than that of valve patients (-5.6 ±0.3dBmm/s/s vs. -4.0 ±1.2dBmm/s/s respectively; p<0.001). Thresholding SCG energy to distinguish patients from controls correctly classifies subjects with a high true-positive rate and low false-positive rate. The ROC for this classification has area-under-curve 0.956. DISCUSSION/SIGNIFICANCE OF FINDINGS: A high potential screening efficacy was observed using a single, linear SCG metric to identify AVD patients with flow abnormalities. If used to complement MRI surveillance protocols for AVD, this method has potential to serve as a quick, inexpensive tool for better tailoring MRI exams to patient needs.
Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.
Methods
Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).
Results
We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.
Conclusions
Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
Aims
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.
Method
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.
Results
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.
Conclusions
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
To explore, from the perspectives of adolescents and caregivers, and using qualitative methods, influences on adolescent diet and physical activity in rural Gambia.
Design:
Six focus group discussions (FGD) with adolescents and caregivers were conducted. Thematic analysis was employed across the data set.
Setting:
Rural region of The Gambia, West Africa.
Participants:
Participants were selected using purposive sampling. Four FGD, conducted with forty adolescents, comprised: girls aged 10–12 years; boys aged 10–12 years; girls aged 15–17 years, boys aged 15–17 years. Twenty caregivers also participated in two FGD (mothers and fathers).
Results:
All participants expressed an understanding of the association between salt and hypertension, sugary foods and diabetes, and dental health. Adolescents and caregivers suggested that adolescent nutrition and health were shaped by economic, social and cultural factors and the local environment. Adolescent diet was thought to be influenced by: affordability, seasonality and the receipt of remittances; gender norms, including differences in opportunities afforded to girls, and mother-led decision-making; cultural ceremonies and school holidays. Adolescent physical activity included walking or cycling to school, playing football and farming. Participants felt adolescent engagement in physical activity was influenced by gender, seasonality, cultural ceremonies and, to some extent, the availability of digital media.
Conclusions:
These novel insights into local understanding should be considered when formulating future interventions. Interventions need to address these interrelated factors, including misconceptions regarding diet and physical activity that may be harmful to health.
Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort.
Methods
Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis.
Results
Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD.
Conclusions
MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.
Emerging data suggest that recovery from mild traumatic brain injury (mTBI) takes longer than previously thought. This paper examines trajectories for cognitive recovery up to 48 months post-mTBI, presenting these visually using a Sankey diagram and growth curve analysis.
Methods:
This sample (n = 301) represents adults (≥16 years) from a population-based Brain Injury Outcomes in the New Zealand Community study over a 4-year follow-up on the CNS-Vital Signs neuropsychological test. Data were collected within 2 weeks of injury, and then at 1, 6, 12 and 48 months post-injury.
Results:
Significant improvement in cognitive functioning was seen up to 6 months post-injury. Using growth curve modelling, we found significant improvements in overall neurocognition from baseline to 6 months, on average participants improved one point per month (0.9; 95% CI 0.42–1.39) p < 0.001. No change in neurocognition was found within the time periods 6–12 months or 12–48 months. The Sankey highlighted that at each time point, a small proportion of participants remained unchanged or declined. Proportionally, few show any improvement after the first 6 months.
Conclusion:
Most individuals remained stable or improved over time to 6 months post-injury. Summary statistics are informative regarding overall trends, but can mask differing trajectories for recovery. The Sankey diagram indicates that not all improve, as well as the potential impact of individuals moving in and out of the study. The Sankey diagram also indicated the level of functioning of those most likely to withdraw, allowing targeting of retention strategies.
Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal–infant bonding. On the basis of expected physiology, maternal–infant bonding may be safe for select cardiac diagnoses.
Methods
This is a single-centre study to assess safety of maternal–infant bonding in prenatal CHD.
Results
In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001).
Conclusion
Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.
Field studies were conducted in North Carolina in 1981 and 1982 to evaluate the efficacy of postemergence over-the-top and postemergence-directed herbicides for control of five morningglory species: entireleaf [Ipomoea hederacea (L.) Jacq. var. integriuscula Gray], tall [Ipomoea purpurea (L.) Roth. ♯3 PHBPU], ivyleaf [Ipomoea hederacea (L.) Jacq. var. hederacea ♯IPOHE], pitted [Ipomoea lacunosa (L.) ♯ IPOLA], and scarlet [Ipomoea coccinea (L.) ♯IPOCC]. The glabrous morningglories (scarlet and pitted) were more easily controlled than the pubescent morningglories (ivyleaf, tall, and entireleaf). Lower soybean injury, higher morningglory control, and greater soybean seed yields were obtained with over-the-top herbicide applications at 4 weeks after planting (WAP) than at 6 WAP. Pitted morningglory was tolerant to low rates of 2,4-DB [4-(2,4-dichlorophenoxy) butyric acid]. This herbicide applied over the top at the R1 stage of soybean growth produced low yields, probably as a result of morningglory interference and herbicide injury to the soybeans. Postemergence-directed applications of linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] and metribuzin [4-amino-6-tert-butyl-3-(methylthio-as-triazin-5(4H)-one] alone or in tank mixtures with 2,4-DB resulted in soybean injury that ranged from 12 to 36%. Highest soybean seed yields (equivalent to weed-free control) from postemergence-directed herbicides were obtained with applications of 2,4-DB, linuron, and a tank mixture of metribuzin and 2,4-DB.
The increasing importance of landscape-scale research and preservation goals within the archaeological profession coincides with expanded threats to the archaeological record through massive energy exploration and infrastructure projects and through the cumulative effects of smaller-scale development. It is further stimulated by the recognition that conservation strategies that span multiple resource classes and disciplines are best formulated at multiple and larger spatial scales. These are key drivers behind efforts to improve the ways that archaeological resources are considered in the context of development-related planning and implementation, including mitigation measures. In a prominent example, recent department-level direction from the Secretary of the Interior calls specifically for landscape-level planning as a critical component of responses to both large-scale development and climate change. This article reviews three current approaches to landscape-level planning in archaeology and calls for increased commitment to advancing their development and effectiveness.
In nature, biomolecules guide the formation of hierarchically-ordered, lightweight, inorganic-organic composites such as corals, shells, teeth and bones. M13 bacteriophage has been used to mimic bio-inspired material development due to its rigid, nanoscale rod-like morphology. Liquid-crystalline monolayers of genetically engineered phage have been used to template crystallization of thin layers of inorganic and metallic materials. We have created thin films composed of engineered M13 phage capable of binding inorganic components. We employed both a dip-cast and a drop-cast film fabrication method on both smooth and rough gold, silica and glass casting surfaces to create thin films and 3D structures of various degrees of hierarchical order. We have found the engineered M13 phage and the inorganic mineral significantly affected both film morphology and the mechanical properties of the film. Similarly, film fabrication parameters such as solution chemistry, temperature, and pulling speed affected film properties. Using a calcium phosphate biomineralized 4E phage, film thickness increased linearly with the number of layers/dips in the phage solution. The stiffness of these composites (Young's modulus) were >80 GPa for mineralized, multilayer films. These materials are an order of magnitude stiffer than the biological equivalent collagen. Stiffness, however, does not appear to increase in a multilayer film beyond a saturation point. Ultimately, we have developed a platform for phage-based bio-composites for developing high performance materials.