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Trimethoprim crystallizes in the triclinic space group P-1 (#2) with a = 10.5085(3), b = 10.5417(2), c = 8.05869(13) Å, α = 101.23371(21), β = 112.1787(3), γ = 112.6321(4)°, V = 743.729 Å3, and Z = 2. A reduced cell search in the Cambridge Structural Database yielded three previous structure determinations, using data collected at 100 K, 173 K, and room temperature. In this work, the sample was ordered from the United States Pharmacopeial Convention (USP) and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.412826 Å) powder diffraction data and optimized using density functional theory techniques. We found similar hydrogen bonding patterns with the previous determinations. In addition, we identified two C–H⋯O hydrogen bonds, which also contribute to the crystal energy. When comparing the previously reported trimethoprim structure determinations, the unit cell length lattice parameters were found to contract at lower temperatures, particularly 100 K. All structures show reasonable agreement, with unit cell length differences ranging between 0.05 and 0.15 Å. The diffraction data for this study were collected on beamline 11-BM at the Advanced Photon Source, and the powder X-ray diffraction pattern of the compound has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).
In this study, the thermal deformation of a machine tool structure due to the heat generated during operation was analyzed, and embedded cooling channels were applied to exchange the heat generated during the operation to achieve thermal error suppression. Then, the finite volume method was used to simulate the effect of cooling oil temperature on thermal deformation, and the effect of thermal suppression was experimentally studied using a feed system combined with a cooler to improve the positioning accuracy of the machine tool. In this study, the supply oil temperature in the structural cooling channels was found to significantly affect the position accuracy of the moving table and moving carrier. If the supply oil temperature in the cooling channels is consistent with the operational ambient temperature, the position accuracy of the moving table in the Y direction and the moving carrier in the X and Z directions has the best performance under different feed rates. From the thermal suppression experiments of the embedded cooling channels, the positioning accuracy of the feed system can be improved by approximately 25.5 % during the dynamic feeding process. Furthermore, when the hydrostatic guideway is cooled and dynamic feeding is conducted, positioning accuracy can be improved by up to 47.8 %. The machining accuracy can be improved by approximately 60 % on average by using the embedded cooling channels in this study. Therefore, thermal suppression by the cooling channels in this study can not only effectively improve the positioning accuracy but also enhance machining accuracy, proving that the method is effective for enhancing machine tool accuracy.
In the nearly a quarter of a century since the addition of the clinically significant distress/impairment criterion to the definition of PTSD in DSM-IV, little research has been done to examine the association of this criterion with symptom group criteria and with the numbing subgroup specifically. This study was conducted to examine these relationships in a large database of disaster survivors consistently studied across 12 different incidents of the full range of disaster typology.
Analysis was conducted on a merged database representing 1187 trauma-exposed survivors of 12 different disasters studied systematically. DSM-IV-TR criteria for disaster-related PTSD were assessed with the Diagnostic Interview Schedule.
PTSD Group C (avoidance/numbing) and numbing specifically were less common and more associated than other symptom groups with criterion F (distress/impairment). Consistently in multivariable models, group C and numbing were independently associated with criterion F. Group D (hyperarousal) was less strongly associated with criterion F. Neither group B (intrusion) nor avoidance were associated with criterion F.
In this and other studies, group C and numbing specifically have been shown to be associated with criterion F, which is consistent with the demonstration that group C and the numbing component specifically are central to the psychopathology of PTSD. The addition of the distress/impairment requirement broadly across the psychiatric diagnoses in DSM-IV added little value to PTSD symptom criteria. Future revisions of diagnostic criteria may benefit by carefully considering these findings to possibly re-include a prominent numbing symptom section.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
The authors demonstrate that gold-binding peptides displayed on the outer membrane of Escherichia coli enhance bioelectrochemical charge transfer by binding gold nanoparticles. Microbial fuel cells were run with different gold-binding peptides displayed and with different nanoparticle sizes, and the results were correlated with transmission electron microscopy (TEM) imaging of nanoparticle binding. When a gold-binding peptide is displayed and 5 nm gold nanoparticles are present, up to 4× power generation over E. coli not displaying a gold-binding peptide is observed. While an enhanced current is observed using the previously published M6G9, the largest enhancement is observed when a new longer peptide named M9G18 is used.
Habitat prioritization and corridor restoration are important steps for reconnecting fragmented habitats and species populations, and spatial modelling approaches are useful in identifying suitable habitat for elusive tropical rainforest mammals. The Endangered Bornean banteng Bos javanicus lowi, a wild bovid endemic to Borneo, occurs in habitat that is highly fragmented as a result of extensive agricultural expansion. Based on the species’ historical distribution in Sabah (Malaysia), we conducted camera-trap surveys in 14 forest reserves during 2011–2016. To assess suitable habitat for the banteng we used a presence-only maximum entropy (MaxEnt) approach with 11 spatial predictors, including climate, infrastructure, land cover and land use, and topography variables. We performed a least-cost path analysis using Linkage Mapper, to understand the resistance to movement through the landscape. The surveys comprised a total of 44,251 nights of camera trapping. We recorded banteng presence in 11 forest reserves. Key spatial predictors deemed to be important in predicting suitable habitat included soil associations (52.6%), distance to intact and logged forests (11.8%), precipitation in the driest quarter (10.8%), distance to agro-forest and regenerating forest (5.7%), and distance to oil palm plantations (5.1%). Circa 11% of Sabah had suitable habitat (7,719 km2), of which 12.2% was in protected forests, 60.4% was in production forests and 27.4% was in other areas. The least-cost path model predicted 21 linkages and a relatively high movement resistance between core habitats. Our models provide information about key habitat and movement resistance for bantengs through the landscape, which is crucial for constructive conservation strategies and land-use planning.
Ca and dairy product intakes may be inversely associated with all-cause and cause-specific mortality, and non-Ca components of dairy products, such as insulin-like growth factor-1, may be independently associated with mortality. We investigated associations of Ca and dairy product intakes with all-cause, all-cancer, colorectal cancer (CRC) and CHD mortality among 35 221 55- to 69-year-old women in the prospective Iowa Women’s Health Study, who were cancer-free in 1986. We assessed diet using a Willett FFQ, and associations using multivariable Cox proportional hazards regression. We estimated residuals from linear regression models of dairy products with dietary Ca to investigate total and specific dairy products independent of their Ca content. Through 2012, 18 687 participants died, including 4665 from cancer (including 574 from CRC) and 3603 from CHD. For those in the highest relative to the lowest quintiles of intake, the multivariable-adjusted hazard ratios (HR) and 95 % CI for total Ca (dietary plus supplemental) were 0·88 (0·83, 0·93; P trend=0·001) for all-cause mortality, 0·91 (0·81, 1·02; P trend=0·34) for all-cancer mortality, 0·60 (0·43, 0·83; P trend=0·002) for CRC mortality and 0·73 (0·64, 0·83; P trend <0·0001) for CHD mortality. The corresponding HR for associations of whole milk, whole milk residuals, and low-/non-fat milk residuals with all-cause mortality were 1·20 (95 % CI 1·13, 1·27), 1·20 (95 % CI 1·13, 1·28) and 0·91 (95 % CI 0·86, 0·96), respectively. These results suggest that Ca may be associated with lower risk of all-cause, CRC and CHD mortality, and that non-Ca components of milk may be independently associated with mortality.
OBJECTIVES/SPECIFIC AIMS: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences.The objective was to test the effectiveness of a prediabetes SDM intervention. METHODS/STUDY POPULATION: This was a cluster-randomized controlled trial in 20 primary care clinics within a large regional health system. Participants were overweight/obese adults with prediabetes (BMI>24 kg/m2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics.Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention; DPP, DPP +/− metformin, metformin only, or usual care. RESULTS/ANTICIPATED RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n=351) than controls receiving usual care (n = 1,028; 38% vs. 2%, p<.001). At 12-months follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (−5.3 vs. −0.2, p < .001). DISCUSSION/SIGNIFICANCE OF IMPACT: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4-months and weight loss at 12-months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk.
Many seed quality tests are conducted by first randomly assigning seeds into replicates of a given size. The replicate results are then used to check whether or not any problems occur in the realization of the test. The two main tools developed for this verification are the ratio of the observed variance of the replicate results to a theoretical variance and the tolerance for the range of the results. In this paper, we derive the theoretical distribution and its related properties of the sequence of numbers of seeds with a given quality attribute present in the replicates. From these theoretical results, we revisit the two quality checking tools widely used for the germination test. We show a precaution to be taken when relying on the variance ratio to check for under- or over-dispersion of the replicate results. This has led to the development of tables providing credible intervals of the variance ratio. The International Seed Testing Association tolerance tables for the range of the results are also compared with tolerances computed from the exact theoretical distribution of the range, leading us to recommend a revision of these tables.
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
This work focuses on the development of a system to control the formation of bone to complement developments that have enabled potent regeneration of bony tissue. Scaffolds were fabricated with chemically modified RNA encoding for bone morphogenetic protein-9 (cmBMP9) and capped with salicylic acid (SA)-containing polymer (SAPAE). The goal was to determine if SAPAE could inhibit the formation of bone in a pilot animal study since cmBMP9 has been demonstrated to be highly effective in regenerating bone in a rat calvarial defect model. The results indicated that cmBMP9 increased bone formation (30% increase in area covered compared to control) and that SAPAE trended toward reducing the bone formation. These results suggest SAPAE could be useful as a chemical agent in reducing unwanted bone formation in implants loaded with cmBMP9.
Traditional decision rules have limitations when a new technology is less effective and less costly than a comparator. We propose a new probabilistic decision framework to examine non-inferiority in effectiveness and net monetary benefit (NMB) simultaneously. We illustrate this framework using the example of repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT) for treatment-resistant depression.
We modeled the quality-adjusted life-years (QALYs) associated with the new intervention (rTMS), an active control (ECT), and a placebo control, and we estimated the fraction of effectiveness preserved by the new intervention through probabilistic sensitivity analysis (PSA). We then assessed the probability of cost-effectiveness using a traditional cost-effectiveness acceptability curve (CEAC) and our new decision-making framework. In our new framework, we considered the new intervention cost-effective in each simulation of the PSA if it preserved at least 75 percent of the effectiveness of the active control (thus demonstrating non-inferiority) and had a positive NMB at a given willingness-to-pay threshold (WTP).
rTMS was less effective (i.e., associated with fewer QALYs) and less costly than ECT. The traditional CEAC approach showed that the probabilities of rTMS being cost-effective were 100 percent, 39 percent, and 14 percent at WTPs of $0, $50,000, and $100,000 per QALY gained, respectively. In the new decision framework, the probabilities of rTMS being cost-effective were reduced to 23 percent, 21 percent, and 13 percent at WTPs of $0, $50,000, and $100,000 per QALY, respectively.
This new framework provides a different perspective for decision making with considerations of both non-inferiority and WTP thresholds.
Nearby star-forming galaxies offer a unique environment to study the populations of young (<100 Myr) accreting binaries. These systems are tracers of past populations of massive stars that heavily affect their immediate environment and parent galaxies. Using a Chandra X-ray Visionary program, we investigate the young neutron-star binary population in the low metallicity of the Small Magellanic Cloud (SMC) by reaching quiescent X-ray luminosity levels (~few times 1032 erg/s). We present the first measurement of the formation efficiency of high-mass X-ray binaries (HMXBs) as a function of the age of their parent stellar populations by using 3 indicators: the number ratio of HMXBs to OB stars, to the SFR, and to the stellar mass produced during the specific star-formation burst they are associated with. In all cases, we find that the HMXB formation efficiency increases as a function of time up to ~40–60 Myr, and then gradually decreases.
Background: Localization of intramedullary spine tumors can be difficult. Various intraoperative aids have previously been described, but have limited use due to expense, complexity, and time. Intravenous fluorescein is an inexpensive and safe drug that may be useful in the localization of such tumors. We describe a technical description of the intra-operative use of fluorescein as an aid in the localization of a intramedullary spine tumour. Methods: In this technical report, the authors present a case example of a 56 year old man presenting with a intramedullary tumor at the level of C5/6. Intra-operatively intravenous Fluorescein was administered and the Pentero microscope BLUE™ 400 feature was used to accurately identify the lesion. Multiple biopsies of the fluorescent tissue were taken. Results: After 10 cardiac cycles the fluorescent coloring was isolated to what was thought to be the intramedullary lesion. Our myelotomy was made based on the uptake of this fluorescent coloring and multiple biopsies were taken. Final pathology confirmed this tissue was consistent with a high grade glioma. Conclusions: The use of intravenous fluorescein was a valuable aid in localizing the lesion and minimizing the size of our myelotomy. The use of intravenous fluorescein to localize high grade intramedullary spinal cord tumours appears to be safe, accurate, and inexpensive.
We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.
A 2,000-bed tertiary-care psychiatric hospital.
Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)–based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.
The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1–C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0–5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21–45 and 26–58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.
WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.
Introduction: Approximately 50% of patients discharged from the Emergency Department (ED) after syncope have no cause found. Long-term outcomes among syncope patients are not well studied, to guide physicians regarding outpatient testing and follow-up. The objective of this study was to conduct a systematic review for long-term (one year) outcomes among ED patients with syncope. We aim to use the results of this review to guide us in prospective analysis of one year outcomes with our large database of syncope patients. Methods: We searched Cochrane Central Register of Controlled Trials, Medline and Medline in Process, PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from the inception to June, 2017. We included studies that reported long-term outcomes among adult ED patients (16 years or older) with syncope. We excluded studies on pediatric patients, and studies that included syncope mimickers: pre-syncope, seizure, intoxication, loss of consciousness after head trauma. We also excluded case reports, letters to the editor and review articles. Outcomes included death, syncope recurrence requiring hospitalization, arrhythmias and procedural interventions for arrhythmias. We selected articles based on title and abstract review during phase-1 and conducted full article review during phase-2. Meta-analysis was performed by pooling the outcomes using random effects model (RevMan v.5.3; Cochrane Collaboration). Results: Initial literature search generated 2094 articles after duplicate removal. 50 articles remained after phase-1 (=0.85) and 16 articles were included in the systematic review after phase-2 (=0.86). The 16 included studies enrolled a total of 44,755 patients. Pooled analysis at 1-year follow-up showed the following outcomes: 7% mortality; 14% recurrence of syncope requiring hospitalization; one study reported that 0.6% of patients had a pacemaker inserted; and two studies reported 0.8 11.5% of patients suffered new arrhythmias. Conclusion: An important proportion of ED patients with syncope suffer outcomes at 1-year. Appropriate follow-up is needed to prevent long-term adverse outcomes. Further prospective research to identify patients at risk for long-term important cardiac outcomes and death is needed.
To develop an artificial intelligence (AI)-based algorithm which can automatically detect food items from images acquired by an egocentric wearable camera for dietary assessment.
To study human diet and lifestyle, large sets of egocentric images were acquired using a wearable device, called eButton, from free-living individuals. Three thousand nine hundred images containing real-world activities, which formed eButton data set 1, were manually selected from thirty subjects. eButton data set 2 contained 29 515 images acquired from a research participant in a week-long unrestricted recording. They included both food- and non-food-related real-life activities, such as dining at both home and restaurants, cooking, shopping, gardening, housekeeping chores, taking classes, gym exercise, etc. All images in these data sets were classified as food/non-food images based on their tags generated by a convolutional neural network.
A cross data-set test was conducted on eButton data set 1. The overall accuracy of food detection was 91·5 and 86·4 %, respectively, when one-half of data set 1 was used for training and the other half for testing. For eButton data set 2, 74·0 % sensitivity and 87·0 % specificity were obtained if both ‘food’ and ‘drink’ were considered as food images. Alternatively, if only ‘food’ items were considered, the sensitivity and specificity reached 85·0 and 85·8 %, respectively.
The AI technology can automatically detect foods from low-quality, wearable camera-acquired real-world egocentric images with reasonable accuracy, reducing both the burden of data processing and privacy concerns.