Diabat method for polymorph free energies: Extension to molecular crystals

Lattice-switch Monte Carlo and the related diabat methods have emerged as efficient and accurate ways to compute free energy differences between polymorphs. In this work, we introduce a one-to-one mapping from the reference positions and displacements in one molecular crystal to the positions and displacements in another. Two features of the mapping facilitate lattice-switch Monte Carlo and related diabat methods for computing polymorph free energy differences. First, the mapping is unitary so that its Jacobian does not complicate the free energy calculations. Second, the mapping is easily implemented for molecular crystals of arbitrary complexity. We demonstrate the mapping by computing free energy differences between polymorphs of benzene and carbamazepine. Free energy calculations for thermodynamic cycles, each involving three independently computed polymorph free energy differences, all return to the starting free energy with a high degree of precision. The calculations thus provide a force field independent validation of the method and allow us to estimate the precision of the individual free energy differences

Serologic Surveillance of Selected Viral and Bacterial Pathogens in South Carolina’s Feral Swine Population

Feral swine (Sus scrofa) are considered an invasive species that is comprised of the wild descendants of domestic swine, European wild boar, and hybrids of these two species. Feral swine were historically associated with the major river drainages in Coastal South Carolina. However, natural range expansion and human release and relocation of feral swine appear to be sources of their expansion into areas not previously occupied. Although an exact estimate of feral swine population numbers is not available, in 2006 feral swine were reported in 42 of 46 South Carolina counties, compared to 46 of 46 counties reporting feral swine activity in 2011. Feral swine can serve as reservoirs for a number of diseases including pseudorabies, swine brucellosis (Brucella spp.), porcine respiratory and reproductive syndrome and porcine circovirus which may be passed to livestock and, in some cases, native wildlife and humans. The National Wildlife Disease Program within the US Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services conducted serologic surveys for pseudorabies virus, brucellosis, porcine circovirus, and porcine respiratory and reproductive syndrome virus in South Carolina feral pig populations from 2007- 2012. During that period, we opportunistically sampled and collected serum from 545 feral pigs. Overall, 111 of 544 (20.40%) animals tested positive for antibodies to pseudorabies, 87 of 545 (15.96%) animals tested positive for antibodies to brucellosis, 171 of 306 (55.88%) animals tested positive for antibodies to porcine circovirus, and seven of 312 (2.24%) animals tested positive for antibodies to porcine respiratory and reproductive syndrome. Positive cases of pseudorabies and brucellosis were spatially limited to populations closely associated with the major river drainages in Coastal South Carolina. These positive cases of pseudorabies and brucellosis were found in areas of long established pig populations. The seven positive cases of porcine respiratory and reproductive syndrome were limited to one geographic cluster within the Congaree and Wateree river confluence and two clusters along the PeeDee River Drainage. These clusters of seropositive cases indicate a more geographically localized distribution of porcine respiratory and reproductive syndrome. Interestingly, positive cases of porcine circovirus appeared to be evenly distributed across all sample locations in South Carolina. A more spatially and temporally consistent sampling strategy is recommended to investigate linear spread of pathogens along river drainages and throughout the feral swine population in South Carolina

Comparison of Accu Chek Inform II point-of-care test blood glucose meter with Hexokinase Plasma method for a diabetes mellitus population during surgery under general anesthesia

Purpose Blood glucose (BG) concentrations of patients with diabetes mellitus (DM) are monitored during surgery to prevent hypo- and hyperglycemia. Access to point-of-care test (POCT) glucose meters at an operating room will usually provide monitoring at shorter intervals and may improve glycemic control. However, these meters are not validated for patients under general anesthesia. Methods This cross-sectional study included 75 arterial BG measurements from 75 patients (71 with DM, mostly insulin dependent) who underwent elective non-cardiac surgery under general anesthesia. Arterial blood samples were taken at least 60 minutes after induction. One drop of blood was used for Accu Chek Inform II (ACI II) POCT BG meter and the residual blood was sent to the clinical laboratory for a Hexokinase Plasma reference method. A Bland-Altman plot was used to visualize the differences between both methods, and correlation was assessed using the intra-class correlation coefficient (ICC). Results The results showed an estimated mean difference of 0.8 mmol/L between ACI II and the reference method, with limits of agreement equal to -0.6 and 2.2 mmol/L. In general, the reference method produced higher values than ACI II. ICC was 0.955 (95% CI 0.634-0.986), P &lt; 0.001, and concordance correlation coefficient (CCC) was 0.955 (95% CI 0.933-0.970). Conclusion Arterial BG measurements during surgery in patients with DM under general anesthesia using POCT BG meter are in general lower than laboratory measurements, but the ICC and CCC show a clinically acceptable correlation. We conclude that POCT measurements conducted on arterial specimens using the ACI II provide sufficiently accurate results for glucose measurement during surgery under general anesthesia.</p

Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox

High molecular weight homologues of gp91phox, the superoxide-generating subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, have been identified in human (h) and Caenorhabditis elegans (Ce), and are termed Duox for “dual oxidase” because they have both a peroxidase homology domain and a gp91phox domain. A topology model predicts that the enzyme will utilize cytosolic NADPH to generate reactive oxygen, but the function of the ecto peroxidase domain was unknown. Ce-Duox1 is expressed in hypodermal cells underlying the cuticle of larval animals. To investigate function, RNA interference (RNAi) was carried out in C. elegans. RNAi animals showed complex phenotypes similar to those described previously in mutations in collagen biosynthesis that are known to affect the cuticle, an extracellular matrix. Electron micrographs showed gross abnormalities in the cuticle of RNAi animals. In cuticle, collagen and other proteins are cross-linked via di- and trityrosine linkages, and these linkages were absent in RNAi animals. The expressed peroxidase domains of both Ce-Duox1 and h-Duox showed peroxidase activity and catalyzed cross-linking of free tyrosine ethyl ester. Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the stabilization of cuticular extracellular matrix

Two-year use of flash glucose monitoring is associated with sustained improvement of glycemic control and quality of life (FLARE-NL-6)

INTRODUCTION: The FreeStyle Libre (FSL) is a flash glucose monitoring (FGM) system. The Flash Monitor Register in the Netherlands (FLARE-NL-4) study previously demonstrated the positive effects of FSL-FGM use during 1 year on glycemic control, quality of life and disease burden among persons with diabetes mellitus (DM). The present follow-up study assesses the effects of FSL-FGM after 2 years. RESEARCH DESIGN AND METHODS: Patients included in the FLARE-NL-4 study who continued FSL-FGM during the 1-year study period were invited to participate (n=687). Data were collected using questionnaires (the 12-Item Short Form Health Survey version 2 (SF-12(v2)) and the EuroQol 5-Dimension 3-Level (EQ-5D-3L) for quality of life), including self-reported hemoglobin A1c (HbA1c). RESULTS: A total of 342 patients agreed to participate: mean age 48.0 (±15.6) years, 52% men and 79.5% with type 1 DM. HbA1c decreased from 60.7 (95% CI 59.1 to 62.3) mmol/mol before use of FSL-FGM to 57.3 (95% CI 55.8 to 58.8) mmol/mol after 1 year and 57.8 (95% CI 56.0 to 59.5) mmol/mol after 2 years. At the end of the 2-year follow-up period, 260 (76%) persons were still using the FSL-FGM and 82 (24%) had stopped. The main reason for stopping FSL-FGM was financial constraints (55%). Concerning the whole 2-year period, there was a significant decrease in HbA1c among persons who continued use of FSL-FGM (−3.5 mmol/mol, 95% CI −6.4 to –0.7), while HbA1c was unaltered compared with baseline among persons who stopped FSL-FGM (−2.4 mmol/mol, 95% CI −7.5 to 2.7): difference between groups 2.2 (95% CI −1.3 to 5.8) mmol/mol. After 2 years, persons who continued use of FSL-FGM had higher SF-12 mental component score and higher EQ-5D Dutch tariff score and felt less often anxious or depressed compared with persons who discontinued FSL-FGM. CONCLUSIONS: Although the considerable number of non-responders limits generalizability, this study suggests that persons who continue to use FSL-FGM for 2 years may experience sustained improvement in glycemic control and quality of life

Quantitative analysis of orthopedic metal artefact reduction in 64-slice computed tomography scans in large head metal-on-metal total hip replacement, a phantom study

Purpose: Quantification of the effect of O-MAR on decreasing metal artefacts caused by large head metal on metal total hip arthroplasty (MoM THA) in a dedicated phantom setup of the hip. Background: Pathological reactions of the hip capsule on Computed tomography (CT) can be difficult to diagnose due to different metal artefacts. The O-MAR algorithm deploys an iterative loop where the metal sinogram is identified, extracted, and subsequently serves as a mask to correct the measured sinogram. Main goal of this study is to quantify the ability of the O-MAR technique to correct deviation in medullary bone attenuation caused by streak artefacts from the large-head MoM THA embedded in a phantom. Secondary goal is to evaluate the influence of O-MAR on CNR. Methods: The phantom was designed as a Perspex box (PMMA) containing water and a supplementary MOM THA surrounded by Perspex columns comprising calibrated calcium pellets. Each column contains 200 mg of hydroxyapatite/calcium carbonate to simulate healthy bone tissue. Scans were obtained with and without a MoM THA at different dose levels. Different reconstructions were made with filter A, iDose(4) level 5 and with and without O-MAR. The scans without the prosthesis were used as the baseline. Information about the attenuation in Hounsfield units, image noise in standard deviation within the ROI's were extracted and the CNR was calculated. Results: Pellet L0 and R0 (proximal of the MoM THA) were defined as reference, lacking any disturbance by metal artefacts; L5, L6 and L8 were respectively visually categorized as 'light' 'medium' and 'heavy disturbance'. Significant improvements in attenuation deviation caused by metal artefact were 43, 68 and 32 %, for respectively pellet L5, L6 and L8 (p <0.001). Significant CNR improvements were present for L5 and L6 and were respectively 72 and 52 % (p <0.001). O-MAR showed no improvement on CNR for L8. Conclusion: This phantom study significantly increases image quality by the use of O-MAR in the presence of metal artefacts by significantly reducing metal artefacts subsequently and increasing CNR on a 64 slice CT system in light and medium disturbance of the imag

Flash Glucose Monitoring in the Netherlands:Increased monitoring frequency is associated with improvement of glycemic parameters

AIMS: To evaluate the association between flash glucose monitoring (FLASH) frequency and glycemic parameters during real-life circumstances in the Netherlands. METHODS: Obtained glucose readings were de-identified and uploaded to a dedicated database when FLASH reading devices were connected to internet. Data between September 2014 and March 2020, comprising 16,331 analyzable readers (163,762 sensors) were analyzed. Scan rate per reader was determined and each reader was sorted into 20 equally sized rank ordered groups (n=817 each). RESULTS: Users performed a median of 11.5 [IQR 7.7-16.7] scans per day. Those in the lowest and highest ventiles scanned on average 3.7 and 40.0 times per day and had an eHbA1c of 8.6% (71 mmol/mol) and 6.9% (52 mmol/mol), respectively. Increasing scan rates were associated with more time in target range (3.9-10 mmol/L), less time in hyperglycemia (>10 mmol/L), and a lower standard deviation of glucose. An eHbA1c of 7.0% (53 mmol/mol) translated in approximately 65% time in target range, 30% time in hyperglycemia and 5% time in hypoglycemia (<3.9 mmol/L). CONCLUSIONS: These outcomes among Dutch FLASH users suggest that with higher scan rate glycemic control improves