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In a novel approach, SLA 3D-printed Pd(PPh3)4 containing stirrer beads have been used to catalyse the Suzuki–Miyaura reaction between a range of substrates.

The monoterpene camphor is produced in glandular secretory trichomes of the medicinal plant Artemisia annua, which also produces the antimalarial drug artemisinin. We have found that, depending on growth conditions, camphor can accumulate at levels ranging from 1- 10% leaf dry weight (LDW) in the Artemis F1 hybrid, which has been developed for commercial production of artemisinin at up to 1% LDW. We discovered that a camphor null (camphor-0) phenotype segregates in the progeny of self-pollinated Artemis material. Camphor-0 plants also show reduced levels of other less abundant monoterpenes and increased levels of the sesquiterpene precursor farnesyl pyrophosphate plus sesquiterpenes, including enzymatically derived artemisinin pathway intermediates but not artemisinin. One possible explanation for this is that high camphor concentrations in the glandular secretory trichomes play an important role in generating the hydrophobic conditions required for the non-enzymatic conversion of dihydroartemisinic acid tertiary hydroperoxide to artemisinin. We established that the camphor-0 phenotype associates with a genomic deletion that results in loss of a Bornyl diPhosphate Synthase (AaBPS) gene candidate. Functional characterization of the corresponding enzyme in vitro confirmed it can catalyze the first committed step in not only camphor biosynthesis but also in a number of other monoterpenes, accounting for over 60% of total volatiles in A. annua leaves. This in vitro analysis is consistent with loss of monoterpenes in camphor-0 plants. The AaBPS promoter drives high reporter gene expression in A. annua glandular secretory trichomes of juvenile leaves with expression shifting to non-glandular trichomes in mature leaves, which is consistent with AaBPS transcript abundance.

Introduction Chemotherapy administration in real-world cancer care can differ extensively from clinical trials. It is important to understand real-world practice to identify dose reductions, delays, regimen changes and early discontinuations that impact cancer outcomes. Such variables require knowledge of intended regimens, which may not be well-documented in structured data in electronic health records (EHRs). We examined EHR data from the Kaiser Permanente Northern California (KPNC) site of the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study to develop a process to identify each patient’s intended regimen. Methods In this study of women diagnosed and treated with primary stage I-IIIA breast cancer at KPNC from 2006-2019, and ages 18+y at diagnosis, we analyzed treatment patterns using structured EHR data on the drugs, dosages, and dates at which they were administered (from which intervals and total length can be derived). Chemotherapy agents were identified using the NCI’s CANMED database augmented with other sources. We used these data to categorize patients into the 22 drug combinations described in the National Cancer Care Network (NCCN) guidelines for breast cancer treatment. Within these 22 drug combinations, women were then subcategorized into 45 distinct chemotherapy administration schedules, defined as NCCN guideline regimens (NGRs). For this step, algorithms were developed that categorized patients into NGRs if they received the exact regimen described in the guidelines. For the second step, we conducted a manual review of the EHR data for patients who were unable to be categorized. This enabled us to gradually loosen the criteria (in terms of cycle intervals or number of cycles) so patients whose chemotherapy administration aligned closely with NGRs were categorized into each of the 45 NGRs. Clear patterns emerged of regimens that were administered to multiple patients, despite being outside of the NCCN guidelines, which we have defined as non-standard NGRs. For example, in the drug combination TC (cyclophosphamide and docetaxel) the NGR was TC every 21 days for 4 cycles. We found approximately 1 in 10 patients received 6 cycles, which we defined as a non-NGR. For the remaining uncategorized patients, medical chart abstraction was undertaken as a third step, at which point patients were categorized into either existing regimens or new non-NGRs if their intended regimen had not been previously described in the guidelines. Results Among 31,418 women with breast cancer, 12,427 (39.6%) received chemotherapy. We determined the intended chemotherapy regimens for 6,559 (52.8%) receiving the 45 NGRs using EHR data. We further expanded the algorithms through a manual review of the EHR data, which enabled us to categorize 2,977 (24.0%) additional women into their intended regimens. Abstracted medical notes were reviewed for the remaining patients for whom we had not been able to identify the intended regimen. Across both the manual review and abstraction processes, we were able to identify additional non-standard NGR regimens. In total, 9,536 (76.7%) of women were categorized into their intended regimen through the algorithm/manual review process, while 2891 (23.3%) of women underwent medical chart abstraction to identify the intended regimen. Conclusion Here, we describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens at a granularity and scale not seen previously. We are adapting this method at a second OBCD study site, Kaiser Permanente Washington, where all women have undergone medical chart abstraction. We hope this methodology leads to increased feasibility and efficiency of use of large-scale clinical data, in turn improving cancer care delivery, patient outcome evaluation, and other real-world questions. Citation Format: Jenna Bhimani, Kelli O’Connell, Rachael P. Burganowski, Isaac J. Ergas, Marilyn J. Foley, Grace B. Gallagher, Jennifer J. Griggs, Narre Heon, Tatjana Kolevska, Yuriy Kotsurovskyy, Candyce H. Kroenke, Kanichi G. Nakata, Sonia Persaud, Donna R. Rivera, Janise M. Roh, Sara Tabatabai, Emily Valice, Erin J. Bowles, Elisa V. Bandera, Lawrence H. Kushi, Elizabeth D. Kantor. A methodology for using real-world data from electronic health records to assess chemotherapy administration in women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-16.

Background: Most cytotoxic drugs are dosed according to body surface area (BSA), yet not all patients receive the full BSA-determined dose. Prior work suggests that dose reduction may occur more frequently in obese patients, likely due to concern about inducing toxicity at high doses. Other factors, such as race/ethnicity, have been suggested to be associated with dosing, yet the factors associated with dose reduction remain poorly understood, with little known about dosing patterns in integrated healthcare delivery systems and how such patterns have changed over time. Methods: We examined chemotherapy dosing in 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California. All study participants were a part of the Pathways Study, diagnosed between 2006-2013, and treated with the common breast cancer regimen, ACT (cyclophosphamide and doxorubicin, followed by paclitaxel). We explored the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. We assessed dosing using first cycle dose proportion (< 90% expected dose) and average relative dose intensity (ARDI, a metric of dose intensity over the entire course of chemotherapy). Results: Overall, 8% of women received a dose reduction >10% in the first cycle of chemotherapy and 21.2% of patients had an ARDI < 90%. Obesity was a strong predictor of dose reduction, both in the first cycle and across all cycles. In the first cycle, 21.9% of severely obese patients (body mass index, BMI: 35+ kg/m2) were dose reduced, whereas no normal weight patients (BMI: 18.5-< 25 kg/m2) experienced a first cycle dose reduction. Across all cycles, 38.4% of severely obese women had an ARDI < 90%, as compared 12.8% of normal weight women. In logistic regression models adjusted for age, race/ethnicity, and white blood cell count, obese women had 4.1-fold higher odds of receiving a dose reduction of 10% or more over the course of chemotherapy than their normal weight counterparts (95% CI: 1.9, 8.9; p-trend: 0.006). Increasing age was positively associated with dose reduction across the course of chemotherapy, as was the presence of comorbidity. Importantly, dose reduction was less common in later calendar years. Sensitivity analyses revealed that the positive association between obesity and dosing was robust to further adjustment for these other significantly associated factors. Impact: These results offer insight on factors associated with variation in chemotherapy dosing for a common breast cancer treatment regimen. Larger studies are required to evaluate relevance of these findings to other treatment regimens. Further work will be needed to determine whether dose reductions impact breast cancer outcomes. Citation Format: Elizabeth D. Kantor, Kelli O’Connell, Isaac J. Ergas, Emily Valice, Janise M. Roh, Jenna Bhimani, Narre Heon, Jennifer J. Griggs, Jean Lee, Erin J. Bowles, Donna R. Rivera, Tatjana Kolevska, Elisa Bandera, Lawrence H. Kushi. Assessment of Breast Cancer Chemotherapy Dose Reduction in an Integrated Healthcare Delivery System [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-09.

BACKGROUND Chyle leak (CL) is an uncommon complication of pancreatico-duodenectomy (PD). Its incidence, risk factors, and effect on prognosis are not well described and optimum management remains debated. This study aims to calculate incidence of CL following PD and identify risk factors. Following a literature review, we have proposed a management algorithm. METHODS This is a retrospective review of all patients who underwent PD between January 2006 and April 2020 at a tertiary hepatopancreaticobiliary unit in the UK. The following data were obtained: age, gender, American Society of Anesthesiologists grade, body mass index, co-morbidities, duration of surgery, tumour histology, length of stay and mortality. RESULTS A total of 560 patients were included. Seventeen developed CL (3.04%). Median age was 64 years (range 50-81). Sixteen (94.1%) patients still had their surgical drain in at the time of CL diagnosis. One (5.9%) did not and had free intra-abdominal fluid on computed tomography; a diagnosis was made after an ultrasound-guided drain had been inserted. CL patients were more likely to have higher body mass index (mean 30.5 kg/m2 (range 17-43) versus 26.7 kg/m2 (22-38)) (P = 0.02) and longer duration of operation (mean 6.2 h (range 4.3-9.0) versus 5.6 (3.0-11.0)) (P = 0.03). All cases of CL resolved without operative intervention. CL did not affect length of stay (median 10 days (range 4-41) versus 11 (4-34)). CONCLUSIONS In our series, 3.04% of patients who underwent PD developed CL. No patients required a return to theatre, and none had CL recurrence.

In this paper, we describe a modular post-printing loading protocol for a 3D printed gastro-retentive drug delivery system. Fused Deposition Modelling (FDM) 3D printing was exploited for the rapid prototyping of a modular floating system (caps-in-cap). Optimized models were produced as blank PVA scaffolds, and a morphological analysis of the FDM printed models was conducted to develop a straightforward protocol for drug-loading. The 3D printed gastro-retentive systems were then subjected to microwave irradiation in oversaturated solutions of anhydrous caffeine for drug loading, and research focused on an analysis of the impact of microwave irradiation on the chemical and physical properties of the polymer and the drug. The drug-loading efficiency, thermal and chemical characteristics of components, the stability of the drug and the morphology of processed printouts are characterised and described. Parameters of this unexplored microwave-assisted post-printing loading technique were evaluated and adequately set up, and the process resulted in the preservation of the polymeric matrix and enhancement of drug loading. Hence, microwave impregnation confirmed its potential in superseding the traditional pre- and post-printing loading methods, such as soaking techniques, being faster and more efficient and providing a new paradigm approach to personalised drug delivery.

Background: The benefits of laparoscopic hemi-hepatectomy compared to open hemi-hepatectomy are not clear. Objective: This study aims to share our experience with the laparoscopic hemi-hepatectomy compared to an open approach. Methods: A total of 40 consecutive laparoscopically started hemi-hepatectomy (intention-to-treat analysis) cases between August 2012 and October 2015 were matched against open cases using the following criteria: laterality of surgery and pathology (essential criteria); American Society of Anesthesiologists score, body mass index, pre-operative bilirubin, neo-adjuvant chemotherapy, additional procedures, portal vein embolization, and presence of cirrhosis/fibrosis on histology (secondary criteria); age and gender (tertiary criteria). Hand-assisted and extended hemi-hepatectomy cases were excluded from the study. The two groups were compared for blood loss, operative time, hospital stay, morbidity, mortality, and oncological outcomes. All complications were quantified using the Clavien–Dindo classification. Results: Two groups were well matched (p = 1.00). In the two groups, 10 patients had left and 30 had right hemi-hepatectomy. Overall conversion rate was 15%. Median length of hospital and high dependency unit stay was less in the intention to treat laparoscopic hemi-hepatectomy group: 6 versus 8 days, p = 0.025 and 1 versus 2 days, p = 0.07. Median operative time was longer in the intention to treat laparoscopic hemi-hepatectomy group: 420 min (range: 389.5–480) versus 305 min (range: 238.8–348.8; p = 0.001). Intra-operative blood loss was equivalent, but the overall blood transfusions were higher in the intention to treat laparoscopic hemi-hepatectomy (50 vs 29 units, p = 0.36). The overall morbidity (18 vs 20 patients, p = 0.65), mortality (2.5%), and the positive resection margin status were similar (18% vs 21%, p = 0.76). The 1- (87.5% vs 92.5%, p = 0.71) and 3-year survival (70% vs 72.5%, p = 1.00) was also similar. Conclusions: We observed lower hospital and high dependency unit stay in the laparoscopic group. However, the laparoscopic approach was associated with longer operating time and a non-significant increase in blood transfusion requirements. There was no difference in morbidity, mortality, re-admission rate, and oncological outcomes.

The number of inferior vena cava (IVC) filters placed to prevent pulmonary embolism has dramatically increased since their inception. This chapter covers the general principles for IVC filter placement and removal including a discussion on standard approaches, imaging, and supplies needed. Advanced techniques to use in cases of complex removal, including balloon repositioning, wire loops, and the use of forceps or laser extractors are outlined.

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

Introduction There is a paucity of information on micronutrient status in patients with pancreatico-biliary malignancies referred for surgery. Deficiency states could impact recovery from surgery. The purpose of this study was to investigate the frequency of deficiency states in our specialist Hepato-Biliary and Pancreatic (HPB) unit. Methods Patients with suspected pancreatico-biliary malignancies referred to our surgical team between October 2019 and July 2020, and seen by a dietitian were included in the study. Serum levels of vitamins A, D, E, B12, and folate, and minerals zinc, selenium, copper and iron were obtained. Results Forty-eight patients were eligible for inclusion, 28 males and 20 females with a median age of 68 years. Pancreatic cancer was suspected in 40 patients, bile duct cancer in four patients, and duodenal cancer in four patients. Zinc, vitamin D, selenium and iron were the most frequently occurring micronutrient deficiencies. Zinc deficiency was found in 83% patients and vitamin D insufficiency in 57%. Selenium deficiency was less frequent but found in 24% cases, while iron deficiency suggested by low transferrin saturation was found in 23% patients. Conclusions Micronutrient deficiencies and borderline status may be more frequent in this patient group than generally acknowledged. Routine analysis of specific vitamins and minerals may be useful to identify deficiency/sub-clinical deficiency states. Further more extensive studies are needed to inform practice and enable guideline development.

Introduction: \ud The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic.\ud \ud Methods: \ud A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved.\ud \ud Results: \ud Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic.\ud \ud Conclusion: \ud The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

International audience; The Ultracold Neutron Asymmetry (UCNA) experiment was designed to measure the β-decay asymmetry parameter, A0, for free neutron decay. In the experiment, polarized ultracold neutrons are transported into a decay trap, and their β-decay electrons are detected with ≈4π acceptance into two detector packages which provide position and energy reconstruction. The experiment also has sensitivity to bn, the Fierz interference term in the neutron β-decay rate. In this work, we determine bn from the energy dependence of A0 using the data taken during the UCNA 2011–2013 run. In addition, we present the same type of analysis using the earlier 2010 A dataset. Motivated by improved statistics and comparable systematic errors compared to the 2010 data-taking run, we present a new bn measurement using the weighted average of our asymmetry dataset fits, to obtain bn=0.066±0.041stat±0.024syst which corresponds to a limit of −0.012

Development of endoscopic devices to manage surgical complications has revolutionized the endoscopic industry. With the constant development of new endoscopic techniques, these devices have consistently pushed the envelope of endoluminal surgery applications. This chapter will focus on endoluminal therapeutic interventions for the treatment and management of surgical complications.

Palatability and patient acceptability are critical attributes of dispersible tablet formulation. Co-processed excipients could provide improved organoleptic profile due to rational choice of excipients and manufacturing techniques. The aim of this study was to identify the most suitable co-processed excipient to use within directly compressible dispersible tablet formulations. Nine excipients, selected based on successful manufacturability, were investigated in a randomised, preference and acceptability testing in 24 healthy adult volunteers. Excipients were classified in order of preference as follows (from most preferred): SmartEx QD100 > F-Melt Type C > F-Melt Type M > MicroceLac > Ludiflash > CombiLac > Pharmaburst 500 > Avicel HFE-102 > Avicel PH-102. Broad differences were identified in terms of acceptability, with SmartEx QD100 being ‘very acceptable’, F-Melt Type C, F-Melt Type M and MicroceLac being ‘acceptable’, Ludiflash, CombiLac and Pharmaburst 500 being ‘neutral’ and Avicel products being ‘very unacceptable’ based on ratings using five-point hedonic scales. Organoleptic differences were ascribed to different composition and physical properties of excipients, resulting in dissimilar taste and mouth-feel. Excipients with particle size in water larger than 200–250 μm were considered poorly acceptable, which supports the use of this value as a threshold for maximum particle size of dispersible formulation. The most promising co-processed excipients for directly compressible dispersible tablets were successfully identified.

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr’s index ˂ 20), excellent tabletability (tensile strength > 3.0 MPa at 0.85 solid fraction), very low friability (

Background To ascertain if post-operative drain fluid lipase is superior to amylase in routinely detecting clinically significant post-operative pancreatic fistulae (POPF). Method Between January 2015 and March 2016 data were collected on all patients undergoing pancreatic surgery at a regional referral centre. Routine drain fluid analysis was performed on post-operative patients as part of a locally defined enhanced recovery protocol. POPF was diagnosed in accordance with the recently updated International Study Group of Pancreatic Surgery guidance. Results During the study period, there were 68 pancreatic resections. The median age was 69.1 years. A total of 11 (15.9%) patients developed clinically significant POPF (nine type B and two type C). The median drain amylase result in patients with type B or C leak was 532 IU/L (interquartile range (IQR) 264-833). This was significantly higher than those without a clinical fistula (median 38, IQR 15-376, P = 0.012). The median drain lipase result was 1504 IU/L (IQR 746-2236). This was significantly higher than those without a clinical fistula (median 57, IQR 13-1277, P = 0.012). Fluid amylase had a sensitivity of 81.8% and specificity of 69.2%; fluid lipase had a sensitivity of 91% and specificity of 64.9%. Conclusion Our experience suggests drain fluid amylase or lipase results are not sufficiently sensitive or specific to reassure clinicians and rule out clinically significant POPF. However, if biochemical tests are used to aid decision-making, then lipase is a more sensitive biochemical marker than amylase for the routine detection of clinically significant POPF.

This paper covers the current changes in personal injury and wrongful death litigation in the state of Idaho.

Current changes to personal injury and wrongful death litigation in the state of Utah.

Background It is well established that individual medications that affect the central nervous system (CNS) increase falls risk in older adults. However, less is known about risks associated with taking multiple CNS-active medications. Methods Employing a new user design, we used data from the Adult Changes in Thought study, a prospective cohort of community-dwelling people aged 65 and older without dementia. We created a time-varying composite measure of CNS-active medication exposure from electronic pharmacy fill data and categorized into mutually exclusive categories: current (within prior 30 days), recent (31–90 days), past (91–365 days), or nonuse (no exposure in prior year). We calculated standardized daily dose and identified new initiation. Cox proportional hazards models examined the associations between exposures and the outcome of fall-related injury identified from health plan electronic databases. Results Two thousand five hundred ninety-five people had 624 fall-related injuries over 15,531 person-years of follow-up. Relative to nonuse, fall-related injury risk was significantly greater for current use of CNS-active medication (hazard ratio [HR] = 1.95; 95% CI = 1.57–2.42), but not for recent or past use. Among current users, increased risk was noted with all doses. Risk was increased for new initiation compared with no current use (HR = 2.81; 95% CI = 2.09–3.78). Post hoc analyses revealed that risk was especially elevated with new initiation of opioids. Conclusions We found that current use, especially new initiation, of CNS-active medications was associated with fall-related injury in community-dwelling older adults. Increased risk was noted with all dose categories. Risk was particularly increased with new initiation of opioids.

The Wisconsin Clinical Laboratory Network (WCLN) at the University of Wisconsin–Madison is a partnership of 138 clinical and public health laboratories (as of February 2019) coordinated by the Wisconsin State Laboratory of Hygiene. This article describes the WCLN, its current activities, and lessons learned through this partnership. A laboratory technical advisory group, which consists of representatives from clinical laboratories, provides clinical laboratory perspective to the WCLN and fosters communication among laboratories. Activities and resources available through the WCLN include annual regional meetings, annual technical workshops, webinars, an email listserv, laboratory informational messages, in-person visits by a WCLN coordinator to clinical laboratories, and laboratory-based surveillance data and summaries distributed by the Wisconsin State Laboratory of Hygiene. One challenge to maintaining the WCLN is securing continual funding for network activities. Key lessons learned from this partnership of more than 20 years include the importance of in-person meetings, the clinical perspective of the laboratory technical advisory group, and providing activities and resources to clinical laboratories to foster sharing of data and clinical specimens for public health surveillance and outbreak response.

The INCOMPASS field campaign combines airborne and ground measurements of the 2016 Indian monsoon, towards the ultimate goal of better predicting monsoon rainfall. The monsoon supplies the majority of water in South Asia, but forecasting from days to the season ahead is limited by large, rapidly developing errors in model parametrizations. The lack of detailed observations prevents thorough understanding of the monsoon circulation and its interaction with the land surface: a process governed by boundary- layer and convective-cloud dynamics. INCOMPASS used the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 aircraft for the first project of this scale in India, to accrue almost 100 h of observations in June and July 2016. Flights from Lucknow in the northern plains sampled the dramatic contrast in surface and boundary-layer structures between dry desert air in the west and the humid environment over the northern Bay of Bengal. These flights were repeated in pre-monsoon and monsoon conditions. Flights from a second base at Bengaluru in southern India measured atmospheric contrasts from the Arabian Sea, over the Western Ghats mountains, to the rain shadow of southeast India and the south Bay of Bengal. Flight planning was aided by forecasts from bespoke 4 km convection-permitting limited-area models at the Met Office and India's NCMRWF. On the ground, INCOMPASS installed eddy- covariance flux towers on a range of surface types, to provide detailed measurements of surface fluxes and their modulation by diurnal and seasonal cycles. These data will be used to better quantify the impacts of the atmosphere on the land surface, and vice versa. INCOMPASS also installed ground instrumentation supersites at Kanpur and Bhubaneswar. Here we motivate and describe the INCOMPASS field campaign. We use examples from two flights to illustrate contrasts in atmospheric structure, in particular the retreating mid-level dry intrusion during the monsoon onset.

Aims To assess the potential association between the change in diameter of colorectal liver metastases between pre-operative imaging and liver resection and disease-free survival in patients who do not receive pre-operative liver-directed chemotherapy. Materials and methods Analysis of a prospectively maintained database of patients undergoing liver resection for colorectal liver metastases between 2005 and 2012 was undertaken. Change in tumour size was assessed by comparing the maximum tumour diameter at radiological diagnosis determined by imaging and the maximum tumour diameter measured at examination of the resected specimen in 157 patients. Results The median interval from first scan to surgery was 99 days and the median increase in tumour diameter in this interval was 38%, equivalent to a tumour doubling time (DT) of 47 days. Tumour DT prior to liver resection was longer in patients with T1 primary tumours (119 days) than T2-4 tumours (44 days) and shorter in patients undergoing repeat surgery for intra-hepatic recurrence (33 days) than before primary resection (49 days). The median disease-free survival of the whole cohort was 1.57 years (0.2–7.3) and multivariate analysis revealed no association between tumour DT prior to surgery and disease-free survival. Conclusions The rate of growth of colorectal liver metastases prior to surgery should not be used as a prognostic factor when considering the role of resection.

The elucidation and prediction of how changes in a protein result in altered activities and selectivities remain a major challenge in chemistry. Two hurdles have prevented accurate family-wide models: obtaining (i) diverse datasets and (ii) suitable parameter frameworks that encapsulate activities in large sets. Here, we show that a relatively small but broad activity dataset is sufficient to train algorithms for functional prediction over the entire glycosyltransferase superfamily 1 (GT1) of the plant Arabidopsis thaliana. Whereas sequence analysis alone failed for GT1 substrate utilization patterns, our chemical–bioinformatic model, GT-Predict, succeeded by coupling physicochemical features with isozyme-recognition patterns over the family. GT-Predict identified GT1 biocatalysts for novel substrates and enabled functional annotation of uncharacterized GT1s. Finally, analyses of GT-Predict decision pathways revealed structural modulators of substrate recognition, thus providing information on mechanisms. This multifaceted approach to enzyme prediction may guide the streamlined utilization (and design) of biocatalysts and the discovery of other family-wide protein functions. Bioinformatic analysis coupled to substrate-reactivity profiling for the glycosyltransferase (GT) enzyme superfamily supports the development of ‘GT-Predict’ as a tool for functional prediction of GT–substrate relationships.

EPJ Web of Conferences, 219, ISSN:2100-014X, ISSN:2101-6275, International Workshop on Particle Physics at Neutron Sources (PPNS 2018), Grenoble, France, May 24–26, 2018, ISBN:978-2-7598-9082-8

It has been proposed recently that a previously unobserved neutron decay branch to a dark matter particle (χ) could account for the discrepancy in the neutron lifetime observed in experiments that use two different measurement techniques. One of the possible final states discussed includes a single χ along with an e^+e^− pair. We use data from the UCNA (Ultracold Neutron Asymmetry) experiment to set limits on this decay channel. Coincident electron-like events are detected with ∼4π acceptance using a pair of detectors that observe a volume of stored Ultracold Neutrons (UCNs). The summed kinetic energy (E_(e^+e^−)) from such events is used to set limits, as a function of the χ mass, on the branching fraction for this decay channel. For χ masses consistent with resolving the neutron lifetime discrepancy, we exclude this as the dominant dark matter decay channel at ≫ 5σlevel for 100 keV < E_(e^+e^−) < 644 keV. If the χ + e^+e^− final state is not the only one, we set limits on its branching fraction of 90% confidence level.

OBJECTIVES To compare the strength of fixation of percutaneous screw versus plate/screw fixation in a paired cadaver model of OTA 41-B3 (Schatzker type II) split-depression fractures of the lateral tibial plateau. METHODS Six matched pairs of cadaveric knees were acquired. An OTA 41-B3 (Schatzker type II) split-depression fracture was created in all specimens using a standardized method. One specimen from each matched pair of knees was fixed with percutaneous screws, and the other was fixed with a plate/screw construct. All specimens underwent augmentation of the central metaphyseal defect with calcium phosphate. Mean residual displacement (depression) was measured on thin-slice high-resolution computed tomography using a standardized methodology following 3 experimental conditions: (1) after they were fixed, before loading; (2) unloaded cycling (simulating postoperative range of motion exercises); and (3) loaded cycling (simulating postoperative weight-bearing). Load to failure was also compared. RESULTS After adjustment for baseline measurements, there was no significant difference in mean residual depression of the lateral tibial plateau between treatments groups after unloaded or loaded cyclic testing. Mean residual depression was less than 1 mm in both the treatment groups. Load to failure was statistically equivalent between treatment groups. CONCLUSIONS In our cadaveric study, in combination with calcium phosphate augmentation for both methods, percutaneous screw fixation conferred comparable strength of fixation compared with plate/screw constructs for treatment of OTA 41-B3 (Schatzker type II) tibial plateau fractures.

Background: The neutron β-decay asymmetry parameter A_0 defines the angular correlation between the spin of the neutron and the momentum of the emitted electron. Values for A_0 permit an extraction of the ratio of the weak axial-vector to vector coupling constants, λ≡gA/gV, which under assumption of the conserved vector current hypothesis (gV=1) determines gA. Precise values for gA are important as a benchmark for lattice QCD calculations and as a test of the standard model. Purpose: The UCNA experiment, carried out at the Ultracold Neutron (UCN) source at the Los Alamos Neutron Science Center, was the first measurement of any neutron β-decay angular correlation performed with UCN. This article reports the most precise result for A_0 obtained to date from the UCNA experiment, as a result of higher statistics and reduced key systematic uncertainties, including from the neutron polarization and the characterization of the electron detector response. Methods: UCN produced via the downscattering of moderated spallation neutrons in a solid deuterium crystal were polarized via transport through a 7 T polarizing magnet and a spin flipper, which permitted selection of either spin state. The UCN were then contained within a 3-m long cylindrical decay volume, situated along the central axis of a superconducting 1 T solenoidal spectrometer. With the neutron spins then oriented parallel or anti-parallel to the solenoidal field, an asymmetry in the numbers of emitted decay electrons detected in two electron detector packages located on both ends of the spectrometer permitted an extraction of A_0. Results: The UCNA experiment reports a new 0.67% precision result for A_0 of A_0=−0.12054(44)_(stat)(68)_(syst), which yields λ=gA/gV=−1.2783(22). Combination with the previous UCNA result and accounting for correlated systematic uncertainties produces A0=−0.12015(34)stat(63)syst and λ=gA/gV=−1.2772(20). Conclusions: This new result for A0 and gA/gV from the UCNA experiment has provided confirmation of the shift in values for gA/gV that has emerged in the published results from more recent experiments, which are in striking disagreement with the results from older experiments. Individual systematic corrections to the asymmetries in older experiments (published prior to 2002) were >10%, whereas those in the more recent ones (published after 2002) have been of the scale of

Breast cancer screening in the United States was first recommended to women in 1976. Over the past decade, mammography screening has changed from film screen mammography to primarily digital mammography, which, as of 2016, accounts for over 97% of all mammograms performed in the United States. Several systematic reviews, which have included results from up to 9 randomized clinical trials from the United States, Europe, and Canada, have demonstrated a reduced risk of breast cancer mortality associated with breast cancer screening. Potential harms from breast cancer screening include false-positive mammograms (which may lead to unnecessary additional imaging and benign breast biopsies), overdiagnosis, and radiation exposure. This chapter summarizes evidence from randomized controlled trials for mortality benefit; current society and task force recommendations for mammography screening; evaluation of the evidence; risk–benefit analysis; and supplemental screening in high-risk women.

The Wisconsin State Laboratory of Hygiene challenged Wisconsin laboratories to examine their biosafety practices and improve their culture of biosafety. One hundred three clinical and public health laboratories completed a questionnaire-based, microbiology-focused biosafety risk assessment. Greater than 96% of the respondents performed activities related to specimen processing, direct microscopic examination, and rapid nonmolecular testing, while approximately 60% performed culture interpretation. Although they are important to the assessment of risk, data specific to patient occupation, symptoms, and travel history were often unavailable to the laboratory and, therefore, less contributory to a microbiology-focused biosafety risk assessment than information on the specimen source and test requisition. Over 88% of the respondents complied with more than three-quarters of the mitigation control measures listed in the survey. Facility assessment revealed that subsets of laboratories that claim biosafety level 1, 2, or 3 status did not possess all of the biosafety elements considered minimally standard for their respective classifications. Many laboratories reported being able to quickly correct the minor deficiencies identified. Task assessment identified deficiencies that trended higher within the general (not microbiology-specific) laboratory for core activities, such as packaging and shipping, direct microscopic examination, and culture modalities solely involving screens for organism growth. For traditional microbiology departments, opportunities for improvement in the cultivation and management of highly infectious agents, such as acid-fast bacilli and systemic fungi, were revealed. These results derived from a survey of a large cohort of small- and large-scale laboratories suggest the necessity for continued microbiology-based understanding of biosafety practices, vigilance toward biosafety, and enforcement of biosafety practices throughout the laboratory setting.

BackgroundThe aim of this study was to compare the socioeconomic profile of patients undergoing liver resection for colorectal liver metastasis (CLM) in a regional hepatopancreatobiliary unit with that of the local population. A further aim was to determine if degree of deprivation is associated with tumour recurrence after resection.MethodsA retrospective analysis of patients undergoing liver resection for CLM was performed. Geodemographic segmentation was used to divide the population into five categories of socioeconomic status (SES).ResultsDuring a 7‐year period, 303 patients underwent resection for CLM. The proportion of these patients in the two least deprived categories of SES was greater than that of the local population (50.2% versus 40.2%) and the proportion in the two most deprived categories was lower (18.3% versus 30.1%) (P < 0.001). There was no difference in recurrence rate (P = 0.867) or disease‐free survival among categories of SES (P = 0.913). Multivariate analysis demonstrated no association between SES and tumour recurrence (P = 0.700).ConclusionsLiver resection for CLM is performed more commonly among the least socioeconomically deprived population than among the most deprived. However, degree of deprivation was not associated with tumour recurrence after resection.

Background:\ud Risk prediction techniques commonly used in liver surgery include the American Society of Anesthesiologists (ASA) grading, Charlson Comorbidity Index (CCI) and cardiopulmonary exercise tests (CPET). This study compares the utility of these techniques along with the number of segments resected as predictive tools in liver surgery.\ud \ud Methods:\ud A review of a unit database of patients undergoing liver resection between February 2008 and January 2015 was undertaken. Patient demographics, ASA, CCI and CPET variables were recorded along with resection size. Clavien-Dindo grade III–V complications were used as a composite outcome in analyses. Association between predictive variables and outcome was assessed by univariate and multivariate techniques.\ud \ud Results:\ud One hundred and seventy-two resections in 168 patients were identified. Grade III–V complications occurred after 42 (24.4%) liver resections. In univariate analysis of CPET variables, ventilatory equivalents for CO2 (VEqCO2) was associated with outcome. CCI score, but not ASA grade, was also associated with outcome. In multivariate analysis, the odds ratio of developing grade III–V complications for incremental increases in VEqCO2, CCI and number of liver segments resected were 1.09, 1.49 and 2.94, respectively.\ud \ud Conclusions:\ud Of the techniques evaluated, resection size provides the simplest and most discriminating predictor of significant complications following liver surgery.

Background: VEPTR (vertical expandable prosthetic titanium rib) expansion thoracoplasty is used to manage thoracic insufficiency syndrome in early-onset scoliosis. Literature regarding the effects of this technique on pulmonary function is scarce. The aim of this study was to report the intermediate-term results of VEPTR expansion thoracoplasty. Methods: Twenty-one children with thoracic insufficiency syndrome underwent VEPTR expansion thoracoplasty from 2002 to 2012 and had complete chart data, preoperative and follow-up radiographs, and pulmonary function tests performed at the index implantation, first expansion, and last expansion. Pulmonary function tests with forced and passive deflation techniques developed for children under general anesthesia were performed prior to the index implantation and each expansion surgery under the same anesthetic conditions. Pulmonary and radiographic parameters were analyzed longitudinally. Results: Mean follow-up was six years, and mean age at implantation was 4.8 years. The mean number of expansion procedures per patient was eleven, and the mean number of pulmonary function tests was ten. The mean interval between surgical procedures was 6.4 months. Mean forced vital capacity (FVC) increased from 0.65 to 0.96 L (p < 0.0001). However, the percentage of the predicted FVC decreased from 77% to 58%. Respiratory system compliance normalized on the basis of body weight, Crs/kg, decreased by 39%, from 1.4 to 0.86 mL/cm H2O/kg. The mean Cobb angle before treatment was 80°, and the mean maximum thoracic kyphosis angle was 57° (range, 7° to 107°). The initial coronal correction was maintained at the time of final follow-up (67°); however, there was a trend toward a decrease in the maximum thoracic kyphosis angle (to 66°, p = 0.08). Clinically apparent proximal thoracic kyphosis occurred in four patients, and spinal imbalance occurred in seven. The mean gain in T1-T12 height during the treatment period was 18 mm (2.9 mm/year). Conclusions: FVC improved over time; however, this increase in lung volume did not keep up with the growth of the child, as the percentage of the predicted FVC decreased, and the chest wall stiffness increased. Coronal correction was maintained, but the increase in proximal thoracic kyphosis is concerning. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Minimizing the inflammatory events that follow intestinal transplantation may influence immediate graft function and improve outcome. Ischemic preconditioning (IPc) has been shown to ameliorate early inflammatory responses, and it may also attenuate the potentially damaging inflammation after intestinal transplantation. Herein, we examine the influence of intestinal IPc on inflammatory indices (tissue expression of ICAM-1, CD11a, and CD44 and serum levels of the soluble ICAM-1, sICAM-1) after heterotopic intestinal transplantation.Lewis rats received full-length preconditioned or non-preconditioned Brown Norway intestinal allografts in the absence of immunosuppression. Preconditioned grafts were subjected to 1 cycle of 10 minutes of ischemia-reperfusion. Preconditioned and non-preconditioned isografts acted as controls. Blood was collected on alternate days post-transplant, and graft tissue harvested on sacrifice. ICAM-1, CD44, and CD11a expression was determined by immunohistochemistry, and the area of staining was quantified using image analysis. Serum soluble ICAM-1 levels were determined using an RD Systems Quantikine enzyme immunoassay.(1) IPc ameliorated serum levels of sICAM-1 until severe rejection (day 7) overcame this down-regulation when compared to non-preconditioned allografts (day 3: 34,304 vs 40,479 pg/mL; day 5: 52,441 vs 61,593 pg/mL; day 7: 75,114 vs 73,309 pg/mL; day 9: 72,872 vs 76,314 pg/mL, respectively). (2) ICAM-1 expression was significantly lower in preconditioned allografts (1.02 vs 2.01 mm(2)). (3) CD44 tissue levels were also found to be lower in preconditioned allografts (0.86 vs 1.13 mm(2)). (4) There was a significant relationship between tissue ICAM-1 expression and serum levels of soluble ICAM-1 (P .02).IPc improves inflammatory indices in the early stages following intestinal transplantation, and this might lead to a preserved cellular, architectural, and functional graft status. Furthermore, our results support the use of soluble ICAM-1 as a marker of endothelial activation, and thence of inflammation and developing rejection.