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Background: Postoperative ileus (POI) is a common complication following colorectal surgery and is mediated in part by the cholinergic anti-inflammatory pathway (CAIP). Neostigmine (acetylcholinesterase inhibitor), co-administered with glycopyrrolate, is frequently given for neuromuscular reversal before tracheal extubation and modulates the CAIP. An alternative reversal agent, sugammadex (selective rocuronium or vecuronium binder), acts independently from the CAIP. The aim of our study was to assess the impact of neuromuscular reversal agents used during anaesthesia on gastrointestinal recovery. Methods: Three hundred thirty-five patients undergoing elective colorectal surgery at the Royal Adelaide Hospital between January 2019 and December 2021 were retrospectively included. The primary outcome was GI-2, a validated composite measure of time to diet tolerance and passage of stool. Demographics, 30-day complications and length of stay were collected. Univariate and multivariate analyses were performed. Results: Two hundred twenty-four (66.9%) patients (129 [57.6%] males and 95 [42.4%] females, median age 64 [19–90] years) received neostigmine/glycopyrrolate and 111 (33.1%) received sugammadex (62 [55.9%] males and 49 [44.1%] females, median age 67 [18–94] years). Sugammadex patients achieved GI-2 sooner after surgery (median 3 (0–10) vs. 3 (0–12) days, p = 0.036), and reduced time to first stool (median 2 (0–10) vs. 3 (0–12) days, p = 0.035). Rates of POI, complications and length of stay were similar. On univariate analysis, POI was associated with smoking history, previous abdominal surgery, colostomy formation, increased opioid use and postoperative hypokalaemia (p < 0.05). POI was associated with increased complications, including anastomotic leak and prolonged hospital stay (p < 0.001). On multivariate analysis, neostigmine, bowel anastomoses and increased postoperative opioid use (p < 0.05) remained predictive of time to GI-2. Conclusions: Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and postoperative opioid use were associated with delayed time to achieving GI-2. [ABSTRACT FROM AUTHOR]

Abstract The Dipterocarpaceae family is ubiquitous across mainland and maritime south-east Asia. Species within the family are often so well-adapted to – and prolific within – ecologically distinct forest types, that they are used as habitat indicators within forestry and ecological research. The limited work on the classification of Dipterocarpaceae pollen under light microscopy, however, means that paleoecologists working in the region are currently unable to link fossil pollen to indicator species/assemblages with any confidence. As a consequence, ecologically meaningful and habitat-specific data are homogenized in the paleorecord. This study explores whether the classification of pollen from representative south-east Asian Dipterocarpaceae species can be resolved at a higher taxonomic resolution. This will provide paleoecologists with a tool to (1) better assess shifts in forest types (and hence climate/elevation envelopes) through time, and (2) predict species response to future regional change. Our revised classification scheme is based on an analysis of the pollen morphology of Dipterocarpaceae species from two globally significant ecoregions in south-east Asia – the seasonally dry tropical forests of mainland south-east Asia, and the Sulawesi lowland rainforests of Wallacea – under the light microscope. Results of this analysis show that, using a range of morphological metrics – notably grain size, size-to-wall thickness ratios and exine structure – mainland and Wallacean Dipterocarpaceae pollen can be readily classified into three taxonomic groups – Vatica , Dipterocarpus and Shorea/Hopea/Anisoptera/Pentacme types. At an intra-ecoregional scale, each assemblage can be further broken down into six groups. Some of these groupings appear useful for the classification of certain indicator pollen types within the family, including those taxa representative of key open – and closed – canopy dry forest habitats in the mainland seasonal tropics, the delimitation of peat/swamp forest types in both ecoregions, and the identification of lowland mafic forest types in Sulawesi. Additionally, being able to split the Dipterocarpaceae within these ecologically important ecoregions at a higher taxonomic resolution is of potential conservation significance, permitting long-term assessment of the adaptation capacity of different genera/species to climatic change or disturbance events. Highlights • Dipterocarpaceae pollen from mainland SE Asia and Wallacea can be split into three major groups. • Key parameters for splitting pollen are size, size-to-wall-ratios, and exine structure. • Pollen taxa can be further grouped using these, and other metrics at an intraregional scale. • In some cases, key habitat types can be inferred from these classifications. • This has implications for paleoecological interpretations from the plant microfossil record. [ABSTRACT FROM AUTHOR]

The formation of a self-consistent crystalline structure is a well-known phenomenon in complex plasmas. In most experiments, the pressure and rf power are the main controlling parameters in determining the phase of the system. We have studied the effect of the externally applied magnetic field on the configuration of plasma crystals, suspended in the sheath of a radio-frequency discharge using the Magnetized Dusty Plasma Experiment device. Experiments are performed at a fixed pressure and rf power where a crystalline structure is formed within a confining ring. The magnetic field is then increased from 0 to 1.28 T. We report on the breakdown of the crystalline structure with the increasing magnetic field. The magnetic field affects the dynamics of the plasma particles and first leads to a rotation of the crystal. At a higher magnetic field, there is a radial variation (shear) in the angular velocity of the moving particles which we believe to lead to the melting of the crystal. This melting is confirmed by evaluating the variation of the pair correlation function as a function of magnetic field. [ABSTRACT FROM AUTHOR]

Background: β-defensins are small, cationic, antimicrobial peptides found in species across the plant and animal kingdoms. In addition to microbiocidal activity, roles in immunity as well as reproduction have more recently been documented. β-defensin genes in Ovis aries (domestic sheep) have been poorly annotated, having been identified only by automatic gene prediction algorithms. The objective of this study was to use a comparative genomics approach to identify and characterise the β-defensin gene repertoire in sheep using the bovine genome as the primary reference. Results: All 57 currently predicted bovine β-defensin genes were used to find orthologous sequences in the most recent version of the sheep genome (OAR v4.0). Forty three genes were found to have close genomic matches (>70% similarity) between sheep and cattle. The orthologous genes were located in four clusters across the genome, with 4 genes on chromosome 2, 19 genes on chromosome 13, 5 genes on chromosome 20 and 15 genes on chromosome 26. Conserved gene order for the β-defensin genes was apparent in the two smaller clusters, although gene order was reversed on chromosome 2, suggesting an inversion between sheep and cattle. Complete conservation of gene order was also observed for chromosome 13 β-defensin orthologs. More structural differences were apparent between chromosome 26 genes and the orthologous region in the bovine reference genome, which is known to be copy-number variable. In this cluster, the Defensin-beta 1 (DEFB1) gene matched to eleven Bovine Neutrophil beta-Defensin (BNBD) genes on chromosome 27 with almost uniform similarity, as well as to tracheal, enteric and lingual anti-microbial peptides (TAP, EAP and LAP), suggesting that annotation of the bovine reference sequence is still incomplete. qPCR was used to profile the expression of 34 β-defensin genes, representing each of the four clusters, in the ram reproductive tract. Distinct site-specific and differential expression profiles were detected across the reproductive tract of mature rams with preferential β-defensin gene expression in the epididymis, recapitulating observations for orthologous genes in other species. Conclusions: This is the first comprehensive analysis of β-defensin genes encoded by the ovine reference sequence, and the first report of an expanded repertoire of β-defensin genes in this species. The preferential expression of these genes in the epididymis suggests a role in fertility, possibly providing immunoprotection for sperm within the female reproductive tract. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the pharmacokinetics of single- and multi-dose ceftiofur crystalline-free acid ( CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1-3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48-h intervals. Blood samples were collected at pre-determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents ( CFAE) were measured using high-performance liquid chromatography. Following single-dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 μg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi-dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 μg/mL and ≥2.0 μg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve ( AUC0→∝) was 246.2 ± 30.7 h × μg/mL and 172.7 ± 27.14 h × μg/mL following single- and multi-dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well- tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi-dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals. [ABSTRACT FROM AUTHOR]

The NHS England Radiotherapy Service Specification calls for routine use of patient-reported outcome measures (PROMs). However, barriers exist at patient, healthcare professional and service levels. The aim of the present study was to determine the current use of PROMs within radiotherapy services in England. The current attitudes, barriers and enablers to the implementation of PROMs in radiotherapy practice were evaluated and practical recommendations to inform future implementation were developed. A mixed-methods approach was adopted to obtain quantitative and qualitative data. An online questionnaire was developed and disseminated to all radiotherapy operational delivery network managers across England. The questionnaire consisted of 12 open and closed questions relating to PROMs use, with the option to provide free-text responses. Inductive thematic analysis was conducted on free-text comments, whereas descriptive statistics were used to analyse quantitative data. In total, 182 responses were received from 40 of the 50 radiotherapy providers, resulting in a response rate of 84%. The current use of PROMs was analysed, including rationale for use, tools used, format of PROMs collection and timing within the radiotherapy pathway. Most respondents indicated that PROMs were used in the context of clinical trials only. Through thematic analysis, four identical key themes were identified relating to both barriers and enablers to PROMs use; these included IT infrastructure, time, human/financial resources and training/education. A fifth theme, standardisation, was identified as a key enabler to PROMs use. Our findings show that outside of clinical trials, PROMs are not routinely used in radiotherapy services due to barriers identified at professional and service levels. Here we provide recommendations to mitigate the barriers identified and implement PROMs in radiotherapy, including training for healthcare professionals and standardisation of PROMs tools and storage. This study provides a key first step in driving PROMs implementation within radiotherapy services across England. • Outside of clinical trials, PROMs were not widely used within radiotherapy services. • Common PROMs used included QOL, anxiety/depression and urinary/bowel function tools. • PROMs are completed using either paper or electronic forms, by staff or patients. • Barriers include IT infrastructure, time, resources (staff/finances) and training. • Enablers included IT, time, resources, training and standardisation. [ABSTRACT FROM AUTHOR]

This study used three-dimensional information from Stealth navigation technology during simulated right internal jugular vein cannulation to define the initial needle trajectory taken when using three approaches: landmark (LM), short-axis (SAX) ultrasound and long-axis (LAX) ultrasound. Nineteen volunteers indicated the entry site and needle direction (track) they would use in performing right internal jugular vein cannulation by the three approaches. The likelihood of cannulation success, arterial puncture and needle direction were recorded. Volunteers were asked to assess the suitability of the simulation system for validity and educational benefit. The SAX track crossed the jugular vein more frequently than the LAX and LM tracks (SAX: 94%; LAX: 80%; LM: 47% [SAX versus LM, P <0.01]). The mean indicated needle direction in the coronal plane for LM, SAX and LAX were -4, 13 and 11 degrees, respectively. The track associated with the LAX technique would have entered the carotid artery by 16% of volunteers. At needle depths of over 40 mm, the track crossed the vertebral artery at the following rates (LM: 11%; SAX: 16%; LAX: 16%). The use of Stealth technology to provide three-dimensional feedback of the needle path taken during simulated right internal jugular cannulation was considered realistic (16/19) and of benefit for 18 of 19 (95%) respondents. The SAX track was associated with the highest likelihood of successful jugular cannulation and the lowest cross rate of the carotid artery. The simulation model using Stealth was considered to be valuable and realistic by participants despite some limitations. [ABSTRACT FROM AUTHOR]

This study used three-dimensional information from Stealth navigation technology during simulated right internal jugular vein cannulation to define the initial needle trajectory taken when using three approaches: landmark (LM), short-axis (SAX) ultrasound and long-axis (LAX) ultrasound. Nineteen volunteers indicated the entry site and needle direction (track) they would use in performing right internal jugular vein cannulation by the three approaches. The likelihood of cannulation success, arterial puncture and needle direction were recorded. Volunteers were asked to assess the suitability of the simulation system for validity and educational benefit. The SAX track crossed the jugular vein more frequently than the LAX and LM tracks (SAX: 94%; LAX: 80%; LM: 47% [SAX versus LM, P <0.01]). The mean indicated needle direction in the coronal plane for LM, SAX and LAX were -4, 13 and 11 degrees, respectively. The track associated with the LAX technique would have entered the carotid artery by 16% of volunteers. At needle depths of over 40 mm, the track crossed the vertebral artery at the following rates (LM: 11%; SAX: 16%; LAX: 16%). The use of Stealth technology to provide three-dimensional feedback of the needle path taken during simulated right internal jugular cannulation was considered realistic (16/19) and of benefit for 18 of 19 (95%) respondents. The SAX track was associated with the highest likelihood of successful jugular cannulation and the lowest cross rate of the carotid artery. The simulation model using Stealth was considered to be valuable and realistic by participants despite some limitations. [ABSTRACT FROM AUTHOR]

The present study investigates the historical unconditioned merger of palatal /ç/ (< Middle High German /x/) and postalveolar /ʃ/ into alveolopalatal /ɕ/ in certain varieties of Central German. It will be shown that the phonemicization of the alveolopalatal was the final stage in a gradual reduction of segmental markedness. Thus, /ç/ and /ʃ/ are argued to be featurally complex segments, while /ɕ/ is featurally simplex. Independent support for the proposed analysis can be found in the concomitant reduction of markedness in the vowel system of the dialects in question. The present study sheds light on the factors involved in explaining context-free phonological change and the historical source of the alveolopalatal /ɕ/. [ABSTRACT FROM AUTHOR]

Quantitative ultrasound methods can provide valuable information about the microstructure of a material or tissue. This works well when the common assumptions of homogeneity, isotropy, and diffuse scattering conditions are valid. In biological tissues, however, these assumptions are often violated because the microstructure of biological tissues is often heterogeneous and anisotropic. The microstructure of biological tissues can change with disease, and therefore accurate identification and description of a tissue's microstructure can offer important clinical insight. To address the challenge of evaluating the microstructure of biological tissues, here we introduce a novel parameter called the correlation length ratio (CLR), a ratio of lateral to axial correlation lengths for backscattered echo signals. We developed it to determine the presence of fiber-like structures in soft tissues by comparing this value in tissue to a threshold determined from a reference material that is homogeneous, isotropic, and provides diffuse scattering. We tested this novel parameter in phantoms with spherical scattering sources, in an anisotropic phantom (containing elongated fibers), and in human biceps muscle. We found that the CLR accurately detected the presence of elongated structures in both the anisotropic phantom and muscle. These results encourage further exploration of this novel parameter in microstructurally complex tissues. [ABSTRACT FROM AUTHOR]

Climate services are largely supported by climate reanalyses and by satellite Fundamental (Climate) Data Records (F(C)DRs). This paper demonstrates how the development and the uptake of F(C)DR benefit from radiance simulations, using reanalyses and radiative transfer models. We identify three classes of applications, with examples for each application class. The first application is to validate assumptions during F(C)DR development. Hereto we show the value of applying advanced quality controls to geostationary European (Meteosat) images. We also show the value of a cloud mask to study the spatio‐temporal coherence of the impact of the Mount Pinatubo volcanic eruption between Advanced Very High Resolution Radiometer (AVHRR) and the High‐resolution Infrared Radiation Sounder (HIRS) data. The second application is to assess the coherence between reanalyses and observations. Hereto we show the capability of reanalyses to reconstruct spectra observed by the Spektrometer Interferometer (SI‐1) flown on a Soviet satellite in 1979. We also present a first attempt to estimate the random uncertainties from this instrument. Finally, we investigate how advanced bias correction can help to improve the coherence between reanalysis and Nimbus‐3 Medium‐Resolution Infrared Radiometer (MRIR) in 1969. The third application is to inform F(C)DR users about particular quality aspects. We show how simulations can help to make a better‐informed use of the corresponding F(C)DR, taking as examples the Nimbus‐7 Scanning Multichannel Microwave Radiometer (SMMR), the Meteosat Second Generation (MSG) imager, and the Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave Water Vapor Profiler (SSM/T‐2). Key Points: Radiance simulations can help characterize two essential inputs of climate services, satellite data records and reanalysesUncertainties in observations collected by the Spektrometer Interferometer‐1 flown on a Soviet satellite in 1979 were estimatedRadiance simulations of satellite instruments can provide information on the quality and realism of climate reanalyses [ABSTRACT FROM AUTHOR]

Pharmacologic methods of treating and preventing HIV have advanced tremendously in recent years. Understandings of HIV risk and recommendations for risk-reduction strategies have also changed substantially. A majority of new cases of HIV in many developed countries are now acquired through sex with long-term partners who are unaware of their HIV-positive status, rather than from casual or anonymous sexual encounters. Persons with bipolar disorder and substance use disorders are at particularly high risk. Mental health providers who work with LGBT persons and other populations at higher risk for HIV need to understand strategies their patients are using for HIV risk reduction, and to refer appropriate patients for consideration for pre-exposure prophylaxis (PrEP). PrEP is the daily use of an antiretroviral (ARV) medication for prevention of HIV infection in higher-risk individuals. The United States approved tenofovir + emtracitabine for PrEP in 2012; this is under review in several European countries, Canada, and Australia, and is already prescribed off-label in many. Additionally, studies have shown that treatment with ARV medications to an “undetectable viral load” greatly reduces the risk of further transmission by persons already infected with HIV, called “treatment as prevention” (TasP). As of September 2015, WHO recommends early ARV treatment for all persons with HIV, and consideration of PrEP for men who have sex with men. This paper reviews findings from the PrEP studies (especially iPrEx, iPrEx Ole, IPERGAY, and PROUD) and TasP, and looks at their impact on LGBT and HIV+ communities, with relevance for mental health providers. [ABSTRACT FROM AUTHOR]

An obituary for surgeon Rear Admiral David A. Coppock is presented.

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development. 70 non-pregnant women were recruited, from which 21 were GBS positive at baseline. GBS recto-vaginal colonisation and capsule polysaccharides specific antibody levels in serum, and in the vaginal and nasal mucosa were followed for three months. Colonisation and GBS serotypes present fluctuated over time. [ABSTRACT FROM AUTHOR]

As the global food demand increases, the use of pesticides will continue to increase with significant growth in low- and middle-income countries. Agricultural systems in which pesticides are used are complex with significant and often unknown biological, human, and physical-chemical interactions. These interactions include climate and hydrology, soil type, selection and use of best management practices, chemical fate and transport, application technology, and land use socioeconomics. The objective of this review article is to highlight key research opportunities identified from recent special meetings and workshops on advancing pesticide exposure assessments and mitigation. Research is needed in using advanced analytics and forensics to better understand the distribution of pesticides in the environment through novel monitoring and detection. Higher-tier modeling approaches can help inform monitoring a priori to better characterize pesticide distributions in the environment. Current pesticide exposure assessments are largely focused on the field or watershed scale, but advancements are needed to move toward landscape-scale analyses capable of analyzing for interacting ecosystems. Assessing the effects of complex, low-dose chemical mixtures on non-target aquatic organisms must advance with new quantitative high-throughput experimental methods focused on identifying interactions and not just additive effects. Field mitigation measures are currently considered as part of the pesticide exposure and risk assessment process using qualitative, fixedefficiency type approaches, but we specifically call for the use of existing quantitative tools moving forward. These mechanistic modeling and simulation tools can capture the inherent complexity within an agroecological system. There is a need for risk assessment to be more predictive of population and community-level impacts as part of environmentally relevant scenarios. Finally, it is imperative that professional societies take a more proactive role in promoting the transdisciplinary collaboration of biological and agricultural engineers with other disciplines contributing to advances in ecological risk assessment. [ABSTRACT FROM AUTHOR]

The author discusses role of opioids in the treatment of chronic pain. Topics discussed include lack of understanding about opioid abuse potential and the risk of addiction in healthcare settings, efficacy of long-term opioid use in the treatment of chronic pain, and development and use of non-opioid pain medications for pain management.

As diagnostic groups are increasingly called upon to participate in experimental campaigns at remote facilities, there is a need to develop portable versions of plasma diagnostic systems. One such diagnostic is laser induced fluorescence (LIF). Here, we describe a portable LIF apparatus that eliminates the need for an optical table, beam splitters, and an optical chopper. All of the light exiting the laser system is coupled through optical fibers to the experiment and housekeeping diagnostics. The collected light is coupled through an optical fiber as well. A key feature is modulation of the tapered amplifier current instead of physical modulation of the laser output. Using this portable LIF system, measurements of ion temperature, ion flow, and relative metastable ion density are reported for two different remote experiments. [ABSTRACT FROM AUTHOR]

Pulmonary veno-occlusive disease (PVOD) is a rare subtype of pulmonary arterial hypertension (PAH) characterised by preferential remodelling of the pulmonary venules. Differentiation from other subtypes of PAH is essential as the management can differ significantly; for example, initiation of vasodilator therapy may cause fatal pulmonary oedema in a patient with PVOD misdiagnosed with idiopathic PAH. PVOD also carries a substantially worse prognosis. Lung biopsy is required for definitive diagnosis, but this is hazardous, and ideally, should be avoided in pulmonary hypertension. Computed tomography (CT) may suggest the diagnosis, directing the patient towards specialist review. Potential distinguishing CT features between PVOD and other subtypes of PAH include interlobular septal thickening, mediastinal lymphadenopathy, and centrilobular ground-glass opacities. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the definitive treatment for eligible patients. Therefore, early radiological identification of this challenging diagnosis facilitates timely referral for transplant. [ABSTRACT FROM AUTHOR]

• CHIMERA will be uniquely capable of 'semi-integral' testing of fusion components. • Key systems have required specific development activities. • The large array first wall heating system is under qualification. • Certain diagnostics are de-risked via testing in a pulsed magnet field. • An integrated systems model of the commissioning mock-up is producing first results. The CHIMERA fusion technology facility will enable testing of large in-vessel component modules under reactor-like conditions of combined in-vacuum thermal power density and magnetic field. With an integral large superconducting magnet and a PWR-like water loop, CHIMERA is also ideally placed for experiments on liquid metal breeding blanket prototypes. Facility construction is underway at the UKAEA site in South Yorkshire. The superconducting magnet is fully wound and terminated, and the bespoke pulsed magnet power supply has been delivered. Even before construction and commissioning is complete, a parallel and supporting research and development programme is in progress and is reported here. A bespoke infrared heating system has been developed, capable of applying 0.5 MW/m2 to component surfaces up to the size of the ITER test blanket module first wall. The modules of this heater are highly specialised and designed to endure the high magnetic forces from the CHIMERA static and pulsed magnets. CHIMERA will feature a range of diagnostics, including load cells to measure static and pulsed magnetic forces, and induced current sensors, all of which have been tested to confirm acceptable operation in the pulsed magnetic field. Manufacture of the test mock-up to be used for facility commissioning is underway. Testing will be enhanced with simulation 'digital twin' capability, and a development project is now producing first virtual test results, informing commissioning of the CHIMERA device. [ABSTRACT FROM AUTHOR]

Background: ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended Phase 2 dose (RP2D).Methods: Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement.Results: 80 patients were enrolled, 61 in dose-escalation/food-effect cohorts and 19 with pre-defined tumour types in the expansion cohort. The most common ARQ 087-related adverse events were fatigue (49%), nausea (46%), aspartate aminotransferase (AST) increase (30%), and diarrhoea (23%). Four patients (5%) experienced grade 1 treatment-related hyperphosphataemia. Dose-limiting toxicity was reversible grade 3 AST increase. The RP2D was 300 mg QD. Pharmacokinetics were linear and dose-proportional from 25 to 325 mg QD, and were unaffected by food. Statistically significant changes (P-value<0.05) suggest phosphate and FGF19 levels as markers of target engagement. In 18 evaluable patients with FGFR genetic alterations, 3 confirmed partial responses (two intrahepatic cholangiocarcinomas (iCCA) with FGFR2 fusions and one urothelial cancer with FGFR2 and FGF19 amplification) and two durable stable disease at ⩾16 weeks with tumour reduction (FGFR2 fusion-positive iCCA and adrenocortical carcinoma with FGFR1 amplification) were observed.Conclusions: ARQ 087 had manageable toxicity at the RP2D of 300 mg QD, showed pharmacodynamics effects, and achieved objective responses, notably in patients with FGFR2 genetic alterations. [ABSTRACT FROM AUTHOR]

Background Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). Methods Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest. The combined impact of clinical, pathological and immune parameters on survival was analysed using log rank testing and Cox regression analyses. Results Upregulation of HLA-E was associated with an improved disease-free and disease-specific survival in univariate analysis (HR 0.58 95% CI 0.37–0.89; HR 0.42 95% CI 0.25–0.73, respectively). In multivariate analysis, the presence of NK cells predicts survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09–0.91) when HLA-E expression is upregulated; but it is associated with a worse prognosis when HLA-E expression is normal (HR 13.43, 95% CI 1.70–106.14). By contrast, the prognostic benefit of T cells was not modulated by HLA-E expression. Conclusions Taken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to explain our observations. [ABSTRACT FROM AUTHOR]

We conducted a cohort study of adult ward patients who had a Medical Emergency Team (MET) call triggered by confirmed or suspected sepsis in an Australian tertiary centre to assess the predictive utility of systemic inflammatory response syndrome (SIRS) and quick Sepsis-Related Organ Failure Assessment (qSOFA) scores for 28-day mortality over a 12-month period. Sepsis was the causative aetiology in 970 MET calls for 646 patients with a mean age of 68 years and median Charlson Comorbidity score (CCS) of 3.0. Four hundred and seven (63%) patients had microbiological identification of a causative organism with 35 (9%) demonstrating multi-drug resistance. The 28-day mortality rate was 22%. Independent risk factors for 28-day mortality included age (incidence rate ratio [IRR] 1.038; P <0.001) and CCS (IRR 1.102; P <0.001). qSOFA positive patients had a three-fold risk of 28 day mortality compared to those who were negative (IRR 3.15; P=0.02). Both the SIRS and qSOFA score had poor sensitivity (86% versus 62%, respectively) for mortality as a sole diagnostic tool and should be investigated as part of a multiparameter panel within a large prospective study. [ABSTRACT FROM AUTHOR]

The effect of anisotropy and spatial dispersion of a metamaterial on the Talbot effect may be engineered in principle. This has profound implications for applications of the Talbot effect such as the design of a multimode interference coupler (MMI). The paper describes how a metamaterial can suppress the modal phase error which otherwise limits the scaling of MMI port dimension. A binary multilayer dielectric material described by the Kronig-Penney model is shown to provide a close approximation to the required dispersion relation. Results of simulations of a multi-slotted waveguide MMI engineered to provide a polarising beam splitter function are given as an example of the method. [ABSTRACT FROM AUTHOR]

The use of the x-ray absorption K-edge slope is investigated as a model-free diagnostic of the electronic temperature in warm dense matter. Data are reported for aluminum in a wide domain of densities (approximately one to three times the solid density) and temperatures (~0.1-10eV). Measurements are obtained from laser-shock compression where both temperature and density are independently determined from optical diagnostics. They are compared with two different theoretical approaches, respectively, based on quantum molecular dynamics and multiple scattering. Extrapolation for other absorption edges and materials is discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the effects of Mulligan's tape ( MT) and kinesio tape ( KT) with no tape ( NT) on hip and knee kinematics and kinetics during running. Twenty-nine female recreational runners performed a series of 'run-throughs' along a 10-m runway under the three taping conditions. Two force plates and a 14-camera Vicon motion analysis system ( Oxford Metrics, Inc., Oxford, UK) captured kinematic and kinetic data for each dependent variable from ground contact to toe off. Comparisons of each dependent variable under three taping conditions were assessed through Statistical Package for the Social Sciences ( SPSS; SPSS, Inc., Chicago, Illinois, USA; P-value < 0.01) using repeated measure analyses of variance. For each dependent variable with a P-value < 0.01, repeated measures with pairwise comparisons and Bonferroni adjustment were conducted to compare the three taping conditions. MT induced a significant reduction in anterior and posterior hip forces, knee flexion angular velocity, knee extensor moments, and hip flexion and extension moments compared with NT and KT ( P = 0.001). There was no difference in hip or knee, kinematics or kinetics, between KT and NT ( P = 1.000). MT appears to influence hip and knee biomechanics during running in an asymptomatic sample, whereas KT appeared to be biomechanically not different from NT. [ABSTRACT FROM AUTHOR]

Objective To explore the feasibility of using shear wave speed (SWS) estimates to detect differences in cervical softening pre- and post-ripening in women undergoing induction of labor. Methods Subjects at 37-41 weeks' gestation undergoing cervical ripening before induction of labor were recruited (n=20). Examinations, performed prior to administration of misoprostol and 4 h later included Bishop score, transvaginal ultrasound measurement of cervical length, and 10 replicate SWS measurements using an ultrasound system equipped with a prototype transducer (128 element, 3mm diameter, 14mm aperture) attached to the clinician's hand. Subjects were divided into two groups, 'not-in-labor' and 'marked-progression', based on cervical evaluation at the second examination. Measurements were compared via individual paired hypotheses tests and using a linear mixed model, with the latter also used to compare groups. Spearman's rank correlation coefficient was used to compare SWS with Bishop score. The linear mixed model can take into account clustered data and accommodate multiple predictors simultaneously. Results TheWilcoxon signed-rank paired test established a significant difference in pre- and post-ripening SWS,with mean SWS estimates of 2.53±0.75 and 1.54±0.31 m/s, respectively (P<0.001) in the not-in-labor group (decrease in stiffness) and 1.58±0.33 and 2.35±0.65 m/s for the marked-progression group (increase in stiffness). The linear mixed model corroborated significant differences in pre- and post-ripening measurements in individual subjects (P<0.001) as well as between groups (P<0.0001). SWS estimates were significantly correlated with digitally-assessed cervical softness and marginally correlated with Bishop score as assessed by Spearman's rank correlation coefficient. Conclusions In-vivo SWS estimates detected stiffness differences before and after misoprostol-induced softening in term pregnancies. This ultrasonic shear elasticity imaging technique shows promise for assessing cervical softness. [ABSTRACT FROM AUTHOR]

Background:The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice.Method:Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13.Results:Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks.Conclusions:HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage. [ABSTRACT FROM AUTHOR]

Background:Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.Methods:Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.Findings:Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).Interpretation:Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response. [ABSTRACT FROM AUTHOR]

Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).Interpretation: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response. [ABSTRACT FROM AUTHOR]

Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice.Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13.Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks.Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage. [ABSTRACT FROM AUTHOR]

Accurate determination of the complex shear modulus of soft tissues and soft-tissue-like materials in the 10–300 Hz frequency range is very important to researchers in MR elastography and acoustic radiation force impulse (ARFI) imaging. A variety of instruments for making such measurements has been reported, but none of them is easily reproduced, and none have been tested to conform to causality via the Kramers–Kronig (K-K) relations. A promising linear oscillation instrument described in a previous brief report operates between 20 and 160 Hz, but results were not tested for conformity to the K-K relations. We have produced a similar instrument with our own version of the electronic components and have also accounted for instrumental effects on the data reduction, which is not addressed in the previous report. The improved instrument has been shown to conform to an accurate approximation of the K-K relations over the 10–300 Hz range. The K-K approximation is based on the Weichert mechanical circuit model. We also found that the sample thickness must be small enough to obtain agreement with a calibrated commercial rheometer. A complete description of the improved instrument is given, facilitating replication in other labs. [ABSTRACT FROM AUTHOR]

Introduction/Background In recent years, the Functional Movement Screen (FMS™) has been used for the prevention of disability. Some studies have reported that corrective exercise to improve FMS score is an effective method of preventing injuries (Bodden et al., 2015; Justin et al., 2017). However, measurement instrument to assess FMS™ are not available in high school's. The purpose of this research is to clarify the effectiveness of corrective exercises without specific FMS measurement instruments on FMS score, physical function, and throwing performance in high school baseball players. Material and method High school baseball players were randomly assigned to two groups; 37 in the training group and 34 in the control group. All subjects were evaluated for FMS score, eyes closed single leg stance time, subjective fatigue, as well as pitching ball speed and control at the beginning of the intervention and at 2-months follow-up. Baseball players in training group conducted the corrective exercises 4 times per week for 2 months. Results When comparing the 2 groups group, pitching ball control significantly decreased in the training group compared to prior to the intervention. After 2 months, deep squat, hurdle step, inline lunge, active straight-leg raise, trunk stability pushup, rotary stability, total score of FMS, and pitching ball control showed significant better results in the training group compared to the control group. Conclusion Results of this study showed that corrective exercises improved asymmetries, trunk stability, movement pattern, proprioception, total FMS score, and pitching ball control without using special instruments following a 2-months training period. Corrective exercises to improve FMS are effective even in high school baseball players without using special measurement instruments. [ABSTRACT FROM AUTHOR]

Introduction/Background In recent years, neuromuscular training (NMT) using a balance board has become a common form of exercise to prevent ankle sprain. Previous studies of effectiveness of this approach have focused on adults, and there are few studies investigating junior high school students. The purpose of this study was to clarify the effect of the NMT using a balance board upon ankle injury in junior high school basketball players. Material and method Hundred and six junior high school basketball players without concurrent injuries were recruited. All players were randomly assigned with 40 allocated to a control group and 66 to a NME group. Subjects in the NME group completed an ankle injury prevention program including single calf rising, single leg squat, dribble with single leg, handling with single leg and pass with single leg on the floor for 2 weeks and those on the balance board for the following 6 weeks. Ankle injury rates were calculated and compared by occurrence of injury's per 1000 practice hours in the control and NME groups. Results The number of ankle inversion injuries were 17 in the control group and 13 in the NME group. Ankle injury rate per 1,000 hours revealed 4.43 in the control and 1.99 in NME group, respectively. Serious injuries, judged by single calf raise, where time loss to sport exceeded 1-week were 4 in the control group and 1 in the NME group. Average time loss in days in the control group (1.98 ± 0.59) was significantly greater than that in the NME group (1.37 ± 0.17). Conclusion Our study showed that NMT using a balance board reduced the occurrence of ankle sprain in junior high school basketball players. In addition, NMT may have contributed to a reduction in the severity of ankle injury. [ABSTRACT FROM AUTHOR]

The full melting of a two-dimensional plasma crystal was induced in a principally stable monolayer by localized laser stimulation. Two distinct behaviors of the crystal after laser stimulation were observed depending on the amount of injected energy: (i) below a well-defined threshold, the laser melted area recrystallized; (ii) above the threshold, it expanded outwards in a similar fashion to mode-coupling instability-induced melting, rapidly destroying the crystalline order of the whole complex plasma monolayer. The reported experimental observations are due to the fluid mode-coupling instability, which can pump energy into the particle monolayer at a rate surpassing the heat transport and damping rates in the energetic localized melted spot, resulting in its further growth. This behavior exhibits remarkable similarities with impulsive spot heating in ordinary reactive matter. [ABSTRACT FROM AUTHOR]