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Background The rapid technical development and portability of ultrasound systems over recent years has had a profound impact on the area of point-of-care-ultrasound (POCUS), both in general medicine and in obstetrics and gynecology. The use of POCUS enables the clinician to perform the ultrasound scan either at the medical office or the patient’s bedside and used as an extension of the physical examination. Real-time images can immediately be correlated with the patient’s symptoms, and any changes in a (critical) patient’s condition can be more rapidly detected. POCUS in OBGYN POCUS is also suitable for time-critical scenarios, and depending on the situation and its dynamics, the course and results of any therapy may be observed in real time. POCUS should be considered to be a routine extension of practice for most OB/GYN clinicians as it can give immediate answers to what could be life-threatening situations for the mother and/or baby. With its proven usefulness, the applications and use of POCUS should be incorporated in teaching programs for medical students, OBGYN residents and emergency physicians.

As a medical imaging modality, ultrasound is used by a wide cross-section of practitioners including radiologists, obstetricians, gynecologists, gastroenterologists, urologists and cardiologists. The increasing popularity of ultrasound as a diagnostic tool is due not only to the ease of use and portability of systems, but also to the perceived safety aspect of the examination. This latter point needs to be examined. As with any reusable medical device, the ultrasound transducer, also known as a probe, could potentially be a vector for the transmission of pathogenic viruses and fungi between patients if not correctly disinfected after each use. This transmission risk is magnified for an endocavity transducer that has come in contact with the vagina, anal canal or oral cavity, as it could be contaminated with organisms transmitted by blood or mucosal, genital or rectal secretions. Based on the Spaulding system, transducers that come in contact with mucous membranes are classified as semi-critical devices that require high-level disinfection (HLD) after each patient procedure. This HLD process should eliminate all microorganisms except high numbers of bacterial endospores. Only a small number of countries worldwide have implemented transducer reprocessing guidelines that adhere to the Spaulding classification and recommend HLD for endocavity transducers. Overall, there is a lack of conformity among global health agencies regarding the use of HLD for endocavity transducers. This is primarily due to the perception that the infection transmission risk is negligible and that if an endocavity transducer has been covered with a single-use sheath for the procedure, then low-level disinfection provides sufficient protection against pathogen transmission. The objective of this study was to review the published risk of infection transmission from endocavity transducers. By highlighting the outbreaks and case reports that implicate pathogen transmission from transducers, we posit that HLD should be a global standard of practice for the reprocessing of endocavity transducers. It requires substantial time for national health administrations to develop and legislate new recommendations, and for practice changes to be accepted and implemented by healthcare providers. We recommend that Joint Commission International (JCI) and other equivalent organizations enforce the use of HLD of endocavity ultrasound transducers during their accreditation reviews.Als bildgebendes Verfahren in der Medizin wird Ultraschall von Ärzten verschiedenster Fachrichtungen eingesetzt, darunter Radiologen, Geburtshelfer, Gynäkologen, Gastroenterologen, Urologen und Kardiologen. Die zunehmende Beliebtheit von Ultraschall als diagnostisches Hilfsmittel ist nicht nur auf die einfache Handhabung und Tragbarkeit der Systeme zurückzuführen, sondern auch auf die vermeintlichen Sicherheitsaspekte der Untersuchung. Dieser letztgenannte Punkt muss untersucht werden. Wie bei jedem wiederverwendbaren medizinischen Gerät könnte der Ultraschallkopf, der auch als Sonde bezeichnet wird, potenziell ein Vektor für die Übertragung pathogener Viren und Pilze zwischen den Patienten sein, wenn er nicht nach jedem Gebrauch korrekt desinfiziert wird. Dieses Übertragungsrisiko ist bei einer endokavitären Sonde, die mit der Vagina, dem Analkanal oder der Mundhöhle in Kontakt gekommen ist, erhöht, da diese mit Organismen kontaminiert sein könnte, die durch Blut oder durch Schleimhaut-, Genital- oder Rektalsekrete übertragen werden. Auf der Grundlage des Spaulding-Klassifikationssystems werden Schallköpfe, die mit Schleimhäuten in Kontakt kommen, als semikritische Geräte eingestuft, die nach jedem Patienteneingriff ein High-level-Desinfektionsverfahren (HLD) erfordern. Dieses HLD-Verfahren sollte alle Mikroorganismen mit Ausnahme vieler bakterieller Endosporen eliminieren. Nur wenige Länder weltweit haben Richtlinien für die Aufbereitung von Schallköpfen eingeführt, die sich an die Spaulding-Klassifikation halten und HLD für endokavitäre Sonden empfehlen. Insgesamt besteht unter den globalen Gesundheitsbehörden ein Mangel an Konformität hinsichtlich des Einsatzes der HLD für endokavitäre Sonden. Dies ist in erster Linie auf die Auffassung zurückzuführen, dass das Risiko der Infektionsübertragung vernachlässigbar ist und dass, wenn eine endokavitäre Sonde für den Eingriff mit einer Einweghülle abgedeckt wurde, eine Desinfektion auf niedrigem Niveau einen ausreichenden Schutz gegen die Übertragung von Krankheitserregern bietet. Das Ziel dieser Studie war es, Publikationen zum Risiko der Infektionsübertragung durch endokavitäre Sonden zu überprüfen. Indem wir die Ausbrüche und Fallberichte hervorheben, die eine Erregerübertragung durch Schallköpfe nahelegen, stellen wir fest, dass HLD weltweit Praxisstandard für die Aufbereitung von endokavitären Sonden werden sollte. Die Entwicklung und Verabschiedung neuer Empfehlungen durch die nationalen Gesundheitsbehörden sowie die Akzeptanz und Umsetzung von praktischen Änderungen bei Gesundheitsdienstleistern erfordern einen erheblichen Zeitaufwand. Wir empfehlen, dass die Joint Commission International (JCI) und andere gleichwertige Organisationen während ihrer Akkreditierungsprüfungen den Einsatz der HLD bei endokavitären Ultraschallsonden einfordern.

In view of the challenges of the current coronavirus (COVID-19) pandemic and to protect both patients and ultrasound providers (physicians, sonographers, allied professionals), ISUOG has compiled the following expert-opinion-based guidance for the performance of ultrasound investigations in pregnancy and for gynecological indications.

The severe acute respiratory syndrome coronavirus (SARS‐CoV‐2), an enveloped virus, is the causative agent of the disease known as COVID‐19 (coronavirus disease‐2019). Proper infection prevention and control measures and good hygiene practices are essential to prevent spread of COVID‐19 and protect both patients and the healthcare worker. These guidelines are relevant to all ultrasound practitioners and provides guidance on cleaning and disinfection of ultrasound equipment, the environment and PPE (protective personal equipment) during the COVID‐19 outbreak in the Australasian region.

Background Ultrasound probe covers should be used for any ultrasound procedure where there is contact with body fluids or mucous membranes. The type and quality of probe covers used in clinical practice differ widely and studies in the early 1990s showed that condoms were more superior for use with transvaginal examinations than commercial probe covers. Since then, although products have changed, there have been no further studies to assess the breakage rate of different probe covers. The objectives of this study were to assess the integrity of the most commonly used probe covers for transvaginal ultrasound examinations under clinical conditions and report the breakage rate. Methods The study was conducted in public and private hospitals and private practices. A total of 500 covers for each of 10 brands of commercial covers and condoms (latex and latex free) were distributed to ultrasound practitioners. The transvaginal ultrasound examination practice was unchanged except that all covers were placed in a container for assessment instead of discarding post ultrasound examination. All covers were collected and subjected to a water leak test. Covers that broke upon deployment onto the ultrasound probe prior to the ultrasound examination were recorded. All covers that were broken or had microtears or leaks were recorded as well as photographed. Statistical analysis was performed along with Chi-squared analysis of the data and significance considered at P Results None of the commercial covers broke upon deployment onto the ultrasound probe prior to ultrasound examination. A total of 5000 probe covers were examined post-transvaginal ultrasound examinations. The breakage rate for condoms ranged from 0.4% to 13% and for commercial covers 0–5%. Statistical analysis of the data by comparison of p-values revealed that the best performing group were the commercial non-latex probe covers and worst performing group were the non-latex condoms. Conclusion The breakage rates for commercial covers were not as high as previously reported and do not break upon deployment onto the ultrasound probe. This is the first comprehensive study that thoroughly evaluated the integrity of commercial covers and condoms used for transvaginal ultrasound examination in a clinical setting, with regards to brand, numbers and types of covers assessed.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes., Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

As ultrasound technology rapidly evolves and is used more frequently in every area of medical diagnosis and treatment, it may be overlooked as a potential vector in the transmission of a health care-associated infection. A survey on disinfection and hygiene practice in medical ultrasound was disseminated via the World Federation for Ultrasound in Medicine and Biology (WFUMB) to its six member federations and associated ultrasound societies globally. One thousand twenty-nine responses were obtained across a broad range of ultrasound practitioners. A total of 76% of respondents used transducer covers every time to scan open wounds and 71% when blood and bodily fluids were present or for an interventional procedure. Approved high-level disinfectants are not always used, even when blood comes into contact with the transducer or after endocavity scans. Alcohol-based wipes were used by many respondents to clean both external transducers and endocavity transducers. Open-ended responses indicated that a large caseload hindered the time required for cleaning and that access to clear guidelines would be beneficial. Global survey results indicate that some users do not comply with disinfection practice, and there is a gap in knowledge on basic infection prevention and control education within the ultrasound unit. As the infectious status of a patient is not often disclosed prior to an ultrasound examination, training in suitable protocols for the cleaning and disinfection of ultrasound equipment is imperative to mitigate the risk of potential infection.

INTRODUCTION: The availability of obstetric point‐of‐care ultrasound (PoCUS) services has been shown to improve pregnancy outcomes in regional and remote areas both in Australia and around the world. There is an increasing demand for efficient, cost‐effective PoCUS courses for monitoring the fetus in the third trimester of pregnancy. AIM: To compare the effectiveness of targeted PoCUS courses provided for health professionals that assess the fetus during the third trimester of pregnancy. METHOD: The skill‐teaching curriculum and competency outcomes of six obstetric PoCUS courses were compared. There were 55 learners with no prior ultrasound experience including 23 with English as a second language. Course duration ranged from 4 to 18 h, didactic lecture time up to 6 h and practical scanning sessions of 3–12 h. Learner/tutor ratio varied from 1:1 to 6:1. All courses included the teaching of knobology, image optimisation and probe manipulation. Practical sessions included supervised scanning of ultrasound phantoms and scanning women in the third trimester of pregnancy. The teaching outcomes that were assessed included image optimisation, determination of fetal lie, fetal heart rate, measuring the single deepest pocket of amniotic fluid, identifying the placental position and basic fetal biometry. The same pre‐ and post‐course multiple choice test and course evaluation forms were used for every programme. RESULTS: All participants achieved the limited course objectives, regardless of the differences in the course formats. CONCLUSION: This study confirms that obstetric PoCUS courses can provide the initial basic knowledge and scanning skills required to perform limited scope third‐trimester scanning.

INTRODUCTION: Inconsistent reporting practices in third trimester ultrasound, the choice of reference charts in particular, have the potential to misdiagnose abnormal fetal growth. But this may lead to unnecessary anxiety and confusion amongst patients and clinicians and ultimately influence clinical management. Therefore, we sought to determine the extent of variability in choice of fetal biometry and Doppler reference charts and reporting practices in Australia and New Zealand. METHODS: Clinicians performing and/or reporting obstetric ultrasound were invited to answer questions about fetal biometry and Doppler charts in a web‐based survey. RESULTS: At least four population‐based charts are in current use. The majority of respondents (78%) report the percentile for known gestational age (GA) alongside measurements and 63% using a cut‐off of estimated fetal weight (EFW) < 10(th) percentile when reporting small for gestational age (SGA) and/or fetal growth restriction (FGR). The thresholds for the use of fetal and maternal Doppler in third trimester ultrasound varied in terms of the GA, EFW cut‐off, and how measures were reported. The majority of respondents were not sure of which Doppler charts were used in their practice. CONCLUSION: This survey revealed inconsistencies in choice of reference chart and reporting practices. The potential for misdiagnosis of abnormal fetal growth remains a significant issue.

Although the prevalence of incidental findings revealed during an obstetric ultrasound examination is low, the findings may include adnexal and cervical masses, uterine or urinary congenital malformations, free fluid in the pouch of Douglas or tortuous vessels (varices). Adnexal masses are the most common finding and vary in imaging characteristics. They are mainly unilateral, cystic masses with a low risk of malignancy that are treated conservatively. The International Ovarian Tumor Analysis scoring models may be helpful in differentiating benign from malignant masses. For those masses >5 cm, follow-up is recommended, and resection could be considered to avoid risk of torsion, rupture and hemorrhage, which may compromise pregnancy outcome. Uterine masses such as fibroids are commonly diagnosed early in the first trimester and should be followed up during pregnancy to evaluate any changes. Transabdominal and transvaginal ultrasound is the first-line test for the diagnosis of such incidentalomas; however, magnetic resonance ultrasound may have a useful role in excluding malignancy potential. As a result of their low frequency and the lack of good evidence, there are no specific guidelines on the management of incidentalomas detected at obstetric scans. Their management should follow the related general guidelines for ovarian, cervical and uterine masses, with individualized management depending on the pregnancy status.

BACKGROUND: It is unclear whether a low total 25(OH)D concentration is a cause or consequence of illnesses. To address this knowledge gap, studies measuring free and total 25(OH)D during the evolution and resolution of an inflammatory process are required.OBJECTIVES: Serum total and free 25(OH)D concentrations would transiently decline after cruciate surgery in dogs.ANIMALS: Seventeen client-owned dogs with a spontaneous cranial cruciate ligament rupture (CCLR).METHODS: A longitudinal cohort study involving the measurement of serum concentrations of total and free 25(OH)D, total calcium, creatinine, albumin, phosphate, C-reactive protein and plasma ionized calcium, at 1 day before and a median time of 1 and 60 days after surgical treatment of CCLR.RESULTS: Median serum concentrations of total 25(OH)D before surgery (80.3 nmoL/L [range, 43.5-137.3]) significantly declined immediately after surgery; (64.8 nmoL/L [range, 36.3-116.5] 1 day after surgery, P CONCLUSION AND CLINICAL IMPORTANCE: This study reveals the difficulties of assessing vitamin D status in dogs following elective surgery.

Epileptic seizures are among the most common presenting symptom in patients with glioma. The etiology of glioma‐related seizures is complex and not completely understood. Studies using adult glioma patient tissue and adult glioma mouse models, show that neurons adjacent to the tumor mass, peritumoral neurons, are hyperexcitable and contribute to seizures. Although it is established that there are phenotypic and genotypic distinctions in gliomas from adult and pediatric patients, it is unknown whether these established differences in pediatric glioma biology and the microenvironment in which these glioma cells harbor, the developing brain, differentially impacts surrounding neurons. In the present study, we examine the effect of patient‐derived pediatric glioma cells on the function of peritumoral neurons using two pediatric glioma models. Pediatric glioma cells were intracranially injected into the cerebrum of postnatal days 2 and 3 (p2/3) mouse pups for 7 days. Electrophysiological recordings showed that cortical layer 2/3 peritumoral neurons exhibited significant differences in their intrinsic properties compared to those of sham control neurons. Peritumoral neurons fired significantly more action potentials in response to smaller current injection and exhibited a depolarization block in response to higher current injection. The threshold for eliciting an action potential and pharmacologically induced epileptiform activity was lower in peritumoral neurons compared to sham. Our findings suggest that pediatric glioma cells increase excitability in the developing peritumoral neurons by exhibiting early onset of depolarization block, which was not previously observed in adult glioma peritumoral neurons., The effect of pediatric glioma cells on the function of surrounding neurons during early development is unknown. We intrancranially injected patient‐derived pediatric glioma cells in young pups and examined on the function of peritumoral neurons. Pediatric glioma cells induced changes in the intrinsic properties of periturmoral neurons, lowered the threshold of hyperexcitability and exhibited an early onset of depolarization block.

Cranial cruciate ligament rupture (CCLR) is one of the most common orthopaedic disorders diagnosed in dogs yet the factors which influence postoperative clinical outcomes are poorly understood. Low vitamin D status has been linked to poorer clinical outcomes in human patients undergoing elective orthopaedic surgery. The aim of this study was to examine the relationship between pre-operative vitamin D status, as defined by serum 25 hydroxyvitamin D (25(OH)D) concentrations, and initial disease severity and clinical outcomes in dogs undergoing surgical treatment for a CCLR. Serum 25(OH)D concentrations were measured in 44 dogs with a CCLR on the day before surgery. C-reactive protein concentrations were measured at a median time of 1 day post-surgery and the patient's clinical and radiographic response to CCLR surgical treatment was assessed at a median timepoint of 60 days post-surgery. Serum 25(OH)D concentrations in dogs with a CCLR was not significantly different to a population of healthy dogs (median 74.1 nmol/L and 88.40 nmol/L, respectively). There was no significant correlation between pre-operative serum 25(OH)D concentrations and length of pre-diagnosis clinical signs, pre-operative lameness scores or day 1 post-operative CRP concentrations. Thirty nine of the 44 dogs were re-examined at a median 60 days post-surgery. There was no relationship between the day 60 lameness scores and pre-operative serum 25(OH)D concentrations. In summary, we discovered that the vitamin D status of dogs with a CCLR was not significantly lower than healthy dogs and pre-operative serum 25(OH)D concentrations were not correlated to either pre-surgical disease severity or post-operative clinical outcomes.

Mini abstractWe tested usability, safety, and ability to manage elective surgery flow of a multidisciplinary pathway adopting the SWALIS-2020 model in an interhospital setting during the COVID-19 pandemic. This pilot included 295 adults. The pathway prioritized, monitored and scheduled surgery in an 840.000-inhabitants area. Using the COVID-19-GOA-Sur-MDT-SWALIS-2020 model may be warranted.Structured abstractThe COVID-19 outbreak burdens non-COVID elective surgery patients with figures similar to the SARS-Cov-2, by creating an overwhelming demand, increasing waiting times and costs. New tools are urgently needed to manage elective access. The study assesses the “SWALIS-2020” model’s ability to prioritize and optimize access to surgery during the pandemic.A 2020 March - May feasibility-pilot study, tested a software-aided, inter-hospital, multidisciplinary pathway. All specialties patients in the Genoa Departments referred for urgent elective surgery were included in a multidisciplinary pathway adopting a modified Surgical Waiting List InfoSystem (SWALIS) cumulative prioritization method (PAT-2020) based on waiting time and clinical urgency, in three subcategories: A1-15 days (certain rapid disease progression), A2-21 days (probable progression), and A3-30 days (potential progression).Following the feasibility study (N=55 patients), 240 referrals were evaluated in 4 weeks without major criticalities (M/F=73/167, Age=68.7±14.0). Waiting lists were prioritized and monitored, and theatres allocated based on demand. The SWALIS-2020 score (% of waited-against-maximum time) at operation was 88.7±45.2 at week 1 and then persistently over 100% (efficiency), over a controlled variation (equity), with a difference between A3 (153.29±103.52) vs. A1 (97.24 ± 107.93) (p The pathway has selected the very few patients with the greatest need, optimizing access even with +30% capacity weekly modifications. We will use the pathway to manage active, backlog, and hidden waiting lists throughout the further pandemic phases, and are looking for collaboration for multi-center research.https://www.isrctn.com/ISRCTN11384058.

Ultrasound is becoming a fundamental first-line diagnostic tool for most medical specialties and an innovative tool to teach anatomy, physiology and pathophysiology to undergraduate and graduate students. However, availability of structured training programs during medical school is lagging behind and many physicians still acquire all their ultrasound skills during postgraduate training.There is wide variation in medical student ultrasound education worldwide. Sharing successful educational strategies from early adopter medical schools and learning from leading education programs should advance the integration of ultrasound into the university medical school curricula. In this overview, we present current approaches and suggestions by ultrasound societies concerning medical student educa-tion throughout the world. Based on these examples, we formulate a consensus statement with suggestions on how to integrate ultrasound teaching into the preclinical and clinical medical curricula.

Background Rett syndrome (RTT) is an X-linked neurodevelopmental disorder predominantly caused by alterations of the methyl-CpG-binding protein 2 (MECP2) gene. The gut microbiome has been implicated in neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) as a regulator of disease severity. Although the gut microbiome has been previously characterized in humans with RTT, the impact of MECP2 mutation on the composition of the gut microbiome in animal models where the host and diet can be experimentally controlled remains to be elucidated.Methods We evaluated the microbial community through 16S sequencing of fecal samples collected across postnatal development as behavioral symptoms appear and progress in a novel zinc-finger nuclease rat model of RTT. Additionally, we profiled fecal levels of fatty acids in MecP2 deficient rats. Lastly, we compared our results to predicted functional shifts in the microbiota of females with RTT compared to their mothers to further examine the translational potential of the current RTT rat model.Results We have identified microbial taxa that are differentially abundant across key timepoints in a zinc-finger nuclease rat model of RTT compared to WT. Furthermore, we have characterized functional categories of gut microbes that are similarly affected in females with RTT and female RTT rats, including similar alterations in pathways related to short chain fatty acid (SCFA) activity. Lastly, we have demonstrated that SCFA levels are decreased in the feces of RTT rats compared to WT.Limitations The current study is potentially limited by age related differences in the microbiome of RTT participants and controls as well as medication effects on the microbiome. Additionally, the current study did not assess male MeCP2-deficient rats, and it may be relevant in future studies to address potentially disparate microbial changes in male and female rats and humans with RTT.Conclusions The results of our studies establish distinct microbial community shifts that occur in RTT across developmental time points independently of diet or environmental factors. We identify p105 as a key translational timepoint at which microbial shifts most closely mirror reported microbiota communities in RTT patients. Overall, these results represent an important step in translational RTT research.

The 2017 survey of Faculty Attitude on Technology conducted by Insider Higher Ed reported on the low percentage of partnerships between university faculty and instructional designers in online course development. Experts said it is not a surprise because instructional designers are underutilized and their role in Higher Education is still not clear. This qualitative study examined the faculty members’ perceptions about their mentorship relations with instructional designers when they designed and developed asynchronous online courses. This study also explored factors that may lead to successful mentorship relationships between instructional designers as mentors and faculty members as mentees. Higher education administration, university faculty, and instructional designers will benefit from the results of this study.

Australia has established guidelines on cleaning for reusable ultrasound probes and accompanying equipment. This is a preliminary study investigating cleanliness standards of patient-ready ultrasound equipment in 5 separate health care facilities within a major city.The cleanliness was assessed using rapid adenosine triphosphate (ATP) testing used with a sampling algorithm which mitigates variability normally associated with ATP testing. Each surface was initially sampled in duplicate for relative light units (RLUs) and checked for compliance with literature recommended levels of cleanliness (100 RLUs). Triplicate sampling was undertaken where necessary. A cleaning intervention step (CIS) followed using a disposable detergent wipe, and the surface was retested for ATP.There were 253 surfaces tested from the 5 health care facilities with 26% (66/253) demonstrating either equivocal or apparent lack of cleanliness. The CIS was conducted on 148 surfaces and demonstrated that for 91% (135/148) of surfaces, the cleaning standards could be improved significantly (P .001). For 6% (9/148) of devices and surfaces, the CIS needed to be repeated at least once to achieve the intended level of cleanliness (25 RLUs).This study indicates that ATP testing is an effective, real-time, quality assurance tool for cleanliness monitoring of ultrasound probes and associated equipment.

The purpose of this document is to guide ultrasound practitioners in providing accurate information on the assessment of gestational age, viability and fetal development in the first trimester. In the presence of twins and higher order multiple pregnancies, it is also intended to assess chorionicity and amnionicity which have implications for risk assessment and continuing antenatal care. This guideline has been adopted by the ASUM Council and is applicable to all ultrasound practitioners.

Background: Cardiovascular disease (CVD) is the number 1 killer of women in the United States, yet few younger women are aware of this fact. CVD campaigns focus little attention on physicia...

Introduction/Aims Australasia is witnessing a rapidly increasing use of diagnostic medical ultrasound in clinical practice with industry statistics giving a conservative estimate of ten million scans performed annually in Australia and New Zealand. Ultrasound practice has broadened from its traditional use in radiology, obstetrics and gynaecology, vascular and cardiology specialties to embrace emergency medicine, rheumatology, midwifery, physiotherapy, paramedics and other point of care practice. With this expansion of practice comes an increase in the potential risk for ultrasound transmitted bacterial or viral infection due to suboptimal cleaning habits of transducers, cords and keyboards. Results/Conclusion This study describes results of an Australasian survey on the disinfection and hygiene practice in medical ultrasound. Results highlighted a significant need for updated guidelines and education on infection prevention and control in medical ultrasound.

Ultrasound equipment used in trans-abdominal (TA) and trans-vaginal (TV) examination may carry bacterial contamination and pose risks to infection control during ultrasound examination. We aimed to describe the prevalence of bacterial contamination on ultrasound probes, gel, machine keyboard and cords and examined the effectiveness of low- and high-level disinfection techniques. This study was performed at a public hospital and a private practice. A total of 171 swabs were analyzed and bacterial species were identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis and polymerase chain reaction (PCR). Sixty percent of TA probes and 14% of TV probes had evidence of bacterial contamination after an ultrasound examination. Low-level disinfection was partially effective, but 4% of probes were still contaminated by spore-forming species. Some heated gel samples were highly contaminated with the environmental bacterium Brevundimonas aurantiaca, suggesting the gel was conducive to bacterial growth. Ultrasound machines, probe cords and gels were identified as potential sources of bacterial contamination and need to be cleaned and changed regularly to minimize risks of infection.

Background: Chronic Enteropathies (CE) are a common cause of morbidity in dogs. Chronic enteropathies are diagnosed in dogs with chronic gastrointestinal clinical signs (>3 weeks), inflammatory changes on intestinal biopsies and where no other underlying cause is determined based on a thorough, standardised diagnostic workup. Based on response to therapy, CE are sub-classified into food-responsive, antibiotic-responsive or steroid-responsive enteropathies. A significant proportion of dogs with a CE are food-responsive; however, there are limited peer-reviewed publications describing the clinical efficacy of the commercially available diets used to treat CE. Methods: In this study, we evaluated the response of 15 dogs with a CE to a commercially available dietetic food (Hill’s TM Prescription Diet TM i/d TM Sensitive Canine Dry). The dogs underwent a standard diagnostic evaluation, and did not receive concurrent anthelmintic, antibiotic, glucocorticoid or gastroprotectant therapies. The clinical efficacy of the dietary treatment was assessed by comparing the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) before and a median of 13 days after dietary therapy. Results: We found that the CIBDAI significantly decreased following the introduction of the dietetic food (median CIBDAI score pre treatment 9, post treatment 2 (p

Objective: Currently prescribed antiepileptic drugs (AEDs) are ineffective in treating approximately 30% of epilepsy patients. Sulfasalazine (SAS) is an US Food and Drug Administration (FDA)–approved drug for the treatment of Crohn disease that has been shown to inhibit the cystine/glutamate antiporter system xc‐ (SXC) and decrease tumor‐associated seizures. This study evaluates the effect of SAS on distinct pharmacologically induced network excitability and determines whether it can further decrease hyperexcitability when administered with currently prescribed AEDs. Methods: Using in vitro cortical mouse brain slices, whole‐cell patch‐clamp recordings were made from layer 2/3 pyramidal neurons. Epileptiform activity was induced with bicuculline (bic), 4‐aminopyridine (4‐AP) and magnesium‐free (Mg2+‐free) solution to determine the effect of SAS on epileptiform events. In addition, voltagesensitive dye (VSD) recordings were performed to characterize the effect of SAS on the spatiotemporal spread of hyperexcitable network activity and compared to currently prescribed AEDs. Results: SAS decreased evoked excitatory postsynaptic currents (eEPSCs) and increased the decay kinetics of evoked inhibitory postsynaptic currents (eIPSCs) in layer 2/3 pyramidal neurons. Although application of SAS to bic and Mg2+‐free–induced epileptiform activity caused a decrease in the duration of epileptiform events, SAS completely blocked 4‐AP–induced epileptiform events. In VSD recordings, SAS decreased VSD optical signals induced by 4‐AP. Co‐application of SAS with the AED topiramate (TPM) caused a significantly further decrease in the spatiotemporal spread of VSD optical signals. Significance: Taken together this study provides evidence that inhibition of SXC by SAS can decrease network hyperexcitability induced by three distinct pharmacologic agents in the superficial layers of the cortex. Furthermore, SAS provided additional suppression of 4‐AP–induced network activity when administered with the currently prescribed AED TPM. These findings may serve as a foundation to assess the potential for SAS or other compounds that selectively target SXC as an adjuvant treatment for epilepsy. Foundation for the National Institutes of Health, Grant/Award Number: 5R01‐NS036692, R01‐NS052634 and R01CA227149

Idiopathic retinal detachment is a serious common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. Genetic correlations between retinal detachment and high myopia or cataract operation were high, respectively 0.46 (SE=0.08) and 0.44 (SE=0.07), in the UK Biobank dataset and in line with known epidemiological associations. Meta-analysis of genome-wide association studies using UK Biobank retinal detachment cases (N=3977) and two cohorts, each comprising ∼1000 rhegmatogenous retinal detachment patients, uncovered 11 genome-wide significant association signals, near or withinZC3H11B, BMP3, COL22A1, DLG5, PLCE1, EFEMP2, TYR, FAT3, TRIM29, COL2A1andLOXL1.Replication in the 23andMe dataset, where retinal detachment is self-reported by participants, firmly establishes association at six lociFAT3, COL22A1, TYR, BMP3, ZC3H11BandPLCE1.The former two seem to particularly impact on retinal detachment, the latter three shed light on shared aetiologies with cataract, myopia and glaucoma.Author SummaryRetinal detachments are common conditions that may lead to permanent severe sight reduction or blindness; they are a major cause of emergency eye surgery. The most common type of retinal detachment follows a break in the retina and is thought to be in part genetically determined but little is known about the contributing individual genetic risk variants. The condition prevalence increases with age and with common eye conditions such as myopia, cataract or glaucoma. We showed that the retinal detachment cases derived from self-report or hospitalisation records in the large UK Biobank dataset show very similar characteristics to samples of carefully clinically evaluated retinal detachment with break cases and therefore could be used to perform genetic analysis of the condition. Association studies require large sample of cases and by pooling Biobank and clinical cases, this study identifies 11 novel significant associations, six of which were further replicated in an independent population-based dataset (23andMe). Two of the replicated findings seem to specifically underline retinal detachment risk while three others highlight shared genetic risk with myopia, cataract and/or glaucoma, paving the way to better understanding of these conditions and of their overlap.

Objectives To identify gaps in Australian sonographer's knowledge and application of as low as reasonably achievable (ALARA) principles during first trimester imaging; Identify relationships between demographic variables and knowledge or application of the Output Display Standard (ODS) value thermal index (TI) and compare Australian sonographers to their international peers. Methods Australian Sonographer Accreditation Registered (ASAR)-registered sonographers completed a voluntary questionnaire over September 2015 after institutional ethics approval (RDSE-48-15). Seventeen questions detailed their demographics (5); knowledge of ultrasound bioeffects terminology and ALARA principles (9); behaviour surrounding ALARA and first trimester imaging (2) and continuing bioeffects education (1). Exclusion criteria was non-ASAR status. Descriptive (mode frequency) and inferential statistics (Fisher exact test) were used. Significance level was 95%. Results Ninety-five valid surveys were collected. Ninety-nine per cent knew the meaning of ALARA, 93.55% correctly defined ‘TI’ and 85.39% knew where to find the TI value via the ODS. Half never monitor the ODS. No correlation (P = 0.094) was found between experience and ODS monitoring. No statistical difference (P = 0.189) existed between obstetric and non-obstetric sonographers who knew the meaning of TIB (87.18% vs. 76.92%) or those who correctly identified it as the setting for 11–14-week examinations (30.77% vs. 30.77%). When using Doppler during obstetric examinations, no difference existed (P = 0.293), between obstetric and non-obstetric sonographers’ knowledge of ASUM/WFUMB guidelines for maximum TI (47.37% vs. 46.15%). Conclusions Despite poor ODS usage, Australian sonographers outperform their international peers for ALARA literacy, and show better application of ALARA principles in the first trimester. No relationships were found between demographic variables and knowledge or conscious monitoring of ODS.

Clinical decisions are often based on the results of third trimester sonograms, particularly with small or large babies and so accuracy of estimating fetal weight (EFW) is essential. There are numerous EFW formula available and yet in Australia no one formula has been recommended for use due to the lack of clinical evidence as to their accuracy. Objectives: 1 To assess inter/intra observer error for fetal parameter measurements with multiple observers. 2 To compare six of the most commonly used EFW formulae and analyse inter/intra formulae variations for different weight range. Method: EFW of 121 pregnancies assessed within 7 days of birth by measuring the BPD, OFD, HC, AC, FL and comparing to actual birth weight. Results: Inter-observer error: 1.3 to 3.1%. Intra-observer error: 1.1 to 1.9% depending on fetal parameter. Accuracy of each EFW formula changed with different weight ranges. For all formulae the highest random error occurred in the macrosomic group. The lowest random error in all weight groups was the Hadlock B formula incorporating the HC/AC/FL (7.7%). Conclusion: Considering the possible problems of head moulding this study suggests the use of: Hadlock FP et al (1982) - Formula B - incorporating HC/AC/FL.

The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY Cell 2018;173:P1728–P1741.e13.The ketogenic diet (KD) is used ...

Fetal measurements have been a contentious issue in ultrasound departments worldwide for decades. With a plethora of literature on measuring planes, mathematical formulae, local charts, and differences in fetal size due to various factors, deciding which charts to use can be confusing. Australia has not been immune to this issue. In 2001, ASUM recommended the use of the Campbell Westerway charts for CRL, BPD, OFD, HC, AC, FL & HL, which were formulated from an Australian population. Despite this recommendation, there are currently at least eight fetal growth charts in clinical use around Australia. 1 Unfortunately, it is not uncommon to find different charts on different machines within the same department, which is confusing for follow‐up growth studies, and affects parents, clinicians and researchers alike. For example, a baby diagnosed as small for gestational age (SGA) by one practitioner is later that day found to be ‘normal’ with a different reference chart at the referral hospital. This makes counselling challenging: why does this difference exist? Is it due to the chart or the quality of scanning? Is the baby at risk or not? The issue illustrates the problem of a lack of uniform ultrasound reporting, which may be particularly noticeable in countries like Australia where scans are commonly performed in small private practices. In general terms, fetal growth can be assessed using charts that are: 1 Derived from the observed distributions of fetal size for gestational age in a defined population 2 Customised on the basis of maternal characteristics such as maternal parity, height and ethnicity including an estimate of fetal weight based on Hadlock's proportionality equation 3 Standards derived from a healthy population purposely selected to reflect optimal growth, based on observed measurements of fetuses that are free from adverse constraints on growth and which are independent of time or place. SGA is most commonly defined as the 10th centile of estimated fetal weight (EFW) or abdominal circumference (AC). It must be realised that the apparent ‘prevalence’ of SGA will always be close to the 10th centile when reference or customised charts are used. This is despite the fact that the prevalence of other perinatal conditions differs greatly around the world: for example, differences in rates of pre‐eclampsia or gestational diabetes are readily accepted, without a call for local definitions, demonstrating the illogical nature of insisting on an SGA prevalence that is “fixed” at 10%. So which fetal biometry charts should be used from the hundreds available around the world? After over five decades of obstetric ultrasound there has been no implementation of an international standard. Contrast this with the consensus on optimal growth in paediatrics. Since the 1970s, it has been observed that growth in children depends more on their environment and nutritional state, than ethnic origin. 2 In 1996, the WHO Multicentre Growth Reference Study (MGRS) was established to prove whether this hypothesis was indeed correct for babies born in diverse populations around the world. Across six countries, researchers followed the growth and development of 8406 healthy, breast‐fed babies until 5 years of age. 3 They demonstrated that, under such conditions, growth was remarkably similar in childhood. 4 This led to the release of the WHO Child Growth Standards in 2006 and these have subsequently been adopted in over 130 countries. 5 In Australia, national unification of child growth monitoring occurred in 2012, when the NHMRC recommended the WHO Child Growth Standards for use in all infants aged 0 to 2 years of age. 6 The current situation in fetal medicine Identifying babies experiencing poor or excessive growth in utero is challenging. Despite ASUM recommending the Campbell Westerway charts in 2000,7 there has been no consensus on fetal growth monitoring, no publication of an ‘Australian standard’, and consequently several charts have been used. For most practitioners, the choice of fetal growth chart is determined either by their institutional protocol, professional society, imaging software program, or the default chart installed by the ultrasound machine manufacturer. However, charts differ greatly not only in the centile thresholds and trajectories, but also the quality of the studies upon which they were based: two comprehensive systematic reviews evaluated the quality of published ultrasound charts for fetal dating with crown‐rump length 8 and fetal growth monitoring. 9 Across the 112 studies identified, there were several important potential sources of methodological bias including: failure to define gestational age accurately; inconsistent population definitions and inclusion and exclusion criteria; lack of image standardisation protocols, and retrospective analysis of images captured for clinical purposes. This resulted in a large amount of variation in centile thresholds when different charts were used: for example, the 10th centile for AC at 36 weeks' gestation ranged from 276 to 292 mm even among the best studies. Open in a separate window Figure 1 Abdominal circumference.

The common starling (Sturnus vulgaris) has a proven invasion history in many countries, and at a continental scale in North America and Australasia. In Australia, starlings are firmly established throughout the eastern states and Tasmania. Incursions of starlings into Western Australia (WA) represent a significant threat to this State’s agricultural, public amenity and biodiversity assets. We present models of starling population dynamics that incorporate environmental and control effort variability. We incorporate knowledge of starling ecology with economic data to assess the potential economic cost of starlings establishing in WA, evaluating the cost–benefits for each management scenario. We calculated starling population size will approach carrying capacity in WA within as little as 30 years if left unchecked. A population of this size could cost the WA economy up to $43.7 million annually in 2011/2012 dollars. Over a 50 year horizon, the conservative benefit–cost ratio for ongoing detection and control at the current level of expenditure is 6.03:1. However, even under current levels of control, starling numbers are projected to increase to almost 11 million by 2061. Further improvements in the efficiency of starling detection and control and/or an increased level of expenditure on detection and control are required.

We aimed to compare the value of transabdominal (TA) and transvaginal (TV) approaches for assessing the risk of a low-lying placenta. This involved a comparison of TA and TV measurements between the leading placental edge and the internal cervical os. We also assessed the intra-/interobserver variation for these measurements and the efficacy of TA measures in screening for a low placenta. Methodology Transabdominal and TV measurements of the leading placental edge to the internal cervical os were performed on 369 consecutive pregnancies of 16–41 weeks' gestation. The difference (TA-TV) from the mean was calculated and plotted against gestational age. Bland-Altman plots and paired t-tests were used to look at the differences in TA/TV measurement. Screening performance of a transabdominal approach was compared to a transvaginal ‘gold standard'. Nonparametric methods were used to calculate the area under the receiver operator characteristics (ROC) curve. Intra-/interobserver variations were also calculated. Results Of the pregnancies, 278 had a leading placental edge that was visible with the TV approach. Differences (TA-TV) ranged from −50 mm to +57 mm. Bland-Altman plot shows that TA measurements overestimated the distance compared with the TV measurements; the average difference in measurement was 12.0 mm (95% confidence interval 9.9–14.1). The sensitivity, specificity and negative predictive values of a TA approach were 18.2%, 97.5% and 87.2%, respectively. The receiver operator characteristics area between gestational weeks 16–23 was 0.81 (95% CI: 0.76–0.86). Conclusion The TA approach has a low sensitivity for detecting a low-lying placenta as choosing a TA cut-off with sensitivity >90% will decrease the specificity to 50%.

A learning plan is a tool to guide the development of knowledge, skills and professional attitudes required for practice. A learning plan is an ideal tool for both supervisors and mentors to guide the process of teaching and learning a medical ultrasound examination. A good learning plan will state the learning goal, identify the learning activities and resources needed to achieve this goal, and highlight the outcome measures, which when achieved indicate the goal has been accomplished. A skill acquisition plan provides a framework for task acquisition and skill stratification; and is an extension of the application of the student learning plan. One unique feature of a skill acquisition plan is it requires the tutor to first undertake a task analysis. The task steps are progressively learnt in sequence, termed scaffolding. The skills to develop and use a learning or skill acquisition plan are also learnt, but are an integral component to the ultrasound tutors skill set. This paper will provide an outline of how to use and apply a learning and skill acquisition plan. We will review how these tools can be personalised to each student and skill teaching environment.

As ultrasound technology rapidly evolves and is used more frequently in every area of medical diagnosis, it can be overlooked as a potential vector in the transmission of a healthcare associated infection. The infectious status of a patient is not often disclosed prior to an ultrasound examination and if the ultrasound probe involves contact with blood or bodily fluids, this can pose a risk of transmission of potential pathogens from patient to patient, or patient to operator. An overview of recent research relating to infection prevention around ultrasound will be discussed.

Best practice guidelines for the disinfection of ultrasound transducers and infection prevention in ultrasound departments are generally recommended by either government health groups or the ultrasound societies of individual countries. The literature shows a wide variance in not only transducer cleaning methods but basic hygiene practices in the ultrasound workplace. This paper describes results from a UK survey of disinfection of ultrasound transducers and hygiene practice in the workplace. The survey revealed that some ultrasound practitioners did not follow current guidelines with regard to the correct disinfection method of transducers, cords or ultrasound machine keyboards. Furthermore, the survey exposed the lack of training from the product manufacturers on how to use the disinfection product appropriately. These inconsistencies may be responsible for compliance issues and highlight the need for an awareness campaign and a unified approach to infection control by ultrasound practitioners.

Over the last decade, the use of portable ultrasound scanners has enhanced the concept of point of care ultrasound (PoC-US), namely, “ultrasound performed at the bedside and interpreted directly by the treating clinician.” PoC-US is not a replacement for comprehensive ultrasound, but rather allows physicians immediate access to clinical imaging for rapid and direct solutions. PoC-US has already revolutionized everyday clinical practice, and it is believed that it will dramatically change how ultrasound is applied in daily practice. However, its use and teaching are different from continent to continent and from country to country. This World Federation for Ultrasound in Medicine and Biology position paper discusses the current status and future perspectives of PoC-US. Particular attention is given to the different uses of PoC-US and its clinical significance, including within emergency and critical care medicine, cardiology, anesthesiology, rheumatology, obstetrics, neonatology, gynecology, gastroenterology and many other applications. In the future, PoC-US will be more diverse than ever and be included in medical student training.

Biological invasions are not only a major threat to biodiversity, they also have major impacts on local economies and agricultural production systems. Once established, the connection of local populations into metapopulation networks facilitates dispersal at landscape scales, generating spatial dynamics that can impact the outcome of pest-management actions. Much planning goes into landscape-scale invasive species management. However, effective management requires knowledge on the interplay between metapopulation network topology and management actions. We address this knowledge gap using simulation models to explore the effectiveness of two common management strategies, applied across different extents and according to different rules for selecting target localities in metapopulations with different network topologies. These management actions are: (i) general population reduction, and (ii) reduction of an obligate resource. The reduction of an obligate resource was generally more efficient than population reduction for depleting populations at landscape scales. However, the way in which local populations are selected for management is important when the topology of the metapopulation is heterogeneous in terms of the distribution of connections among local populations. We tested these broad findings using real-world scenarios of European rabbits (Oryctolagus cuniculus) infesting agricultural landscapes in Western Australia. Although management strategies targeting central populations were more effective in simulated heterogeneous metapopulation structures, no difference was observed in real-world metapopulation structures that are highly homogeneous. In large metapopulations with high proximity and connectivity of neighbouring populations, different spatial management strategies yield similar outcomes. Directly considering spatial attributes in pest-management actions will be most important for metapopulation networks with heterogeneously distributed links. Our modelling framework provides a simple approach for identifying the best possible management strategy for invasive species based on metapopulation structure and control capacity. This information can be used by managers trying to devise efficient landscape-oriented management strategies for invasive species and can also generate insights for conservation purposes.

The elimination of this virus worldwide is a long way off and it is important for healthcare professionals to understand the symptoms. Susan Campbell outlines what to look for and the changes in UK legislation concerning pet quarantine A zoonotic disease, rabies is an encephalitis caused by the rabies virus. It is estimated that there are about 55,000 cases of rabies each year worldwide, almost all in developing countries (Health Protection Agency 2012). Rabies has the highest death rate of any type of viral infection, yet is almost 100 per cent preventable (Briggs 2010, NHS Choices 2011). This article explains recent changes in UK quarantine laws and discusses whether we are any closer to the eradication of rabies.

SUMMARY Purpose: Patients with gliomas frequently present with seizures, but the factors associated with seizure development are still poorly understood. In this study, we assessed peritumoral synaptic network activity in a glioma animal model and tested the contribution of aberrant glutamate release from gliomas on glioma-associated epileptic network activity. Methods: In vitro brain slices were made from gliomaimplanted mice. Using extracellular field recordings, we analyzed peritumoral epileptiform activity induced by Mg 2+ -free medium in slices from tumor-bearing animals and sham-operated controls. We assessed the effect of sulfasalazine (SAS), a blocker of system x c and glutamate release, on spontaneous and evoked activity in tumorassociated slices. Key Findings: Tumor-associated cortical networks were hyperexcitable. The onset latency of Mg 2+ -free‐induced epileptiform activity was significantly shorter in tumorbearing slices, and the incidence of Mg 2+ -free‐induced ictal-like events was higher. Block of glutamate release from system x c decreased the response area of evoked activity and completely blocked Mg 2+ -free‐induced ictallike, but not interictal-like events. Significance: Control of seizures in patients with gliomas is an essential component of clinical management; therefore, understanding the origin of seizures is vital. This work provides evidence that peritumoral synaptic network activity is disrupted by tumor masses resulting in network excitability. We show that blocking glutamate release via system x c with SAS, a drug already approved by the U.S. Food and Drug Administration (FDA), can inhibit Mg 2+ -free‐induced ictal-like epileptiform events similar to other chemicals used to decrease seizure activity. We, therefore, suggest that further studies should consider SAS a promising agent to aid in the treatment of seizures associated with gliomas.

Purpose The study investigated the efficacy and cost-effectiveness of a cognitive-behavioral weight management program, complemented by an interactive Web site and brief telephone/e-mail coaching. Methods In 2006–2007, 1755 overweight, non-active-duty TRICARE beneficiaries were randomized to one of three conditions with increasing intervention intensity: written materials and basic Web access (RCT1), plus an interactive Web site (RCT2), plus brief telephone/e-mail coaching support (RCT3). The study assessed changes in weight, blood pressure, and physical activity from baseline to 6, 12, and 15–18 months. (Study retention was 31% at 12 months.) Average and incremental cost-effectiveness and cost-offset analyses were conducted. Results Participants experienced significant weight loss (− 4.0%, − 4.0%, and − 5.3%, respectively, in each RCT group after 12 months and − 3.5%, − 3.8%, and − 5.1%, respectively, after 15 to 18 months), increased physical activity, and decreased blood pressure. Cost-effectiveness ratios were $900 to $1100/quality-adjusted life year (QALY) for RCT1 and RCT2 and $1900/QALY for RCT3. The cost recovery period to the government was 3 years for RCTs 1 and 2 and 6 years for RCT3. Conclusion A relatively inexpensive cognitive-behavioral weight management intervention improved patient outcomes. Extrapolation of savings for the entire TRICARE population would significantly reduce direct medical costs.

Epileptic seizures are a common and poorly understood comorbidity for individuals with primary brain tumors. To investigate peritumoral seizure etiology, we implanted human-derived glioma cells into severe combined immunodeficient mice. Within 14-18 d, glioma-bearing mice developed spontaneous and recurring abnormal electroencephalogram events consistent with progressive epileptic activity. Acute brain slices from these mice showed marked glutamate release from the tumor mediated by the system x(c)(-) cystine-glutamate transporter (encoded by Slc7a11). Biophysical and optical recordings showed glutamatergic epileptiform hyperexcitability that spread into adjacent brain tissue. We inhibited glutamate release from the tumor and the ensuing hyperexcitability by sulfasalazine (SAS), a US Food and Drug Administration-approved drug that blocks system x(c)(-). We found that acute administration of SAS at concentrations equivalent to those used to treat Crohn's disease in humans reduced epileptic event frequency in tumor-bearing mice compared with untreated controls. SAS should be considered as an adjuvant treatment to ameliorate peritumoral seizures associated with glioma in humans.

Background— Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. Methods and Results— A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between ≈2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log–transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 ( P =6.4×10 −52 ) was 46.0 kb upstream from F3 , coagulation factor III (tissue factor). At 1q24, rs6687813 ( P =2.4×10 −14 ) was 79.7 kb downstream of F5 , coagulation factor V. At 4q32, rs13109457 ( P =2.9×10 −18 ) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA . Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log–transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. Conclusions— Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported.