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Supplementary Figure S1. Western blot characterization of antibodies against BCKDH-E1 and BCKDH-pSer-E1

Supplementary Figure S2. Brain Metastatic Cells Contain High Levels of Glycogen

Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. Cancer Res; 75(3); 554–65. ©2014 AACR.

Purpose Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres. Methods Thirty-eight patients, median age = 60 (45–83), attended for GAE using 100–300 μm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0–100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively. Results Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53–66) at baseline to 36 (SD = 24, 95% CI 28–44) at 3 months (p p p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p Conclusion GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.

PURPOSE Genicular artery embolisation (GAE) is a novel treatment for patients with knee osteoarthritis (OA). Cadaveric dissection was undertaken to provide a complete description of the relevant arterial anatomy in order to perform safe and effective GAE. MATERIALS Twenty human lower limb specimens were dissected. The morphology of the genicular arteries and presence of anastomotic connections was recorded and compared with angiographic images from patients having undergone GAE. Vessels were measured to investigate the risk of non-target embolisation (NTE), taking a diameter of 300 microns as the threshold for significance. RESULTS The descending genicular artery (DGA) is the dominant vessel in medial OA, with 95% of cases revealing vessel division into muscular, saphenous and osteoarticular branches from a single pedicle. The superior medial genicular artery (SMGA) had a shared origin with the middle genicular artery (MGA) in 25% of cases. NTE to the MGA may damage the cruciate ligaments. In 85% of cases, there was an anastomosis between the DGA and SMGA, often encountered at angiography. The mean diameter of the anastomoses was 850 micron, presenting a risk for NTE. An anastomosis between the Inferior Medial Genicular Artery (IMGA) and medial sural artery was found in 5% of cases; the medial sural artery supplies blood to the tibial nerve and should be avoided. The IMGA and inferior lateral genicular artery provided supply to the patellofemoral joint in 69% and 88% of cases, respectively. CONCLUSION An in-depth knowledge of genicular artery anatomy is required for interventional radiologists to perform safe and effective GAE in patients with knee osteoarthritis.

Objectives: Bladder stone management in patients with reconstructed bladders drained by Mitrofanoff catheterizable channels, with no urethral access, generates multiple challenges. Trans-Mitrofanoff access limits the size of endoscopic stone fragmenting devices, risking prolonged procedures, incomplete stone clearance and damage to the continent conduit. Access through previous surgical access sites risks bowel injury. This case series reports outcomes in patients undergoing percutaneous cystolitholapaxy (PCCL), using ultrasound-guided access and direct track closure, thereby limiting radiation exposure and avoiding suprapubic catheters (SPCs). Patients and methods: Seven PCCL procedures were performed in five patients with closed urethras. Average age 32 years, primary diagnoses: spina bifida, vertebrae, anus, trachea, esophagus, renal (VATER) syndrome, bladder exstrophy and traumatic brain injury. Four used Mitrofanoff stomas and one an SPC. Average largest stone was 18.57 mm (range 10–30 mm). Five procedures were for multiple stones (range 2–30 stones). Results: Each PCCL achieved complete stone clearance. Average operative time: 146 min (range 72–250 min). No intraoperative blood loss or bladder perforation. Postoperative median length of stay was 2 days. Conclusion: PCCL is a safe, minimally invasive alternative to open surgery for large and multiple bladder stones in individuals with complex lower urinary tract anatomy, specifically reconstructed bladders drained by Mitrofanoff catheterizable channels with no urethral access. Level of evidence: Level 4

A 57-year-old man with no medical history and

Summary ParagraphDespite social distancing and shelter-in-place policies, COVID-19 continues to spread in the United States. A lack of timely information about factors influencing COVID-19 spread and testing has hampered agile responses to the pandemic. We developed How We Feel, an extensible web and mobile application that aggregates self-reported survey responses, to fill gaps in the collection of COVID-19-related data. How We Feel collects longitudinal and geographically localized information on users’ health, behavior, and demographics. Here we report results from over 500,000 users in the United States from April 2, 2020 to May 12, 2020. We show that self-reported surveys can be used to build predictive models of COVID-19 test results, which may aid in identification of likely COVID-19 positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation, as well as for household and community exposure, occupation, and demographics being strong risk factors for COVID-19. We further reveal factors for which users have been SARS-CoV-2 PCR tested, as well as the temporal dynamics of self-reported symptoms and self-isolation behavior in positive and negative users. These results highlight the utility of collecting a diverse set of symptomatic, demographic, and behavioral self-reported data to fight the COVID-19 pandemic.

Despite social distancing and shelter-in-place policies, COVID-19 continues to spread in the United States. A lack of timely information about factors influencing COVID-19 spread and testing has hampered agile responses to the pandemic. We developed How We Feel, an extensible web and mobile application that aggregates self-reported survey responses, to fill gaps in the collection of COVID-19-related data. How We Feel collects longitudinal and geographically localized information on users' health, behavior, and demographics. Here we report results from over 500,000 users in the United States from April 2, 2020 to May 12, 2020. We show that self- reported surveys can be used to build predictive models of COVID-19 test results, which may aid in identification of likely COVID-19 positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation, as well as for household and community exposure, occupation, and demographics being strong risk factors for COVID-19. We further reveal factors for which users have been SARS-CoV-2 PCR tested, as well as the temporal dynamics of self- reported symptoms and self-isolation behavior in positive and negative users. These results highlight the utility of collecting a diverse set of symptomatic, demographic, and behavioral self- reported data to fight the COVID-19 pandemic.

There has been a recent trend for the construct of addiction to be applied to sexual behaviours. A growing number of people recounting excessive sexual thoughts or behaviours have been categorized as suffering from sex “addiction”. Sex addiction is said to involve a pathological relationship to sex, with the symptomology akin to drug dependence. Opposing interpretations have argued that sex addiction is used as a stigmatizing label for those who deviate from a socially constructed sexual standard. A Foucauldian form of discourse analysis was used to analyse semi-structured interviews with nine men who identified as sex-addicts or as highly sexual though not addicted to sex. Our analysis explores how sexual addiction is constructed by some interviewees, and focuses on the discursive theme of losing control, used by interviewees to construct their positioning and moral status. Socio-political and ideological connotations of a loss of control were constructed using psychological and biomedical discou...

Uncaging promoter and enhancer dynamics In order to understand cellular differentiation, it is important to understand the timing of the regulation of gene expression. Arner et al. used cap analysis of gene expression (CAGE) to analyze gene enhancer and promoter activities in a number of human and mouse cell types. The RNA of enhancers was transcribed first, followed by that of transcription factors, and finally by genes that are not transcription factors. Science , this issue p. 1010

Scientific Data, 4, ISSN:2052-4463

In embryonic development, cells differentiate through stereotypical sequences of intermediate states to generate particular mature fates. By contrast, driving differentiation by ectopically expressing terminal transcription factors (direct programming) can generate similar fates by alternative routes. How differentiation in direct programming relates to embryonic differentiation is unclear. We applied single-cell RNA sequencing to compare two motor neuron differentiation protocols: a standard protocol approximating the embryonic lineage, and a direct programming method. Both initially undergo similar early neural commitment. Later, the direct programming path diverges into a novel transitional state rather than following the expected embryonic spinal intermediates. The novel state in direct programming has specific and uncharacteristic gene expression. It forms a loop in gene expression space that converges separately onto the same final motor neuron state as the standard path. Despite their different developmental histories, motor neurons from both protocols structurally, functionally, and transcriptionally resemble motor neurons isolated from embryos.

Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that the long non-coding RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 is dynamically regulated by neuronal activity in vitro and in vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 and KCNIP1, and induces a neuronal hyper-potentiation phenotype in iPSC-derived human cortical neurons following antisense oligonucleotide knockdown. Next generation sequencing reveals a strong association of NEAT1 with increased ion channel gene expression upon activation of iPSC-derived neurons following NEAT1 knockdown. Furthermore, we show that while NEAT1 is acutely down-regulated in response to neuronal activity, repeated stimulation results in NEAT1 becoming chronically unresponsive in independent in vivo rat model systems relevant to temporal lobe epilepsy. We extended previous studies showing increased NEAT1 expression in resected cortical tissue from high spiking regions of patients suffering from intractable seizures. Our results indicate a role for NEAT1 in modulating human neuronal activity and suggest a novel mechanistic link between an activity-dependent long non-coding RNA and epilepsy.

With the advancement of reconfigurable tooling and manufacturing systems, aerospace enterprises are looking for mixed production solutions to gain leading competitive edge. An accurate similarity metric will be necessary and crucial for making sound mix-production decisions. Although most literatures studied similarity coefficients for grouping part families in cellular manufacturing systems, they are not applicable to aircraft assemblies which involve large amount of manual work dealing with large heavy components and assemblies. This paper proposes a new similarity metric that incorporates both component level similarity and system level similarity of aircraft assemblies. The similarity in components level is modeled based on part-operation and operation-operation incidence matrices. The similarity in assembly level is modeled by similarity system theory associated with a newly proposed operation quota-based weighting method. A digital manufacturing tool has been developed for the automated implementation of the new models. Both the models and the tool have been validated by six pairs of real-life panel assembly examples. Results showed that the new similarity index gives clear indication to the degree of commonality in panel assemblies, and a quick and accurate similarity result can be generated by the digital tool.

Down syndrome (DS) is a complex developmental disorder with diverse pathologies that affect multiple tissues and organ systems. Clear mechanistic description of how trisomy of chromosome 21 gives rise to most DS pathologies is currently lacking and is limited to a few examples of dosage-sensitive trisomic genes with large phenotypic effects. The recent advent of cellular reprogramming technology offers a promising way forward, by allowing derivation of patient-derived human cell types in vitro. We present general strategies that integrate genomics technologies and induced pluripotent stem cells to identify molecular networks driving different aspects of DS pathogenesis and describe experimental approaches to validate the causal requirement of candidate network defects for particular cellular phenotypes. This overall approach should be applicable to many poorly understood complex human genetic diseases, whose pathogenic mechanisms might involve the combined effects of many genes.

BackgroundIatrogenic ureteral injuries arise as serious complication following obstetrics, gynecological, general, and urological surgery with incidence in the range of 0.5–10%. Retrograde placement of double-J ureteric stent is a possible treatment option if the injury is not recognized at the time of surgery.PurposeTo assess technical success and long-term outcome associated with retrograde ureteric stent insertion for iatrogenic ureteric injury.Material and MethodsBetween 1999 and 2011, 26 patients with initially unrecognized iatrogenic ureteric injury underwent initial management with retrograde ureteric stenting. Full case-notes were available for review in 25 patients.ResultsThe mean interval from injury to attempted stenting was 19.4 days. Successful retrograde ureteric stenting was achieved in 21/25 patients (81%). Retrograde stenting failed in four patients, and nephrostomy followed by alternative procedures were performed instead. At a median follow-up interval of 9.7 months, normal anatomy was demonstrated on 12/21 patients (57%) and a stricture was observed in 6/21 patients (28%) with three requiring surgical intervention.ConclusionRetrograde stenting is a safe and efficient initial management in patients with iatrogenic ureteric injuries.

Disrupted-In-Schizophrenia 1 (DISC1) was identified as a risk factor for psychiatric illness through its disruption by a balanced chromosomal translocation, t(1;11)(q42.1;q14.3), that co-segregates with schizophrenia, bipolar disorder and depression. We previously reported that the translocation reduces DISC1 expression, consistent with a haploinsufficiency disease model. Here we report that, in lymphoblastoid cell lines, the translocation additionally results in the production of abnormal transcripts due to the fusion of DISC1 with a disrupted gene on chromosome 11 (DISC1FP1/Boymaw). These chimeric transcripts encode abnormal proteins, designated CP1, CP60 and CP69, consisting of DISC1 amino acids 1–597 plus 1, 60 or 69 amino acids, respectively. The novel 69 amino acids in CP69 induce increased α-helical content and formation of large stable protein assemblies. The same is predicted for CP60. Both CP60 and CP69 exhibit profoundly altered functional properties within cell lines and neurons. Both are predominantly targeted to mitochondria, where they induce clustering and loss of membrane potential, indicative of severe mitochondrial dysfunction. There is currently no access to neural material from translocation carriers to confirm these findings, but there is no reason to suppose that these chimeric transcripts will not also be expressed in the brain. There is thus potential for the production of abnormal chimeric proteins in the brains of translocation carriers, although at substantially lower levels than for native DISC1. The mechanism by which inheritance of the translocation increases risk of psychiatric illness may therefore involve both DISC1 haploinsufficiency and mitochondrial deficiency due to the effects of abnormal chimeric protein expression. GenBank accession numbers: DISC1FP1 (EU302123), Boymaw (GU134617), der 11 chimeric transcript DISC1FP1 exon 2 to DISC1 exon 9 (JQ650115), der 1 chimeric transcript DISC1 exon 4 to DISC1FP1 exon 4 (JQ650116), der 1 chimeric transcript DISC1 exon 6 to DISC1FP1 exon 3a (JQ650117).

Only relatively recently has it become clear that mammalian genomes encode tens of thousands of long non-coding RNAs (lncRNAs). A striking 40% of these are expressed specifically in the brain, where they show precisely regulated temporal and spatial expression patterns. This begs the question, what is the functional role of these many lncRNA transcripts in the brain? Here we canvass a growing number of mechanistic studies that have elucidated central roles for lncRNAs in the regulation of nervous system development and function. We also survey studies indicating that neurological and psychiatric disorders may ensue when these mechanisms break down. Finally, we synthesize these insights with evidence from comparative genomics to argue that lncRNAs may have played important roles in brain evolution, by virtue of their abundant sequence innovation in mammals and plausible mechanistic connections to the adaptive processes that occurred recently in the primate and human lineages.

Introduction ILD is physiologically characterised by restrictive ventilatory pattern, impaired gas exchange, maintained airway patency and increased elastic lung recoil pressure. Spirometric values are often well-preserved but the shape of the flow volume (FVL) can suggest enhanced mechanical emptying of the lungs. Previously spirometry has identified upper airways obstruction,1 but limited data exists for the use of an index to describe possible ILD. Method Retrospective PFT data was analysed (n = 119). The slope of the line from PEF to RV (PEF/FVC ratio) was calculated and correlated against other PFT variables. Pearson’s correlation was applied between the ratio and markers of ILD, data from table previously presented at the ARPT conference 2015*. 30 patients (27m, 3f) were selected for CT analysis and qualitative verification of Traction Bronchiectasis (TBX). CT scan had to be within 6 months of PFTs, FVC >70% predicted and a PEF/FVC > 2.0 (range 2.11–4.36). Information on location within the lung and level of severity was obtained. Results Of the 30 patients, 27 were found to have TBX, (3 mild, 17 moderate and 8 severe), 3 patients had no evidence of TBX. No correlation was found between magnitude of PEF/FVC and severity of TBX. Conclusion Structural changes from TBX may cause stenting of the airways from fibrotic tissue, holding them open during forced expiration.2 Our volume corrected PEF/FVC predicts reduced TLC and RV percent predicted, indicating reduced lung volumes and lung stiffness in patients with restrictive lung disease. The evidence of TBX on CT imaging supports the hypothesis that airways are held open during forced expiration, allowing increased efficiency of lung emptying in patients with a PEF/FVC >2.0. The magnitude of the ratio did not correlate with TBX severity but further work to determine a cut off ratio to predict future fibrosis is required. This index may be of use indicate a value beyond which TBX is likely to be present. Reference Empey DW. Assessment of upper airway obstruction. BMJ 1972;3:503–505. Woodring JH, Barrett PA, Rehm SR, et al. Acquired tracheomegaly in adults as a complication of diffuse pulmonary fibrosis. AJR 1989;152(4):743–747.

Unpredicted contactor failure can interrupt production and affect the uptime and throughput of manufacturing. Usually the life of a contactor is based on the manufacturers' life test data. However, due to the way of how the contactor is operated and the environment it is operated in, the working life of a contactor can vary significantly. In this paper, a novel technology has been investigated to predict potential failures of DC actuated contactors by monitoring their DC coil current and contactor currents. Three parameters are derived from this set of data to monitor the health of contactors: contact over-travel, armature pull-in time and coil current differential. Contact over-travel provides information on the remaining life of contacts and coil current differential provides indication of contact weld and carrier jam due to debris. The armature pull-in time provides information on contactor closing speed. Prototype contactors have been built and AC4 tests have been carried out for evaluation. Test results show that the contact over-travel parameter agrees well with contact mass loss data taken after contactors failed. The derived armature pull-in time agrees well with that measured by a laser displacement sensor. The defined parameters provide effective monitoring and prediction of potential contactor failures.

Well-characterized species introductions provide opportunities to compare the genetic signatures of known founder effects across classes of molecular markers. The release of small numbers of house finches (Carpodacus mexicanus) into the eastern United States in the 1940s led to substantial interest in the effects of this introduction on genetic diversity in this now abundant species, an issue that has been highlighted by a recent Mycoplasma disease epidemic that most intensively affects the introduced and potentially genetically depauperate house finch populations. Previous studies comparing genetic diversity levels in native and introduced house finch populations produced seemingly disparate results: comparisons based on amplified fragment length polymorphism, RFLP mtDNA, and allozyme markers found essentially equivalent levels of diversity in eastern and western populations, whereas microsatellite markers showed clear reductions in diversity in the introduced populations. Here we employ sequence variation at the ND2 mtDNA locus to further compare levels of diversity between the four native and five introduced house finch populations that were previously examined in the microsatellite study. We found substantially lower ND2 haplotype richness and diversity across all introduced populations of house finches. The majority of sequence variation (78%) was detected within subpopulations, with the remainder (22%) explained by the historical status of each population (native or introduced). Our results are consistent with previous microsatellite evidence for a founder effect during the introduction of eastern house finches, and suggest that the mtDNA founder effect was particularly severe, likely owing to a male-biased sex ratio at the time of introduction coupled with the lower effective population size of clonally inherited markers. We discuss how the inconsistencies between past studies of house finch diversity can inform the usefulness of distinct marker sets for detecting molecular signatures of founder events.

SUMMARY This article documents the development of the catalog at the Schomburg Center for Research in Black Culture (NYPL), from its early heginnings up through digital access as is now evident in its Internet presentation, The Digital Schomburg. The role of this unique library as educator and producer is discussed, as well as the cataloging decisions and processes required in mounting The Digital Schomburg. Links to a number of Digital Schomburg resources are provided.

Schizophrenia (SZ) is a complex disease characterized by impaired neuronal functioning. Although defective alternative splicing has been linked to SZ, the molecular mechanisms responsible are unknown. Additionally, there is limited understanding of the early transcriptomic responses to neuronal activation. Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.

The disciplinary status of health informatics remains unclear. Is it an art or a science? Does it have a body of theory? A survey was devised for UK academics that teach or research health informatics. Forty-six responses were received, twenty-five from the target group (representing between a quarter and a third of the population of interest). Health informatics is not perceived to have a well-known and clearly definable body of theory, but there is a clear demand for a more theoretical basis for the discipline. Journals and conferences were rated as the best sources of theory and seven key textbooks were identified.

There are few empirical data to support the widely accepted practice of screening depressives for causative thyroid disease, as summarized in the previous article of this series. We therefore formed, as a null hypothesis, the proposal that ambulatory depressives do not comprise an enriched sample for unsuspected clinical hypo- or hyperthyroidism. To investigate this issue we studied a prospectively assessed sample of 166 consecutive medically healthy outpatients who a) met criteria for a current major depressive episode and b) underwent thyroid function testing consisting of determination of serum total thyroxine (T4) and free thyroxine index (FTI); 105 of the 166 patients also had thyrotropin (TSH) determination. Laboratory thyroid testing was mandated by drug treatment protocol and was therefore not influenced by clinician-related testing factors. The clinic did not participate in thyroid related research and therefore was not likely subject to thyroid related patient selection or referral bias. Caseness was defined by abnormal FTI confirmed by subsequent testing. Prevalence rates for abnormal total T4 and TSH were also calculated. Only one case (0.6%) of hypothyroidism and no cases of hyperthyroidism were found. Four patients (2.4%) had decreased total T4 but normal FTI while two (1.2%) had high total T4 with normal FTI. Elevated TSH was found in only two (1.9%). Thus prevalence of hypo- or hyperthyroidism in patients with major depressive disorder does not differ from that reported for the general population. These data indicate that thyroid screening guidelines which have been developed for the general population may therefore be preferable to routinely screening all ambulatory depressives. A strategy for testing ambulatory depressives is suggested: That all ambulatory depressives be routinely screened for signs, symptoms, and specific risk factors for hyper or hypo-thyroidism, but that routine junction testing is not indicated. Depression 1:220–224 (1993). © 1993 Wiley-Liss, Inc.

In the preparation of osseointegrated dental implant sites, the use of bone drilling with conventional external irrigation has been shown to be thermally non-injurious to bovine bone, when employed as a model for dental implantology. The use of internal irrigation drilling systems is promoted on the basis of improved delivery of coolant to the bone/drill interface, which should subsequently improve local debridement and cooling, and therefore reduce thermal insults to the bone. The aim of this bovine model study was to compare the temperatures that were generated with external and internal irrigation systems during bone preparation for dental implants. A constant drill load of 1.7 kg was applied throughout the drilling procedures via a drilling rig. The burs that were used for both irrigation methods were a 2 mm twist drill for cutting the channel and a 3.25 mm drill for trephining this channel. The principal recorded parameter was the change in temperature generated via the drilling procedure. The 2 mm twist drills produced a maximum change in temperature of only 3.0 degrees C and 3.1 degrees C for the internal and external irrigation systems, respectively. Maximum changes for the 3.25 mm drills were 1.34 degrees C and 1.62 degrees C, respectively. Using the t-test, no statistical benefit was observed for one irrigant delivery system over the other. The clinical benefit of using the more expensive internal irrigation systems is therefore deemed unjustifiable, on the grounds that these systems do not appear to reduce the thermal challenge to the bone over and above that of simple flood irrigation.

Clinical Radiology 69 (2014) S11eS21 S19 Results of 1st audit round: CTavg 27%, median 15%, range 0-90% CRavg 11%, median 8%, range 2-38% 1 CR report made no sense. Targets not met. Types of errors similar sounding words, lack of punctuations, words cut off, extra words. 1st action plan: 1. Presented at departmental and hospital audit meeting 2. Recommend RIS that would support auto-transcription of ’clinical details’ 3. Feedback to reporter 4. Repeat audit in 6 months Results of 2nd round: March April 2014. CTe avg 23%; median 5%; range 0-100% CReavg18%; median 8%; range 2e84% Targets not met. Reporter A continues to have high VR error rate. Other reporters have good improvement. Overall improvement in CT errors. CR errors have deteriorated. Errors are mainly of voice recognition and punctuation. Majority of errors are mild and in clinical details. 2nd action plan:1. Present at departmental audit meeting 2. Urgent recommendation of RIS that would support auto-transcription of ‘clinical details’ 3. Feedback to reporter Radiology registrar on-call reporting accuracy Authors: Victoria Chan*, Heiko Peschl, Matthew Smedley, Nassim Parvizi, James Briggs Background: At our Trust, oncall registrars (ST3+) issue verified reports, subsequently checked by consultants within 24 hours. Clinical teams should be contacted when there are discrepancies to allow for changes in management. Standard, indicator and target: An RCR AuditLive template proposed a 2-5% error rate for on-call reporting (2% for significant errors,5% for all discrepancies affecting management). Methodology: All on-call registrar reports were comparedwith consultant addendums for February 2013.Discrepancies were categorised according to grading system, 1 1⁄4 minor error with no significance,2 1⁄4 minor error affecting long-term outcome, 3 1⁄4 major error affecting long-term outcome,4 1⁄4 major error affecting immediate outcome. Results of 1st audit round: Total of 646 reports,77(11.9%) had corrections:22 scored1(3.4%),25 scored2(3.9%),22 scored3(3.4%),8 scored4(1.2%). 1st action plan: This audit demonstrates that issuing on-call reports by registrars is safe with only a small proportion of acutely significant discrepancies.It also emphasises the value of Consultant review, with subsequent amendments impacting upon management. Results of 2nd round: Follow-up audit for February 2014 had total of 770 reports,66(8.6%) had corrections:34 scored 1(4.4%),17 scored 2(2.2%),13 scored 3(1.7%),2 scored 4(0.3%). 2nd action plan: Again, the on-call registrar reporting accuracywaswithin ’general target’ despite increased workload in 2014.Nevertheless,we recommend regularmonitoring of on-call workload and registrar reporting accuracy to ensure a high standard for patient care and safety. Unexpected findings e the importance of safety nets Authors: Sean J. McIlhone*, Bhavin Rawal, Jeremy Lynch, Priya Narayanan, Catriona Davies Background: Timely communication of reports and alerting clinicans to critical/unexpected findings is essential for patient safety and in preventing serious untoward incidents. Following the RCR’s updated guidance on this issue (1), we audited the existing ’safety net’ procedures in our imaging department. * Guarantor and correspondent: Victoria Chan * Guarantor and correspondent: Sean J. McIlhone * Guarantor and correspondent: Jessie Gil * Guarantor and correspondent: Matthew Pickford Standard, indicator and target: 100% of patients with unexpected findings should either: Have their report faxed to the referring clinician or Be added to a relevant MDT meeting for discussion. Methodology: Data Set: All emails regarding unexpected findings that were sent to radiology secretaries during a one month period (November 2013) were retrieved from the radiology information system. These emails may request for the report to be urgently faxed to the referring clinician OR request that the patient is added to the relevant MDT meeting. Hospital records were then analysed to ensure these patients had been followed up as appropriate. Results of 1st audit round: Of the email requests for a report to be faxed, 94% (50/53) had records confirming that a fax had been sent. Average time lag 1⁄4 3 days Of the email requests for MDT discussion, 90% (43/48) of patient records confirmed they were discussed at MDT. Average time lag 1⁄4 7 days All remaining patients were accounted for and followed up. 1st action plan: 1. Standardise the format of email requests and of the electronic record showing the request was actioned 2. Departmental meeting to suggest a more robust and failsafe method of communicating urgent findings to clinicians Patient satisfaction with day case provision of interventional radiology procedures Authors: Jessie Gil*, James H. Briggs, Brenda Shanahan, Mark Bratby, Raman Uberoi Background: Day case intervention reduces patient stay, can improve patient experience and reduce overall procedural cost. Provision of good patient experience an important measure of care. Standard, indicator and target: Standards were locally agreed, based on NICE standards (1) . 90% of patients should have been pre-assessed and 90% should receive written information in advance. We wished for mean satisfaction score of 4 out of 5. Methodology: Patient perception was assessed using a 13 part survey comprising binary questions and scaled responses (1-very poor to 5excellent). Data were collected over eight weeks. Results of 1st audit round: 53 patients were surveyed. 93% had preadmission consultation. 86.7% had received written information. Mean scores to other questions all met the agreed standard. 1st action plan: Improved systems for administering information leaflets. Results of 2nd round: 52 Patients were surveyed. 76.9%were pre-assessed by telephone or in person, fewer than 50% of patients received written information and 3.8% had no pre-admission information. Standards for satisfactionwith the consent process and addressing consent questions were again met. Patients were highly satisfied with the availability of staff to answer questions and their reassurance post-procedure. Overall patient satisfaction was ’very good’ or better. 2nd action plan: Overall satisfaction was increased and met targets, but improved administration to ensure higher rates of pre-assessment and written information provision is required. Non-contrast CT KUB in acute renal colic Authors: Matthew Pickford*, George Yeung Background: We perceived a low diagnostic yield for CT KUB when balanced against radiation exposure in our younger patients, particularly young women. We therefore audited our detection rates for stones and other significant pathology. Standard, indicator and target: The highest and lowest detection rates identified by literature review for stones and other significant pathology

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

Interstitial brachytherapy for recurrent gliomas normally necessitates the invasive application of a stereotactic frame by screw-fixation which must be kept on for several hours. The use of a relocatable stereotactic frame offers many advantages over conventional systems. We present our experience in 18 patients and verify that the frame used is accurate, comfortable, well tolerated and associated with no major disadvantages.

A case of malignant oxyphilic granular-cell tumor (oncocytoma) has been presented. A review of the recent literature has disclosed fourteen additional examples of this type of tumor—thirteen benign and one malignant.

Recent aspects of homolytic aromatic substitutions.- A General protocol for systematic synthesis design.- Rearrangements and interconversions of carbenes and nitrenes.

This paper is limited to the soft copy display of electro-optical imagery obtained by reconnaissance systems. The topic is further limited to the author's human factors experience in developing techniques, analyses and procedures which have contributed to the development of soft copy (CRT) displays, having image quality (interpretability) equal or superior to hard copy (film). The results of an early study comparing hard and soft copy by photo interpreters are reviewed. Following this is a description and discussion of various techniques, aids, and analyses which contributed to the results. These include: a discussion of image quality, its measurement, and its visual side; a digital target for measuring a display's potential for high quality presentations; a procedure for determining a display's "best gamma" function; an analytical approach determining a display's size, and pixel spacing and size; and the importance of facility lighting, including some recent experimental data. Finally, an interpretation of the various experiences is given.