d=3 Bosonic Vector Models Coupled to Chern-Simons Gauge Theories

We study three dimensional O(N)_k and U(N)_k Chern-Simons theories coupled to a scalar field in the fundamental representation, in the large N limit. For infinite k this is just the singlet sector of the O(N) (U(N)) vector model, which is conjectured to be dual to Vasiliev's higher spin gravity theory on AdS_4. For large k and N we obtain a parity-breaking deformation of this theory, controlled by the 't Hooft coupling lambda = 4 \pi N / k. For infinite N we argue (and show explicitly at two-loop order) that the theories with finite lambda are conformally invariant, and also have an exactly marginal (\phi^2)^3 deformation. For large but finite N and small 't Hooft coupling lambda, we show that there is still a line of fixed points parameterized by the 't Hooft coupling lambda. We show that, at infinite N, the interacting non-parity-invariant theory with finite lambda has the same spectrum of primary operators as the free theory, consisting of an infinite tower of conserved higher-spin currents and a scalar operator with scaling dimension \Delta=1; however, the correlation functions of these operators do depend on lambda. Our results suggest that there should exist a family of higher spin gravity theories, parameterized by lambda, and continuously connected to Vasiliev's theory. For finite N the higher spin currents are not conserved.Comment: 34 pages, 29 figures. v2: added reference

Reducing non-attendance rates for assessment at an eating disorders service: a quality improvement initiative

Rates of non-attendance at initial appointments within community eating disorder (ED) services are frequently high, although this has received relatively little research attention and no reports of interventions designed to address this. The current report describes outcomes following a change of procedure introducing a ‘partial booking’ system. Attendance rates at first appointments (N = 1260) were audited following introduction of a system designed to reduce non-attendance in January 2013 within a UK ED service. Rates were compared following implementation of the new system, using a historical control group for comparison, and showed a decline from 20.4 to 15.1%, a medium-sized effect. Use of a system asking patients to book an appointment reduced non-attendance at initial appointments and may be of use to similar services experiencing high non-attendance rates. Opt-in initiatives can reduce burden resulting from long waiting times and can be easily adapted to individual services

Hyperammonemic Coma—Barking Up the Wrong Tree

Hepatic encephalopathy and myxedema coma share clinical features: coma, ascites, anemia, impaired liver functions, and a “metabolic” electroencephalogram (EEG). Hyperammonemia, a hallmark of hepatic encephalopathy, has also been described in hypothyroidism. Differentiation between the 2 conditions, recognition of their possible coexistence, and the consequent therapeutic implications are of utmost importance. We describe a case of an 82-year-old woman with a history of mild chronic liver disease who presented with hyperammonemic coma unresponsive to conventional therapy. Further investigation disclosed severe hypothyroidism. Thyroid hormone replacement resulted in gain of consciousness and normalization of hyperammonemia. In patients with an elevated ammonia level, altered mental status, and liver disease, who do not have a clear inciting event for liver disease decompensation, overwhelming evidence of hepatic decompensation, or who do not respond to appropriate therapy for hepatic encephalopathy, hypothyroidism should be considered and evaluated

MRS-guided HDR brachytherapy boost to the dominant intraprostatic lesion in high risk localised prostate cancer

BACKGROUND: It is known that the vast majority of prostate cancers are multifocal. However radical radiotherapy historically treats the whole gland rather than individual cancer foci.Magnetic resonance spectroscopy (MRS) can be used to non-invasively locate individual cancerous tumours in prostate. Thus an intentionally non-uniform dose distribution treating the dominant intraprostatic lesion to different dose levels than the remaining prostate can be delivered ensuring the maximum achievable tumour control probability.The aim of this study is to evaluate, using radiobiological means, the feasibility of a MRS-guided high dose rate (HDR) brachytherapy boost to the dominant lesion.\ud \ud METHODS: Computed tomography and MR/MRS were performed for treatment planning of a high risk localised prostate cancer. Both were done without endorectal coil, which distorts shape of prostate during the exams.Three treatment plans were compared:- external beam radiation therapy (EBRT) only- combination of EBRT and HDR brachytherapy- combination of EBRT and HDR brachytherapy with a synchronous integrated boost to the dominant lesionThe criteria of plan comparison were: the minimum, maximum and average doses to the targets and organs at risk; dose volume histograms; biologically effective doses for organs at risk and tumour control probability for the target volumes consisting of the dominant lesion as detected by MR/MRS and the remaining prostate volume.\ud \ud RESULTS: Inclusion of MRS information on the location of dominant lesion allows a safe increase of the dose to the dominant lesion while dose to the remaining target can be even substantially decreased keeping the same, high tumour control probability. At the same time an improved urethra sparing was achieved comparing to the treatment plan using a combination of EBRT and uniform HDR brachytherapy.\ud \ud CONCLUSIONS: MRS-guided HDR brachytherapy boost to dominant lesion has the potential to spare the normal tissue, especially urethra, while keeping the tumour control probability high

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Efficacy and tolerability of gemtuzumab ozogamicin (anti-CD33 monoclonal antibody, CMA-676, Mylotarg(®)) in children with relapsed/refractory myeloid leukemia

BACKGROUND: Gemtuzumab ozogamicin (GO) is a cytotoxic anti-CD33 monoclonal antibody that has given promising preliminary results in adult myeloid CD33+ AML. We conducted a retrospective multicenter study of 12 children treated with GO on a compassionate basis (median age 5.5 y). Three patients (2 MDS/AML, 1 JMML) were refractory to first-line treatment, 8 patients with de novo AML were in refractory first relapse, and one patient with de novo AML was in 2(nd )relapse after stem cell transplantation (SCT). CD33 expression exceeded 20% in all cases. METHODS: GO was administered alone, at a unit dose of 3–9 mg/m(2), once (3 patients), twice (3 patients), three (5 patients) or five times (1 patient). Mean follow-up was 128 days (8–585 d). RESULTS: There were three complete responses (25%) leading to further curative treatment (SCT). Treatment failed in the other nine patients, and only one patient was alive at the end of follow-up. NCI-CTC grade III/IV adverse events comprised hematological toxicity (n = 12), hypertransaminasemia (n = 2), allergy and hyperbilirubinemia (1 case each). There was only one major adverse event (grade IV allergy). No case of sinusoidal obstruction syndrome occurred. CONCLUSION: These results warrant a prospective trial of GO in a larger population of children with AML

Analysis of folylpoly-γ-glutamate synthetase gene expression in human B-precursor ALL and T-lineage ALL cells

BACKGROUND: Expression of folylpoly-γ-glutamate synthetase (FPGS) gene is two- to three-fold higher in B-precursor ALL (Bp- ALL) than in T-lineage ALL (T-ALL) and correlates with intracellular accumulation of methotrexate (MTX) polyglutamates and lymphoblast sensitivity to MTX. In this report, we investigated the molecular regulatory mechanisms directing FPGS gene expression in Bp-ALL and T-ALL cells. METHODS: To determine FPGS transcription rate in Bp-ALL and T-ALL we used nuclear run-on assays. 5'-RACE was used to uncover potential regulatory regions involved in the lineage differences. We developed a luciferase reporter gene assay to investigate FPGS promoter/enhancer activity. To further characterize the FPGS proximal promoter, we determined the role of the putative transcription binding sites NFY and E-box on FPGS expression using luciferase reporter gene assays with substitution mutants and EMSA. RESULTS: FPGS transcription initiation rate was 1.6-fold higher in NALM6 vs. CCRF-CEM cells indicating that differences in transcription rate led to the observed lineage differences in FPGS expression between Bp-ALL and T-ALL blasts. Two major transcripts encoding the mitochondrial/cytosolic and cytosolic isoforms were detected in Bp-ALL (NALM6 and REH) whereas in T-ALL (CCRF-CEM) cells only the mitochondrial/cytosolic transcript was detected. In all DNA fragments examined for promoter/enhancer activity, we measured significantly lower luciferase activity in NALM6 vs. CCRF-CEM cells, suggesting the need for additional yet unidentified regulatory elements in Bp-ALL. Finally, we determined that the putative transcription factor binding site NFY, but not E-box, plays a role in FPGS transcription in both Bp- and T-lineage. CONCLUSION: We demonstrated that the minimal FPGS promoter region previously described in CCRF-CEM is not sufficient to effectively drive FPGS transcription in NALM6 cells, suggesting that different regulatory elements are required for FPGS gene expression in Bp-cells. Our data indicate that the control of FPGS expression in human hematopoietic cells is complex and involves lineage-specific differences in regulatory elements, transcription initiation rates, and mRNA processing. Understanding the lineage-specific mechanisms of FPGS expression should lead to improved therapeutic strategies aimed at overcoming MTX resistance or inducing apoptosis in leukemic cells

Computed tomographic analysis of the quality of trunk muscles in asymptomatic and symptomatic lumbar discectomy patients

Background: No consensus exists on how rehabilitation programs for lumbar discectomy patients with persistent complaints after surgery should be composed. A better understanding of normal and abnormal postoperative trunk muscle condition might help direct the treatment goals. Methods: A three-dimensional CT scan of the lumbar spine was obtained in 18 symptomatic and 18 asymptomatic patients who had undergone a lumbar discectomy 42 months to 83 months (median 63 months) previously. The psoas muscle (PS), the paraspinal muscle mass (PA) and the multifidus muscle (MF) were outlined at the L3, L4 and L5 level. Of these muscles, fat free Cross Sectional Area (CSA) and fat CSA were determined. CSA of the lumbar erector spinae (LES = longissimus thoracis + iliocostalis lumborum) was calculated by subtracting MF CSA from PA CSA. Mean muscle CSA of the left and right sides was calculated at each level. To normalize the data for interpersonal comparison, the mean CSA was divided by the CSA of the L3 vertebral body (mCSA = normalized fat-free muscle CSA; fCSA = normalized fat CSA). Differences in CSA between the pain group and the pain free group were examined using a General Linear Model (GLM). Three levels were examined to investigate the possible role of the level of operation. Results: In lumbar discectomy patients with pain, the mCSA of the MF was significantly smaller than in pain-free subjects (p = 0.009) independently of the level. The mCSA of the LES was significantly smaller in pain patients, but only on the L3 slice (p = 0.018). No significant difference in mCSA of the PS was found between pain patients and pain-free patients (p = 0.462). The fCSA of the MF (p = 0.186) and of the LES (p = 0.256) were not significantly different between both populations. However, the fCSA of the PS was significantly larger in pain patients than in pain-free patients. (p = 0.012). The level of operation was never a significant factor. Conclusions: CT comparison of MF, LES and PS muscle condition between lumbar discectomy patients without pain and patients with protracted postoperative pain showed a smaller fat-free muscle CSA of the MF at all levels examined, a smaller fat-free muscle CSA of the LES at the L3 level, and more fat in the PS in patients with pain. The level of operation was not found to be of importance. The present results suggest a general lumbar muscle dysfunction in the pain group, in particular of the deep stabilizing muscle system