Traumatic Retrobulbar Haemorrhage: Aetio-pathology and management

Retrobulbar haematoma following blunt orbital trauma is a rare,but potentially serious complication, since it can evolve rapidly from visual impairment to permanent loss of vision. This sight-threatening situation most commonly arises from orbital bleeding accompanying undisplaced fractures of the orbital walls, an event that increases the pressure inside theorbit and results in vascular damage to the optic nerve. The clinical presentation includes pain, exophthalmos with proptosis, and internal ophthalmoplegia, with impairment or loss of the pupillary reXex. A thin-layer orbital CT scan is an essential diagnostic aid. Therapy is based on orbitaldecompression, via different surgical approaches, with the intention of reducing the pressure on the nerve and vascular structures inside the orbit. Emergent management is of utmost importance as any delay between the onset of symptoms and treatment can have a significant effect onrecovery

Towards Understanding and Harnessing the Potential of Clause Learning

Efficient implementations of DPLL with the addition of clause learning are the fastest complete Boolean satisfiability solvers and can handle many significant real-world problems, such as verification, planning and design. Despite its importance, little is known of the ultimate strengths and limitations of the technique. This paper presents the first precise characterization of clause learning as a proof system (CL), and begins the task of understanding its power by relating it to the well-studied resolution proof system. In particular, we show that with a new learning scheme, CL can provide exponentially shorter proofs than many proper refinements of general resolution (RES) satisfying a natural property. These include regular and Davis-Putnam resolution, which are already known to be much stronger than ordinary DPLL. We also show that a slight variant of CL with unlimited restarts is as powerful as RES itself. Translating these analytical results to practice, however, presents a challenge because of the nondeterministic nature of clause learning algorithms. We propose a novel way of exploiting the underlying problem structure, in the form of a high level problem description such as a graph or PDDL specification, to guide clause learning algorithms toward faster solutions. We show that this leads to exponential speed-ups on grid and randomized pebbling problems, as well as substantial improvements on certain ordering formulas

Interactions Between Spermine-Derivatized Tentacle Porphyrins And The Human Telomeric DNA G-Quadruplex

G-rich DNA sequences have the potential to fold into non-canonical G-Quadruplex (GQ) structures implicated in aging and human diseases, notably cancers. Because stabilization of GQs at telomeres and oncogene promoters may prevent cancer, there is an interest in developing small molecules that selectively target GQs. Herein, we investigate the interactions of meso-tetrakis-(4-carboxysperminephenyl)porphyrin (TCPPSpm4) and its Zn(II) derivative (ZnTCPPSpm4) with human telomeric DNA (Tel22) via UV-Vis, circular dichroism (CD), and fluorescence spectroscopies, resonance light scattering (RLS), and fluorescence resonance energy transfer (FRET) assays. UV-Vis titrations reveal binding constants of 4.7 × 10⁶ and 1.4 × 10⁷ M⁻¹ and binding stoichiometry of 2–4:1 and 10–12:1 for TCPPSpm4 and ZnTCPPSpm4, respectively. High stoichiometry is supported by the Job plot data, CD titrations, and RLS data. FRET melting indicates that TCPPSpm4 stabilizes Tel22 by 36 ± 2 °C at 7.5 eq., and that ZnTCPPSpm4 stabilizes Tel22 by 33 ± 2 °C at ~20 eq.; at least 8 eq. of ZnTCPPSpm4 are required to achieve significant stabilization of Tel22, in agreement with its high binding stoichiometry. FRET competition studies show that both porphyrins are mildly selective for human telomeric GQ vs duplex DNA. Spectroscopic studies, combined, point to end-stacking and porphyrin self-association as major binding modes. This work advances our understanding of ligand interactions with GQ DNA

Chylous Leak During Posterior Approach to Juvenile Scoliosis Surgery: A Case Report.

CaseWe report the first documented case of chylous leak recognized intraoperatively during posterior spinal instrumentation and fusion for juvenile scoliosis in a female patient with a history of thoracotomy and decortication for an empyema.ConclusionsThoracic duct injury can lead to severe morbidity and mortality because of chylothorax formation. Although chylous leaks are a well-documented complication of the anterior approach to spine surgery, leaks during the posterior approach are rarely reported. When these chylous leaks are recognized intraoperatively, the likelihood of serious complications may be minimized by drain placement before closure

Strategies to enhance the efficacy of chemotherapy

Chemotherapy, alongside radiotherapy and surgery remains the mainstay of treatment for many cancers. However as our understanding of the biology of malignancy improves targeted therapies are being developed, which need to be integrated with existing standard chemotherapeutics. This thesis discusses three studies that aim to address this challenge. In the first part of this thesis, the activity of lomeguatrib, a novel agent that acts as a pseudosubstrate for the DNA-repair protein MGMT, was investigated in a range of solid tumours. Following a single administration, it was found to deplete MGMT in primary CNS, colorectal and prostate cancers. The lomeguatrib dose required to achieve this was independent of pre-treatment MGMT expression in these tumour types. MGMT expression appears to correlate with sensitivity to irinotecan, a standard treatment for metastatic colorectal cancer. Combination treatment with lomeguatrib and irinotecan was investigated in patients with metastatic colorectal cancer. Treatment with this couplet was tolerable, no pharmacokinetic drug interactions were seen and complete MGMT depletion was observed. In this heavily pre-treated group of patients, there was no increase in efficacy with treatment with the couplet over irinotecan alone. The latter part of the thesis describes an ongoing early phase trial investigating combination treatment with decitabine, a hypomethylating agent and standard ECF chemotherapy in patients with advanced oesophagogastric cancer. The maximum tolerated dose of decitabine in this combination was established, the main toxicity myelosuppression was manageable. Preliminary tumour DNA pyrosequencing results confirmed changes in methylation of the MAGE 1A gene in tumour tissue associated with immunohistochemical changes in protein product expression of a number of genes following decitabine treatment. These studies have described early phase work for two very different targeted treatment approaches that may be used alongside standard chemotherapy. Clinical studies to explore both of these further are planned

N-Methylmesoporphyrin IX Fluorescence As A Reporter Of Strand Orientation In Guanine Quadruplexes

Guanine quadruplexes (GQ) are four-stranded DNA structures formed by guanine-rich DNA sequences. The formation of GQs inhibits cancer cell growth, although the detection of GQs invivo has proven difficult, in part because of their structural diversity. The development of GQ-selective fluorescent reporters would enhance our ability to quantify the number and location of GQs, ultimately advancing biological studies of quadruplex relevance and function. N-methylmesoporphyrin IX (NMM) interacts selectively with parallel-stranded GQs; in addition, its fluorescence is sensitive to the presence of DNA, making this ligand a possible candidate for a quadruplex probe. In the present study, we investigated the effect of DNA secondary structure on NMM fluorescence. We found that NMM fluorescence increases by about 60-fold in the presence of parallel-stranded GQs and by about 40-fold in the presence of hybrid GQs. Antiparallel GQs lead to lower than 10-fold increases in NMM fluorescence. Single-stranded DNA, duplex, or i-motif, induce no change in NMM fluorescence. We conclude that NMM shows promise as a turn-on\u27 fluorescent probe for detecting quadruplex structures, as well as for differentiating them on the basis of strand orientation

Interference management with mismatched partial channel state information

We study the fundamental limits of communications over multi-layer wireless networks where each node has only limited knowledge of the channel state information. In particular, we consider the scenario in which each source-destination pair has only enough information to perform optimally when other pairs do not interfere. Beyond that, the only other information available at each node is the global network connectivity. We propose a transmission strategy that solely relies on the available limited knowledge and combines coding with interference avoidance. We show that our proposed strategy goes well beyond the performance of interference avoidance techniques. We present an algebraic framework for the proposed transmission strategy based on which we provide a guarantee of the achievable rate. For several network topologies, we prove the optimality of our proposed strategy by providing information-theoretic outer-bounds

Wireless Network Coding with Local Network Views: Coded Layer Scheduling

One of the fundamental challenges in the design of distributed wireless networks is the large dynamic range of network state. Since continuous tracking of global network state at all nodes is practically impossible, nodes can only acquire limited local views of the whole network to design their transmission strategies. In this paper, we study multi-layer wireless networks and assume that each node has only a limited knowledge, namely 1-local view, where each S-D pair has enough information to perform optimally when other pairs do not interfere, along with connectivity information for rest of the network. We investigate the information-theoretic limits of communication with such limited knowledge at the nodes. We develop a novel transmission strategy, namely Coded Layer Scheduling, that solely relies on 1-local view at the nodes and incorporates three different techniques: (1) per layer interference avoidance, (2) repetition coding to allow overhearing of the interference, and (3) network coding to allow interference neutralization. We show that our proposed scheme can provide a significant throughput gain compared with the conventional interference avoidance strategies. Furthermore, we show that our strategy maximizes the achievable normalized sum-rate for some classes of networks, hence, characterizing the normalized sum-capacity of those networks with 1-local view.Comment: Technical report. A paper based on the results of this report will appea

Outbreak of acute hepatitis C following the use of anti-hepatitis C virus--screened intravenous immunoglobulin therapy

BACKGROUND and AIMS: Hepatitis C virus (HCV) infection has been associated with intravenous (IV) immunoglobulin (Ig), and plasma donations used to prepare IV Ig are now screened to prevent transmission. Thirty-six patients from the United Kingdom received infusions from a batch of anti-HCV antibody-screened intravenous Ig (Gammagard; Baxter Healthcare Ltd., Thetford, Norfolk, England) that was associated with reports of acute hepatitis C outbreak in Europe. The aim of this study was to document the epidemiology of this outbreak. METHODS: Forty-six patients from the United Kingdom treated with Gammagard (34 exposed and 12 unexposed to the batch) returned epidemiological questionnaires. RESULTS: Eighty-two percent of the exposed patients (28 of 34) became positive for HCV RNA. Eighteen percent of the patients (6 of 34) who had infusions with this batch tested negative for HCV RNA, but 2 of the patients had abnormal liver function and subsequently seroconverted to anti-HCV antibody positive. Twenty-seven percent of the patients (9 of 34) developed jaundice, and 79% (27 of 34) had abnormal liver transferase levels. Virus isolates (n=21), including an isolate from the implicated batch, were genotype 1a and virtually identical by sequence analysis of the NS5 region, consistent with transmission from a single source. CONCLUSIONS: Hepatitis C infection can be transmitted by anti-HCV-screened IV Ig. Careful documentation of IV Ig batch numbers and regular biochemical monitoring is recommended for all IV Ig recipients

SYNTHESIS, CHARACTERIZATION AND ELECTROCHEMICAL INVESTIGATION OF NOVEL 17-MEMBERED DIOXADIAZA NAPTHALDEHYDE BASED MACROCYCLIC LIGAND AND ITS COMPLEXES OF Co (III), Ni (II) AND Cu (II) PERCHLORATE IONS

Objective: The objective of this research is to synthesis hitherto, novel unreported [17]-membered dioxadiaza napthaldehyde based macrocyclic ligand (L) and to synthesize its Co(III), Ni(II) and Cu(II) metal ion complexes.Methods: The synthesis of the ligand has been accomplished by two different synthetic routes each involving two stages. 2-Hydroxy-1-Napthaldehyde in the presence of potassium carbonate was treated with α,α'-dibromo-m-xylene to yield the dial derivative (I). The dial derivative (I) was further made to undergo Schiff base condensation with 1,2-diaminobenzene to yield the bright yellow macrocycle (L) in good yield. In the second method the Schiff base condensed product Napthaloph was synthesized and allowed to undergo Williamson's condensation with α,α'-dibromo-m-xylene to yield the ligand (L).Results: The ligand and its complexes were characterized by elemental analysis, electronic spectroscopy, IR, Conductivity measurements, EPR, magnetic susceptibility, 1H NMR and MS. The neutral seventeen membered tetradentate dioxadiaza ligand (L) readily complexes with Co(III), Ni(II) and Cu(II) perchlorate salts in 1:1 mole ratio to yield complexes of formulae [Co(L)X2]ClO4, [Ni(L)X2], [Cu(L)X]ClO4, (X = Cl-, Br-and NO3-). The complexes were also synthesized by the metal template method. The yield of the template procedure was found to be greater than the non-template method.Conclusion: A hitherto 2, 10-dioxa-21,29-diaza-heptacyclo-[29.4.2.1[4,8].0[1,32].0[11,20].0[14,19].0[23,28].0[32,37]]-tetraconta-4, 6, 8, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39-octatecaene. The [17]-membered tetradentate dioxadiaza macrocycle (L) was found to accommodate Co3+, Ni2+, and Cu2+ions with ease due to the presence of flexible alkyl groups. Further studies with the inner-transition metal ions will be highly informative in understanding the coordinating capabilities of lanthanides and actinides.Â