Clean nitrations: Novel syntheses of nitramines and nitrate esters by nitrodesilylation reactions using dinitrogen pentoxide (N2O5)

In this novel nitration method dinitrogen pentoxide (N2O5) in an inert solvent is used as the nitrating agent, thereby removing the need for strong acids as the reaction medium. The N2O5 cleaves heteroatom-silicon bonds, in silylamines and silyl ethers respectively, to yield the desired energetic groupings (nitramines or nitrate esters respectively) without liberation of acids which would occur with conventional substrates (amines or alcohols). These nitrodesilylation reactions proceed cleanly and in good yield, and the scope of the reaction is illustrated by. 29 examples, some of which produce high energy compounds, notably plasticisers and an energetic polymer precursor. These reactions are therefore potentially clean nitrations for the manufacture of energetic compounds which will minimise the impact of this activity on the environment in the future

An environmentally-friendly route to nitramines and nitrate esters via nitrodesilylation chemistry using dinitrogen pentoxide

Nitramines and nitrate esters are synthesised conventionally using strongly acidic nitration media such as sulphuric-nitric acid mixtures, and the resulting spent liquors from these nitrations are difficult to dispose of without damage to the environment. The novel method described here dispenses with the need for strong acids as the reaction medium and instead uses dinitrogen pentoxide (N20 5) in an inert solvent as the nitrating agent. The N20 5 cleaves heteroatom-silicon bonds, in silylamines and silyl ethers respectively, to yield the desired energetic groupings (nitramines or nitrate esters respectively) without liberation of acids which would occur with conventional substrates (amines or alcohols). These nitrodesilylation reactions proceed cleanly and in good yield, and furthermore them co-product, a silyl nitrate, can be used to effect further nitrations, hence eliminating the need for disposal. The scope of the reaction will be illustrated by 25 examples, some of which produce high energy compounds, notably plasticisers and an energetic polymer precursor, whilst in others novel energetic functions such as N-nitroaziridines can be accessed directly for the first time. When taken in conjunction with the current advances in N20 5 chemistry in other fields, which have made this reagent available on large scale at reasonable cost, the use of clean routes to energetic materials such as those described here constitutes a powerful reason for changing the methods of manufacture of energetic materials in the next centur

Studies of Novel Nitro Substituted Nitrogen Heterocyclic Compounds

Extensive nitration studies have been carried out towards the preparation of a series of high energy insensitive explosives. Systems investigated include quinoxalines, quinazolines and pyrazines. A novel candidate explosive, 2,5-diamino-3,6-dinitropyrazine (ANPZ-i) has been produced via a novel nitration of the precursor dialkoxypyrazine compound. Oxidation of ANPZ-i towards the di-N-oxide derivative was studied but no degree of oxidation could be achieved. A range of benzodiazines (quinazolines and quinoxalines) were nitrated giving a series of novel nitro-substituted compounds. 2,4-Diamino-6,8-dinitroquinazoline was both oxidised and aminated successfully, but it was found in general that a high level of functionalisation of the heterocyclic rings was difficult to attain. In summary a novel candidate explosive has been prepared, along with a series of novel nitro-explosive precursor compounds. It is hoped that this work can feed into future research into high energy insensitive fillers

Preparation of 2, 5-Diamino-3, 6-Dinitropyrazine (ANPZ-i): A Novel Candidate High Energy Insensitive Explosive

2,5‐Diamino‐3,6‐dinitropyrazine (ANPZ‐i) has been prepared via the electrophilic nitration of 2,5‐diethoxypyrazine using nitronium tetrafluoroborate in sulpholane and subsequent amination under autoclave conditions. Molecular modelling studies have been carried out which indicate that ANPZ‐i should have a similar performance to RDX but with an expected higher insensitivity. ANPZ‐i (1) is therefore a novel candidate high energy insensitive explosive

Is heavy eccentric calf training superior to wait-and-see, sham rehabilitation, traditional physiotherapy and other exercise interventions for pain and function in mid-portion Achilles tendinopathy?

Background: Mid-portion Achilles tendinopathy (AT) is prevalent amongst athletic and non-athletic populations with pain, stiffness and impaired function typically reported. While different management options exist, loading protocols remain the best available intervention and have been shown to be effective in the management of AT. Trials investigating loading in AT have used a variety of different protocols, and recent narrative reviews suggest that no protocol is superior to another when comparing outcomes in pain and function. However, there has been no systematic review or meta-analysis completed to determine this. Furthermore, the narrative review did not consider wait-and-see or sham interventions, thus a systematic review and met-analysis which includes wait-and see or sham interventions is warranted. Methods: A systematic review and meta-analyses will be conducted as per the PRISMA guidelines. The databases PUBMED, CINAHL (Ovid) and CINAHL (EBSCO) will be searched for articles published from inception to 31 December 2017. Our search focuses on studies examining the improvement of pain and function when completing a loading program for mid-portion AT. Only randomised/ quasi-randomised trials will be included while case reports and case series will be excluded. The primary outcome assessing pain and function will be the Victorian Institute Sports Assessment - Achilles (VISA-A). Two reviewers will screen articles, extract data and assess the risk of bias independently with a third reviewer resolving any disagreements between the two reviewers. A meta-analysis will then be performed on the data (if appropriate) to determine if the traditional heavy load calf training protocol described by Alfredson is superior to wait-and-see, sham intervention, traditional physiotherapy, and other forms of exercise rehabilitation. Discussion: This systematic review and meta-analysis will allow us to investigate if there are difference in pain and function when comparing wait-and-see, sham interventions, traditional physiotherapy and different exercise interventions to the traditional heavy eccentric calf training protocol for mid-portion Achilles tendon pain. Systematic review registration: PROSPERO registration number CRD42018084493

Evaluation of the utilization of the preanaesthetic clinics in a University teaching hospital

BACKGROUND: Dedicated out-patient preanaesthetic clinics are relatively recent phenomenon and information is sparse from developing world. This study attempted to evaluate the utilization of adult and paediatric preanaesthetic clinics and its impact on the cancellations of surgery in Trinidad. METHODS: All patients scheduled to have elective surgery during the period of twelve weeks were enrolled for prospective collection of data including demographics, the admitting diagnoses, surgical procedure, category of surgery and specialty, and the patients' attendance to preanaesthetic clinics. Cancellations on the day of surgery along with reasons were recorded. The difference between patients who attended and did not attend the clinic was analysed. RESULTS: Of 424 patients scheduled for procedures during the study period, 213 were adults and 211 were children. Overall 39% of adults and 46% of the children scheduled for surgery had previously attended the preanaesthetic clinic. Among adults, general surgery patients were the largest majority to attend the preanaesthetic clinic. The paediatric preanaesthetic clinic was mostly utilized by paediatric general surgery. Overall 30% of procedures in adults and 26% of those in children were cancelled. There was a statistically significant difference in cancellations between patients who attended and did not attend the preanaesthetic clinic (p = 0.004). There was a 52% more chance of the procedure getting cancelled if the patient did not attend the clinic. CONCLUSION: The study highlights the inadequate use of the preanaesthetic clinics and the impact of the clinics on last-minute cancellations

Theories of Reference: What Was the Question?

The new theory of reference has won popularity. However, a number of noted philosophers have also attempted to reply to the critical arguments of Kripke and others, and aimed to vindicate the description theory of reference. Such responses are often based on ingenious novel kinds of descriptions, such as rigidified descriptions, causal descriptions, and metalinguistic descriptions. This prolonged debate raises the doubt whether different parties really have any shared understanding of what the central question of the philosophical theory of reference is: what is the main question to which descriptivism and the causal-historical theory have presented competing answers. One aim of the paper is to clarify this issue. The most influential objections to the new theory of reference are critically reviewed. Special attention is also paid to certain important later advances in the new theory of reference, due to Devitt and others

Oral Health Status of Patients with Mental Disorders in Southwest Ethiopia

BACKGROUND: Psychiatric disorders are known to be a risk factor for the development of different oral health problems especially for dental caries and periodontal diseases. In spite of this fact, no study has been conducted to reveal its magnitude in Ethiopia. Hence, this study was conducted to determine the oral health status of psychiatric patients at Jimma University Specialized Hospital (JUSH), Psychiatric Clinic. METHODS: A hospital based cross- sectional study was used from January to May 2011. A total of 240 participants were included in the study. Dental examination was done to measure indices of oral health: decayed, missing, and filled teeth (DMFT) index and community periodontal index (CPI). Oral examination was performed using mirror, probe and explorer by experienced dental doctors. A simple random sampling technique was implemented to collect data. ANOVA test, binary logistic and multinomial logistic regression analyses were done using SPSS 16.0 statistical software. RESULTS: The mean DMFT score among the psychiatric patients was 1.94 ± 2.12 (mean ± SD) with 1.28 ± 1.69, 0.51 ± 1.19 and 0.14 ± 0.48 (mean ± SD) for decayed, missed and filled teeth respectively. Only about 24% of the psychiatric patients had a healthy CPI score. Incorrect tooth brushing technique was significantly associated with a DMFT score greater than 2 (AOR = 3.58; 95% CI: 1.65, 7.79). The habit of sweet intake was also associated with dental caries (AOR = 2.91; 95% CI: 1.43, 5.95). Similarly, patients with a smoking habit also demonstrated statistically significant association with dental caries (AOR = 18.98; 95% CI: 5.06, 71.24). CONCLUSION: The oral health status of the psychiatric patients was poor. Thus, health education about oral hygiene should be given for psychiatric patients so they can avoid the frequent intake of sweets, smoking and learn correct tooth brushing technique

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

The Human Gonadotropin Releasing Hormone Type I Receptor Is a Functional Intracellular GPCR Expressed on the Nuclear Membrane

The mammalian type I gonadotropin releasing hormone receptor (GnRH-R) is a structurally unique G protein-coupled receptor (GPCR) that lacks cytoplasmic tail sequences and displays inefficient plasma membrane expression (PME). Compared to its murine counterparts, the primate type I receptor is inefficiently folded and retained in the endoplasmic reticulum (ER) leading to a further reduction in PME. The decrease in PME and concomitant increase in intracellular localization of the mammalian GnRH-RI led us to characterize the spatial distribution of the human and mouse GnRH receptors in two human cell lines, HEK 293 and HTR-8/SVneo. In both human cell lines we found the receptors were expressed in the cytoplasm and were associated with the ER and nuclear membrane. A molecular analysis of the receptor protein sequence led us to identify a putative monopartite nuclear localization sequence (NLS) in the first intracellular loop of GnRH-RI. Surprisingly, however, neither the deletion of the NLS nor the addition of the Xenopus GnRH-R cytoplasmic tail sequences to the human receptor altered its spatial distribution. Finally, we demonstrate that GnRH treatment of nuclei isolated from HEK 293 cells expressing exogenous GnRH-RI triggers a significant increase in the acetylation and phosphorylation of histone H3, thereby revealing that the nuclear-localized receptor is functional. Based on our findings, we conclude that the mammalian GnRH-RI is an intracellular GPCR that is expressed on the nuclear membrane. This major and novel discovery causes us to reassess the signaling potential of this physiologically and clinically important receptor