999 resultados para Annual ring
Resumo:
Background
Product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.
Methods
A silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger has been developed and tested in vitro and in cynomolgus macaques for its potential to continuously monitor environmental temperature and accurately determine episodes of ring insertion and removal.
Results
In vitro studies demonstrated that DST nano-T temperature loggers encapsulated in medical grade silicone elastomer were able to accurately and continuously measure environmental temperature. The devices responded quickly to temperature changes despite being embedded in different thickness of silicone elastomer. Prototype vaginal rings measured higher temperatures compared with a subcutaneously implanted device, showed high sensitivity to diurnal fluctuations in vaginal temperature, and accurately detected periods of ring removal when tested in macaques.
Conclusions
Vaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials.
Resumo:
In this Letter, an unambiguous synthetic strategy is reported for the preparation of enantiomerically purecis-5-halo-piperazic acid derivatives in single diastereoisomer form. Contrary to the recent report by Shin and co-workers (Chem. Lett. 2001, 1172), in which it is claimed that the Ph3P and N-chlorosuccinimide (NCS)-mediated chlorination of (3R,5S)-trans-N(1),N(2)-di-t-Boc-5-hydroxy-piperazic acid derivative 1proceeds with retention of configuration at C(5) to give 2, we now show that this and related Ph3P-mediated halogenations all occur with SN2 inversion at the alcohol center, as is customary for such reactions. Specifically, we demonstrate that the (3R,5S)-trans-5-Cl-piperazic acid derivative 2 claimed by Shin and co-workers (Chem. Lett. 2001, 1172) is in actual fact the chlorinated (3S,5R)-enantiomer 6, which must have been prepared from the cis-(3S,5S)-alcohol 3, a molecule whose synthesis is not formally described in the Shin paper. We further show here that the cis-(3R,5R)-5-Cl-Piz 13 claimed by Shin and co-workers inChem. Lett. 2001, 1172, is also (3S,5R)-trans-5-Cl-Piz 6. Authentic 13 has now been synthesized by us, for the very first time, here. Since Lindsley and Kennedy have recently utilized the now invalid Shin and co-workers’ retentive Ph3P/NCS chlorination procedure on 1 in their synthetic approach to piperazimycin A (Tetrahedron Lett. 2010, 51, 2493), it follows that their claimed 5-Cl-Piz-containing dipeptide 25 probably has the alternate structure 26, where the 5-Cl-Piz residue has a 3,5-cis-configuration. The aforementioned stereochemical misassignments appear to have come from a mix-up of starting materials by Shin and co-workers (Chem. Lett. 2001, 1172), and an under-appreciation of the various steric and conformational effects that operate in N(2)-acylated piperazic acid systems, most especially rotameric A1,3-strain. The latter has now been unambiguously delineated and defined here under the banner of the A1,3-rotamer effect.
Resumo:
The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified.
Resumo:
The paper reports of a flat spiral phase plate structure based on reflectarray frequency selective surface, FSS, technology for the generation of helical far-field radiation patterns with circular polarization (CP) properties. Double split ring slot FSS is used as a means for adjusting the phase across the reflectarray. Simulations presented demonstrate generation of reflected helical beams at 10 GHz for CP wave incident on the structure. The far-field measurements are in a good agreement with the simulations and demonstrate a null of -11dB in the centre of the radiation pattern attributed to the helical wavefront.
Resumo:
This paper reviews decisions from the Northern Ireland and England and Wales High Courts and Courts of Appeal as well as the UK Supreme Court relating to tort and principally to the tort of negligence in the past 12 months or so.
In structure, the paper will be presented in four parts. First, three preliminary points relating to contemporary features of the NI civil courts: personal litigants – Devine v McAteer [2012] NICA 30 (7 September 2012); pre-action protocols – Monaghan v Graham [2013] NIQB 53 (3 May 2013); and the rise of alternative dispute resolution. On the last named issue, the recent decision of PGF II SA v OMFS Company 1 Ltd [2013] EWCA Civ 1288 (23 October 2013) on unreasonable refusal to mediate, will be discussed.
Second, the paper moves to consider the law of negligence generally and case law from the NI High Court reiterating Lord Hoffmann’s view in Tomlinson v Congleton Borough Council [2004] 1 AC 46 that no duty of care arises from obvious risks of injury. In this, reference will be made to the application of the above “Hoffmann principle” in West Sussex County Council v Pierce [2013] EWCA Civ 1230 (16 October 2013), which concerned an accident sustained by a child at school. A similar set of facts was presented recently to the UK Supreme Court in Woodland v Essex County Council [2013] UKSC 66 (23 October 2013). The decision there, on non-delegable duties of care, will have a significant impact for schools in the provision of extracurricular activities.
Third, I will review a NI case of note on the duty of care of solicitors in the context of professional negligence in the context of conflicting advice by counsel.
Fourth, I will examine a series of cases on employer liability and including issues such as the duty of care towards the volunteer worker; tort and safety at work principles generally; and, more specifically, the duty of care of the employer towards an employee who suffers psychiatric illness as a result of stress and/or harassment at work. On the issue of workplace stress, the NI courts have made extensive reference to the Hale LJ principles found in the Court of Appeal decision of Hatton v Sutherland [2002] 1 All ER 1 and applied to those who have suffered trauma in reporting on or policing “the troubles” in Northern Ireland. On the issue of statutory harassment at work, the paper will also mention the UK Supreme Court’s decision in Hayes v Willoughby [2013] UKSC 17 (20 March 2013).
2003- First WEKNOW Annual Conference on Drinking Water in Europe, Kuopio, Finland, 12th-14th October
Resumo:
Administration of biomacromolecular drugs in effective quantities from conventional vaginal rings is hampered by poor drug permeability in the polymers from which rings are commonly constructed. Here, we report the formulation development and testing of rod insert rings for sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP (JNJ peptide), both of which have potential as HIV microbicides. Rod inserts were prepared comprising antiviral peptides T-1249 or JNJ peptide in combination with a hydrophilic excipient (sodium chloride, sodium glutamate, lactose or zinc acetate) dispersed at different loadings within a medical grade silicone elastomer. The inserts were tested for weight change and swelling when immersed in simulated vaginal fluid (SVF). Dye migration into the inserts was also assessed visually over 28 days. In vitro release of T-1249 and JNJ peptide from rings containing various insert types was tested. Weight change and degree of swelling of rods immersed in SVF was dependent on the type and concentration of excipient present. The rods displayed the following rank order in terms of weight change: sodium glutamate > zinc acetate ≈ sodium chloride > lactose. The weight change and degree of swelling of the inserts did not correlate with the level of dye uptake observed. In vitro release of T-1249 was improved through addition of lactose, sodium chloride and sodium glutamate, while release of JNJ peptide was improved through addition of sodium chloride or sodium glutamate. Sustained release of hydrophobic peptides can be achieved using a rod insert ring design formulated to include a hydrophilic excipient. Release rates were dependent upon the type of excipient used. The degree of release improvement with different inserts partially reflects their ability to imbibe surrounding fluid and swell in aqueous environments.