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Figure 6 Effect of estrogen on IGF-I, IGF-II and IGF-IR expression in HCS-2 8 cells. HCS-2 8 cells were cultured for 48 h in 1% CTS in the presence of vehicle 01% ethanol, lane 2 ; , E2 10 nM, lane 3 ; , letrozole 10 M, lane 4 ; or ICI 182, 780 10 M, lane 5 ; . Human testis was used as a positive control lane 1 ; . Expression of IGF-I A ; , IGF-II B ; and -actin C ; was analyzed by RT-PCR and expression of IGF-IR D ; was analyzed by Western immunoblot as described in the Material and Methods. Not stated METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE Weighting According to a Rating Scheme Scheme Given ; RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE Levels of Evidence Ia: Evidence from meta-analysis of randomised controlled trials Ib: Evidence from at least one randomised controlled trial IIa: Evidence from at least one controlled study without randomisation IIb: Evidence from at least one other type of quasi-experimental study III: Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies, and case-control studies IV: Evidence from expert committee reports or opinions and or clinical experience of respected authorities METHODS USED TO ANALYZE THE EVIDENCE Meta-Analysis Review of Published Meta-Analyses Systematic Review with Evidence Tables DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE Sifting and Reviewing the Evidence Studies retrieved were assessed for their quality and relevance in answering the key clinical questions identified by the guideline development group. For studies where the Guideline Development Group's GDG ; concern was that of what intervention seemed to be most effective, then in the assessment of those studies the key concern was the quality of the study in terms of the various aspects of study validity. Firstly, if a study credibly demonstrated the causal relationship between treatment and outcome then it was said to have internal validity. Secondly, if the findings could be generalised from the specific study sample to a wider population then it was said to be generalisable or to have external validity. Thirdly, if the study actually measured what it says it measures then it was said to have construct validity. Outcomes Used 6 of 37, for example, letrozole iui.

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Letrozole 2.5 mg n 1655 ; Placebo n 2594 ; Placebo n 613 ; Patient Choice.
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Conclusion: our data are in agreement with other non-european studies, designed to establish normal values in children and using polysomnography in a hospital setting, therefore, the findings and the proposed normative data in these studies can be interpreted also in a european setting. Results * At first interim analysis median follow-up 2.4 years ; there was a significant improvement in the estimated 4 year DFS in favour of the letrozole group compared with placebo HR, 0.57; 95% CI 0.43-0.75; p 0.00008 ; .This corresponds to an absolute benefit of 6.0% in the terms of DFS at 4 years 92.8% vs. 86.8%, NNT 17 and lopid.
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Routine universal precautions should be implemented postoperatively refer to UHB Infection Control Policy ; . Dressing changes post-surgery including brain biopsy ; should be carried out using universal precautions including the use of disposable gloves and aprons and disposable equipment materials. All clinical waste should be disposed of in Griff bins for incineration as per disposal of CJD Infected Waste Policy. Spillage contamination of CSF, tissue and blood should be cleared up as detailed in g ; below. Table 15: age-specific annual incidence of first stroke per 1000 population ; in three english populations, with 95% confidence intervals and lopressor. I went to this web site to find out the long term effects of this drug.
24 the rr of hip fracture among patients receiving letrozole vs no extended adjuvant therapy was estimated to be 15, based on the ratio of the incidence of bone fracture among patients receiving letrozole vs placebo in the updated analysis of the ma trial and lotrimin. Females MNH 347; KDH 158 ; were affected among the severely malnourished patients. Most of the severely malnourished children were in 1-2 years old age group. Children aged 4 years old were less affected by severe malnutrition Table 1 ; . Malaria was the leading co-morbidity with total prevalence of 21% at MNH among the admitted severely malnourished children. This was followed by HIV AIDS, lower respiratory tract infection and pulmonary tuberculosis. At KDH, co-morbidity with diarrhoea was more prevalent 45% ; than other infections. This was followed by malaria and candidiasis Table 2.

The enclosed GAU Benefit Grid is effective September 1, 2006 - December 31, 2007. General Assistance Unemployable is a state-funded program for individuals with short-term disabilities that prevent them from working for at least 90 days. There must be a verifiable physical and or mental impairment that prevents the adult from being gainfully employed. Effective for DOS 9 1 06, Facility Claims billed on a UB-92 ; will be paid by Health and Recovery Services Administration as follows and metrogel.

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Dermatological products, oral cosmetic liquids, contact lens solutions and tablets. In May 1992, the Food and Drug Administration 14 ; listed 11 technologies capable of satisfying the definition of tamper-evident packaging, while a twelfth was added for sealed cartons. The list includes film wrappers, blister packs, bubble packs, heat-shrunk bands or wrappers, paper foil or plastic packs, bottles with inner mouth seals, tape seals, breakable cap-ring systems, sealed tubes or plastic blindend heat-sealed tubes, sealed cartons, aerosol containers and all metal and composite cans. Child-resistant closures. Tragic accidents involving the drug intoxication of children has led to new legislation making it difficult for drug packaging to be opened by young children, while allowing adults easy access. Such packaging is designated as child-resistant. Certain protocols for child-resistant packaging were established in the USA in 1966. In 1970, the Poison-Prevention Packaging Act was passed and placed under the jurisdiction of the Food and Drug Administration. This Act was transferred in 1973 to the Consumer Product Safety Commission, which is responsible for drugs and household substances 15 ; . The use of child-resistant packaging has proved effective in reducing child mortality from intoxication by oral prescription drugs, and it is now recognized worldwide that children must be protected against such intoxication. The ISO has published an internationally agreed standard test procedure for reclosable child-resistant packaging 16 ; . In Europe several norms have been introduced, which complement the ISO standard 17, 18 ; . The European Committee for Standardization CEN ; has defined a child-resistant package as one "which makes it difficult for young children to gain access to the contents, but which is not too difficult for adults to use properly in accordance with the requirement of this European standard" 19 ; . The three most common reclosable child-resistant types of closure are the "pressturn", the "squeezeturn" and a combination lock. To determine whether a packaging is child-resistant, it must be subjected to the ISO test procedure for reclosable child-resistant packaging 14 ; . Most designs that are child-resistant require two hands to open the closure. Such packaging can cause problems for elderly people, and can even lead to the deliberate purchase of drugs with packaging that and mobic.
Partner, The Fish & Neave IP Group of Ropes & Gray LLP New York ; Partner, The Fish & Neave IP Group of Ropes & Gray LLP New York ; Assistant Counsel, Merck & Co., Inc. Rahway, NJ ; The effective term of a patent covering a marketed product can be less than the full 20 years if the product is not brought to market by the patent's issue date. This situation is of special interest for pharmaceutical products where the regulatory review required for market approval can take many months or even years. In light of Hatch-Waxman reforms, choosing a mode of patent extension tailored to fit your particular situation takes on newfound urgency. This hands-on session will provide you with practical advice, as well as tips and techniques for how to extend your patent. The session leaders will take you through the intricacies of the four major ways of getting an extension on your patent, and provide you with the tools that you need to accomplish this goal in this time of changing rules and regulations. Points of discussion include: 1. Extension of patent term under 35 U.S.C. 156 and 37 CFR 1.710 1.791 Important benchmarks in the drug's development and patent timelines Eligibility for patent term extension Regulatory review period determinations How to calculate the patent term restored - respective roles of the FDA and PTO in granting patent extensions - third-party challenges -- "diligence" Definitions for "drug product" and "regulatory review period" 2. The preparation and submission of a patent term restoration application 3. Patent term extensions outside the U.S. 4. Patent term adjustment due to delays in prosecution before the USPTO and strategies for: Diligence in prosecution by the patent applicant Calculating the adjustment period 5. Extensions obtained through FDA Pediatric Exclusivity and Orphan Drug Exclusivity: Criteria for eligibility Opportunities and pitfalls Latest regulatory and legal developments 6. Obtaining patent coverage for pharmaceuticals through the use of second-generation patents, e.g., Maintaining patent position for second-generation products Approaches taken by pharmaceutical companies in obtaining second-generation patents Enforcement of second-generation patents, for example, letrozole liver. In this regard, it has been found that the major by-product produced in accordance with the synthesis method of the invention is 4 benzonitrile hereinafter isoletrozole ; , which has the structural formula iv ; : letrozole and isoletrozole are structurally similar, have similar physical properties, e, g and moduretic. Was statistically significantly higher with letrozole 36.7% versus 10%, odds ratio 4.82, 95% confidence interval 1.04 to 29.88 ; . Given that letrozole may have benefit in women with CC-resistant PCOS, it is appropriate to determine whether aromatase inhibitors are equivalent to CC as first-line treatment for ovulation induction in women with PCOS. However, such a study of equivalence would require a sample size so large that it would be financially challenging to organise. Consequently, smaller studies comparing aromatase inhibitors with CC are likely to be carried out. To date, the results of two randomised trials comparing CC 100 mg per day ; and letrozole 2.5 mg per day ; as first-line treatment for five days from day 3 onwards have been published 14, 15 ; . In the first trial involving106 women with PCOS, the mean endometrial thickness and ovulation rate were significantly higher, and the numbers of follicles 17 mm on the day of hCG administration were significantly lower, with letrozole 14 ; . Although the clinical pregnancy rate per patient was higher with letrozole 21.6% versus 9.1% ; , the difference was not statistically significant. In the second trial involving 80 women with PCOS, similar although slightly higher ; rate of ovulation and median endometrial thickness were observed with CC, and the numbers of follicles 15 mm in diameter on the day of HCG was significantly lower with letrozole 15 ; . The clinical pregnancy rate was non-significantly higher with letrozole 22.5% versus 17.5% ; . When the data from these two trials were pooled using meta-analysis with a fixed effects model, the clinical pregnancy rate was not statistically significantly different odds ratio 1.94, 95% confidence interval 0.88 to 4.23 ; . Although the trend in clinical pregnancy rates was higher for letrozole crude combined proportions of 22% for letrozole versus 12.6% for CC ; , the total sample size of 186 from these two trials does not provide sufficient power to detect a clinically meaningful difference between the two preparations. Collectively, these observations of a trend towards a possible higher efficacy of letrozole when used in women with infertility due to PCOS, either as a first-line treatment or after adding metformin in those resistant to CC, suggest that letrozole may be an effective and better alternative to CC in the management of these patients, but further trials are required to adequately test these hypotheses. In addition to the use of CC for ovulation induction, it is now well accepted that CC can be used for superovulation in regularly ovulating women with unexplained infertility ; to stimulate the development of more than one follicle so that the likelihood of pregnancy can be increased. Failure to conceive with this approach is believed to be the result of some of the adverse peripheral effects of CC. Although the next step generally is to stimulate multiple follicle development with gonadotropins, the use of aromatase inhibitors may be worthy of consideration. A study was undertaken to evaluate the proof of principle of using aromatase inhibitors in women with unexplained infertility that failed to have the desired outcome with CC 10 ; . seven women with unexplained infertility, the prior use of CC resulted in ovulation but the endometrial development was poor 6 mm thickness ; . These women all ovulated after receiving letrozole in a subsequent cycle, using the same regimen as discussed above, and one clinical pregnancy 14.3% ; was achieved. The endometrium was significantly thicker and the estrogen level was significantly lower than when CC had been used in previous cycles. A search for randomised trials comparing CC with letrozoe in women with unexplained infertility identified one double-blind 16 ; , two randomised with computer generated lists 17, 18 ; and one quasi-randomised based on attendance order ; 19 ; trials. The pregnancy outcome data in the double-blind trial were only provided in percentages, but the actual numbers could be estimated from the information provided. In all trials letrozloe was administered for five days from day 3 of the cycle, but in three of the trials 16, 17, 19 ; the dose of letrozlle was 2.5 mg day, whereas in the fourth trial 18 ; , the dose was 7.5 mg day. CC in all trials was administered at a dose of 100 mg day for five days from day 3 of the cycle. In total, there were 264 subjects who received one or more cycles of treatment. Owing to significant statistical heterogeneity across the trials, the pregnancy outcome data were pooled using the random effects model. When CC was compared to letrozole, the common odds ratio for clinical pregnancy per patient was 0.89, 95% confidence interval 0.46 to 1.65. After excluding the trial with the higher dose of letrozole 18 ; , the common odds ratio was 1.08, 95% confidence interval 0.34 to 3.47. Although the numbers of subjects studied are not large enough to make precise inferences, the limited data fail to demonstrate any preference for CC or letrozole in women with unexplained infertility. No differences were observed in endometrial thickness. These findings are in contrast to those in women with PCOS. Estradiol levels, as expected, were lower in the group receiving letrozole. Interestingly, a study.

Dosimeter will be invaluable for appropriate triage at both echelon I and echelon II. Many years and multiple meetings were required for the development of NATO Standardization Agreement STANAG ; 2866, "Radiation Injuries and Effects of Radiation on Operational Effectiveness of Personnel." Although this is no longer a STANAG, it is useful guidance for medical personnel who must make triage decisions on the nuclear battlefield. With a known dose of radiation, the medical officer can accurately advise the commander on the medical consequences of the commander's decisions. Bio-triage of radiation injury is not possible at echelon I since there is no laboratory capability. Physical dosimetry is the only possibility, unless the physician at the battalion aid station is satisfied with using clinical symptomatology. Lymphocyte counts are available at the echelon II medical company; however, holding patients for 48 hours to observe changes in lymphocyte counts is not practicable. The medical companies have limited cots usually not more than 40 ; . The need for cots for other patients precludes retaining patients for observation. Thus, triage for radiation-injury-only casualties is difficult without the prompt knowledge of the radiation dose. The wrist-watch dosimeter is not adequate as a basis for life or death decisions. For combined-injury patients, initial triage decisions will have to be made on the basis of the other injuries, with the radiation injury ignored unless the casualty sustained a non-survivable radiation dose as evidenced by prompt or early clinical symptoms. Combat Developments at the Army Medical Department AMEDD ; Center and School maintains a large patient-condition model for determining workloads, logistical support, and personnelresource requirements for tactical scenarios. Included in this model are five radiation-casualty conditions, ranging from casualties with radiation exposure and minimal symptoms who are evacuated to a hospital for evaluation with return to duty in 2 days, to the other extreme, casualties who die from radiation injuries in approximately 1 week. Current combat scenarios suggest that in the event and nordette.

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CONTINUING CONTROVERSIES IN REFRACTIVE SURGERY FOR AIRCREW Dr Rob Scott There are a number of options for refractive correction in aircrew. Spectacles work extremely well though there are problems with misting, reduced visual field and optical aberrations. They do not interface well with helmet mounted devices and the majority of aviators prefer not to use them. High water content soft contact lenses solve many of these problems and are popular in aviation, but have some associated risks and are not universally tolerated. More modern options include corneal and intraocular surgery for ametropia. Corneal surgery for aircrew includes the excimer laser treatments; laser in-situ keratomileusis LASIK ; , laser epithelial keratomileusis LASEK ; and photorefractive keratectomy. The Royal Air Force allows the latter two procedures in its aircrew. Other corneal procedures include corneal inlays, intrastromal corneal rings and conductive keratoplasty. Intraocular lens procedures include phakic lens implants and clear lens extraction. In aircrew, a suitable refractive procedure must be appropriate to their aviation activities and environment. The length of time where an aviator is declared unfit flying duties varies from 3-12 months depending on the procedure. The refractive effects of the surgery are evaluated and any deterioration of contrast sensitivity, night vision or sensitivity to glare is measured, before a return to aviation duties is allowed. According to the introduction to the paper [1], which summarises some of the information about this, the correct anResults swer is C. Roads are safer in the UK, so the same answer to the same question is even more likely in the UK. In the study period, there were 4, 031 admissions to the study units, comprising 21, 412 patient-days about 10% of the 214, 000 patient days in adult, nonobstetric units at the two Adverse drug event hospitals ; . An ADE is defined as an injury resulting from medical intervention relating to a drug. This definition is dif ferent from The study found 247 ADEs and 194 potential ADEs. Extrapothat of an adverse drug reaction ADR ; , defined by WHO as lated, this amounted to 1900 ADEs per hospital per year, with, "noxious and unintended, and which occurs at doses used in for every 100 admissions, 6.5 ADEs and 5.5 potential ADEs. man for prophylaxis, diagnosis or therapy".The ADR defi- Of all ADEs, 1% were fatal, 12% life-threatening, 30% serious nition is likely to be idiosyncratic and rare, and would, for and 57% significant. instance, not include an unintended misprescription of a larger than therapeutic dose of a drug which caused harm The rate of ADEs was highest in medical intensive care units because it was an overdose. Such an event would be an ADE. 19 per 1, 000 patient-days ; and relatively similar among surgical intensive care and medical and surgical general care It should not occur and is likely to be preventable. , units 9 - 11 per 1, 000 patient-days and ocuflox and letrozole, because what is letrozole. And letrozole, and the steroid, exemestane, has resulted in a resurgence in the use of this class of drugs in the treatment of breast cancer. Until recently, megestrol acetate was the most commonly used second-line agent in the treatment of hormone-responsive metastatic breast cancer. Two Phase III trials, however, that compared anastrozole to megestrol acetate, showed an overall survival benefit in favour of anastrazole with a hazard ratio of 0.78 P 0.025 ; .30 These encouraging results led to the initiation of trials in which the newer aromatase inhibitors were compared to tamoxifen, the standard of care, in the setting of hormone-receptor positive, locally advanced, or metastatic postmenopausal breast cancer. The results of two such trials, one based in North America31 and the other in Europe, 32 have now been reported. The data from these two trials, that were of similar design, have been pooled and show that anastrazole is at least as effective as tamoxifen for the treatment of postmenopausal women with advanced breast cancer in terms of median time to progression TTP, 8.5 months compared to 7.0 months, hazard ratio 1.12 ; . Several clinical trials designed to test the efficacy of aromatase inhibitors in preventing relapse after definitive surgery for early breast cancer are ongoing or have recently closed to accrual. One of these, the ATAC anastrazole alone, tamoxifen alone, or in combination ; trial, compared anastrazole to tamoxifen and to a combination of the two treatments. The early results of this large trial involving more than 9, 000 women were reported at the San Antonio Breast Cancer Symposium in December 2001. Over a median follow-up period of 33 months, anastrazole was associated with a 19% improvement in diseasefree survival compared to tamoxifen. The presentation of this result sparked considerable debate and has been discussed in several articles and commentaries in the oncology literature.33 The consensus is that longer follow-up is required to show whether the advantage of anastrazole over tamoxifen will be sustained over time. For now, tamoxifen is still considered by most to be the standard of care for postmenopausal breast cancer patients with steroidhormone receptor positive disease.34.
BREAST Follow-up of patients treated with sentinel node biopsy at the IEO: the node-negative patients The sentinel node biopsy performed with local anesthesia in palpable breast tumors with maximum diameter 2.5 cm The radioguided sentinel node biopsy at the internal mammary chain: pilot study on patients affected by infiltrating breast carcinoma located in the internal mammary quadrants Radioguided occult lesion localization ROLL ; in breast surgery Low-dose tamoxifen and 4-HPR in early breast cancer. A phase III study to evaluate Oetrozole as adjuvant endocrine therapy for postmenopausal women with receptor ER and or PgR ; positive tumors. Primary chemotherapy combined with chemotherapy in operable breast cancer. perioperative and oxybutynin.
Figure 1. The forehead-zygomatic FZ ; gradient of SPL and location of forehead F ; and zygomatic Z ; densely innervated facial skin zones 2 ; . Nishimura C & Nagumo J 1985 ; Ergonomics 28, 905-913. Podshibiakin AK 1960 ; Abstr. diss. doct. of medical sciences.

Patients with any stage of ovarian cancer are candidates for clinical trials. In addition to testing high-dose or combinations of chemotherapy, agents with unique actions are being investigated. LH-RH Agonists. Luteinizing hormone-releasing hormones LH-RH ; agonists also called GnRH agonists ; include leuprolide Lupron ; , goserelin Zoladex ; , and deslorelin. These agents are able to block the release of two major reproductive hormones, and there is some indication that this action may help prevent cell proliferation. Immunotherapy. A number of therapies are under investigation that use agents that boost the body's own immune response to specifically attack ovarian cancer cells. To date, they have produced only minor effects. Experimental therapies that are in clinical trials include a vaccinations that use specially designed antibodies called monoclonal antibodies or MAbs ; to boost the immune responses against tumor-associated factors, such as CA125 or HER-2 neu. Vaccines against HERS neu are also being investigated. Gene Therapy. Gene therapies generally work in one of two ways: One approach involves genes that are used to convert inactive agents into cancer-fighting drugs. The other major approach uses genetic therapies to repair molecular defects that are causing uncontrolled cell proliferation. For example, some investigators are using techniques to deliver a normal p53 gene, which suppresses cancer cell growth, into ovarian cancer cells. Antiangiogenesis Agents. Angiogenesis, the formation of new blood vessels that feed the growth of a cancerous tumor, is a critical process in the spread of ovarian cancer. Drugs that block this process are under investigation for ovarian cancer and include thalidomide, gefinitib Iressa ; , and carboxyamido-triazole CAI ; . Aromatase Inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many body tissues. The include anastrozole Arimidex ; and letrozole Femara ; . A 2002 study suggested they might be. Prelude to considering this and other inhibitors as preventive treatments of breast cancer. The study design also has allowed assessment of the effects of letrozole on bone resorption markers and lipids, which are also important to consider in the preventive setting.

Both the piercer and the client, and with cooperation can ensure a safe and successful experience. Information is the Key Unsafe, unethical, and uneducated piercers thrive in areas where complete, accurate information is not made available to both the general public and those who seek to protect them. Making oral piercings illegal forces consumers who still seek them to patronize unregulated, underground establishments. Only by supporting the dissemination of accurate information and the efforts of conscientious professionals can the risks of piercing truly be controlled. To disparage the efforts of a burgeoning profession without full and appropriate information is not an accurate or helpful response. Since many individuals still desire oral piercings and intend to get them, it is far more constructive to provide accurate information and specific guidelines on safe piercing procedure and how to choose a practitioner. The APP is a non-profit organization dedicated to health, education and safety of piercers and the public. We are a group of committed professionals who uphold an extremely high standard of safety and hygiene. We support the development of appropriate regulations and standards to ensure the improvement of our art form and the continued safety of our clientele, for instance, letrozole prescribing. Labels can be supplied in rolls or tablet form for the same low price. Other sizes available at your request at little or no additional charge and levocetirizine.

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As outlined in a recent edition of PostScript, the Scottish Medicines Consortium SMC ; is now actively assessing new products, the first being imatinib Glivec ; . SMC has concluded that imatinib is the first treatment to offer major improvement in the clinical response in chronic myeloid leukaemia. This approach appears to provide an advance in the treatment of the disease. Accordingly, SMC advice to NHS Boards and Area Drug & Therapeutic Committees ADTCs ; is to recommend imatinib for restricted use within NHS Scotland. It should be used for the treatment of chronic myeloid leukaemia CML ; under the overall supervision of haematologists oncologists and within the context of the current guidance on this medicine that was compiled by the British Society for Haematology for its submission to NICE in November 2001. It is expected that clinicians will gather outcome data that will, in turn, further inform clinical practice. SMC also envisages that the majority of newly diagnosed patients with CML will be entered into the SPIRIT STI571 Prospective International Randomised Trial ; study comparing imatinib alone against treatment with imatinib plus interferon or cytarabine Ara-C ; . It is worth noting that the National Institute for Clinical Excellence NICE ; will not issue advice on imatinib until later in 2002. The SMC work programme is gathering pace, but there is still some overlap between it and the work of local ADTCs. In the immediate future, information about products due to be reviewed will be distributed to ADTCs to help with local planning purposes. Confidential, commercially sensitive information is submitted to SMC by companies, and at present discussions are being held to decide on wider availability of the list of pending products. In the longer term it is hoped that that information will be available on the SMC website.
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