Delay-dependent amplification of a probe pulse via stimulated Rayleigh scattering

Stimulated Rayleigh scattering of pump and probe light pulses of close carrier frequencies is considered. A nonzero time delay between the two pulses is shown to give rise to amplification of the delayed (probe) pulse accompanied by attenuation of the pump, both on resonance and off resonance. In either case, phase-matching effects are shown to provide a sufficiently large gain, which can exceed significantly direct one-photon-absorption losses

Hymecromone Administration in Real Clinical Practice: Results of the Prospective Multicentre Observational Study in the Republic of Kazakhstan

Introduction. This multicentre prospective non-interventional observational study was conducted to obtain additional data about Odeston efficacy and safety in routine clinical practice. The objectives of the study included collection of clinical characteristics of patients, evaluation of Odeston effects in treatment of biliary pain and changes in the gallbladder emptying, evaluation of compliance to therapy, and treatment effect satisfaction.Materials and methods. The study was conducted from July 2020 to April 2021 at the premises of 60 study sites in 4 cities of the Republic of Kazakhstan. Patients having indications for Odeston administration according to the patient leaflet were enrolled. The study included 2 patient visits and an intermediate telephone contact. A visual analogue scale and RAPID questionnaire were used to characterise biliary pain; severity of associated symptoms, bowel habit and a quality of life according the SF-12 were also assessed. A rate of a ≥50 % reduction in symptom severity was used as a primary efficacy criterion; a rate of a ≥10 improvement in the SF-12 quality of life score was used as a secondary efficacy criterion. Compliance to treatment was evaluated using a number of days on Odeston. Treatment satisfaction was assessed using 5 grades.Results. 877 patients, 68.2 % of females and 31.8 % of males, were included in the study; the mean age was 46.0 ± 14.9 years. Primary functional biliary disorder was diagnosed in 65.3 % of patients, chronic non-calculous cholecystitis — 51.4 %, uncomplicated gallbladder disease — in 8.9 %, biliary sludge — 38.4 %, sphincter of Oddi functional disorder — 5.3 % of patients. A dose of Odeston was prescribed at the discretion of the physician. Group A patients received 600 mg (n = 89), group B received 1200 mg of Odeston a day (n = 788). In group B, an incidence of pronounced pain interference with daily living activities was higher. In both groups, the mean VAS scores were reduced to 1 point on treatment, a primary efficacy criterion was achieved in 77.3 % of patients in group A and in 79.8 % of patients in group B, р < 0.05. In both groups, a reduction in the incidence of constipation and diarrhea (р < 0,001) and an increase in the mean scores of physical and mental functioning were noted (р < 0.001, though a secondary efficacy criterion was not achieved (a ≥10 change in the SF-12 score). A prevalence of ultrasonographic sings of biliary sludge was reduced, and an increased gallbladder emptying was observed (p < 0.001). 77.4 % of patients in a total group of patients reported about drug administration for 21 days. A number of patients who were completely satisfied with treatment was higher in group B (p = 0.027).Conclusions. It was found that biliary pain interfered with daily living activities and commonly accompanied by other symptoms of gastrointestinal dysmotility. Odeston effectively reduces the severity of biliary pain, corrects dyspeptic disorders and normalizes stool pattern in patients with functional and organic diseases of the biliary system. Treatment satisfaction was higher with a dose of 1200 mg a day, particularly in more pronounced interference of pain with daily living activities

A New U.S.-U.S.S.R. Seismological Program

On July 9, 1986, a team of researchers from the University of California, San Diego; University of Nevada, Reno; and the University of Colorado, Boulder established the first of three seismic stations to be located in the vicinity of the Soviet nuclear test site in eastern Kazakhstan (KTS) (see cover). Under an agreement reached between the Soviet Academy of Sciences and the Natural Resources Defense Council, a nonprofit U.S. environmental organization, these stations, which are configured to meet the specifications of the proposed new global seismographic network [Incorporated Research Institutions for Seismology (IRIS), 1984], will be complemented by three similarly equipped stations to be installed in the vicinity of the U.S. nuclear test site in southern Nevada (NTS). The stations are to be operated cooperatively by Soviet and U.S. personnel (Figure 1)

A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

<p>Abstract</p> <p>Background</p> <p>Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials.</p> <p>Methods/Design</p> <p>The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express²paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control.</p> <p>Discussion</p> <p>The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at <url>http://www.clinicaltrials.gov</url>, identification numbers NCT00484315 and NCT00489541.</p

Современный взгляд на проблему постхолецистэктомического синдрома (по материалам Экспертного совета, состоявшегося 4 мая 2019 г. в городе Алматы, Казахстан)

Gallstone disease is revealed in 10–20% of the population with a clear tendency to affect the younger population. In a clinically manifested course, cholecystectomy remains the treatment of choice. Symptoms and signs persist or even become more severe after gallbladder surgery in 10-15% of cases (“postcholecystectomy syndrome”). Postcholecystectomy syndrome includes heterogeneous disorders of liver, pancreas, duodenum, sphincter of Oddi, etc. that can be associated with errors or negative consequences of surgical intervention. Often, symptoms may persist because of previously unrecognized chronic diseases of neighboring organs. The spectrum of effective conservative measures is rather limited. The Advisory Board was held on May 4, 2019, in Almaty (Kazakhstan) to re-estimate the definitions and categories related to the issue of the postcholecystectomy syndrome and to develop the diagnostic and treatment algorithm for patients with the postcholecystectomy dysfunction of the sphincter of Oddi. The statements discussed by the interdisciplinary team of gastroenterologists and surgeons were addressed to general practitioners, therapists, gastroenterologists, and surgeons. The Advisory Board emphasized that organic and functional biliary diseases manifest mainly by biliary pain, main characteristics of which were defined in the Rome IV consensus based on the statistical analysis of a large pool of clinical data. For a more accurate bile duct system assessment and the exclusion of cholelithiasis, the examination algorithm was proposed, which included abdominal ultrasound investigation, endoscopic ultrasound investigation of the pancreatobiliary area, and magnetic resonance cholangiopancreatography. Diagnostic algorithm for differentiation of functional biliary disorders from organic gastrointestinal pathology was developed. Sphincter of Oddi dysfunction may be considered as a postcholecystectomy syndrome manifestation in 1.5-3% of cases. Apart from rational nutrition, conservative management of functional gastrointestinal diseases implies  pharmacological therapy. The efficacy of non-steroidal anti-inflammatory drugs, prokinetics, nitrates, antispasmodics, calcium channel antagonists, botulinum toxin, and hymecromone was demonstrated in previous studies. Papillosphincterotomy is not effective in relieving biliary pain in cases of the sphincter of Oddi dysfunction. The proposed algorithm for the management of patients with the postcholecystectomy syndrome was presented.Желчнокаменная болезнь выявляется у 10–20% населения и имеет четкую тенденцию к «омоложению». При наличии клинических симптомов основным методом лечения остается холецистэктомия, после которой у 10–15% пациентов клинические проявления сохраняются либо усиливаются (для обозначения таких ситуаций применяют термин «постхолецистэктомический  синдром»). Постхолецистэктомический синдром объединяет неоднородные расстройства, включая  нарушения функции печени, поджелудочной железы, двенадцатиперстной кишки, сфинктера Одди  пр., которые могут быть связаны с погрешностями или последствиями хирургических манипуляций. Зачастую причиной сохранения жалоб оказываются ранее нераспознанные хронические заболевания других органов. Арсенал эффективных средств медикаментозной и  немедикаментозной коррекции относительно невелик. С целью стандартизировать определения и  категории, касающиеся проблемы постхолецистэктомического синдрома, и разработать алгоритм обследования и лечения пациентов с постхолецистэктомической дисфункцией сфинктера  Одди 4 мая 2019 г. в городе Алматы (Казахстан) состоялся совет экспертов – представителей  междисциплинарной команды из гастроэнтерологов и хирургов. Целевая аудитория – врачи общей  практики, терапевты, гастроэнтерологи, хирурги. Согласно решению Экспертного совета, основным  клиническим проявлением органических и функциональных заболеваний желчных путей  является билиарная боль, подробные характеристики которой были выделены в материалах IV Римского консенсуса на основании статистического анализа большого объема клинических данных. Для более точной оценки состояния протоковой системы и исключения желчнокаменной болезни в план обследования включают ультразвуковое исследование органов брюшной полости,  эндоскопическое ультразвуковое исследование панкреато-билиарной зоны, магнитно-резонансную  холангиопанкреатографию. Функциональные билиарные расстройства необходимо дифференцировать с органическими заболеваниями органов пищеварения; с этой целью  рекомендован план обследования пациентов. Дисфункцию сфинктера Одди можно рассматривать как вариант постхолецистэктомического синдрома; на долю таких случаев приходится 1,5–3%. Консервативное ведение при функциональных заболеваниях органов пищеварения, помимо  рационального питания, подразумевает лекарственную терапию. Показана эффективность  нестероидных противовоспалительных препаратов, прокинетиков, нитратов, спазмолитиков, антагонистов кальциевых каналов, ботулотоксина и гимекромона. Папиллосфинктеротомия при  дисфункции сфинктера Одди не обладает должной эффективностью в купировании билиарной  боли. Разработан алгоритм ведения пациентов при появлении билиарной боли и другой  симптоматики после холецистэктомии

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat