Gene therapies are gaining momentum as promising early successes in clinical studies accumulate and examples of regulatory approval for licensing increase. Investigators are advancing with cautious ...optimism that effective, durable, and safe therapies will provide benefit to patients-not only those with single-gene disorders but those with complex acquired diseases as well. While the strategies being translated from the lab to the clinic are numerous, this review focuses on the clinical research that has forged the gene therapy field as it currently stands.
Summary Background Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine ...coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths. Methods Between Nov 1 and Dec 22, 2014, we systematically reviewed PubMed, Scopus, and official websites to identify HPV immunisation programmes worldwide, and retrieved age-specific HPV vaccination coverage rates up to October, 2014. To estimate the coverage and number of vaccinated women, retrieved coverage rates were converted into birth-cohort-specific rates, with an imputation algorithm to impute missing data, and applied to global population estimates and cervical cancer projections by country and income level. Findings From June, 2006, to October, 2014, 64 countries nationally, four countries subnationally, and 12 overseas territories had implemented HPV immunisation programmes. An estimated 118 million women had been targeted through these programmes, but only 1% were from low-income or lower-middle-income countries. 47 million women (95% CI 39–55 million) received the full course of vaccine, representing a total population coverage of 1·4% (95% CI 1·1–1·6), and 59 million women (48–71 million) had received at least one dose, representing a total population coverage of 1·7% (1·4–2·1). In more developed regions, 33·6% (95% CI 25·9–41·7) of females aged 10–20 years received the full course of vaccine, compared with only 2·7% (1·8–3·6) of females in less developed regions. The impact of the vaccine will be higher in upper-middle-income countries (178 192 averted cases by age 75 years) than in high-income countries (165 033 averted cases), despite the lower number of vaccinated women (13·3 million vs 32·2 million). Interpretation Many women from high-income and upper-middle-income countries have been vaccinated against HPV. However, populations with the highest incidence and mortality of disease remain largely unprotected. Rapid roll-out of the vaccine in low-income and middle-income countries might be the only feasible way to narrow present inequalities in cervical cancer burden and prevention. Funding PATH, Instituto de Salud Carlos III, and Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR).
We propose a distributed algorithm, named Distributed Alternating Direction Method of Multipliers (D-ADMM), for solving separable optimization problems in networks of interconnected nodes or agents. ...In a separable optimization problem there is a private cost function and a private constraint set at each node. The goal is to minimize the sum of all the cost functions, constraining the solution to be in the intersection of all the constraint sets. D-ADMM is proven to converge when the network is bipartite or when all the functions are strongly convex, although in practice, convergence is observed even when these conditions are not met. We use D-ADMM to solve the following problems from signal processing and control: average consensus, compressed sensing, and support vector machines. Our simulations show that D-ADMM requires less communications than state-of-the-art algorithms to achieve a given accuracy level. Algorithms with low communication requirements are important, for example, in sensor networks, where sensors are typically battery-operated and communicating is the most energy consuming operation.
Distributed Basis Pursuit Mota, J. F. C.; Xavier, J. M. F.; Aguiar, P. M. Q. ...
IEEE transactions on signal processing,
04/2012, Letnik:
60, Številka:
4
Journal Article
Recenzirano
Odprti dostop
We propose a distributed algorithm for solving the optimization problem Basis Pursuit (BP). BP finds the least ℓ 1 -norm solution of the underdetermined linear system Ax = b and is used, for example, ...in compressed sensing for reconstruction. Our algorithm solves BP on a distributed platform such as a sensor network, and is designed to minimize the communication between nodes. The algorithm only requires the network to be connected, has no notion of a central processing node, and no node has access to the entire matrix A at any time. We consider two scenarios in which either the columns or the rows of A are distributed among the compute nodes. Our algorithm, named D-ADMM, is a decentralized implementation of the alternating direction method of multi- pliers. We show through numerical simulation that our algorithm requires considerably less communications between the nodes than the state-of-the-art algorithms.
The free-electron laser, first proposed by Madey in 1971, has significantly reduced laser wavelengths to the vacuum ultraviolet and soft X-ray regions. Recently, an X-ray free-electron laser (XFEL) ...was operated at 1.2 Aa at the Linac Coherent Light Source (LCLS). Here, we report the successful generation of sub-angstrom laser light using a compact XFEL source, combining a short-period undulator with an 8 GeV electron beam. The shortest wavelength attained-0.634 Aa (63.4 pm)-is four orders of magnitude smaller than the 694 nm generated by Maiman's first laser. The maximum power exceeded 10 GW with a pulse duration of 10 super(-14) s. This achievement will contribute to the widespread use of XFEL sources and provide broad opportunities for exploring new fields in science.
Upadacitinib is an oral selective Janus kinase inhibitor to treat rheumatoid arthritis. The efficacy and safety of upadacitinib as compared with abatacept, a T-cell costimulation modulator, in ...patients with rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (DMARDs) are unclear.
In this 24-week, phase 3, double-blind, controlled trial, we randomly assigned patients in a 1:1 ratio to receive oral upadacitinib (15 mg once daily) or intravenous abatacept, each in combination with stable synthetic DMARDs. The primary end point was the change from baseline in the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP; range, 0 to 9.4, with higher scores indicating more disease activity) at week 12, assessed for noninferiority. Key secondary end points at week 12 were the superiority of upadacitinib over abatacept in the change from baseline in the DAS28-CRP and the percentage of patients having clinical remission according to a DAS28-CRP of less than 2.6.
A total of 303 patients received upadacitinib, and 309 patients received abatacept. From baseline DAS28-CRP values of 5.70 in the upadacitinib group and 5.88 in the abatacept group, the mean change at week 12 was -2.52 and -2.00, respectively (difference, -0.52 points; 95% confidence interval CI, -0.69 to -0.35; P<0.001 for noninferiority; P<0.001 for superiority). The percentage of patients having remission was 30.0% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P<0.001 for superiority). During the treatment period, one death, one nonfatal stroke, and two venous thromboembolic events occurred in the upadacitinib group, and more patients in the upadacitinib group than in the abatacept group had elevated hepatic aminotransferase levels.
In patients with rheumatoid arthritis refractory to biologic DMARDs, upadacitinib was superior to abatacept in the change from baseline in the DAS28-CRP and the achievement of remission at week 12 but was associated with more serious adverse events. Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis. (Funded by AbbVie; SELECT-CHOICE Clinicaltrials.gov number, NCT03086343.).
This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The ...group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.
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