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This article shows that the structure of bilingual material from standard parsing and alignment tools is not optimal for training syntax-based statistical machine translation (SMT) systems. We present three modifications to the MT training data to improve the accuracy of a state-of-the-art syntax MT system: re-structuring changes the syntactic structure of training parse trees to enable reuse of substructures; re-labeling alters bracket labels to enrich rule application context; and re-aligning unifies word alignment across sentences to remove bad word alignments and refine good ones. Better structures, labels, and word alignments are learned by the EM algorithm. We show that each individual technique leads to improvement as measured by BLEU, and we also show that the greatest improvement is achieved by combining them. We report an overall 1.48 BLEU improvement on the NIST08 evaluation set over a strong baseline in Chinese/English translation. [ABSTRACT FROM AUTHOR]

This article provides information on industrial relations in Great Britain as of September to December 1974. The proposal of the Government for an Employment Protection Act took the form of a consultative document, open to comment by interested parties before the end of October 1974, and suggested a comprehensive package of new rights for trade unions, as a second stage in the Government's program on Industrial Relations. Government attempts to hold prices stable by subsidies were negated by massive increases in imports costs and wage rises.

This article highlights the chronicle on the industrial relations in Great Britain. During the period under review, industrial action was staged in hospitals by nurses and other health workers in support of a demand for special pay rises above the stage three limits. Following further unofficial action, and the threat by the 100,000 strong Royal College of Nursing to invoke mass resignations from the Health Service and a re-signing as temporary, higher paid nurses, May 23, 1974 the Secretary of State for the Health Service ordered a special enquiry into nurses pay to be set up, under the chairmanship of Lord Halsbury, with any recommended increases backdated to May 23, 1974.

This article focuses on the impact of rapid development of multi-national business enterprises on trade unions in Great Britain. This article is based upon a survey of British-based multinational enterprises, which was adapted from that carried out by Professor Blake, thus enabling a comparison of the responses of American and British multinational firms to the same union developments to be carried out. An index of multinational companies establishing their level of internationality was constructed and used as a guide in the selection of a sample of companies of different sizes in a range of manufacture, extraction and process industries. Firms operating mainly or entirely in the financial and service sector were not included.

A combination of ultrahigh-speed optical imaging (5 × 106 frames/s), B-mode ultrasound and passive cavitation detection was used to study the vaporization process and determine both the acoustic droplet vaporization (ADV) and inertial cavitation (IC) thresholds of phospholipid-coated perfluorobutane nanodroplets (PFB NDs, diameter = 237 ± 16 nm). PFB NDs have not previously been studied with ultrahigh-speed imaging and were observed to form individual microbubbles (1-10 μm) within two to three cycles and subsequently larger bubble clusters (10-50 μm). The ADV and IC thresholds did not statistically significantly differ and decreased with increasing pulse length (20-20,000 cycles), pulse repetition frequency (1-100 Hz), concentration (108-1010 NDs/mL), temperature (20°C-45°C) and decreasing frequency (1.5-0.5 MHz). Overall, the results indicate that at frequencies of 0.5, 1.0 and 1.5 MHz, PFB NDs can be vaporized at moderate peak negative pressures (<2.0 MPa), pulse lengths and pulse repetition frequencies. This finding is encouraging for the use of PFB NDs as cavitation agents, as these conditions are comparable to those required to achieve therapeutic effects with microbubbles, unlike those reported for higher-boiling-point NDs. The differences between the optically and acoustically determined ADV thresholds, however, suggest that application-specific thresholds should be defined according to the biological/therapeutic effect of interest. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is the most common birth defect, and up to 50% of infants with CHD require cardiovascular surgery early in life. Current clinical practice often involves thymus resection during cardiac surgery, detrimentally affecting T-cell immunity. However, epidemiological data indicate that CHD patients face an elevated risk for infections and immune-mediated diseases, independent of thymectomy. Hence, we examined whether the cardiac defect impacts thymus function in individuals with CHD. We investigated thymocyte development in 58 infants categorized by CHD complexity. To assess the relationship between CHD complexity and thymic function, we analyzed T-cell development, thymic output, and biomarkers linked to cardiac defects, stress, or inflammation. Patients with highly complex CHD exhibit thymic atrophy, resulting in low frequencies of recent thymic emigrants in peripheral blood, even prior to thymectomy. Elevated plasma cortisol levels were detected in all CHD patients, while high NT-proBNP and IL-6 levels were associated with thymic atrophy. Our findings reveal an association between complex CHD and thymic atrophy, resulting in reduced thymic output. Consequently, thymus preservation during cardiovascular surgery could significantly enhance immune function and the long-term health of CHD patients. [ABSTRACT FROM AUTHOR]

Gas-loaded nanobubbles have potential as a method of oxygen delivery to increase tumour oxygenation and therapeutically alleviate tumour hypoxia. However, the mechanism(s) whereby oxygen-loaded nanobubbles increase tumour oxygenation are unknown; with their calculated oxygen-carrying capacity being insufficient to explain this effect. Intra-tumoural hypoxia is a prime therapeutic target, at least partly due to hypoxia-dependent stimulation of the formation and function of bone-resorbing osteoclasts which establish metastatic cells in bone. This study aims to investigate potential mechanism(s) of oxygen delivery and in particular the possible use of oxygen-loaded nanobubbles in preventing bone metastasis via effects on osteoclasts. Lecithin-based nanobubbles preferentially interacted with phagocytic cells (monocytes, osteoclasts) via a combination of lipid transfer, clathrin-dependent endocytosis and phagocytosis. This interaction caused general suppression of osteoclast differentiation via inhibition of cell fusion. Additionally, repeat exposure to oxygen-loaded nanobubbles inhibited osteoclast formation to a greater extent than nitrogen-loaded nanobubbles. This gas-dependent effect was driven by differential effects on the fusion of mononuclear precursor cells to form pre-osteoclasts, partly due to elevated potentiation of RANKL-induced ROS by nitrogen-loaded nanobubbles. Our findings suggest that oxygen-loaded nanobubbles could represent a promising therapeutic strategy for cancer therapy; reducing osteoclast formation and therefore bone metastasis via preferential interaction with monocytes/macrophages within the tumour and bone microenvironment, in addition to known effects of directly improving tumour oxygenation. [ABSTRACT FROM AUTHOR]

• Increasing the volumetric concentration of PFP led to an increase in the size of lipid-coated PFP NDs. • Increasing sonication intensity and time led to a decrease in ND size. • The ND coating layer can be labelled with lipophilic fluorophores without affecting the overall ND size. • NDs were stable at 4 °C for one week, and at 37 °C for 110 min. • Ultrasound (0.5 MHz, 2–4 MPa) caused vaporisation of NDs within a tissue-mimicking phantom. Liquid perfluorocarbon nanodroplets (NDs) are an attractive alternative to microbubbles (MBs) for ultrasound-mediated therapeutic and diagnostic applications. ND size and size distribution have a strong influence on their behaviour in vivo , including extravasation efficiency, circulation time, and response to ultrasound stimulation. Thus, it is desirable to identify ways to tailor the ND size and size distribution during manufacturing. In this study phospholipid-coated NDs, comprising a perfluoro-n-pentane (PFP) core stabilised by a DSPC/PEG40s (1,2-distearoyl- sn -glycero-3-phosphocholine and polyoxyethylene(40)stearate, 9:1 molar ratio) shell, were produced in phosphate-buffered saline (PBS) by sonication. The effect of the following production-related parameters on ND size was investigated: PFP concentration, power and duration of sonication, and incorporation of a lipophilic fluorescent dye. ND stability was also assessed at both 4 °C and 37 °C. When a sonication pulse of 6 s and 15% duty cycle was employed, increasing the volumetric concentration of PFP from 5% to 15% v/v in PBS resulted in an increase in ND diameter from 215.8 ± 16.8 nm to 408.9 ± 171.2 nm. An increase in the intensity of sonication from 48 to 72 W (with 10% PFP v/v in PBS) led to a decrease in ND size from 354.6 ± 127.2 nm to 315.0 ± 100.5 nm. Increasing the sonication time from 20 s to 40 s (using a pulsed sonication with 30% duty cycle) did not result in a significant change in ND size (in the range 278–314 nm); however, when it was increased to 60 s, the average ND diameter reduced to 249.7 ± 9.7 nm, which also presented a significantly lower standard deviation compared to the other experimental conditions investigated (i.e., 9.7 nm vs. > 49.4 nm). The addition of the fluorescent dye DiI at different molar ratios did not affect the ND size distribution. NDs were stable at 4 °C for up to 6 days and at 37 °C for up to 110 min; however, some evidence of ND-to-MB phase transition was observed after 40 min at 37 °C. Finally, phase transition of NDs into MBs was demonstrated using a tissue-mimicking flow phantom under therapeutic ultrasound exposure conditions (ultrasound frequency: 0.5 MHz, acoustic pressure: 2–4 MPa, and pulse repetition frequency: 100 Hz). [ABSTRACT FROM AUTHOR]

Background: In the current United Kingdom population the incidence of diabetic peripheral neuropathy is increasing. The presence of diabetic neuropathy affects decision making and treatment options. This study seeks to evaluate if the vibrations generated from a mobile phone can be used to screen patients for diabetic peripheral neuropathy., Methods: This study comprised of 61 patients; a control group of 21 patients; a lower limb injury group of 19 patients; a diabetic peripheral neuropathy group of 21 patients. The control and injury group were recruited randomly from fracture clinics. The diabetic peripheral neuropathy group were randomly recruited from the diabetic foot clinic. The 61 patients were examined using a 10g Semmes-Weinstein monofilament, a 128Hz tuning fork and a vibrating mobile phone. The points tested were, index finger, patella, lateral malleoli, medial malleoli, heel, first and fifth metatarsal heads., Results: The most accurate location of all the clinical tests was the head of the 1st metatarsal at 0.86. The overall accuracy of the tuning fork was 0.77, the ten gram monofilament 0.79 and the mobile phone accuracy was 0.88. The control group felt 420 of 441 tests (95%). The injury group felt 349 of 399 tests (87%). The neuropathic group felt 216 of 441 tests (48%). There is a significant difference in the number of tests felt between the control and both the injury and neuropathic groups. p<0.0001 using N-1 Two Proportion Test., Conclusion: A mobile phone is an accurate screening tool for diabetic peripheral neuropathy. The most accurate location to test for diabetic peripheral neuropathy is the head of the 1st metatarsal. Screening for diabetic peripheral neuropathy in the index finger and patella were inaccurate. An injury to the lower limb affects the patient's vibration sensation, we would therefore recommend screening the contralateral limb to the injury., Level of Evidence: This study represents level II evidence of a new diagnostic investigation., (Copyright © 2016 European Foot and Ankle Society. All rights reserved.)

Frequency analysis of the photoacoustic radiofrequency signals and oxygen saturation estimates were used to monitor the in-vivo response of a novel, thermosensitive liposome treatment. The liposome encapsulated doxorubicin (HaT-DOX) releasing it rapidly (<20 s) when the tumor was exposed to mild hyperthermia (43 °C). Photoacoustic imaging (VevoLAZR, 750/850 nm, 40 MHz) of EMT-6 breast cancer tumors was performed 30 min pre- and post-treatment and up to 7 days post-treatment (at 2/5/24 h timepoints). HaT-DOX-treatment responders exhibited on average a 22% drop in oxygen saturation 2 h post-treatment and a decrease (45% at 750 nm and 73% at 850 nm) in the slope of the normalized PA frequency spectra. The spectral slope parameter correlated with treatment-induced hemorrhaging which increased the optical absorber effective size via interstitial red blood cell leakage. Combining frequency analysis and oxygen saturation estimates differentiated treatment responders from non-responders/control animals by probing the treatment-induced structural changes of blood vessel.

The hydroxypyrroloindolenine (Hpi) motif forms the fundamental core of the pentacyclic natural product, brevianamide E, the concise stereoselective synthesis of which, via oxidative cyclization, is described., (© 2011 American Chemical Society)

The topic of an existing healthcare crisis has resounded in articles, papers, and the media for years. Amidst the ongoing healthcare crisis, several other global and economic crises have arisen to further complicate the focus for resolve. This article takes a basic look at the foundation of U.S. healthcare and evaluates the inappropriate incentives that currently drive the industry and prevent meaningful change. The commentary identifies causes of administrative and fiscal waste while proposing alternative concepts for consideration and further discussion.

Cyclisation and cross-linking strategies are important for the synthesis of cyclic and bicyclic peptides. These macrolactams are of great interest due to their increased biological activity compared to linear analogues. Herein, we describe the synthesis of a cyclic peptide containing an Hpi toxicophore, reminiscent of phakellistatins and omphalotins. The first intraannular cross-linking of such a peptide is then presented: using neat TFA to catalyse a Savige-Fontana tryptathionylation, the Hpi-containing peptide is converted to a bicyclic amatoxin analogue. As such, this methodology represents an efficient cyclisation method for cross-linking peptides and exposes a heretofore unrealised relationship between two different classes of peptide natural products. This finding increases the degree of potential chemical space for library generation.

The amatoxins are a family of toxic bicyclic peptides that inhibit RNA polymerase II. Herein we discuss an improved synthesis of these compounds from easily obtainable amino acids by means of a solid-phase methodology. Interestingly, we obtained two products of the same mass following our final macrocyclisation, relating to a similar distribution of products described in some previous reports. One of these products was the desired amatoxin; Pro(2)-Ile(3)-S-deoxo-amaninamide 1 b. The other compound, after thorough investigation, was confirmed to be the epimer Pro(2)-D-allo-Ile(3)-S-deoxo-amaninamide 1 a, not an atropisomer structure as previously suggested in syntheses of related amanitin analogues. Crystallographic data of 1 a confirms the presence of a betaII-turn, rather than a betaI-turn common to the natural toxin and 1 b. This difference explains the large variation in CD spectra, although it seems to have relatively little effect on the bioactivity in vitro. These data provide new insights into the bicyclic amatoxin structure.

The tryptathionine linkage is a crosslink formed between tryptophan and cysteine. This feature is characteristic of the bicyclic peptides: the phallotoxins and the amatoxins. These peptides both bind to protein folds of their respective targets (F-actin and RNA pol II, respectively) with extremely high affinities. Studies on these peptides have shown that the tryptathionine crosslink is essential for this binding affinity. Tryptathionines have been investigated for many years and several syntheses exist for their formation. In this review, we report on the various methodologies employed in tryptathionine synthesis, and discuss some of the advantages and disadvantages associated with each of them., (Copyright (c) 2007 Wiley Periodicals, Inc.)

The healthcare industry is in the unenviable position of having a perception of declining customer service. Reimbursement for professional services continues to decrease while the volume of patients needed to sustain a viable practice increases. As a result, many providers are concerned about not having the time to provide the high level of care they once did, and patients are frustrated with--and focused on--customer service issues that affect the well-being of the medical office, staff and patient relations. To improve the service provided to patients, some offices are turning to the boutique model as an option that will financially support rising overhead and allow the provider and staff to improve the services offered to each individual patient. These practices are met with different opinions, however, and providers choosing to move in this direction need to plan carefully and assess the long-term effects. Feelings can be strong regarding the rising cost of healthcare, yet the boutique model likely is not the right fit for many providers and patients.

In no other industry are the consumers of goods or services so unaware and uninvolved in the reimbursement for the goods or services received. The United States healthcare industry has created and allowed to perpetuate a "hands-off" compensation approach that has created a consumer mentality proving quite difficult to change. In this article, the author describes the origin of this outdated approach and suggests a restructured office and clear communication with patients as starting points to change this deep-rooted mind-set. He describes how an up-front approach to patients' financial responsibilities and proactive staff can help reduce miscommunication between provider, patient, and insurance carrier and improve your practice's cash flow. The author also suggests that the patient's financial burden will continue to increase and offers tips to maintain positive patient relationships, improve your accounts receivable management, and protect you financially.

Clinical technology within the U.S. healthcare system is among the most advanced in the world. Basic administrative capabilities are lagging, however. Lack of standardization affecting the ability to integrate diverse systems and the prohibitive costs associated with acquisition and implementation are two major obstacles to improving administrative capacities. This article describes the basics of electronic medical records (EMR) implementation failures and successes and the evolution of the electronic health record (EHR) as part of the future of healthcare IT and continuity of care.