Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.

To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling. Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples. Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands. 753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing. Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection. Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%. Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.published_or_final_versio

Treatment of knee osteoarthritis with Lyprinol®, lipid extract of the green-lipped mussel - A double-blind placebo-controlled study

Treatment of osteoarthritis (OA) includes pain control and improvement of patients' function and quality of life. While conventional treatment such as non-steroidal anti-inflammatory drugs and simple analgesics may achieve these goals, their use is not without side-effects. The use of "natural remedies" and "folklore medicines" is therefore commonly practised by patients with OA. Lyprinol® is a lipid extract of the green-lipped mussel which is rich in omega-3 fatty acids and has previously been shown to have anti-inflammatory effects in both in vitro and animal studies. The aim of this study was to compare the effects of Lyprinol® with placebo on the signs and symptoms and patient quality of life in the treatment of knee OA. Eighty patients with knee OA were randomized to receive either Lyprinol® or placebo for six months. All were allowed paracetamol rescue treatment during the study and were reviewed at week 0, 2, 4, 8, 12, 18 and 24 for arthritis assessment and safety evaluation. Assessment of the patients' arthritis included the use of a 100 mm visual analog scale (VAS) for pain, patient's and physician's global assessment of arthritis, a validated Chinese version of the Oxford Knee Score (COKS), a validated Chinese version of the Arthritis Impact Measurement Scale 2-short form (CAIMS2-SF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Improvement in almost all of the arthritis assessment parameters was observed in both groups of patients studied. However, there was a greater improvement in the perception of pain as measured by the VAS, and patients' global assessment of arthritis in those who took Lyprinol® when compared with controls from week 4 following adjustment for the change in the amount of paracetamol used between study visits. Patients who took Lyprinol® but not placebo also had improved scores in the CAIMS2-SF physical function and psychological status domains from week 4. However, changes in these scores did not differ significantly between the two groups at various study visits. When used over six months, Lyprinol® was safe and well tolerated with no serious side-effects reported. Further, there were no significant differences in the overall incidence of adverse reactions or withdrawal from study as a result of trial drug toxicity between Lyprinol® and placebo treated patients. In conclusion, Lyprinol®, a lipid extract of the green-lipped mussel, may be considered a safe option in the treatment of OA.link_to_subscribed_fulltex

Dilemmas, conspiracies, and Sophie’s choice: vignette themes and ethical judgments

Knowledge about ethical judgments has not advanced appreciably after decades of research. Such research, however, has rarely addressed the possible importance of the content of such judgments; that is, the material appearing in the brief vignettes or scenarios on which survey respondents base their evaluations. Indeed, this content has seemed an afterthought in most investigations. This paper closely examined the vast array of vignettes that have appeared in relevant research in an effort to reduce this proliferation to a more concise set of overarching vignette themes. Six generic themes emerged from this process, labeled here as Dilemma, Classic, Conspiracy, Sophie’s Choice, Runaway Trolley, and Whistle Blowing. Each of these themes is characterized by a unique combination of four key factors that include the extent of protagonist personal benefit from relevant vignette activities and victim salience in vignette descriptions. Theme identification enabled inherent ambiguities in vignettes that threaten construct validity to come into sharp focus, provided clues regarding appropriate vignette construction, and may help to make sense of patterns of empirical findings that heretofore have seemed difficult to explain

Ethical judgments: what do we know, where do we go?

Investigations into ethical judgments generally seem fuzzy as to the relevant research domain. We first attempted to clarify the construct and determine domain parameters. This attempt required addressing difficulties associated with pinpointing relevant literature, most notably the varied nomenclature used to refer to ethical judgments (individual evaluations of actions' ethicality). Given this variation in construct nomenclature and the difficulties it presented in identifying pertinent focal studies, we elected to focus on research that cited papers featuring prominent and often-used measures of ethical judgments (primarily, but not exclusively, the Multidimensional Ethics Scale). Our review of these studies indicated a preponderance of inferences and conclusions unwarranted by empirical evidence (likely attributable at least partly to inconsistent nomenclature). Moreover, ethical judgments related consistently to few respondent characteristics or any other variables, emergent relationships may not always be especially meaningful, and much research seems inclined to repetition of already verified findings. Although we concluded that knowledge about ethical judgments seems not to have advanced appreciably after decades of investigation, we suggested a possible path forward that focuses on the content of what is actually being judged as reflected in the myriad of vignettes used in the literature to elicit judgments