Spasmodic dysphonia, perceptual and acoustic analysis: presenting new diagnostic tools

In this article, we investigate whether (1) the IINFVo (Impression, Intelligibility, Noise, Fluency and Voicing) perceptual rating scale and (2) the AMPEX (Auditory Model Based Pitch Extractor) acoustical analysis are suitable for evaluating adductor spasmodic dysphonia (AdSD). Voice recordings of 12 patients were analysed. The inter-rater and intra-rater consistency showed highly significant correlations for the IINFVo rating scale, with the exception of the parameter Noise. AMPEX reliably analyses vowels (correlation between PUVF (percentage of frames with unreliable F0/voicing 0.748), running speech (correlation between PVF (percentage of voiced frames)/voicing 0.699) and syllables. Correlations between IINFVo and AMPEX range from 0.608 to 0.818, except for noise. This study indicates that IINFVo and AMPEX could be robust and complementary assessment tools for the evaluation of AdSD. Both the tools provide us with the valuable information about voice quality, stability of F0 (fundamental frequency) and specific dimensions controlling the transitions between voiced and unvoiced segments

Voicing quantification is more relevant than period perturbation in substitution voices: an advanced acoustical study

Quality of substitution voicing—i.e., phonation with a voice that is not generated by the vibration of two vocal folds—cannot be adequately evaluated with routinely used software for acoustic voice analysis that is aimed at ‘common’ dysphonias and nearly periodic voice signals. The AMPEX analysis program (Van Immerseel and Martens) has been shown previously to be able to detect periodicity in irregular signals with background noise, and to be suited for running speech. The validity of this analysis program is first tested using realistic synthesized voice signals with known levels of cycle-to-cycle perturbations and additive noise. Second, exhaustive acoustic analysis is performed of the voices of 116 patients surgically treated for advanced laryngeal cancer and recorded in seven European academic centers. All of them read out a short phonetically balanced passage. Patients were divided into six groups according to the oscillating structures they used to phonate. Results show that features related to quantification of voicing enable a distinction between the different groups, while the features reporting F0-instability fail to do so. Acoustic evaluation of voice quality in substitution voices thus best relies upon voicing quantification

Incorporating a gender perspective into the development of clinical guidelines: a training course for guideline developers

<p>Abstract</p> <p>Background</p> <p>Dutch guideline-developing organizations do not focus systematically on differences between men and women when developing guidelines, even though there is increasing evidence that being male or female may have an effect on health and health outcomes. In collaboration with two prominent Dutch guideline-developing organizations, we designed a training course to encourage systematic attention to sex differences in guideline development procedures.</p> <p>Methods</p> <p>The course is targeted towards guideline developers. Its aims are to improve awareness concerning the relevance of considering sex differences in the guideline development process, as well as the competence and skills necessary for putting this into practice. The design and teaching methods of the course are based on adult learning styles and principles of changing provider behaviour. It was adjusted to the working methods of guideline organizations. The course was taught to, and evaluated by, a group of staff members from two guideline organizations in the Netherlands.</p> <p>Results</p> <p>The course consists of five modules, each of which corresponds to a key step in the guideline development process. The participants rated the training course positively on content, programme, and trainers. Their written comments suggest that the course met its objectives.</p> <p>Conclusion</p> <p>The training course is the first to address sex differences in guideline development. Results from the pilot test suggest that the course achieved its objectives. Because its modules and teaching methods of the course are widely transferable, the course could be useful for many organizations that are involved in developing guidelines. Follow-up studies are needed to assess the long-term effect of the course on the actions of guideline developers and its utility in other settings.</p

The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis

BACKGROUND AND PURPOSE: Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. METHODS: We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks) to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. RESULTS: We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p < .001). A multiple regression model explained 79% of the variance in placebo variability (F = 59.7; p < 0.0001). Significant predictors are, among others, the duration of the study (beta = .31), the quality of the study (beta = .18), the fact whether a study is a prevention trial (beta = .44), whether dropouts have been documented (beta = -.20), or whether additional treatments have been documented (beta = -.17). Healing rates with placebo are lower in the following diagnoses; neoplasms (beta = -.21), nervous diseases (beta = -.10), substance abuse (beta = -.14). Without prevention trials the amount of variance explained is 42%. CONCLUSION: Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated

Valorizing the 'Irulas' traditional knowledge of medicinal plants in the Kodiakkarai Reserve Forest, India

A mounting body of critical research is raising the credibility of Traditional Knowledge (TK) in scientific studies. These studies have gained credibility because their claims are supported by methods that are repeatable and provide data for quantitative analyses that can be used to assess confidence in the results. The theoretical importance of our study is to test consensus (reliability/replicable) of TK within one ancient culture; the Irulas of the Kodiakkarai Reserve Forest (KRF), India. We calculated relative frequency (RF) and consensus factor (Fic) of TK from 120 Irulas informants knowledgeable of medicinal plants. Our research indicates a high consensus of the Irulas TK concerning medicinal plants. The Irulas revealed a diversity of plants that have medicinal and nutritional utility in their culture and specific ethnotaxa used to treat a variety of illnesses and promote general good health in their communities. Throughout history aboriginal people have been the custodians of bio-diversity and have sustained healthy life-styles in an environmentally sustainable manner. However this knowledge has not been transferred to modern society. We suggest this may be due to the asymmetry between scientific and TK, which demands a new approach that considers the assemblage of TK and scientific knowledge. A greater understanding of TK is beginning to emerge based on our research with both the Irulas and Malasars; they believe that a healthy lifestyle is founded on a healthy environment. These aboriginal groups chose to share this knowledge with society-at-large in order to promote a global lifestyle of health and environmental sustainability

Bone Loss in Diabetes: Use of Antidiabetic Thiazolidinediones and Secondary Osteoporosis

Clinical evidence indicates that bone status is affected in patients with type 2 diabetes mellitus (T2DM). Regardless of normal or even high bone mineral density, T2DM patients have increased risk of fractures. One class of antidiabetic drugs, thiazolidinediones (TZDs), causes bone loss and further increases facture risk, placing TZDs in the category of drugs causing secondary osteoporosis. Risk factors for development of TZD-induced secondary osteoporosis are gender (women), age (elderly), and duration of treatment. TZDs exert their antidiabetic effects by activating peroxisome proliferator-activated receptor-γ (PPAR-γ) nuclear receptor, which controls glucose and fatty acid metabolism. In bone, PPAR-γ controls differentiation of cells of mesenchymal and hematopoietic lineages. PPAR-γ activation with TZDs leads to unbalanced bone remodeling: bone resorption increases and bone formation decreases. Laboratory research evidence points toward a possible separation of unwanted effects of PPAR-γ on bone from its beneficial antidiabetic effects by using selective PPAR-γ modulators. This review also discusses potential pharmacologic means to protect bone from detrimental effects of clinically used TZDs (pioglitazone and rosiglitazone) by using combinational therapy with approved antiosteoporotic drugs, or by using lower doses of TZDs in combination with other antidiabetic therapy. We also suggest a possible orthopedic complication, not yet supported by clinical studies, of delayed fracture healing in T2DM patients on TZD therapy

Caenorhabditis elegans Cyclin D/CDK4 and Cyclin E/CDK2 Induce Distinct Cell Cycle Re-Entry Programs in Differentiated Muscle Cells

Cell proliferation and differentiation are regulated in a highly coordinated and inverse manner during development and tissue homeostasis. Terminal differentiation usually coincides with cell cycle exit and is thought to engage stable transcriptional repression of cell cycle genes. Here, we examine the robustness of the post-mitotic state, using Caenorhabditis elegans muscle cells as a model. We found that expression of a G1 Cyclin and CDK initiates cell cycle re-entry in muscle cells without interfering with the differentiated state. Cyclin D/CDK4 (CYD-1/CDK-4) expression was sufficient to induce DNA synthesis in muscle cells, in contrast to Cyclin E/CDK2 (CYE-1/CDK-2), which triggered mitotic events. Tissue-specific gene-expression profiling and single molecule FISH experiments revealed that Cyclin D and E kinases activate an extensive and overlapping set of cell cycle genes in muscle, yet failed to induce some key activators of G1/S progression. Surprisingly, CYD-1/CDK-4 also induced an additional set of genes primarily associated with growth and metabolism, which were not activated by CYE-1/CDK-2. Moreover, CYD-1/CDK-4 expression also down-regulated a large number of genes enriched for catabolic functions. These results highlight distinct functions for the two G1 Cyclin/CDK complexes and reveal a previously unknown activity of Cyclin D/CDK-4 in regulating metabolic gene expression. Furthermore, our data demonstrate that many cell cycle genes can still be transcriptionally induced in post-mitotic muscle cells, while maintenance of the post-mitotic state might depend on stable repression of a limited number of critical cell cycle regulators

Development of a heart failure filter for Medline: an objective approach using evidence-based clinical practice guidelines as an alternative to hand searching

<p>Abstract</p> <p>Background</p> <p>Heart failure is a highly debilitating syndrome with a poor prognosis primarily affecting the elderly. Clinicians wanting timely access to heart failure evidence to provide optimal patient care can face many challenges in locating this evidence.</p> <p>This study developed and validated a search filter of high clinical utility for the retrieval of heart failure articles in OvidSP Medline.</p> <p>Methods</p> <p>A Clinical Advisory Group was established to advise study investigators. The study set of 876 relevant articles from four heart failure clinical practice guidelines was divided into three datasets: a Term Identification Set, a Filter Development Set, and a Filter Validation Set. A further validation set (the Cochrane Validation Set) was formed using studies included in Cochrane heart failure systematic reviews. Candidate search terms were identified via word frequency analysis. The filter was developed by creating combinations of terms and recording their performance in retrieving items from the Filter Development Set. The filter's recall was then validated in both the Filter Validation Set and the Cochrane Validation Set. A precision estimate was obtained post-hoc by running the filter in Medline and screening the first 200 retrievals for relevance to heart failure.</p> <p>Results</p> <p>The four-term filter achieved a recall of 96.9% in the Filter Development Set; 98.2% in the Filter Validation Set; and 97.8% in the Cochrane Validation Set. Of the first 200 references retrieved by the filter when run in Medline, 150 were deemed relevant and 50 irrelevant. The post-hoc precision estimate was therefore 75%.</p> <p>Conclusions</p> <p>This study describes an objective method for developing a validated heart failure filter of high recall performance and then testing its precision post-hoc. Clinical practice guidelines were found to be a feasible alternative to hand searching in creating a gold standard for filter development. Guidelines may be especially appropriate given their clinical utility. A validated heart failure filter is now available to support health professionals seeking reliable and efficient access to the heart failure literature.</p

Food for pollinators: quantifying the nectar and pollen resources of urban flower meadows

Planted meadows are increasingly used to improve the biodiversity and aesthetic amenity value of urban areas. Although many ‘pollinator-friendly’ seed mixes are available, the floral resources these provide to flower-visiting insects, and how these change through time, are largely unknown. Such data are necessary to compare the resources provided by alternative meadow seed mixes to each other and to other flowering habitats. We used quantitative surveys of over 2 million flowers to estimate the nectar and pollen resources offered by two exemplar commercial seed mixes (one annual, one perennial) and associated weeds grown as 300m2 meadows across four UK cities, sampled at six time points between May and September 2013. Nectar sugar and pollen rewards per flower varied widely across 65 species surveyed, with native British weed species (including dandelion, Taraxacum agg.) contributing the top five nectar producers and two of the top ten pollen producers. Seed mix species yielding the highest rewards per flower included Leontodon hispidus, Centaurea cyanus and C. nigra for nectar, and Papaver rhoeas, Eschscholzia californica and Malva moschata for pollen. Perennial meadows produced up to 20x more nectar and up to 6x more pollen than annual meadows, which in turn produced far more than amenity grassland controls. Perennial meadows produced resources earlier in the year than annual meadows, but both seed mixes delivered very low resource levels early in the year and these were provided almost entirely by native weeds. Pollen volume per flower is well predicted statistically by floral morphology, and nectar sugar mass and pollen volume per unit area are correlated with flower counts, raising the possibility that resource levels can be estimated for species or habitats where they cannot be measured directly. Our approach does not incorporate resource quality information (for example, pollen protein or essential amino acid content), but can easily do so when suitable data exist. Our approach should inform the design of new seed mixes to ensure continuity in floral resource availability throughout the year, and to identify suitable species to fill resource gaps in established mixes