An exploration of clinical variables that enhance therapeutic alliance in patients seeking care for musculoskeletal pain: A mixed methods approach.

INTRODUCTION/OBJECTIVES: Therapeutic alliance (TA) is an integral part of building a patient and clinician relationship. TA begins at the initial encounter; however, the specific TA behavioural practices that are most impactful and linked to pain reduction and improved function remain unclear. The primary objective of this study was to explore physical therapist behaviours and interactions during the initial physical therapy evaluation and how they related to the patient's perception of TA. A secondary objective was to explore the relationship between TA, pain intensity, and function. METHODS: A mixed methods study was conducted. Pain intensity, TA and self-reported function were assessed at three time points. Spearman's Rho (ρ) was used to quantify if there was an association between increased TA and function and reduced pain intensity, while a checklist of TA themes and behavioural practices was used for the qualitative analysis. RESULTS: There was a statistically significant negative correlation between patient-perceived TA and pain intensity immediately after the initial evaluation (ρ = -0.39 [p = 0.048]). Behavioural practices associated with higher TA included information gathering, pausing to listen, using humour and transitions, and use of clarifying questions. Behavioural practices associated with patient-perceived lower TA interactions were lack of touch, the absence of pain neuroscience education, and not restating what the patient said during the interview. CONCLUSION: This study highlights a relationship between TA and reduction of pain intensity after the initial evaluation and identifies key behavioural practices that could positively and negatively impact TA during the clinical encounter.

Caveats to Exogenous Organic Delivery from Ablation, Dilution, and Thermal Degradation.

A hypothesis in prebiotic chemistry argues that organics were delivered to the early Earth in abundance by meteoritic sources. This study tests that hypothesis by measuring how the transfer of organic matter to the surface of Earth is affected by energy-dissipation processes such as ablation and airbursts. Exogenous delivery has been relied upon as a source of primordial material, but it must stand to reason that other avenues (i.e., hydrothermal vents, electric discharge) played a bigger role in the formation of life as we know it on Earth if exogenous material was unable to deliver significant quantities of organics. For this study, we look at various properties of meteors such as initial velocity and mass of the object, and atmospheric composition to see how meteors with different initial velocities and masses ablate. We find that large meteors do not slow down fast enough and thus impact the surface, vaporizing their components; fast meteors with low masses are vaporized during entry; and meteors with low velocities and high initial masses reach the surface. For those objects that survive to reach the surface, about 60 to >99% of the mass is lost by ablation. Large meteors that fragment are also shown to spread out over increasingly larger areas with increasing mass, and small meteors (~1 mm) are subjected to intense thermal heating, potentially degrading intrinsic organics. These findings are generally true across most atmospheric compositions. These findings provide several caveats to extraterrestrial delivery models that—while a viable point source of organics—likely did not supply as much prebiotic material as an effective endogenous production route.

Progressive growth in epibulbar complex choristomas: report of 2 cases and review of literature.

PURPOSE: To report 2 patients with progressive complex choristomas and to review the literature on this subject. DESIGN: Interventional case reports. METHODS: Clinical and pathologic correlation was performed on 2 patients with progressive epibulbar choristomas. PubMed database was searched to identify all the previously reported cases of progressive epibulbar choristomas (using key words choristoma, dermoid, growth, progression, and evolution). RESULTS: Growth of the epibulbar choristomas was noted in infancy in 1 patient with oculoectodermal syndrome and in puberty in another otherwise healthy patient. Both lesions were identified histopathologically as complex choristomas. In addition to the characteristic choristomatous tissues, both lesions demonstrated increased vascularity, inflammatory infiltrate, and fibroblast proliferation within myxomatous stroma. Review of the literature identified 4 patients with progressive complex choristomas, 1 of whom demonstrated histopathologic findings similar to those of the 2 cases reported here. CONCLUSIONS: Epibulbar choristomas rarely enlarge, likely secondary to reactive changes within the tissue manifested by increased vascularity, inflammatory cell infiltration, and fibroblast proliferation with deposition of myxomatous stroma.

Subjective frequency norms for 330 Spanish simple and compound words.

Ratings were collected from 102 native speakers of Spanish on the subjective frequency of occurrence of 330 Spanish words, including 120 deverbal compounds and their constituents. These ratings were found to be highly reliable, whether items were analyzed together or separately by type (i.e., compounds, nouns, verbs), as evidenced by indexes of internal consistency and test-retest reliability that were equal to or greater than .98. The validity of the normative ratings was attested to by statistically significant correlations with objective frequency, estimated at .63 for all items together, and .41, .51, and .78 for compounds, nouns, and verbs, respectively. Among the substantive issues addressed was the potential dependency in ratings for compounds and their associated verb-noun constituents. No relationship was discerned, supporting the idea that compound and constituent ratings are statistically independent in this experimental task. The theoretical and methodological implications of the findings are discussed. The ratings can be downloaded from http://brm.psychonomic-journals.org/content/supplemental.

[Imagery norms and subjective frequency of 1,760 monosyllabic words in the French language]. / Normes d'imagerie et de fréquence subjective pour 1,760 mots monosyllabiques de la langue française.

This study aimed at providing subjective frequency and imageability norms for a sample of 1,760 monosyllabic French words and thereby, increasing the pool of normative data available for research in cognitive science and language processing. The results indicate that the reliability of the estimates is high, with coefficients ranging between .93 and .99 for the frequency and imageability ratings. External validity was investigated by calculating correlations with ratings drawn from all similar studies and for which the number of shared items was sufficient. These coefficients vary between .73 and .88 for subjective frequency and between .64 and .97 for imageability. The correlation between subjective frequency and imageability in the present study was significant and relatively high (r = .64). The implications of these results for the selection of experimental stimuli for research are discussed.

Serotonin-immunoreactive neurons in the postnatal MAO-A KO mouse lateral superior olive project to the inferior colliculus.

During development, serotonin (5-HT) accumulates in thalamic, noradrenergic, and auditory brainstem neurons that are non-serotonergic in the adult. As demonstrated in somatosensory thalamocortical projections, this accumulation of 5-HT is necessary for the precise organization of afferent terminal arborizations. Accumulation of 5-HT in the auditory brainstem appears to be most robust in the lateral superior olive (LSO) and as demonstrated in the MAO-A knockout mouse, is present at birth and begins to taper off at postnatal day 7 (P7). During the same developmental period, 5-HT-positive terminal endings in the inferior colliculus (IC) have been reported to be more numerous than in the adult [O. Cases, C. Lebrand, B. Giros, T. Vitalis, E. De Maeyer, M. Caron, D. Price, P. Gaspar, I. Seif, Plasma membrane transporters of serotonin, dopamine and norepinephrine mediate serotonin accumulation in atypical locations in the developing brain of monoamine oxidase A knock-outs, J. Neurosci. 18 (1998) 6914-6927]. It has been hypothesized that the serotonergic terminal fibers in the IC belong to neurons whose cell bodies reside in the LSO. Here, we provide evidence based on morphological and tract-tracing data that LSO neurons containing serotonin in the perinatal mouse, project to the IC. These data suggest that, similar to thalamocortical projections in other sensory systems, 5-HT may play a role in regulating development of LSO terminal arbors in the IC.

Corroborating biased indicators: global and local agreement among objective and subjective estimates of printed word frequency.

The internal validity of several types of experiments in experimental psychology and neuroscience depends in part on the possibility of controlling or manipulating critical lexical variables such as word frequency of occurrence. Two ways of estimating this variable are (1) objective frequency counts and (2) subjective ratings of word frequency. Each method produces estimates that generally agree (i.e., they are highly correlated) but that disagree substantially concerning the relative frequency of a number of words. To investigate this issue more closely, the global and local agreement of subjective frequency estimates was examined in detail for a pool of 6,202 words drawn from the OMNILEX database of French words (Desrochers, 2006; www.omnilex.uottawa.ca). The results indicated that objective and subjective frequencies are strongly correlated, subjective frequencies share a significant amount of bias variance with other lexical characteristics (e.g., imageability), and the codeterminants of subjective frequency are in an antagonistic relationship with one another. The implications of these results for the selection of lexical stimuli are discussed, and multiple variables to aid in item selection are reported. Supplemental materials for this study may be downloaded from brm.psychonomic-journals.org/content/supplemental.

Subjective frequency and imageability ratings for 3,600 French nouns.

Subjective frequency and imageability estimates for a sample of 3,600 French nouns were collected from two independent groups of 72 young adults each. Both groups received standard instructions and provided their ratings on a 7-point scale. The timing, sequencing, presentation of lexical stimuli, and recording of responses were controlled by a computer. All estimates of internal consistency and test-retest reliability (> or =.98) confirm the high level of precision and reliability of the ratings. Correlations with ratings drawn from similar studies were found to be positive and significant for subjective frequency (r > or = .85) and for imageability (r > or = .69). Subjective frequency was positively and significantly correlated with objective frequency estimates drawn from 10 different sources (r > or = .42). Subjective frequency and imageability were significantly correlated (r = .26), a relationship that was driven primarily by a sudden drop in imageability ratings for words with a subjective frequency rating below 2.5. The methodological implications of these findings are discussed. The ratings can be downloaded as supplemental materials from brm.psychonomic-journals.org/content/supplemental.

Experimental evidence that the serotonin transporter mediates serotonin accumulation in LSO neurons of the postnatal mouse.

During the same postnatal period of development when their terminal projection patterns in the midbrain are maturing, lateral superior olivary (LSO) neurons are immunoreactive for serotonin (5-HT). As there is no evidence that LSO neurons synthesize 5-HT, it is likely that they accumulate 5-HT via the 5-HT transporter. To determine if the 5-HT transporter is responsible for 5-HT inside postnatal mouse LSO neurons, pups (postnatal ages 5-6) were treated with fluoxetine and LSO neurons examined for 5-HT. We also evaluated whether LSO neurons containing 5-HT expressed the 5-HT transporter. To further rule out any potential synthesis of 5-HT, brainstem sections of mice at postnatal ages when 5-HT staining is the most robust were stained for the rate-limiting enzyme in the synthesis of 5-HT, tryptophan hydroxylase. Fluoxetine treatment reduced or in most cases, completely eliminated the number of neurons in the LSO stained for 5-HT. Postnatal LSO neurons containing 5-HT were immunoreactive for the 5-HT transporter; in older animals in which 5-HT was no longer observed in the LSO neurons, 5-HT transporter expression was similarly absent. Further, LSO neurons in mice at any age did not stain for tryptophan hydroxylase. These results indicate that LSO neurons express the functional 5-HT transporter to internalize 5-HT; this mechanism may serve to regulate extracellular 5-HT levels during maturation of their terminal endings in the inferior colliculus.

An SPSS implementation of the nonrecursive outlier deletion procedure with shifting z score criterion (Van Selst & Jolicoeur, 1994).

Sophisticated univariate outlier screening procedures are not yet available in widely used statistical packages such as SPSS. However, SPSS can accept user-supplied programs for executing these procedures. Failing this, researchers tend to rely on simplistic alternatives that can distort data because they do not adjust to cell-specific characteristics. Despite their popularity, these simple procedures may be especially ill suited for some applications (e.g., data from reaction time experiments). A user friendly SPSS Production Facility implementation of the shifting z score criterion procedure (Van Selst & Jolicoeur, 1994) is presented in an attempt to make it easier to use. In addition to outlier screening, optional syntax modules can be added that will perform tedious database management tasks (e.g., restructuring or computing means).

From phonemes to meaning: John Steinbeck's work examined.

Two novels were selected from two distinct periods in John Steinbeck's career, and text samples from each were pooled according to era. Using quantitative measures of text emotion, between-sample and norm-relative comparisons were computed to evaluate a priori expectations regarding differences in the use of implicit emotional information. These hypotheses reflected abstract characteristics that transcend the focus of a single novel. Analysis of word-based measures did not yield the between-sample differences expected. Rather, the hypotheses were supported by distinct patterns of phoneme distribution. The findings confirm and extend previous work by demonstrating that authors of prose manipulate the emotional quality of phonemes, and that the associated patterns can occur at a more abstract level than previously demonstrated.

In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers.

PURPOSE: The objective of this study was to evaluate the in vitro dissolution and in vivo absorption of D,L-threo-methylphenidate (MPH) from a novel bimodal release formulation (Ritalin LA capsule) compared with an immediate-release formulation (Ritalin IR tablet) in healthy volunteers. METHODS: The bimodal release formulation contains 50% of the dose in the immediate-release (IR) beads and 50% in polymethacrylate-coated, delayed-release (DR) beads. To better understand the impact of dissolution from the DR beads on oral absorption of MPH, three Ritalin LA formulations with different dissolution profiles for the DR beads (referred to as slow-, medium and fast-release formulations) were prepared, and tested together with the immediate-release formulation in 18 healthy male and female volunteers after a single oral dose under fasted conditions. The rate and extent of oral absorption of MPH were evaluated based on the overall Cmax, tmax and AUC values, as well as the Cmax, tmax and AUC values for each individual peak of the bimodal plasma concentration-time profile. The in vivo absorption-time profile was also examined by deconvolution. RESULTS: All three Ritalin LA formulations demonstrated similar bimodal plasma concentration-time profiles with two peak concentrations observed at approximately 2 and approximately 6 h post dose, mimicking that of Ritalin IR tablets given 4 h apart. Deconvolution results showed that the absorption of MPH was biphasic, with a rapid absorption phase between 0 to approximately 2 h, and a somewhat slower second absorption between approximately 3-6 h, consistent with the in vitro bimodal release characteristics of Ritalin LA formulation. The three Ritalin LA formulations were bioequivalent to one another based on the overall Cmax and AUC values and the corresponding values describing the first and second peaks, although their in vitro dissolution profiles for the DR beads were different. Compared with Ritalin IR, the Ritalin LA formulation demonstrated a similar rate of absorption for the first peak, a lower second Cmax and a higher trough concentration between peaks, as well as similar overall plasma AUC. CONCLUSIONS: Following a single oral drug administration, Ritalin LA demonstrated a two-peak plasma concentration-time profile, similar to that of the IR formulation given 4 h apart, but with less fluctuation in the plasma concentration-time profile. The in vivo biphasic absorption of MPH appeared to be well correlated with the bimodal dissolution characteristics of this new Ritalin LA formulation, and some changes in the dissolution profiles for the DR beads appeared not to affect the overall bioavailability of MPH in humans.

Foreign particles testing in orally inhaled and nasal drug products.

The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) presents this paper in order to contribute to public discussion regarding best approaches to foreign particles testing in orally inhaled and nasal drug products (OINDPs) and to help facilitate development of consensus views on this subject. We performed a comprehensive review of industry experience and best practices regarding foreign particles testing in OINDPs, reviewed current guidances and techniques, and considered health and safety perspectives. We also conducted and assessed results of an industry survey on U.S. Food and Drug Administration requirements for foreign particles testing. We provide here a result of our review and survey: a summary of industry best practices for testing and controlling foreign particles in OINDPs and proposals for developmental characterization and quality control strategies for foreign particles. We believe that clear consensus-based recommendations and standards for foreign particles testing and control in OINDPs are needed. The proposals contained in this paper could provide a starting point for developing such consensus recommendations and standards.

A New Method for Simultaneous Measurement of Cl- , Br- , NO3- , SCN- , and I- at Sub-ppm Levels in Ground Water.

Ion-exchange high performance liquid chromatography coupled with ultraviolet absorption detection is shown to be a rapid and sensitive method for analysis of some common anions in water. Sensitivity of measurement is approximately 50 ppb for NO-2 , NO-3 , Br- , I- , and SCN- while Cl- has a detection limit in the one to ten ppm range. Chromatograms require 8 to 13 minutes to complete. Analyses are performed on either of two stationary phases (Whatman SAX 10 µm or Brownlee anion exchange) depending on the anions of interest in the analysis and their interferences.