An inability to exclude visual noise in migraine

- Purpose: People with migraine are relatively poor at judging the direction of motion of coherently moving signal dots when interspersed with noise dots drifting in random directions, a task known as motion coherence. Although this has been taken as evidence of impoverished global pooling of motion signals, it could also arise from unreliable coding of local direction (of each dot), or an inability to segment signal from noise (noise-exclusion). The aim of this study was to determine how these putative limits contribute to impoverished motion processing in migraine. - Methods: Twenty-two participants with migraine (mean age, 34.7 ± 8.3 years; 16 female) and 22 age- and sex-matched controls (mean age, 34.4 ± 6.2 years) performed a motion-coherence task and a motion-equivalent noise task, the latter quantifying local and global limits on motion processing. In addition, participants were tested on analogous equivalent noise paradigms involving judgments of orientation and size, so that the specificity of any findings (to visual dimension) could be ascertained. - Results: Participants with migraine exhibited higher motion-coherence thresholds than controls (P = 0.01, independent t-test). However, this difference could not be attributed to deficits in either local or global processing since they performed normally on all equivalent noise tasks (P > 0.05, multivariate ANOVA). - Conclusions: These findings indicate that motion perception in the participants with migraine was limited by an inability to exclude visual noise. We suggest that this is a defining characteristic of visual dysfunction in migraine, a theory that has the potential to integrate a wide range of findings in the literature

Osteoarthritis: a narrative review of molecular approaches to disease management

Osteoarthritis (OA) is a chronic, progressive degenerative whole joint disease that affects the articular cartilage, subchondral bone, ligaments, capsule, and synovium. While it is still believed to be a mechanically driven disease, the role of underlying co-existing inflammatory processes and mediators in the onset of OA and its progression is now more appreciated. Post-traumatic osteoarthritis (PTOA) is a subtype of OA that occurs secondary to traumatic joint insults and is widely used in pre-clinical models to help understand OA in general. There is an urgent need to develop new treatments as the global burden is considerable and expanding. In this review, we focus on the recent pharmacological advances in the treatment of OA and summarize the most significant promising agents based on their molecular effects. Those are classified here into broad categories: anti-inflammatory, modulation of the activity of matrix metalloproteases, anabolic, and unconventional pleiotropic agents. We provide a comprehensive analysis of the pharmacological advances in each of these areas and highlight future insights and directions in the OA field

Preferred reporting items for studies mapping onto preference-based outcome measures: The MAPS statement

'Mapping' onto generic preference-based outcome measures is increasingly being used as a means of generating health utilities for use within health economic evaluations. Despite publication of technical guides for the conduct of mapping research, guidance for the reporting of mapping studies is currently lacking. The MAPS (MApping onto Preference-based measures reporting Standards) statement is a new checklist, which aims to promote complete and transparent reporting of mapping studies. The primary audiences for the MAPS statement are researchers reporting mapping studies, the funders of the research, and peer reviewers and editors involved in assessing mapping studies for publication. A de novo list of 29 candidate reporting items and accompanying explanations was created by a working group comprised of six health economists and one Delphi methodologist. Following a two-round, modified Delphi survey with representatives from academia, consultancy, health technology assessment agencies and the biomedical journal editorial community, a final set of 23 items deemed essential for transparent reporting, and accompanying explanations, was developed. The items are contained in a user friendly 23 item checklist. They are presented numerically and categorised within six sections, namely: (i) title and abstract; (ii) introduction; (iii) methods; (iv) results; (v) discussion; and (vi) other. The MAPS statement is best applied in conjunction with the accompanying MAPS explanation and elaboration document. It is anticipated that the MAPS statement will improve the clarity, transparency and completeness of reporting of mapping studies. To facilitate dissemination and uptake, the MAPS statement is being co-published by eight health economics and quality of life journals, and broader endorsement is encouraged. The MAPS working group plans to assess the need for an update of the reporting checklist in five years' time. This statement was published jointly in Applied Health Economics and Health Policy, Health and Quality of Life Outcomes, International Journal of Technology Assessment in Health Care, Journal of Medical Economics, Medical Decision Making, PharmacoEconomics, and Quality of Life Research

Book Reviews

Book Reviews The Roosevelt Court: A Study in Judicial Politics and Values By C.Herman Pritchett New York: The Macmillan Company, 1948, Pp. 314,$5.00 Lions Under the Throne By Charles P. Curtis, Jr. Boston: Houghton, Mifflin Company, 1947. Pp. 361.$3.50 The Nine Young Men By Wesley McCune New York: Harper & Bros.,1947. Pp. 293. $3.50 reviewer: William N. Ethridge, Jr. ========================== A Declaration of Legal Faith By Wiley Rutledge Lawrence, Kansas:University of Kansas Press, 1947. Pp. 82.$2.00 reviewer: M. G. Dakin The Papers of Walter Clark: 1857-1901, Vol. 1 Edited by Aubrey Lee Brooks and Hugh T. Leffler Chapel Hill, N. C.: University of North Carolina Press. 1948. Pp. xv, 607. $6.00 reviewer: A. B. Neil State Labor Relations Acts By Charles C. Killingsworth Chicago: University of Chicago Press, 1948. Pp. 328.$4.00 reviewer: C. M. Updegraff ============================== Book Notes Dangerous Words By Philip Wittenberg New York: Columbia University Press, 1947. Pp. 335. $5.00 Essentials of Libel By Paul P. Ashley Seattle: University of Washington Press, 1948. Pp. 71.$1.50. Law in Action Edited by Amicus Curiae, With an Introduction by Roscoe Pound New York: Crown Publishers, 1947. Pp. xiv, 498. $3.00 The Trial of Christ from a Legal and Scriptural Viewpoint By David K. Breed St. Louis: Thomas Law Book Company, 1948. Pp. 90.$2.5

On the Creation of Acceptable Conjoint Analysis Experimental Designs

Conjoint analysis studies typically utilize orthogonal fractional factorial experimental designs to construct a set of hypothetical stimuli. Occasionally, these designs include environmentally correlated attributes that can lead to stimulus profiles that are not representative of the subject's environment. To date, no one has proposed a remedy well-grounded in statistical theory. This note presents a new methodology utilizing combinatorial optimization procedures for creating modified fractional factorial designs that are as “orthogonal” as possible, which do not contain nonrepresentative stimulus profiles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72641/1/j.1540-5915.1991.tb00357.x.pd

Branching on multi-aggregated variables

open5siopenGamrath, Gerald; Melchiori, Anna; Berthold, Timo; Gleixner, Ambros M.; Salvagnin, DomenicoGamrath, Gerald; Melchiori, Anna; Berthold, Timo; Gleixner, Ambros M.; Salvagnin, Domenic

Macrophage Sub-Populations and the Lipoxin A4 Receptor Implicate Active Inflammation during Equine Tendon Repair

Macrophages (Mϕ) orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mϕ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured), sub-acute (3–6 weeks post injury) and chronically injured (>3 months post injury) superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mϕ sub-populations were quantified based on surface antigen expression of CD172a (pan Mϕ), CD14highCD206low (pro-inflammatory M1Mϕ), and CD206high (anti-inflammatory M2Mϕ) to assess potential polarised phenotypes. In addition, the Lipoxin A4 receptor (FPR2/ALX) was used as marker for resolving inflammation. Normal tendons were negative for both Mϕ and FPR2/ALX. In contrast, M1Mϕ predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mϕ polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by tenocytes was significantly upregulated in sub-acute but not chronic injury. Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in sub-acute and chronic injuries in contrast to low level expression in normal tendons. The combination of reduced FPR2/ALX expression and persistence of the M2Mϕ phenotype in chronic injury suggests a potential mechanism for incomplete resolution of inflammation after tendon injury. To investigate the effect of pro-inflammatory mediators on lipoxin A4 (LXA4) production and FPR2/ALX expression in vitro, normal tendon explants were stimulated with interleukin-1 beta and prostaglandin E2. Stimulation with either mediator induced LXA4 release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken together, our data suggests that although tenocytes are capable of mounting a protective mechanism to counteract inflammatory stimuli, this appears to be of insufficient duration and magnitude in natural tendon injury, which may potentiate chronic inflammation and fibrotic repair, as indicated by the presence of M2Mϕ

Histopathological and immunohistochemical evaluation of cellular response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch for tendon repair

We investigated endogenous tissue response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch intended for tendon repair. A sheep tendon injury model characterised by a natural history of consistent failure of healing was chosen to assess the biological potential of woven and aligned electrospun fibres to induce a reparative response. Patches were implanted into 8 female adult English Mule sheep. Significant infiltration of tendon fibroblasts was observed within the electrospun component of the patch but not within the woven component. The cellular infiltrate into the electrospun fibres was accompanied by an extensive network of new blood vessel formation. Tendon fibroblasts were the most abundant scaffold-populating cell type. CD45+, CD4+ and CD14+ cells were also present, with few foreign body giant cells. There were no local or systemic signs of excessive inflammation with normal hematology and serology for inflammatory markers three months after scaffold implantation. In conclusion, we demonstrate that an endogenous healing response can be safely induced in tendon by means of biophysical cues using a woven and electrospun patch

Physical Activity Levels of Patients Undergoing Bariatric Surgery in the Longitudinal Assessment of Bariatric Surgery (LABS) Study

Background- Bariatric surgery candidates' physical activity (PA) level may contribute to the variability of weight loss and body composition changes following bariatric surgery. However, there is little research describing the PA of patients undergoing bariatric surgery to inform PA recommendations in preparation for, and following, surgery. Objectives- Describe PA assessment in the LABS-2 study and report pre-surgery PA level. Examine relationships between objectively determined PA level and 1) BMI and 2) self-reported purposeful exercise. Setting- Six sites in the U.S. Methods- Participants wore an accelerometer and completed a PA diary. Standardized measures of height and weight were obtained. Results- Of 757 participants, 20% were sedentary (<5000 steps/day), 34% low active (5000-7499 steps/day), 27% somewhat active (7500-9999 steps/day), 14% active (10000-12499 steps/day), and 6% were highly active (greater than or equal to 12500 steps/day). BMI was inversely related to mean steps/day and mean steps/minute during the most active 30 minutes each day. The most commonly reported activities were walking, 44%; gardening, 11%; playing with children, 10%; and stretching, 7%. Self-report of minutes of exercise accounted for 2% of the variance in objectively determined steps. Conclusion- Patients present for bariatric surgery with a wide range of PA levels, with almost half categorized as somewhat active or active. BMI is inversely related to total amount and intensity of PA. Few patients report a regular pre-operative exercise regimen suggesting most PA is accumulated from activities of daily living. Patient report of daily minutes of walking or exercise may not be a reliable indication of their PA level. Originally published Surgery for Obesity and Related Diseases, Vol. 4, No. 6, Nov-Dec 200

Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine