Arbitration using the closest offer principle of arbitrator behaviour

In this paper we introduce a model of arbitration decision making which generalizes several previous models of both conventional arbitration and final offer arbitration. We derive the equilibrium offers that risk neutral disputants would propose, and show how these offers would vary under different arbitration procedures. In particular, we show that optimal offers made under conventional arbitration will always be more extreme than those made under final offer arbitration.Natural Sciences and Engineering Research Council (NSERC) Discovery Gran

People’s beliefs about the meaning of crepitus in patellofemoral pain and the impact of these beliefs on their behaviour : a qualitative study

BACKGROUND: A feature of patellofemoral pain is joint crepitus. Several causes of crepitus have been described, but previous research has focused on the pathological meaning of crepitus. No research has demonstrated a definitive link between noise and pathology and its importance and meaning to patients is unresearched. OBJECTIVE: To explore the beliefs of patients with non-osteoarthritic patellofemoral pain regarding their crepitus, and how this impacts on their behaviour. DESIGN: Qualitative design using semi-structured interviews. METHOD: A general inductive approach was used as this is a previously unresearched topic. Underpinned by the health beliefs model, an interview schedule was used to reflect different elements. Inductive thematic analysis was used to generate themes to represent the dataset. Participants were 11 patients diagnosed with non-osteoarthritic patellofemoral pain, crepitus as one of their symptoms, referred to an outpatient clinic. RESULTS/FINDINGS: Three key themes emerged all with sub-themes within them. Firstly, belief about the noise had a sub-theme of search for and perceived meaning of noise. Symbolising ageing was another sub-theme whereby participants described feelings of premature ageing. The final sub-theme was emotional response with participants feeling a range of negative emotions. The second theme of the influence of others reveals participants describing two distinctly different relationships, one with friends and family and one with professionals. The final theme was avoiding the noise. A sub-theme of altering movement shows participants describing fear-avoidant behaviour. CONCLUSION: Crepitus is a poorly understood symptom that creates negative emotions, inaccurate etiological beliefs and ultimately leads to altered behaviour

Many Paths to Alzheimer's Disease: A Unifying Hypothesis Integrating Biological, Chemical, and Physical Risk Factors

Sporadic Alzheimer's disease (AD) is a complex, multifactorial disease. We should therefore expect to find many factors involved in its causation. The known neuropathology seen at autopsy in patients dying with AD is not consistently seen in all patients with AD and is sometimes seen in patients without dementia. This suggests that patients follow different paths to AD, with different people having slightly different combinations of predisposing physical, chemical and biologic risk factors, and varying neuropathology. This review summarizes what is known of the biologic and chemical predisposing factors and features in AD. We postulate that, underlying the neuropathology of AD is a progressive failure of neurons, with advancing age or other morbidity, to rid themselves of entropy, i.e., the disordered state resulting from brain metabolism. Understanding the diverse causes of AD may allow the development of new therapies targeted at blocking the paths that lead to dementia in each subset of patients

Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy.

Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-length Manduca sexta sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains. The structural elongation of the particle observed in cryo-EM was corroborated in solution using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO

Bile acids and neurological disease

This review will focus on how bile acids are being used in clinical trials to treat neurological diseases due to their central involvement with the gut-liver-brain axis and their physiological and pathophysiological roles in both normal brain function and multiple neurological diseases. The synthesis of primary and secondary bile acids species and how the regulation of the bile acid pool may differ between the gut and brain is discussed. The expression of several bile acid receptors in brain and their currently known functions along with the tools available to manipulate them pharmacologically are examined, together with discussion of the interaction of bile acids with the gut microbiome and their lesser-known effects upon brain glucose and lipid metabolism. How dysregulation of the gut microbiome, aging and sex differences may lead to disruption of bile acid signalling and possible causal roles in a number of neurological disorders are also considered. Finally, we discuss how pharmacological treatments targeting bile acid receptors are currently being tested in an array of clinical trials for several different neurodegenerative diseases

Neuroprotective role for RORA in Parkinson’s disease revealed by analysis of post-mortem brain and a dopaminergic cell line

Parkinson's disease (PD) is almost twice as prevalent in men, which has largely been attributed to neuroprotective effect of oestradiol in women. RORA (retinoic acid receptor-related orphan receptor alpha) regulates the transcription of central aromatase, the enzyme responsible for local oestradiol synthesis, simultaneously, RORA expression is regulated by sex hormones. Moreover, RORA protects neurones against oxidative stress, a key mechanism contributing to the loss of dopaminergic neurones in PD. Therefore, we hypothesized that there would be sex differences in RORA expression in the substantia nigra pars compacta (SNpc), which could contribute to sex differences observed in PD prevalence and pathogenesis. In a case control study, qPCR and western blot analyses were used to quantify gene and protein expression in the SNpc of post-mortem brains (n = 14 late-stage PD and 11 age and sex matched controls). The neuroprotective properties of a RORA agonist were then investigated directly using a cell culture toxin-based model of PD coupled with measures of viability, mitochondrial function and apoptosis. RORA was expressed at significantly higher levels in the SNpc from control females' brains compared to males. In PD, we found a significant increase in SNpc RORA expression in male PD compared to female PD. Treatment with a RORA agonist showed a significant neuroprotection in our cell culture model of PD and revealed significant effects on intracellular factors involved in neuronal survival and demise. This study is the first to demonstrate a sex specific pattern of RORA protein and gene expression in the SNpc of controls post-mortem human brains, and to show that this is differentially altered in male and female PD subjects, thus supporting a role for RORA in sex-specific aspects of PD. Furthermore, our in vitro PD model indicates mechanisms whereby a RORA agonist exerts its neuroprotective effect, thereby highlighting the translational potential for RORA ligands in PD

Validation of the Symptoms and Functioning Severity Scale in Residential Group Care

Tests that measure the emotional and behavioral problems of children and youth are typically not normed and standardized on youth diagnosed with disruptive behavior, particularly those youth in residential care. Yet professional standards mandate that before instruments are used with a specific population the psychometric properties need to be studied and re-established: specifically, psychometric properties, including validity, need to be evaluated (AERA, APA, & NCME, 1999). The purpose of the present study was to assess the validity characteristics of the Symptoms and Functioning Severity Scale (SFSS; Bickman, et al., 2010), a widely used test developed for use in outpatient clinics, with youth in a residential care program. The convergent validity of the SFSS was established with the large correlations (.78-.86) with the CBCL. Several binary classification analyses including specificity, area under the receiver operating characteristic curve, positive and negative likelihood ratios, and the Youden Index supported the validity of the SFSS. However, the sensitivity index was somewhat low indicating the test may produce a high level of false negatives. Limitations, future research and implications are discussed

Psychometric Evaluation of the Symptoms and Functioning Severity Scale (SFSS) Short Forms with Out-of-Home Care Youth

BACKGROUND—There is a need for brief progress monitoring measures of behavioral and emotional symptoms for youth in out-of-home care. The Symptoms and Functioning Severity Scale (SFSS; Bickman et al., 2010) is one measure that has clinician and youth short forms (SFSS-SFs); however, the psychometric soundness of the SFSS-SFs with youth in out-of-home care has yet to be examined. OBJECTIVE—The objective was to determine if the psychometric characteristics of the clinician and youth SFSS-SFs are viable for use in out-of-home care programs. METHODS—The participants included 143 youth receiving residential treatment and 52 direct care residential staff. The current study assessed internal consistency and alternate forms reliability for SFSS-SFs for youth in a residential care setting. Further, a binary classification test was completed to determine if the SFSS-SFs similarly classified youth as the SFSS full version for low- and elevated-severity. RESULTS—The internal consistency for the clinician and youth SFSS-SFs was adequate (α = .75 to .82) as was the parallel forms reliability (r = .85 to .97). The sensitivity (0.80 to 0.95), specificity (0.88 to 0.97), and overall accuracy (0.89 to 0.93) for differentiating low and elevated symptom severity was acceptable. CONCLUSIONS—The clinician and youth SFSS-SFs have acceptable psychometrics and may be beneficial for progress monitoring and additional research should clarify their potential for progress monitoring of youth in out-of-home programs

The Child Outcomes of a Behavior Model

Within 3-tier behavioral models, universal interventions are expected to prevent the onset of problem behavior in a majority of children altogether and to sustain improvements in child outcomes by the selected and indicated interventions. A cohort longitudinal design was used to assess the extent to which a 3-tier model achieves these expected outcomes. The respective universal, selected, and indicated interventions included Behavior and Academic Support and Enhancement. First Step to Success, and MultiSystemic Therapy. A total of 407 children in Grades K-3 from 1 of 4 longitudinal cohorts participated. The results of 2-level linear growth analyses indicate that the 3-tier behavior model achieved the anticipated outcomes with respect to social behavior. The results, limitations, and implications are discussed