Canada’s Same-Sex Marriage Law: Exception to or Exemplar of Canada’s Family Policy?

Family policy in Canada is primarily concerned with assisting parents raise their children. This fairly singular approach to family policy is ironic given that Canada does not have a nationally-coordinated family policy. The development of a national family policy has been hampered by Canada’s decentralized governmental structure (i.e., federal and provincial, as well as territorial, governments) and other factors such as diverse geography and different traditions (e.g., a tradition of common law in English Canada, and civil law in Quebec). A recent addition to Canada’s family policy is Bill C-38, The Civil Marriage Act (2005), the law legalizing same-sex marriage. To put Canada’s same-sex marriage law into context, this article presents some preliminary statistics about same-sex marriage in Canada, and considers whether same-sex marriage legislation is a good example of Canadian family policy, or an exception to the rule that Canadian family policy focuses primarily on helping parents socialize their children

Validation of the self-reported hearing questions in the Irish Longitudinal Study on Ageing against the Whispered Voice Test

BACKGROUND: Self report questions are often used in population studies to assess sensory efficacy and decline. These questions differ in their validity in assessing sensory impairment depending on the wording of the question and the characteristics of the population. We tested the validity of the self-report questions on hearing efficacy (self reported hearing, ability in following a conversation, use of a telephone and use of hearing aids) used in The Irish Longitudinal Study on Ageing (TILDA). METHODS: We tested sensitivity and specificity, positive and negative predictive values of each question against the Whispered Voice Test, a relatively easy to administer and cost effective alternative to the standard audiometric test. RESULTS: In this population the question ‘Is your hearing (with or without a hearing appliance)/ Excellent/Very Good/Good/Fair/Poor?’ showed the best diagnostic value in relation to the other questions (sensitivity 55.56% and specificity 94.67%). The question ‘Can you use a normal telephone?’ was deemed ineffective because of a very poor sensitivity (5.56%) and was proposed for exclusion from subsequent waves of TILDA. CONCLUSIONS: We showed that this validity check was useful to select the questions that most effectively assess hearing deficits and provided crucial information for the subsequent waves. We argue that longitudinal studies using self-reports of sensory efficacy would benefit from a similar check

Novel approaches to assess cellular interactions and their role in the pathology and treatment of lymphoproliferative disorders

Background: Migration and homing are essential to B-lymphocyte mediated immunity, and are driven by rapid, directed, and appropriate reorganisation of the actin cytoskeleton. Important observations have linked the cytoskeletal-rearrangements made by leukaemic B-lymphocytes of chronic lymphocytic leukaemia (CLL) to disease pathology. In particular, cytoskeletal alterations mediated by B-cell receptor (BCR) engagement or chemokine-binding are recognised to be central to the migration of CLL cells to lymphoid tissues, where they engage in the complex cellular and molecular interactions that underlie their survival, proliferation, and drug resistance. Further emphasising this importance, has been the observation that highly effective small molecule inhibitors that target key components of the BCR signalling machinery, such as Bruton’s tyrosine kinase (BTK), disrupt the migratory behaviour of CLL cells, and that this may, at least in part, underlie their clinical effect. Detailed characterisation of the highly dynamic cytoskeletal alterations in CLL may, therefore, inform novel therapeutic interventions, particularly for subsets with unmet clinical needs, such as those with mutations affecting the tumour protein P53 (TP53), ataxia telangiectasia mutated (ATM), or Notch receptor 1 (NOTCH1) genes, which are all more frequent in IGHV-unmutated disease. This work describes the development of techniques to characterise and quantify morphological responses to inhibitors, aiming to produce a quantitative description of cytoskeletal changes relating to specific signalling pathways, and to suggest rational drug combinations in the disorder. Methods: Primary CLL cells were cultured at high density with autologous T-lymphocytes and monocytes in the presence of specific signal inhibitors. The morphological responses of leukaemic cells were determined using a range of microscopic techniques, including scanning electron microscopy, and immunocytofluorescent detection of cytoskeletal and plasma membrane components. Cytoskeletal alterations were evaluated via computer-aided morphometric analyses of cell shape parameter, homotypic cellular interactions, and migration, generating a precise description of changes to the polymerised F-actin cytoskeleton and cell behaviour. Matrigel™ matrix models were combined with transmission electron microscopy to study cellular morphology within a 3D tumour microenvironment (TME)-like setting. Immunogold labelling of specific proteins within neoplastic lymphocytes was performed to allow visualisation of protein localisation changes in response to signal inhibition at the ultrastructure level. Results: This study tested inhibitors targeting different signalling pathways as a ‘proof of principle’ evaluation to determine whether the morphological and behavioural responses induced could be effectively distinguished from one another and quantitatively described. Inhibition of BTK by ibrutinib resulted in uniform populations of globular cells with retained polarity and, consequently, increased amoeboid motility. BTK blockage is recognised to impair integrin-mediated retention of leukaemic cells within tissue niches, leading to the observed peripheral blood lymphocytosis seen in CLL patients receiving ibrutinib. Reduced integrin-mediated motility was associated with impaired homotypic cellular interactions within IGHV-mutated cases specifically, indicating that this subgroup may have a greater dependency on elongated-type migration for permitting pro-survival cellular contact than their IGHV-unmutated counterparts. Disruption of Rho-associated protein kinase 1 (ROCK1) activity by Y-27632 lead to impaired actomyosin-mediated retraction of cytoskeletal processes. Loss of the ROCK1-induced cytoskeletal asymmetry required for effective cell migration resulted in reduced CLL cellular interactions; however, CXCL12-driven motility was attenuated in IGHV¬-mutated cases alone. The Abelson kinase 1 (ABL1) inhibitor imatinib caused CLL cells to acquire a globular phenotype with frequent microvilli, similar to that of B-lymphocytes isolated directly from the peripheral blood. Transient cellular interactions were markedly reduced by imatinib, whereas elongated-type motility, being a largely ABL1-independent process, was unaltered. The morphological and behavioural responses of CLL cells were compared to those observed in mantle cell lymphoma (MCL) cell lines. These cells lines, which were utilised as a surrogate model for BTK inhibitor sensitivity in CLL, demonstrated that the establishment of anterior-posterior morphology, mediated by the activity of ROCK1 and ABL1, is essential for effective trafficking of B-lymphocytes to protective niches, regardless of ibrutinib sensitivity. Blockage of NOCTH1 signalling by gamma-secretase inhibitors (GSIs) PF-03084014 and R04929097 resulted in varying morphological responses, possibly indicating differences in NOTCH1 activation between CLL cases. Despite chemotaxis being identified as a key NOTCH1-regulated process, CLL and NOTCH1-mutated MCL cells demonstrated enhanced directional transmigration with GSI treatments. MCL cell lines were utilised to model the effects of GSI sensitivity in CLL. In contrast, NOTCH1-unmutated MCL cells displayed unaltered migration with PF-03084014 pre-treatment, consistent with reports of low GSI sensitivity in MCL cells exhibiting unmutated NOTCH1, and reduced chemotaxis with R04929097. The developed 3D ex vivo culture system preserved CLL cell viability, migration, and dynamic cellular interactions, as demonstrated by flow cytometry and time-lapse live-cell imaging. Interrogation with transmission electron microscopy enabled high-resolution visualisation of cell morphology within a TME-like setting; however, further optimisation of immunogold labelling of effector proteins is required. Conclusion: Using novel imaged-based morphometric analyses, distinct signal inhibitor-induced cytoskeletal adaptations were identified in CLL B-lymphocytes. This approach may be applied to prognostically-defined subgroups or resistant cases to provide in-depth characterisation of morphological responses to novel therapeutic agents and to assess treatment responses within the TME. These observations, when combined with transcriptional data, may allow more effective combinational targeting of behavioural signatures unique to the patient and, thus, improve treatment outcomes in the disease.Plymouth and District Leukaemia Fun

Barriers to Utilizing Medicaid Smoking Cessation Benefits

Introduction. Smoking is the number one preventable cause of deathin the United States. Under the Affordable Care Act, Kansas Medicaidcovers all seven FDA-approved smoking cessation therapies.However, it is estimated only 3% of Kansas Medicaid smokers usetreatment compared to the national estimate of 10%. The objectiveis to determine systemic barriers in place that prevent optimal utilizationof Medicaid smoking cessation benefits among KU MedicalCenter Internal Medicine patients. Methods. For this quality improvement project, a population of 169Kansas Medicaid smokers was identified who had been seen at the KUInternal Medicine Clinic from January 1, 2015 - February 16, 2016.Phone surveys were completed with 62 individuals about smokingstatus, interest in using smoking cessation treatment options, andawareness of Medicaid coverage of treatment. Results. Of the 62 respondents, 24 (39%) were prescribed pharmacotherapyand 41 (66%) were interested in using smoking cessationtreatment. There were eight who had quit smoking. Of the remaining54 smokers, 31 (57%) were unaware that Medicaid would coverpharmacotherapy. Of 24 participants who received a prescription forpharmacotherapy, 13 (54%) were able to fill the prescription at no costusing the Medicaid benefit. Conclusion. The majority of respondents were interested in usingsmoking cessation treatment, yet three main barriers existed to usingMedicaid smoking cessation benefits: physicians not prescribingtreatment to patients, patients not aware of Medicaid coverage, andinadequate pharmacy filling. Improved physician and patient awarenessof Medicaid coverage will facilitate more patients receivingsmoking cessation therapy and ultimately quitting smoking.KS J Med 2017;10(4):88-91

Randomised cluster trial to support informed parental decision-making for the MMR vaccine

Background In the UK public concern about the safety of the combined measles, mumps and rubella [MMR] vaccine continues to impact on MMR coverage. Whilst the sharp decline in uptake has begun to level out, first and second dose uptake rates remain short of that required for population immunity. Furthermore, international research consistently shows that some parents lack confidence in making a decision about MMR vaccination for their children. Together, this work suggests that effective interventions are required to support parents to make informed decisions about MMR. This trial assessed the impact of a parent-centred, multi-component intervention (balanced information, group discussion, coaching exercise) on informed parental decision-making for MMR. Methods This was a two arm, cluster randomised trial. One hundred and forty two UK parents of children eligible for MMR vaccination were recruited from six primary healthcare centres and six childcare organisations. The intervention arm received an MMR information leaflet and participated in the intervention (parent meeting). The control arm received the leaflet only. The primary outcome was decisional conflict. Secondary outcomes were actual and intended MMR choice, knowledge, attitude, concern and necessity beliefs about MMR and anxiety. Results Decisional conflict decreased for both arms to a level where an 'effective' MMR decision could be made one-week (effect estimate = -0.54, p < 0.001) and three-months (effect estimate = -0.60, p < 0.001) post-intervention. There was no significant difference between arms (effect estimate = 0.07, p = 0.215). Heightened decisional conflict was evident for parents making the MMR decision for their first child (effect estimate = -0.25, p = 0.003), who were concerned (effect estimate = 0.07, p < 0.001), had less positive attitudes (effect estimate = -0.20, p < 0.001) yet stronger intentions (effect estimate = 0.09, p = 0.006). Significantly more parents in the intervention arm reported vaccinating their child (93% versus 73%, p = 0.04). Conclusions Whilst both the leaflet and the parent meeting reduced parents' decisional conflict, the parent meeting appeared to enable parents to act upon their decision leading to vaccination uptake

An objective index of walkability for research and planning in the Sydney Metropolitan Region of New South Wales, Australia: an ecological study

Background: Walkability describes the capacity of the built environment to support walking for various purposes. This paper describes the construction and validation of two objective walkability indexes for Sydney, Australia. Methods: Walkability indexes using residential density, intersection density, land use mix, with and without retail floor area ratio were calculated for 5,858 Sydney Census Collection Districts in a geographical information system. Associations between variables were evaluated using Spearman’s rho (ρ). Internal consistency and factor structure of indexes were estimated with Cronbach’s alpha and principal components analysis; convergent and predictive validity were measured using weighted kappa (κw) and by comparison with reported walking to work at the 2006 Australian Census using logistic regression. Spatial variation in walkability was assessed using choropleth maps and Moran’s I. Results: A three-attribute abridged Sydney Walkability Index comprising residential density, intersection density and land use mix was constructed for all Sydney as retail floor area was only available for 5.3% of Census Collection Districts. A four-attribute full index including retail floor area ratio was calculated for 263 Census Collection Districts in the Sydney Central Business District. Abridged and full walkability index scores for these 263 areas were strongly correlated (ρ=0.93) and there was good agreement between walkability quartiles (κw=0.73). Internal consistency ranged from 0.60 to 0.71, and all index variables loaded highly on a single factor. The percentage of employed persons who walked to work increased with increasing walkability: 3.0% in low income-low walkability areas versus 7.9% in low income-high walkability areas; and 2.1% in high income-low walkability areas versus 11% in high income-high walkability areas. The adjusted odds of walking to work were 1.05 (0.96–1.15), 1.58 (1.45–1.71) and 3.02 (2.76–3.30) times higher in medium, high and very high compared to low walkability areas. Associations were similar for full and abridged indexes. Conclusions: The abridged Sydney Walkability Index has predictive validity for utilitarian walking, will inform urban planning in Sydney, and will be used as an objective measure of neighbourhood walkability in a large population cohort. Abridged walkability indexes may be useful in settings where retail floor area data are unavailable

Maximum Power Efficiency and Criticality in Random Boolean Networks

Random Boolean networks are models of disordered causal systems that can occur in cells and the biosphere. These are open thermodynamic systems exhibiting a flow of energy that is dissipated at a finite rate. Life does work to acquire more energy, then uses the available energy it has gained to perform more work. It is plausible that natural selection has optimized many biological systems for power efficiency: useful power generated per unit fuel. In this letter we begin to investigate these questions for random Boolean networks using Landauer's erasure principle, which defines a minimum entropy cost for bit erasure. We show that critical Boolean networks maximize available power efficiency, which requires that the system have a finite displacement from equilibrium. Our initial results may extend to more realistic models for cells and ecosystems.Comment: 4 pages RevTeX, 1 figure in .eps format. Comments welcome, v2: minor clarifications added, conclusions unchanged. v3: paper rewritten to clarify it; conclusions unchange

Comparison of the microbial population in rabbits and guinea pigs by next generation sequencing

<div><p>This study aimed to determine the microbial composition of faeces from two groups of caecotrophagic animals; rabbits and guinea pigs. In addition the study aimed to determine the community present in the different organs in the rabbit. DNA was extracted from seven of the organs in wild rabbits (n = 5) and from faecal samples from domesticated rabbits (n = 6) and guinea pigs (n = 6). Partial regions of the small ribosomal sub-unit were amplified by PCR and then the sequences present in each sample were determined by next generation sequencing. Differences were detected between samples from rabbit and guinea pig faeces, suggesting that there is not a microbial community common to caecotrophagic animals. Differences were also detected in the different regions of the rabbits’ digestive tracts. As with previous work, many of the organisms detected were Firmicutes or unclassified species and there was a lack of Fibrobacteres, but for the first time we observed a high number of Bacteroidetes in rabbit samples. This work re-iterates high levels of Firmicutes and unclassified species are present in the rabbit gut, together with low number of Fibrobacteres. This suggests that in the rabbit gut, organisms other than the Fibrobacteres must be responsible for fibre digestion. However observation of high numbers of Bacteroidetes suggests that this phylum may indeed have a role to play in digestion in the rabbit gut.</p></div

Development and initial validation of the Northwick Park Therapy Dependency Assessment

Objectives: To describe the development and initial validation of the Northwick Park Therapy Dependency Assessment (NPTDA) as a measure of therapy interventions in neurorehabilitation