The effects of artificially induced anisometropia on stereomobilization

Stereomobilization refers to the time required to activate stereopsis and perceive depth. Previous studies have examined the temporal effects of stereomobilization but very few have focused on the effects of unbalanced corrections, such as those seen with monovision contact lens fits. A color Macintosh computer was used to asses the effects of increasing anisometropia on stereomobilization in 37 subjects. For each increased anisometropic difference between the eyes, stereomobilization demonstrated a significant reduction in percent correct with shortened presentation times. It was also found that patients tested with larger amounts of induced anisometropia needed to view targets for significantly longer periods of time to gain the same stereoscopic information that a person with lower levels of anisometropia could achieve in a fraction of the time. Of the times tested that were similar to a previous study by Thompson and Yudcovitch (1996), there was no significant difference (p\u3e0.05) found between the two data sets, thus demonstrating the repeatability of their experiment

Magnets, magic, and other anomalies:In defense of methodological naturalism

Funding for this research was provided by the John Templeton Foundation, grant number 59023Recent critiques of methodological naturalism (MN) claim that it fails by conflicting with Christian belief and being insufficiently humble. We defend MN by tracing the real history of the debate, contending that the story as it is usually told is mythic. We show how MN works in practice, including among real scientists. The debate is a red herring. It only appears problematic because of confusion among its opponents about how scientists respond to experimental anomalies. We conclude by introducing our preferred approach, Science‐Engaged Theology.PostprintPeer reviewe

Aerodynamic roughness parameters in cities: inclusion of vegetation

A widely used morphometric method (Macdonald et al. 1998) to calculate the zero-plane displacement (zd) and aerodynamic roughness length (z0) for momentum is further developed to include vegetation. The adaptation also applies to the Kanda et al. (2013) morphometric method which considers roughness-element height variability. Roughness-element heights (mean, maximum and standard deviation) of both buildings and vegetation are combined with a porosity corrected plan area and drag formulation. The method captures the influence of vegetation (in addition to buildings), with the magnitude of the effect depending upon whether buildings or vegetation are dominant and the porosity of vegetation (e.g. leaf-on or leaf-off state). Application to five urban areas demonstrates that where vegetation is taller and has larger surface cover, its inclusion in the morphometric methods can be more important than the morphometric method used. Implications for modelling the logarithmic wind profile (to 100 m) are demonstrated. Where vegetation is taller and occupies a greater amount of space, wind speeds may be slowed by up to a factor of three

Design principles in housing for people with complex physical and cognitive disability: towards an integrated framework for practice

To develop a research-based environmental framework to guide the design and construction of suitable residential dwellings for individuals with complex disability. An environmental approach to housing design and development recognises that there are physical, psychological and social components relating to housing design, dwelling location and the neighbourhood context, and that these elements interact to affect the physical, psychological, and social wellness of individuals. Following theoretical review and synthesis, a comprehensive set of design features that are conducive to residents’ wellness and quality of life are described. It is clear that housing design and development for people with complex disability ought to consider the physical, social, natural, symbolic, and care environment in relation to housing design, dwelling location, and the neighbourhood context for improved housing outcomes. An integrated housing design and development framework is presented. It is hoped this practical matrix/evaluative tool will inform future inclusive housing design and development decisions in Australia and internationally. The application of this framework is especially relevant to political climates striving to achieve design innovation to increase housing choice for people with complex disability

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect

CD6 and Syntaxin Binding Protein 6 Variants and Response to Tumor Necrosis Factor Alpha Inhibitors in Danish Patients with Rheumatoid Arthritis

<div><h3>Background</h3><p>TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA).</p> <h3>Methodology and Principal Findings</h3><p>In the DANBIO Registry we identified 237 TNFα inhibitor naïve patients with RA (81% women; median age 56 years; disease duration 6 years) who initiated treatment with infliximab (n = 160), adalimumab (n = 56) or etanercept (n = 21) between 1999 and 2008 according to national treatment guidelines. Clinical response was assessed at week 26 using EULAR response criteria. Based on literature, we selected 213 INDELS potentially related to RA and treatment response using the GeneVa® (Compugen) <em>in silico</em> database of 350,000 genetic variations in the human genome. Genomic segments were amplified by polymerase chain reaction (PCR), and genotyped by Sanger sequencing or fragment analysis. We tested the association between genotypes and EULAR good response versus no response, and EULAR good response versus moderate/no response using Fisher’s exact test. At baseline the median DAS28 was 5.1. At week 26, 68 (29%) patients were EULAR good responders, while 81 (34%) and 88 (37%) patients were moderate and non-responders, respectively. A 19 base pair insertion within the CD6 gene was associated with EULAR good response vs. no response (OR = 4.43, 95% CI: 1.99–10.09, p = 7.211×10⁻⁵) and with EULAR good response vs. moderate/no response (OR = 4.54, 95% CI: 2.29–8.99, p = 3.336×10⁻⁶). A microsatellite within the syntaxin binding protein 6 (STXBP6) was associated with EULAR good response vs. no response (OR = 4.01, 95% CI: 1.92–8.49, p = 5.067×10⁻⁵).</p> <h3>Conclusion</h3><p>Genetic variations within CD6 and STXBP6 may influence response to TNFα inhibitors in patients with RA.</p> </div

Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS

Suicidal Behavior and Alcohol Abuse

Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically-related intermediate phenotypes might influence the relationship between alcohol and suicide. Psychiatric disorders, including psychosis, mood disorders and anxiety disorders, as well as susceptibility to stress, might increase the risk of suicidal behavior, but may also have reciprocal influences with alcohol drinking patterns. Increased suicide risk may be heralded by social withdrawal, breakdown of social bonds, and social marginalization, which are common outcomes of untreated alcohol abuse and dependence. People with alcohol dependence or depression should be screened for other psychiatric symptoms and for suicidality. Programs for suicide prevention must take into account drinking habits and should reinforce healthy behavioral patterns

A rapid synthesis of the evidence on interventions supporting self-management for people with long-term conditions. (PRISMS Practical systematic RevIew of Self-Management Support for long-term conditions)

Background: Despite robust evidence concerning self-management for some long-term conditions (LTCs), others lack research explicitly on self-management and, consequently, some patient groups may be overlooked. Aim: To undertake a rapid, systematic overview of the evidence on self-management support for LTCs to inform health-care commissioners and providers about what works, for whom, and in what contexts. Methods: Self-management is ‘the tasks . . . individuals must undertake to live with one or more chronic conditions . . . [including] . . . having the confidence to deal with medical management, role management and emotional management of their conditions’. We convened an expert workshop and identified characteristics of LTCs potentially of relevance to self-management and 14 diverse exemplar LTCs (stroke, asthma, type 2 diabetes mellitus, depression, chronic obstructive pulmonary disease, chronic kidney disease, dementia, epilepsy, hypertension, inflammatory arthropathies, irritable bowel syndrome, low back pain, progressive neurological disorders and type 1 diabetes mellitus). For each LTC we conducted systematic overviews of systematic reviews of randomised controlled trials (RCTs) of self-management support interventions (‘quantitative meta-reviews’); and systematic overviews of systematic reviews of qualitative studies of patients’ experiences relating to self-management (‘qualitative meta-reviews’). We also conducted an original systematic review of implementation studies of self-management support in the LTCs. We synthesised all our data considering the different characteristics of LTCs. In parallel, we developed a taxonomy of the potential components of self-management support. Results: We included 30 qualitative systematic reviews (including 515 unique studies), 102 quantitative systematic reviews (including 969 RCTs), and 61 studies in the implementation systematic review. Effective self-management support interventions are multifaceted, should be tailored to the individual, their culture and beliefs, a specific LTC and position on the disease trajectory, and underpinned by a collaborative/communicative relationship between the patient and health-care professional (HCP) within the context of a health-care organisation that actively promotes self-management. Self-management support is a complex intervention and although many components were described and trialled in the studies no single component stood out as more important than any other. Core components include (1) provision of education about the LTC, recognising the importance of understanding patients’ pre-existing knowledge and beliefs about their LTC; (2) psychological strategies to support adjustment to life with a LTC; (3) strategies specifically to support adherence to treatments; (4) practical support tailored to the specific LTC, including support around activities of daily living for disabling conditions, action plans in conditions subject to marked exacerbations, intensive disease-specific training to enable self-management of specific clinical tasks; and (5) social support as appropriate. Implementation requires a whole-systems approach which intervenes at the level of the patient, the HCP and the organisation. The health-care organisation is responsible for providing the means (both training and time/material resources) to enable HCPs to implement, and patients to benefit from, self-management support, regularly evaluating self-management processes and clinical outcomes. More widely there is a societal need to address public understanding of LTCs. The lack of public story for many conditions impacted on patient help-seeking behaviour and public perceptions of need. Conclusions: Supporting self-management is inseparable from the high-quality care for LTCs. Commissioners and health-care providers should promote a culture of actively supporting self-management as a normal, expected, monitored and rewarded aspect of care. Further research is needed to understand how health service managers and staff can achieve this culture change in their health-care organisations. Study registration: This study is registered as PROSPERO CRD42012002898. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so