Sleep duration, sleep variability, and impairments of visual attention

Attentional networks are sensitive to sleep deprivation. However, variation in attentional performance as a function of normal sleep parameters is under-studied. We examined whether attentional performance is influenced by 1) individual differences in sleep duration; 2) sleep duration variability; and/or 3) their interaction. Fifty-seven healthy participants (61.4% female; mean age=32.37 years; SD=8.68) completed questionnaires, wore wrist actigraphy for one week, and subsequently completed the Attention Network Test. Sleep duration and sleep duration variability did not predict orienting score, executive control score or error rates. Sleep duration variability appeared to moderate the association between sleep duration with overall reaction time (β = -.34, t= -2.13, p=.04) and alerting scores (β= .43, t=2.94, p=.01), though further inspection of the data suggested that these were spurious findings. Time of testing was a significant predictor of alerting score (β=.35, t=2.96, p=.01), chronotype of orienting (β=.31, t=2.28, p=.03) and age of overall reaction time (β=.35, t=2.70, p=.01). Our results highlight the importance of examining the associations between variations in sleep-wake patterns and attentional networks in samples with greater variation in sleep, as well as the importance of rigorously teasing apart mechanisms of the sleep homeostat from those related to the circadian rhythm in studies examining cognition

Towards reflexive, dynamic and accountable community development practice

This thesis explores the limits and possibilities for community development practice to maintain dynamism and integrity in a professional context. There is a particular emphasis upon reflexivity and its relevance in processes of accountability towards both communities and state policy. The study was born out of dissonance surrounding the researcher’s community development practice mid-way through New Labour’s 1997 to 2010 administration. It argues that New Labour’s social functionalist approach proved to be problematic for the maintenance the reflexive and personal commitment necessary to the central dynamic of community development work. Although not specifically designed to consider feminist community development approaches, the questions emerged from the researcher’s feminist analysis of contemporary practice and the research itself was designed from this perspective. The design of the methods applied to the empirical research for this study are based upon those used in reflexive and transformative community development practice. The empirical work involves a case study surrounding the conditions for community development professional practice in North East England in 2007, ten years into New Labour’s last administration. This consisted of semi-structured interviews with a sample of twenty-four self-defined community development practitioners. Focus groups were conducted in 2009 to share the findings and to assist the researcher to take the analysis further. Aiming to generalize from a particular historical moment when the Government seemed to be supportive of community development work, during New Labour’s 1997 to 2010 administration, the thesis highlights some inherent tensions within the relationship between the state and the dynamism of community development and illustrates lessons that are widely applicable to its everyday practice. In conclusion this thesis argues that for community development practice to maintain dynamism and integrity in a state policy context it is vital that its personal dynamic is integral to forming future conceptions of professionalism. Moreover that supporting the personal and relational elements of community development practice requires the creation of liminal spaces where self-determination and the agency can be exercised. For, it is only under these practice conditions that the intersubjective relationships necessary for bilateral and horizontal professional accountability can be nurtured and developed

Unknowable bodies, unthinkable sexualities: lesbian and transgender legal invisibility in the Toronto women's bathhouse raid

Although litigation involving sexual orientation and gender identity discrimination claims has generated considerable public attention in recent years, lesbian and transgender bodies and sexualities still remain largely invisible in Anglo-American courts. While such invisibility is generally attributed to social norms that fail to recognize lesbian and transgender experiences, the capacity to 'not see' or 'not know' queer bodies and sexualities also involves wilful acts of ignorance. Drawing from R. v Hornick (2002) a Canadian case involving the police raid of a women's bathhouse, this article explores how lesbian and transgender bodies and sexualities are actively rendered invisible via legal knowledge practices, norms and rationalities. It argues that limited knowledge and limited thinking not only regulate the borders of visibility and belonging, but play an active part in shaping identities, governing conduct and producing subjectivity

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

Generalised Witt algebras and idealizers

Let $\Bbbk$ be an algebraically closed field of characteristic zero, and let $\Gamma$ be an additive subgroup of $\Bbbk$. Results of Kaplansky-Santharoubane and Su classify intermediate series representations of the generalised Witt algebra $W_\Gamma$ in terms of three families, one parameterised by ${\mathbb A}^2$ and two by ${\mathbb P}^1$. In this note, we use the first family to construct a homomorphism $\Phi$ from the enveloping algebra $U(W_\Gamma)$ to a skew extension of ${\Bbbk}[a,b]$. We show that the image of $\Phi$ is contained in a (double) idealizer subring of this skew extension and that the representation theory of idealizers explains the three families. We further show that the image of $U(W_\Gamma)$ under $\Phi$ is not left or right noetherian, giving a new proof that $U(W_\Gamma)$ is not noetherian. We construct $\Phi$ as an application of a general technique to create ring homomorphisms from shift-invariant families of modules. Let $G$ be an arbitrary group and let $A$ be a $G$-graded ring. A graded $A$-module $M$ is an intermediate series module if $M_g$ is one-dimensional for all $g \in G$. Given a shift-invariant family of intermediate series $A$-modules parametrised by a scheme $X$, we construct a homomorphism $\Phi$ from $A$ to a skew-extension of ${\Bbbk}[X]$. The kernel of $\Phi$ consists of those elements which annihilate all modules in $X$.Comment: 9 pages; to appear in J. Algebr

An evaluation of the Cygnet parenting support programme for parents of children with autism spectrum conditions

Parents of children on the autistic spectrum often struggle to understand the condition and, related to this, manage their child’s behaviour. Cygnet is a parenting intervention which aims to help parents address these difficulties, consequently improving parenting confidence. It is widely used in the United Kingdom (UK). Despite this, there have been few evaluations. This paper reports a small-scale pragmatic evaluation of Cygnet as it was routinely delivered in two English cities. A non-randomised controlled study of outcomes for parents (and their children) was conducted. Data regarding intervention fidelity and delivery costs were also collected. Parents either attending, or waiting to attend, Cygnet were recruited (intervention group: IG, n=35; comparator group: CG, n=32). Parents completed standardised measures of child behaviour and parenting sense of competence pre- and post-intervention, and at three-month follow-up (matched time points for CG). Longer-term outcomes were measured for the IG. IG parents also set specific child behaviour goals. Typically, the programme was delivered as specified by the manual. Attending Cygnet was associated with significant improvements in parenting satisfaction and the specific child behaviour goals. Findings regarding other outcomes were equivocal and further evaluation is required. We conclude that Cygnet is a promising intervention for parents of children with autism in terms of, at least, some outcomes

Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers

$\textbf{Background:}$ Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes $\textit{BRCA1}$ or $\textit{BRCA2}$. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. $\textbf{Methods:}$ We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through populationbased GWAS: for BC (overall, estrogen receptor [ER]–positive, and ER-negative) and for OC. Using data from 15 252 female $\textit{BRCA1}$ and 8211 $\textit{BRCA2}$ carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. $\textbf{Results:}$ The PRS for ER-negative BC displayed the strongest association with BC risk in $\textit{BRCA1}$ carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, $P$ = 8.2 $\times$ 10$^{-53}$). In $\textit{BRCA2}$ carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, $P$ = 7.2 $\times$ 10$^{-20}$). The OC PRS was strongly associated with OC risk for both $\textit{BRCA1}$ and $\textit{BRCA2}$ carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom AR deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for $\textit{BRCA2}$ carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. $\textbf{Conclusions:}$ BC and OC PRS are predictive of cancer risk in $\textit{BRCA1}$ and $\textit{BRCA2}$ carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management.Cancer Research U

3 dimensional modelling of early human brain development using optical projection tomography

BACKGROUND: As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain. Optical Projection Tomography (OPT) is a new technology which has been developed for rapidly generating digital 3D models of intact specimens. We have assessed the resolution of unstained neuronal structures within a Carnegie Stage (CS)17 OPT model and tested its use as a framework onto which anatomical structures can be defined and gene expression data mapped. RESULTS: Resolution of the OPT models was assessed by comparison of digital sections with physical sections stained, either with haematoxylin and eosin (H&E) or by immunocytochemistry for GAP43 or PAX6, to identify specific anatomical features. Despite the 3D models being of unstained tissue, peripheral nervous system structures from the trigeminal ganglion (~300 μm by ~150 μm) to the rootlets of cranial nerve XII (~20 μm in diameter) were clearly identifiable, as were structures in the developing neural tube such as the zona limitans intrathalamica (core is ~30 μm thick). Fourteen anatomical domains have been identified and visualised within the CS17 model. Two 3D gene expression domains, known to be defined by Pax6 expression in the mouse, were clearly visible when PAX6 data from 2D sections were mapped to the CS17 model. The feasibility of applying the OPT technology to all stages from CS12 to CS23, which encompasses the major period of organogenesis for the human developing central nervous system, was successfully demonstrated. CONCLUSION: In the CS17 model considerable detail is visible within the developing nervous system at a minimum resolution of ~20 μm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations