Genetic professionals' reports of nondisclosure of genetic risk information within families

Patients attending genetic clinics are often the main gatekeepers of information for other family members. There has been much debate about the circumstances under which professionals may have an obligation, or may be permitted, to pass on personal genetic information about their clients but without their consent to other family members. We report findings from the first prospective study investigating the frequency with which genetics professionals become concerned about the failure of clients to pass on such information to their relatives. In all, 12 UK and two Australian regional genetic services reported such cases over 12 months, including details of actions taken by professionals in response to the clients' failure to disclose information. A total of 65 cases of nondisclosure were reported, representing

Ion channel gates: comparative analysis of energy barriers.

The energetic profile of an ion translated along the axis of an ion channel should reveal whether the structure corresponds to a functionally open or closed state of the channel. In this study, we explore the combined use of Poisson–Boltzmann electrostatic calculations and evaluation of van der Waals interactions between ion and pore to provide an initial appraisal of the gating state of a channel. This approach is exemplified by its application to the bacterial inward rectifier potassium channel KirBac3.1, where it reveals the closed gate to be formed by a ring of leucine (L124) side chains. We have extended this analysis to a comparative survey of gating profiles, including model hydrophobic nanopores, the nicotinic acetylcholine receptor, and a number of potassium channel structures and models. This enables us to identify three gating regimes, and to show the limitation of this computationally inexpensive method. For a (closed) gate radius of 0.4 nm

Northern Ireland's Consent to the Climate Change Act 2008: An Illusion?

This is the first in a two-part analysis of Northern Ireland’s engagement with the climate governance regime created by the UK Climate Change Act 2008. It contends that UK devolution has shaped this national regime and may itself be shaped by the national low carbon transition, particularly in the case of the UK’s most devolved region. In essence, while Northern Ireland’s consent to the application of the Act appeared to represent a long-term commitment to share power in the interests of present and future generations and thus to devolution itself, this first article argues that it was also potentially illusory. The second article argues that making an effective commitment to climate governance will require its devolved administration to allow constitutional arrangements designed for conflict resolution to mature. Failure to do so will have important implications for the UK’s putative ‘national’ low carbon transition and the longer term viability of devolution in the region.

The Social Politics of Breastfeeding: Norms, Situations and Policy Implications

This paper aims to explore the assumptions concerning the dynamics of human action underpinning breastfeeding promotion campaigns in the UK. Drawing on qualitative interviews with mothers, the ways in which three problematic assumptions shape both the promotion and experience of contemporary breastfeeding promotion campaigns are explored, in the light of Joas’s theorisation of action’s creativity and pragmatism. Public health efforts to establish breastfeeding as a rational standard against which good mothering can be judged, in ways which rely on a de-contextualised understanding of human action as instrumentally rational, where bodies are imagined as pliable instruments of human intentions, are explored as they play out in the experiences of women embarking on motherhood. The paper concludes that a target-driven health-promotion policy, relying on a mechanistic account of social and emotional life, is contributing to the burden of early motherhood in ways that are not conducive to infant and maternal health and attachment.

Photometric observations of the Type Ia SN 2002er in UGC 10743

Extensive light and colour curves for the Type Ia supernova (SN Ia) SN 2002er are presented as part of the European Supernova Collaboration. We have collected UBVRI photometry from 11 different telescopes covering the phases from 7 d before until 619 d after maximum light. Corrections for the different instrumental systems and the non-thermal spectrum of the supernova (S-corrections) have been applied. With the densely sampled light curves we can make detailed comparisons to other well-observed objects. SN 2002er most closely resembles SN 1996X after maximum, but clearly shows a different colour evolution before peak light and a stronger shoulder in V and R bands compared to other well-observed SNe Ia. In particular, the rise time appears to be longer than what is expected from the rise time versus decline rate relation. We use several methods to determine the reddening towards SN 2002er based on the colour evolution at near peak and at late phases. The uvoir (bolometric) light curve shows great similarity with SN 1996X, but also indications of a higher luminosity, longer rise time and a more pronounced shoulder 25 d past maximum. The interpretation of the light curves was carried out with two independent light curve codes. Both find that given the luminosity of SN 2002er the Ni-56 mass exceeds 0.6 M-circle dot with preferred values near 0.7 M-circle dot. Uncertainties in the exact distance to SN 2002er are the most serious limitation of this measurement. The light-curve modelling also indicates a high level of mixing of the nickel in the explosion of SN 2002er.

Transient pumping of a Ni-like Ag x-ray laser with a subpicosecond pump pulse in a traveling-wave irradiation geometry

We report what is to our knowledge the first demonstration of a transient x-ray laser pumped by a 350-fs pulse in a traveling-wave irradiation geometry. For a 500-fs pump pulse the traveling-wave irradiation was found to have a strong effect on enhancing the Ni-like silver 4d-4p lasing emission at 13.9 nm. The signal enhancement was significantly less when the pulse duration was lengthened to 1.7 ps. The experimental observations are well reproduced by a simple model when the duration of gain is taken of the order of 15-20 ps. For the 500-fs pulse a gain coefficient of 14.5 cm(-1) was measured for plasma lengths up to 7 mm. Refraction of the amplified photons is believed to be the main cause of the limitation of the effective amplification length. (C) 2000 Optical Society of America.

Potentiation of Inflammatory CXCL8 Signalling Sustains Cell Survival in PTEN-deficient Prostate Carcinoma

Background: Inflammation and genetic instability are enabling characteristics of prostate carcinoma (PCa). Inactivation of the tumour suppressor gene phosphatase and tensin homolog (PTEN) is prevalent in early PCa. The relationship of PTEN deficiency to inflammatory signalling remains to be characterised.

Objective: To determine how loss of PTEN functionality modulates expression and efficacy of clinically relevant, proinflammatory chemokines in PCa.

Design, setting and participants: Experiments were performed in established cell-based PCa models, supported by pathologic analysis of chemokine expression in prostate tissue harvested from PTEN heterozygous (Pten(+/-)) mice harbouring inactivation of one PTEN allele.

Interventions: Small interfering RNA (siRNA)- or small hairpin RNA (shRNA)-directed strategies were used to repress PTEN expression and resultant interleukin-8 (CXCL8) signalling, determined under normal and hypoxic culture conditions.

Outcome measurements and statistical analysis: Changes in chemokine expression in PCa cells and tissue were analysed by real-time polymerase chain reaction (PCR), immunoblotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry; effects of chemokine signalling on cell function were assessed by cell cycle analysis, apoptosis, and survival assays.

Results and limitations: Transient (siRNA) or prolonged (shRNA) PTEN repression increased expression of CXCL8 and its receptors, chemokine (C-X-C motif) receptor (CXCR) 1 and CXCR2, in PCa cells. Hypoxia-induced increases in CXCL8, CXCR1, and CXCR2 expression were greater in magnitude and duration in PTEN-depleted cells. Autocrine CXCL8 signalling was more efficacious in PTEN-depleted cells, inducing hypoxia-inducible factor-1 (HIF-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) transcription and regulating genes involved in survival and angiogenesis. Increased expression of the orthologous chemokine KC was observed in regions displaying atypical cytologic features in Pten(+/-) murine prostate tissue relative to normal epithelium in wild-type PTEN (Pten(WT)) glands. Attenuation of CXCL8 signalling decreased viability of PCa cells harbouring partial or complete PTEN loss through promotion of G1 cell cycle arrest and apoptosis. The current absence of clinical validation is a limitation of the study.

Conclusions: PTEN loss induces a selective upregulation of CXCL8 signalling that sustains the growth and survival of PTEN-deficient prostate epithelium.

Educational assessment policy and practice - a matter of ethics

Long-standing concerns within the field of educational assessment consider the impact of assessment policy and practice as matters of equity, inequality and social justice.Yet educational assessment policy and practice continues to have powerful social consequences for key users such as children and young people.This paper re-positions these consequences as a matter of ethics.It uses the work of Messick to frame how ethical matters extend beyond test instruments into the realm of uses and impact. A case study of the 11+ school transfer system in Northern Ireland is presented to illustrate ethical dilemmas emerging as a consequence of actions and decisions of using assessment systems for particular purposes.In looking forward to how we might attend to ethical matters in assessment policy and practice, a consideration of a children’s rights approach is outlined that may provide a moral and legal framework for action.

Anticipatory Planning Reveals Segmentation of Cortical Motor Output During Action Observation

It has been argued that the variation in brain activity that occurs when observing another person reflects a representation of actions that is indivisible, and which plays out in full once the intent of the actor can be discerned. We used transcranial magnetic stimulation to probe the excitability of corticospinal projections to 2 intrinsic hand muscles while motions to reach and grasp an object were observed. A symbolic cue either faithfully indicated the required final orientation of the object and thus the nature of the grasp that was required, or was in conflict with the movement subsequently displayed. When the cue was veridical, modulation of excitability was in accordance with the functional role of the muscles in the action observed. If however the cue had indicated that the alternative grasp would be required, modulation of output to first dorsal interosseus was consistent with the action specified, rather than the action observed-until the terminal phase of the motion sequence during which the object was seen lifted. Modulation of corticospinal output during observation is thus segmented-it progresses initially in accordance with the action anticipated, and if discrepancies are revealed by visual input, coincides thereafter with that of the action seen.

Effects of continuing professional development on group work practices in Scottish primary schools

The present study investigated the effects of a continuing professional development (CPD) initiative that provided collaborative group work skills training for primary school teachers. The study collected data from 24 primary school classrooms in different schools in a variety of urban and rural settings. The sample was composed of 332 pupils, aged 9-12 years old, and 24 primary school teachers. Results indicated that the CPD initiative had a significant impact on the attainment of pupils in science. In addition, data indicated that the CPD promoted effective discourse and pupil dialogue during science lessons. Pre-test and post-test observation scores were significantly different in terms of children giving of suggestions or courses of actions, offering of explanations, and telling someone to say something or carry out an action. Increases in effective dialogue were significantly correlated to increased science attainment, and teacher evaluations of the impact of the CPD were positive. Significant correlations were found between teacher evaluation of impact upon pupil learning and increased attainment in science. The design and structure of CPD initiatives and the implications for practice, policy and future research are explored.

Assessment of a zoomed global model for the North Sea by comparison with a conventional nested regional model

Assessment of marine downscaling of global model simulations to the regional scale is a prerequisite for understanding ocean feedback to the atmosphere in regional climate downscaling. Major difficulties arise from the coarse grid resolution of global models, which cannot provide sufficiently accurate boundary values for the regional model. In this study, we first setup a stretched global model (MPIOM) to focus on the North Sea by shifting poles. Second, a regional model (HAMSOM) was performed with higher resolution, while the open boundary values were provided by the stretched global model. In general, the sea surface temperatures (SSTs) in the two experiments are similar. Major SST differences are found in coastal regions (root mean square difference of SST is reaching up to 2°C). The higher sea surface salinity in coastal regions in the global model indicates the general limitation of this global model and its configuration (surface layer thickness is 16 m). By comparison, the advantage of the absence of open lateral boundaries in the global model can be demonstrated, in particular for the transition region between the North Sea and Baltic Sea. On long timescales, the North Atlantic Current (NAC) inflow through the northern boundary correlates well between both model simulations (R~0.9). After downscaling with HAMSOM, the NAC inflow through the northern boundary decreases by ~10%, but the circulation in the Skagerrak is stronger in HAMSOM. The circulation patterns of both models are similar in the northern North Sea. The comparison suggests that the stretched global model system is a suitable tool for long-term free climate model simulations, and the only limitations occur in coastal regions. Regarding the regional studies focusing on the coastal zone, nested regional model can be a helpful alternative.

The Human Rights Act 1998 – Future Prospects

It is now over fifteen years since the Human Rights Act was enacted in November 1998. Although in legal terms it is difficult to argue with the proposition that the Act is working in an effective manner, in political terms the Act remains one of the most highly debated pieces of legislation on the UK statute books. In recent years there have been numerous calls for the repeal of the Act, and for its replacement with a ‘UK Bill of Rights’. Such calls led to the establishment of a Commission on a Bill of Rights, which issued its final report in December 2012. Little progress has since been made on the issue. One notable occurrence however was the introduction of the Human Rights Act 1998 (Repeal and Substitution) Bill, a Private Member’s Bill which was eventually withdrawn in March 2013. This article seeks to assess the current situation regarding the bill of rights debate, and ultimately the question of the future prospects of the Human Rights Act, an issue of immense legal significance. Overall, it will be questioned whether the enactment of a UK Bill of Rights would constitute an improvement on the current position under the Human Rights Act.

The European Convention on Human Rights Act 2003 – Ten Years On

The European Convention on Human Rights Act 2003 has now been in force in Ireland for ten years. This article analyses the Act itself and the impact which it has had on the Irish courts during the first decade of its operation. The use of the European Convention on Human Rights in the Irish courts prior to the enactment of the legislation is discussed, as are the reasons for the passing of the Act. The relationship between the Act and the Irish Constitution is examined, as is the jurisprudence of the Irish courts towards the interpretative obligation found in section 2(1), and the duty placed upon organs of the State by section 3(1). The article ends with a number of observations regarding the impact which the Act has had on the Irish courts at a more general level. Comparisons will be drawn with the UK’s Human Rights Act 1998 throughout the discussion.

A Novel Bradykinin-Related Dodecapeptide (RVALPPGFTPLR) from the Skin Secretion of the Fujian Large-Headed Frog (Limnonectes fujianensis) Exhibiting Unusual Structural and Functional Features

Bradykinin-related peptides (BRPs) are significant components of the defensive skin secretions of many anuran amphibians, and these secretions represent the source of the most diverse spectrum of such peptides so far encountered in nature. Of the many families of bioactive peptides that have been identified from this source, the BRPs uniquely appear to represent homologues of counterparts that have specific distributions and receptor targets within discrete vertebrate taxa, ranging from fishes through mammals. Their broad spectra of actions, including pain and inflammation induction and smooth muscle effects, make these peptides ideal weapons in predator deterrence. Here, we describe a novel 12-mer BRP (RVALPPGFTPLR-RVAL-(L1, T6, L8)-bradykinin) from the skin secretion of the Fujian large-headed frog (Limnonectes fujianensis). The C-terminal 9 residues of this BRP (-LPPGFTPLR) exhibit three amino acid substitutions (L/R at Position 1, T/S at Position 6 and L/F at Position 8) when compared to canonical mammalian bradykinin (BK), but are identical to the kinin sequence present within the cloned kininogen-2 from the Chinese soft-shelled turtle (Pelodiscus sinensis) and differ from that encoded by kininogen-2 of the Tibetan ground tit (Pseudopodoces humilis) at just a single site (F/L at Position 8). These data would imply that the novel BRP is an amphibian defensive agent against predation by sympatric turtles and also that the primary structure of the avian BK, ornithokinin (RPPGFTPLR), is not invariant within this taxon. Synthetic RVAL-(L1, T6, L8)-bradykinin was found to be an antagonist of BK-induced rat tail artery smooth muscle relaxation acting via the B2-receptor.

Second Equal Treatment Act for the commercial sector

This book analyses one of the first pieces of legislation promoted by Angela Merkel, who started her political career as a minister for women's equality under Helmut Kohl. The name of the Act, Second Equal Treatment Act, allured to the Equal Treatment Act of the 1950s which implemented the barest minimum requirements to make the German constitution's demand to guarantee equal rights for women more than a hollow formula. However, this Act, while abolishing blatant discrimination of women through statute in fields such as family law, did nothing to further substantive equality. In 1990, when Germany was reunited, women from Eastern Germany had a first hand experience what the absence of such furtherance meant under capitalism. Used to being at nor risk to fall into poverty just because they divorced, or decided to become a mother without male protection, to being in full employment and not at the mercy of payments by their husbands, women from Eastern Germany were dismissed in large numbers, and found themselves sent back to the kitchen. The first minister for women affairs from their ranks made the "2nd Equality Act", but this act did little more than the minimum required by the EEC legislation. Again, substantive equality was not addressed through German Federal legislation. This was left to some of the German states - whose competences were limited to the public services. Most of those states which did create positive action measures for women employed in the public services were governed not by Christian Democrats - but this was the theme of another book.