Report of the Coding Committee of the Association for European Paediatric Cardiology

IN 1999 AND EARLY 2000, THE ASSOCIATION FOR European Paediatric Cardiology published the European Paediatric Cardiac Code as independent but linked Short and Long Lists, containing 650 and 3876 primary terms respectively. The historical background and rationale for development of this coding system has been previously detailed, but essentially it followed a series of meeting of the coding committee of the Association between 1997-1999, during which a pre-existing Long List was adopted and then used to create the condensed Short List. The system was published as the recommended standard coding system for use across Europe, covering the diagnosis and therapy of children with congenital and acquired cardiac disease. The scope of the lists was to encompass the needs of all those involved with such patients, from the fetal cardiologist through to the specialist in adult congenital heart disease; and from the general paediatric cardiologist and cardiac surgeon, to those specialising in transcatheter interventions, paediatric electrophysiology, and paediatric echocardiographers. In addition, the code was crossmapped to the 9th and 10th revisions of the International Classification of Diseases ("ICD-9” and "ICD-10”) provided by the World Health Organisation in order to facilitate returns to central government, a requirement in most countries. In so doing, it was hoped to address the concerns of many centres that such information submitted by professional coding staff was often inaccurate due to the complex nature of congenital cardiac disease, together with the limited scope and vague terminology of the International listing

On the absence of ferromagnetism in typical 2D ferromagnets

We consider the Ising systems in $d$ dimensions with nearest-neighbor ferromagnetic interactions and long-range repulsive (antiferromagnetic) interactions which decay with a power, $s$, of the distance. The physical context of such models is discussed; primarily this is $d=2$ and $s=3$ where, at long distances, genuine magnetic interactions between genuine magnetic dipoles are of this form. We prove that when the power of decay lies above $d$ and does not exceed $d+1$, then for all temperatures, the spontaneous magnetization is zero. In contrast, we also show that for powers exceeding $d+1$ (with $d\ge2$) magnetic order can occur.Comment: 15 pages, CMP style fil

Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity

Mutations in LRRK2 are a common cause of familial and idiopathic Parkinson’s disease (PD). Recently, the LRRK2 GTPase domain R1398H variant was suggested in genetic studies to confer protection against PD but mechanistic data supporting this is lacking. Here, we present evidence that R1398H affects GTPase function, axon outgrowth, and Wnt signaling in a manner opposite to pathogenic LRRK2 mutations. LRRK2 R1398H GTPase domain dimerization and GTP hydrolysis were increased whereas GTP binding was reduced, leading to a decrease in active GTP-bound LRRK2. This protective variant also increased axon length of primary cortical neurones in comparison to wild-type LRRK2, whereas the R1441G LRRK2 pathogenic mutant decreased axon outgrowth. Importantly, R1398H enhanced the stimulatory effect of LRRK2 on canonical Wnt signaling whereas the G2385R risk variant, in accordance with all previously tested pathogenic LRRK2 mutants, had the opposite effect. Molecular modeling placed R1398H in close proximity to PD-causing mutations suggesting that this protective LRRK2 variant, like familial mutations, affects intramolecular RocCOR domain interactions. Thus, our data suggest that R1398H LRRK2 is a bona fide protective variant. The opposite effects of protective versus PD associated LRRK2 variants on GTPase function and canonical Wnt signaling activity also suggests that regulation of these two basic signaling mechanisms is important for neuronal function. We conclude that LRRK2 mediated Wnt signaling and GTPase function are fundamental in conferring disease susceptibility and have clear implications for therapeutic target identification

Past Arctic aliens have passed away, current ones may stay

Published version. Source at http://doi.org/10.1007/s10530-015-0937-9.Increased human activity and climate change are expected to increase the numbers and impact of alien species in the Arctic, but knowledge of alien species is poor in most Arctic regions. Through field investigations over the last 10 years, and review of alien vascular plant records for the high Arctic Archipelago Svalbard over the past 130 years, we explored long term trends in persistence and phenology. In total, 448 observations of 105 taxa have been recorded from 28 sites. Recent surveys at 18 of these sites revealed that alien species had disappeared at half of them. Investigations at a further 49 sites characterised by former human activity and/or current tourist landing sites did not reveal any alien species. Patterns of alien species distribution suggest that greater alien species richness is more likely to be aligned with ongoing human inhabitation than sites of transient use. The probability of an alien species being in a more advanced phenological stage increased with higher mean July temperatures. As higher mean July temperatures are positively correlated with more recent year, the latter finding suggests a clear warming effect on the increased reproductive potential of alien plants, and thus an increased potential for spread in Svalbard. Given that both human activity and temperatures are expected to increase in the future, there is need to respond in policy and action to reduce the potential for further alien species introduction and spread in the Arctic

The psychometric properties of three self-report screening instruments for identifying frail older people in the community

Background: Frailty is highly prevalent in older people. Its serious adverse consequences, such as disability, are considered to be a public health problem. Therefore, disability prevention in community-dwelling frail older people is considered to be a priority for research and clinical practice in geriatric care. With regard to disability prevention, valid screening instruments are needed to identify frail older people in time. The aim of this study was to evaluate and compare the psychometric properties of three screening instruments: the Groningen Frailty Indicator (GFI), the Tilburg Frailty Indicator (TFI) and the Sherbrooke Postal Questionnaire (SPQ). For validation purposes the Groningen Activity Restriction Scale (GARS) was added. Methods: A questionnaire was sent to 687 community-dwelling older people (>= 70 years). Agreement between instruments, internal consistency, and construct validity of instruments were evaluated and compared. Results: The response rate was 77%. Prevalence estimates of frailty ranged from 40% to 59%. The highest agreement was found between the GFI and the TFI (Cohen's kappa = 0.74). Cronbach's alpha for the GFI, the TFI and the SPQ was 0.73, 0.79 and 0.26, respectively. Scores on the three instruments correlated significantly with each other (GFI - TFI, r = 0.87; GFI - SPQ, r = 0.47; TFI - SPQ, r = 0.42) and with the GARS (GFI - GARS, r = 0.57; TFI - GARS, r = 0.61; SPQ - GARS, r = 0.46). The GFI and the TFI scores were, as expected, significantly related to age, sex, education and income. Conclusions: The GFI and the TFI showed high internal consistency and construct validity in contrast to the SPQ. Based on these findings it is not yet possible to conclude whether the GFI or the TFI should be preferred; data on the predictive values of both instruments are needed. The SPQ seems less appropriate for postal screening of frailty among community-dwelling older peopl

A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover.

Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is regulated. Here, we show that oligomerization of a homologous bacterial Roco protein depends on the nucleotide load. The protein is mainly dimeric in the nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding, leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD-associated mutation stabilizes the dimer and decreases the GTPase activity. This work thus provides insights into the conformational cycle of Roco proteins and suggests a link between oligomerization and disease-associated mutations in LRRK2

Is inhibition of kinase activity the only therapeutic strategy for LRRK2-associated Parkinson's disease?

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial Parkinson's disease (PD). Variation around the LRRK2 locus also contributes to the risk of sporadic PD. The LRRK2 protein contains a central catalytic region, and pathogenic mutations cluster in the Ras of complex protein C terminus of Ras of complex protein (mutations N1437H, R1441G/C and Y1699C) and kinase (G2019S and I2020T) domains. Much attention has been focused on the kinase domain, because kinase-dead versions of mutant LRRK2 are less toxic than kinase-active versions of the same proteins. Furthermore, kinase inhibitors may be able to mimic this effect in mouse models, although the currently tested inhibitors are not completely specific. In this review, we discuss the recent progress in the development of specific LRRK2 kinase inhibitors. We also discuss non-kinase-based therapeutic strategies for LRRK2-associated PD as it is possible that different approaches may be needed for different mutations