Best friends and better coping: Facilitating psychological resilience through boys’ and girls’ closest friendships

This is a novel investigation of whether, and how, a single close supportive friendship may facilitate psychological resilience in socio-economically vulnerable British adolescents. A total of 409 adolescents (160 boys, 245 girls, four unknown), aged between 11 and 19 years, completed self-report measures of close friendship quality, psychological resilience, social support, and other resources. Findings revealed a significant positive association between perceived friendship quality and resilience. This relationship was facilitated through inter-related mechanisms of developing a constructive coping style (comprised of support-seeking and active coping), effort, a supportive friendship network, and reduced disengaged and externalising coping. While protective processes were encouragingly significantly present across genders, boys were more vulnerable to the deleterious effects of disengaged and externalizing coping than girls. We suggest that individual close friendships are an important potential protective mechanism accessible to most adolescents. We discuss implications of the resulting Adolescent Friendship and Resilience Model for resilience theories and integration into practice.

Empowering Human Services Organizations to Embrace Evidence-informed Practice: International Best Practices

Human service organizations are increasingly using knowledge as a mechanism for implementing change. Knowledge emerging from many sources that may include academic publications, grey literature, and service user and practitioner wisdom contributes toward informing best practice. The question is: how do we harness this knowledge to make practice more effective? This paper synthesizes the lessons learned from eight international organizations that have made a commitment to knowledge mobilization as an important priority in their mission and operation. The paper provides a conceptual model, tools and resources to help human services organizations create strategies for building, enhancing or sustaining their knowledge mobilization efforts. The paper describes a flexible blueprint for human service organizations to leverage knowledge mobilization efforts at all levels of service delivery.

On the diversity of superluminous supernovae: ejected mass as the dominant factor

We assemble a sample of 24 hydrogen-poor superluminous supernovae(SLSNe). Parameterizing the light-curve shape through rise and declinetime-scales shows that the two are highly correlated. Magnetar-poweredmodels can reproduce the correlation, with the diversity in rise anddecline rates driven by the diffusion time-scale. Circumstellarinteraction models can exhibit a similar rise-decline relation, but onlyfor a narrow range of densities, which may be problematic for thesemodels. We find that SLSNe are approximately 3.5 mag brighter and havelight curves three times broader than SNe Ibc, but that the intrinsicshapes are similar. There are a number of SLSNe with particularly broadlight curves, possibly indicating two progenitor channels, butstatistical tests do not cleanly separate two populations. The generalspectral evolution is also presented. Velocities measured from Fe II aresimilar for SLSNe and SNe Ibc, suggesting that diffusion timedifferences are dominated by mass or opacity. Flat velocity evolution inmost SLSNe suggests a dense shell of ejecta. If opacities in SLSNe aresimilar to other SNe Ibc, the average ejected mass is higher by a factor2-3. Assuming κ = 0.1 cm2 g-1, we estimate amean (median) SLSN ejecta mass of 10 M⊙ (6M⊙), with a range of 3-30 M⊙. Doubling theassumed opacity brings the masses closer to normal SNe Ibc, but with ahigh-mass tail. The most probable mechanism for generating SLSNe seemsto be the core collapse of a very massive hydrogen-poor star, forming amillisecond magnetar.

Genetic provenance and best practice woodland management: a case study in native alder (Alnus glutinosa)

In recent years, the native woodlands of Europe, including those of Britain and Ireland, have increasingly come under threat from a range of biotic and abiotic factors, and are therefore a conservation priority demanding careful management in order to realise their inherent ecological and cultural benefits. Because the distribution of genetic variation across populations and regions is increasingly considered an important component of woodland management, we carried out a population genetic analysis on black alder (Alnus glutinosa) across Northern Ireland in order to inform “best practice” strategies. Our findings suggest that populations harbour high levels of genetic diversity, with very little differentiation between populations. Significant F IS values were observed in over half of the populations analysed, however, which could reflect inbreeding as a result of the patchy occurrence of alder in Northern Ireland, with scattered, favourable damp habitats being largely isolated from each other by extensive tracts of farmland. Although there is no genetic evidence to support the broad-scale implementation of tree seed zones along the lines of those proposed for native woodlands in Great Britain, we suggest that the localised occurrence of rare chloroplast haplotypes should be taken into account on a case-by-case basis. This, coupled with the identification of populations containing high genetic diversity and that are broadly representative of the region as a whole, will provide a sound genetic basis for woodland management, both in alder and more generally for species that exhibit low levels of genetic differentiation.

Autosomal dominant retinitis pigmentosa:a new multi-allelic marker (D3S621) genetically linked to the disease locus (RP4)

We report the characterization of a new eight-allele microsatellite (D3S621) isolated from a human chromosome 3 library. Two-point and multi-locus genetic linkage analysis have shown D3S621 to co-segregate with the previously mapped RP4 (theta m = 0.12, Zm = 4.34) and with other genetic markers on the long arm of the chromosome, including D3S14 (R208) (theta m = 0.00, Zm = 15.10), D3S47 (C17) (theta m = 0.11, Zm = 4.95), Rho (theta m = 0.07, Zm = 1.37), D3S21 (L182) (theta m = 0.07, Zm = 2.40) and D3S19 (U1) (theta m = 0.13, Zm = 2.78). This highly informative marker, with a polymorphic information content of 0.78, should be of considerable value in the extension of linkage data for autosomal dominant retinitis pigmentosa with respect to locii on the long arm of chromosome 3.

Autosomal dominant retinitis pigmentosa:linkage to rhodopsin and evidence for genetic heterogeneity

Retinitis pigmentosa (RP) is the most prevalent human retinopathy of genetic origin. Chromosomal locations for X-linked RP and autosomal dominant RP genes have recently been established. Multipoint analyses with ADRP and seven markers on the long arm of chromosome 3 demonstrate that the gene for rhodopsin, the pigment of the rod photoreceptors, cosegregates with the disease locus with a maximum lod score of approximately 19, implicating rhodopsin as a causative gene. Recent studies have indicated the presence of a point mutation at codon 23 in exon 1 of rhodopsin which results in the substitution of histidine for the highly conserved amino acid proline, suggesting that this mutation is a cause of rhodopsin-linked ADRP. This mutation is not present in the Irish pedigree in which ADRP has been mapped close to rhodopsin. Another mutation in the rhodopsin gene or in a gene closely linked to rhodopsin may be involved. Moreover, the gene in a second ADRP pedigree, with Type II late onset ADRP, does not segregate with chromosome 3q markers, indicating that nonallelic as well as perhaps allelic genetic heterogeneity exists in the autosomal dominant form of this disease.

Epidermolysis bullosa:evidence for linkage to genetic markers on chromosome 1 in a family with the autosomal dominant simplex form

DNA from members of a three-generation pedigree of Irish origin, displaying an autosomal dominant simplex form of epidermolysis bullosa of the epidermolytic, simplex, or Koebner variety (EBS2), was analyzed for linkage with a set of markers derived from the long arm of chromosome 1. Two-point analysis revealed positive lod scores for five of these markers, AT3 (Z = 2.107, theta = 0), APOA2 (Z = 1.939, theta = 0.15), D1S66 (Z = 1.204, theta = 0), D1S13 (Z = 1.026, theta = 0.15), and D1S65 (Z = 0.329, theta = 0.15). Multilocus analysis, incorporating the markers D1S19, D1S16, D1S13, APOA2, D1S66, AT3, and D1S65, resulted in a lod score of 3 maximizing at AT3. These data strongly support previous tentative indications of linkage between EBS2 and genetic markers on the long arm of chromosome 1.

Autosomal dominant retinitis pigmentosa (ADRP):localization of an ADRP gene to the long arm of chromosome 3

Members of a large pedigree of Irish origin presenting with early onset Type I autosomal dominant retinitis pigmentosa (ADRP) have been typed for D3S47 (C17), a polymorphic marker from the long arm of chromosome 3. Significant, tight linkage of ADRP to D3S47, with a lod score of 14.7 maximizing at 0.00 recombination, has been obtained, hence localizing the ADRP gene (RP1) segregating in this pedigree to 3q.

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2sigma;2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2sigma;2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca<inf>o</inf>²⁺) homeostasis. To elucidate the role of AP2sigma;2 in Ca<inf>o</inf>²⁺ regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2sigma;2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2sigma;2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2sigma;2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2sigma;2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2sigma;2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.

Selecting the best targeted agent in first-line treatment of unresectable liver metastases from colorectal cancer:does the bench have the answers?

For physicians facing patients with organ-limited metastases from colorectal cancer, tumor shrinkage and sterilization of micrometastatic disease is the main goal, giving the opportunity for secondary surgical resection. At the same time, for the majority of patients who will not achieve a sufficient tumor response, disease control remains the predominant objective. Since FOLFOX or FOLFIRI have similar efficacies, the challenge is to define which could be the most effective targeted agent (anti-EGFR or anti-VEGF) to reach these goals. Therefore, a priori molecular identification of patients that could benefit from anti-EGFR or anti-VEGF monoclonal antibodies (i.e. the currently approved targeted therapies for metastatic colorectal cancer) is of critical importance. In this setting, the KRAS mutation status was the first identified predictive marker of response to anti-EGFR therapy. Since it has been demonstrated that tumors with KRAS mutation do not respond to anti-EGFR therapy, KRAS status must be determined prior to treatment. Thus, for KRAS wild-type patients, the choices that remain are either anti-VEGF or anti-EGFR. In this review, we present the most updated data from translational research programs dealing with the identification of biomarkers for response to targeted therapies.