An Outcome Evaluation of the Implementation of the Triple P – Positive Parenting Program in Hong Kong

The present study evaluated the effectiveness of the Positive Parenting Program (Triple P) with a sample of Chinese parents of children with early onset conduct related problems in Hong Kong. The participants consisted of 91 parents whose children attended maternal and child health centers and child assessment centers for service, and were between three to seven years old. Participants were randomly assigned to the intervention (TP) and a waitlist control group (WL. There was no significant difference in pre-intervention measures between the two groups. However, at post intervention, participants in the TP group reported significantly lower levels of child behavior problems, lower dysfunctional parenting styles, and higher parent sense of competence, compared to the WL group. Implications of these findings for the use of Triple P with families of Chinese descent are discussed

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility

We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with three or more cases of breast cancer. We identified one novel germline variant, R117G, in two separate families. To evaluate the possible association of R117G and two germline variants repo

Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone

It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions

A Novel Mass Hierarchy and Discrete Excitation Spectra from Quantum-Fluctuating D-branes

We elaborate further on a recently proposed scenario for generating a mass hierarchy through quantum fluctuations of a single D3 brane, which represents our world embedded in a bulk five-dimensional space time. In this scenario, the quantum fluctuations of the D3-brane world in the bulk direction, quantified to leading order via a `recoil' world-sheet logarithmic conformal field theory approach, result in the dynamical appearance of a supersymmetry breaking (obstruction) scale alpha. This may be naturally taken to be at the TeV range, in order to provide a solution to the conventional gauge-hierarchy problem. The bulk spatial direction is characterized by the dynamical appearance of an horizon located at +- 1/alpha, inside which the positive energy conditions for the existence of stable matter are satisfied. To ensure the correct value of the four-dimensional Planck mass, the bulk string scale M_s is naturally found to lie at an intermediate energy scale of 10^{14} GeV. As an exclusive feature of the D3-brane quantum fluctuations (`recoil') we find that, for any given M_5, there is a discrete mass spectrum for four-dimensional Kaluza-Klein (KK) modes of bulk graviton and/or scalar fields. KK modes with masses 0 <= m < sqrt{2}alpha << M_s are found to have wavefunctions peaked, and hence localized, on the D3 brane at z=0.Comment: 21 pages latex, three eps figures incorporate

A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers

Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3.54). These hotspots may b

Football friends: adolescent boys’ friendships inside an English professional football (soccer) academy.

This qualitative research draws on data from semi-structured, in-depth interviews to examine the friendships of twelve adolescent (14 and 15-year-old) boys within a professional football club Academy: a setting marked by competition for places. Findings highlight how boys fail to develop ‘deep’ friendships with other boys inside the club; their peer-relationships, even when described as ‘friendships,’ are devoid of trust and emotional intimacy. Instead, ‘being mates’ is experienced within parameters of instrumentalism and individualism leading to superficial and inauthentic friendships. There is some indication that boys developed closer friendships with boys outside of the Academy, suggesting that competition is implicated negatively in friendship-building and hinders the capabilities of these boys to develop close friendships with teammates. Concluding this paper, we acknowledge limitations of our data, discuss implications and challenges for football academies, and highlight directions for future research