The Link Between Classical Reserving and Granular Reserving Through Double Chain Ladder and its Extensions

The relationship of the chain ladder method to mathematical statistics has long been debated in actuarial science. During the nineties it became clear that the originally deterministic chain ladder can be seen as an autoregressive time series or as a multiplicative Poisson model. This paper draws on recent research and concludes that chain ladder can be seen as a structured histogram. This gives a direct link between classical aggregate methods and continuous granular methods. When the histogram is replaced by a smooth counter part, we have a continuous chain ladder model. Re-inventing classical chain ladder via double chain ladder and its extensions introduces statistically solid approaches of combining paid and incurred data with direct link to granular data approaches. This paper goes through some of the extensions of double chain ladder and introduces new approaches to incorporating and modelling incurred data

Cash flow generalisations of non-life insurance expert systems estimating outstanding liabilities

For as long as anyone remembers non-life insurance companies have used the so called chain ladder method to reserve for outstanding liabilities. When historical payments of claims are used as observations then chain ladder can be understood as estimating a multiplicative model. In most non-life insurance companies a mixture of paid data and expert knowledge, incurred data, is used as observations instead of just payments. This paper considers recent statistical cash flow models for asset-liability hedging, capital allocation and other management decision tools, and develops two new such methods incorporating available incurred data expert knowledge into the outstanding liability cash flow model. These two new methods unbundle the incurred data to aggregates of estimates of the future cash flow. By a re-distribution to the right algorithm, the estimated future cash flow is incorporated in the overall estimation process and considered as data. A statistical validation technique is developed for these two new methods and they are compared to the other recent cash flow methods. The two methods show to have a very good performance on the real-life data set considered

Determination of RET Sequence Variation in an MEN2 Unaffected Cohort Using Multiple-Sample Pooling and Next-Generation Sequencing

Multisample, nonindexed pooling combined with next-generation sequencing (NGS) was used to discover RET proto-oncogene sequence variation within a cohort known to be unaffected by multiple endocrine neoplasia type 2 (MEN2). DNA samples (113 Caucasians, 23 persons of other ethnicities) were amplified for RET intron 9 to intron 16 and then divided into 5 pools of <30 samples each before library prep and NGS. Two controls were included in this study, a single sample and a pool of 50 samples that had been previously sequenced by the same NGS methods. All 59 variants previously detected in the 50-pool control were present. Of the 61 variants detected in the unaffected cohort, 20 variants were novel changes. Several variants were validated by high-resolution melting analysis and Sanger sequencing, and their allelic frequencies correlated well with those determined by NGS. The results from this unaffected cohort will be added to the RET MEN2 database

Magnetic Dipole Sum Rules for Odd-Mass Nuclei

Sum rules for the total- and scissors-mode M1 strength in odd-A nuclei are derived within the single-j interacting boson-fermion model. We discuss the physical content and geometric interpretation of these sum rules and apply them to ^{167}Er and ^{161}Dy. We find consistency with the former measurements but not with the latter.Comment: 13 pages, Revtex, 1 figure, Phys. Rev. Lett. in pres

Effect of maternal panic disorder on mother-child interaction and relation to child anxiety and child self-efficacy

To determine whether mothers with panic disorder with or without agoraphobia interacted differently with their children than normal control mothers, 86 mothers and their adolescents (aged between 13 and 23 years) were observed during a structured play situation. Maternal as well as adolescent anxiety status was assessed according to a structured diagnostic interview. Results showed that mothers with panic disorder/agoraphobia showed more verbal control, were more criticizing and less sensitive during mother-child interaction than mothers without current mental disorders. Moreover, more conflicts were observed between mother and child dyadic interactions when the mother suffered from panic disorder. The comparison of parenting behaviors among anxious and non-anxious children did not reveal any significant differences. These findings support an association between parental over-control and rejection and maternal but not child anxiety and suggest that particularly mother anxiety status is an important determinant of parenting behavior. Finally, an association was found between children’s perceived self-efficacy, parental control and child anxiety symptoms

Nuclear Scissors Mode with Pairing

The coupled dynamics of the scissors mode and the isovector giant quadrupole resonance are studied using a generalized Wigner function moments method taking into account pair correlations. Equations of motion for angular momentum, quadrupole moment and other relevant collective variables are derived on the basis of the time dependent Hartree-Fock-Bogoliubov equations. Analytical expressions for energy centroids and transitions probabilities are found for the harmonic oscillator model with the quadrupole-quadrupole residual interaction and monopole pairing force. Deformation dependences of energies and $B(M1)$ values are correctly reproduced. The inclusion of pair correlations leads to a drastic improvement in the description of qualitative and quantitative characteristics of the scissors mode.Comment: 36 pages, 5 figures, the results of calculation by another method and the section concerning currents are adde

First observation of scissors mode states in an odd-mass nucleus

Nuclear resonance fluorescence experiments are reported to search for enhanced M1 scissors mode states in the deformed odd-mass nucleus Dy163. A concentration of dipole strengths near 3 MeV excitation energy is found, which fits nicely into the systematics observed for M1 excitations in the neighboring even-even Dy isotopes. The observed strength distribution and the decay branching ratios are discussed in the context of the interacting boson-fermion model.Dirección General de Investigación Científica y Técnica PB89-063

Analysis of multiple single nucleotide polymorphisms closely positioned in the ovine PRNP gene using linear fluorescent probes and melting curve analysis

<p>Abstract</p> <p>Background</p> <p>Resistance and susceptibility to scrapie has been associated with single nucleotide polymorphisms located within codons 136, 154 and 171 of the ovine prion protein gene (<it>PRNP</it>). Dual-labelled HyBeacon probes were developed to analyse single and clustered polymorphisms within these and neighbouring codons.</p> <p>Methods</p> <p>Extracted DNAs and unpurified blood samples were genotyped with respect to polymorphisms in <it>PRNP </it>codons 136, 141, 154 and 171. PCR amplicons were investigated using a LightTyper instrument, measuring the stability of probe/target hybridisation through peak melting temperatures and determining the sequence of nucleotides at polymorphic sites.</p> <p>Results</p> <p>The performance of HyBeacon assays was evaluated in a validation study comparing genotypes with those obtained using a primer extension assay (Sequenom MassEXTEND) analysed on a MALDI-ToF mass spectrometer. Over 12,000 sheep samples were successfully genotyped, reliably detecting A¹³⁶, V¹³⁶, T¹³⁶, T¹³⁷, L¹⁴¹, F¹⁴¹R¹⁵⁴, H¹⁵⁴, L¹⁶⁸, R¹⁷¹, Q¹⁷¹, H¹⁷¹and K¹⁷¹sequence variants using only 4 HyBeacon probes.</p> <p>Conclusion</p> <p>HyBeacon assays provide an extremely robust and accurate method for the analysis of single and clustered <it>PRNP </it>polymorphisms in a high-throughput format. The flexibility of the diagnostic tests ensures that samples are correctly genotyped even in the presence of additional sequence variations that flank the polymorphisms of interest. Such sequence variations may also be neutralised using universal bases such as 5-nitroindole if required.</p

Germline Mutations in NFKB2 Implicate the Noncanonical NF-κB Pathway in the Pathogenesis of Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by antibody deficiency, poor humoral response to antigens, and recurrent infections. To investigate the molecular cause of CVID, we carried out exome sequence analysis of a family diagnosed with CVID and identified a heterozygous frameshift mutation, c.2564delA (p.Lys855Serfs∗7), in NFKB2 affecting the C terminus of NF-κB2 (also known as p100/p52 or p100/p49). Subsequent screening of NFKB2 in 33 unrelated CVID-affected individuals uncovered a second heterozygous nonsense mutation, c.2557C>T (p.Arg853∗), in one simplex case. Affected individuals in both families presented with an unusual combination of childhood-onset hypogammaglobulinemia with recurrent infections, autoimmune features, and adrenal insufficiency. NF-κB2 is the principal protein involved in the noncanonical NF-κB pathway, is evolutionarily conserved, and functions in peripheral lymphoid organ development, B cell development, and antibody production. In addition, Nfkb2 mouse models demonstrate a CVID-like phenotype with hypogammaglobulinemia and poor humoral response to antigens. Immunoblot analysis and immunofluorescence microscopy of transformed B cells from affected individuals show that the NFKB2 mutations affect phosphorylation and proteasomal processing of p100 and, ultimately, p52 nuclear translocation. These findings describe germline mutations in NFKB2 and establish the noncanonical NF-κB signaling pathway as a genetic etiology for this primary immunodeficiency syndrome