Fractal relationships and spatial distribution of ore body modelling

The nature of spatial distributions of geological variables such as ore grades is of primary concern when modelling ore bodies and mineral resources. The aim of any mineral resource evaluation process is to determine the location, extent, volume and average grade of that resource by a trade off between maximum confidence in the results and minimum sampling effort. The principal aim of almost every geostatistical modelling process is to predict the spatial variation of one or more geological variables in order to estimate values of those variables at locations that have not been sampled. From the spatial analysis of these variables, in conjunction with the physical geology of the region of interest, the location, extent and volume, or series of discrete volumes, whose average ore grade exceeds a specific ore grade cut off value determined\u27 by economic parameters can be determined, Of interest are not only the volume and average grade of the material but also the degree of uncertainty associated with each of these. Geostatistics currently provides many methods of assessing spatial variability. Fractal dimensions also give us a measure of spatial variability and have been found to model many natural phenomenon successfully (Mandelbrot 1983, Burrough 1981), but until now fractal modelling techniques have not been able to match the versatility and accuracy of geostatistical methods. Fractal ideas and use of the fractal dimension may in certain cases provide a better understanding of the way in which spatial variability manifests itself in geostatistical situations. This research will propose and investigate a new application of fractal simulation methods to spatial variability and spatial interpolation techniques as they relate to ore body modelling. The results show some advantages over existing techniques of geostatistical simulation

Homologous recombination DNA repair defects in PALB2-associated breast cancers

© 2019, The Author(s). Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD

Patients’ views of treatment focused genetic testing (TFGT): some lessons for the mainstreaming of BRCA1 and BRCA2 testing

This paper explores patients' views and experiences of undergoing treatment-focused BRCA1 and BRCA2 genetic testing (TFGT), either offered following triaging to clinical genetics (breast cancer) or as part of a mainstreamed care pathway in oncology (ovarian cancer). Drawing on 26 in-depth interviews with patients with breast or ovarian cancer who had undergone TFGT, this retrospective study examines patients' views of genetic testing at this point in their care pathway, focusing on issues, such as initial response to the offer of testing, motivations for undergoing testing, and views on care pathways. Patients were amenable to the incorporation of TFGT at an early stage in their cancer care irrespective of (any) prior anticipation of having a genetic test or family history. While patients were glad to have been offered TFGT as part of their care, some questioned the logic of the test's timing in relation to their cancer treatment. Crucially, patients appeared unable to disentangle the treatment role of TFGT from its preventative function for self and other family members, suggesting that some may undergo TFGT to obtain information for others rather than for self

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs

Field hockey the coach and the player

xii, 259 p.; 24 cm

Vestibular schwannoma in a patient with neurofibromatosis type 1: clinical report and literature review

We describe a young patient with typical neurofibromatosis type 1 on the basis of a mutation in the NF1 gene, who was diagnosed with a unilateral vestibular schwannoma caused by a somatic mutation in the NF2 gene. This combination has not been described before. This report highlights the requirement for ongoing surveillance regarding other manifestations of neurofibromatosis type 2 in such patients, as mosaicism cannot be ruled out. In addition to the NF1 mutation, the NF2 mutation should be considered in such cases if pre-implantation genetic diagnosis in undertaken

A NEW X-RAY AMPLIFIER PUMPED BY THE KINETIC ENERGY OF CLUSTERS

A new type of laser amplifier with high gain (80%) and high amplification in the visible and ultraviolet range will still provide sufficient amplification for wavelengths of 100 Angstroms or less by a sequence of injections of energetic solid particles (pellets or clusters). Based on the experimental fact that electrons are laterally emitted from the focus of a laser a free electron laser amplifier was proposed based on the inversion of this experiment. That consists in converting translational electron into optical and oscillation energy of the laser beam. An energy transfer can be expected only from the transient processes of laser pulses. The generalization of this free electron laser towards the injection of solid clusters or dust particles with synchronized and calibrated high kinetic energies and other diffraction properties leads to a very highly efficient (80%) laser with high gain even in the x-ray range. The transient switching process is then extended to the conditions of high density plasma clouds produced from the injected solid particles. In combination with this switching, it is the inversion of the ejection of plasma from the beam axis at nonlinear (ponderomotive) force self-focusing. The processes of the momentum transfer are then well understood and the deformation of phase fronts in plasma can be used for controlled bending, or focusing of x-ray beams, or for correcting of other insufficient beam quality. A proof of principle experiment is discussed

A Model for Peer Experiential and Reciprocal Supervision (PEERS) for Genetic Counselors: Development and Preliminary Evaluation Within Clinical Practice

A model for practising genetic counselors to obtain clinical supervision via reciprocal peer observation and feedback was developed and trialled. The model was developed in response to a perceived lack of opportunity for immediate observational feedback for practising genetic counselors. The aims reached by consensus were to facilitate learning new approaches and skills, to revitalise current ways of practising, and to enhance supervision skills in a two-way process, where the observer learnt from the counselor, and vice-versa. The genetic counselors agreed on a process of paired reciprocal observation whereby the observer was present in the room during the counseling session, and a reflective feedback discussion was arranged within 24 h of the session. Four main themes emerged from analysis of the recorded discussions were (i) "I wasn't sure if I-": voicing of doubts or internal questions that occurred during session for the counselor conducting the session, (ii) "I really liked that": positive feedback and validation from the observer, (iii) "I wonder whether-": offering of alternative views, insights and strategies by the observer, and (iv) "That's a real thing for me to take away and think about": evidence of learning by both observers and counselors