A specific RAD51 haplotype increases breast cancer risk in Jewish non-Ashkenazi high-risk women

While the precise genes involved in determining familial breast cancer risk in addition to BRCA1/2 are mostly unknown, one strong candidate is RAD51. Jewish non-Ashkenazi women at high-risk for breast/ovarian cancer and ethnically matched controls were genotyped using four single nucleotide polymorphisms spanning the RAD51 genomic region, and the resulting haplotypes were constructed using the GERBIL algorithm. A total of 314 individuals were genotyped: 184 non-Ashkenazi high-risk women (119 with breast cancer), and 130 unaffected, average-risk ethnically matched controls. Using GEBRIL, three frequent haplotypes were constructed. One of the haplotypes (TGTA -coined haplotype 3) was present in 7.3% (19/260 haplotypes) of controls (n = 130) and in 16.8% (40/238 haplotypes) of high-risk breast cancer patients (n = 119, P = 0.001). A specific RAD51 haplotype is more prevalent among non-Ashkenazi Jewish high-risk women than in average-risk population

A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer

BackgroundThe traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.MethodsThis is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient’s choice. Our primary objective is to determine the rate of ‘failure’ of disease management in respective AS and surgical arms as defined by: i) AS arm – surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.DiscussionThe results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.Registration detailsThis prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery

Israel's Future Wars: Universal Lessons of a Peculiar Case; Strategic Insights, v. 10, Special issue (October 2011), 117-123. Topic: Global Trends and Future Warfare ; Part III: New Actors and Belligerents

This article appeared in Strategic Insights, v.10, Special issue (October 2011), 117-123. Topic: Global Trends and Future Warfare ; Part III: New Actors and BelligerentsThe following paper examines Israel's views toward future armed conflicts. It discusses four main themes: Israel's traditional security doctrine since the days of its establishment; the emergence of new threats over the last decade and their future significance; Israel's evolving response; and the question of what, if any, relevance this has for the United States. The main argument of this paper is that, while one could conceive Israel's situation as a window to the future and benefit from studying various aspects of its force structure and employment, one should also be very cautious in making comparisons to Israel's unique situation and responses.Approved for public release; distribution is unlimited

Reconstructing cancer karyotypes from short read data: the half empty and half full glass

Abstract Background During cancer progression genomes undergo point mutations as well as larger segmental changes. The latter include, among others, segmental deletions duplications, translocations and inversions.The result is a highly complex, patient-specific cancer karyotype. Using high-throughput technologies of deep sequencing and microarrays it is possible to interrogate a cancer genome and produce chromosomal copy number profiles and a list of breakpoints (“jumps”) relative to the normal genome. This information is very detailed but local, and does not give the overall picture of the cancer genome. One of the basic challenges in cancer genome research is to use such information to infer the cancer karyotype. We present here an algorithmic approach, based on graph theory and integer linear programming, that receives segmental copy number and breakpoint data as input and produces a cancer karyotype that is most concordant with them. We used simulations to evaluate the utility of our approach, and applied it to real data. Results By using a simulation model, we were able to estimate the correctness and robustness of the algorithm in a spectrum of scenarios. Under our base scenario, designed according to observations in real data, the algorithm correctly inferred 69% of the karyotypes. However, when using less stringent correctness metrics that account for incomplete and noisy data, 87% of the reconstructed karyotypes were correct. Furthermore, in scenarios where the data were very clean and complete, accuracy rose to 90%–100%. Some examples of analysis of real data, and the reconstructed karyotypes suggested by our algorithm, are also presented. Conclusion While reconstruction of complete, perfect karyotype based on short read data is very hard, a large fraction of the reconstruction will still be correct and can provide useful information

Mission Command and Bitsuism in the Israeli Defence Forces: Complementary or Contradictory in Today's Counter-Insurgency Campaign?

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Additional file 5: Figure S3-S8. of Reconstructing cancer karyotypes from short read data: the half empty and half full glass

Results of different simulated scenarios. (DOCX 33 kb

La Charente

15 mars 18961896/03/15 (A25,N10919)-1896/03/15.Appartient à l’ensemble documentaire : PoitouCh

Additional file 12: Figures S10-S11. of Reconstructing cancer karyotypes from short read data: the half empty and half full glass

Results on real samples LUAD 6, LUSC 5. (DOCX 314 kb

Additional file 1: Figure S1. of Reconstructing cancer karyotypes from short read data: the half empty and half full glass

An example of graphs that represent equivalent yet not identical solutions. (DOCX 60 kb