Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.

Whole exome sequencing (WES), targeted gene panel sequencing and single nucleotide polymorphism (SNP) arrays are increasingly used for the identification of actionable alterations that are critical to cancer care. Here, we compared The Cancer Genome Atlas (TCGA) and the Genomics Evidence Neoplasia Information Exchange (GENIE) breast cancer genomic datasets (array and next generation sequencing (NGS) data) in detecting genomic alterations in clinically relevant genes. We performed an in silico analysis to determine the concordance in the frequencies of actionable mutations and copy number alterations/aberrations (CNAs) in the two most common breast cancer histologies, invasive lobular and invasive ductal carcinoma. We found that targeted sequencing identified a larger number of mutational hotspots and clinically significant amplifications that would have been missed by WES and SNP arrays in many actionable genes such as PIK3CA, EGFR, AKT3, FGFR1, ERBB2, ERBB3 and ESR1. The striking differences between the number of mutational hotspots and CNAs generated from these platforms highlight a number of factors that should be considered in the interpretation of array and NGS-based genomic data for precision medicine. Targeted panel sequencing was preferable to WES to define the full spectrum of somatic mutations present in a tumor

The role of social cognition in decision making

Successful decision making in a social setting depends on our ability to understand the intentions, emotions and beliefs of others. The mirror system allows us to understand other people's motor actions and action intentions. ‘Empathy’ allows us to understand and share emotions and sensations with others. ‘Theory of mind’ allows us to understand more abstract concepts such as beliefs or wishes in others. In all these cases, evidence has accumulated that we use the specific neural networks engaged in processing mental states in ourselves to understand the same mental states in others. However, the magnitude of the brain activity in these shared networks is modulated by contextual appraisal of the situation or the other person. An important feature of decision making in a social setting concerns the interaction of reason and emotion. We consider four domains where such interactions occur: our sense of fairness, altruistic punishment, trust and framing effects. In these cases, social motivations and emotions compete with each other, while higher-level control processes modulate the interactions of these low-level biases

Penerapan Model Pembelajaran Learning Cycle 5e untuk Meningkatkan Keterampilan Proses Sains Siswa

Penelitian bertujuan untuk mendapatkan gambaran mengenai peningkatan Keterampilan Proses Sains siswa setelah diterapkan model pembelajaran Learning Cycle 5E. Metode penelitian yang digunakan dalam penelitian ini adalah metode eksperimen. Desain penelitian yang digunakan adalah poor experimental design, dengan rancangan penelitian one group pretest-posttest design. Penelitian ini dilaksanakan di SMA Negeri 7 Tangerang Selatan. Populasi penelitian ini adalah siswa kelas XI IPA tahun ajaran 2016/2017. Sampel yang digunakan adalah siswa kelas XI IPA 1, sampel diambil dari populasi menggunakan teknik purposive sampling. Instrumen yang digunakan dalam penelitian ini antara lain instrumen tes yang berupa soal pilihan ganda dan lembar observasi. Berdasarkan hasil analisis yang dilakukan diperoleh besar peningkatan keterampilan proses sains setelah diterapkan model pembelajaran Learning Cycle 5E dengan N-gain sebesar 0,5696 yang termasuk dalam kategori peningkatan sedang

Post-HPV-vaccination mast cell activation syndrome: Possible vaccine-triggered escalation of undiagnosed pre-existing mast cell disease?

For nearly a decade, case reports and series have emerged regarding dysautonomias-particularly postural orthostatic tachycardia syndrome (POTS)-presenting soon after vaccination against human papilloma virus (HPV). We too have observed a number of such cases (all following vaccination with the Gardasil product), and have found several to have detectable mast cell activation syndrome (MCAS) as well as histories suggesting that MCAS was likely present long before vaccination. We detail 11 such cases here, posing a hypothesis that HPV vaccination (at least with the Gardasil product) may have triggered or exacerbated MCAS in teenagers previously not recognized to have it. Only recently recognized, MCAS is being increasingly appreciated as a prevalent and chronic multisystem disorder, often emerging early in life and presenting with inflammatory ± allergic phenomena following from known mast cell (MC) mediator effects. There is rising recognition, too, of associations of MCAS with central and peripheral neuropathic disorders, including autonomic disorders such as POTS. Given the recognized potential for many antigens to trigger a major and permanent escalation of baseline MC misbehavior in a given MCAS patient, we hypothesize that in our patients described herein, vaccination with Gardasil may have caused pre-existing (but not yet clinically recognized) MCAS to worsen to a clinically significantly degree, with the emergence of POTS and other issues. The recognition and management of MCAS prior to vaccinations in general may be a strategy worth investigating for reducing adverse events following HPV vaccinations and perhaps even other types of vaccinations

Optimal combination of signals from co-located gravitational wave interferometers for use in searches for a stochastic background

This article derives an optimal (i.e., unbiased, minimum variance) estimator for the pseudo-detector strain for a pair of co-located gravitational wave interferometers (such as the pair of LIGO interferometers at its Hanford Observatory), allowing for possible instrumental correlations between the two detectors. The technique is robust and does not involve any assumptions or approximations regarding the relative strength of gravitational wave signals in the detector pair with respect to other sources of correlated instrumental or environmental noise. An expression is given for the effective power spectral density of the combined noise in the pseudo-detector. This can then be introduced into the standard optimal Wiener filter used to cross-correlate detector data streams in order to obtain an optimal estimate of the stochastic gravitational wave background. In addition, a dual to the optimal estimate of strain is derived. This dual is constructed to contain no gravitational wave signature and can thus be used as on "off-source" measurement to test algorithms used in the "on-source" observation.Comment: 14 pages, 4 figures, submitted to Physical Review D Resubmitted after editing paper in response to referee comments. Removed appendices A, B and edited text accordingly. Improved legibility of figures. Corrected several references. Corrected reference to science run number (S1 vs. S2) in text and figure caption

The Impact of Mobile Technology on Micro and Small Enterprises in Zimbabwe in the Post-Hyperinflation Economic Era

This paper investigates the impact of mobile technology on Micro and Small Enterprises (MSEs) in the developing world in the post-hyperinflation era. Data was collected from a multi-staged sample of 114 MSE owners within the capital province of Zimbabwe, namely Harare. The data was collected and analysed using descriptive quantitative survey methods, which comprised of hard-copy questionnaires, structured interviews and online questionnaires. The findings suggest that mobile technology has incremental, transformational and production influence on MSEs in Zimbabwe. The findings show that mobile technology amplifies communication and relations with customers, MSE’s productivity and MSE’s revenues. Mobile technology is also spurring new and innovative offerings such as mobile money, mobile banking and mobile advertising for the MSEs. The paper also provide the evidence that mobile technology is contributing to the creation of jobs in the indirect mobile industry sector, such as mobile money service and mobile application development. The paper generates insights that inform and compel creation of policies that enable and support the creation and growth of business in the mobile money, mobile retail services and mobile application development sectors

Randomisation of Pulse Phases for Unambiguous and Robust Quantum Sensing

We develop theoretically and demonstrate experimentally a universal dynamical decoupling method for robust quantum sensing with unambiguous signal identification. Our method uses randomisation of control pulses to suppress simultaneously two types of errors in the measured spectra that would otherwise lead to false signal identification. These are spurious responses due to finite-width $\pi$ pulses, as well as signal distortion caused by $\pi$ pulse imperfections. For the cases of nanoscale nuclear spin sensing and AC magnetometry, we benchmark the performance of the protocol with a single nitrogen vacancy centre in diamond against widely used non-randomised pulse sequences. Our method is general and can be combined with existing multipulse quantum sensing sequences to enhance their performance

Early Posttherapy Hospitalizations Among Survivors of Childhood Leukemia and Lymphoma

Long-term survivors of childhood cancers are at increased risk for hospitalization. To test the hypothesis that many treatment-related morbidities are identifiable in the early post-therapy period, we determined the rates and causes for hospitalization among survivors of leukemia and lymphoma during the first three years post-therapy. Using a health plan claims database, we identified patients aged 0-21 years-old treated for leukemia or lymphoma from 2000-2010. Survivors were matched 10:1 with similar children without a history of cancer. Hospitalization rates over three years were compared using Cox proportional hazards regression and risks of cause-specific hospitalization were compared using log-binomial models. Nineteen percent of childhood leukemia and lymphoma survivors were hospitalized in the first three years off therapy. Leukemia survivors (N=529) experienced over six times (HR: 6.3, 95%CI: 4.9-8.0) and lymphoma survivors (N=454) over three times the hospitalization rate of controls (HR: 3.2, 95%CI: 2.5-4.2). Compared with children without a cancer history, survivors were at increased risk for hospitalization due to infectious causes (leukemia RR: 60.0, 95%CI: 23.4-154.0; lymphoma RR: 10.0, 95%CI: 4.4-22.9). Additionally, lymphoma survivors were at increased risk for cardiovascular-(RR: 15.0, 95%CI: 5.4-42.0) and pulmonary-(RR: 8.1, 95%CI: 3.9-16.8) related hospitalizations. These findings highlight the morbidity experienced by survivors and suggest that treatment-associated complications may be emerging soon after therapy completion