Identification of neutral tumor evolution across cancer types

A.S. is supported by The Chris Rokos Fellowship in Evolution and Cancer. B.W. is supported by the Geoffrey W. Lewis Post-Doctoral Training fellowship. This work was supported by the Wellcome Trust (105104/Z/14/Z). C.P.B. acknowledges funding from the Wellcome Trust through a Research Career Development Fellowship (097319/Z/11/Z). This work was supported by a Cancer Research UK Career Development Award to T.A.G. M.J.W. is supported by a UK Medical Research Council student fellowship

Screening, intervention and outcome in autism and other developmental disorders: the role of randomized controlled trials

We draw attention to a number of important considerations in the arguments about screening and outcome of intervention in children with autism and other developmental disorders. Autism screening in itself never provides a final clinical diagnosis, but may well identify developmental deviations indicative of autism—or of other developmental disorders—that should lead to referral for further clinical assessment. Decisions regarding population or clinic screening cannot be allowed to be based on the fact that prospective longitudinal RCT designs over decades could never be performed in complex developmental disorders. We propose an alternative approach. Early screening for autism and other developmental disorders is likely to be of high societal importance and should be promoted and rigorously evaluated

Modelling and measurement of the absolute level of power radiated by antenna integrated THz UTC photodiodes

We determine the output impedance of uni-travelling carrier (UTC) photodiodes at frequencies up to 400 GHz by performing, for the first time, 3D full-wave modelling of detailed UTC photodiode structures. In addition, we demonstrate the importance of the UTC impedance evaluation, by using it in the prediction of the absolute power radiated by an antenna integrated UTC, over a broad frequency range and confirming the predictions by experimental measurements up to 185 GHz. This is done by means of 3D full-wave modelling and is only possible since the source (UTC) to antenna impedance match is properly taken into account. We also show that, when the UTC-to-antenna coupling efficiency is modelled using the classical junction-capacitance/series-resistance concept, calculated and measured levels of absolute radiated power are in substantial disagreement, and the maximum radiated power is overestimated by a factor of almost 7 dB. The ability to calculate the absolute emitted power correctly enables the radiated power to be maximised through optimisation of the UTC-to-antenna impedance match

A Tale of Three Signatures: practical attack of ECDSA with wNAF

One way of attacking ECDSA with wNAF implementation for the scalar multiplication is to perform a side-channel analysis to collect information, then use a lattice based method to recover the secret key. In this paper, we reinvestigate the construction of the lattice used in one of these methods, the Extended Hidden Number Problem (EHNP). We find the secret key with only 3 signatures, thus reaching the theoretical bound given by Fan, Wang and Cheng, whereas best previous methods required at least 4 signatures in practice. Our attack is more efficient than previous attacks, in particular compared to times reported by Fan et al. at CCS 2016 and for most cases, has better probability of success. To obtain such results, we perform a detailed analysis of the parameters used in the attack and introduce a preprocessing method which reduces by a factor up to 7 the overall time to recover the secret key for some parameters. We perform an error resilience analysis which has never been done before in the setup of EHNP. Our construction is still able to find the secret key with a small amount of erroneous traces, up to 2% of false digits, and 4% with a specific type of error. We also investigate Coppersmith's methods as a potential alternative to EHNP and explain why, to the best of our knowledge, EHNP goes beyond the limitations of Coppersmith's methods

The evolution of nursing research in Portugal

Trabalho apresentado em 3º Congresso Internacional do CiiEM, 20-22 junho 2018, Almada, PortugalN/

Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial

© 2021 The Authors Background: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated. Methods: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18–75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118). Findings: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group. Interpretation: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects. Funding: Research Grants Council, Hong Kong

Cell migration leads to spatially distinct but clonally related airway cancer precursors

Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree

Reply to 'Neutral tumor evolution?'

No abstract availabl

1 Gbaud QPSK Wireless Receiver using an Opto-Electronic Mixer

This paper presents the first demonstration of a uni-travelling carrier photodiode (UTC-PD) used as a receiver of a wirelessly transmitted quadrature phase shift keying (QPSK) signal. In this demonstration, a 1 Gbaud QPSK signal centered at 33.5 GHz was transmitted over a wireless distance of 1.4 m. At the receiver, a UTC-PD is used to down-convert the RF signal to an intermediate frequency (IF) of 9.5 GHz by mixing the RF signal with a heterodyne signal at 24 GHz. The down-converted signal is captured by a real time digital oscilloscope for further digital signal processing. The error vector magnitude (EVM) of the demodulated signal was measured to be 18%, which corresponds to a bit error rate (BER) of 10-8