Updating the parameters of a threshold scheme by minimal broadcast

Threshold schemes allow secret data to be protected among a set of participants in such a way that only a prespecified threshold of participants can reconstruct the secret from private information (shares) distributed to them on a system setup using secure channels. We consider the general problem of designing unconditionally secure threshold schemes whose defining parameters (the threshold and the number of participants) can later be changed by using only public channel broadcast messages. In this paper, we are interested in the efficiency of such threshold schemes, and seek to minimize storage costs (size of shares) as well as optimize performance in low-bandwidth environments by minimizing the size of necessary broadcast messages. We prove a number of lower bounds on the smallest size of broadcast message necessary to make general changes to the parameters of a threshold scheme in which each participant already holds shares of minimal size. We establish the tightness of these bounds by demonstrating optimal schemes.S. G. Barwick, Wen-Ai Jackson and Keith M. Marti

Inference for Parameters Defined by Moment Inequalities: A Recommended Moment Selection Procedure

This paper is concerned with tests and confi dence intervals for parameters that are not necessarily identifi ed and are de fined by moment inequalities. In the literature, different test statistics, critical value methods, and implementation methods (i.e., the asymptotic distribution versus the bootstrap) have been proposed. In this paper, we compare these methods. We provide a recommended test statistic, moment selection critical value method, and implementation method. We provide data-dependent procedures for choosing the key moment selection tuning parameter kappa and a size-correction factor eta.National Science Foundation (U.S.) (grant SES-0751517

An Update on the Phenotype, Genotype and Neurobiology of ADCY5-Related Disease.

Adenylyl cyclase 5 (ADCY5)-related phenotypes comprise an expanding disease continuum, but much remains to be understood about the underlying pathogenic mechanisms of the disease. ADCY5-related disease comprises a spectrum of hyperkinetic disorders involving chorea, myoclonus, and/or dystonia, often with paroxysmal exacerbations. Hypotonia, developmental delay, and intellectual disability may be present. The causative gene encodes adenylyl cyclase, the enzyme responsible for the conversion of adenosine triphosphate (ATP) to cyclic adenosine-3',5'-monophosphate (cAMP). cAMP is a second messenger that exerts a wide variety of effects via several intracellular signaling pathways. ADCY5 is the most commonly expressed isoform of adenylyl cyclase in medium spiny neurons (MSNs) of the striatum, and it integrates and controls dopaminergic signaling. Through cAMP pathway, ADCY5 is a key regulator of the cortical and thalamic signaling that control initiation of voluntary movements and prevention of involuntary movements. Gain-of-function mutations in ADCY5 have been recently linked to a rare genetic disorder called ADCY5-related dyskinesia, where dysregulation of the cAMP pathway leads to reduced inhibitory activity and involuntary hyperkinetic movements. Here, we present an update on the neurobiology of ADCY5, together with a detailed overview of the reported clinical phenotypes and genotypes. Although a range of therapeutic approaches has been trialed, there are currently no disease-modifying treatments. Improved in vitro and in vivo laboratory models will no doubt increase our understanding of the pathogenesis of this rare genetic movement disorder, which will improve diagnosis, and also facilitate the development of precision medicine approaches for this, and other forms of hyperkinesia

Dominant mutations of the Notch ligand Jagged1 cause peripheral neuropathy

Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development and homeostasis. Dysregulated Notch signaling has also been implicated in human disease, including multiple forms of cancer, and represents an emerging therapeutic target. Successful development of such therapeutics requires a detailed understanding of potential on-target toxicities. Here, we identify autosomal dominant mutations of the canonical Notch ligand Jagged1 (or JAG1) as a cause of peripheral nerve disease in 2 unrelated families with the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2 (CMT2). Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Our studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Together, our findings highlight a critical role for JAG1 in maintaining peripheral nerve integrity, particularly in the recurrent laryngeal nerve, and provide a basis for the evaluation of peripheral neuropathy as part of the clinical development of Notch pathway-modulating therapeutics.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.G1002279/MRC_/Medical Research Council/United Kingdom R25 NS065729/NS/NINDS NIH HHS/United States Z01 AG000949/ImNIH/Intramural NIH HHS/United States R01 NS062869/NS/NINDS NIH HHS/United States F31 NS105404/NS/NINDS NIH HHS/United Statespre-print, post-print, publisher's version/PD

Imaging in myeloma with focus on advanced imaging techniques.

In recent years, there have been major advances in the imaging of myeloma with whole body MRI incorporating diffusion-weighted imaging, emerging as the most sensitive modality. Imaging is now a key component in the work-up of patients with a suspected diagnosis of myeloma. The International Myeloma Working Group now specifies that more than one focal lesion on MRI or lytic lesion on whole body low-dose CT or fludeoxyglucose (FDG) PET/CT fulfil the criteria for bone damage requiring therapy. The recent National Institute for Health and Care Excellence myeloma guidelines recommend imaging in all patients with suspected myeloma. In addition, there is emerging data supporting the use of functional imaging techniques (WB-DW MRI and FDG PET/CT) to predict outcome and evaluate response to therapy. This review summarises the imaging modalities used in myeloma, the latest guidelines relevant to imaging and future directions

From attosecond to zeptosecond coherent control of free-electron wave functions using semi-infinite light fields

Light-electron interaction in empty space is the seminal ingredient for free-electron lasers and also for controlling electron beams to dynamically investigate materials and molecules. Pushing the coherent control of free electrons by light to unexplored timescales, below the attosecond, would enable unprecedented applications in light-assisted electron quantum circuits and diagnostics at extremely small timescales, such as those governing intramolecular electronic motion and nuclear phenomena. We experimentally demonstrate attosecond coherent manipulation of the electron wave function in a transmission electron microscope, and show that it can be pushed down to the zeptosecond regime with existing technology. We make a relativistic pulsed electron beam interact in free space with an appropriately synthesized semi-infinite light field generated by two femtosecond laser pulses reflected at the surface of a mirror and delayed by fractions of the optical cycle. The amplitude and phase of the resulting coherent oscillations of the electron states in energymomentum space are mapped via momentum-resolved ultrafast electron energy-loss spectroscopy. The experimental results are in full agreement with our theoretical framework for light-electron interaction, which predicts access to the zeptosecond timescale by combining semi-infinite X-ray fields with free electrons.Comment: 22 pages, 6 figure

Health Researchers' Use of Social Media: Scoping Review.

BackgroundHealth researchers are increasingly using social media in a professional capacity, and the applications of social media for health researchers are vast. However, there is currently no published evidence synthesis of the ways in which health researchers use social media professionally, and uncertainty remains as to how best to harness its potential.ObjectiveThis scoping review aimed to explore how social media is used by health researchers professionally, as reported in the literature.MethodsThe scoping review methodology guided by Arksey and O'Malley and Levac et al was used. Comprehensive searches based on the concepts of health research and social media were conducted in MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, and Web of Science databases, with no limitations applied. Articles were screened at the title and abstract level and at full text by two reviewers. One reviewer extracted data that were analyzed descriptively to map the available evidence.ResultsA total of 8359 articles were screened at the title and abstract level, of which 719 were also assessed at full text for eligibility. The 414 articles identified for inclusion were published in 278 different journals. Studies originated from 31 different countries, with the most prevalent being the United States (52.7% [218/414]). The health discipline of the first authors varied, with medicine (33.3% [138/414]) being the most common. A third of the articles covered health generally, with 61 health-specific topics. Papers used a range of social media platforms (mean 1.33 [SD 0.7]). A quarter of the articles screened reported on social media use for participant recruitment (25.1% [104/414]), followed by practical ways to use social media (15.5% [64/414]), and use of social media for content analysis research (13.3% [55/414]). Articles were categorized as celebratory (ie, opportunities for engagement, 72.2% [299/414]), contingent (ie, opportunities and possible limitations, 22.7% [94/414]) and concerned (ie, potentially harmful, 5.1% [21/414]).ConclusionsHealth researchers are increasingly publishing on their use of social media for a range of professional purposes. Although most of the sentiment around the use of social media in health research was celebratory, the uses of social media varied widely. Future research is needed to support health researchers to optimize their social media use

Design of an electron microscope phase plate using a focused continuous-wave laser

We propose a Zernike phase contrast electron microscope that uses an intense laser focus to convert a phase image into a visible image. We present the relativistic quantum theory of the phase shift caused by the laser-electron-interaction, study resonant cavities for enhancing the laser intensity, and discuss applications in biology, soft materials science, and atomic and molecular physics.Comment: 5 pages, 3 figure

Clinical translation of positive metastases identified on prostate-specific membrane antigen positron emission tomography/computed tomography imaging in the management of de novo synchronous oligometastatic prostate cancer

Recent randomised evidence supports the diagnostic superiority of prostate-specific membrane antigen (PSMA) PET/CT, over conventional imaging, in the detection of distant occult metastasis in men with newly diagnosed high-risk prostate cancer. This may result in a rise in the detection of de novo synchronous hormone-sensitive “oligometastatic” prostate cancer. We outline the evidence supporting PSMA PET/CT imaging in primary staging. We also discuss the translation of positive areas, with a high probability of distant metastasis, into clinical therapeutic targets for metastasis-directed interventions. Finally, we highlight the role of PSMA PET/CT as an imaging biomarker. This may have future utility in disease monitoring and prediction of response to systemic, local cytoreductive and metastasis-directed interventions. Patient Summary: A new whole-body scan can accurately detect cancer deposits, in men in whom distant prostate cancer spread is suspected. This may be useful to monitor and predict response to drug therapy, treatments to the prostate and cancer deposits