Sparsity and Incoherence in Compressive Sampling

We consider the problem of reconstructing a sparse signal $x^0\in\R^n$ from a limited number of linear measurements. Given $m$ randomly selected samples of $U x^0$, where $U$ is an orthonormal matrix, we show that $\ell_1$ minimization recovers $x^0$ exactly when the number of measurements exceeds $$m\geq \mathrm{Const}\cdot\mu^2(U)\cdot S\cdot\log n,$$ where $S$ is the number of nonzero components in $x^0$, and $\mu$ is the largest entry in $U$ properly normalized: $\mu(U) = \sqrt{n} \cdot \max_{k,j} |U_{k,j}|$. The smaller $\mu$, the fewer samples needed. The result holds for ``most'' sparse signals $x^0$ supported on a fixed (but arbitrary) set $T$. Given $T$, if the sign of $x^0$ for each nonzero entry on $T$ and the observed values of $Ux^0$ are drawn at random, the signal is recovered with overwhelming probability. Moreover, there is a sense in which this is nearly optimal since any method succeeding with the same probability would require just about this many samples

An Experimental Study of Effects of Step Roughness in Skimming Flows on Stepped Chutes

On a spillway chute, a stepped design increases the rate of energy dissipation on the chute itself and reduces the size of a downstream energy dissipator. Up to date, the effects of step roughness on the flow properties remain unknown despite the practical relevance to damaged concrete steps, rock chutes and gabions weirs. New measurements were conducted in a large-size laboratory facility with two step conditions (smooth and rough) and three types of step roughness. Detailed air-water flow properties were measured systematically for several flow rates. The results showed faster flow motion on rough step chutes. Although the finding is counter-intuitive, it is linked with the location of the inception point of free-surface aeration being located further downstream than for a smooth stepped chute for an identical flow rate. In the aerated flow region, the velocities on rough-step chutes were larger than those of smooth chute flows for a given flow rate and dimensionless location from the inception point of free-surface aeration both at step edges and between step edges. The results suggest that design guidelines for smooth (concrete) stepped spillway may not be suitable to rough stepped chutes including gabion stepped weirs, and older stepped chutes with damaged steps

Keeping the faith: reflections on religious nurture among young British Sikhs

Although young Sikhs are regularly accused of not attending gurdwara and not being interested in Sikhism, many young Sikhs are now learning about Sikhism outside traditional religious institutions. Using data gathered as part of a research project studying the transmission of Sikhism among 18- to 30-year-old British Sikhs, this essay explores how young Sikhs are learning about Sikhism in their pre-adult life stage. Examining the influences of the family and the school environment and the various methods used in gurdwaras, this essay offers a retrospective look on the ways in which young Sikhs are nurtured and socialised into Sikhism, providing an understanding from the perspective of young Sikhs themselves about which methods actually work and why

Treatment outcome of tubercular lymphadenopathy cases treated under dots: a five year follow up study

Background: Treatment of tubercular lymphadenopathy consists of at least 6 months of therapy with antitubercular drugs as DOTS in India. Some studies recommend that extension of therapy for some time may lead to lesser recurrence and relapse. This study was planned to assess the outcome of DOTS therapy in lymph node tuberculosis (TB) cases treated under RNTCP and to find out the prevalence of relapse in these patients in southern Rajasthan.Methods: This was a retrospective analysis of 275 cases of lymph node tuberculosis treated with DOTS under RNTCP. An immediate outcome of these cases was recorded and further traceable 81 patients were interviewed for long term outcome.Results: In our study population, treatment completion rate was 93.09%, defaulter rate was 4% and death reported in 3.7% (3/81) cases. We observed relapse rate of 9.1% after treatment completion. A total of 7.04% patients received extended treatment and none of them had relapsed during our follow up.Conclusions: Our study confirms that the efficacy of DOTS treatment is quite good in cases of tubercular lymphadenopathy but still requires review of programmatic strategy. An extension of antitubercular therapy is recommended because patients treated with DOTS had a little higher relapse rate in comparison to whom the treatment extended who had no recurrence and relapse

Molecular Characterisation of Small Molecule Agonists Effect on the Human Glucagon Like Peptide-1 Receptor Internalisation

The glucagon-like peptide receptor (GLP-1R), which is a G-protein coupled receptor (GPCR), signals through both Gαs and Gαq coupled pathways and ERK phosphorylation to stimulate insulin secretion. The aim of this study was to determine molecular details of the effect of small molecule agonists, compounds 2 and B, on GLP-1R mediated cAMP production, intracellular Ca2+ accumulation, ERK phosphorylation and its internalisation. In human GLP-1R (hGLP-1R) expressing cells, compounds 2 and B induced cAMP production but caused no intracellular Ca2+ accumulation, ERK phosphorylation or hGLP-1R internalisation. GLP-1 antagonists Ex(9-39) and JANT-4 and the orthosteric binding site mutation (V36A) in hGLP-1R failed to inhibit compounds 2 and B induced cAMP production, confirming that their binding site distinct from the GLP-1 binding site on GLP-1R. However, K334A mutation of hGLP-1R, which affects Gαs coupling, inhibited GLP-1 as well as compounds 2 and B induced cAMP production, indicating that GLP-1, compounds 2 and B binding induce similar conformational changes in the GLP-1R for Gαs coupling. Additionally, compound 2 or B binding to the hGLP-1R had significantly reduced GLP-1 induced intracellular Ca2+ accumulation, ERK phosphorylation and hGLP-1R internalisation. This study illustrates pharmacology of differential activation of GLP-1R by GLP-1 and compounds 2 and B

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed

Development and user-testing of a digital patient decision aid to facilitate shared decision-making for people with stable angina

Background Research shows that people with stable angina need decision support when considering elective treatments. Initial treatment is with medicines but patients may gain further benefit with invasive percutaneous coronary intervention (PCI). Choosing between these treatments can be challenging for patients because both confer similar benefits but have different risks. Patient decision aids (PtDAs) are evidence-based interventions that support shared decision-making (SDM) when making healthcare decisions. This study aimed to develop and user-test a digital patient decision aid (CONNECT) to facilitate SDM for people with stable angina considering invasive treatment with elective PCI. Methods A multi-phase study was conducted to develop and test CONNECT (COroNary aNgioplasty dECision Tool) using approaches recommended by the International Patient Decision Aid Standards Collaboration: (i) Steering Group assembled, (ii) review of clinical guidance, (iii) co-design workshops with patients and cardiology health professionals, (iv) first prototype developed and ‘alpha’ tested (semi-structured cognitive interviews and 12-item acceptability questionnaire) with patients, cardiologists and cardiac nurses, recruited from two hospitals in Northern England, and (v) final PtDA refined following iterative user-feedback. Quantitative data were analysed descriptively and qualitative data from the interviews analysed using deductive content analysis. Results CONNECT was developed and user-tested with 34 patients and 29 cardiology health professionals. Findings showed that CONNECT was generally acceptable, usable, comprehensible, and desirable. Participants suggested that CONNECT had the potential to improve care quality by personalising consultations and facilitating SDM and informed consent. Patient safety may be improved as CONNECT includes questions about symptom burden which can identify asymptomatic patients unlikely to benefit from PCI, as well as those who may need to be fast tracked because of worsening symptoms. Conclusions CONNECT is the first digital PtDA for people with stable angina considering elective PCI, developed in the UK using recommended processes and fulfilling international quality criteria. CONNECT shows promise as an approach to facilitate SDM and should be evaluated in a clinical trial. Further work is required to standardise the provision of probabilistic risk information for people considering elective PCI and to understand how CONNECT can be accessible to underserved communities