Dual first-order methods are essential techniques for large-scale constrained convex optimization. However, when recovering the primal solutions, we need $T(epsilon^{-2})$ iterations to achieve an $epsilon$-optimal primal solution when we apply an algorithm to the non-strongly convex dual problem with $T(epsilon^{-1})$ iterations to achieve an $epsilon$-optimal dual solution, where $T(x)$ can be $x$ or $sqrt{x}$. In this paper, we prove that the iteration complexity of the primal solutions and dual solutions have the same $Oleft(frac{1}{sqrt{epsilon}} ight)$ order of magnitude for the accelerated randomized dual coordinate ascent. When the dual function further satisfies the quadratic functional growth condition, by restarting the algorithm at any period, we establish the linear iteration complexity for both the primal solutions and dual solutions even if the condition number is unknown. When applied to the regularized empirical risk minimization problem, we prove the iteration complexity of $Oleft(nlog n+sqrt{frac{n}{epsilon}} ight)$ in both primal space and dual space, where $n$ is the number of samples. Our result takes out the $left(log frac{1}{epsilon} ight)$ factor compared with the methods based on smoothing/regularization or Catalyst reduction. As far as we know, this is the first time that the optimal $Oleft(sqrt{frac{n}{epsilon}} ight)$ iteration complexity in the primal space is established for the dual coordinate ascent based stochastic algorithms. We also establish the accelerated linear complexity for some problems with nonsmooth loss, e.g., the least absolute deviation and SVM.

We consider the problem of estimating the latent structure of a social network based on the observed information diffusion events, or cascades, where the observations for a given cascade consist of only the timestamps of infection for infected nodes but not the source of the infection. Most of the existing work on this problem has focused on estimating a diffusion matrix without any structural assumptions on it. In this paper, we propose a novel model based on the intuition that an information is more likely to propagate among two nodes if they are interested in similar topics which are also prominent in the information content. In particular, our model endows each node with an influence vector (which measures how authoritative the node is on each topic) and a receptivity vector (which measures how susceptible the node is for each topic). We show how this node-topic structure can be estimated from the observed cascades, and prove the consistency of the estimator. Experiments on synthetic and real data demonstrate the improved performance and better interpretability of our model compared to existing state-of-the-art methods.

We present LCE, a Local Cascade Ensemble for traditional (tabular) multivariate data classification, and its extension LCEM for Multivariate Time Series (MTS) classification. LCE is a new hybrid ensemble method that combines an explicit boosting-bagging approach to handle the usual bias-variance tradeoff faced by machine learning models and an implicit divide-and-conquer approach to individualize classifier errors on different parts of the training data. Our evaluation firstly shows that the hybrid ensemble method LCE outperforms the state-of-the-art classifiers on the UCI datasets and that LCEM outperforms the state-of-the-art MTS classifiers on the UEA datasets. Furthermore, LCEM provides explainability by design and manifests robust performance when faced with challenges arising from continuous data collection (different MTS length, missing data and noise).

Ye Zhang
Sep 3, 2014; 34:11929-11947
Cellular

Ye Zhang
Sep 3, 2014; 34:11929-11947
Cellular

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness.

SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.

Everything we do at FAO aims at ensuring a better future. Sure, we need to tackle the huge food and environmental challenges we face today. But we always keep an eye on what that means for tomorrow. More than just quick fixes, we look for sustainable solutions that will benefit generations to come. The future of our world depends on today’s [...]

How the beloved figure has become a lightning rod in a heated environmental debate

<span class="topsy_trackback_comment"><span class="topsy_twitter_username"><span class="topsy_trackback_content">Coldplay und Taio Cruz erhalten ASCAP Awards | RSS Feeds – IMC ...: Coldplay und Taio Cruz erhalten... http://bit.ly/d9aHcK #indiemusictips</span></span>

Madagascar is putting its self-proclaimed, plant-based "cure" for COVID-19 on sale and several countries in Africa have already put in orders for purchase, despite warnings from the World Health Organization that its efficacy is unproven.

The Kevin Koe curling team has split with second Colton Flasch after being eliminated from the recent men's national championship in Kingston, Ont., in a tiebreaker game. Flasch joined the foursome in 2018.

The OM Madagascar team mobilises the Malagasy church for prayer through radio programmes and SMS messages.

Madagascar’s ongoing crisis continues to defy definition. Some call Andry Rajoelina’s taking power in March 2009 a popular uprising. Others say this was a military-supported coup, pure and simple. The legitimacy of the new regime remains in question both internally and externally, and peace agreements mediated by the international community lie in tatters.

While the reality and extent of the coup announced yesterday by military officers is still uncertain, the latest events demonstrate the fragility of the situation in Madagascar and the urgent need for a new international strategy to end the long crisis. Negotiations should now focus on international support to the electoral process based on strict conditions.

A l’approche de la décision de la SADC, il est important qu’elle porte toute son attention sur les mesures qui permettent de garantir l’équité de traitement entre les protagonistes. Sans modifier le texte de la feuille de route, les autorités ont la possibilité de prouver leur volonté de garantir la neutralité du processus, afin que l’opposition soit libre de faire le choix d’entrer ou non dans cette transition sur une base équilibrée. Le rejet des autorités de ces mesures exposerait leur absence de volonté de voir se dérouler une transition et des élections crédibles. Il démontrerait également leur choix de plonger le pays dans l’instabilité plutôt que d’accepter des mesures qui renforcent la transition. Le refus de l’opposition d’adhérer au processus ne pourrait plus être justifié par un déséquilibre de la solution proposée.

During the last few months, new options for resolving the Madagascar crisis have emerged in the form of the most recent roadmap proposed by the mediation team of the Southern African Development Community (SADC). Accepted by the authorities and rejected by elements of the opposition, the roadmap remains the subject of debate and there is still no agreement on how to achieve a peaceful transition. In a few weeks from now, the SADC is due to make a statement on the document and accept, reject or amend it. There are other options for changing the course of events without changing the roadmap and these should be explored as quickly as possible.

Madagascar, one of the world’s poorest countries, has been mired in political crisis, since 2009, when 34-year-old former radio disc jockey Andry Rajoelina toppled President Marc Ravalomanana in a military coup d’état.

Madagascar’s recent elections marked an ostensible return to democracy, but unless the new government works hard to implement meaningful political, economic and social reforms, the prospect of further crisis is just a matter of time.

A NEW bar and fine dining restaurant offering dishes with “Glasgow at its very heart” is to open in a historic City Centre building.

Jill Gascoine, actress and novelist

What's the story?

Cardiovascular risk factors predict the development of premature atherosclerosis. As the number of risk factors increases, so does the extent of these lesions. Assessment of cardiovascular risk factors is an accepted practice in adults but is not used in pediatrics.

In this study, the authors discuss how the presence of ≥2 cardiovascular risk factors is associated with vascular changes in adolescents. The findings were compared with the Patholobiological Determinants of Atherosclerosis in Youth risk score to demonstrate that a simple method of clustering is a reliable tool to use in clinical practice. (Read the full article)

Smoking during pregnancy has been related to thicker carotid intima media thickness in young adults, and this was also shown in neonates.

This study is the first to show that the effect of smoking during pregnancy on the vasculature of children is (still) visible at the age of 5 years. Pregnancy appears to be the critical period for this damage to occur. (Read the full article)

Overweight and obese children have a higher prevalence of several cardiovascular disease (CVD) risk factors. There is growing evidence demonstrating that CVD risk factors present during childhood persist into adulthood.

US adolescents had no significant change in prehypertension/hypertension and borderline-high/ high low-density lipoprotein cholesterol prevalence from 1999–2000 to 2007–2008; however, prediabetes/diabetes increased by 14%. (Read the full article)

The causes of Perthes disease are unknown. There is considerable evidence that the disease has a vascular mechanism, although the nature of this is unknown. There is some suggestion that affected individuals may have a heightened cardiovascular risk in adulthood.

Children with Perthes disease have reduced vascular caliber, which is independent of body height, and abnormal functional vascular measures. These findings may be important in the mechanism of disease and may have implications on long-term vascular morbidity. (Read the full article)

Excessive weight gain over the first 18 months of life may have consequences for later body size. However, the relationship of weight gain in this period to atherogenic risk factors in later childhood is not well characterized.

Early postnatal weight gain from birth to 18 months is independently associated with childhood overweight and obesity, excess central adiposity, and greater arterial wall thickness at age 8 years. (Read the full article)

Atherosclerotic cardiovascular diseases are rooted in childhood. Vascular intima-media thickness (IMT) and elasticity are early surrogate markers of atherosclerosis. In adults, cardiorespiratory fitness is associated with enhanced arterial elasticity and decreased IMT.

Fitness was favorably associated with aortic IMT and elasticity in adolescents. The association was independent of several cardiometabolic risk factors. In fit adolescents, the increase in IMT during the preceding 6 years was smaller compared with low-fit peers. (Read the full article)

Uric acid (UA) is associated with hypertension in children, after body weight adjustment. Whether the whole spectrum of variables, such as visceral adiposity, insulin resistance, puberty, and renal function, influence the relationship between UA and blood pressure is unknown.

In a cohort of children at relatively high cardiovascular risk, the association between UA and blood pressure levels is independent of several well-known factors implicated in the development of hypertension, such as insulin resistance, pubertal status, and renal function. (Read the full article)

Kawasaki disease (KD) results in coronary aneurysm formation and an increased risk of cardiovascular complications. Modern treatment of acute KD with intravenous immunoglobulin substantially reduces the rate of acute aneurysm formation.

This study reveals that long-term cardiovascular outcomes for KD patients in the current era are not significantly different than matched controls without KD. Late cardiovascular complications are almost exclusively seen in patients with persistent coronary aneurysms. (Read the full article)

Caffeine has predictable effects on cardiovascular function in both adults and children. Our previous work has shown that there are gender differences in this cardiovascular response, with boys having a greater change in heart rate and blood pressure than girls.

This study shows that the gender differences in cardiovascular response to caffeine emerge after puberty and there are some differences in postpubertal girls across the menstrual cycle. (Read the full article)

Cardiovascular risk begins in childhood. New clinical guidelines established a care strategy for lowering risks. Incorporation of guidelines into routine practice lags due to barriers related to knowledge and attitudes about guidelines, as well as behaviors of practitioners, patients, and clinical systems.

This study demonstrated that a multifaceted approach including tools, education, and support for changes in practice systems can accelerate the adoption of guidelines during routine pediatric well-child visits, compared with dissemination of the guidelines alone. (Read the full article)

Adolescents and adults born early preterm have higher blood pressure and altered glucose metabolism compared with their term born peers. Evidence of an atherogenic lipid profile is inconsistent. Whether these risks apply to those born less preterm is not known.

In adolescence, girls have higher blood pressure and boys a more atherogenic lipid profile than their term born peers. Overall, our results are consistent with a dose-response relationship between shorter length of gestation and increasing levels of cardiovascular risk factors. (Read the full article)

Administration of repeat doses of antenatal glucocorticoids to women at risk for preterm birth after an initial course reduces neonatal morbidity, without affecting rates of neurologic disability in early childhood. However, data on long-term effects on cardiometabolic health are limited.

Exposure to repeat doses of antenatal betamethasone did not increase cardiovascular risk factors at early school age. Clinicians wishing to use repeat antenatal glucocorticoids can be reassured that the risk of future cardiometabolic disease from this therapy is low. (Read the full article)

Microvasculature alterations are associated with increased risk of hypertension in adults. Not much is known about the association of retinal vessel caliber with cardiovascular risk factors among children.

Narrower retinal arteriolar caliber is associated with higher blood pressure, mean arterial pressure, and pulse pressure in school-age children, whereas wider retinal venular caliber is associated with higher carotid-femoral pulse wave velocity. Microvascular adaptations might influence cardiovascular health from childhood onward. (Read the full article)

The resignation of the former U.S. Department of Education staffer, who has led ASCD since mid-2015, follows a long run of membership declines for the organization.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicentre trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90ms mean QTc-prolongation per 100ng/mL increase in piperaquine concentration. The effect of piperaquine on absolute QTc-interval estimated a mean maximum QTc-interval of 456ms (EC₅₀=209ng/mL). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98-2.46% risk of having QTc-prolongation > 60ms in all treatment settings. Although piperaquine administration resulted in QTc-prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy, and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (NFX) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than that in BZ-treated mice. These results were associated with an increase in the number of eosinophils and reticulocytes and level of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the LXA₄ receptor antagonist, Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of acute phase of Chagas disease that are beneficial for chronic patients.

Peroxidases are a group of heterogeneous family of enzyme that plays diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defence system of Leishmania. In view of developing new and novel therapeutics, we have performed in silico studies in order to search for ligand library and identification of new drug candidates and its physiological role against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant anti-leishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family which was derived from the scaffold of DBeQ, targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus have broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibits the parasite's ascorbate peroxidase leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

David S. Freedman
Jun 1, 1999; 103:1175-1182
ARTICLES

"I find my job very exciting; every day is new, as we are creating a brand in the Indian market which is a challenge in itself," says Rahul Vira, CEO, Skechers, South Asia.

2019 Recovery MonthEvent includes recovery walk, treatment information, live performances and recovery stories WILMINGTON (Sept. 19, 2019) –The Treatment Access Center (TASC), the primary liaison between the Department of Health and Social Services’ Division of Substance Abuse and Mental Health (DSAMH) and the criminal justice system, will host its first event celebrating Recovery Month. Celebrating […]

Para los residentes de Delaware, este no es momento de ser complacientes. A partir de las 8:00 a.m. del martes, 28 de abril, los residentes de Delaware deberán usar mascarilla en lugares públicos, incluidos mercados, tiendas, farmacias, consultorios médicos y medios de transporte público. La situación que enfrentamos es muy grave, con nuevos casos de […]

The next Grand Tour episode has been delayed, and host Jeremy Clarkson put producer Andy Wilman on the spot to answer the internet’s questions to when the episode will be released. The live session on Youtube revealed some good insights.