Yen-Chi Chen.

Source: The Annals of Statistics, Volume 47, Number 4, 2174--2203.

Abstract:
In this paper we study the $alpha $-cluster tree ($alpha $-tree) under both singular and nonsingular measures. The $alpha $-tree uses probability contents within a set created by the ordering of points to construct a cluster tree so that it is well defined even for singular measures. We first derive the convergence rate for a density level set around critical points, which leads to the convergence rate for estimating an $alpha $-tree under nonsingular measures. For singular measures, we study how the kernel density estimator (KDE) behaves and prove that the KDE is not uniformly consistent but pointwise consistent after rescaling. We further prove that the estimated $alpha $-tree fails to converge in the $L_{infty }$ metric but is still consistent under the integrated distance. We also observe a new type of critical points—the dimensional critical points (DCPs)—of a singular measure. DCPs are points that contribute to cluster tree topology but cannot be defined using density gradient. Building on the analysis of the KDE and DCPs, we prove the topological consistency of an estimated $alpha $-tree.

Yiyi Liu, Joshua L. Warren, Hongyu Zhao.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1733--1752.

Abstract:
Understanding the heterogeneity of cells is an important biological question. The development of single-cell RNA-sequencing (scRNA-seq) technology provides high resolution data for such inquiry. A key challenge in scRNA-seq analysis is the high variability of measured RNA expression levels and frequent dropouts (missing values) due to limited input RNA compared to bulk RNA-seq measurement. Existing clustering methods do not perform well for these noisy and zero-inflated scRNA-seq data. In this manuscript we propose a Bayesian hierarchical model, called BasClu, to appropriately characterize important features of scRNA-seq data in order to more accurately cluster cells. We demonstrate the effectiveness of our method with extensive simulation studies and applications to three real scRNA-seq datasets.

Amir Najafi, Seyed Abolfazl Motahari, Hamid R. Rabiee.

Source: Bernoulli, Volume 26, Number 2, 1535--1559.

Abstract:
A Bernoulli Mixture Model (BMM) is a finite mixture of random binary vectors with independent dimensions. The problem of clustering BMM data arises in a variety of real-world applications, ranging from population genetics to activity analysis in social networks. In this paper, we analyze the clusterability of BMMs from a theoretical perspective, when the number of clusters is unknown. In particular, we stipulate a set of conditions on the sample complexity and dimension of the model in order to guarantee the Probably Approximately Correct (PAC)-clusterability of a dataset. To the best of our knowledge, these findings are the first non-asymptotic bounds on the sample complexity of learning or clustering BMMs.

Laura Anderlucci, Angela Montanari, Cinzia Viroli.

Source: Statistical Science, Volume 34, Number 2, 280--300.

Abstract:
In this paper, we retrace the recent history of statistics by analyzing all the papers published in five prestigious statistical journals since 1970, namely: The Annals of Statistics , Biometrika , Journal of the American Statistical Association , Journal of the Royal Statistical Society, Series B and Statistical Science . The aim is to construct a kind of “taxonomy” of the statistical papers by organizing and clustering them in main themes. In this sense being identified in a cluster means being important enough to be uncluttered in the vast and interconnected world of the statistical research. Since the main statistical research topics naturally born, evolve or die during time, we will also develop a dynamic clustering strategy, where a group in a time period is allowed to migrate or to merge into different groups in the following one. Results show that statistics is a very dynamic and evolving science, stimulated by the rise of new research questions and types of data.

Eight COVID-19 cases are now connected to that workplace, including six employees.

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)

The prevalence of asthma and smoking among adolescents in Jordan is high. Well-designed, school-based, peer-led education programs can have a positive impact on asthma self-management in adolescents. Student peer leaders can be useful and responsible partners in health promotion programs.

A peer-led asthma education program —Adolescent Asthma Action—for adolescents developed in Australia was adapted to suit non–English-speaking cultures in the Middle East. Peer-led education led to improved self-management of asthma and motivated students to avoid smoking. (Read the full article)

Social and environmental risks related to substandard housing contribute to adverse health outcomes. Partnerships between the health care and legal systems can help families address such risks and help clinicians understand the legal context of health.

A medical-legal partnership colocated in a pediatric primary care setting identified and treated a large cluster of poor quality, substandard housing. Housing improvements were possible because of strong collaboration between clinicians, attorneys, community partners, and families. (Read the full article)

Gaining intravenous access in children can be difficult. Recently, several near-infrared devices have been introduced attempting to support intravenous cannulation by visualizing veins underneath skin. Only one of those devices has been evaluated systemically thus far and results are inconclusive.

Although it was possible to visualize veins with near-infrared in most patients, the VascuLuminator did not improve the success of cannulation. An explanation is that the main problem is probably not localization of the vein but insertion of the cannula. (Read the full article)

Chlorhexidine cleansing of the cord can reduce mortality in high-risk settings. Time to separation may increase with topical applications of chlorhexidine; 1 previous community trial quantified this increase and did not measure whether caretakers perceived the delay.

Single and multiple cleansing of the umbilical cord increases time to separation by ~50%, or an average of 2 to 2.5 days. Caretakers were able to detect this difference and expressed dissatisfaction, while still accepting the intervention. (Read the full article)

At least half of the achievement gap for low-income, minority children is present at kindergarten entry; however, there are no population-level early childhood interventions that effectively engage and support families and teachers to ameliorate the impact of adversity on achievement.

This study evaluated ParentCorps, a family-centered, school-based intervention to promote self-regulation and learning for all children entering school in disadvantaged, urban neighborhoods. ParentCorps results in higher kindergarten achievement among low-income, minority children. (Read the full article)

Individuals with autism spectrum disorders have a higher comorbidity burden than the general pediatric population, including higher rates of seizures, psychiatric illness, and gastrointestinal disorders.

Comorbidities do not occur evenly. Our clustering analysis reveals subgroups characterized by seizure, psychiatric disorders, and complex multisystem disorders including auditory and gastrointestinal disorders. Correlations between seizure, psychiatric disorders, and gastrointestinal disorders are validated on a sample from a second hospital. (Read the full article)

Integrated or collaborative care intervention models have revealed gains in provider care processes and outcomes in adult, child, and adolescent populations with mental health disorders. However optimistic, conclusions are not definitive due to methodologic limitations and a dearth of studies.

This randomized trial provides further evidence for the efficacy of an on-site intervention (Doctor Office Collaborative Care) coordinated by care managers for children's behavior problems. The findings provide support for integrated behavioral health care using novel provider and caregiver outcomes. (Read the full article)

Resistance exercise is known to have a robust effect on glycemic control and cardiometabolic health among children and adolescents, even in the absence of weight loss.

Normalized strength capacity is associated with lower cardiometabolic risk clustering in boys and girls, even after adjustment for cardiorespiratory fitness, level of physical activity, and BMI. (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)

Adolescent relationship abuse (ARA) is prevalent in confidential clinic settings such as school health centers (SHCs) and is associated with poor health outcomes. No evidence-based interventions target reduction of ARA in the SHC setting.

This study provides the first evidence of the potential benefits of a brief provider-delivered universal education and counseling intervention in SHCs to address and prevent a major public health problem: ARA. (Read the full article)

Frequency of influenza vaccination is low, partially because of missed opportunities to vaccinate. Barriers to implementing successful influenza vaccination reminders in the electronic health record include alert fatigue and incomplete vaccination information due to scattered records.

A noninterruptive, immunization information system–linked influenza vaccination reminder can increase vaccination late in the winter when fewer vaccine doses are usually administered. Tailoring the reminder to clinicians’ needs can increase its use. (Read the full article)

Although pediatric professional guidelines emphasize addressing a child’s social environment in the context of well child care, it remains unclear whether screening for unmet basic needs at visits increases low-income families’ receipt of community-based resources.

This study demonstrates that systematically screening and referring for social determinants of health during primary care can lead to the receipt of more community resources for families. (Read the full article)

Exclusive breastfeeding until 6 months of an infant’s age is described as the safest, most powerful and cost-effective intervention to reduce infant morbidity and mortality globally. In developing countries, only ~25% of infants are exclusively breastfed for 6 months.

We developed a psycho-educational intervention combining education with techniques of cognitive-behavioral therapy, integrated it into the routine work of community health workers, which increased the rate and duration of exclusive breastfeeding until 6 months of an infant’s age. (Read the full article)

Parent refusal and delay of childhood vaccines has increased in recent years and is believed to cluster in communities. Such clustering could pose public health risks and barriers to achieving quality benchmarks for immunization coverage.

We found that underimmunization and vaccine refusal cluster geographically. Spatial scan analysis may be a useful tool to identify locations where clinicians may face challenges to achieving benchmarks for immunization coverage and that deserve special focus for interventions. (Read the full article)

Sleep deprivation is a worldwide problem in adolescents. The effectiveness of sleep education in enhancing sleep knowledge with consequent modification of sleep habits remains uncertain, in view of small sample sizes and lack of control groups in previous studies.

This large-scale, cluster randomized controlled study found that a school-based sleep education program was effective in enhancing sleep knowledge and improving behavioral and mental health, but it had no significant impact on sleep duration or pattern among adolescents. (Read the full article)

More than 200 million children <5 years are not reaching their developmental potential. Lack of stimulating caregiving is a major cause, and effective scalable interventions are needed. Integrating parenting with health services has been recommended, but there are few evaluations.

An innovative parenting intervention can be delivered at routine visits for primary health care, with benefits to child cognitive development and parenting knowledge. This approach using films, discussion, and practice has the potential for delivery at scale. (Read the full article)

As the government says India has been able to prevent community transmission of the coronavirus, there are concerns about at least three different clusters of cases in Delhi, in which the primary...

The units situated within the corporate limits have been allowed to have 25-30% workforce capacity initially and the units situated outside the corporation will have 50% workforce capacity.

According to officials who traced the movement of the group, the entire group travelled in a second class coach (S9) of AP Sampark Kranti Express. They first got down on March 13 at Ramagundam in Peddapalli district of Telangana.

Hi all,

I have a question regarding the manufacture : how to check a cluster of same net vias spacing, with have no shape or cline covered

Whitepaper called Exploiting CAN-Bus using Instrument Cluster Simulator.

Bull / IBM AIX Clusterwatch / Watchware suffers from having trivial admin credentials, system file writes, and OS command injection vulnerabilities.

UN Secretary General Antonio Guterres on Friday said the coronavirus pandemic keeps unleashing “a tsunami of hate and xenophobia, scapegoating and scaremongering” and appealed for “an all-out effort to end hate speech globally”.The UN chief said “anti-foreigner sentiment has surged online and in the streets, anti-Semitic conspiracy theories have spread, and Covid-19-related anti-Muslim attacks have occurred”. Migrants and refugees “have been vilified as a source of the virus – and then denied…

South Korea confirmed 12 new coronavirus cases on Friday, its first increase above 10 in five days, as authorities warned numbers would increase as it had identified a new cluster of infections linked to a 29-year-old man.The IT company employee had spread the virus to at least 14 others as he wandered around the capital Seoul and four neighbouring cities over a long weekend period at the start of the month, said the Korea Centres for Disease Control and Prevention.While the 12 cases were those…

Title: Workers With Cluster Headaches Take Twice as Many Sick Days
Category: Health News
Created: 2/6/2020 12:00:00 AM
Last Editorial Review: 2/6/2020 12:00:00 AM

Endogenous viral elements (EVEs) are found in many eukaryotic genomes. Despite considerable knowledge about genomic elements such as transposons (TEs) and retroviruses, we still lack information about nonretroviral EVEs. Aedes aegypti mosquitoes have a highly repetitive genome that is covered with EVEs. Here, we identified 129 nonretroviral EVEs in the AaegL5 version of the A. aegypti genome. These EVEs were significantly associated with TEs and preferentially located in repeat-rich clusters within intergenic regions. Genome-wide transcriptome analysis showed that most EVEs generated transcripts although only around 1.4% were sense RNAs. The majority of EVE transcription was antisense and correlated with the generation of EVE-derived small RNAs. A single genomic cluster of EVEs located in a 143 kb repetitive region in chromosome 2 contributed with 42% of antisense transcription and 45% of small RNAs derived from viral elements. This region was enriched for TE-EVE hybrids organized in the same coding strand. These generated a single long antisense transcript that correlated with the generation of phased primary PIWI-interacting RNAs (piRNAs). The putative promoter of this region had a conserved binding site for the transcription factor Cubitus interruptus, a key regulator of the flamenco locus in Drosophila melanogaster. Here, we have identified a single unidirectional piRNA cluster in the A. aegypti genome that is the major source of EVE transcription fueling the generation of antisense small RNAs in mosquitoes. We propose that this region is a flamenco-like locus in A. aegypti due to its relatedness to the major unidirectional piRNA cluster in Drosophila melanogaster.

RiVax is a promising recombinant ricin toxin A subunit (RTA) vaccine antigen that has been shown to be safe and immunogenic in humans and effective at protecting rhesus macaques against lethal-dose aerosolized toxin exposure. We previously used a panel of RTA-specific monoclonal antibodies (MAbs) to demonstrate, by competition enzyme-linked immunosorbent assay (ELISA), that RiVax elicits similar serum antibody profiles in humans and macaques. However, the MAb binding sites on RiVax have yet to be defined. In this study, we employed hydrogen exchange-mass spectrometry (HX-MS) to localize the epitopes on RiVax recognized by nine toxin-neutralizing MAbs and one nonneutralizing MAb. Based on strong protection from hydrogen exchange, the nine MAbs grouped into four spatially distinct epitope clusters (namely, clusters I to IV). Cluster I MAbs protected RiVax's α-helix B (residues 94 to 107), a protruding immunodominant secondary structure element known to be a target of potent toxin-neutralizing antibodies. Cluster II consisted of two subclusters located on the "back side" (relative to the active site pocket) of RiVax. One subcluster involved α-helix A (residues 14 to 24) and α-helices F-G (residues 184 to 207); the other encompassed β-strand d (residues 62 to 69) and parts of α-helices D-E (154 to 164) and the intervening loop. Cluster III involved α-helices C and G on the front side of RiVax, while cluster IV formed a sash from the front to back of RiVax, spanning strands b, c, and d (residues 35 to 59). Having a high-resolution B cell epitope map of RiVax will enable the development and optimization of competitive serum profiling assays to examine vaccine-induced antibody responses across species.

The type VI secretion system (T6SS) is a weapon for delivering effectors into target cells that is widespread in Gram-negative bacteria. The T6SS is a highly versatile machine, as it can target both eukaryotic and prokaryotic cells, and it has been proposed that T6SSs are adapted to the specific needs of each bacterium. The expression of T6SS gene clusters and the activation of the secretion apparatus are therefore tightly controlled. In enteroaggregative Escherichia coli (EAEC), the sci1 T6SS gene cluster is subject to a complex regulation involving both the ferric uptake regulator (Fur) and DNA adenine methylase (Dam)-dependent DNA methylation. In this study, an additional, internal, promoter was identified within the sci1 gene cluster using +1 transcriptional mapping. Further analyses demonstrated that this internal promoter is controlled by a mechanism strictly identical to that of the main promoter. The Fur binding box overlaps the –10 transcriptional element and a Dam methylation site, GATC-32. Hence, the expression of the distal sci1 genes is repressed and the GATC-32 site is protected from methylation in iron-rich conditions. The Fur-dependent protection of GATC-32 was confirmed by an in vitro methylation assay. In addition, the methylation of GATC-32 negatively impacted Fur binding. The expression of the sci1 internal promoter is therefore controlled by iron availability through Fur regulation, whereas Dam-dependent methylation maintains a stable ON expression in iron-limited conditions.

IMPORTANCE Bacteria use weapons to deliver effectors into target cells. One of these weapons, the type VI secretion system (T6SS), assembles a contractile tail acting as a spring to propel a toxin-loaded needle. Its expression and activation therefore need to be tightly regulated. Here, we identified an internal promoter within the sci1 T6SS gene cluster in enteroaggregative E. coli. We show that this internal promoter is controlled by Fur and Dam-dependent methylation. We further demonstrate that Fur and Dam compete at the –10 transcriptional element to finely tune the expression of T6SS genes. We propose that this elegant regulatory mechanism allows the optimum production of the T6SS in conditions where enteroaggregative E. coli encounters competing species.

Mutation and translocation of fibroblast growth factor receptors often lead to aberrant signaling and cancer. This work focuses on the t(8;22)(p11;q11) chromosomal translocation which creates the breakpoint cluster region (BCR) fibroblast growth factor receptor1 (FGFR1) (BCR-FGFR1) fusion protein. This fusion occurs in stem cell leukemia/lymphoma, which can progress to atypical chronic myeloid leukemia, acute myeloid leukemia, or B-cell lymphoma. This work focuses on the biochemical characterization of BCR-FGFR1 and identification of novel therapeutic targets. The tyrosine kinase activity of FGFR1 is required for biological activity as shown using transformation assays, interleukin-3 independent cell proliferation, and liquid chromatography/mass spectroscopy analyses. Furthermore, BCR contributes a coiled-coil oligomerization domain, also essential for oncogenic transformation by BCR-FGFR1. The importance of salt bridge formation within the coiled-coil domain is demonstrated, as disruption of three salt bridges abrogates cellular transforming ability. Lastly, BCR-FGFR1 acts as a client of the chaperonin heat shock protein 90 (Hsp90), suggesting that BCR-FGFR1 relies on Hsp90 complex to evade proteasomal degradation. Transformed cells expressing BCR-FGFR1 are sensitive to the Hsp90 inhibitor Ganetespib, and also respond to combined treatment with Ganetespib plus the FGFR inhibitor BGJ398. Collectively, these data suggest novel therapeutic approaches for future stem cell leukemia/lymphoma treatment: inhibition of BCR oligomerization by disruption of required salt bridges; and inhibition of the chaperonin Hsp90 complex.

Burkholderia sp. strain SG-MS1 and Pseudomonas sp. strain SG-MS2 have previously been found to mineralize (+)-pinoresinol through a common catabolic pathway. Here, we used comparative genomics, proteomics, protein semipurification, and heterologous expression to identify a flavoprotein from the vanillyl alcohol oxidase/p-cresol methyl hydroxylase (VAO/PCMH) enzyme family in SG-MS2 that carries out the initial hydroxylation of (+)-pinoresinol at the benzylic carbon. The cognate gene is translationally coupled with a downstream cytochrome gene, and the cytochrome is required for activity. The flavoprotein has a unique combination of cofactor binding and cytochrome requirements for the VAO/PCMH family. The heterologously expressed enzyme has a K_m of 1.17 μM for (+)-pinoresinol. The enzyme is overexpressed in strain SG-MS2 upon exposure to (+)-pinoresinol, along with 45 other proteins, 22 of which were found to be encoded by genes in an approximately 35.1-kb cluster also containing the flavoprotein and cytochrome genes. Homologs of 18 of these 22 genes, plus the flavoprotein and cytochrome genes, were also found in a 38.7-kb cluster in SG-MS1. The amino acid identities of four of the other proteins within the SG-MS2 cluster suggest they catalyze conversion of hydroxylated pinoresinol to protocatechuate and 2-methoxyhydroquinone. Nine other proteins upregulated in SG-MS2 on exposure to (+)-pinoresinol appear to be homologs of proteins known to comprise the protocatechuate and 2-methoxyhydroquinone catabolic pathways, but only three of the cognate genes lie within the cluster containing the flavoprotein and cytochrome genes.

IMPORTANCE (+)-Pinoresinol is an important plant defense compound, a major food lignan for humans and some other animals, and the model compound used to study degradation of the β-β' linkages in lignin. We report a gene cluster, in one strain each of Pseudomonas and Burkholderia, that is involved in the oxidative catabolism of (+)-pinoresinol. The flavoprotein component of the α-hydroxylase which heads the pathway belongs to the 4-phenol oxidizing (4PO) subgroup of the vanillyl alcohol oxidase/p-cresol methyl hydroxylase (VAO/PCMH) enzyme family but constitutes a novel combination of cofactor and electron acceptor properties for the family. It is translationally coupled with a cytochrome gene whose product is also required for activity. The work casts new light on the biology of (+)-pinoresinol and its transformation to other bioactive molecules. Potential applications of the findings include new options for deconstructing lignin into useful chemicals and the generation of new phytoestrogenic enterolactones from lignans.

As lightning crackled in the clouds, the GOES-16 weather satellite watched all the violent action from 22,000 miles away.

As the US deals with a Covid-19 catastrophe in its meatworks, the Melbourne factory points to the potential for outbreaks in Australia

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Working in an abattoir at the best of times is tough. The hours are long, the labour is intensive and, for rank and file labourers, the pay is low.

Now, in the Covid-19 crisis, workers have one more thing to worry about – around the world their factories have proved to be a hotbed of infection. As Australia moves to ease lockdown laws, meat workers may still be at the frontline of exposure and infection.

A new union-released report accuses Qantas of downplaying the risks of coronavirus before an outbreak at Adelaide Airport — but the airline has denied any wrongdoing.

Victoria's total of COVID-19 cases rises to 1,361, as Chief Health Officer Brett Sutton reveals authorities are investigating three cases linked to a Melbourne aged care facility.

At least three groups of cruise ships, with 15 in total, are clustered together off Coco Cay and Great Stirrup Cay in the Bahamas and about 12 are off the coast of Manila, in the Philippines.

Another aged care facility has been hit with a coronavirus outbreak with three people testing positive and more cases expected to emerge.

There are now 45 cases of the deadly respiratory infection linked to Cedar Meats in Brooklyn, west Melbourne.

Brittany Cooper, a professor at Rutger's Department of Women's, Gender, and Sexuality Studies, lambasted Trump and his supporters, who she declared were 'willing to die' for him.

Two hospitals in Burnie, northwest Tasmania, were closed on Monday amid a cluster of more than 60 COVID-19 cases, including about 45 staff, associated with the facilities.

The probe was launched earlier this month after Professor Brendan Murphy made the suggestion to a New Zealand parliamentary committee.

Two workers and two close contacts are among the new cases bringing the total from the Brooklyn facility in Melbourne's west to 75.