Tracking the genomic evolution of breast cancer metastasis

Therapeutic choices for metastatic tumors are, in most cases, based upon the histological and molecular analysis of the corresponding primary tumor. Understanding whether and to what extent the genomic landscape of metastasis differs from the tumors from which they originated is critical yet largely unknown. A recent report tackled this key issue by comparing the genomic and transcriptional profile of a metastatic lobular breast tumor with that of the primary tumor surgically removed 9 years earlier. The extent of the differences suggests a high degree of mutational heterogeneity between primary and metastatic lesions and indicates that significant evolution occurs during breast cancer progression

SL(2,R) Chern-Simons, Liouville, and Gauge Theory on Duality Walls

We propose an equivalence of the partition functions of two different 3d gauge theories. On one side of the correspondence we consider the partition function of 3d SL(2,R) Chern-Simons theory on a 3-manifold, obtained as a punctured Riemann surface times an interval. On the other side we have a partition function of a 3d N=2 superconformal field theory on S^3, which is realized as a duality domain wall in a 4d gauge theory on S^4. We sketch the proof of this conjecture using connections with quantum Liouville theory and quantum Teichmuller theory, and study in detail the example of the once-punctured torus. Motivated by these results we advocate a direct Chern-Simons interpretation of the ingredients of (a generalization of) the Alday-Gaiotto-Tachikawa relation. We also comment on M5-brane realizations as well as on possible generalizations of our proposals.Comment: 53+1 pages, 14 figures; v2: typos corrected, references adde

Skeletal muscle atrophy in heart failure with diabetes: from molecular mechanisms to clinical evidence

Two highly prevalent and growing global diseases impacted by skeletal muscle atrophy are chronic heart failure (HF) and type 2 diabetes mellitus (DM). The presence of either condition increases the likelihood of developing the other, with recent studies revealing a large and relatively poorly characterized clinical population of patients with coexistent HF and DM (HFDM). HFDM results in worse symptoms and poorer clinical outcomes compared with DM or HF alone, and cardiovascular‐focused disease‐modifying agents have proven less effective in HFDM indicating a key role of the periphery. This review combines current clinical knowledge and basic biological mechanisms to address the critical emergence of skeletal muscle atrophy in patients with HFDM as a key driver of symptoms. We discuss how the degree of skeletal muscle wasting in patients with HFDM is likely underpinned by a variety of mechanisms that include mitochondrial dysfunction, insulin resistance, inflammation, and lipotoxicity. Given many atrophic triggers (e.g. ubiquitin proteasome/autophagy/calpain activity and supressed IGF1‐Akt‐mTORC1 signalling) are linked to increased production of reactive oxygen species, we speculate that a higher pro‐oxidative state in HFDM could be a unifying mechanism that promotes accelerated fibre atrophy. Overall, our proposal is that patients with HFDM represent a unique clinical population, prompting a review of treatment strategies including further focus on elucidating potential mechanisms and therapeutic targets of muscle atrophy in these distinct patients

Determinants of medication adherence to antihypertensive medications among a Chinese population using Morisky medication adherence scale

<b>Background and objectives</b> Poor adherence to medications is one of the major public health challenges. Only one-third of the population reported successful control of blood pressure, mostly caused by poor drug adherence. However, there are relatively few reports studying the adherence levels and their associated factors among Chinese patients. This study aimed to study the adherence profiles and the factors associated with antihypertensive drug adherence among Chinese patients.<p></p> <b>Methods</b> A cross-sectional study was conducted in an outpatient clinic located in the New Territories Region of Hong Kong. Adult patients who were currently taking at least one antihypertensive drug were invited to complete a self-administered questionnaire, consisting of basic socio-demographic profile, self-perceived health status, and self-reported medication adherence. The outcome measure was the Morisky Medication Adherence Scale (MMAS-8). Good adherence was defined as MMAS scores greater than 6 points (out of a total score of 8 points).<p></p> <b>Results</b> From 1114 patients, 725 (65.1%) had good adherence to antihypertensive agents. Binary logistic regression analysis was conducted. Younger age, shorter duration of antihypertensive agents used, job status being employed, and poor or very poor self-perceived health status were negatively associated with drug adherence.<p></p> <b>Conclusion</b> This study reported a high proportion of poor medication adherence among hypertensive subjects. Patients with factors associated with poor adherence should be more closely monitored to optimize their drug taking behavior

Conflict in pedestrian networks

Encouraging pedestrian activity is increasingly recognised as beneficial for public health, the environment and the economy. As our cities become more crowded, there is a need for urban planners to take into account more explicitly pedestrian needs. The term that is now in use is that a city should be ‘walkable’. For route planning, whereas much attention has been given to shortest path, in distance or time, much less attention has been paid to flow levels and the difficulties they pose on the route. This paper considers problems posed by conflicting paths, for example cross-traffic. We use network centrality measures to make a first estimate of differing levels of conflict posed at the network nodes. We take special note of the role of collective motion in determining network usage. A small case study illustrates the method

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Quantum physics in inertial and gravitational fields

Covariant generalizations of well-known wave equations predict the existence of inertial-gravitational effects for a variety of quantum systems that range from Bose-Einstein condensates to particles in accelerators. Additional effects arise in models that incorporate Born reciprocity principle and the notion of a maximal acceleration. Some specific examples are discussed in detail.Comment: 25 pages,1 figure,to appear in "Relativity in Rotating Frame

Exome Sequencing Reveals Comprehensive Genomic Alterations across Eight Cancer Cell Lines

It is well established that genomic alterations play an essential role in oncogenesis, disease progression, and response of tumors to therapeutic intervention. The advances of next-generation sequencing technologies (NGS) provide unprecedented capabilities to scan genomes for changes such as mutations, deletions, and alterations of chromosomal copy number. However, the cost of full-genome sequencing still prevents the routine application of NGS in many areas. Capturing and sequencing the coding exons of genes (the “exome”) can be a cost-effective approach for identifying changes that result in alteration of protein sequences. We applied an exome-sequencing technology (Roche Nimblegen capture paired with 454 sequencing) to identify sequence variation and mutations in eight commonly used cancer cell lines from a variety of tissue origins (A2780, A549, Colo205, GTL16, NCI-H661, MDA-MB468, PC3, and RD). We showed that this technology can accurately identify sequence variation, providing ∼95% concordance with Affymetrix SNP Array 6.0 performed on the same cell lines. Furthermore, we detected 19 of the 21 mutations reported in Sanger COSMIC database for these cell lines. We identified an average of 2,779 potential novel sequence variations/mutations per cell line, of which 1,904 were non-synonymous. Many non-synonymous changes were identified in kinases and known cancer-related genes. In addition we confirmed that the read-depth of exome sequence data can be used to estimate high-level gene amplifications and identify homologous deletions. In summary, we demonstrate that exome sequencing can be a reliable and cost-effective way for identifying alterations in cancer genomes, and we have generated a comprehensive catalogue of genomic alterations in coding regions of eight cancer cell lines. These findings could provide important insights into cancer pathways and mechanisms of resistance to anti-cancer therapies

Ecological implications of a flower size/number trade-off in tropical forest trees

Peer reviewedPublisher PD

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally