Acupuncture for chronic neck pain: a pilot for a randomised controlled trial

Background: Acupuncture is increasingly being used for many conditions including chronic neck pain. However the evidence remains inconclusive, indicating the need for further well-designed research. The aim of this study was to conduct a pilot randomised controlled parallel arm trial, to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain. Methods: Patients whose GPs had diagnosed neck pain were recruited from one general practice, and randomised to receive usual GP care only, or acupuncture ( up to 10 treatments over 3 months) as an adjunctive treatment to usual GP care. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ) at 3 months. The primary analysis was to determine the sample size for the full scale study. Results: Of the 227 patients with neck pain identified from the GP database, 28 (12.3%) consenting patients were eligible to participate in the pilot and 24 (10.5%) were recruited to the trial. Ten patients were randomised to acupuncture, receiving an average of eight treatments from one of four acupuncturists, and 14 were randomised to usual GP care alone. The sample size for the full scale trial was calculated from a clinically meaningful difference of 5% on the NPQ and, from this pilot, an adjusted standard deviation of 15.3%. Assuming 90% power at the 5% significance level, a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14%. In order to achieve this sample, one would need to identify patients from databases of GP practices with a total population of 230,000 patients, or approximately 15 GP practices roughly equal in size to the one involved in this study (i.e. 15,694 patients). Conclusion: This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for neck pain

On-chip beam rotators, polarizers and adiabatic mode converters through low-loss waveguides with variable cross-sections

Photonics integrated circuitry would benefit considerably from the ability to arbitrarily control waveguide cross-sections with high precision and low loss, in order to provide more degrees of freedom in manipulating propagating light. Here, we report on a new optical-fibres-compatible glass waveguide by femtosecond laser writing, namely spherical phase induced multi-core waveguide (SPIM-WG), which addresses this challenging task with three dimensional on-chip light control. Precise deformation of cross-sections is achievable along the waveguide, with shapes and sizes finely controllable of high resolution in both horizontal and vertical transversal directions. We observed that these waveguides have high refractive index contrast of 0.017, low propagation loss of 0.14 dB/cm, and very low coupling loss of 0.19 dB coupled from a single mode fibre. SPIM-WG devices were easily fabricated that were able to perform on-chip beam rotation through varying angles, or manipulate polarization state of propagating light for target wavelengths. We also demonstrated SPIM-WG mode converters that provide arbitrary adiabatic mode conversion with high efficiency between symmetric and asymmetric non-uniform modes; examples include circular, elliptical modes and asymmetric modes from ppKTP waveguides which are generally applied in frequency conversion and quantum light sources. Created inside optical glass, these waveguides and devices have the capability to operate across ultra-broad bands from visible to infrared wavelengths. The compatibility with optical fibre also paves the way toward packaged photonic integrated circuitry, which usually needs input and output fibre connections

Engineering of quantum dot photon sources via electro-elastic fields

The possibility to generate and manipulate non-classical light using the tools of mature semiconductor technology carries great promise for the implementation of quantum communication science. This is indeed one of the main driving forces behind ongoing research on the study of semiconductor quantum dots. Often referred to as artificial atoms, quantum dots can generate single and entangled photons on demand and, unlike their natural counterpart, can be easily integrated into well-established optoelectronic devices. However, the inherent random nature of the quantum dot growth processes results in a lack of control of their emission properties. This represents a major roadblock towards the exploitation of these quantum emitters in the foreseen applications. This chapter describes a novel class of quantum dot devices that uses the combined action of strain and electric fields to reshape the emission properties of single quantum dots. The resulting electro-elastic fields allow for control of emission and binding energies, charge states, and energy level splittings and are suitable to correct for the quantum dot structural asymmetries that usually prevent these semiconductor nanostructures from emitting polarization-entangled photons. Key experiments in this field are presented and future directions are discussed.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Growth disrupting mutations in epigenetic regulatory molecules are associated with abnormalities of epigenetic aging.

Germline mutations in fundamental epigenetic regulatory molecules including DNA methyltransferase 3 alpha (DNMT3A) are commonly associated with growth disorders, whereas somatic mutations are often associated with malignancy. We profiled genome-wide DNA methylation patterns in DNMT3A c.2312G > A; p.(Arg771Gln) carriers in a large Amish sibship with Tatton-Brown-Rahman syndrome (TBRS), their mosaic father, and 15 TBRS patients with distinct pathogenic de novo DNMT3A variants. This defined widespread DNA hypomethylation at specific genomic sites enriched at locations annotated as genes involved in morphogenesis, development, differentiation, and malignancy predisposition pathways. TBRS patients also displayed highly accelerated DNA methylation aging. These findings were most marked in a carrier of the AML-associated driver mutation p.Arg882Cys. Our studies additionally defined phenotype-related accelerated and decelerated epigenetic aging in two histone methyltransferase disorders: NSD1 Sotos syndrome overgrowth disorder and KMT2D Kabuki syndrome growth impairment. Together, our findings provide fundamental new insights into aberrant epigenetic mechanisms, the role of epigenetic machinery maintenance, and determinants of biological aging in these growth disorders

Proteomic Analysis of Human Skin Treated with Larval Schistosome Peptidases Reveals Distinct Invasion Strategies among Species of Blood Flukes

Schistosome parasites are a major cause of disease in the developing world, but the mechanism by which these parasites first infect their host has been studied at the molecular level only for S. mansoni. In this paper, we have mined recent genome annotations of S. mansoni and S. japonicum, a zoonotic schistosome species, to identify differential expansion of peptidase gene families that may be involved in parasite invasion and subsequent migration through skin. Having identified a serine peptidase gene family in S. mansoni and a cysteine peptidase gene family in S. japonicum, we then used a comparative proteomic approach to identify potential substrates of representative members of both classes of enzymes from S. mansoni in human skin. The results of this study suggest that while these species evolved to use different classes of peptidases in host invasion, both are capable of cleaving components of the epidermis and dermal extracellular matrix, as well as proteins involved in the host immune response against the migrating parasite

Recommender Systems

The ongoing rapid expansion of the Internet greatly increases the necessity of effective recommender systems for filtering the abundant information. Extensive research for recommender systems is conducted by a broad range of communities including social and computer scientists, physicists, and interdisciplinary researchers. Despite substantial theoretical and practical achievements, unification and comparison of different approaches are lacking, which impedes further advances. In this article, we review recent developments in recommender systems and discuss the major challenges. We compare and evaluate available algorithms and examine their roles in the future developments. In addition to algorithms, physical aspects are described to illustrate macroscopic behavior of recommender systems. Potential impacts and future directions are discussed. We emphasize that recommendation has a great scientific depth and combines diverse research fields which makes it of interests for physicists as well as interdisciplinary researchers.Comment: 97 pages, 20 figures (To appear in Physics Reports

Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence

In recent years it has become increasingly clear that articular cartilage harbours a viable pool ofprogenitor cells and interest has focussed on their role during development and disease. Analysis ofprogenitor numbers using fluorescence-activated sorting techniques has resulted in wide-rangingestimates, which may be the result of context-dependent expression of cell surface markers. Wehave used a colony-forming assay to reliably determine chondroprogenitor numbers in normal andosteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P < 0.0001). Intriguingly,cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilagerevealed the presence of a divergent progenitor subpopulation characterised by an early senescentphenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidaseactivity, lower average telomere lengths but retained the capacity to undergo multi-lineagedifferentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be asignificant component of the pathological process. This study shows that although early senescenceis an inherent property of a subset of activated progenitors, there is also a pool of progenitors withextended viability and regenerative potential residing within osteoarthritic cartilage

Acromioclavicular joint dislocation: a comparative biomechanical study of the palmaris-longus tendon graft reconstruction with other augmentative methods in cadaveric models

<p>Abstract</p> <p>Background</p> <p>Acromioclavicular injuries are common in sports medicine. Surgical intervention is generally advocated for chronic instability of Rockwood grade III and more severe injuries. Various methods of coracoclavicular ligament reconstruction and augmentation have been described. The objective of this study is to compare the biomechanical properties of a novel palmaris-longus tendon reconstruction with those of the native AC+CC ligaments, the modified Weaver-Dunn reconstruction, the ACJ capsuloligamentous complex repair, screw and clavicle hook plate augmentation.</p> <p>Hypothesis</p> <p>There is no difference, biomechanically, amongst the various reconstruction and augmentative methods.</p> <p>Study Design</p> <p>Controlled laboratory cadaveric study.</p> <p>Methods</p> <p>54 cadaveric native (acromioclavicular and coracoclavicular) ligaments were tested using the Instron machine. Superior loading was performed in the 6 groups: 1) in the intact states, 2) after modified Weaver-Dunn reconstruction (WD), 3) after modified Weaver-Dunn reconstruction with acromioclavicular joint capsuloligamentous repair (WD.ACJ), 4) after modified Weaver-Dunn reconstruction with clavicular hook plate augmentation (WD.CP) or 5) after modified Weaver-Dunn reconstruction with coracoclavicular screw augmentation (WD.BS) and 6) after modified Weaver-Dunn reconstruction with mersilene tape-palmaris-longus tendon graft reconstruction (WD. PLmt). Posterior-anterior (horizontal) loading was similarly performed in all groups, except groups 4 and 5. The respective failure loads, stiffnesses, displacements at failure and modes of failure were recorded. Data analysis was carried out using a one-way ANOVA, with Student's unpaired t-test for unpaired data (S-PLUS statistical package 2005).</p> <p>Results</p> <p>Native ligaments were the strongest and stiffest when compared to other modes of reconstruction and augmentation except coracoclavicular screw, in both posterior-anterior and superior directions (p < 0.005).</p> <p>WD.ACJ provided additional posterior-anterior (P = 0. 039) but not superior (p = 0.250) stability when compared to WD alone.</p> <p>WD+PLmt, in loads and stiffness at failure superiorly, was similar to WD+CP (p = 0.066). WD+PLmt, in loads and stiffness at failure postero-anteriorly, was similar to WD+ACJ (p = 0.084).</p> <p>Superiorly, WD+CP had similar strength as WD+BS (p = 0.057), but it was less stiff (p < 0.005).</p> <p>Conclusions and Clinical Relevance</p> <p>Modified Weaver-Dunn procedure must always be supplemented with acromioclavicular capsuloligamentous repair to increase posterior-anterior stability. Palmaris-Longus tendon graft provides both additional superior and posterior-anterior stability when used for acromioclavicular capsuloligamentous reconstruction. It is a good alternative to clavicle hook plate in acromioclavicular dislocation.</p

An Integrated Approach to the Prediction of Chemotherapeutic Response in Patients with Breast Cancer

BACKGROUND: A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective. METHODS AND RESULTS: Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide) chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06). Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8%) of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), representing a viable alternative therapy. CONCLUSIONS: Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding microRNA and mRNA expression profiles. Importantly, we also present evidence to support the concept that analysis of molecular variables can present a rational strategy to identifying alternative therapeutic opportunities