An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones

Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Ore reporter mouse system in conjunction with Ore-expressing HSV-1 recombinants we have previously shown that activation of the IE ICPO promoter can precede latency establishment in at least 30 % of latently infected cells. During productive infection of non-neuronal cells, IE promoter activation is largely dependent on the transactivator VP16 a late structural component of the virion. Of significance, VP16 has recently been shown to exhibit altered regulation in neurones; where its de novo synthesis is necessary for IE gene expression during both lytic infection and reactivation from latency. In the current study, we utilized the Ore reporter mouse model system to characterize the full extent of viral promoter activity compatible with cell survival and latency establishment. In contrast to the high frequency activation of representative IE promoters prior to latency establishment, cell marking using a virus recombinant expressing Ore under VP16 promoter control was very inefficient. Furthermore, infection of neuronal cultures with VP16 mutants reveals a strong VP16 requirement for IE promoter activity in non-neuronal cells, but not sensory neurones. We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism

A review of the peri-operative management of paediatric burns: Identifying adverse events

Background. Burn injuries are common in poverty-stricken countries. The majority of patients with large and complex burns are referred to burn centres. Of the children who qualify for admission, according to burn admission criteria, about half require some kind of surgical procedure to obtain skin cover. These range from massive full-thickness fire burns to skin grafts for small, residual unhealed wounds. Burn anaesthetic procedures are of the most difficult to perform and are known for high complication rates. Reasons include peri-operative sepsis, bleeding, issues around thermoregulation, the hypermetabolic state, nutritional and electrolyte issues, inhalation injuries and the amount of movement during procedures to wash patients, change drapes and access different anatomical sites. The appropriate execution of surgery is therefore of the utmost importance for both minor and major procedures.Objective. To review the peri-operative management and standard of surgical care of burnt children.Methods. This was a retrospective review and analysis of standard peri-operative care of burnt children at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. A total of 558 children were operated on and supervised by the first author. Factors that could adversely affect surgical and anaesthetic outcomes were identified.Results. There were 257 males and 301 females in this study, with an average age of 50.1 months and average weight of 19.5 kg. The total body surface area involved was 1 - 80%, with an average of 23.5%. Inhalational injury was present in 11.3%, pneumonia in 13.1%, wound sepsis in 20.8%, and septicaemia in 9.7%, and organ dysfunction in more than one organ was seen in 6.1%. The average theatre temperature during surgery was 30.0°C. Core temperatures recorded at the start, halfway through and at completion of surgery were 36.9°C, 36.8°C and 36.5°C, respectively. The average preoperative and postoperative haemoglobin levels were 11.28 g/dL and 9.64 g/dL, respectively. Blood loss was reduced by the use of clysis from 1.5 mL/kg/% burn to 1.4 mL/kg/% burn. Adverse intraoperative events were seen in 17.6% of children.Conclusion. Burn surgery is a high-risk procedure and comorbidities are common. Anaesthesia and surgery must be well planned and executed with special reference to temperature control, rapid blood loss, preceding respiratory illnesses and measures to reduce blood loss

[Accepted Manuscript] Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2)

Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15-99years) diagnosed with ovarian cancer during 1995-2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). Survival from type I epithelial ovarian tumours for women diagnosed during 2005-09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20-45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology

Charge Density Wave-Assisted Tunneling Between Hall Edge States

We study the intra-planar tunneling between quantum Hall samples separated by a quasi one-dimensional barrier, induced through the interaction of edge degrees of freedom with the charge density waves of a Hall crystal defined in a parallel layer. A field theory formulation is set up in terms of bosonic (2+1)-dimensional excitations coupled to (1+1)-dimensional fermions. Parity symmetry is broken at the quantum level by the confinement of soliton-antisoliton pairs near the tunneling region. The usual Peierls argument allows to estimate the critical temperature $T_c$, so that for $T > T_c$ mass corrections due to longitudinal density fluctuations disappear from the edge spectrum. We compute the gap dependence upon the random global phase of the pinned charge density wave, as well as the effects of a voltage bias applied across the tunneling junction.Comment: Additional references + 1 figure + more detailed discussions. To be published in Phys. Rev.

1/Nc1/N_c Expansion for Excited Baryons

We derive consistency conditions which constrain the possible form of the strong couplings of the excited baryons to the pions. The consistency conditions follow from requiring the pion-excited baryon scattering amplitudes to satisfy the large-N_c Witten counting rules and are analogous to consistency conditions used by Dashen, Jenkins and Manohar and others for s-wave baryons. The consistency conditions are explicitly solved, giving the most general allowed form of the strong vertices for excited baryons in the large-N_c limit. We show that the solutions to the large-N_c consistency conditions coincide with the predictions of the nonrelativistic quark model for these states, extending the results previously obtained for the s-wave baryons. The 1/N_c corrections to these predictions are studied in the quark model with arbitrary number of colors N_c.Comment: 56 pages, REVTeX; one new Appendix added containing a discussion of the results in the language of quark operator

Numerical evidence for `multi-scalar stars'

We present a class of general relativistic soliton-like solutions composed of multiple minimally coupled, massive, real scalar fields which interact only through the gravitational field. We describe a two-parameter family of solutions we call ``phase-shifted boson stars'' (parameterized by central density rho_0 and phase delta), which are obtained by solving the ordinary differential equations associated with boson stars and then altering the phase between the real and imaginary parts of the field. These solutions are similar to boson stars as well as the oscillating soliton stars found by Seidel and Suen [E. Seidel and W.M. Suen, Phys. Rev. Lett. 66, 1659 (1991)]; in particular, long-time numerical evolutions suggest that phase-shifted boson stars are stable. Our results indicate that scalar soliton-like solutions are perhaps more generic than has been previously thought.Comment: Revtex. 4 pages with 4 figures. Submitted to Phys. Rev.

Case-based review and olinical guidance on the use of genomic assays for early-stage breast cancer: Breast Cancer Therapy Expert Group (BCTEG)

In addition to classical clinicopathologic factors, such as hormone receptor positivity, human epidermal growth factor receptor 2 (HER2) status, and tumor size, grade, and lymph node status, a number of commercially available genomic tests may be used to help inform treatment decisions for early breast cancer patients. Although these tests improve our understanding of breast cancer and help to individualize treatment decisions, clinicians face challenges when deciding on the most appropriate test to order, and the advantages, if any, of one test over another. The Breast Cancer Therapy Expert Group (BCTEG) recently convened a roundtable meeting to discuss issues surrounding the use of genomic testing in early breast cancer, with the goal of providing practical guidance on the use of these tests by the community oncologist, for whom breast cancer may be only one of many tumor types they treat. The group recognizes that genomic testing can provide important prognostic (eg, risk for recurrence), and in some cases predictive, information (eg, benefit of chemotherapy, or extended adjuvant endocrine therapy), which can be used to help guide treatment decisions in breast cancer. The available tests differ in the types of information they provide, and in the patient populations and clinical trials that were conducted to validate them. We summarize the discussion of the BCTEG on this topic, and we also consider several patient cases and clinical scenarios in which genomic testing may, or may not, be useful to guide treatment decisions for the practicing community oncologist

Semiclassical Study of Baryon and Lepton Number Violation in High-Energy Electroweak Collisions

We make use of a semiclassical method for calculating the suppression exponent for topology changing transitions in high-energy electroweak collisions. In the Standard Model these processes are accompanied by violation of baryon and lepton number. By using a suitable computational technique we obtain results for s-wave scattering in a large region of initial data. Our results show that baryon and lepton number violation remains exponentially suppressed up to very high energies of at least 30 sphaleron masses (250 TeV). We also conclude that the known analytic approaches inferred from low energy expansion provide reasonably good approximations up to the sphaleron energy (8 TeV) only.Comment: 23 pages, 18 figures. Phys.Rev.D journal version (two references added