Drosophila RecQ4 Is Directly Involved in Both DNA Replication and the Response to UV Damage in S2 Cells.

The RecQ4 protein shows homology to both the S.cerevisiae DNA replication protein Sld2 and the DNA repair related RecQ helicases. Experimental data also suggest replication and repair functions for RecQ4, but the precise details of its involvement remain to be clarified.Here we show that depletion of DmRecQ4 by dsRNA interference in S2 cells causes defects consistent with a replication function for the protein. The cells show reduced proliferation associated with an S phase block, reduced BrdU incorporation, and an increase in cells with a subG1 DNA content. At the molecular level we observe reduced chromatin association of DNA polymerase-alpha and PCNA. We also observe increased chromatin association of phosphorylated H2AvD--consistent with the presence of DNA damage and increased apoptosis.Analysis of DmRecQ4 repair function suggests a direct role in NER, as the protein shows rapid but transient nuclear localisation after UV treatment. Re-localisation is not observed after etoposide or H₂O₂ treatment, indicating that the involvement of DmRecQ4 in repair is likely to be pathway specific.Deletion analysis of DmRecQ4 suggests that the SLD2 domain was essential, but not sufficient, for replication function. In addition a DmRecQ4 N-terminal deletion could efficiently re-localise on UV treatment, suggesting that the determinants for this response are contained in the C terminus of the protein. Finally several deletions show differential rescue of dsRNA generated replication and proliferation phenotypes. These will be useful for a molecular analysis of the specific role of DmRecQ4 in different cellular pathways

Analysis of Dislocation Mechanism for Melting of Elements

The melting of elemental solids is modelled as a dislocation-mediated transition on a lattice. Statistical mechanics of linear defects is used to obtain a new relation between melting temperature, crystal structure, atomic volume, and shear modulus that is accurate to 17% for at least half of the Periodic Table.Comment: 8 pages, LaTeX, to appear in Solid State Com

What are the participants’ perspectives of taking melatonin for the treatment of nocturia in Multiple Sclerosis? -a qualitative study embedded within a double blind RCT

Background: Multiple Sclerosis (MS) is a chronic neurological disorder caused by neurodegeneration within the central nervous system. It results in impaired physical, cognitive and psychological functioning and can also lead to lower urinary tract symptoms including nocturia. While clinical trials have suggested an association between nocturia and melatonin secretion, to our knowledge, no qualitative research has been conducted on the experience of taking melatonin to treat nocturia in progressive MS within a clinical trial. Methods: 17 semi-structured qualitative interviews were conducted as part of a double-blind, randomised, placebo controlled, crossover, clinical trial with consenting adults with MS. Interviews explored participants’ experiences of nocturia associated with MS and their experience of taking melatonin as a trial treatment for nocturia versus a placebo. Data was analysed using a thematic analysis. Results: Themes on the experience of nocturia revealed participants’ understandings of nocturia, the impact it had on their night and increased daily fatigue. Themes on the intervention showed perceived improvements to nocturia, sleep and energy and negative effects including lethargy, a lack of significant change and physical side effects including vivid dreams.Conclusion: This qualitative exploration revealed an association between nocturia and increased levels of fatigue during the day by those with MS. However, perspectives towards the effectiveness of melatonin as a potential treatment varied as both placebo and melatonin were perceived as having very similar effects

Melting as a String-Mediated Phase Transition

We present a theory of the melting of elemental solids as a dislocation-mediated phase transition. We model dislocations near melt as non-interacting closed strings on a lattice. In this framework we derive simple expressions for the melting temperature and latent heat of fusion that depend on the dislocation density at melt. We use experimental data for more than half the elements in the Periodic Table to determine the dislocation density from both relations. Melting temperatures yield a dislocation density of (0.61\pm 0.20) b^{-2}, in good agreement with the density obtained from latent heats, (0.66\pm 0.11) b^{-2}, where b is the length of the smallest perfect-dislocation Burgers vector. Melting corresponds to the situation where, on average, half of the atoms are within a dislocation core.Comment: 18 pages, LaTeX, 3 eps figures, to appear in Phys. Rev.

Incidence and survival for cancer in children and young adults in the North of England, 1968–1995: a report from the Northern Region Young Persons’ Malignant Disease Registry

The Northern Region Young Persons’ Malignant Disease Registry records information on young people under 25 years old diagnosed with cancer in the Northern Region of England. Incidence and survival rates were calculated for children and young adults diagnosed with cancer between 1968 and 1995. There were 2099 (M:F 1.28:1) children (age 0–14 years) and 2217 (M:F 1.23:1) young adults (15–24 years) diagnosed with a first cancer between 1968 and 1995. The age-standardized rate (ASR) for childhood cancer was 121 per million 0 to 14 year-olds per year. For young adults the ASR was 175 per million 15 to 24 year-olds, per year. Incidence of childhood cancer increased over time at a rate of 12 extra cases per million children, per decade (P< 0.001). In young adults incidence rates increased by 16 extra cases per million 15 to 24 year-olds, per decade (P< 0.001). For childhood cancer 5-year survival was 42% for those diagnosed 1968–1977, 57% for 1978–1987 and 71% (95% CI 67–75) for 1988–1995. Survival for young adults over the three periods was 45%, 62% and 73% (95% CI 70–78) respectively. The cumulative risk of developing cancer before the age of 25 is 1 in 285. Over the 28-year period there were significant improvements in survival and modest increases in incidence in both children and young adults. © 2000 Cancer Research Campaig

Crystalline Order on a Sphere and the Generalized Thomson Problem

We attack generalized Thomson problems with a continuum formalism which exploits a universal long range interaction between defects depending on the Young modulus of the underlying lattice. Our predictions for the ground state energy agree with simulations of long range power law interactions of the form 1/r^{gamma} (0 < gamma < 2) to four significant digits. The regime of grain boundaries is studied in the context of tilted crystalline order and the generality of our approach is illustrated with new results for square tilings on the sphere.Comment: 4 pages, 5 eps figures Fig. 2 revised, improved Fig. 3, reference typo fixe

Unchanged incidence and increased survival in children with neuroblastoma in Denmark 1981–2000: a population-based study

Treatment results for neuroblastoma in Denmark have been poorer than in other Nordic countries, so we investigated whether a change in incidence, stage distribution and survival had occurred between 1981 and 2000. Clinical data were retrieved from the medical charts of 160 children <15 years of age with extra-cranial neuroblastoma (n=139) or ganglioneuroblastoma (n=21) diagnosed in Denmark between 1981 and 2000. The minimal follow-up time was 52 months. Statistical analyses were performed in STATA. The incidence was 8.55 per million children below 15 years of age (world standard 9.6) and 42.6 per million children below 12 months of age, and it has remained unchanged since 1970. The median age at diagnosis was 27 months. In all, 32% of the children were aged below 12 months at diagnosis, 53% had metastatic disease and in 12% the diagnosis was made incidentally. Prognostic factors such as age, stage and site of primary tumour were the same as in other studies and did not change. During the study period, the mortality rate decreased steadily, and the 5-year survival rate increased from 38% in 1981–1985 to 59% in 1996–2000, corresponding to the level found in other Western countries. Increased survival was also seen in children with metastatic disease. Participation in international studies, better supportive care and possibly postoperative autologous stem cell transplantation may have contributed to the increased survival

Comparative effectiveness of endovascular versus open repair of ruptured abdominal aortic aneurysm in the Medicare population

ObjectiveEndovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA) is increasingly used for emergent treatment of ruptured AAA (rAAA). We sought to compare the perioperative and long-term mortality, procedure-related complications, and rates of reintervention of EVAR vs open aortic repair of rAAA in Medicare beneficiaries.MethodsWe examined perioperative and long-term mortality and complications after EVAR or open aortic repair performed for rAAA in all traditional Medicare beneficiaries discharged from a United States hospital from 2001 to 2008. Patients were matched by propensity score on baseline demographics, coexisting conditions, admission source, and hospital volume of rAAA repair. Sensitivity analyses were performed to evaluate the effect of bias that might have resulted from unmeasured confounders.ResultsOf 10,998 patients with repaired rAAA, 1126 underwent EVAR and 9872 underwent open repair. Propensity score matching yielded 1099 patient pairs. The average age was 78 years, and 72.4% were male. Perioperative mortality was 33.8% for EVAR and 47.7% for open repair (P < .001), and this difference persisted for >4 years. At 36 months, EVAR patients had higher rates of AAA-related reinterventions than open repair patients (endovascular reintervention, 10.9% vs 1.5%; P < .001), whereas open patients had more laparotomy-related complications (incisional hernia repair, 1.8% vs 6.2%; P < .001; all surgical complications, 4.4% vs 9.1%; P < .001). Use of EVAR for rAAA increased from 6% of cases in 2001 to 31% in 2008, whereas during the same interval, overall 30-day mortality for admission for rAAA, regardless of treatment, decreased from 55.8% to 50.9%.ConclusionsEVAR for rAAA is associated with lower perioperative and long-term mortality in Medicare beneficiaries. Increasing adoption of EVAR for rAAA is associated with an overall decrease in mortality of patients hospitalized for rAAA during the last decade

Liquid antiferromagnets in two dimensions

It is shown that, for proper symmetry of the parent lattice, antiferromagnetic order can survive in two-dimensional liquid crystals and even isotropic liquids of point-like particles, in contradiction to what common sense might suggest. We discuss the requirements for antiferromagnetic order in the absence of translational and/or orientational lattice order. One example is the honeycomb lattice, which upon melting can form a liquid crystal with quasi-long-range orientational and antiferromagnetic order but short-range translational order. The critical properties of such systems are discussed. Finally, we draw conjectures for the three-dimensional case.Comment: 4 pages RevTeX, 4 figures include