Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

The optical afterglow and host galaxy of GRB 000926

We present the discovery of the Optical Transient (OT) of the long-duration gamma-ray burst GRB 000926. The optical transient was detected independently with the Nordic Optical Telescope and at Calar Alto 22.2 hours after the burst. At this time the magnitude of the transient was R = 19.36. The transient faded with a decay slope of about 1.7 during the first two days after which the slope increased abruptly (within a few hours) to about 2.4. The light-curve started to flatten off after about a week indicating the presence of an underlying extended object. This object was detected in a deep image obtained one month after the GRB at R=23.87+/-0.15 and consists of several compact knots within about 5 arcsec. One of the knots is spatially coincident with the position of the OT and hence most likely belongs to the host galaxy. Higher resolution imaging is needed to resolve whether all the compact knots belong to the host galaxy or to several independent objects. In a separate paper we present a discussion of the optical spectrum of the OT, and its inferred redshift (Møller et al., in prep.). Based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden. Based on observations made at the 2.2-m telescope of the German-Spanish Calar Alto Observatory. Based on observations made with the Isaac Newton Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias

Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains Differentially Modulates Src Kinase Activity in Brain Maturation

Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG. We demonstrate in newborn (P1) mice that PAG negatively regulates Src family kinases (SFK). P1 Pag1-/- mouse brains show decreased recruitment of Csk into lipid rafts, reduced phosphorylation of the inhibitory tyrosines within SFKs, and an increase in SFK activity of >/ = 50%. While in brain of P1 mice, PAG and Csk are highly and ubiquitously expressed, little Csk is found in adult brain suggesting altered modes of SFK regulation. In adult brain Pag1-deficiency has no effect upon Csk-distribution or inhibitory tyrosine phosphorylation, but kinase activity is now reduced (−20–30%), pointing to the development of a compensatory mechanism that may involve PSD93. The distribution of the Csk-homologous kinase CHK is not altered. Importantly, since the activities of Fyn and Src are decreased in adult Pag1-/- mice, thus presenting the reversed phenotype of P1, this provides the first in vivo evidence for a Csk-independent positive regulatory function for PAG in the brain

Performance of the Electromagnetic Pixel Calorimeter Prototype EPICAL-2

The first evaluation of an ultra-high granularity digital electromagnetic calorimeter prototype using 1.0-5.8 GeV/c electrons is presented. The $25\times10^6$ pixel detector consists of 24 layers of ALPIDE CMOS MAPS sensors, with a pitch of around 30~$\mu$m, and has a depth of almost 20 radiation lengths of tungsten absorber. Ultra-thin cables allow for a very compact design. The properties that are critical for physics studies are measured: electromagnetic shower response, energy resolution and linearity. The stochastic energy resolution is comparable with the state-of-the art resolution for a Si-W calorimeter, with data described well by a simulation model using GEANT and Allpix$^2$. The performance achieved makes this technology a good candidate for use in the ALICE FoCal upgrade, and in general demonstrates the strong potential for future applications in high-energy physics.Comment: 30 pages, 19 figures, submitted to JINS

Observations of the pulsating subdwarf B star Feige 48: Constraints on evolution and companions

Since pulsating subdwarf B (sdBV or EC14026) stars were first discovered (Kilkenny et al, 1997), observational efforts have tried to realize their potential for constraining the interior physics of extreme horizontal branch (EHB) stars. Difficulties encountered along the way include uncertain mode identifications and a lack of stable pulsation mode properties. Here we report on Feige 48, an sdBV star for which follow-up observations have been obtained spanning more than four years, which shows some stable pulsation modes. We resolve the temporal spectrum into five stable pulsation periods in the range 340 to 380 seconds with amplitudes less than 1%, and two additional periods that appear in one dataset each. The three largest amplitude periodicities are nearly equally spaced, and we explore the consequences of identifying them as a rotationally split l=1 triplet by consulting with a representative stellar model. The general stability of the pulsation amplitudes and phases allows us to use the pulsation phases to constrain the timescale of evolution for this sdBV star. Additionally, we are able to place interesting limits on any stellar or planetary companion to Feige 48.Comment: accepted for publication in MNRA

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy

Extensor tendon release in tennis elbow: results and prognostic factors in 80 elbows

Purpose The objectives of this study were to evaluate the results in the outpatient treatment of recalcitrant lateral epicondylitis with release of the common extensor origin according to Hohmann and to determine any prognostic factors. Methods Eighty tennis elbows in 77 patients with a characteristic history of activity-related pain at the lateral epicondyle interfering with the activities of daily living refractory to conservative care for at least 6 months and a confirmatory physical examination were included. Clinical outcome was evaluated using the QuickDASH score system. Data were collected before the operation and at the medians of 18 months (range 6–36 months; short term) and 4 years (range 3–6 years; medium term) postoperatively. Results The mean QuickDASH was improved both at the short- and the medium-term follow-ups and did not change significantly between the follow-ups. At the final followup, the QuickDASH was improved in 78 out of 80 elbows and 81% was rated as excellent or good (QuickDASH\40 points). We found a weak correlation between residual symptoms (a high QuickDASH score) at the final follow-up and high level of baseline symptoms (r = 0.388), acute occurrence of symptoms (r = 0.362), long duration of symptoms (r = 0.276), female gender (r = 0.269) and young age (r = 0.203), whereas occurrence in dominant arm, a work-related cause or strenuous work did not correlate significantly with the outcome. Conclusion Open lateral extensor release performed as outpatient surgery results in improved clinical outcome at both short- and medium-term follow-ups with few complications. High baseline disability, sudden occurrence of symptoms, long duration of symptoms, female gender and young age were found to be weak predictors of poor outcome

Family members' experience with in-hospital health care after severe traumatic brain injury : a national multicentre study.

Background Family member’s experience and satisfaction of health care in the acute care and in-patient rehabilitation are important indicators of the quality of health care services provided to patients with severe traumatic brain injury (TBI). The objective was to assess family members’ experience of the health care provided in-hospital to patients with severe TBI, to relate experiences to family member and patient demographics, patients’ function and rehabilitation pathways. Methods Prospective national multicentre study of 122 family members of patients with severe TBI. The family experience of care questionnaire in severe traumatic brain injury (FECQ-TBI) was applied. Independent sample t-tests or analysis of variance (ANOVA) were used to compare the means between 2 or more groups. Paired samples t-tests were used to investigate differences between experience in the acute and rehabilitation phases. Results Best family members` experience were found regarding information during the acute phase, poorest scores were related to discharge. A significantly better care experience was reported in the acute phase compared with the rehabilitation phase (p < 0.05). Worst family members` experience was related to information about consequences of the injury. Patient’s dependency level (p < 0.05) and transferral to non-specialized rehabilitation were related to a worse family members` experience (p < 0.01). Conclusions This study underscores the need of better information to family members of patients with severe TBI in the rehabilitation as well as the discharge phase. The results may be important to improve the services provided to family members and individuals with severe TBI

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure