Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial

Intraperitoneal treatment with interferon-γ (IFN-γ) has been shown to achieve surgically documented responses in the second-line therapy of ovarian cancer. To assess its efficacy in the first-line therapy, we conducted a randomized controlled trial with 148 patients who had undergone primary surgery for FIGO stage Ic–IIIc ovarian cancer. In the control arm women received 100 mg m−2cisplatin and 600 mg m−2cyclophosphamide, the experimental arm included the above regimen with IFN-γ 0.1 mg subcutaneously on days 1, 3, 5, 15, 17 and 19 of each 28-day cycle. Progression-free survival at 3 years was improved from 38% in controls to 51% in the treatment group corresponding to median times to progression of 17 and 48 months (P = 0.031, relative risk of progression 0.48, confidence interval 0.28–0.82). Three-year overall survival was 58% and 74% accordingly (n.s., median not yet reached). Complete clinical responses were observed in 68% with IFN-γ versus 56% in controls (n.s.). Toxicity was comparable in both groups except for a mild flu-like syndrome, experienced by most patients after administration of IFN-γ. Thus, with acceptable toxicity, the inclusion of IFN-γ in the first-line chemotherapy of ovarian cancer yielded a benefit in prolonging progression-free survival. © 2000 Cancer Research Campaig

The pseudo‐brookite spin‐glass system studied by means of muon spin relaxation

Zero-field muon spin relaxation (µSR) experiments have been performed on the spin glass Fe1.75Ti1.25O5. Above the spin-glass temperature of 44 K a distinct exponential µSR rate (¿) is observed, while below Tg a square-root exponential decay occurs, indicating fast spin fluctuations. Near 8 K, a maximum in ¿ is indicative of transverse spin ordering. The low ¿ values and the sharp ¿ peak at Tg are very promising for the study of spin freezing models like the Vogel–Fulcher law or the power law

Cosmological constraints combining H(z), CMB shift and SNIa observational data

Recently H(z) data obtained from differential ages of galaxies have been proposed as a new geometrical probe of dark energy. In this paper we use those data, combined with other background tests (CMB shift and SNIa data), to constrain a set of general relativistic dark energy models together with some other models motivated by extra dimensions. Our analysis rests mostly on Bayesian statistics, and we conclude that LCDM is at least substantially favoured, and that braneworld models are less favoured than general relativistic ones.Comment: 17 pages, 11 figures; improved discussion, new figures, updated to match published versio

The sensitivity of ECG contamination to surgical implantation site in brain computer interfaces.

BACKGROUND Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. OBJECTIVES Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. METHODS Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. RESULTS The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. CONCLUSIONS Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration

Phocid Seal Leptin: Tertiary Structure and Hydrophobic Receptor Binding Site Preservation during Distinct Leptin Gene Evolution

The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus

Overlap of cognitive concepts in chronic widespread pain: An exploratory study

<p>Abstract</p> <p>Background</p> <p>A wide variety of cognitive concepts have been shown to play an important role in chronic widespread pain (CWP). Although these concepts are generally considered to be distinct entities, some might in fact be highly overlapping. The objectives of this study were to (i) to establish inter-relationships between self-efficacy, cognitive coping styles, fear-avoidance cognitions and illness beliefs in patients with CWP and (ii) to explore the possibility of a reduction of these cognitions into a more limited number of domains.</p> <p>Methods</p> <p>Baseline measurement data of a prospective cohort study of 138 patients with CWP were used. Factor analysis was used to study the associations between 16 different cognitive concepts.</p> <p>Results</p> <p>Factor analysis resulted in three factors: 1) negative emotional cognitions, 2) active cognitive coping, and 3) control beliefs and expectations of chronicity.</p> <p>Conclusion</p> <p>Negative emotional cognitions, active cognitive coping, control beliefs and expectations of chronicity seem to constitute principal domains of cognitive processes in CWP. These findings contribute to the understanding of overlap and uniqueness of cognitive concepts in chronic widespread pain.</p

Aryl hydrocarbon receptor (AhR) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study

BACKGROUND: Bone marrow stromal cells produce cytokines required for the normal growth and development of all eight hematopoietic cell lineages. Aberrant cytokine production by stromal cells contributes to blood cell dyscrasias. Consequently, factors that alter stromal cell cytokine production may significantly compromise the development of normal blood cells. We have shown that environmental chemicals, such as aromatic hydrocarbon receptor (AhR) agonists, suppress B lymphopoiesis by modulating bone marrow stromal cell function. Here, we extend these studies to evaluate the potential for two prototypic AhR agonists, 7,12-dimethylbenz [a]anthracene (DMBA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), to alter stromal cell cytokine responses. METHODS: Bone marrow stromal cells were treated with AhR agonists and bacterial lipopolysaccharide (LPS) to mimic innate inflammatory cytokine responses and to study the effects of AhR ligands on those responses. Steady state cytokine RNA levels were screened by RNAse protection assays (RPA) and quantified by real-time PCR. Cytokine (IL-6) protein production was measured by ELISA. NF-κB EMSAs were used to study IL-6 transcriptional regulation. RESULTS: RPAs indicated that AhR(+ )bone marrow stromal cells consistently up-regulated genes encoding IL-6 and LIF in response to LPS, presumably through activation of Toll-like receptor 4. Pre-treatment with low doses of DMBA or TCDD selectively abrogated IL-6 gene induction but had no effect on LIF mRNA. Real-time-PCR indicated a significant inhibition of IL-6 mRNA by AhR ligands within 1 hour of LPS challenge which was reflected in a profound down-regulation of IL-6 protein induction, with DMBA and TCDD suppressing IL-6 levels as much as 65% and 88%, respectively. This potent inhibitory effect persisted for at least 72 hours. EMSAs measuring NF-κB binding to IL-6 promoter sequences, an event known to induce IL-6 transcription, indicated a significant decrease in the LPS-mediated induction of DNA-binding RelA/p50 and c-Rel/p50 heterodimers in the presence of DMBA. CONCLUSIONS: Common environmental AhR agonists can suppress the response to bacterial lipopolysaccharide, a model for innate inflammatory responses, through down-regulation of IL-6, a cytokine critical to the growth of several hematopoietic cell subsets, including early B cells. This suppression occurs at least at the level of IL-6 gene transcription and may be regulated by NF-κB

Effects of work ability and health promoting interventions for women with musculoskeletal symptoms: A 9-month prospective study

<p>Abstract</p> <p>Background</p> <p>Women working in the public human service sector in 'overstrained' situations run the risk of musculoskeletal symptoms and long-term sick leave. In order to maintain the level of health and work ability and strengthen the potential resources for health, it is important that employees gain greater control over decisions and actions affecting their health – a process associated with the concept of self-efficacy. The aim of this study was to describe the effects of a self-efficacy intervention and an ergonomic education intervention for women with musculoskeletal symptoms, employed in the public sector.</p> <p>Methods</p> <p>The design of the study was a 9-month prospective study describing the effects of two interventions, a comprehensive self-efficacy intervention (<it>n </it>= 21) and an ergonomic education intervention (<it>n </it>= 21). Data were obtained by a self-report questionnaire on health- and work ability-related factors at baseline, and at ten weeks and nine months follow-up. Within-group differences over time were analysed.</p> <p>Results</p> <p>Over the time period studied there were small magnitudes of improvements within each group. Within the self-efficacy intervention group positive effects in perceived work ability were shown. The ergonomic education group showed increased positive beliefs about future work ability and a more frequent use of pain coping strategies.</p> <p>Conclusion</p> <p>Both interventions showed positive effects on women with musculoskeletal symptoms, but in different ways. Future research in this area should tailor interventions to participants' motivation and readiness to change.</p