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Early science with the Karoo Array Telescope: a mini-halo candidate in galaxy cluster Abell 3667
No full textAbell 3667 is among the most well-studied galaxy clusters in the Southern hemisphere. It is known to host two giant radio relics and a head-tail radio galaxy as the brightest cluster galaxy. Recent work has suggested the additional presence of a bridge of diffuse synchrotron emission connecting the north-western radio relic with the cluster centre. In this work, we present full-polarization observations of Abell 3667 conducted with the Karoo Array Telescope at 1.33 and 1.82 GHz. Our results show both radio relics as well as the brightest cluster galaxy. We use ancillary higher resolution data to subtract the emission from this galaxy, revealing a localised excess, which we tentatively identify as a radio mini-halo. This mini-halo candidate has an integrated flux density of 67.2 ± 4.9 mJy beam-1 at 1.37 GHz, corresponding to a radio power of P1.4 GHz = 4.28 ± 0.31 × 1023 W Hz-1, consistent with established trends in mini-halo power scaling
Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy
No full textBackground Oral cancers are the sixth most common cancer worldwide, yet the prognosis following a diagnosis of oral cavity or oropharyngeal cancers remains poor, with approximately 50% survival at five years. Despite a sharp increase in research into molecularly targeted therapies and a rapid expansion in the number of clinical trials assessing new targeted therapies, their value for treating oral cancers is unclear. Therefore, it is important to summarise the evidence to determine the efficacy and toxicity of targeted therapies and immunotherapies for the treatment of these cancers. Objectives To assess the effects of molecularly targeted therapies and immunotherapies, in addition to standard therapies, for the treatment of oral cavity or oropharyngeal cancers. Search methods We searched the following electronic databases: Cochrane Oral Health Group Trials Register (to 3 February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 1), MEDLINE via Ovid (1946 to 3 February 2015) and EMBASE via Ovid (1980 to 3 February 2015). We searched the US National Institutes of Health Trials Register (clinicaltrials.gov), the World Health Organization Clinical Trials Registry Platform, the American Society of Clinical Oncology conference abstracts and the Radiation Therapy Oncology Group clinical trials protocols for ongoing trials. We placed no restrictions on the language or date of publication. Selection criteria We included randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared targeted therapy or immunotherapy, plus standard therapy, with standard therapy alone. Data collection and analysis Two review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias of the included studies. We attempted to contact study authors for missing data or clarification where necessary. We combined sufficiently similar studies in meta-analyses using random-effects models when there were at least four studies and fixed-effect models when fewer than four studies. We obtained or calculated a hazard ratio (HR) and 95% confidence interval (CI) for the primary outcomes where possible. For dichotomous outcomes, we reported risk ratios (RR) and 95% CIs. Main results Twelve trials (2488 participants) satisfied the inclusion criteria. In the included trials, 12% of participants (298 participants) had tumours of the oral cavity and 59% (1468 participants) had oropharyngeal tumours. The remaining 29% had tumours of the larynx or hypopharynx and less than 1% had tumours at other sites. No included trial was at low risk of bias; seven had an unclear risk of bias, and five had a high risk of bias. We grouped trials by intervention type into three main comparisons: standard therapy plus epidermal growth factor receptor monoclonal antibody (EGFR mAb) therapy (follow-up period 24 to 70 months); standard therapy plus tyrosine kinase inhibitors (TKIs) (follow-up period 40 to 60 months) and standard therapy plus immunotherapy (follow-up period 24 to 70 months), all versus standard therapy alone. Moderate quality evidence showed that EGFR mAb therapy may result in 18% fewer deaths when added to standard therapy (HR of mortality 0.82; 95% CI 0.69 to 0.97; 1421 participants, three studies, 67% oropharyngeal tumours, 2% oral cavity tumours). There was also moderate quality evidence that EGFR mAb may result in 32% fewer locoregional failures when added to radiotherapy (RT) (HR 0.68; 95% CI 0.52 to 0.89; 424 participants, one study, 60% oropharyngeal tumours). A subgroup analysis separating studies by type of standard therapy (radiotherapy (RT) or chemoradiotherapy (CRT)) showed some evidence that adding EGFR mAb therapy to RT may result in a 30% reduction in the number of people whose disease progresses (HR 0.70; 95% CI 0.54 to 0.91; 424 participants, one study, 60% oropharyngeal tumours, unclear risk of bias). For the subgroup comparing EGFR mAb plus CRT with CRT alone there was insufficient evidence to determine whether adding EGFR mAb therapy to CRT impacts on progression-free survival (HR 1.08; 95% CI 0.89 to 1.32; 891 participants, one study, 70% oropharyngeal tumours, high risk of bias). The high subgroup heterogeneity meant that we were unable to pool these subgroups. There was evidence that adding cetuximab to standard therapy may result in increased skin toxicity and rash (RR 6.56; 95% CI 5.35 to 8.03; 1311 participants, two studies), but insufficient evidence to determine any difference in skin toxicity and rash in the case of nimotuzumab (RR 1.06; 95% CI 0.85 to 1.31; 92 participants, one study). There was insufficient evidence to determine whether TKIs added to standard therapy impacts on overall survival (HR 0.99; 95% CI 0.62 to 1.57; 271 participants, two studies; very low quality evidence), locoregional control (HR 0.89; 95% CI 0.53 to 1.49; 271 participants, two studies; very low quality evidence), disease-free survival (HR 1.51; 95% CI 0.61 to 3.71; 60 participants, one study; very low quality evidence) or progression-free survival (HR 0.80; 95% CI 0.51 to 1.28; 271 participants, two studies; very low quality evidence). We did find evidence of an increase in skin rash (erlotinib: RR 6.57; 95% CI 3.60 to 12.00; 191 participants, one study; lapatinib: RR 2.02; 95% CI 1.23 to 3.32; 67 participants, one study) and gastrointestinal complaints (lapatinib: RR 15.53; 95% CI 2.18 to 110.55; 67 participants, one study). We found very low quality evidence from one small trial that adding recombinant interleukin (rIL-2) to surgery may increase overall survival (HR 0.52; 95% CI 0.31 to 0.87; 201 participants, 62% oral cavity tumours, 38% oropharyngeal tumours) and there was insufficient evidence to determine whether rIL-2 impacts on adverse effects. Authors' conclusions We found some evidence that adding EGFR mAb to standard therapy may increase overall survival, progression-free survival and locoregional control, while resulting in an increase in skin toxicity for some mAb (cetuximab). There is insufficient evidence to determine whether adding TKIs to standard therapies changes any of our primary outcomes. Very low quality evidence from a single study suggests that rIL-2 combined with surgery may increase overall survival compared with surgery alone
An In-Situ Atomic Force Microscopy Study of the Dissolution of Nanoporous SAPO-34 and SAPO-18
No full textMerchants of Print: from Venice to Manchester
No full textThe story of how the world-leading collection of Aldines found its way to the industrial heartlands of nineteenth and early twentieth century Manchester is an object lesson in cultural translation and a vital chapter in the history of knowledge transfer and the emergence of nineteenth-century ‘bibliomania’. Through an examination of the provenance of both specific Aldine collections, like those of George John 2nd Earl Spencer (1758-1834) and the political economist Richard Copley Christie (1830-1901) and the accession of individual volumes like those found in the bequests of the gynaecologist David Lloyd Roberts (1835-1920) and in the library of the Northern Congregational College, this exhibition will examine the geneaology of the Manchester Aldine collection. The trajectory of specific volumes within it, such as those owned by the likes of Pietro Bembo, Jean Grolier, Henri II and Agostino Barbarigo, will be woven into a consideration of the nexus of social, political and educational relationships through which the relation of cultural and financial capital were negotiated by Manchester’s nineteenth-century merchant princes
Rethinking the Place Product from the Perspective of the Service-Dominant Logic of Marketing
No full textAllogeneic Transplant Following Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma and Systemic Anaplastic Large Cell Lymphoma.
No full textBrentuximab vedotin is an antibody drug conjugate that induces durable objective responses in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Fifteen of 160 patients who participated in two pivotal phase 2 studies received a consolidative allogeneic stem cell transplant (allo-SCT) following brentuximab vedotin treatment. This case series describes their experience. The studies were approved by Institutional Review Boards prior to patient enrollment. Patients received 1.8 mg/kg brentuximab vedotin every 3 weeks for up to 16 cycles. The estimated 2-year progression-free survival (PFS) rate was 66%, and the median PFS has not yet been reached. Eleven of the 15 patients were alive and the estimated 2-year survival rate was 80%. The safety of brentuximab vedotin treatment in this series was consistent with the known safety profile in this setting. Brentuximab vedotin is a compelling option for reducing tumor burden to facilitate a consolidative allo-SCT
Low birth rates and reproductive skew limit the viability of Europe's captive eastern black rhinoceros, Diceros bicornis michaeli
No full textDense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis.
No full textPsoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8(+) memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA