Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe

CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited. Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints). Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK

First- and second-order contributions to depth perception in anti-correlated random dot stereograms.

The binocular energy model of neural responses predicts that depth from binocular disparity might be perceived in the reversed direction when the contrast of dots presented to one eye is reversed. While reversed-depth has been found using anti-correlated random-dot stereograms (ACRDS) the findings are inconsistent across studies. The mixed findings may be accounted for by the presence of a gap between the target and surround, or as a result of overlap of dots around the vertical edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2 or 38.4 arc min) (2) the correlation of dots or (3) the border orientation (circular target, or horizontal or vertical edge) affected the perception of depth. Reversed-depth from ACRDS (circular no-gap condition) was seen by a minority of participants, but this effect reduced as the gap size increased. Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with the effect increasing with the gap size. The inconsistency across conditions can be accounted for by the relative reliability of first- and second-order depth detection mechanisms, and the coarse spatial resolution of the latter

Evaluation of Senegal supply chain intervention on contraceptive stockouts using routine stock data.

BACKGROUND: Until 2011, stockouts of family planning commodities were common in Senegalese public health facilities. Recognizing the importance of addressing this problem, the Government of Senegal implemented the Informed Push Model (IPM) supply system, which involves logisticians to collect facility-level stock turnover data once a month and provide contraceptive supplies accordingly. The aims of this paper were to evaluate the impact of IPM on contraceptive availability and on stockout duration. METHODS AND FINDINGS: To estimate the impact of the IPM on contraceptive availability, stock card data were obtained from health facilities selected through multistage sampling. A total number of 103 health facilities pertaining to 27 districts and nine regions across the country participated in this project. We compared the odds of contraceptive stockouts within the health facilities on the 23 months after the intervention with the 18 months before. The analysis was performed with a logistic model of the monthly time-series. The odds of stockout for any of the five contraceptive products decreased during the 23 months post-intervention compared to the 18 months pre-intervention (odds ratio, 95%CI: 0.34, 0.22-0.51). To evaluate the impact of the IPM on duration of stockouts, a mixed negative binomial zero-truncated regression analysis was performed. The IPM was not effective in reducing the duration of contraceptive stockouts (incidence rate ratio, 95%CI: 0.81, 0.24-2.7), except for the two long-acting contraceptives (intrauterine devices and implants). Our model predicted a decrease in stockout median duration from 23 pre- to 4 days post-intervention for intrauterine devices; and from 19 to 14 days for implants. CONCLUSIONS: We conclude that the IPM has resulted in greater efficiency in contraceptive stock management, increasing the availability of contraceptive methods in health facilities in Senegal. The IPM also resulted in decreased duration of stockouts for intrauterine devices and implants, but not for any of the short-acting contraception (pills and injectables)

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Citywide Trauma Experience in Mwanza, Tanzania: A Need for Urgent Intervention.

Trauma remains a leading cause of morbidity and mortality in resource limited countries. There is paucity of published reports on trauma care in Tanzania, particularly the study area. This study was carried out to describe our experiences in trauma management outlining the etiological spectrum, injury characteristics and treatment outcome of trauma patients at our local setting and compare our results with those from other centers in the world. A descriptive prospective study of trauma patients was conducted at Bugando Medical Centre from April 2010 to March 2012. Statistical data analysis was done using SPSS software version 17.0. A total of 5672 trauma patients were enrolled in the study. The male to female ratio was 2.3: 1. The majority of patients were in the 2nd decade of life. Road traffic accident was the most common cause of trauma accounting for 60.7% of cases. The majority of patients (76.6%) sustained blunt injuries. Musculoskeletal (68.5%) and head/neck (52.6%) were the most frequent body region injured. Soft tissue injuries (open wounds) and fractures were the most common injuries accounting for 82.8% and 76.8% respectively. Majority of patients (74.4%) were treated surgically with wound debridement (94.0%) being the most frequently performed procedure. Postoperative complications were recorded in 31.5% of cases.The overall median duration of hospitalization was 26 days (range 1 day to 144 days). Mortality rate was 16.7%. Patients who had polytrauma, burn injuries and those who had tetanus and long bone fractures stayed longer in the hospital and this was statistically significant (P < 0.001), whereas the age > 65 years, severe trauma, admission Systolic Blood Pressure < 90 mmHg, presence of tetanus, severe head injury, the duration of loss of consciousness, the need for intensive care unit admission and finding of space occupying lesion on CT scan of the brain significantly influenced mortality (P < 0.001). Trauma resulting from road traffic accidents remains a major public health problem in this part of Tanzania. Urgent preventive measures targeting at reducing the occurrence of road traffic accidents is necessary to reduce the incidence of trauma in this region

Effects of the neurogranin variant rs12807809 on thalamocortical morphology in schizophrenia

10.1371/journal.pone.0085603PLoS ONE812-POLN