Search

Simple Summary: The landscape of non-small cell lung cancer has changed dramatically over the past decade. This is largely due to the introduction of immunotherapy, and in particular, immune checkpoint blockade inhibitors. Anti-PD-1 immunotherapy is now standard treatment for patients with non-small cell lung cancer. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Moreover, some patients experience adverse effects from the treatment. In this review, we explain the modes of actions of common immunotherapy strategies, summarise the clinical trials that have led to the widespread use of immunotherapy and present some current challenges in the field of immunotherapy. Immunotherapy has revolutionised anti-cancer treatment in solid organ malignancies. Specifically, the discovery of CTLA-4 followed by PD-1 in the early 2000s led to the practice-changing clinical development of immune checkpoint inhibitors (ICI). Patients with lung cancer, including both small cell (SCLC) and non-small cell lung cancer (NSCLC), benefit from the most commonly used form of immunotherapy in immune checkpoint inhibitors (ICI), resulting in increased survival and quality of life. In NSCLC, the benefit of ICIs has now extended from advanced NSCLC to earlier stages of disease, resulting in durable benefits and the even the emergence of the word 'cure' in long term responders. However, not all patients respond to immunotherapy, and few patients achieve long-term survival. Patients may also develop immune-related toxicity, a small percentage of which is associated with significant mortality and morbidity. This review article highlights the various types of immunotherapeutic strategies, their modes of action, and the practice-changing clinical trials that have led to the widespread use of immunotherapy, with a focus on ICIs in NSCLC and the current challenges associated with advancing the field of immunotherapy. [ABSTRACT FROM AUTHOR]

An experimental study on the Richtmyer-Meshkov instability (RMI) is presented, which used a new experimental facility at Texas A&M University built for conducting shock-accelerated, inhomogeneous, inclined fluid interface experiments. The RMI develops from the misalignment of the pressure and density gradients for which the inclined shock tube facility is uniquely well suited since a fluid interface can be created at a prescribed angle to the incident shock. Measurements of the evolving RMI are taken using planar laser Mie scattering images for both the pre- and post-reshock regimes, which capture the qualitative evolution of the interface. Statistical measurements demonstrate that the inclined interface initial conditions have a high degree of run-to-run repeatability. The interface mixing width is scaled using the method developed in author's previous work and shows that the non-dimensional mixing width grows linearly in the pre-reshock regime and then levels off at the onset of reshock, after which it grows linearly again. Mie scattering images at late times exhibit the evolution of a secondary shear instability on the primary vortex feature, which has never been resolved in simulations of the inclined interface RMI. A 2D velocity field is obtained for this feature using particle image velocimetry and processed to indicate the strength of the vorticity present. Images of the interface after reshock reveal the inversion of the bubble and spike features and the decay of prominent features toward a turbulent state. [ABSTRACT FROM AUTHOR]

Although gender differences in cognitive abilities are frequently reported, the magnitude of these differences and whether they hold practical significance in the educational outcomes of boys and girls is highly debated. Furthermore, when gender gaps in reading, mathematics and science literacy are reported they are often attributed to innate, biological differences rather than social and cultural factors. Cross-cultural evidence may contribute to this debate, and this study reports national gender differences in reading, mathematics and science literacy from 65 nations participating in the 2009 round of the Programme for International Student Assessment (PISA). Consistently across all nations, girls outperform boys in reading literacy, d =-.44. Boys outperform girls in mathematics in the USA, d=.-2 and across OECD nations, d = .13. For science literacy, while the USA showed the largest gender difference across all OECD nations, d=.14, gender differences across OECD nations were non-significant, and a small female advantage was found for non-OECD nations, d =2.09. Across all three domains, these differences were more pronounced at both tails of the distribution for low- and high-achievers. Considerable cross-cultural variability was also observed, and national gender differences were correlated with gender equity measures, economic prosperity, and Hofstede's cultural dimension of power distance. Educational and societal implications of such gender gaps are addressed, as well as the mechanisms by which gender differences in cognitive abilities are culturally mediated. [ABSTRACT FROM AUTHOR]

Background: The challenge of finding practical, patient-rated outcome measures is a key issue in the evaluation of health care systems and interventions. The ORIDL (Outcome in Relation to Impact on Daily Living) instrument (formerly referred to as the Glasgow Homoeopathic Hospital Outcomes Scale or GHHOS) has been developed to measure patient's views of the outcome of their care by asking about change, and relating this to impact on daily life. The aim of the present paper is to describe the background and potential uses of the ORIDL, and to report on its preliminary validation in a series of three studies in secondary and primary care. Methods: In the first study, 105 patients attending the Glasgow Homoeopathic Hospital (GHH) were followed-up at 12 months and changes in health status were measured by the EuroQol (EQOL) and the ORIDL. In the second study, 187 new patients at the GHH were followed-up at 3, 12, and 33 months, using the ORIDL, the Short Form 12 (SF-12), and the Measure Yourself Medical Outcome Profile (MYMOP). In study three, 323 patients in primary care were followed for 1 month post-consultation using the ORIDL and MYMOP. In all 3 studies the Patient Enablement Instrument (PEI) was also used as an outcome measure. Results: Study 1 showed substantial improvements in main complaint and well-being over 12 months using the ORIDL, with two-thirds of patients reporting improvements in daily living. These improvements were not significantly correlated with changes in serial measures of the EQOL between baseline and 12 months, but were correlated with the EQOL transitions measure. Study 2 showed step-wise improvements in ORIDL scores between 3 and 33 months, which were only weakly associated with similar changes in SF-12 scores. However, MYMOP change scores correlated well with ORIDL scores at all time points. Study 3 showed similar high correlations between ORIDL scores and MYMOP scores. In all 3 studies, ORIDL scores were also significantly correlated with PEI-outcome scores. Conclusion: There is significant agreement between patient outcomes assessed by the ORIDL and the EQOL transition scale, the MYMOP, and the PEI-outcome instrument, suggesting that the ORIDL may be a valid and sensitive tool for measuring change in relation to impact on life. [ABSTRACT FROM AUTHOR]

The article addresses the issue surrounding the enlargement of the European Union (EU) and whether it will threaten Europeanization. Several national and international surveys, including the Eurobarometer and the World Values Survey, can provide information about the underlying values of European citizens, thus offering a way of assessing just how cohesive the EU is as a unit over time. The notion behind the enlargement is European coherence and the aim for economic interdependence.

Provides information on the concept, objectives and procedures of the power politics simulation game. Benefits from the simulation; Mechanism of the simulation game; Sequence of events.

Movement patterns of the Southern Rock Lobster Jasus edwardsii in Victoria, Australia were investigated from 8,533 tag-recapture events across a 20-year period (1992–2012). In total, 83% of lobsters were recaptured within 1 km of their tagging site and 93% within 5 km. While largely resident, elevated movements were observed within specific regions, with the overall direction of movement being from inshore to offshore areas. Movement was not impacted by lobster sex, size, or reproductive stage. The fishery for Southern Rock Lobster within Victoria is currently managed into two zones with separate total allowable commercial catches in each area. Given the high levels of site fidelity, our findings suggest that management of the resource at this spatial scale is appropriate and that consideration of significant movement between zones is not warranted in fishery stock assessment models. [ABSTRACT FROM AUTHOR]

The article presents the author's view on a study that shows the significance of nanowires in storing and exchanging quantum information in condensed-matter systems. It mentions the experiment on the unique material properties of indium arsenide (InAs) semiconductor nanowiere to control the quantum state of an electron spin using electric fields. Moreover, it shows that the experiment addresses the defect by moving from magnetic to all-electric files to achieve control over the electron spin.

Uninterruptible power system, photovoltaics inverters, home appliances, motor drives, and automotive systems require highly efficient, reliable, and compact single-phase inverters. This paper presents different industrial design approach and experimental performance of high power density (100 W/in3) single-phase inverter with power output of 2 kVA that was presented for Google Little Box challenge. Multiple technical challenges were addressed, different methodologies described to achieve high power density and high efficiency reliable design. High power density was achieved by using the combination of optimized forced air cooled heatsinks, fully digital control, optimized component packaging, and by the introduction of a series active filter that enabled to reduce the size of dc bus capacitors. Low-loss high flux density magnetic materials such as Amoflux powder iron for power inductors and nanocrystalline magnetic materials for electromagnetic interference filter were also used. To minimize inverter switching losses, SiC devices operating at low switching frequency were adopted. Also, an innovative ground current control strategy is devised to minimize the ground leakage currents. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To characterize the magnitude and variance of the change of glucose and glucagon-like peptide-1 (GLP-1) concentrations, and to identify determinants of glucose control up to 2 years after gastric bypass (GBP). RESEARCH DESIGN AND METHODS--Glucose and GLP-1 concentrations were measured during an oral glucose challenge before and 1, 12, and 24 months after GBP in 15 severely obese patients with type 2 diabetes. RESULTS--Glucose area under the curve from 0 to 180 min (AUC0-180) started decreasing in magnitude (P < 0.05) 1 month after surgery. GLP-1 AUC0-180 increased in magnitude 1 month after GBP (P < 0.05), with increased variance only after 1 year Due to image rights restrictions, multiple line equation(s) cannot be graphically displayed.. GLP-1 AUC0-180 was positively associated with insulin AUC0-180 (P = 0.025). CONCLUSIONS--The increase in variance of GLP-1 at 1 and 2 years after GBP suggests mechanisms other than proximal gut bypass to explain the enhancement of GLP-1 secretion. The association between GLP-1 and insulin concentrations supports the idea that the incretins are involved in glucose control after GBP. [ABSTRACT FROM AUTHOR]

Surface-functionalized nanomaterials are of interest as theranostic agents that detect disease and track biological processes using hyperpolarized magnetic resonance imaging (MRI). Candidate materials are sparse however, requiring spinful nuclei with long spin-lattice relaxation (T1) and spin-dephasing times (T2), together with a reservoir of electrons to impart hyperpolarization. Here, we demonstrate the versatility of the nanodiamond material system for hyperpolarized 13C MRI, making use of its intrinsic paramagnetic defect centers, hours-long nuclear T1 times, and T2 times suitable for spatially resolving millimeter-scale structures. Combining these properties, we enable a new imaging modality, unique to nanoparticles, that exploits the phase-contrast between spins encoded with a hyperpolarization that is aligned, or anti-aligned with the external magnetic field. The use of phase-encoded hyperpolarization allows nanodiamonds to be tagged and distinguished in an MRI based on their spin-orientation alone, and could permit the action of specific bio-functionalized complexes to be directly compared and imaged. [ABSTRACT FROM AUTHOR]

Examines the changing pattern of alcohol abuse in female acute medical admissions in Great Britain. Health problems caused by alcohol; Distribution of blood alcohol concentrations; Failure in detecting a rise on alcohol related illness.