Summary Background Assessment of progress in cancer control at the population level is increasingly important. Population-based survival trends provide a key insight into the overall effectiveness of ...the health system, alongside trends in incidence and mortality. For this purpose, we aimed to provide a unique measure of cancer survival. Methods In this observational study, we analysed trends in survival with population-based data for 7·2 million adults diagnosed with a first, primary, invasive malignancy in England and Wales during 1971–2011 and followed up to the end of 2012. We constructed a survival index for all cancers combined using data from the National Cancer Registry and the Welsh Cancer Intelligence and Surveillance Unit. The index is designed to be independent of changes in the age distribution of patients with cancer and of changes in the proportion of lethal cancers in each sex. We analysed trends in the cancer survival index at 1, 5, and 10 years after diagnosis for the selected periods 1971–72, 1980–81, 1990–91, 2000–01, 2005–06, and 2010–11. We also estimated trends in age-sex-adjusted survival for each cancer. We define the difference in net survival between the oldest (75–99 years) and youngest (15–44 years) patients as the age gap in survival. We evaluated the absolute change (%) in the age gap since 1971. Findings The overall index of net survival increased substantially during the 40-year period 1971–2011, both in England and in Wales. For patients diagnosed in 1971–72, the index of net survival was 50% at 1 year after diagnosis. 40 years later, the same value of 50% was predicted at 10 years after diagnosis. The average 10% survival advantage for women persisted throughout this period. Predicted 10-year net survival adjusted for age and sex for patients diagnosed between 2010 and 2011 ranged from 1·1% for pancreatic cancer to 98·2% for testicular cancer. Net survival for the oldest patients (75–99 years) was persistently lower than for the youngest (15–44 years), even after adjustment for the much higher mortality from causes other than cancer in elderly people. Interpretation These findings support substantial increases in both short-term and long-term net survival from all cancers combined in both England and Wales. The net survival index provides a convenient, single number that summarises the overall patterns of cancer survival in any one population, in each calendar period, for young and old men and women and for a wide range of cancers with very disparate survival. The persistent sex difference is partly due to a more favourable cancer distribution in women than men. The very wide differences in survival for different cancers, and the persistent age gap in survival, suggest the need for renewed efforts to improve cancer outcomes. Future monitoring of the cancer survival index will not be possible unless the current crisis of public concern about sharing of individual data for public health research can be resolved. Funding Cancer Research UK.
Summary Millions of people will continue to be diagnosed with cancer every year for the foreseeable future. These patients all need access to optimum health care. Population-based cancer survival is ...a key measure of the overall effectiveness of health systems in management of cancer. Survival varies very widely around the world. Global surveillance of cancer survival is needed, because unless these avoidable inequalities are measured, and reported on regularly, nothing will be done explicitly to reduce them.
Parkinson disease (PD) is a multifactorial neurodegenerative disorder, the etiology of which remains largely unknown. Progressive impairment of voluntary motor control, which represents the primary ...clinical feature of the disease, is caused by a loss of midbrain substantia nigra dopamine (DA) neurons. We present here a synthetic overview of cell-autonomous mechanisms that are likely to participate in DA cell death in both sporadic and inherited forms of the disease. In particular, we describe how damage to vulnerable DA neurons may arise from cellular disturbances produced by protein misfolding and aggregation, disruption of autophagic catabolism, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, or loss of calcium homeostasis. Where pertinent, we show how these mechanisms may mutually cooperate to promote neuronal death.
In this review, Michel and coworkers present a synthetic overview of cell-autonomous mechanisms involved in dopamine cell death in Parkinson disease, including protein misfolding and aggregation, disruption of autophagic catabolism, endoplasmic reticulum stress, mitochondrial dysfunction, and loss of calcium homeostasis.
AbstractObjectiveTo assess the effectiveness of the NHS Cancer Plan (2000) and subsequent national cancer policy initiatives in improving cancer survival and reducing socioeconomic inequalities in ...survival in England.DesignPopulation based cohort study.SettingEngland.PopulationMore than 3.5 million registered patients aged 15-99 with a diagnosis of one of the 24 most common primary, malignant, invasive neoplasms between 1996 and 2013.Main outcome measuresAge standardised net survival estimates by cancer, sex, year, and deprivation group. These estimates were modelled using regression model with splines to explore changes in the cancer survival trends and in the socioeconomic inequalities in survival.ResultsOne year net survival improved steadily from 1996 for 26 of 41 sex-cancer combinations studied, and only from 2001 or 2006 for four cancers. Trends in survival accelerated after 2006 for five cancers. The deprivation gap observed for all 41 sex-cancer combinations among patients with a diagnosis in 1996 persisted until 2013. However, the gap slightly decreased for six cancers among men for which one year survival was more than 65% in 1996, and for cervical and uterine cancers, for which survival was more than 75% in 1996. The deprivation gap widened notably for brain tumours in men and for lung cancer in women.ConclusionsLittle evidence was found of a direct impact of national cancer strategies on one year survival, and no evidence for a reduction in socioeconomic inequalities in cancer survival. These findings emphasise that socioeconomic inequalities in survival remain a major public health problem for a healthcare system founded on equity.
To advance our understanding of the environmental fate and transport of macro- and micro-plastic debris, robust and reproducible methods, technologies, and analytical approaches are necessary for in ...situ plastic-type identification and characterization. This investigation compares four spectroscopic techniques: attenuated total reflectance–Fourier transform infrared spectroscopy (ATR–FTIR), near-infrared (NIR) reflectance spectroscopy, laser-induced breakdown spectroscopy (LIBS), and X-ray fluorescence (XRF) spectroscopy, coupled to seven classification methods, including machine learning classifiers, to determine accuracy for identifying type of both consumer plastics and marine plastic debris (MPD). With machine learning classifiers, consumer plastic types were identified with 99, 91, 97, and 70% success rates for ATR–FTIR, NIR reflectance spectroscopy, LIBS, and XRF, respectively. The classification of MPD had similar or lower success rates, likely arising from alterations to the plastic from environmental weathering processes with success rates of 99, 81, 76, and 66% for ATR–FTIR, NIR reflectance spectroscopy, LIBS, and XRF, respectively. Success rates indicate that ATR–FTIR, NIR reflectance spectroscopy, and LIBS coupled with machine learning classifiers can be used to identify both consumer and environmental plastic samples.
The control and manipulation of the electron spin in semiconductors is central to spintronics, which aims to represent digital information using spin orientation rather than electron charge. Such ...spin-based technologies may have a profound impact on nanoelectronics, data storage, and logic and computer architectures. Recently it has become possible to induce and detect spin polarization in otherwise non-magnetic semiconductors (gallium arsenide and silicon) using all-electrical structures, but so far only at temperatures below 150 K and in n-type materials, which limits further development. Here we demonstrate room-temperature electrical injection of spin polarization into n-type and p-type silicon from a ferromagnetic tunnel contact, spin manipulation using the Hanle effect and the electrical detection of the induced spin accumulation. A spin splitting as large as 2.9 meV is created in n-type silicon, corresponding to an electron spin polarization of 4.6%. The extracted spin lifetime is greater than 140 ps for conduction electrons in heavily doped n-type silicon at 300 K and greater than 270 ps for holes in heavily doped p-type silicon at the same temperature. The spin diffusion length is greater than 230 nm for electrons and 310 nm for holes in the corresponding materials. These results open the way to the implementation of spin functionality in complementary silicon devices and electronic circuits operating at ambient temperature, and to the exploration of their prospects and the fundamental rules that govern their behaviour.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition. We previously demonstrated that administration of Akkermansia muciniphila to ...mice prevents the development of obesity and associated complications. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders.
Summary Background Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE—the largest cooperative study of population-based cancer survival in Europe—has shown ...persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. Methods In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000–07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999–2001, 2002–04, and 2005–07). Findings 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999–2001 to 2005–07 were for prostate cancer (73·4% 95% CI 72·9–73·9 vs 81·7% 81·3–82·1), non-Hodgkin lymphoma (53·8% 53·3–54·4 vs 60·4% 60·0–60·9), and rectal cancer (52·1% 51·6–52·6 vs 57·6% 57·1–58·1). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type. Interpretation The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities. Funding Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation.
Abstract Introduction Despite the advancements in technology and organized training for surgeons in laparoscopic surgery, the persistent challenge of not being able to feel the resistance and ...characteristics of the tissue, including pulsations, remains unmet. A recently developed grasper (Optigrip®) with real time haptic feedback, based on photonic technology, aims to address this issue by restoring the tactile sensation for surgeons. The key question is whether pulsations can be detected and at what minimal size level they become clinical significant. Methods To simulate arterial conditions during laparoscopic procedures, four different silicone tubes were created, representing the most prevalent arteries. These tubes were connected to a validated pressure system, generating a natural pulse ranging between 80 and 120 mm Hg. One control tube without pressure was added. The surgeons had to grasp these tubes blindly with the conventional grasper or the haptic feedback grasper in a randomized order. They then indicated whether they felt the pressure or not and the percentage of correct answers was calculated. Results The haptic grasper successfully detected 96% of all pulsations, while the conventional grasper could only detect 6%. When considering the size of the arteries, the Optigrip® identified pulsations in 100% the 4 and 5 mm arteries and 92% of the smallest arteries. The conventional grasper was only able to feel the smallest arteries in 8%. These differences were highly significant ( p < 0.0001). Conclusion This study demonstrated that the newly developed haptic feedback grasper enables detection of arterial pulsations during laparoscopy, filling an important absence in tactile perception within laparoscopic surgery.
Here, we show that the ponderomotive force associated with laser speckles can scatter electrons in a laser-produced plasma in a manner similar to Coulomb scattering. Analytic expressions for the ...effective collision rates are given. The electron-speckle collisions become important at high laser intensity or during filamentation, affecting both long- and short-pulse laser intensity regimes. As an example, we find that the effective collision rate in the laser-overlap region of hohlraums on the National Ignition Facility is expected to exceed the Coulomb collision rate by 1 order of magnitude, leading to a fundamental change to the electron transport properties. At the high intensities characteristic of short-pulse laser-plasma interactions (I ≳ 1017 W cm–2), the scattering is strong enough to cause the direct absorption of laser energy, generating hot electrons with energy scaling as E ≈ 1.44 (I/1018 W cm–2)1/2 MeV , close to experimentally observed results.
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