Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation. MATERIALS AND METHODS: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined 'cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to 'early' or 'late' ToD of ICIs were collected from each report and pooled. RESULTS: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups. CONCLUSIONS: Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.

European cancer mortality predictions for the year 2024 with focus on colorectal cancer.

BACKGROUND: We predicted cancer mortality figures for 2024 for the European Union (EU), its five most populous countries, and the UK. We focused on mortality from colorectal cancer (CRC). MATERIALS AND METHODS: Based on cancer death certification and population data from the World Health Organization and Eurostat databases from 1970 until the most available year, we predicted deaths and age-standardized rates (ASRs) for 2024 for all cancers and the 10 most common cancer sites. We fitted a linear regression to the most recent trend segment identified by the joinpoint model. The number of avoided deaths since the peak in 1988-2024 was estimated for all cancers and CRC. RESULTS: We predicted 1 270 800 cancer deaths for 2024 in the EU, corresponding to ASRs of 123.2/100 000 men (-6.5% versus 2018) and 79.0/100 000 women (-4.3%). Since 1988, about 6.2 million cancer deaths have been avoided in the EU and 1.3 million in the UK. Pancreatic cancer displayed unfavorable predicted rates for both sexes (+1.6% in men and +4.0% in women) and lung cancer for women (+0.3%). The focus on CRC showed falls in mortality at all ages in the EU, by 4.8% for men and 9.5% for women since 2018. The largest declines in CRC mortality are predicted among those 70+ years old. In the UK, projected ASRs for CRC at all ages are favorable for men (-3.4% versus 2018) but not for women (+0.3%). Below age 50 years, CRC mortality showed unfavorable trends in Italy and the UK, in Poland and Spain for men, and in Germany for women. CONCLUSIONS: Predicted cancer mortality rates remain favorable in the EU and the UK, mainly in males due to earlier smoking cessation compared to females, underlining the persisting major role of tobacco on cancer mortality in Europe. Attention should be paid to the predicted increases in CRC mortality in young adults.

Broadband serrodyne phase modulation for optical frequency standards and spectral purity transfer.

We perform low phase noise, efficient serrodyne modulation for optical frequency control and spectral purity transfer between two ultrastable lasers. After characterizing serrodyne modulation efficiency and its bandwidth, we estimate the phase noise induced by the modulation setup by developing a novel, to the best of our knowledge, composite self-heterodyne interferometer. Exploiting serrodyne modulation, we phase locked a 698 nm ultrastable laser to a superior ultrastable laser source at 1156 nm by means of a frequency comb as a transfer oscillator. We show that this technique is a reliable tool for ultrastable optical frequency standards.

European cancer mortality predictions for the year 2023 with focus on lung cancer.

BACKGROUND: We predicted cancer mortality figures for 2023 for the European Union (EU-27), its five most populous countries, and the UK. We also focused on mortality from lung cancer. MATERIALS AND METHODS: Using cancer death certification and population data from the World Health Organization and Eurostat databases for 1970-2018, we predicted numbers of deaths and age-standardized rates (ASRs) for 2023 for all cancers combined and the 10 most common cancer sites. We investigated the changes in trends over the observed period. The number of avoided deaths over the period 1989-2023 were estimated for all cancers as well as lung cancer. RESULTS: We predicted 1 261 990 cancer deaths for 2023 in the EU-27, corresponding to ASRs of 123.8/100 000 men (-6.5% versus 2018) and 79.3 for women (-3.7%). Over 1989-2023, ∼5 862 600 cancer deaths were avoided in the EU-27 compared with peak rates in 1988. Most cancers displayed favorable predicted rates, with the exceptions of pancreatic cancer, which was stable in EU men (8.2/100 000) and rose by 3.4% in EU women (5.9/100 000), and female lung cancer, which, however, tends to level off (13.6/100 000). Steady declines are predicted for colorectal, breast, prostate, leukemia, stomach in both sexes, and male bladder cancers. The focus on lung cancer showed falls in mortality for all age groups in men. Female lung cancer mortality declined in the young (-35.8%, ASR: 0.8/100 000) and middle-aged (-7%, ASR: 31.2/100 000) but still increased by 10% in the elderly (age 65+ years). CONCLUSIONS: The advancements in tobacco control are reflected in favorable lung cancer trends, and should be pushed further. Greater efforts on the control of overweight and obesity, alcohol consumption, infection and related neoplasms, together with improvements in screening, early diagnosis, and treatments may achieve a further 35% reduction in cancer mortality in the EU by 2035.

European cancer mortality predictions for the year 2022 with focus on ovarian cancer.

BACKGROUND: Cancer mortality rates, though not absolute numbers of deaths, have been decreasing over the last three decades in Europe. MATERIALS AND METHODS: We estimated projections and the number of avoided deaths for total cancer mortality and 10 major cancer sites, between 1989 and 2022, for the European Union (EU), the UK, France, Germany, Italy, Poland and Spain using cancer death certification and population data since 1970 from the World Health Organization and Eurostat. RESULTS: In the EU, we predict 1 269 200 cancer deaths in 2022; corresponding age-standardized rates (world) fall 6% to 126.9 deaths/100 000 in men and 4% to 80.2/100 000 women since 2017. Male lung cancer is expected to fall 10% reaching 30.9/100 000. The rise in female lung cancer mortality slowed (+2% to 13.8/100 000). We estimated 369 000 (23%) avoided deaths in 2022 alone and a total of 5 394 000 (12%) deaths since the peak rate in 1988. Stomach, colorectal, breast and prostate cancers showed substantial declines, between 5% and 16% over the past 5 years. Pancreatic cancer remained stable in men (8.1/100 000) and rose 3% in women (5.9/100 000), becoming the third cause of cancer mortality in the EU (87 300 deaths), overtaking breast cancer (86 300 deaths). The fall in uterine cancers slowed down (-4%) to 4.7/100 000. Bladder cancer fell 9% in men, but was stable in women. Leukaemias fell more than 10%. Ovarian cancer mortality declined over the past decade in all considered countries. EU predicted rates were 4.3/100 000 (-13%) all ages, 1.2/100 000 (-26%) at 20-49, 15.3/100 000 (-11%) at 50-69 and 32.3/100 000 (-11%) at 70-79 years. CONCLUSIONS: We predicted additional declines in cancer mortality rates for 2022. The slowdown in female lung cancer mortality reflects some levelling of smoking in women. Favourable ovarian cancer trends are likely to continue and are largely attributable to the spreading oral contraceptive use and some impact of improved diagnosis and management.

Circadian and chemotherapy-related changes in urinary modified nucleosides excretion in patients with metastatic colorectal cancer.

Urinary levels of modified nucleosides reflect nucleic acids turnover and can serve as non-invasive biomarkers for monitoring tumour circadian dynamics, and treatment responses in patients with metastatic colorectal cancer. In 39 patients, median overnight urinary excretion of LC-HRMS determinations of pseudouridine, was ~ tenfold as large as those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~ 100-fold as large as those of adenosine and cytidine. An increase in any nucleoside excretion after chemotherapy anticipated plasma carcinoembryonic antigen progression 1-2 months later and was associated with poor survival. Ten fractionated urines were collected over 2-days in 29 patients. The median value of the rhythm-adjusted mean of urinary nucleoside excretion varied from 64.3 for pseudouridine down to 0.61 for cytidine. The rhythm amplitudes relative to the 24-h mean of 6 nucleoside excretions were associated with rest duration, supporting a tight link between nucleosides turnover and the rest-activity rhythm. Moreover, the amplitude of the 1-methylguanosine rhythm was correlated with the rest-activity dichotomy index, a significant predictor of survival outcome in prior studies. In conclusion, urinary excretion dynamics of modified nucleosides appeared useful for the characterization of the circadian control of cellular proliferation and for tracking early responses to treatments in colorectal cancer patients.

European cancer mortality predictions for the year 2021 with focus on pancreatic and female lung cancer.

BACKGROUND: We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer. MATERIALS AND METHODS: We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardised (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2021. RESULTS: We predicted 1 267 000 cancer deaths for 2021 in the EU, corresponding to age-standardised rates of 130.4/100 000 men (-6.6% since 2015) and 81.0/100 000 for women (-4.5%). We estimated further falls in male lung cancer rates, but still trending upward in women by +6.5%, reaching 14.5/100 000 in 2021. The breast cancer predicted rate in the EU was 13.3/100 000 (-7.8%). The rates for stomach and leukaemias in both sexes and for bladder in males are predicted to fall by >10%; trends for other cancer sites were also favourable, except for the pancreas, which showed stable patterns in both sexes, with predicted rates of 8.1/100 000 in men and 5.6/100 000 in women. Rates for pancreatic cancer in EU men aged 25-49 and 50-64 years declined, respectively, by 10% and 1.8%, while for those aged 65+ years increased by 1.3%. Rates fell for young women only (-3.4%). Over 1989-2021, about 5 million cancer deaths were avoided in the EU27 compared with peak rates in 1988. CONCLUSION: Overall cancer mortality continues to fall in both sexes. However, specific focus is needed on pancreatic cancer, which shows a sizeable decline for young men only. Tobacco control remains a priority for the prevention of pancreatic and other tobacco-related cancers, which account for one-third of the total EU cancer deaths, especially in women, who showed less favourable trends.

Characterization of the vertical evolution of the three-dimensional turbulence for fatigue design of tidal turbines.

A system of two coupled four-beam acoustic Doppler current profilers was used to collect turbulence measurements over a 36-h period at a highly energetic tidal energy site in Alderney Race. This system enables the evaluation of the six components of the Reynolds stress tensor throughout a large proportion of the water column. The present study provides mean vertical profiles of the velocity, the turbulence intensity and the integral lengthscale along the streamwise, spanwise and vertical direction of the tidal current. Based on our results and considering a tidal-stream energy convertor (TEC) aligned with the current main direction, the main elements of turbulence prone to affect the structure (material fatigue) and to alter power generation would likely be: (i) the streamwise turbulence intensity (Ix), (ii) the shear stress, [Formula: see text], (iii) the normal stress, [Formula: see text] and (iv) the vertical integral lengthscale (Lz). The streamwise turbulence intensity, (Ix), was found to be higher than that estimated at other tidal energy sites across the world for similar height above bottom. Along the vertical direction, the length (Lz) of the large-scale turbulence eddies was found to be equivalent to the rotor diameter of the TEC Sabella D10. It is considered that the turbulence metrics presented in this paper will be valuable for TECs designers, helping them optimize their designs as well as improve loading prediction through the lifetime of the machines. This article is part of the theme issue 'New insights on tidal dynamics and tidal energy harvesting in the Alderney Race'.

European cancer mortality predictions for the year 2020 with a focus on prostate cancer.

BACKGROUND: Current cancer mortality figures are important for disease management and resource allocation. We estimated mortality counts and rates for 2020 in the European Union (EU) and for its six most populous countries. MATERIALS AND METHODS: We obtained cancer death certification and population data from the World Health Organization and Eurostat databases for 1970-2015. We estimated projections to 2020 for 10 major cancer sites plus all neoplasms and calculated the number of avoided deaths over 1989-2020. RESULTS: Total cancer mortality rates in the EU are predicted to decline reaching 130.1/100 000 men (-5.4% since 2015) and 82.2 in women (-4.1%) in 2020. The predicted number of deaths will increase by 4.7% reaching 1 428 800 in 2020. In women, the upward lung cancer trend is predicted to continue with a rate in 2020 of 15.1/100 000 (higher than that for breast cancer, 13.5) while in men we predicted further falls. Pancreatic cancer rates are also increasing in women (+1.2%) but decreasing in men (-1.9%). In the EU, the prostate cancer predicted rate is 10.0/100 000, declining by 7.1% since 2015; decreases for this neoplasm are ∼8% at age 45-64, 14% at 65-74 and 75-84, and 6% at 85 and over. Poland is the only country with an increasing prostate cancer trend (+18%). Mortality rates for other cancers are predicted to decline further. Over 1989-2020, we estimated over 5 million avoided total cancer deaths and over 400 000 for prostate cancer. CONCLUSION: Cancer mortality predictions for 2020 in the EU are favourable with a greater decline in men. The number of deaths continue to rise due to population ageing. Due to the persistent amount of predicted lung (and other tobacco-related) cancer deaths, tobacco control remains a public health priority, especially for women. Favourable trends for prostate cancer are largely attributable to continuing therapeutic improvements along with early diagnosis.

Cancer mortality in Europe in 2015 and an overview of trends since 1990.

BACKGROUND: Cancer mortality in Europe has been decreasing since the late 1980s or 1990s in some countries with different patterns in many areas. In this study, we updated trends in cancer mortality in Europe. MATERIALS AND METHODS: We extracted data from the World Health Organization mortality database for 24 cancer sites, 36 European countries and the European Union (EU) as a whole over the 1990-2017 period. We computed age-standardized death rates per 100 000 person-years, and we carried out a joinpoint regression analysis of mortality trends from all cancers and selected major neoplasms. The estimated annual percent change (APC) for each identified linear segment, and the weighted average APC (AAPC) over the entire study period were provided as summary measures of the changes in rates over the time period. RESULTS: In 2015, the age-standardized mortality rates from all cancers in the EU were 137.5 deaths per 100 000 in men and 85.7 in women. Eastern European countries showed the highest rates with values over 150 deaths per 100 000 in men and over 100 deaths per 100 000 in women. Mortality from all cancers in the EU declined annually by 1.5% in men since 2006 and by 0.8% in women since 2007. Most cancer sites showed decreasing trends, with steady declines over the whole period for cancers of stomach, intestines, lung in men, breast and prostate. Unfavourable mortality trends persisted for cancers of liver, lung in women, pancreas, besides skin and kidney in men. CONCLUSIONS: The downward trends in total cancer mortality in Europe still continue over the last decade. However, the trends were less favourable in most eastern European countries. Tobacco control in men (but not in women), improvements in diagnosis and therapy were the main underlying factors of these trends.

European cancer mortality predictions for the year 2019 with focus on breast cancer.

BACKGROUND: To overcome the lag with which cancer statistics become available, we predicted numbers of deaths and rates from all cancers and selected cancer sites for 2019 in the European Union (EU). MATERIALS AND METHODS: We retrieved cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2014. We obtained estimates for 2019 with a linear regression on number of deaths over the most recent trend period identified by a logarithmic Poisson joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2019. RESULTS: We estimated about 1 410 000 cancer deaths in the EU for 2019, corresponding to age-standardized rates of 130.9/100 000 men (-5.9% since 2014) and 82.9 women (-3.6%). Lung cancer trends in women are predicted to increase 4.4% between 2014 and 2019, reaching a rate of 14.8. The projected rate for breast cancer was 13.4. Favourable trends for major neoplasms are predicted to continue, except for pancreatic cancer. Trends in breast cancer mortality were favourable in all six countries considered, except Poland. The falls were largest in women 50-69 (-16.4%), i.e. the age group covered by screening, but also seen at age 20-49 (-13.8%), while more modest at age 70-79 (-6.1%). As compared to the peak rate in 1988, over 5 million cancer deaths have been avoided in the EU over the 1989-2019 period. Of these, 440 000 were breast cancer deaths. CONCLUSION: Between 2014 and 2019, cancer mortality will continue to fall in both sexes. Breast cancer rates will fall steadily, with about 35% decline in rates over the last three decades. This is likely due to reduced hormone replacement therapy use, improvements in screening, early diagnosis and treatment. Due to population ageing, however, the number of breast cancer deaths is not declining.

Shared and Study-specific Dietary Patterns and Head and Neck Cancer Risk in an International Consortium.

BACKGROUND: A few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available. METHODS: We used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models. RESULTS: We identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk. CONCLUSION: Multi-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

Cancer mortality and predictions for 2018 in selected Australasian countries and Russia.

Background: Predicted cancer mortality figures and rates are useful for public health planning. Materials and methods: We retrieved cancer death certification data for 10 major cancer sites and total cancers from the World Health Organization (WHO) database and population data from WHO and United Nations Population Division databases. We obtained figures for Russia, Israel, Hong Kong, Japan, the Philippines, Korea, and Australia in 1970-2015. We predicted numbers of deaths by age group and age-standardized rates (world population) for 2018 by applying a linear regression to mortality data of each age group over the most recent trend segment identified by a joinpoint regression model. Results: Russia had the highest predicted total cancer mortality rates, 158.5/100 000 men and 84.1/100 000 women. Men in the Philippines showed the lowest rates for 2018 (84.6/100 000) and Korean males the most favourable predicted fall (21% between 2012 and 2018). Women in Korea had the lowest total cancer predicted rate (52.5/100 000). Between 1993 and 2018, i.e. by applying the 1993 rates to populations in subsequent years, a substantial number of cancer deaths was avoided in Russia (1 000 000 deaths, 821 000 in men and 179 000 in women), Israel (40 000 deaths, 21 000 in men and 19 000 in women), Hong Kong (63 000 deaths, 40 000 in men and 23 000 in women), Japan (651 000 deaths, 473 000 in men and 178 000 in women), Korea (327 000 deaths, 250 000 in men and 77 000 in women), and Australia (181 000 deaths, 125 000 in men and 56 000 in women). No appreciable reduction in cancer deaths was found in the Philippines. Conclusion: Overall, we predicted falls in cancer mortality. However, these are less marked and later compared with the European Union and United States. Substantial numbers of deaths were avoided in all countries considered except the Philippines. Lung cancer mortality remains exceedingly high in Russian men, despite recent falls.

Ectonucleotidase-Mediated Suppression of Lupus Autoimmunity and Vascular Dysfunction.

OBJECTIVES: CD39 and CD73 are surface enzymes that jut into the extracellular space where they mediate the step-wise phosphohydrolysis of the autocrine and paracrine danger signals ATP and ADP into anti-inflammatory adenosine. Given the role of vascular and immune cells' "purinergic halo" in maintaining homeostasis, we hypothesized that the ectonucleotidases CD39 and CD73 might play a protective role in lupus. METHODS: Lupus was modeled by intraperitoneal administration of pristane to three groups of mice: wild-type (WT), CD39-/-, and CD73-/-. After 36 weeks, autoantibodies, endothelial function, kidney disease, splenocyte activation/polarization, and neutrophil activation were characterized. RESULTS: As compared with WT mice, CD39-/- mice developed exaggerated splenomegaly in response to pristane, while both groups of ectonucleotidase-deficient mice demonstrated heightened anti-ribonucleoprotein production. The administration of pristane to WT mice triggered only subtle dysfunction of the arterial endothelium; however, both CD39-/- and CD73-/- mice demonstrated striking endothelial dysfunction following induction of lupus, which could be reversed by superoxide dismutase. Activated B cells and plasma cells were expanded in CD73-/- mice, while deficiency of either ectonucleotidase led to expansion of TH17 cells. CD39-/- and CD73-/- mice demonstrated exaggerated neutrophil extracellular trap release, while CD73-/- mice additionally had higher levels of plasma cell-free DNA. CONCLUSION: These data are the first to link ectonucleotidases with lupus autoimmunity and vascular disease. New therapeutic strategies may harness purinergic nucleotide dissipation or signaling to limit the damage inflicted upon organs and blood vessels by lupus.

European cancer mortality predictions for the year 2018 with focus on colorectal cancer.

Background: We projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer. Materials and methods: We obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970-2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models. Results: EU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100 000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1 382 000 when compared with 1 333 362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100 000 for 2018 (13.9 in 2012, +5.8%) and 94 500 expected deaths, higher than the rate of 13.7 and 92 700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100 000 men (-6.7%) and 9.2 in women (-7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose +2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392 300 cancer deaths were avoided compared with peak rates in the late 1980s. Conclusion: We predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and-above age 50 years-organized screening may account for recent favourable colorectal cancer trends.

Measuring molecular frequencies in the 1-10 µm range at 11-digits accuracy.

High-resolution spectroscopy in the 1-10 µm region has never been fully tackled for the lack of widely-tunable and practical light sources. Indeed, all solutions proposed thus far suffer from at least one of three issues: they are feasible only in a narrow spectral range; the power available for spectroscopy is limited; the frequency accuracy is poor. Here, we present a setup for high-resolution spectroscopy, whose approach can be applied in the whole 1-10 µm range. It combines the power of quantum cascade lasers (QCLs) and the accuracy achievable by difference frequency generation using an orientation patterned GaP crystal. The frequency is measured against a primary frequency standard using the Italian metrological fibre link network. We demonstrate the performance of the setup by measuring a vibrational transition in a highly-excited metastable state of CO around 6 µm with 11 digits of precision.

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target.

Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils - neutrophil extracellular traps (NETs), in particular - in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1-KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1-deficient mice by infusion of WT neutrophils, while an anti-PSGL-1 monoclonal antibody inhibited APS IgG-mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS.

Cancer mortality predictions for 2017 in Latin America.

BACKGROUND: From most recent available data, we predicted cancer mortality statistics in selected Latin American countries for the year 2017, with focus on lung cancer. MATERIALS AND METHODS: We obtained death certification data from the World Health Organization and population data from the Pan American Health Organization database for all neoplasms and selected cancer sites. We derived figures for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela. Using a logarithmic Poisson count data joinpoint model, we estimated number of deaths and age-standardized (world population) mortality rates in 2017. RESULTS: Total cancer mortality rates are predicted to decline in all countries. The highest mortality rates for 2017 are in Cuba, i.e. 132.3/100 000 men and 93.3/100 000 women. Mexico had the lowest predicted rates, 64.7/100 000 men and 60.6/100 000 women. In contrast, the total number of cancer deaths is expected to rise due to population ageing and growth. Men showed declines in lung cancer trends in all countries and age groups considered, while only Colombian and Mexican women had downward trends. Stomach and (cervix) uteri rates are predicted to continue their declines, though mortality from these neoplasms remains comparatively high. Colorectal, breast and prostate cancer rates were predicted to decline moderately, as well as leukaemias. There was no clear pattern for pancreatic cancer. Between 1990 and 2017 about 420 000 cancer deaths were avoided in 5 of the 7 countries, no progress was observed in Brazil and Cuba. CONCLUSION: Cancer mortality rates for 2017 in seven selected Latin American countries are predicted to decline, though there was appreciable variability across countries. Mortality from major cancers-including lung and prostate-and all cancers remains comparatively high in Cuba, indicating the need for improved prevention and management.

European cancer mortality predictions for the year 2017, with focus on lung cancer.

BACKGROUND: We predicted cancer mortality figures in the European Union (EU) for the year 2017 using most recent available data, with a focus on lung cancer. MATERIALS AND METHODS: We retrieved cancer death certification data and population figures from the World Health Organisation and Eurostat databases. Age-standardized (world standard population) rates were computed for France, Germany, Italy, Poland, Spain, the UK and the EU overall in 1970-2012. We obtained estimates for 2017 by implementing a joinpoint regression model. RESULTS: The predicted number of cancer deaths for 2017 in the EU is 1 373 500, compared with 1 333 400 in 2012 (+3%). Cancer mortality rates are predicted to decline in both sexes, reaching 131.8/100 000 men (-8.2% when compared with 2012) and 84.5/100 000 women (-3.6%). Mortality rates for all selected cancer sites are predicted to decline, except pancreatic cancer in both sexes and lung cancer in women. In men, pancreatic cancer rate is stable, in women it increases by 3.5%. Lung cancer mortality rate in women is predicted to rise to 14.6/100 000 in 2017 (+5.1% since 2012, corresponding to 92 300 predicted deaths), compared with 14.0/100 000 for breast cancer, corresponding to 92 600 predicted deaths. Only younger (25-44) women have favourable lung cancer trends, and rates at this age group are predicted to be similar in women (1.4/100 000) and men (1.2/100 000). In men lung cancer rates are predicted to decline by 10.7% since 2012, and falls are observed in all age groups. CONCLUSION: European cancer mortality projections for 2017 confirm the overall downward trend in rates, with a stronger pattern in men. This is mainly due to different smoking prevalence trends in different generations of men and women. Lung cancer rates in young European women are comparable to those in men, confirming that smoking has the same impact on lung cancer in the two sexes.