Excess mortality among essential workers in England and Wales during the COVID-19 pandemic: an updated analysis

BACKGROUND: Excess mortality from all causes combined during the COVID-19 pandemic in England and Wales in 2020 was predominantly higher for essential workers. In 2021, the vaccination programme had begun, new SARS-CoV-2 variants were identified and different policy approaches were used. We have updated our previous analyses of excess mortality in England and Wales to include trends in excess mortality by occupation for 2021. METHODS: We estimated excess mortality for working age adults living in England and Wales by occupational group for each month in 2021 and for the year as a whole. RESULTS: During 2021, excess mortality remained higher for most groups of essential workers than for non-essential workers. It peaked in January 2021 when all-cause mortality was 44.6% higher than expected for all occupational groups combined. Excess mortality was highest for adults working in social care (86.9% higher than expected). CONCLUSION: Previously, we reported excess mortality in 2020, with this paper providing an update to include 2021 data. Excess mortality was predominantly higher for essential workers during 2021. However, unlike the first year of the pandemic, when healthcare workers experienced the highest mortality, the highest excess mortality during 2021 was experienced by social care workers

Worldwide trends in esophageal cancer survival, by sub-site, morphology, and sex: an analysis of 696,974 adults diagnosed in 60 countries during 2000-2014 (CONCORD-3)

BACKGROUND: Esophageal cancer survival is poor worldwide, though there is some variation. Differences in the distribution of anatomical sub-site and morphological sub-type may help explain international differences in survival for all esophageal cancers combined. We estimated survival by anatomic sub-site and morphological sub-type to understand further the impact of topography and morphology on international comparisons of esophageal cancer survival. METHODS: We estimated age-standardized one-year and five-year net survival among adults (15-99 years) diagnosed with esophageal cancer in each of 60 participating countries to monitor survival trends by calendar period of diagnosis (2000-2004, 2005-2009, 2010-2014), sub-site, morphology, and sex. RESULTS: For adults diagnosed during 2010-2014, tumors in the lower third of the esophagus were the most common, followed by tumors of overlapping sub-site and sub-site not otherwise specified. The proportion of squamous cell carcinomas diagnosed during 2010-2014 was generally higher in Asian countries (50%-90%), while adenocarcinomas were more common in Europe, North America and Oceania (50%-60%). From 2000-2004 to 2010-2014, the proportion of squamous cell carcinoma generally decreased, and the proportion of adenocarcinoma increased. Over time, there were few improvements in age-standardized five-year survival for each sub-site. Age-standardized one-year survival was highest in Japan for both squamous cell carcinoma (67.7%) and adenocarcinoma (69.0%), ranging between 20%-60% in most other countries. Age-standardized five-year survival from squamous cell carcinoma and adenocarcinoma was similar for most countries included, around 15%-20% for adults diagnosed during 2010-2014, though international variation was wider for squamous cell carcinoma. In most countries, survival for both squamous cell carcinoma and adenocarcinoma increased by less than 5% between 2000-2004 and 2010-2014. CONCLUSIONS: Esophageal cancer survival remains poor in many countries. The distributions of sub-site and morphological sub-type vary between countries, but these differences do not fully explain international variation in esophageal cancer survival

Survival from five common cancers in Georgia, 2015-2019 (CONCORD).

BACKGROUND: Population-based cancer survival is a key metric of the effectiveness of health systems in managing cancer. Data from population-based cancer registries are essential for producing reliable and robust cancer survival estimates. Georgia established a national population-based cancer registry on 1 January 2015. This is the first analysis of population-based cancer survival from Georgia. METHODS: Data were available from the national cancer registry for 16,359 adults who were diagnosed with a cancer of the stomach, colon, rectum, breast (women) or cervix during 2015-2019. We estimated age-specific and age-standardised net survival at one, two and three years after diagnosis for each cancer, by sex. RESULTS: The data were of extremely high quality, with less than 2% of data excluded from each dataset. For the patients included in analyses, at least 80% of the tumours were microscopically verified. Age-standardised three-year survival from stomach cancer was 30.6%, similar in men and women. For colon cancer, three-year survival was 60.1%, with survival 4% higher for men than for women. Three-year survival from rectal cancer was similar for men and women, at 54.7%. For women diagnosed with breast cancer, three-year survival was 84.4%, but three-year survival from cervical cancer was only 67.2%. CONCLUSION: Establishment of a national cancer registry with obligatory cancer registration has enabled the first examination of population-based cancer survival in Georgia. Maintenance of the registry will facilitate continued surveillance of both cancer incidence and survival in the country

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000-2014 (CONCORD-3)

Background Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods We analyzed individual data for adults (15-99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000-2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results The study included 556,237 adults. In 2010-2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%-38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000-2004 and 2005-2009. These improvements were more noticeable among adults diagnosed aged 40-70 years than among younger adults. Conclusions To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000-2014 (CONCORD-3)

BACKGROUND Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. METHODS We analyzed individual data for adults (15-99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000-2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. RESULTS The study included 556,237 adults. In 2010-2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%-38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000-2004 and 2005-2009. These improvements were more noticeable among adults diagnosed aged 40-70 years than among younger adults. CONCLUSIONS To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

Terminal Continuation (TC) RNA Amplification Enables Expression Profiling Using Minute RNA Input Obtained from Mouse Brain

A novel methodology named terminal continuation (TC) RNA amplification has been developed to amplify RNA from minute amounts of starting material. Utility of the TC RNA amplification method is demonstrated with two new modifications including obviating the need for second strand synthesis, and purifying the amplification template using column filtration prior to in vitro transcription (IVT). Using four low concentrations of RNA extracted from mouse brain (1, 10, 25 and 50 ng), one round TC RNA amplification was compared to one round amplified antisense RNA (aRNA) in conjunction with column filtration and drop dialysis purification. The TC RNA amplification without second strand synthesis performed extremely well on custom-designed cDNA array platforms, and column filtration was found to provide higher positive detection of individual clones when hybridization signal intensity was subtracted from corresponding negative control hybridization signal levels. Results indicate that TC RNA amplification without second strand synthesis, in conjunction with column filtration, is an excellent method for RNA amplification from extremely small amounts of input RNA from mouse brain and postmortem human brain, and is compatible with microaspiration strategies and subsequent microarray analysis

Does the morphology of cutaneous melanoma help to explain the international differences in survival? Results from 1 578 482 adults diagnosed during 2000-2014 in 59 countries (CONCORD-3).

BACKGROUND: CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000-2014. Clinical evidence suggests marked international differences in the proportion of lethal acral and nodular subtypes of cutaneous melanoma. OBJECTIVES: We aimed to assess whether the differences in morphology may explain global variation in survival. METHODS: Patients with melanoma were grouped into the following seven morphological categories: malignant melanoma, not otherwise specified (International Classification of Diseases for Oncology, third revision morphology code 8720), superficial spreading melanoma (8743), lentigo maligna melanoma (8742), nodular melanoma (8721), acral lentiginous melanoma (8744), desmoplastic melanoma (8745) and other morphologies (8722-8723, 8726-8727, 8730, 8740-8741, 8746, 8761, 8770-8774, 8780). We estimated net survival using the nonparametric Pohar Perme estimator, correcting for background mortality by single year of age, sex and calendar year in each country or region. All-ages survival estimates were standardized using the International Cancer Survival Standard weights. We fitted a flexible parametric model to estimate the effect of morphology on the hazard of death. RESULTS: Worldwide, the proportion of nodular melanoma ranged between 7% and 13%. Acral lentiginous melanoma accounted for less than 2% of all registrations but was more common in Asia (6%) and Central and South America (7%). Overall, 36% of tumours were classified as superficial spreading melanoma. During 2010-2014, age-standardized 5-year net survival for superficial spreading melanoma was 95% or higher in Oceania, North America and most European countries, but was only 71% in Taiwan. Survival for acral lentiginous melanoma ranged between 66% and 95%. Nodular melanoma had the poorest prognosis in all countries. The multivariable analysis of data from registries with complete information on stage and morphology found that sex, age and stage at diagnosis only partially explain the higher risk of death for nodular and acral lentiginous subtypes. CONCLUSIONS: This study provides the broadest picture of distribution and population-based survival trends for the main morphological subtypes of cutaneous melanoma in 59 countries. The poorer prognosis for nodular and acral lentiginous melanomas, more frequent in Asia and Latin America, suggests the need for health policies aimed at specific populations to improve awareness, early diagnosis and access to treatment. What is already known about this topic? The histopathological features of cutaneous melanoma vary markedly worldwide. The proportion of melanomas with the more aggressive acral lentiginous or nodular histological subtypes is higher in populations with predominantly dark skin than in populations with predominantly fair skin. What does this study add? We aimed to assess the extent to which these differences in morphology may explain international variation in survival when all histological subtypes are combined. This study provides, for the first time, international comparisons of population-based survival at 5 years for the main histological subtypes of melanoma for over 1.5 million adults diagnosed during 2000-2014. This study highlights the less favourable distribution of histological subtypes in Asia and Central and South America, and the poorer prognosis for nodular and acral lentiginous melanomas. We found that later stage at diagnosis does not fully explain the higher excess risk of death for nodular and acral lentiginous melanoma compared with superficial spreading melanoma

Unraveling the Early Events of Amyloid-β Protein (Aβ) Aggregation: Techniques for the Determination of Aβ Aggregate Size

The aggregation of proteins into insoluble amyloid fibrils coincides with the onset of numerous diseases. An array of techniques is available to study the different stages of the amyloid aggregation process. Recently, emphasis has been placed upon the analysis of oligomeric amyloid species, which have been hypothesized to play a key role in disease progression. This paper reviews techniques utilized to study aggregation of the amyloid-β protein (Aβ) associated with Alzheimer’s disease. In particular, the review focuses on techniques that provide information about the size or quantity of oligomeric Aβ species formed during the early stages of aggregation, including native-PAGE, SDS-PAGE, Western blotting, capillary electrophoresis, mass spectrometry, fluorescence correlation spectroscopy, light scattering, size exclusion chromatography, centrifugation, enzyme-linked immunosorbent assay, and dot blotting

A Novel Neural Substrate for the Transformation of Olfactory Inputs into Motor Output

Anatomical and physiological experiments in the lamprey reveal the neural circuit involved in transforming olfactory inputs into motor outputs, which was previously unknown in a vertebrate

The histology of ovarian cancer: worldwide distribution and implications for international survival comparisons (CONCORD-2)

Objective Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. Methods The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995â\u80\u932009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included. We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. Results During 2005â\u80\u932009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. Conclusions The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions