Sedimentary inputs to the Nankai subduction zone: The importance of dispersed ash

We examine the importance of dispersed volcanic ash as a critical component of the aluminosilicate sediment entering the Nankai Trough, located south of Japan’s island of Honshu, via the subducting Philippine Sea plate. Multivariate statistical analyses of an extensive major, trace, and rare earth element data set from bulk sediment and discrete ash layers at Integrated Ocean Drilling Program (IODP) Sites C0011 and C0012 quantitatively determine the abundance and accumulation of multiple aluminosilicate inputs to the Nankai subduction zone. We identify the eolian input of continental material to both sites, and we further find that there are an additional three ash sources from Kyushu and Honshu, Japan and other regions. Some of these ash sources may themselves represent mixtures of ash inputs, although the final compositions appear statistically distinct. The dispersed ash comprises 38 ± 7 weight percent (wt%) of the bulk sediment at Site C0011, and 34 ± 4 wt% at Site C0012. When considering the entire sediment thickness at Site C0011, the dispersed ash component supplies 38000 ± 7000 g/cm2 of material to the Nankai subduction system, whereas Site C0012 supplies 20000 ± 3000 g/cm2. These values are enormous compared to the ~2500 g/cm2 (C0011) and ~1200 g/cm2 (C0012) of ash in the discrete ash layers. Therefore, the mass of volcanic ash and chemically equivalent alteration products (e.g., smectite) that are dispersed throughout the stratigraphic succession of bulk sediment appears to be up to 15–17 times greater than the mass of discrete ash layers. The composition of the dispersed ash component at Site C0011 appears linked to that of the discrete layers, and the mass accumulation rate for dispersed ash correlates best with discrete ash layer thickness. In contrast, at Site C0012 the mass accumulation rate for dispersed ash correlates better with the number of ash layers. Together, the discrete ash layers, dispersed ash, and clay-mineral assemblages present a complete record of volcanism and erosion of volcanic sources; and indicate that mass balances and subduction factory budgets should include the mass of dispersed ash for a more accurate assessment of volcanic contributions to large-scale geochemical cycling

Multivariate statistical analysis and partitioning of sedimentary geochemical data sets: General principles and specific MATLAB scripts

Multivariate statistical treatments of large data sets in sedimentary geochemical and other fields are rapidly becoming more popular as analytical and computational capabilities expand. Because geochemical data sets present a unique set of conditions (e.g., the closed array), application of generic off-the-shelf applications is not straightforward and can yield misleading results. We present here annotated MATLAB scripts (and specific guidelines for their use) for Q-mode factor analysis, a constrained least squares multiple linear regression technique, and a total inversion protocol, that are based on the well-known approaches taken by Dymond (1981), Leinen and Pisias (1984), Kyte et al. (1993), and their predecessors. Although these techniques have been used by investigators for the past decades, their application has been neither consistent nor transparent, as their code has remained in-house or in formats not commonly used by many of today’s researchers (e.g., FORTRAN). In addition to providing the annotated scripts and instructions for use, we discuss general principles to be considered when performing multivariate statistical treatments of large geochemical data sets, provide a brief contextual history of each approach, explain their similarities and differences, and include a sample data set for the user to test their own manipulation of the scripts.Keywords: geochemistry, statistics, multivariate statistic

Geochemical approaches to the quantification of dispersed volcanic ash in marine sediment

Volcanic ash has long been recognized in marine sediment, and given the prevalence of oceanic and continental arc volcanism around the globe in regard to widespread transport of ash, its presence is nearly ubiquitous. However, the presence/absence of very fine-grained ash material, and identification of its composition in particular, is challenging given its broad classification as an “aluminosilicate” component in sediment. Given this challenge, many studies of ash have focused on discrete layers (that is, layers of ash that are of millimeter-to-centimeter or greater thickness, and their respective glass shards) found in sequences at a variety of locations and timescales and how to link their presence with a number of Earth processes. The ash that has been mixed into the bulk sediment, known as dispersed ash, has been relatively unstudied, yet represents a large fraction of the total ash in a given sequence. The application of a combined geochemical and statistical technique has allowed identification of this dispersed ash as part of the original ash contribution to the sediment. In this paper, we summarize the development of these geochemical/statistical techniques and provide case studies from the quantification of dispersed ash in the Caribbean Sea, equatorial Pacific Ocean, and northwest Pacific Ocean. These geochemical studies (and their sedimentological precursors of smear slides) collectively demonstrate that local and regional arc-related ash can be an important component of sedimentary sequences throughout large regions of the ocean

Regional-scale input of dispersed and discrete volcanic ash to the Izu-Bonin and Mariana subduction zones

We have geochemically and statistically characterized bulk marine sediment and ash layers at Ocean Drilling Program Site 1149 (Izu-Bonin Arc) and Deep Sea Drilling Project Site 52 (Mariana Arc), and have quantified that multiple dispersed ash sources collectively comprise ~30-35% of the hemipelagic sediment mass entering the Izu-Bonin-Mariana subduction system. Multivariate statistical analyses indicate that the bulk sediment at Site 1149 is a mixture of Chinese Loess, a second compositionally distinct eolian source, a dispersed mafic ash, and a dispersed felsic ash. We interpret the source of these ashes as respectively being basalt from the Izu-Bonin Front Arc (IBFA) and rhyolite from the Honshu Arc. Sr-, Nd-, and Pb isotopic analyses of the bulk sediment are consistent with the chemical/statistical-based interpretations. Comparison of the mass accumulation rate of the dispersed ash component to discrete ash layer parameters (thickness, sedimentation rate, and number of layers) suggests that eruption frequency, rather than eruption size, drives the dispersed ash record. At Site 52, the geochemistry and statistical modeling indicates that Chinese Loess, IBFA, dispersed BNN (boninite from Izu-Bonin), and a dispersed felsic ash of unknown origin are the sources. At Site 1149 the ash layers and the dispersed ash are compositionally coupled, whereas at Site 52 they are decoupled in that there are no boninite layers, yet boninite is dispersed within the sediment. Changes in the volcanic and eolian inputs through time indicate strong arc- and climate-related controls

General population screening for type 1 diabetes using islet autoantibodies at the preschool vaccination visit: a proof-of-concept study (the T1Early study)

Objective: Type 1 diabetes (T1D) screening programmes testing islet autoantibodies (IAbs) in childhood can reduce life-threatening diabetic ketoacidosis. General population screening is required to detect the majority of children with T1D, since in >85% there is no family history. Age 3–5 years has been proposed as an optimal age for a single screen approach. Design: Capillary samples were collected from children attending their preschool vaccination and analysed for IAbs to insulin, glutamic acid decarboxylase, islet antigen-2 and zinc transporter 8 using radiobinding/luciferase immunoprecipitation system assays. Acceptability was assessed using semistructured interviews and open-ended postcard questionnaires with parents. Setting: Two primary care practices in Oxfordshire, UK. Main outcome measures: The ability to collect capillary blood to test IAbs in children at the routine preschool vaccination (3.5–4 years). Results: Of 134 parents invited, 66 (49%) were recruited (median age 3.5 years (IQR 3.4–3.6), 26 (39.4%) male); 63 provided a sample (97% successfully), and one participant was identified with a single positive IAb. Parents (n=15 interviews, n=29 postcards) were uniformly positive about screening aligned to vaccination and stated they would have been less likely to take part had screening been a separate visit. Themes identified included preparedness for T1D and the long-term benefit outweighing short-term upset. The perceived volume of the capillary sample was a potential concern and needs optimising. Conclusions: Capillary IAb testing is a possible method to screen children for T1D. Aligning collection to the preschool vaccination visit can be convenient for families without the need for an additional visit

General population screening for type 1 diabetes using islet autoantibodies at the preschool vaccination visit:a proof-of-concept study (the T1Early study)

Objective: Type 1 diabetes (T1D) screening programmes testing islet autoantibodies (IAbs) in childhood can reduce life-threatening diabetic ketoacidosis. General population screening is required to detect the majority of children with T1D, since in >85% there is no family history. Age 3–5 years has been proposed as an optimal age for a single screen approach. Design: Capillary samples were collected from children attending their preschool vaccination and analysed for IAbs to insulin, glutamic acid decarboxylase, islet antigen-2 and zinc transporter 8 using radiobinding/luciferase immunoprecipitation system assays. Acceptability was assessed using semistructured interviews and open-ended postcard questionnaires with parents. Setting: Two primary care practices in Oxfordshire, UK. Main outcome measures: The ability to collect capillary blood to test IAbs in children at the routine preschool vaccination (3.5–4 years). Results: Of 134 parents invited, 66 (49%) were recruited (median age 3.5 years (IQR 3.4–3.6), 26 (39.4%) male); 63 provided a sample (97% successfully), and one participant was identified with a single positive IAb. Parents (n=15 interviews, n=29 postcards) were uniformly positive about screening aligned to vaccination and stated they would have been less likely to take part had screening been a separate visit. Themes identified included preparedness for T1D and the long-term benefit outweighing short-term upset. The perceived volume of the capillary sample was a potential concern and needs optimising. Conclusions: Capillary IAb testing is a possible method to screen children for T1D. Aligning collection to the preschool vaccination visit can be convenient for families without the need for an additional visit

General population screening for type 1 diabetes using islet autoantibodies at the preschool vaccination visit:a proof-of-concept study (the T1Early study)

Objective: Type 1 diabetes (T1D) screening programmes testing islet autoantibodies (IAbs) in childhood can reduce life-threatening diabetic ketoacidosis. General population screening is required to detect the majority of children with T1D, since in >85% there is no family history. Age 3–5 years has been proposed as an optimal age for a single screen approach. Design: Capillary samples were collected from children attending their preschool vaccination and analysed for IAbs to insulin, glutamic acid decarboxylase, islet antigen-2 and zinc transporter 8 using radiobinding/luciferase immunoprecipitation system assays. Acceptability was assessed using semistructured interviews and open-ended postcard questionnaires with parents. Setting: Two primary care practices in Oxfordshire, UK. Main outcome measures: The ability to collect capillary blood to test IAbs in children at the routine preschool vaccination (3.5–4 years). Results: Of 134 parents invited, 66 (49%) were recruited (median age 3.5 years (IQR 3.4–3.6), 26 (39.4%) male); 63 provided a sample (97% successfully), and one participant was identified with a single positive IAb. Parents (n=15 interviews, n=29 postcards) were uniformly positive about screening aligned to vaccination and stated they would have been less likely to take part had screening been a separate visit. Themes identified included preparedness for T1D and the long-term benefit outweighing short-term upset. The perceived volume of the capillary sample was a potential concern and needs optimising. Conclusions: Capillary IAb testing is a possible method to screen children for T1D. Aligning collection to the preschool vaccination visit can be convenient for families without the need for an additional visit

General population screening for type 1 diabetes using islet autoantibodies at the preschool vaccination visit: a proof-of-concept study (the T1Early study)

Objective: Type 1 diabetes (T1D) screening programmes testing islet autoantibodies (IAbs) in childhood can reduce life-threatening diabetic ketoacidosis. General population screening is required to detect the majority of children with T1D, since in >85% there is no family history. Age 3–5 years has been proposed as an optimal age for a single screen approach. Design: Capillary samples were collected from children attending their preschool vaccination and analysed for IAbs to insulin, glutamic acid decarboxylase, islet antigen-2 and zinc transporter 8 using radiobinding/luciferase immunoprecipitation system assays. Acceptability was assessed using semistructured interviews and open-ended postcard questionnaires with parents. Setting: Two primary care practices in Oxfordshire, UK. Main outcome measures: The ability to collect capillary blood to test IAbs in children at the routine preschool vaccination (3.5–4 years). Results: Of 134 parents invited, 66 (49%) were recruited (median age 3.5 years (IQR 3.4–3.6), 26 (39.4%) male); 63 provided a sample (97% successfully), and one participant was identified with a single positive IAb. Parents (n=15 interviews, n=29 postcards) were uniformly positive about screening aligned to vaccination and stated they would have been less likely to take part had screening been a separate visit. Themes identified included preparedness for T1D and the long-term benefit outweighing short-term upset. The perceived volume of the capillary sample was a potential concern and needs optimising. Conclusions: Capillary IAb testing is a possible method to screen children for T1D. Aligning collection to the preschool vaccination visit can be convenient for families without the need for an additional visit

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK

PisiasNicklasCEOASMultivariateStatisticalAnalysis_SupportingInformation.zip

Multivariate statistical treatments of large data sets in sedimentary geochemical and other fields are rapidly becoming more popular as analytical and computational capabilities expand. Because geochemical data sets present a unique set of conditions (e.g., the closed array), application of generic off-the-shelf applications is not straightforward and can yield misleading results. We present here annotated MATLAB scripts (and specific guidelines for their use) for Q-mode factor analysis, a constrained least squares multiple linear regression technique, and a total inversion protocol, that are based on the well-known approaches taken by Dymond (1981), Leinen and Pisias (1984), Kyte et al. (1993), and their predecessors. Although these techniques have been used by investigators for the past decades, their application has been neither consistent nor transparent, as their code has remained in-house or in formats not commonly used by many of today’s researchers (e.g., FORTRAN). In addition to providing the annotated scripts and instructions for use, we discuss general principles to be considered when performing multivariate statistical treatments of large geochemical data sets, provide a brief contextual history of each approach, explain their similarities and differences, and include a sample data set for the user to test their own manipulation of the scripts.Keywords: multivariate statistics, geochemistry, statisticsKeywords: multivariate statistics, geochemistry, statistic