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Poor dietary choices are major risk factors for obesity and non-communicable diseases, which places an increasing burden on healthcare systems worldwide. To monitor the effectiveness of healthy eating guidelines and strategies, there is a need for objective measures of dietary intake in community settings. Metabolites derived from specific foods present in urine samples can provide objective biomarkers of food intake (BFIs). Whilst the majority of biomarker discovery/validation studies have investigated potential biomarkers for single foods only, this study considered the whole diet by using menus that delivered a wide range of foods in meals that emulated conventional UK eating patterns. Fifty-one healthy participants (range 19–77 years; 57% female) followed a uniquely designed, randomized controlled dietary intervention, and provided spot urine samples suitable for discovery of BFIs within a real-world context. Free-living participants prepared and consumed all foods and drinks in their own homes and were asked to follow the protocols for meal consumption and home urine sample collection. This study also assessed the robustness, and impact on data quality, of a minimally invasive urine collection protocol. Overall the study design was well-accepted by participants and concluded successfully without any drop outs. Compliance for urine collection, adherence to menu plans, and observance of recommended meal timings, was shown to be very high. Metabolome analysis using mass spectrometry coupled with data mining demonstrated that the study protocol was well-suited for BFI discovery and validation. Novel, putative biomarkers for an extended range of foods were identified including legumes, curry, strongly-heated products, and artificially sweetened, low calorie beverages. In conclusion, aspects of this study design would help to overcome several current challenges in the development of BFI technology. One specific attribute was the examination of BFI generalizability across related food groups and across different preparations and cooking methods of foods. Furthermore, the collection of urine samples at multiple time points helped to determine which spot sample was optimal for identification and validation of BFIs in free-living individuals. A further valuable design feature centered on the comprehensiveness of the menu design which allowed the testing of biomarker specificity within a biobank of urine samples.

Thailand is known to exhibit extreme horizontal structural inequalities by ethnicity. While these differences are not publicly recognised because Thailand’s 62 ethnic groups are not legally recognised, they nonetheless affect state-minority relations, particularly the relationship between the dominant Central Thai ethnic community and the Thai Lao, Thailand’s largest ethnic community, which generally votes as a bloc against Central Thai-dominated political parties. To promote greater social, economic, and political inclusion, UN Sustainable Development Goal 10 advocates policies to address inequalities by ethnicity. As the Thai government does not recognise the Thai Lao, this is problematic. This study analyses opinions obtained from ‘establishment’ and ‘local elite’ samples on how to promote greater inclusion for the Thai Lao. It illustrates some of the barriers towards promoting greater socio-economic and political inclusion, including the lack of recognition, as well as opportunities, such as campaigning against racial discrimination and disaggregating data by ethnicity.

Objective:Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.Design:Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.Setting:Urine collection methodologies were developed within home settings.Participants:Different cohorts of free-living volunteers.Results:Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.Conclusions:This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.

Published as: Carayannis, E.G., Draper, J. Optimising peace through a Universal Global Peace Treaty to constrain the risk of war from a militarised artificial superintelligence. AI & Soc (2022). https://doi.org/10.1007/s00146-021-01382-y

Objective: The purpose of this prospective randomized study was to assess using a periodontal ligament (PDL) injection as an aide to decrease palatal infiltration pain. Methods: A total of 133 subjects randomly received a PDL injection and alternative palatal infiltration or a mock PDL injection and conventional palatal infiltration at 2 separate appointments. PDL injection was given in the mid-palatal sulcus of the maxillary first molar. Mock PDL injection consisted of only needle insertion. All subjects then received a palatal infiltration administered into the blanched gingival tissue 3 mm (alternative palatal infiltration) or 7 mm (conventional palatal infiltration) from the gingival collar. Subjects recorded needle insertion and solution deposition pain using a Heft-Parker visual analog scale (VAS). Results: The combined PDL injection and alternative palatal infiltration had significantly decreased mean VAS ratings for needle insertion and solution deposition pain (P < .0001). Incidence of moderate/severe pain for needle insertion and solution deposition was reduced from 65% to 1% and from 65% to 2%, respectively. Conclusion: Providing PDL anesthesia into the mid-palatal sulcus of the maxillary first molar and then administering an alternative palatal infiltration into the blanched collar around the PDL molar site led to significant reductions in needle insertion and solution deposition pain compared with a mock PDL and conventional palatal infiltration.

Thailand has had mandatory military service since 1905 and since 1954 via a lottery system. Beatings and deaths frequently occur among draftees, and photographs and videos in which draftees are injured, tortured, and humiliated are widespread. This article describes for the first time the development and nature of the Thai military draft. The authors analyse the military draft from a nonkilling global political science perspective and present a nonkilling rationale for ending the draft. The article argues that retaining the military draft promotes a killing society and violates human rights, including the right to conscientious objection; causes mental anguish; is inefficient economically; causes corruption; and supports military interventionism. The authors further maintain that physical abuse that has accompanied the Thai version of military conscription constitutes a pro-killing manifestation of the military regime’s approach to maintaining the existing institutional alignment and control in Gl...

The filing and granting of patents, not to mention their litigation, are key to global economic development through encouraging and protecting entrepreneurial and inventive economic activity. However, surprisingly little investigation has been conducted of the filing of patents in the nuclear fusion industry in recent years, and even less of the patent filing activity of nuclear fusion's private sector. We analyse the patents filed by members of the US-based Fusion Industry Association (FIA), by company, year, and patent classification codes, in a way that will be of interest to academics, fusion companies and the overall fusion industry, public sector policy makers, and political decision makers. We find that the FIA now represents a considerable and varied body of intellectual property, with some FIA members beginning to demonstrate extensive patenting, especially in the case of spherical tokamak technology, including with patents for shielding materials and the tritium fuel cycle. These findings adds weight to the notion of a public-private partnership and cost-sharing approach to Fusion Pilot Plants, presently being advocated by the US National Academies of Sciences, Engineering, and Medicine, the US Department of Energy, and the FIA itself.

A high intake of fruit and vegetables (FV) has been associated with reduced risk of a number of chronic diseases, including CVD. The aim of this review is to describe the potential use of biomarkers to assess FV intake. Traditional methods of assessing FV intake have limitations, and this is likely to impact on observed associations with disease outcomes and markers of disease risk. Nutritional biomarkers may offer a more objective and reliable method of assessing dietary FV intake. Some single blood biomarkers, such as plasma vitamin C and serum carotenoids, are well established as indicators of FV intake. Combining potential biomarkers of intake may more accurately predict overall FV intake within intervention studies than the use of any single biomarker. Another promising approach is metabolomic analysis of biological fluids using untargeted approaches to identify potential new biomarkers of FV intake. Using biomarkers to measure FV intake may improve the accuracy of dietary assessment.

This article presents an anatomy of the 2011 Thailand Country Report to the Committee responsible for the UN Convention for the Elimination of All Forms of Racial Discrimination, in which Thailand recognized its largest ethnic minority community, the Thai Lao, to the international community. The article analyses the Country Report as well as the deliberations of the Committee in dialogue with the Thailand Country Delegation. It provides a policy context for the Country Report, including Thailand’s classification of ethnic communities. The article argues the need to minimize racialized discrimination as regards the Thai Lao. Five policy issues, framed in the context of inclusion and which arise from the recognition of the Thai Lao by the Country Report, are considered. The article concludes by discussing how the Thai Lao may be better included in Thailand via political developments towards a social democracy in Thailand, for social democracy can recognize sociocultural rights.

Background Older patients account for a significant proportion of patients undergoing colorectal cancer surgery and are vulnerable to a number of preoperative risk factors that are not often present in younger patients. Further, three preoperative risk factors that are more prevalent in older adults include frailty, sarcopenia, and malnutrition. Although each of these has been studied in isolation, there is little information on the interplay between them in older surgical patients. A particular area of increasing interest is the use of urine metabolomics for the objective evaluation of dietary profiles and malnutrition. Objective Herein, we describe the design, cohort, and standard operating procedures of a planned prospective study of older surgical patients undergoing colorectal cancer resection across multiple institutions in the United Kingdom. The objectives are to determine the association between clinical outcomes and frailty, nutritional status, and sarcopenia. Methods The procedures will include serial frailty evaluations (Clinical Frailty Scale and Groningen Frailty Indicator), functional assessments (hand grip strength and 4-meter walk test), muscle mass evaluations via computerized tomography morphometric analysis, and the evaluation of nutritional status via the analysis of urinary dietary biomarkers. The primary feasibility outcome is the estimation of the incidence rate of postoperative complications, and the primary clinical outcome is the association between the presence of postoperative complications and frailty, sarcopenia, and nutritional status. The secondary outcome measures are the length of hospital stay, 30-day hospital readmission rate, and mortality rate at days 30 and 90. Results Our study was approved by the National Health Service Research Ethics Committee (reference number: 19/WA/0190) via the Integrated Research Application System (project ID: 231694) prior to subject recruitment. Cardiff University is acting as the study sponsor. Our study is financially supported through an external, peer-reviewed grant from the British Geriatrics Society and internal funding resources from Cardiff University. The results will be disseminated through peer-review publications, social media, and conference proceedings. Conclusions As frailty, sarcopenia, and malnutrition are all areas of common derangement in the older surgical population, prospectively studying these risk factors in concert will allow for the analysis of their interplay as well as the development of predictive models for those at risk of commonly tracked surgical complications and outcomes. International Registered Report Identifier (IRRID) PRR1-10.2196/16846

BACKGROUND Older patients account for a significant proportion of patients undergoing colorectal cancer surgery and are vulnerable to a number of preoperative risk factors that are not often present in younger patients. Further, three preoperative risk factors that are more prevalent in older adults include frailty, sarcopenia, and malnutrition. Although each of these has been studied in isolation, there is little information on the interplay between them in older surgical patients. A particular area of increasing interest is the use of urine metabolomics for the objective evaluation of dietary profiles and malnutrition. OBJECTIVE Herein, we describe the design, cohort, and standard operating procedures of a planned prospective study of older surgical patients undergoing colorectal cancer resection across multiple institutions in the United Kingdom. The objectives are to determine the association between clinical outcomes and frailty, nutritional status, and sarcopenia. METHODS The procedures will include serial frailty evaluations (Clinical Frailty Scale and Groningen Frailty Indicator), functional assessments (hand grip strength and 4-meter walk test), muscle mass evaluations via computerized tomography morphometric analysis, and the evaluation of nutritional status via the analysis of urinary dietary biomarkers. The primary feasibility outcome is the estimation of the incidence rate of postoperative complications, and the primary clinical outcome is the association between the presence of postoperative complications and frailty, sarcopenia, and nutritional status. The secondary outcome measures are the length of hospital stay, 30-day hospital readmission rate, and mortality rate at days 30 and 90. RESULTS Our study was approved by the National Health Service Research Ethics Committee (reference number: 19/WA/0190) via the Integrated Research Application System (project ID: 231694) prior to subject recruitment. Cardiff University is acting as the study sponsor. Our study is financially supported through an external, peer-reviewed grant from the British Geriatrics Society and internal funding resources from Cardiff University. The results will be disseminated through peer-review publications, social media, and conference proceedings. CONCLUSIONS As frailty, sarcopenia, and malnutrition are all areas of common derangement in the older surgical population, prospectively studying these risk factors in concert will allow for the analysis of their interplay as well as the development of predictive models for those at risk of commonly tracked surgical complications and outcomes. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/16846

This chapter provides background to the policy situation for language education in Sri Lanka and offers some reflections on policy outcomes, past and present, and prospects for the future. Language education in Sri Lanka is accorded a distinctive role across many dimensions of national life. A close association between religion and language was an essential and inseparable aspect of group cultural identity and education, including language education, was centred on the religious institutions responsible for its provision. The established systems of language education provided by religious institutions suffered a severe disruption following the early 16th-century arrival of the Portuguese who gradually occupied the island’s western and northern coastal areas. Since independence, policy for language education, and language in education, had been characterised by continually shifting parameters dictated by political imperatives against a background of social and ethnic division. Languages education policy in Sri Lanka has been both source and instrument of social and political division for nearly 200 years.

The language and culture map of modern Thailand thus reflects a long history of peoples and their languages in intimate contact, borrowing and blending DNA along with vibrant cultures. Local languages preserve many local knowledge systems that if lost, means a lessening of the wisdom of minority peoples bound up in their medical, agricultural, and aspirational practices and beliefs. Language and language policy since the 1932 revolution have been determined by the military. Multiple problems with Thai public education in peripheral areas include the curriculum being in Spoken Tamil, linguistically a foreign language to non-Tai minorities. In 1928, the 1921 education system was revised, with English, French, and German all becoming electives and up to two foreign languages becoming mandatory at upper secondary to introduce modernity to Thailand. Minority language teaching is now tolerated, especially following the 1997 constitution, which recognised the rights of traditional communities to restore and conserve their customs, knowledge, arts, and ‘good culture.

Background Measurement of multiple food intake exposure biomarkers in urine may offer an objective method for monitoring diet. The potential of spot and cumulative urine samples that have reduced burden on participants as replacements for 24-h urine collections has not been evaluated. Objective The aim of this study was to determine the utility of spot and cumulative urine samples for classifying the metabolic profiles of people according to dietary intake when compared with 24-h urine collections in a controlled dietary intervention study. Methods Nineteen healthy individuals (10 male, 9 female, aged 21-65 y, BMI 20-35 kg/m2) each consumed 4 distinctly different diets, each for 1 wk. Spot urine samples were collected ∼2 h post meals on 3 intervention days/wk. Cumulative urine samples were collected daily over 3 separate temporal periods. A 24-h urine collection was created by combining the 3 cumulative urine samples. Urine samples were analyzed with metabolite fingerprinting by both high-resolution flow infusion electrospray mass spectrometry (FIE-HRMS) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Concentrations of dietary intake biomarkers were measured with liquid chromatography triple quadrupole mass spectrometry and by integration of 1H-NMR data. Results Cross-validation modeling with 1H-NMR and FIE-HRMS data demonstrated the power of spot and cumulative urine samples in predicting dietary patterns in 24-h urine collections. Particularly, there was no significant loss of information when post-dinner (PD) spot or overnight cumulative samples were substituted for 24-h urine collections (classification accuracies of 0.891 and 0.938, respectively). Quantitative analysis of urine samples also demonstrated the relation between PD spot samples and 24-h urines for dietary exposure biomarkers. Conclusions We conclude that PD spot urine samples are suitable replacements for 24-h urine collections. Alternatively, cumulative samples collected overnight predict similarly to 24-h urine samples and have a lower collection burden for participants.

Oak decline syndromes such as Acute Oak Decline (AOD) and Chronic Oak Decline (COD) are becoming increasingly prevalent and with this comes the need for more quantitative, sensitive and standardised visual oak health monitoring. Phenotyping protocols were developed to specifically measure oak decline severity and were based on a comprehensive set of simple to measure phenotypic descriptors. A total of 36 phenotypic measurements describing oak decline status included aspects of tree size, crown condition, the presence of biotic agents and a number of derived composite descriptors. Phenotypic measurements were collected from a total of 174 Quercus robur, surveyed from 9 sites across England and included healthy, AOD, COD and AOD trees in remission. Using these data, the Phenotypic Decline Index (PDI) and the Decline Acuteness Index (DAI) were developed to quantitatively describe and differentiate the acute and chronic oak decline severity spectrum. These decline indexes were derived from unsupervised random forest machine learning models, trained using the collected phenotypic data. The suitability of the decline indexes for describing decline severity and type were assessed by comparing decline index scores to manual decline status classifications along with an assessment of descriptor importance and contribution to the decline index models. Crown condition and trees size descriptors such as ‘composite crown volume’ contributed positively to the PDI. Trees with smaller crowns in poor condition had greater PDI values. Tree stature and the presence of stem bleeding contributed highly to the DAI, allowing differentiation between trees with AOD and COD syndromes. AOD trees had relatively larger stature and the presence of stem bleeding where as COD trees had small stature and stem bleeding was absent. The oak decline indexes are simple but sensitive measures of tree decline severity and allow easy comparisons of oak trees both spatially and temporally. These have the potential to provide useful tools for forest monitoring and management as well application to remote sensing and omics research.

Key Points Question Can real-time streams of secondary information related to suicide be used to accurately estimate suicide fatalities in the US in real time? Findings In this national cross-sectional study, combining information from 8 data streams encompassing various health services and online data sources enabled accurate, real-time estimation of US suicide fatalities with meaningful correlation to week-to-week epidemiological trends and a less than 1% error compared with actual counts. Meaning These findings advance the first efforts to create a population-level system for enabling real-time epidemiological trend monitoring of suicide fatalities., This cross-sectional study uses machine learning to estimate weekly suicide fatalities in the US in near real time., Importance Suicide is a leading cause of death in the US. However, official national statistics on suicide rates are delayed by 1 to 2 years, hampering evidence-based public health planning and decision-making. Objective To estimate weekly suicide fatalities in the US in near real time. Design, Setting, and Participants This cross-sectional national study used a machine learning pipeline to combine signals from several streams of real-time information to estimate weekly suicide fatalities in the US in near real time. This 2-phase approach first fits optimal machine learning models to each individual data stream and subsequently combines predictions made from each data stream via an artificial neural network. National-level US administrative data on suicide deaths, health services, and economic, meteorological, and online data were variously obtained from 2014 to 2017. Data were analyzed from January 1, 2014, to December 31, 2017. Exposures Longitudinal data on suicide-related exposures were obtained from multiple, heterogeneous streams: emergency department visits for suicide ideation and attempts collected via the National Syndromic Surveillance Program (2015-2017); calls to the National Suicide Prevention Lifeline (2014-2017); calls to US poison control centers for intentional self-harm (2014-2017); consumer price index and seasonality-adjusted unemployment rate, hourly earnings, home price index, and 3-month and 10-year yield curves from the Federal Reserve Economic Data (2014-2017); weekly daylight hours (2014-2017); Google and YouTube search trends related to suicide (2014-2017); and public posts on suicide on Reddit (2 314 533 posts), Twitter (9 327 472 tweets; 2015-2017), and Tumblr (1 670 378 posts; 2014-2017). Main Outcomes and Measures Weekly estimates of suicide fatalities in the US were obtained through a machine learning pipeline that integrated the above data sources. Estimates were compared statistically with actual fatalities recorded by the National Vital Statistics System. Results Combining information from multiple data streams, the machine learning method yielded estimates of weekly suicide deaths with high correlation to actual counts and trends (Pearson correlation, 0.811; P

A three-step commercial manufacturing route has been developed for palbociclib, a highly selective, reversible inhibitor of CDK 4/6. The second step, which utilizes a Heck coupling to install the enol ether side chain, is described. A highly regioselective catalyst was identified for this transformation along with reaction conditions that ensure robustness upon scale-up. Effective removal of palladium was accomplished via filtration of insoluble metal and an extractive chelation step. Finally, efficient isolation of coupled product 3 was achieved through careful polymorph control via seeding and an optimized cooling protocol that avoids nucleation of a kinetically favored, slow-filtering polymorph.

This is the first in a series of three papers describing commercial manufacturing process development for palbociclib (1). This manuscript focuses on the SNAr coupling between aminopyridine 3 and chloropyrimidine 7. The regioselectivity of the SNAr coupling was studied from a synthetic and mechanistic perspective. Grignard bases were identified as the preferred class of bases for this reaction, allowing for a simplified process and reduced usage factor for aminopyridine 3. The development of this SNAr reaction into a scalable commercial manufacturing process is also described.

The Isan Culture Maintenance and Revitalization Programme is a four-year, 500,000-euro programme devised and implemented by four municipalities and the College of Local Administration of Khon Kaen University in Northeast Thailand. The design and manufacture — using traditional processes adapted for making Western-style shirts that first became popular in Thailand in the first decade of the twentieth century — of student uniforms for Ban Phai municipality is one of the action lines of the Isan Culture Maintenance and Revitalization Programme. A brief review of Thailand’s decentralization process is followed by a section on school uniforms. The project in Ban Phai had four phases: a survey of citizens’ attitudes towards the use of traditionally designed and woven clothing; a capacity survey to review the local market; design and manufacture of municipal uniforms; and design and manufacture of school uniforms. The result was the production of more than 400 hybrid jackets for municipal officers with local, national and international characteristics and more than 1,200 similarly hybrid student shirts, using both traditional and machined processes and materials.

Campaigns have become popular in public health approaches to suicide prevention; however, limited empirical investigation of their impact on behavior has been conducted. To address this gap, utilization patterns of crisis support services associated with the Department of Veterans Affairs' Veterans Crisis Line (VCL) suicide prevention campaign were examined. Daily call data for the National Suicide Prevention Lifeline, VCL, and 1-800-SUICIDE were modeled using a novel semi-varying coefficient method. Analyses reveal significant increases in call volume to both targeted and broad resources during the campaign. Findings underscore the need for further research to refine measurement of the effects of these suicide prevention efforts.

The Isan Culture Maintenance and Revitalization Programme was a four-year, 500,000- euro programme devised and implemented by four municipalities in Khon Kaen Province together with the College of Local Administration of Khon Kaen University in Northeast Thailand. The programme pursued five different action lines, with Ban Phai Municipality being responsible for traditionally made "ethnic" uniforms, Chum Phae Municipality for designing and installing multilingual signage, Khon Kaen Municipality for implementing the teaching of the Isan language as a subject in municipal schools, and Mueang Phon Municipality responsible for a multimedia collection of cultural performances. In effect, the programme piloted each of these four action lines in a given municipality and then sought to introduce each into the other three municipalities. The College of Local Administration was responsible for project coordination, research and visibility. The latter mainly took the forms of academic papers, research articles and newspaper columns. The principal results and outcomes of the programme included the first municipal multilingual Thai–Isan–English road signage in Northeast Thailand, the first Thai–Isan–English dictionary using a heritage script, the first Isan subject curriculum, a unique archive of Isan cultural performances, and the production of "ethnic" municipal and school uniforms.

Scope: Metabolites derived from specific foods present in urine samples can provide objective biomarkers of food intake (BFIs). This study investigated the possibility that calystegines (a class of iminosugars) may provide BIFs for potato (Solanum tuberosum L.) product exposure. Methods and results: Calystegine content is examined in published data covering a wide range of potato cultivars. Rapid methods are developed for the quantification of calystegines in cooked potato products and human urine using triple quadrupole mass spectrometry. The potential of calystegines as BFIs for potato consumption is assessed in a controlled food intervention study in the United Kingdom and validated in an epidemiological study in Portugal. Calystegine concentrations are reproducibly above the quantification limit in first morning void urines the day after potato consumption, showing a good dose-response relationship, particularly for calystegine A3 . The design of the controlled intervention mimicks exposure to a typical UK diet and showed that neither differences in preparation/cooking method or influence of other foods in the diet has significant impact on biomarker performance. Calystegine biomarkers also perform well in the independent validation study. Conclusion: It is concluded that calystegines have many of the characteristics needed to be considered as specific BFIs for potato product intake. The authors thank the participants in Newcastle and Portugal for their commitment in the food intervention and dietary survey studies, respectively. The researchers acknowledge all the institutions and persons that integrated the activity of the IAN-AF (2015-2016) Consortium at all phases of the Survey. The researchers thank Puffin Produce Ltd. for providing potato tubers.

SCOPE: Metabolites derived from individual foods found in human biofluids after consumption could provide objective measures of dietary intake. For comprehensive dietary assessment, quantification methods would need to manage the structurally diverse mixture of target metabolites present at a wide concentration range. METHODS & RESULTS: We developed a strategy for selection of candidate dietary exposure biomarkers, providing comprehensive coverage. An analytical method for 62 food biomarkers was validated by extensive analysis of chromatographic and ionization behaviour characteristics using triple quadrupole mass spectrometry. We used urine samples from two food intervention studies: one controlled, inpatient study (n = 19) and the other a free-living study where individuals (n = 15) were provided with food as a series of menu plans. As proof-of-principle, we demonstrated that the biomarker panel could discriminate between menu plans by detecting distinctive changes in the concentration in urine of targeted metabolites. We showed quantitative relationships between four biomarker concentrations in urine and dietary intake. CONCLUSIONS: We have demonstrated design concepts for an analytical strategy allowing simultaneous quantification of a comprehensive panel of chemically-diverse biomarkers of a wide range of commonly-consumed foods. We propose that integration of self-reported dietary recording tools with biomarker approaches will provide more robust assessment of dietary exposure. This article is protected by copyright. All rights reserved.

The concept and practice of free migration has long existed, but the modern border pass and common visa have only been used since the establishment of the Schengen Agreement of the European Union in 1995. Since its establishment, the Schengen Visa has been an extraordinary example of the success of a borderless region and led to vibrant in growth and social development. ASEAN, as a new economic community that tries to set itself as a beneficiary of the lessons learned from the European Union, has been struggling in establishing its own common visa region. The reasons encompass economic, political, and social-cultural concerns. This study focuses specifically on the Lao PDR and it aims to assess the preparedness of the country if the region were to establish the common visa system. The study employs a qualitative approach and collects data via an interview questionnaire. Research data are collected from interviews of six high-ranking government officials. Using the theme generating and data coding approach in ATLAS, a qualitative data analysis program, this study found that the preparedness of the Lao PDR in implementing the ASEAN Common Visa (ACV) spans nine key factors: (1) geographical location, (2) visa policy, (3) immigration control, (4) quota of foreign workers in the private sector, (5) information and communications technology (ICT) in connectivity development, (6) electronic systems in the consular sector, (7) infrastructure, (8) population mobility, and (9) attitudes towards the ACV. After categorizing these factors based on economic, political, and social-cultural dimensions, it was found that population mobility is a common concern among the three dimensions. This suggests that the Lao PDR needs to focus on improvements in border management, synchronization of information and communication technology, infrastructure, and human resources development among the relevant sectors.

Objective Expression of the protein marker p 16INK4a is used as a surrogate for human papillomavirus (HPV) infection in biopsies of oral and tonsillar mucosa. While HPV infection accounts for Findings Fifteen of the 24 HGDs (62.5%), fourteen of the 24 LGDs (58.3%) and four of the 24 CMs (16.6%) were positive for p 16INK4a expression. The difference in p16 expression between HGD versus CM and LGD versus CM were analyzed by Wilcoxon signed rank test and statistically significantly different at level with p-values of 0.0001 and 0.0009, respectively. Greater p16 expression was noted in HGDs compared to LGDs (p-value = 0.01960, which was significant at level). A step-down Holm-Bonferroni method to account for multiple comparisons showed adjusted p-values of 0.0003 (HG versus CM), 0.0018 (LG versus CM) and 0.0196 (HG versus low LG) among three groups. Conclusion p16 expression was statistically-significantly greater in LGD and HGD lesions compared to CM, with a trend of greater expression being associated with higher grade of dysplasia.

Discipline Clinique. Introduction et but de l’etude Les campagnes des pouvoirs publics peinant a corriger les mauvaises habitudes alimentaires, nous proposons d’evaluer l’interet d’outils de cuisine connectes a le faire sans contrainte dans le cadre d’une etude pilote de faisabilite. Materiel et methodes Essai controle, randomise selon la methode de Zelen, monocentrique (ClinicalTrials.gov NCT03171571 ) incluant des volontaires sains (representatifs de la population francaise), avec des dispositifs de cuisson connectes (GI) ou feuille de conseils alimentaires (Groupe controle GC). La faisabilite et l’acceptabilite evaluees par l’exhaustivite des recueils obtenus a 0, 6 et 12 mois, a domicile et en consultation, etaient le critere de jugement principal. Les changements a 1 an dans le score Alternate Healthy Eating Index-2010 (AHEI-2010), les variations anthropometriques, la composition corporelle, la pression arterielle, la qualite de vie SF36, l’actimetrie, les parametres sanguins, les biomarqueurs urinaires et le microbiote constituaient les criteres secondaires. Resultats et analyse statistique Resultats positifs concernant l’exhaustivite des donnees obtenues sur 20 sujets (16 femmes), non-fumeurs, en charge des repas a domicile, âge moyen (ecart type ET) = 39,3 (3,2) ans, indice de masse corporelle = 27,3 (1,3) kg/m2, randomises dans le GI (n = 11) ou GC (n = 9). Apres un an : pas de differences significatives entre GI vs GC pour le gain d’1 quintile de l’AHEI-2010, les donnees anthropometriques, de pression arterielle, les parametres sanguins, le nombre de pas et le SF 36. Cependant, la duree mediane du sommeil a augmente de pres d’1 h dans le GI : + 0,9 h/j [0,3–1,2] vs −0,0 [−0,4–0,3] pour GC (p = 0,041). L’analyse du microbiote a montre un effet des outils connectes (augmentation des Firmicutes pour les abondances relatives, p = 0,020) pour le GI. Conclusion Nos resultats preliminaires ont demontre la faisabilite et l’acceptabilite d’une evaluation multi-echelle complete a domicile pour mesurer l’impact des appareils de cuisson connectes sur les habitudes alimentaires et la sante. Les resultats preliminaires originaux devraient etre confirmes par l’essai controle randomise multicentrique en cours sur 160 sujets en France et Royaume-Uni ( NCT03169088 ).

Introduction Prilocaine plain has a high pH and concentration (4%), which could decrease the pain of injection and increase success. The purpose of this study was to compare pain associated with anesthetic solution deposition and the degree of pulpal anesthesia obtained with the combination of prilocaine and lidocaine versus a lidocaine and lidocaine combination when used for inferior alveolar nerve blocks (IANBs). Methods One hundred eighteen asymptomatic subjects were randomly given a combination of 1 cartridge of 4% prilocaine plain plus 1 cartridge of 2% lidocaine with 1:100,000 epinephrine or a combination of 2 cartridges of 2% lidocaine with 1:100,000 epinephrine for the IANB at 2 separate appointments. Subjects rated the pain associated with anesthetic solution deposition of injection. Mandibular teeth were tested with an electric pulp tester every 4 minutes for 57 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 17 minutes and the 80 reading was continuously sustained for 57 minutes. Comparisons for anesthetic success were analyzed using the exact McNemar test, and pain ratings associated with anesthetic solution deposition were analyzed using multiple Wilcoxon matched pairs signed rank tests; both were adjusted using the step-down Bonferroni method of Holm. Results Four percent prilocaine plain was significantly less painful upon anesthetic solution deposition. Pulpal anesthetic success was not significantly different between the 2 combinations. Conclusions The combination of 4% prilocaine plain plus 2% lidocaine with 1:100,000 epinephrine did not increase pulpal anesthetic success for IANBs compared with a combination of 2 cartridges of 2% lidocaine with 1:100,000 epinephrine. Pain associated with anesthetic solution deposition from the first cartridge of 4% prilocaine plain was significantly less when compared with the first cartridge of 2% lidocaine with 1:100,000 epinephrine.

This article considers a fundamental issue in language planning, namely, whether or not to introduce a curriculum for the mother tongue (MT), in the wider context of a complex language planning situation in Thailand. It details recent moves in the consideration of this issue for the Thai Lao (Isan) of Northeast Thailand, Thailand's largest ethnolinguistic minority. The curriculum is being spearheaded by the Isan Culture Maintenance and Revitalization Programme (ICMRP), a four-year programme 90% funded by the European Union. The article reports on a 2012 attitude survey of 1500 purposively sampled citizens of Khon Kaen Municipality, a decentralized Thai municipality, in a comprehensive community-based mixed-method research study designed to determine whether or not to introduce the MT as a subject in the formal curriculum as part of a multilingual education. This article reports on the results of this survey, which were seen as positive, especially for the revitalization of a community script, Tai Noi. The...

Observational studies indicate that wholegrain foods are beneficial for health. However, these findings are restricted by difficulties in accurate assessment of wholegrain food intake in populations due to poor definitions of wholegrain foods, limited information on portion/ serving sizes and lack of detail on the wholegrain content of individual foods. Thus, there is a need to identify biomarker(s) for wholegrain foods, which can be used to accurately assess intake for better correlation with health outcomes and to give strength to observational and intervention studies. Sixty-eight non-smoking healthy volunteers (48% male), mean age 54.5 years, participated in the study. After a wash-out period of 4 weeks during which volunteers avoided all wholegrain foods, they were randomly allocated into two groups; a wholegrain wheat group and a wholegrain rye group. The volunteers were asked to consume 3 servings (48 g) of either whole grain per day for 4 weeks (Dose 1) from a selection of foods provided. After this period, they were asked to double their intake of the same foods (Dose 2) for further 4 weeks. At the end of each period, volunteers provided fasting blood and 24 h urine samples for the measurement of plasma alkylresorcinols and plasma/24 h urine mammalian lignans; enterolactone (ENL) and enterodiol (END).

BACKGROUND: Accurate monitoring of changes in dietary patterns in response to food policy implementation is challenging. Metabolic profiling allows simultaneous measurement of hundreds of metabolites in urine, the concentrations of which can be affected by food intake. We hypothesised that metabolic profiles of urine samples developed under controlled feeding conditions reflect dietary intake and can be used to model and classify dietary patterns of free-living populations.METHODS: In this randomised, controlled, crossover trial, we recruited healthy volunteers (aged 21-65 years, BMI 20-35 kg/m(2)) from a database of a clinical research unit in the UK. We developed four dietary interventions with a stepwise variance in concordance with the WHO healthy eating guidelines that aim to prevent non-communicable diseases (increase fruits, vegetables, whole grains, and dietary fibre; decrease fats, sugars, and salt). Participants attended four inpatient stays (72 h each, separated by at least 5 days), during which they were given one dietary intervention. The order of diets was randomly assigned across study visits. Randomisation was done by an independent investigator, with the use of opaque, sealed, sequentially numbered envelopes that each contained one of the four dietary interventions in a random order. Participants and investigators were not masked from the dietary intervention, but investigators analysing the data were masked from the randomisation order. During each inpatient period, urine was collected daily over three timed periods: morning (0900-1300 h), afternoon (1300-1800 h), and evening and overnight (1800-0900 h); 24 h urine samples were obtained by pooling these samples. Urine samples were assessed by proton nuclear magnetic resonance ((1)H-NMR) spectroscopy, and diet-discriminatory metabolites were identified. We developed urinary metabolite models for each diet and identified the associated metabolic profiles, and then validated the models using data and samples from the INTERMAP UK cohort (n=225) and a healthy-eating Danish cohort (n=66). This study is registered with ISRCTN, number ISRCTN43087333.FINDINGS: Between Aug 13, 2013, and May 18, 2014, we contacted 300 people with a letter of invitation. 78 responded, of whom 26 were eligible and invited to attend a health screening. Of 20 eligible participants who were randomised, 19 completed all four 72 h study stays between Oct 2, 2013, and July 29, 2014, and consumed all the food provided. Analysis of (1)H-NMR spectroscopy data indicated that urinary metabolic profiles of the four diets were distinct. Significant stepwise differences in metabolite concentrations were seen between diets with the lowest and highest metabolic risks. Application of the derived metabolite models to the validation datasets confirmed the association between urinary metabolic and dietary profiles in the INTERMAP UK cohort (pINTERPRETATION: Urinary metabolite models developed in a highly controlled environment can classify groups of free-living people into consumers of diets associated with lower or higher non-communicable disease risk on the basis of multivariate metabolite patterns. This approach enables objective monitoring of dietary patterns in population settings and enhances the validity of dietary reporting.FUNDING: UK National Institute for Health Research and UK Medical Research Council.

In 2012, the SAMHSA-funded National Suicide Prevention Lifeline (Lifeline) completed implementation of the first national Policy for Helping Callers at Imminent Risk of Suicide across its network of crisis centers. The policy sought to: (1) provide a clear definition of imminent risk; (2) reflect the state of evidence, field experience, and promising practices related to reducing imminent risk through hotline interventions; and (3) provide a uniform policy and approach that could be applied across crisis center settings. The resulting policy established three essential principles: active engagement, active rescue, and collaboration between crisis and emergency services. A sample of the research and rationale that underpinned the development of this policy is provided here. In addition, policy implementation, challenges and successes, and implications for interventions to help Lifeline callers at imminent risk of suicide are detailed.

This article examines the introduction of multilingual Thai/Thai Lao/English signage in commercial areas of the Faculty of Humanities and Social Sciences at Khon Kaen University, the principal tertiary university for the 19 million citizens of Northeast Thailand, the majority of whom are of the minority ‘Thai Lao’ ethnicity, an ideological construction that is presented in some detail. This introduction of signage followed a previous study to introduce officially sanctioned multilingual direction-giving signage, including the main faculty sign, in three prominent areas of the Faculty. The survey employed a complex methodology to survey the opinions of 300 students together with observation of students and interviews with members of the faculty. The research type is therefore a mixed-methodology investigation of identity and language policy planning, cultural promotion, glocalization, Gal and Irvine’s semiotic ideology structuration process, the (urban) linguistic landscape and Bourdieu’s theories of socia...

Current suicide assessment relies primarily on the patient's oral history. This article describes the case of a patient who was hospitalized after making an impulsive suicide attempt. Subsequently, social media was used to identify the events leading up to the attempt and to reconstruct a timeline. This evidence helped the patient gain more insight into the severity of his condition and agree to participate in treatment. Facebook and other social media may prove to be helpful adjuncts to suicide prevention efforts both in treatment and in screening for high-risk individuals who may not voluntarily come to clinical attention.

An understanding of causal relations between diet and health is hindered by the lack of robust biological markers of food exposure (1) . The rapid development of metabolomics technology offers opportunity for the identification of urine biomarkers for the intake of a range of foods of high public health importance (2), (3) . Using high mass resolution mass spectrometry and machine learning data analysis, we have discovered potential urinary biomarkers in controlled clinical studies with a range of analytical techniques (2) . To have utility for population monitoring, we aim to validate biomarker performance in free-living individuals using urine samples collected in the home with a minimal impact on normal daily activities. Two complementary multiple reaction monitoring (MRM) routines using triple quadrupole mass spectrometry (QQQ-MS) have been developed to quantify concurrently dietary exposure biomarkers of more than 20 foods of high public health importance in the UK. MRM quantification of metabolite levels in spot urines collected either before bed time or a first morning void identified a sub-set of potential biomarkers that demonstrated robust linkage with reported dietary intake (examples in Table 1). Figure 1 demonstrates the ability of selected biomarkers to report exposure in relation to muscle meat intake from lunch time to bedtime (Beefburger; 106gm, Chicken breast; 130gm; Processed Ham; 40·5 gm) in 6 free-living individuals. Anserine was strongly, and specifically, associated with poultry intake, whilst the urinary outputs of 3-methyl histidine and carnosine reflect striated muscle intake, with levels substantially reduced when meals contain lower quality, and processed, meats with reduced levels of striated muscle content.

Scope Dietary choices modulate the risk of chronic diseases and improving diet is a central component of public health strategies. Food‐derived metabolites present in urine could provide objective biomarkers of dietary exposure. To assist biomarker validation, this work aims to develop a food intervention strategy mimicking a typical annual diet over a short period of time and assesses urine sampling protocols potentially suitable for future deployment of biomarker technology in free‐living populations. Methods and results Six different menu plans comprehensively represent a typical UK annual diet that is split into two dietary experimental periods. Free‐living adult participants (n = 15 and n = 36, respectively) are provided with all their food, as a series of menu plans, over a period of three consecutive days. Multiple spot urine samples are collected and stored at home. Conclusion A successful food exposure strategy is established following a conventional UK eating pattern, which is suitable for biomarker validation in free‐living individuals. The urine sampling procedure is acceptable for volunteers and delivered samples suitable for biomarker quantification. The study design provides scope for validation of existing biomarker candidates and potentially for discovery of new biomarker leads, and should help inform the future deployment of biomarker technology for habitual dietary exposure measurement., Food‐derived metabolites present in urine could provide objective biomarkers of dietary exposure. A food intervention strategy mimicking a typical diet in free‐living individuals is developed and spot urine sampling protocols are assessed. This study provides scope for validating existing biomarker candidates and discovering new biomarker leads, and should help in deploying biomarker technology for dietary exposure measurement in the future.

This article reviews part of the progress of the first year of the Isan Culture Maintenance and Revitalisation Programme (ICMRP), a four-year 540,000 euro series of pilot studies co-funded by the European Union and based in Thailand. The ICMRP is based in four semi-autonomous municipalities in Khon Kaen Province, viz. Ban Phai, Chum Phae, Khon Kaen and Meuang Phon, and facilitated by the College of Local Administration at Khon Kaen University. Its main actions are introducing multilingual Thai–Isan (Thai Lao)–English signage and an atmosphere of multilingualism, revitalising cloth weaving by using traditional methods to supply student uniforms, maintaining and revitalising cultural performances through training schoolchildren and the community and then creating a multimedia educational database complete with lesson plans, and introducing first oral Isan, then written Isan, as part of a mandatory Isan school subject. After providing a brief overview of the ICMRP, this article focuses in detail on the Chum ...

Real-world applications will inevitably entail divergence between samples on which chemometric classifiers are trained and the unknowns requiring classification. This has long been recognized, but there is a shortage of empirical studies on which classifiers perform best in 'external validation' (EV), where the unknown samples are subject to sources of variation relative to the population used to train the classifier. Survey of 286 classification studies in analytical chemistry found only 6.6% that stated elements of variance between training and test samples. Instead, most tested classifiers using hold-outs or resampling (usually cross-validation) from the same population used in training. The present study evaluated a wide range of classifiers on NMR and mass spectra of plant and food materials, from four projects with different data properties (e.g., different numbers and prevalence of classes) and classification objectives. Use of cross-validation was found to be optimistic relative to EV on samples of different provenance to the training set (e.g., different genotypes, different growth conditions, different seasons of crop harvest). For classifier evaluations across the diverse tasks, we used ranks-based non-parametric comparisons, and permutation-based significance tests. Although latent variable methods (e.g., PLSDA) were used in 64% of the surveyed papers, they were among the less successful classifiers in EV, and orthogonal signal correction was counterproductive. Instead, the best EV performances were obtained with machine learning schemes that coped with the high dimensionality (914-1898 features). Random forests confirmed their resilience to high dimensionality, as best overall performers on the full data, despite being used in only 4.5% of the surveyed papers. Most other machine learning classifiers were improved by a feature selection filter (ReliefF), but still did not out-perform random forests.

Scope Understanding relationships between dietary whole grain and health is hindered by incomplete knowledge of potentially bioactive metabolites derived from these foods. We aimed to discover compounds in urine correlated with changes in amounts of whole grain rye consumption. Methods and results After a wash-out period, volunteers consumed 48-g whole grain rye foods per day for 4 wk and then doubled their intake for a further 4 wk. Samples of 24-h urines were analyzed by flow infusion electrospray MS followed by supervised multivariate data analysis. Urine samples from participants who reported high intakes of rye flakes, rye pasta, or total whole grain rye products could not be discriminated adequately from their wash-out samples. However, discrimination was seen in urine samples from participants who reported high whole grain sourdough rye bread consumption. Accurate mass analysis of explanatory signals followed by fragmentation identified conjugates of the benzoxazinoid lactam 2-hydroxy-1,4-benzoxazin-3-one and hydroxylated phenyl acetamide derivatives. Statistical validation showed sensitivities of 84–96% and specificities of 70–81% (p values < 0·05) for elevated concentrations of these signals after preferential whole grain sourdough rye bread consumption. Conclusion Several potentially bioactive alkaloids have been identified in humans consuming fermented whole grain sourdough rye bread.

Although robust associations between dietary intake and population health are evident from conventional observational epidemiology, the outcomes of large-scale intervention studies testing the causality of those links have often proved inconclusive or have failed to demonstrate causality. This apparent conflict may be due to the well-recognised difficulty in measuring habitual food intake which may lead to confounding in observational epidemiology. Urine biomarkers indicative of exposure to specific foods offer information supplementary to the reliance on dietary intake self-assessment tools, such as FFQ, which are subject to individual bias. Biomarker discovery strategies using non-targeted metabolomics have been used recently to analyse urine from either short-term food intervention studies or from cohort studies in which participants consumed a freely-chosen diet. In the latter, the analysis of diet diary or FFQ information allowed classification of individuals in terms of the frequency of consumption of specific diet constituents. We review these approaches for biomarker discovery and illustrate both with particular reference to two studies carried out by the authors using approaches combining metabolite fingerprinting by MS with supervised multivariate data analysis. In both approaches, urine signals responsible for distinguishing between specific foods were identified and could be related to the chemical composition of the original foods. When using dietary data, both food distinctiveness and consumption frequency influenced whether differential dietary exposure could be discriminated adequately. We conclude that metabolomics methods for fingerprinting or profiling of overnight void urine, in particular, provide a robust strategy for dietary exposure biomarker-lead discovery.

Given the recent consideration by the Thai government of a national language policy, this article considers the status of Thailand's treaty obligations regarding linguistic human rights in education. It presents a general background, a brief linguistic profile of Thailand, a concise summary of the concept and importance of linguicide, and a description of relevant treaties, preceded by an analysis using a standard taxonomy. Thailand's domestic legal position concerning linguistic human rights in education is examined in order to analyze the state of compliance with treaty obligations. This is followed by an analysis of the current policy framework and an examination of the extent of policy implementation in the case of Thai Malay in the Deep South, with small linguistic minorities, and in the case of Thailand's main regional languages. The article concludes by reporting on future developments based on the role that the Southeast Asian Ministers of Education Organization considers the role of the mother to...

Background: An understanding of causal relations between diet and health is hindered by the lack of robust biological markers of food exposure. Objective: We aimed to develop a data-driven procedure to discover urine biomarkers indicative of habitual exposure to different foods. Design: The habitual diet of 68 participants was assessed by using 4 food-frequency questionnaires over 3 mo, and participants were assigned to different consumption-frequency classes for 58 dietary components. Flow infusion electrospray-ionization mass spectrometry followed by supervised multivariate data analysis was used to determine whether the chemical composition of urine was related to specific differences in the consumption levels of each food. Results: Foods were eaten habitually in 1 of 5 basic patterns differing in range and distribution of consumption frequency. Overnight, 24-h, and fasting urine samples proved useful for biomarker lead discovery with habitual citrus exposure used as a paradigm. Exposure level discrimination robustness improved linearly as urine samples from low-frequency citrus consumers were compared with urine samples from participants reporting increasingly higher intakes. For all foods, distinctiveness and consumption-frequency range influenced the likelihood that differential dietary exposure could be detected. Model output statistics indicated foods for which biomarker lead discovery was feasible. Metabolites proposed previously as acute intake biomarkers of citrus (proline betaine), oily fish (methylhistidine), coffee (dihydrocaffeic acid derivatives), and tomato (phenolic metabolites) were also biomarkers of habitual exposure. A significance threshold in modeling output statistics was determined to guide the discovery of potential biomarkers for other foods. Conclusion: This data-driven strategy can identify urinary metabolites associated with habitual exposure to specific foods. This trial has the UK registration number 4349 and was registered at isrtcn. org as CCT-NAPN-A13175. Am J Clin Nutr doi: 10.3945/ajcn. 112.048033.

Introduction Dog breeds are a consequence of artificial selection for specific attributes. These closed genetic populations have metabolic and physiological characteristics that may be revealed by metabolomic analysis. Objectives To identify and characterise the drivers of metabolic differences in the fasted plasma metabolome and then determine metabolites differentiating breeds. Methods Fasted plasma samples were collected from dogs maintained under two environmental conditions (controlled and client-owned at home). The former (n = 33) consisted of three breeds (Labrador Retriever, Cocker Spaniel and Miniature Schnauzer) fed a single diet batch, the latter (n = 96), client-owned dogs consisted of 9 breeds (Beagle, Chihuahua, Cocker Spaniel, Dachshund, Golden Retriever, Greyhound, German Shepherd, Labrador Retriever and Maltese) consuming various diets under differing feeding regimens. Triplicate samples were taken from Beagle (n = 10) and Labrador Retriever (n = 9) over 3 months. Non-targeted metabolite fingerprinting was performed using flow infusion electrospray-ionization mass spectrometry which was coupled with multivariate data analysis. Metadata factors including age, gender, sexual status, weight, diet and breed were investigated. Results Breed differences were identified in the plasma metabolome of dogs housed in a controlled environment. Triplicate samples from two breeds identified intra-individual variability, yet breed separation was still observed. The main drivers of variance in dogs maintained in the home environment were associated with breed and gender. Furthermore, metabolite signals were identified that discriminated between Labrador Retriever and Cocker Spaniels in both environments. Conclusion Metabolite fingerprinting of plasma samples can be used to investigate breed differences in client-owned dogs, despite added variance of diet, sexual status and environment. Electronic supplementary material The online version of this article (doi:10.1007/s11306-016-0997-6) contains supplementary material, which is available to authorized users.

Lack of accurate dietary assessment in free-living populations requires discovery of new biomarkers reflecting food intake qualitatively and quantitatively to objectively evaluate effects of diet on health. We provide a proof-of-principle for an analytical pipeline to identify quantitative dietary biomarkers. Tartaric acid was identified by nuclear magnetic resonance spectroscopy as a dose-responsive urinary biomarker of grape intake and subsequently quantified in volunteers following a series of 4-day dietary interventions incorporating 0 g/day, 50 g/day, 100 g/day, and 150 g/day of grapes in standardized diets from a randomized controlled clinical trial. Most accurate quantitative predictions of grape intake were obtained in 24 h urine samples which have the strongest linear relationship between grape intake and tartaric acid excretion (r(2) = 0.90). This new methodological pipeline for estimating nutritional intake based on coupling dietary intake information and quantified nutritional biomarkers was developed and validated in a controlled dietary intervention study, showing that this approach can improve the accuracy of estimating nutritional intakes.

Producing a comprehensive overview of the chemical content of biologically-derived material is a major challenge. Apart from ensuring adequate metabolome coverage and issues of instrument dynamic range, mass resolution and sensitivity, there are major technical difficulties associated with data pre-processing and signal identification when attempting large scale, high-throughput experimentation. To address these factors direct infusion or flow infusion electrospray mass spectrometry has been finding utility as a high throughput metabolite fingerprinting tool. With little sample pre-treatment, no chromatography and instrument cycle times of less than 5 min it is feasible to analyse more than 1,000 samples per week. Data pre-processing is limited to aligning extracted mass spectra and mass-intensity matrices are generally ready in a working day for a month’s worth of data mining and hypothesis generation. ESI-MS fingerprinting has remained rather qualitative by nature and as such ion suppression does not generally compromise data information content as originally suggested when the methodology was first introduced. This review will describe how the quality of data has improved through use of nano-flow infusion and mass-windowing approaches, particularly when using high resolution instruments. The increasingly wider availability of robust high accurate mass instruments actually promotes ESI-MS from a merely fingerprinting tool to the ranks of metabolite profiling and combined with MS/MS capabilities of hybrid instruments improved structural information is available concurrently. We summarise current applications in a wide range of fields where ESI-MS fingerprinting has proved to be an excellent tool for “first pass” metabolome analysis of complex biological samples. The final part of the review describes a typical workflow with reference to recently published data to emphasise key aspects of overall experimental design.