Development of a comprehensive normal-phase liquid chromatography × size-exclusion chromatography platform with ultraviolet spectroscopy and high-resolution mass spectrometry detection for the chemical characterization of complex polyesters.

BACKGROUND: Polyesters are applied in high-end products in many industrial applications, including resins and powder-coating applications. The characterization of the chemical heterogeneities within a polyester is of utmost interest to develop new products or improve existing applications. Unfortunately, characterization is a difficult task, as polyesters may feature distributions in end-group functionality, molecular weight, chemical composition, and degree of branching. Currently, no analytical method can characterize all these interdependent distributions in a single analysis. RESULTS: We report the use of comprehensive normal-phase liquid chromatography × size-exclusion chromatography hyphenated with ultraviolet-light spectroscopy and high-resolution mass spectrometry in parallel (NPLC × SEC-UV/HRMS) to characterize polyesters according to their end-group-functionality and molecular-weight distributions. The chemical composition can be measured with HRMS, while relative quantitation can be performed with UV detection. A supercharging agent was used during ionization allowing to extend the molecular-weight range of the detected chemical species. SIGNIFICANCE: The presented platform allows characterization of polyesters with varying fractions of carboxyl or hydroxyl end-group functionalities and varying distributions of molecular weight, degree of branching, and chemical compositions. The number-average and weight-average molar masses are obtained in the same analysis. This information cannot be obtained by any one-dimensional technique. The developed NPLC × SEC-UV/HRMS platform is a valuable tool for characterizing polyesters in an industrial setting.

Relevance of plasma lipoproteins and small metabolites in assessment of nutritional status among patients with severe injuries.

Background: This study aimed to identify plasma lipoproteins and small metabolites associated with high risk of malnutrition during intensive care unit (ICU) stay in patients with severe injuries. Methods: This observational prospective exploratory study was conducted at two level-1 trauma centers in the Netherlands. Adult patients (aged ≥18 years) who were admitted to the ICU for more than 48 h between July 2018 and April 2022 owing to severe injuries (polytrauma, as defined by Injury Severity Scores of ≥16) caused by blunt trauma were eligible for inclusion. Partial least squares discriminant analysis was used to analyze the relationship of 112 lipoprotein-related components and 23 small metabolites with the risk of malnutrition (modified Nutrition Risk in Critically Ill score). Malnutrition was diagnosed based on Subjective Global Assessment scores. The relationship of lipoprotein properties and small metabolite concentrations with malnutrition (during ICU admission) was evaluated using mixed effects logistic regression. Results: Overall, 51 patients were included. Lower (very) low-density lipoprotein ([V]LDL) (free) cholesterol and phospholipid levels, low particle number, and higher levels of LDL triglycerides were associated with a higher risk of malnutrition (variable importance in projection [VIP] value >1.5). Low levels of most (V)LDL and intermediate-density lipoprotein subfractions and high levels of high-density lipoprotein Apo-A1 were associated with the diagnosis of malnutrition (VIP value >1.5). Increased levels of dimethyl sulfone, trimethylamine N-oxide, creatinine, N, N-dimethylglycine, and pyruvic acid and decreased levels of creatine, methionine, and acetoacetic acid were also indicative of malnutrition (VIP value >1.5). Overall, 14 lipoproteins and 1 small metabolite were significantly associated with a high risk of malnutrition during ICU admission (P <0.05); however, the association did not persist after correcting the false discovery rate (P=0.35 for all). Conclusion: Increased triglyceride in several lipoprotein subfractions and decreased levels of other lipoprotein subfraction lipids and several small metabolites (involved in the homocysteine cycle, ketone body formation, and muscle metabolism) may be indicative of malnutrition risk. Following validation in larger cohorts, these indicators may guide institution of preventive nutritional measures in patients admitted to the ICU with severe injuries.

Electrocardiographic and morphological cardiac remodeling in competitive female athletes - a scoping review.

AIMS: To quantitatively analyse exercise-induced cardiac remodeling (EICR) data in female athletes. METHODS: This scoping review included from the databases Medline, Embase, and Google Scholar, peer-reviewed original English-language articles on female athlete-populations aged ≥18 years containing data on electrocardiography (ECG), echocardiography or cardiac magnetic resonance (CMR), and excluded athletes with cardiovascular conditions. From the extracted ECG data, we calculated prevalence percentages, and from the imaging data we compared the results with the upper reference limits of the general female population (URL). RESULTS: We included 31 articles comprising 4,896 female athletes, aged mean 22.2±4.6 years. On ECG (n=889), most prevalent findings were increased QRS voltages for LV hypertrophy (LVH, n=97), J-point elevation (JPE, n=108), and T-wave inversion (TWI, n=104). On echocardiography (n=4,644), we found increased mean of means BSA-indexed volumes for the LV 67.3 mL/m2 (95%CI 66.8-67.8; URL=61) and right ventricle (RV) 82.7 mL/m2 (95%CI 79.5-86.0; URL=74), while atrial volumes, septal wall thickness and LV mass were within the upper reference limits of the general population (URL). On CMR (n=309), the mean of means volumes of LA (62.0 mL/m2, 95%CI 58.8-65.2; URL=61), LV (103.4 mL/m2, 95%Ci 101.8-105.0; URL=96), and RV (105.3 mL/m2, 95%CI 103.3-110.6; URL=107.2) were >URL. CONCLUSION: Female athletes demonstrate distinct features of electrical (increased QRS voltages for LVH, JPE and TWI) and morphological EICR (biventricular dilatation). On CMR, LA was borderline dilated. Extensive studies on female athletes are needed to understand sex specific EICR.

Prolonged and repetitive exercise induces changes in the heart, both electrical (as seen on the ECG) and in size and shape (as seen on echocardiography or cardiac magnetic resonance imaging. These changes may include wall thickening and increase in chamber volumes. These changes are well-described in male athletes, but not in female athletes. This review highlights the changes in the hearts of healthy female athletes including electrical signs of increased cardiac muscle mass and of altered electrical reloading, and shape changes that include increases in left and right sided chamber volumes with normal ventricular wall thickness and mass.

Fat-soluble vitamins as biomarkers of nutritional status and their relation with complications in polytrauma patients.

BACKGROUND AND AIMS: This exploratory observational prospective study aimed to evaluate fat-soluble vitamin plasma levels during hospital admission and its relation with the development of malnutrition and complications in polytrauma patients, considering the protocolized multivitamin supplementation during intensive care unit (ICU) admission. METHODS: In 49 well-nourished polytrauma (injury severity score ≥ 16) patients admitted to the ICU of two level-1 trauma centers, vitamin A, D, and E levels were assessed weekly during hospital stay. All patients received multivitamin supplementation during ICU stay. Linear mixed-effect models were used to assess a trend in vitamin levels over time during hospital stay. Mixed-effects logistic regression analysis was performed to relate vitamin concentrations with malnutrition, defined as a subjective global assessment score ≤5, and complications. RESULTS: Vitamin A levels increased 0.17 µmol/L per week (95% confidence interval 0.12-0.22, p < 0.001), vitamin D levels increased 1.49 nmol/L per week (95% confidence interval 0.64-2.33, p < 0.01), vitamin E levels increased 1.17 µmol/L per week (95% confidence interval 0.61-1.73, p < 0.001) during hospital stay (29 ± 17 days). Vitamin levels were not related to malnutrition or complications during hospital stay. CONCLUSION: Vitamin A, D, and E levels increased due to supplementation during hospital admission. Plasma levels of vitamins A, D, and E do not seem to be useful as biomarkers for the nutritional status of polytrauma patients during hospital stay. No correlation with complications could be demonstrated.

The Ghana heart initiative - a health system strengthening approach as index intervention model to solving Ghana's cardiovascular disease burden.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, with 80% of these deaths occurring in low-middle income countries (LMICs). In Ghana and across Africa, CVDs have emerged as the leading causes of death primarily due to undetected and under treated hypertension, yet less than 5% of resources allocated to health in these resource-poor countries go into non-communicable diseases (NCD) including CVD prevention and management. Consequently, most countries in Africa do not have contextually appropriate and sustainable health system framework to prevent, detect and manage CVD to achieve Universal Health Coverage (UHC) in CVD care through improved Primary Health Care (PHC) with the aim of achieving Sustainable Development Goals (SDG) in CVD/NCD. In view of this, the Ghana Heart Initiative (GHI) was envisaged as a national strategy to address the identified gaps using a health system and a population-based approach to reduce the national burden of CVDs. The GHI intervention includes the development of guidelines and training manuals; training, equipment support, establishment of a national call/support center, and improvement in the national data capturing system for CVDs and NCD, management of Hypertension, Deep Vein Thrombosis (DVT) and Heart Failure (HF). Following the implementation of the GHI concept, a national CVD Management Guideline was developed and 300-health facilities across the different levels of care including one teaching hospital, was also supported with basic life-saving equipment. In addition, more than 1,500 healthcare workers also reported improvement in their knowledge and skills in the management and treatment of CVD-related cases in their health facilities. These are key contributions to strengthening the health system for CVD care and learning lessons for scale up.

Patients' preferences for secondary prevention following a coronary event.

Objective: Despite clear evidence on the effectiveness of secondary prevention, patients with coronary artery disease frequently fail to reach guideline-based risk factor targets. Integrating patients' preferences into treatment decisions has been recommended to reduce this gap. However, this requires knowledge about patient treatment preferences. Therefore, through a survey study, we aimed to explore which risk factors patients self-perceived, prioritised for improvement, and needed support with after a recent hospitalisation for coronary heart disease. Methods: A digital questionnaire was presented to patients > 18 years recently discharged (≤3 months) from an acute coronary care unit in the Netherlands (Europe). Patients could select from eight cardiovascular risk factors that they (1) self-perceived, (2) prioritised for improvement, and (3) needed support to improve. Patients' perceived risk factors were compared to those documented in the medical records. Results: Respondents (N = 254, 26 % women), mean age 64 (SD 10) years, identified 'physical inactivity' more frequently than their medical records (140 patients vs. 91 records, p < 0.001), while three other risk factors were reported with equal and four with lower frequency. 'Physical inactivity', 'overweight' and 'stress' were most frequently prioritised for improvement (82 %, 88 % and 78 %) and professional support (64 %, 50 % and 58 %), with 87 % preferring lifestyle optimisation if this would reduce drug use. Conclusions: Patients with a recent coronary event show significant disparities in identifying risk factors compared to their medical records. They tend to prefer improving lifestyle- over drug-modifiable risk factors, particularly physical inactivity, overweight and stress, and indicate the need for support in improving these factors.

Prevalence of Cardiovascular Disease and Risk Factors in Ghana: A Systematic Review and Meta-analysis.

Background: The increasing cardiovascular disease (CVD) burden threatens the global population as the major cause of disability and premature death. Data are scarce on the magnitude of CVD among the population in West Africa, particularly in Ghana. This study examined the available scientific evidence to determine the pooled prevalence (PP) of CVD and risk factors in Ghana. Methods: We searched electronic databases such as PubMed, Google Scholar, the Cochrane Library, Science Direct and Africa Journal Online databases to identify literature published from the start of the indexing of the database to 10th February 2023. All articles published in the English language that assessed the prevalence of CVD or reported on CVD in Ghana were included. Two authors independently performed the study selection, assessed the risk of bias, extracted the data and checked by the third author. The effect sizes and pooled odds ratio (POR) were determined using the random-effects DerSimonian-Laird (DL) model. Result: Sixteen studies with 58912 participants from 1954 to 2022 were included in the meta-analysis. Six studies out of 16 reported more than one prevalence of CVD, giving a total of 59 estimates for PP. The PP of CVD in the general population in Ghana was 10.34% (95% Cl: [8.48, 12.20]; l2 99.54%, p < 0.001). Based on the subgroup analysis, the prevalence of CVD was higher in hospital-based settings at 10.74% (95%, confidence interval [Cl]: 8.69, 12.79) than in community-based settings at 5.04% (95% Cl: 2.54, 7.53). The risk factors were male gender (pooled odds ratio [POR]: 1.66; 95% CI: 1.02, 2.70), old age (POR: 1.32; 95% CI: 1.21, 1.45), unemployment (POR: 2.62; 95% CI: 1.33, 5.16), diabetes (POR: 2.79; 95% CI: 1.62, 4.81) and hypertension (POR: 3.41; 95% CI: 1.75, 6.66). Conclusion: The prevalence of CVD was high in Ghana. Urgent interventions are needed for the prevention and management of the high burden of CVD and its risk factors.

Impact of implementing Dutch versus European guideline risk factor targets in older patients with ischaemic heart disease.

BACKGROUND: In patients with ischaemic heart disease (IHD) aged > 70 years, Dutch and European guidelines recommend different treatment targets: low-density lipoprotein cholesterol (LDL-c) < 2.6 versus < 1.4 mmol/l and systolic blood pressure (SBP) < 140 versus < 130 mm Hg, respectively. How this impacts cardiovascular event-free life expectancy has not been investigated. The study objective was to compare estimated lifelong treatment benefits of implementing Dutch and European LDL­c and SBP targets. METHODS: Data from patients aged 71-80 years hospitalised for IHD in 2017-2019 were extracted from the PHARMO Database Network, which links primary and secondary healthcare settings, with follow-up until 31 December 2020. Potential benefit according to treatment strategy (in gain in event-free years) was estimated using the SMART-REACH model. RESULTS: Of the 3003 eligible patients, 1186 (39%) had missing LDL­c and/or SBP measurements. Of the 1817 included patients (36% women, median age at event: 74 years (interquartile range (IQR): 72-77), 84% achieved the Dutch targets for both LDL­c and SBP; for European targets, this was 23% and 61%, respectively. If Dutch targets were met for LDL­c and SBP (n = 1281), the additional effect of reaching European targets was a median gain of 0.6 event-free life years (IQR: 0.3-1.0). The greatest effect could be reached in patients not reaching Dutch targets (n = 501), with a median gain of 0.6 (IQR: 0.2-1.2) and 1.7 (IQR: 1.2-2.5) event-free years with Dutch versus European targets. CONCLUSION: In patients aged > 70 years with IHD, implementation of European targets resulted in a greater gain of event-free years compared with Dutch targets, especially in patients with poorer risk factor control. The considerable number of patients with missing risk factor documentation suggested additional opportunities for risk reduction.

Validation of Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons in the EPIC-Norfolk prospective population cohort.

AIMS: The European Systematic Coronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models are recommended to identify individuals at high 10-year risk for cardiovascular disease (CVD). Independent validation and assessment of clinical utility is needed. This study aims to assess discrimination, calibration, and clinical utility of low-risk SCORE2 and SCORE2-OP. METHODS AND RESULTS: Validation in individuals aged 40-69 years (SCORE2) and 70-79 years (SCORE2-OP) without baseline CVD or diabetes from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population study. We compared 10-year CVD risk estimates with observed outcomes (cardiovascular mortality, non-fatal myocardial infarction, and stroke). For SCORE2, 19 560 individuals (57% women) had 10-year CVD risk estimates of 3.7% [95% confidence interval (CI) 3.6-3.7] vs. observed 3.8% (95% CI 3.6-4.1) [observed (O)/expected (E) ratio 1.0 (95% CI 1.0-1.1)]. The area under the curve (AUC) was 0.75 (95% CI 0.74-0.77), with underestimation of risk in men [O/E 1.4 (95% CI 1.3-1.6)] and overestimation in women [O/E 0.7 (95% CI 0.6-0.8)]. Decision curve analysis (DCA) showed clinical benefit. Systematic Coronary Risk Evaluation 2-Older Persons in 3113 individuals (58% women) predicted 10-year CVD events in 10.2% (95% CI 10.1-10.3) vs. observed 15.3% (95% CI 14.0-16.5) [O/E ratio 1.6 (95% CI 1.5-1.7)]. The AUC was 0.63 (95% CI 0.60-0.65) with underestimation of risk across sex and risk ranges. Decision curve analysis showed limited clinical benefit. CONCLUSION: In a UK population cohort, the SCORE2 low-risk model showed fair discrimination and calibration, with clinical benefit for preventive treatment initiation decisions. In contrast, in individuals aged 70-79 years, SCORE2-OP demonstrated poor discrimination, underestimated risk in both sexes, and limited clinical utility.

To effectively prevent heart disease, it is important to identify individuals who are at a higher risk of developing it. Researchers have developed models that can estimate the likelihood of a healthy person developing heart disease within the next 10 years. This study, involving 22 673 healthy individuals in the UK, aimed to determine if these risk estimation models are accurate and can guide decisions about who should receive preventive treatment.

A multilevel and multicenter assessment of health care system capacity to manage cardiovascular diseases in Africa: a baseline study of the Ghana Heart Initiative.

INTRODUCTION: Cardiovascular diseases (CVD) remain the leading cause of death worldwide, with over 70% of these deaths occurring in low- and middle-income regions such as Africa. However, most countries in Africa do not have the capacity to manage CVD. The Ghana Heart Initiative has been an ongoing national program since 2018, aimed at improving CVD care and thus reducing the death rates of these diseases in Ghana. This study therefore aimed at assessing the impact of this initiative by identifying, at baseline, the gaps in the management of CVDs within the health system to develop robust measures to bolster CVD management and care in Ghana. METHODS: This study employed a cross-sectional study design and was conducted from November 2019 to March 2020 in 44 health facilities in the Greater Accra region. The assessment covered CVD management, equipment availability, knowledge of health workers in CVD and others including the CVD management support system, availability of CVD management guidelines and CVD/NCD indicators in the District Health Information Management System (DHIMS2). RESULTS: The baseline data showed a total of 85,612 outpatient attendants over the period in the study facilities, 70% were women and 364(0.4%) were newly diagnosed with hypertension. A total of 83% of the newly diagnosed hypertensives were put on treatment, 56.3% (171) continued treatment during the study period and less than 10% (5%) had their blood pressure controlled at the end of the study (in March 2020). Other gaps identified included suboptimal health worker knowledge in CVD management (mean score of 69.0 ± 13.0, p < 0.05), lack of equipment for prompt CVD emergency diagnosis, poor management and monitoring of CVD care across all levels of health care, lack of standardized protocol on CVD management, and limited number of indicators on CVD in the National Database (i.e., DHIMS2) for CVD monitoring. CONCLUSION: This study shows that there are gaps in CVD care and therefore, there is a need to address such gaps to improve the capacity of the health system to effectively manage CVDs in Ghana.

Quality of athlete screening for high-risk cardiovascular conditions-A systematic review.

BACKGROUND: Sudden cardiac death (SCD) is the leading medical cause of death in athletes. To prevent SCD, screening for high-risk cardiovascular conditions (HRCC) is recommended. Screening strategies are based on a limited number of studies and expert consensus. However, evidence and efficacy of athlete HRCC screening is unclear. OBJECTIVE: To determine methodological quality and quality of evidence of athlete screening, and screening efficacy to detect HRCC in a systematic review. METHODS: We performed a systematic search of Medline, Embase, Scopus and Cochrane Library up to June 2021. We included articles containing original data of athlete cardiovascular screening, providing details of screening strategies, test results and HRCC detection. We assessed methodological quality of the included articles by QUADAS-2, quality of evidence of athlete HRCC screening by GRADE, and athlete HRCC screening efficacy by SWiM. RESULTS: Of 2720 citations, we included 33 articles (1991-2018), comprising 82 417 athletes (26.7% elite, 73.4% competitive, 21.7% women, 75.2% aged ≤35). Methodological quality was 'very low' (33 articles), caused by absence of data blinding and inappropriate statistical analysis. Quality of evidence was 'very low' (33 articles), due to observational designs and population heterogeneity. Screening efficacy could not be reliably established. The prevalence of HRCC was 0.43% with false positive rate (FPR) 13.0%. CONCLUSIONS: Methodological quality and quality of evidence on athlete screening are suboptimal. Efficacy could not be reliably established. The prevalence of screen detected HRCC was very low and FPR high. Given the limitations of the evidence, individual recommendations need to be prudent.

Hyphenation of liquid chromatography and pyrolysis-flame ionization detection/mass spectrometry for polymer quantification and characterization.

Size-exclusion chromatography (SEC) hyphenated to pyrolysis-gas chromatography (Py-GC) has been demonstrated as a powerful tool in polymer analysis. A main limitation to the wider application of the method are the long second-dimension Py-GC analysis times, resulting in limited first-dimension sampling and/or long overall run times. Therefore, we set out to develop an online hyphenated SEC×Py-MS/FID method, removing the GC separation and allowing for a drastically reduced second-dimension analysis time compared to SEC-Py-GC. The pyrolysis method had a cycle time of 1.31 min, which was facilitated by liquid nitrogen cooling of the programmable temperature vaporizer (PTV) used for pyrolysis. The developed method featured no molar mass discrimination for masses above ±1.3 kDa, rendering it applicable to most commercial polymer systems. The method was demonstrated on multiple samples, including a complex industrial sample, yielding chemical composition heterogeneity and in some cases sequence heterogeneity information over the molar mass distribution.

Unexploited potential of risk factor treatment in patients with atherosclerotic cardiovascular disease.

BACKGROUND: Most patients with atherosclerotic cardiovascular disease remain at (very) high risk for recurrent events due to suboptimal risk factor control. AIMS: This study aimed to quantify the potential of maximal risk factor treatment on 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events in patients 1 year after a coronary event. METHODS AND RESULTS: Pooled data from six studies are as follows: RESPONSE 1, RESPONSE 2, OPTICARE, EUROASPIRE IV, EUROASPIRE V, and HELIUS. Patients aged ≥45 years at ≥6 months after coronary event were included. The SMART-REACH score was used to estimate 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events with current treatment and potential risk reduction and gains in event-free years with maximal treatment (lifestyle and pharmacological). In 3230 atherosclerotic cardiovascular disease patients (24% women), at median interquartile range (IQR) 1.1 years (1.0-1.8) after index event, 10-year risk was median (IQR) 20% (15-27%) and lifetime risk 54% (47-63%). Whereas 70% used conventional medication, 82% had ≥1 drug-modifiable risk factor not on target. Furthermore, 91% had ≥1 lifestyle-related risk factor not on target. Maximizing therapy was associated with a potential reduction of median (IQR) 10-year risk to 6% (4-8%) and of lifetime risk to 20% (15-27%) and a median (IQR) gain of 7.3 (5.4-10.4) atherosclerotic cardiovascular disease event-free years. CONCLUSIONS: Amongst patients with atherosclerotic cardiovascular disease, maximizing current, guideline-based preventive therapy has the potential to mitigate a large part of their risk of recurrent events and to add a clinically important number of event-free years to their lifetime.

Patients with heart disease are at high risk of new cardiac events. This study amongst 3230 patients who had a heart attack or received a stent or bypass surgery shows missed potential for healthy life after a heart attack. The average age of study patients was 61 years, and 24% were women. At 1 year after the cardiac event, nearly one in three (30%) continued smoking, 79% were overweight, 45% reported insufficient physical activity, 40% had high blood pressure, and 65% had a too high LDL ('bad') cholesterol. We calculated that adherence to lifestyle advice and medications could on average halve the risk for another heart attack and add over 7 healthy years of life after a heart attack. This highlights the importance of healthy lifestyle and medication adherence after a heart attack. Key finding:• adherence to lifestyle advice and medications could add over 7 healthy years of life after a heart attack.

Online hyphenation of size-exclusion chromatography and pyrolysis-gas chromatography for polymer characterization.

An understanding of the composition and molecular heterogeneities of complex industrial polymers forms the basis of gaining control of the physical properties of materials. In the current work we report on the development of an online method to hyphenate liquid polymer chromatography with pyrolysis-GC (Py-GC). The designed workflow included a 10-port valve for fractionation of the first-dimension effluent. Collected fractions were transferred to the Py-GC by means of a second LC pump, a 6-port valve was used to control injection in the Py-GC, allowing the second pump to operate continuously. The optimized large volume injection (LVI) method was capable of analyzing 117 µL of the LC effluent in a 6 min GC separation with a total cycle time of 8.45 min. This resulted in a total run time of 2.1 h while obtaining 15 Py-GC runs over the molar mass separation. The method was demonstrated on various real-life samples including a complex industrial copolymer with a bimodal molar mass distribution. The developed method was used to monitor the relative concentration of 5 different monomers over the molar mass distribution. Furthermore, the molar mass-dependent distribution of a low abundant comonomer (styrene, <1% of total composition) was demonstrated, highlighting the low detection limits and increased resolving power of this approach over e.g. online NMR or IR spectroscopy. The developed method provides a flexible and widely applicable approach to LC-Py-GC hyphenation without having to resort to costly and specialized instrumentation.

Packed modulation loops to reduce band broadening in two-dimensional liquid chromatography.

Modulation interfaces employing sample loops are applied in many hyphenated separations such as two-dimensional liquid chromatography (2D-LC). When the first-dimension effluent in 2D-LC is eluted from the modulation loop, dispersion effects occur due to differences in the laminar flow velocity of the filling and emptying flow. These effects were recently studied by Moussa et al. whom recommended the use of coiled loops to promote radial diffusion and reduce this effect. In the 1980s, Coq et al. investigated the use of packed loops, which also promote radial diffusion, in large volume injection 1D-LC. Unfortunately, this concept was never investigated in the context of 2D-LC modulation. Our work evaluates use of packed loops in 2D-LC modulation and compares them to unpacked coiled and uncoiled modulation loops. The effect of the solvents, loop volume, differences in filling and emptying rates, and loop elution direction on the elution profile was investigated. Statistical moments were used as a pragmatic tool to quantify elution profile characteristics. Decreased dispersion was observed in all cases for the packed loops compared to unpacked loops and unpacked coiled loops. In particular for larger loop volumes the dispersion was reduced significantly. Furthermore, countercurrent elution resulted in narrower elution profiles in all cases compared to concurrent elution. We found that packed modulation loops are of high interested when analytes are not refocussed in the second-dimension separation (e.g. for size-exclusion chromatography). Moreover, our work suggests that the use of packed loops may aid in prevention of loop overfilling.

Improving the accuracy of copolymer sequence length determination by pyrolysis gas chromatography: A comprehensive study.

Many industrial polymers which find application in contemporary materials are copolymers. Copolymers feature multiple distributions, that govern their physical properties, including the sequence distribution. Styrene-acrylate copolymers are an important class of polymers, their monomer sequence is typically determined by 13C NMR which suffers from low sensitivity and spectral resolution. A series of studies have shown that Py-GC can be applied to determine the sequence length of copolymers. The accuracy of the trimer assignments and the appropriate calibration approaches yielding reliable data have however not yet been validated. In the present study we propose a comprehensive workflow to ensure the accuracy of the sequence determination by Py-GC, next to NMR. In-depth analysis of the trimers observed in the Py-GC pyrograms of model styrene-acrylate copolymers was performed and specific MS fragments relating to the trimer sequence were assigned. A comparison of a series of copolymers yielded reliable assignments for the trimer signals. The obtained sequence lengths were in agreement with those calibrated with the benchmark method, 13C NMR. Py-GC was found to consistently underestimate the acrylate sequence length. Py-GC calibration with 13C NMR was thus found to be indispensable for the accurate absolute quantification of the sequence length by Py-GC. The calculated randomness did not vary significantly after NMR calibration, indicating that NMR calibration might not be required in all cases to obtain (relative) information on the sequence of a copolymer.

Two-dimensional tools for analyzing polymer microstructure; coupling non-aqueous ion-exchange chromatography to size-exclusion chromatography.

Traditional liquid-chromatographic techniques, such as size-exclusion chromatography, (critical) interaction chromatography, and hydrodynamic chromatography, can all reveal certain aspects of polymers and the underlying distributions. The distribution of incorporated acid groups present in polyacrylates can be determined by non-aqueous ion-exchange chromatography, independent of other distributions present. The microstructural details on how this number of acid groups is incorporated in the polymer remains unknown. A low-molar mass polymer molecule with high acid content and a high-molar mass polymer with a low acid content may have the exact same number of acid groups. To take a next step towards understanding the polymer microstructure of water-borne resins, the distribution of incorporated acid groups over the molar-mass distribution has been investigated. For this purpose, an on-line coupling of non-aqueous ion-exchange chromatography (NAIEX) to size-exclusion chromatography (SEC) was established. Practical considerations regarding the system setup with respect to chromatography modes and column- and valve switching dimensionality are discussed. The orthogonality of NAIEX and SEC is demonstrated. Both liquid chromatography modes may be calibrated using polymer standards, yielding a calibrated separation plane. Cross-sectional data on either the molar mass distribution or the acid group distribution at a certain point of the separation plane is obtained. The value of the designed setup was demonstrated by the detailed characterization of the combined acid-group and molar-mass distribution in polymers with a low acid content, in the order of a few mass-%. Several stages of the emulsion polymerization process could be identified using the combined power of NAIEX and SEC.

Characterization and comparison of smokeless powders by on-line two-dimensional liquid chromatography.

Smokeless powders (SPs) are one of the most commonly used propellants for ammunition but can also be abused as energetic material in improvised explosive devices (IEDs) such as pipe bombs. After a shooting or explosion, unburnt or partially burnt particulates may be observed which can be used for forensic investigation. SPs comprise mainly nitrocellulose (NC) and additives. Therefore, the characterization of both NC and the additives is of significant forensic importance. Typically, the identification, classification, and chemical profiling of smokeless powders are based exclusively on the analysis of the additives. In this study, information regarding the NC base component was combined with the chemical analysis of the additives using two-dimensional liquid chromatography (2D-LC). The system combines size-exclusion chromatography (SEC) and reversed-phase liquid chromatography (RPLC) in an on-line heart-cut 2D-LC configuration. In the first dimension, the NC is characterized by its molecular-weight distribution (MWD) while being separated from the additives. The additives are then transferred to the second-dimension separation using a novel analyte-transfer system. In the second dimension, the additives are separated to obtain a detailed profile of the low-molecular-mass compounds in the SP. With this approach, the MWD of the NC and the composition of the additives in SP have been obtained within an hour. A discrimination power of 90.53% was obtained when studying exclusively the NC MWD, and 99.47% for the additive profile. This novel combination enables detailed forensic comparison of intact SPs. Additionally, no extensive sample preparation is required, making the developed method less labor intensive.

Co-Polymer sequence determination over the molar mass distribution by size-exclusion chromatography combined with pyrolysis - gas chromatography.

The chain sequence of co-polymers strongly affects their physical properties. It is, therefore, of crucial importance for the development and final properties of novel materials. Currently however, few analytical methods are available to monitor the sequence of copolymers. The currently preferred method in copolymer-sequence determination, nuclear-magnetic-resonance spectroscopy (NMR), is insensitive (especially when 13C-NMR is required) and often offers little spectral resolution between signals indicative of different subunits. These limitations are especially challenging when one is interested in monitoring the sequence across the molar-mass distribution or in quantifying low abundant subunits. Therefore, we set out to investigate pyrolysis - gas chromatography (Py-GC) as an alternative method. Py-GC is more sensitive than NMR and offers better resolution between various subunits, but it does require calibration, since the method is not absolute. We devised a method to fuse data from NMR and Py-GC to obtain quantitative information on chain sequence and composition for a set of random and block poly(methyl methacrylate-co-styrene) copolymer samples, which are challenging to analyse as MMA tends to fully depolymerize. We demonstrated that the method can be successfully used to determine the chain sequence of both random and block copolymers. Furthermore, we managed to apply Py-GC to monitor the sequence of a random and a block copolymer across the molar-mass distribution.

Automated Feature Mining for Two-Dimensional Liquid Chromatography Applied to Polymers Enabled by Mass Remainder Analysis.

A fast algorithm for automated feature mining of synthetic (industrial) homopolymers or perfectly alternating copolymers was developed. Comprehensive two-dimensional liquid chromatography-mass spectrometry data (LC × LC-MS) was utilized, undergoing four distinct parts within the algorithm. Initially, the data is reduced by selecting regions of interest within the data. Then, all regions of interest are clustered on the time and mass-to-charge domain to obtain isotopic distributions. Afterward, single-value clusters and background signals are removed from the data structure. In the second part of the algorithm, the isotopic distributions are employed to define the charge state of the polymeric units and the charge-state reduced masses of the units are calculated. In the third part, the mass of the repeating unit (i.e., the monomer) is automatically selected by comparing all mass differences within the data structure. Using the mass of the repeating unit, mass remainder analysis can be performed on the data. This results in groups sharing the same end-group compositions. Lastly, combining information from the clustering step in the first part and the mass remainder analysis results in the creation of compositional series, which are mapped on the chromatogram. Series with similar chromatographic behavior are separated in the mass-remainder domain, whereas series with an overlapping mass remainder are separated in the chromatographic domain. These series were extracted within a calculation time of 3 min. The false positives were then assessed within a reasonable time. The algorithm is verified with LC × LC-MS data of an industrial hexahydrophthalic anhydride-derivatized propylene glycol-terephthalic acid copolyester. Afterward, a chemical structure proposal has been made for each compositional series found within the data.