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During 1996–7 MSRI held a full academic year program on Combinatorics, with special emphasis on the connections with other branches of mathematics, such as algebraic geometry, topology, commutative algebra, representation theory, and convex geometry. The rich combinatorial problems arising from the study of various algebraic structures are the subject of this book, which represents work done or presented at seminars during the program. It contains contributions on matroid bundles, combinatorial representation theory, lattice points in polyhedra, bilinear forms, combinatorial differential topology and geometry, Macdonald polynomials and geometry, enumeration of matchings, the generalized Baues problem, and Littlewood–Richardson semigroups. These expository articles, written by some of the most respected researchers in the field, will continue to be of use to graduate students and researchers in combinatorics as well as algebra, geometry, and topology.
Vitamin A deficiency (VAD) poses significant health risks and is prevalent in children and adolescents in India. This study aimed to determine the effect of seasonal variation and availability of vitamin A-rich (VA-rich) foods on serum retinol in adolescents. Data on serum retinol levels from adolescents (n 2297, mean age 14 years) from the Comprehensive National Nutrition Survey (2016–2018) in India were analysed, with VAD defined as serum retinol < 0·7 µmol/L. Five states were selected based on a comparable under-five mortality rate and the seasonal spread of the data collection period. Dietary data from adolescents and children ≤ 4 years old were used to assess VA-rich food consumption. A linear mixed model framework was employed to analyse the relationship between serum retinol, month of the year and VA-rich food consumption, with a priori ranking to control for multiple hypothesis testing. Consumption of VA-rich foods, particularly fruits and vegetables/roots and tubers, showed seasonal patterns, with higher consumption during summer and monsoon months. Significant associations were found between serum retinol concentrations and age, month of sampling, consumption of VA-rich foods and fish. VAD prevalence was lowest in August, coinciding with higher consumption of VA-rich fruits and foods. Findings highlight the importance of considering seasonality in assessing VAD prevalence and careful interpretation of survey findings. Intentional design, analysis and reporting of surveys to capture seasonal variation is crucial for accurate assessment and interpretation of VAD prevalence, including during monitoring and evaluation of programmes, and to ensure that public health strategies are appropriately informed.
Inadequate recruitment and retention impede clinical trial goals. Emerging decentralized clinical trials (DCTs) leveraging digital health technologies (DHTs) for remote recruitment and data collection aim to address barriers to participation in traditional trials. The ACTIV-6 trial is a DCT using DHTs, but participants’ experiences of such trials remain largely unknown. This study explored participants’ perspectives of the ACTIV-6 DCT that tested outpatient COVID-19 therapeutics.
Methods:
Participants in the ACTIV-6 study were recruited via email to share their day-to-day trial experiences during 1-hour virtual focus groups. Two human factors researchers guided group discussions through a semi-structured script that probed expectations and perceptions of study activities. Qualitative data analysis was conducted using a grounded theory approach with open coding to identify key themes.
Results:
Twenty-eight ACTIV-6 study participants aged 30+ years completed a virtual focus group including 1–4 participants each. Analysis yielded three major themes: perceptions of the DCT experience, study activity engagement, and trust. Participants perceived the use of remote DCT procedures supported by DHTs as an acceptable and efficient method of organizing and tracking study activities, communicating with study personnel, and managing study medications at home. Use of social media was effective in supporting geographically dispersed participant recruitment but also raised issues with trust and study legitimacy.
Conclusions:
While participants in this qualitative study viewed the DCT-with-DHT approach as reasonably efficient and engaging, they also identified challenges to address. Understanding facilitators and barriers to DCT participation and DHT interaction can help improve future research design.
To assess the potential contribution of large-scale food fortification (LSFF) towards meeting dietary micronutrient requirements in Tanzania.
Design:
We used household food consumption data from the National Panel Survey 2014–15 to estimate fortifiable food vehicle coverage and consumption (standardised using the adult female equivalent approach) and the prevalence at risk of inadequate apparent intake of five micronutrients included in Tanzania’s fortification legislation. We modelled four LSFF scenarios: no fortification, status quo (i.e. compliance with current fortification contents) and full fortification with and without maize flour fortification.
Setting:
Tanzania.
Participants:
A nationally representative sample of 3290 Tanzanian households.
Results:
The coverage of edible oils and maize and wheat flours (including products of wheat flour and oil such as bread and cakes) was high, with 91 percent, 88 percent and 53 percent of households consuming these commodities, respectively. We estimated that vitamin A-fortified oil could reduce the prevalence of inadequate apparent intake of vitamin A (retinol activity equivalent) from 92 percent without LSFF to 80 percent with LSFF at current fortification levels. Low industry LSFF compliance of flour fortification limits the contribution of other micronutrients, but a hypothetical full fortification scenario shows that LSFF of cereal flours could substantially reduce the prevalence at risk of inadequate intakes of iron, zinc, folate and vitamin B12.
Conclusions:
The current Tanzania LSFF programme likely contributes to reducing vitamin A inadequacy. Policies that support increased compliance could improve the supply of multiple nutrients, but the prominence of small-scale maize mills restricts this theoretical benefit.
Desorption processes of low-molecular-weight compounds from the surface of smectites into the gas phase determine a number of processes, e.g. those involved in drug delivery and the release of herbicides. The desorption has not been investigated thoroughly and is not well understood. The present study was undertaken in order to understand better the factors influencing these desorption mechanisms. Starting with a very pure standard (Na+-rich) montmorillonite (Kunipia-F), which was exchanged against cations with different hydration properties (Ca2+, Li+, phenyltrimethylammonium, hexyltrimethyl-ammonium), the experiments explored the rate of desorption of volatiles with different chemical functionalities (water, ethanol, ethyl acetate, and toluene). The desorption was monitored by thermogravimetry and differential scanning calorimetry under isothermal conditions, and by ramping the temperature at a constant rate. The experiments were compared with numerical calculations based on finite-element methods and with analytical models. These data point to a two-step mechanism where the desorption follows the curve of the equilibrium desorption isotherms of those molecules on the montmorillonite. The bulk-like volatiles (i.e. volatiles with release kinetics close to that of the bulk liquids) were desorbed in a first step. With a decrease in the degree of coverage of the volatile on the montmorillonite, the desorption was increasingly dominated by the strength of interaction between the volatile and the interlayer cations of the montmorillonite.
Of all the known pillared layered clays (PILC), Al-PILC is the most studied. In spite of that, its use on a commercial scale is not yet possible due to the large amount of water required for its synthesis. The aim of the present work was to take advantage of the beneficial effects of ultrasound radiation for reducing intercalation time, and to optimize the synthesis parameters in order to find a viable industrial means of preparing Al-PILC.
A comprehensive study of the effect of ultrasonic radiation on the parameters which have a direct effect on the amount of water used in the synthesis was conducted, specifically on the effects of: (1) mmol of Al/g of clay ratio (R) by decreasing the volume of A1 solution and keeping the amount of clay constant, (2) the concentration of clay in the initial suspension (or not suspending the clay at all), and (3) the concentration of the A1 precursor solution. The use of ultrasonic radiation produced the expected reduction in exchange time which was attributed to a decrease of the clay-particle size. This decrease of particle size gave rise to an improvement in the diffusion of the A1 precursor towards the core of the clay grain leading to solids with increased surface areas, basal spacing and X-ray diffraction peak definition. By optimizing the synthesis parameters directly involved in the consumption of water, it was possible to decrease the amount used by >60%.
Anaemia is characterised by low hemoglobin (Hb) concentration. Despite being a public health concern in Ethiopia, the role of micronutrients and non-nutritional factors as a determinant of Hb concentrations has been inadequately explored. This study focused on the assessment of serum micronutrient and Hb concentrations and a range of non-nutritional factors, to evaluate their associations with the risk of anaemia among the Ethiopian population (n 2046). It also explored the mediation effect of Zn on the relation between se and Hb. Bivariate and multivariate regression analyses were performed to identify the relationship between serum micronutrients concentration, inflammation biomarkers, nutritional status, presence of parasitic infection and socio-demographic factors with Hb concentration (n 2046). Sobel–Goodman test was applied to investigate the mediation of Zn on relations between serum se and Hb. In total, 18·6 % of participants were anaemic, 5·8 % had iron deficiency (ID), 2·6 % had ID anaemia and 0·6 % had tissue ID. Younger age, household head illiteracy and low serum concentrations of ferritin, Co, Cu and folate were associated with anaemia. Serum se had an indirect effect that was mediated by Zn, with a significant effect of se on Zn (P < 0·001) and Zn on Hb (P < 0·001). The findings of this study suggest the need for designing a multi-sectorial intervention to address anaemia based on demographic group.
Precision medicine has the potential to transform healthcare by moving from one-size-fits-all to personalised treatment and care. This transition has been greatly facilitated through new high-throughput sequencing technologies that can provide the unique molecular profile of each individual patient, along with the rapid development of targeted therapies directed to the Achilles heels of each disease. To implement precision medicine approaches in healthcare, many countries have adopted national strategies and initiated genomic/precision medicine initiatives to provide equal access to all citizens. In other countries, such as Sweden, this has proven more difficult due to regionally organised healthcare. Using a bottom-up approach, key stakeholders from academia, healthcare, industry and patient organisations joined forces and formed Genomic Medicine Sweden (GMS), a national infrastructure for the implementation of precision medicine across the country. To achieve this, Genomic Medicine Centres have been established to provide regionally distributed genomic services, and a national informatics infrastructure has been built to allow secure data handling and sharing. GMS has a broad scope focusing on rare diseases, cancer, pharmacogenomics, infectious diseases and complex diseases, while also providing expertise in informatics, ethical and legal issues, health economy, industry collaboration and education. In this review, we summarise our experience in building a national infrastructure for precision medicine. We also provide key examples how precision medicine already has been successfully implemented within our focus areas. Finally, we bring up challenges and opportunities associated with precision medicine implementation, the importance of international collaboration, as well as the future perspective in the field of precision medicine.
The production of meltwater from glacier ice, which is exposed at the margins of land ice during the summer, is responsible for a large proportion of glacier mass loss. The rate of meltwater production from glacier ice is especially sensitive to its physical structure and chemical composition which combine to determine the albedo of glacier ice. However, the optical properties of near-surface glacier ice are not well known since most prior work has focused on laboratory-grown ice or deep cores. Here, we demonstrate a measurement technique based on diffuse propagation of nanosecond-duration laser pulses in near-surface glacier ice that enables the independent measurement of the scattering and absorption coefficients, allowing for a complete description of the processes governing radiative transfer. We employ a photon-counting detector to overcome the high losses associated with diffuse optics. The instrument is highly portable and rugged, making it optimally suited for deployment in remote regions. A set of measurements taken on Crook and Collier Glaciers, Oregon, serves as a demonstration of the technique. These measurements provide insight into both physical structure and composition of near-surface glacier ice and open new avenues for the analysis of light-absorbing impurities and remote sensing of the cryosphere.
Multiple micronutrient deficiencies are widespread in Ethiopia. However, the distribution of Se and Zn deficiency risks has previously shown evidence of spatially dependent variability, warranting the need to explore this aspect for wider micronutrients. Here, blood serum concentrations for Ca, Mg, Co, Cu and Mo were measured (n 3102) on samples from the Ethiopian National Micronutrient Survey. Geostatistical modelling was used to test spatial variation of these micronutrients for women of reproductive age, who represent the largest demographic group surveyed (n 1290). Median serum concentrations were 8·6 mg dl−1 for Ca, 1·9 mg dl−1 for Mg, 0·4 µg l−1 for Co, 98·8 µg dl−1 for Cu and 0·2 µg dl−1 for Mo. The prevalence of Ca, Mg and Co deficiency was 41·6 %, 29·2 % and 15·9 %, respectively; Cu and Mo deficiency prevalence was 7·6 % and 0·3 %, respectively. A higher prevalence of Ca, Cu and Mo deficiency was observed in north western, Co deficiency in central and Mg deficiency in north eastern parts of Ethiopia. Serum Ca, Mg and Mo concentrations show spatial dependencies up to 140–500 km; however, there was no evidence of spatial correlations for serum Co and Cu concentrations. These new data indicate the scale of multiple mineral micronutrient deficiency in Ethiopia and the geographical differences in the prevalence of deficiencies suggesting the need to consider targeted responses during the planning of nutrition intervention programmes.
To review existing publications using Household Consumption and Expenditure Survey (HCES) data to estimate household dietary nutrient supply to (1) describe scope of available literature, (2) identify the metrics reported and parameters used to construct these metrics, (3) summarise comparisons between estimates derived from HCES and individual dietary assessment data and (4) explore the demographic and socio-economic sub-groups used to characterise risks of nutrient inadequacy.
Design:
This study is a systematic review of publications identified from online databases published between 2000 to 2019 that used HCES food consumption data to estimate household dietary nutrient supply. Further publications were identified by ‘snowballing’ the references of included database-identified publications.
Setting:
Publications using data from low- and lower-middle income countries.
Results:
In total, fifty-eight publications were included. Three metrics were reported that characterised household dietary nutrient supply: apparent nutrient intake per adult-male equivalent per day (n 35), apparent nutrient intake per capita per day (n 24) and nutrient density (n 5). Nutrient intakes were generally overestimated using HCES food consumption data, with several studies finding sizeable discrepancies compared with intake estimates based on individual dietary assessment methods. Sub-group analyses predominantly focused on measuring variation in household dietary nutrient supply according to socio-economic position and geography.
Conclusion:
HCES data are increasingly being used to assess diets across populations. More research is needed to inform the development of a framework to guide the use of and qualified interpretation of dietary assessments based on these data.
In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.
Methods
Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.
Results
Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.
Conclusions
These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.
Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
Methods
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Results
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
Conclusions
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.
Treatment with antipsychotics is associated with an increased risk of type 2 diabetes mellitus (T2D), and increased levels of inflammatory biomarkers are present in patients with T2D. We previously demonstrated that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. This study aims to assess the involvement of cytokines in the therapeutic effects of liraglutide.
Methods
Serum concentrations of 10 cytokines (interferon-γ [IFN-γ], tumor necrosis factor-α, interleukin 1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13) from fasting prediabetic and normal glucose-tolerant (NGT) patients with schizophrenia-spectrum disorders were measured using multiplexed immunoassays. Prediabetic patients were randomized to 16 weeks of treatment with liraglutide or placebo, and cytokines were measured again at the end of the treatment.
Results
IFN-γ (1.98 vs 1.17 pg/ml, P = .001), IL-4 (0.02 vs 0.01 pg/ml, P < .001), and IL-6 (0.73 vs 0.46 pg/ml, P < .001) were significantly higher in prediabetic (n = 77) vs NGT patients (n = 31). No significant changes in cytokine levels following treatment with liraglutide (n = 37) vs placebo (n = 40) were found.
Conclusion
Prediabetic vs NGT patients with schizophrenia treated with clozapine or olanzapine had increased serum levels of several proinflammatory cytokines, further substantiating the link between inflammation and T2D. Treatment with liraglutide did not affect the investigated cytokines. Further testing of these findings in larger numbers of individuals is needed.
The article argues that the impact of law enforcement efforts against corruption deserves more scholarly attention. Drawing on a mixed-methods study from Malawi in southern Africa, where a large-scale law enforcement operation has been investigating and prosecuting those involved in a 2013 corruption scandal known as ‘Cashgate’, the article explores the potential for corruption deterrence from the perspective of government officials in the Malawi civil service. Malawi provides a challenging environment for deterrence due to limited state capacity, weak law enforcement agencies and widespread corruption. Nonetheless, the research findings show that Malawian government officials perceive prosecutions and convictions to deter corruption, both with regards to the law enforcement response to Cashgate specifically and law enforcement efforts in general. The findings from Malawi suggest that law enforcement and criminal justice have the potential to make an important contribution to anti-corruption strategies in Africa and the Global South at large.
Somatoform pain disorder (SPD) is frequently associated with sleep disorders, specifically restless legs syndrome and insomnia, which in turn lowers the pain threshold and worsens pain.
Objectives
The aim of the present study was to investigate differences in wake-EEG by low-resolution electromagnetic tomography (LORETA) and objective and subjective sleep and awakening quality in SPD patients as compared with controls and study acute and chronic effects of trazodone CR on these variables and pain measures.
Methods
Fifteen patients with SPD (F45.4) and co-morbid insomnia (F51.0) were compared with 15 controls and participated in a single-blind, placebo-controlled, cross-over study on the acute effect of 100 mg trazodone CR, followed by a six-week open titration period. Statistics involved clinical, EEG-LORETA, PSG and psychometry.
Results
LORETA showed reduced power, mainly in the beta band in almost all pain matrix areas (SI, SII, ACC, SMA, PFC, PPC, insula, amygdala, hippocampus). PSG demonstrated a lack of deep sleep and increased arousals and stage shifts, with opposite changes induced by trazodone after acute and chronic therapy. Improvement of sleep was associated with improvement of pain, evaluated by visual-analog scales.
Conclusion
Our LORETA findings demonstrate a dysfunctional pain modulation in SPD. Trazodone induced changes in subjective and objective sleep and awakening quality that were opposite to the differences between SPD patients and controls (key-lock principle) and associated with pain improvement.
Selenium (Se) is an essential element for human health. However, our knowledge of the prevalence of Se deficiency is less than for other micronutrients of public health concern such as iodine, iron and zinc, especially in sub-Saharan Africa (SSA). Studies of food systems in SSA, in particular in Malawi, have revealed that human Se deficiency risks are widespread and influenced strongly by geography. Direct evidence of Se deficiency risks includes nationally representative data of Se concentrations in blood plasma and urine as population biomarkers of Se status. Long-range geospatial variation in Se deficiency risks has been linked to soil characteristics and their effects on the Se concentration of food crops. Selenium deficiency risks are also linked to socio-economic status including access to animal source foods. This review highlights the need for geospatially-resolved data on the movement of Se and other micronutrients in food systems which span agriculture–nutrition–health disciplinary domains (defined as a GeoNutrition approach). Given that similar drivers of deficiency risks for Se, and other micronutrients, are likely to occur in other countries in SSA and elsewhere, micronutrient surveillance programmes should be designed accordingly.
Sarcopenia (loss of muscle mass/strength) burdens many older adults – hospitalised older adults being particularly vulnerable. Treating the condition, protein supplementation (PrS) and resistance training (RT) may act synergistically. Therefore, this block-randomised, double-blind, multicentre intervention study, recruiting geriatric patients > 70 years from three medical departments, investigated the effect of PrS combined with RT during hospitalisation and 12 weeks after discharge. Participants were randomly allocated (1:1) to receive PrS (totally 27·5 g whey protein/d, about 2000 kJ/d) or isoenergetic placebo-products (< 1·5 g protein/d) divided into two servings per d to supplement the habitual diet. Both groups were engaged in a standardised, progressive low-intensity RT programme for the lower extremities (hospital: supervised daily/after discharge: self-training 4×/week). From April 2016 to September 2017, 2351 patients were screened, 462 were eligible, and 165 included. Fourteen were excluded and ten dropped out, leaving 141 participants in the intention-to-treat analysis. The average total protein intake during hospitalisation/after discharge was 1·0 (interquartile range (IQR) 0·8, 1·3)/1·1 (IQR 0·9, 1·3) g/kg per d (protein-group) and 0·6 (IQR 0·5, 0·8)/0·9 (IQR 0·6, 1·0) g/kg per d (placebo group). Both groups improved significantly for the primary and secondary endpoints of muscle mass/strength, functional measurements and quality of life, but no additional effect of PrS was seen for the primary endpoint (30-s chair stand test, repetitions, median changes from baseline: (standard test: 0 (IQR 0, 5) (protein group) v. 2 (IQR 0, 6) (placebo group) and modified test: 2 (IQR 0, 5) (protein group) v. 2 (IQR −1, 5) (placebo group)) or any secondary endpoints (Mann–Whitney U tests, P > 0·05). In conclusion, PrS increasing the total protein intake by 0·4 and 0·2 g/kg per d during hospitalisation and after discharge, respectively, does not seem to increase the adaptive response to low-intensity RT in geriatric medical patients.
Dewatering structures are a common feature used to identify melt-out till, and the lack of such structures in till could preclude deposition by melt-out. To assess the conditions under which melt-out till can be deposited without forming dewatering structures, I use geotechnical data and a quasi-two-dimensional model of geothermal melt-out. Critical discharge determined from geotechnical data suggests that low-hydraulic-conductivity till can transport up to 1.3 m3 water a–1m–2 without forming dewatering structures, which is two to three orders of magnitude greater than the volume of meltwater produced at the base of glaciers. The model indicates that debris content of the ice and the ability of the till to drain govern effective pressure during melt-out. If the drainage system is poorly developed or the till comes from debris-poor ice, effective pressure is below zero, the condition under which dewatering structures could form. However, till from relatively debris-rich ice (>40% debris) with a well-developed drainage system (channels every 10 m) can dewater without forming dewatering structures. This suggests that the lack of dewatering structures in till does not necessarily imply deposition by lodgement or deforming bed.