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Owing to the complexity of the sector, industrial activities are often represented with limited technological resolution in integrated energy system models. In this study, we enriched the technological description of industrial activities in the integrated energy system analysis optimisation (IESA-Opt) model, a peer-reviewed energy system optimisation model that can simultaneously provide optimal capacity planning for the hourly operation of all integrated sectors. We used this enriched model to analyse the industrial decarbonisation of the Netherlands for four key activities: high-value chemicals, hydrocarbons, ammonia, and steel production. The analyses performed comprised 1) exploring optimality in a reference scenario; 2) exploring the feasibility and implications of four extreme industrial cases with different technological archetypes, namely a bio-based industry, a hydrogen-based industry, a fully electrified industry, and retrofitting of current assets into carbon capture utilisation and storage; and 3) performing sensitivity analyses on key topics such as imported biomass, hydrogen, and natural gas prices, carbon storage potentials, technological learning, and the demand for olefins. The results of this study show that it is feasible for the energy system to have a fully bio-based, hydrogen-based, fully electrified, and retrofitted industry to achieve full decarbonisation while allowing for an optimal technological mix to yield at least a 10% cheaper transition. We also show that owing to the high predominance of the fuel component in the levelled cost of industrial products, substantial reductions in overnight investment costs of green technologies have a limited effect on their adoption. Finally, we reveal that based on the current (2022) energy prices, the energy transition is cost-effective, and fossil fuels can be fully displaced from industry and the national mix by 2050.

Introduction: Diagnostic genomic sequencing is the emerging standard of care in nephrology. There is a growing need to scale up the implementation of genomic diagnostics nationally to improve patient outcomes., Methods: This pragmatic study provided genomic or genetic testing to patients with suspected monogenic kidney disease through a national network of kidney genetics clinics (KGCs). We sought to evaluate the experiences of implementing genomic diagnostics across Australia and associated diagnostic outcomes between 2013 and 2022., Results: We successfully established and expanded a nationwide network of 20 clinics as of 2022; concurrently developing laboratory, research, and education programs to scale the clinical application of genomics in nephrology. We report on an Australian cohort of 1506 kidney patients, of whom 1322 received their test results. We assessed barriers to implementation in the nephrology context, and where possible, applied real-time solutions to improve clinical processes over 10 years., Conclusion: Developing a multidisciplinary kidney genetics model across multiple health services nationally was highly successful. This model supported optimal care of individuals with monogenic kidney disease in an economically responsible way. It has continued to evolve with technological and service developments and is now set to scale further as genomic testing for kidney patients transitions to health care system funding., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Purpose: HIV-1 Drug Resistance Mutations (DRMs) among Immunological failure (IF) on NRTI based first-line regimens, Thymidine analogue (TA) - AZT & D4T and Non-Thymidine Analogue (NTA) -TDF; and predict viral drug susceptibility to gain vision about optimal treatment strategies for second-line., Methods: Cross-sectionally, 300 HIV-1 infected patients, failing first-line HAART were included. HIV-1 pol gene spanning 20-240 codons of RT was genotyped and mutation pattern was examined, (IAS-USA 2014 and Stanford HIV drug resistance database v7.0)., Results: The median age of the participants was 35 years (IQR 29-40), CD4 T cell count of TDF failures was low at 172 cells/μL (IQR 80-252), and treatment duration was low among TDF failures (24 months vs. 61 months) (p < 0.0001). Majority of the TDF failures were on EFV based first-line (89 % vs 45 %) (p < 0.0001). Level of resistance for TDF and AZT shows, that resistance to TDF was about one-third (37 %) of TDF participants and onefourth (23 %) of AZT participants; resistance to AZT was 17 % among TDF participants and 47 % among AZT participants; resistance to both AZT and TDF was significantly high among AZT participants [21 % vs. 8 %, OR 3.057 (95 % CI 1.4-6.8), p < 0.0001]., Conclusion: Although delayed identification of treatment failure caused high levels of acquired drug resistance in our study. Thus, we must include measures to regularize virological monitoring with integrated resistance testing in LMIC (Low and Middle Income Countries) like in India; this will help to preserve the effectiveness of ARV and ensure the success of ending AIDS as public health by 2030., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

While microplastics (MP) have been found in aquatic ecosystems around the world, the understanding of drivers and controls of their occurrence and distribution have yet to be determined. In particular, their fate and transport in river catchments and networks are still poorly understood. We identified MP concentrations in water and streambed sediment at fifteen locations across the Neuse River Basin in North Carolina, USA. Water samples were collected with two different mesh sizes, a trawl net (>335 μm) and a 64 μm sieve used to filter bailing water samples. MPs >335 μm were found in all the water samples with concentrations ranging from 0.02 to 221 particles per m 3 (p m -3 ) with a median of 0.44 p m -3 . The highest concentrations were observed in urban streams and there was a significant correlation between streamflow and MP concentration in the most urbanized locations. Fourier Transform Infrared (FTIR) analysis indicated that for MPs >335 μm the three most common polymer types were polyethylene, polypropylene, and polystyrene. There were substantially more MP particles observed when samples were analyzed using a smaller mesh size (>64 μm), with concentrations ranging from 20 to 130 p m -3 and the most common polymer type being polyethylene terephthalate as identified by Raman spectroscopy. The ratio of MP concentrations (64 μm to 335 μm) ranged from 35 to 375, indicating the 335 μm mesh substantially underestimates MPs relative to the 64 μm mesh. MPs were detected in 14/15 sediment samples. Sediment and water column concentrations were not correlated. We estimate MP (>64 μm) loading from the Neuse River watershed to be 230 billion particles per year. The findings of this study help to better understand how MPs are spatially distributed and transported through a river basin and how MP concentrations are impacted by land cover, hydrology, and sampling method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Compound-specific isotope analysis (CSIA) has become a valuable tool in understanding the fate of organic contaminants at field sites. However, its application to chlorinated benzenes (CBs), a group of toxic and persistent groundwater contaminants, has received less attention. This study employed CSIA to investigate the occurrence of natural degradation of various CBs and benzene in a contaminated aquifer. Despite the complexity of the study area (e.g., installation of a sheet pile barrier and the presence of a complex set of contaminants), the substantial enrichments in δ 13 C values (i.e., >2‰) for all CBs and benzene across the sampling wells indicate in situ degradation of these compounds. In particular, the 13 C enrichments for 1,2,4-trichlorobenzene (1,2,4-TCB) and 1,2-dichlorobenzene (1,2-DCB) display good correlations with decreasing groundwater concentrations, consistent with the effects of in situ biodegradation. Using the Rayleigh model, the extent of degradation (EoD) is estimated to be 47-99% for 1,2-DCB, and 21-73% for 1,2,4-TCB. The enrichments observed for the other CBs (1,4-DCB and chlorobenzene (MCB)) and benzene at the site are also suggestive of in situ biodegradation. Due to simultaneous degradation and production of 1,4-DCB (a major 1,2,4-TCB degradation product), MCB (from DCB degradation), and benzene (from MCB degradation), the estimation of EoD for these intermediate compounds is more complex but a modelling simulation supports in situ biodegradation of these daughter products. In particular, the fact that the δ 13 C values of MCB and benzene (i.e., daughter products of 1,2,4-TCB) are more enriched than the original δ 13 C value of their parent 1,2,4-TCB provides definitive evidence for the occurrence of in situ biodegradation of the MCB and benzene., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to correlate the indications and diagnostic yield of exome sequencing (ES) in adult patients across various clinical settings. The secondary aim was to examine the clinical utility of ES in adult patients., Methods: Data on demographics, clinical indications, results, management changes, and cascade testing were collected for 250 consecutive patients who underwent ES through an adult genetics department between 2016 and 2021. Data were analyzed using descriptive and inferential statistics. Testing in which traditional gene panels were in standard use, such as in heritable cancers, was excluded., Results: The average age at testing was 43 years (range = 17-80 years). A molecular diagnosis was identified in 29% of patients. Older age at symptom onset did not pre-exclude a substantial diagnostic yield. Patients with syndromic intellectual disability and multiple system disorders had the highest yield. In >50% of patients with an exome diagnosis, the results changed management. Cascade testing occured in at least one family member for 30% of patients with a diagnosis. Diagnostic results had reproductive implications for 26% of patients and 31% of patients' relatives., Conclusion: ES has a robust diagnostic yield and clear clinical utility in adult patients across a range of ages and phenotypes., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Purpose: Our institution introduced a patient-specific heart constraint (PSHC) and a mean heart dose (MHD) constraint of 4 Gy for all patients receiving breast radiation therapy (RT) with a simultaneous boost (SIB). This was introduced as a method to calculate the predicted MHD before optimizing IMRT fields. We sought to determine whether the introduction of a PSHC reduced MHD, while maintaining optimally dosed treatment plans., Material/methods: Patients were retrospectively divided into 2 groups, pre- and postintroduction of the PSHC. The breast and SIB Planning Target Volumes (PTVs) were prescribed to 50 Gy and 57 Gy, respectively, in 25 fractions. Plans were generated using a hybrid IMRT technique, 30 Gy using an open tangential field arrangement, and 27 Gy using IMRT fields. The PSHC was calculated using MHD of open tangential field × 2. A paired t test compared PTV coverage and heart doses between cohorts (P < .05 significant)., Results: A total of 264 patients were included (138 pre-PSHC and 126 post-PSHC) with 137 right-sided and 127 left-sided treatments. MHD was significantly reduced across both right-sided (-0.4 Gy, P < .0001) and left-sided (-1.2 Gy, P < .0001) treatments overall. Left-sided treatments were further examined between free breathing and deep inspiration breath-hold (DIBH). DIBH showed reduction in MHD, although it was not significant (-0.46 Gy, P = .34). Heart V5 Gy showed reduction in right-sided (-1%, P = .002) and left-sided (-9.2%, P < .0001) treatments overall. Left-sided free breathing showed significant reduction (-8.8%, P < .0001), and DIBH also showed significant reduction (-5.1%, P = .0034). Tumor bed doses remained above the 54.15 Gy (95% of 57 Gy) threshold for all plans., Conclusion: Introduction of a PSHC can reduce MHD and V5 Gy for patients receiving whole breast RT with SIB while maintaining optimally dosed plans, with the greatest benefit shown for left-sided, free-breathing treatments., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Currently there is no secured ongoing funding in Australia for next generation sequencing (NGS) such as exome sequencing (ES) for adult neurological disorders. Studies have focused on paediatric populations in research or highly specialised settings, utilised standard NGS pipelines focusing only on small insertions, deletions and single nucleotide variants, and not explored impacts on management in detail. This prospective multi-site study performed ES and an extended bioinformatics repeat expansion analysis pipeline, on patients with broad phenotypes (ataxia, dementia, dystonia, spastic paraparesis, motor neuron disease, Parkinson's disease and complex/not-otherwise-specified), with symptom onset between 2 and 60 years. Genomic data analysis was phenotype-driven, using virtual gene panels, reported according to American College of Medical Genetics and Genomics guidelines. One-hundred-and-sixty patients (51% female) were included, median age 52 years (range 14-79) and median 9 years of symptoms. 34/160 (21%) patients received a genetic diagnosis. Highest diagnostic rates were in spastic paraparesis (10/25, 40%), complex/not-otherwise-specified (10/38, 26%) and ataxia (7/28, 25%) groups. Findings were considered 'possible/uncertain' in 21/160 patients. Repeat expansion detection identified an unexpected diagnosis of Huntington disease in an ataxic patient with negative ES. Impacts on management, such as more precise and tailored care, were seen in most diagnosed patients (23/34, 68%). ES and a novel bioinformatics analysis pipepline had a substantial diagnostic yield (21%) and management impacts for most diagnosed patients, in heterogeneous, complex, mainly adult-onset neurological disorders in real-world settings in Australia, providing evidence for NGS and complementary multiple, new technologies as valuable diagnostic tools., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Cerebral metabolic rate of oxygen (CMRO 2 ), a measure of global oxygen metabolism, reflects resting cellular activity. The mechanisms underlying fatigue and cognitive dysfunction in multiple sclerosis (MS) remain unknown. If fatigue indeed reflects ongoing autoimmune activity and cortical reorganization, and cognitive decline is the result of gray matter atrophy and white matter degeneration, we postulate that changes in CMRO 2 should reflect disease activity and predict these symptoms., Objective: We sought to utilize T 2 -Relaxation-Under-Spin-Tagging (TRUST) and phase-contrast (PC) MRI to measure global CMRO 2 to understand its relationships to white matter microstructure, fatigue and cognitive dysfunction., Methods: We measured venous oxygenation (TRUST) and cerebral blood flow (PC-MRI) in superior sagittal sinus to calculate global CMRO 2 and diffusion tensor imaging (DTI) to evaluate white matter microstructure in healthy controls (HC) and MS patients. Participants underwent neuropsychological examinations including Modified Fatigue Impact Scale (MFIS) and Symbol-Digit-Modalities Test (SDMT)., Results: We observed lower CMRO 2 in MS patients compared to HC. After controlling for demographic and disease characteristics (i.e., age, education, disability, lesion volume), CMRO 2 predicted increased fatigue (MFIS) and reduced cognitive performance (SDMT) in MS patients. Finally, MS patients with higher CMRO 2 have reduced FA in normal-appearing white-matter., Conclusion: Altogether, these results suggest that increased CMRO 2 reflects ongoing demyelination and autoimmune activity which plays an important role in both fatigue and cognitive dysfunction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Child stunting is a public health problem in Malawi. In 2014, the Government of Malawi launched the Right Foods at the Right Time (RFRT) program in Ntchisi district delivering nutrition social and behavior change communication, a small-quantity lipid-based nutrient supplement to children 6-23 months, and nutrition sensitive activities. Monitoring and evaluation (M&E) systems are key aspects of successful program implementation. We describe these and the methodology for an impact evaluation that was conducted for this program. Two monitoring systems using traditional and electronic platforms were established to register and track program delivery and processes including number of eligible beneficiaries, worker performance, program participation, and to monitor input, output, and outcome indicators. The impact evaluation used comparative cross-sectional and longitudinal designs to assess impact on anthropometric and infant and young child feeding outcomes. Three cross-sectional surveys (base-, mid-, and end-line) and two longitudinal cohorts of children followed in 6-month intervals from 6 to 24 months of age, were conducted in sampled households in the program and a neighboring comparison district. Additional M&E included qualitative studies, a process evaluation, and a cost-effectiveness study. The current paper describes lessons from this program's M&E, and demonstrates how multiple implementation research activities can inform course-correction and program scale-up., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations., Methods: In this single-centre (Leicester, UK), prospective, controlled study, we selected cases of natural and non-suspicious unnatural death referred to Her Majesty's (HM) Coroners. We excluded cases younger than 18 years, known to have had a transmittable disease, or who weighed more than 125 kg. Each case was assessed by PMCTA, followed by autopsy. Pathologists were masked to the PMCTA findings, unless a potential risk was shown. The primary endpoint was the accuracy of the cause of death diagnosis from PMCTA against a gold standard of autopsy findings, modified by PMCTA findings only if additional substantially incontrovertible findings were identified., Findings: Between Jan 20, 2010, and Sept 13, 2012, we selected 241 cases, for which PMCTA was successful in 204 (85%). Seven cases were excluded from the analysis because of procedural unmasking or no autopsy data, as were 24 cases with a clear diagnosis of traumatic death before investigation; 210 cases were included. In 40 (19%) cases, predictable toxicology or histology testing accessible by PMCT informed the result. PMCTA provided a cause of death in 193 (92%) cases. A major discrepancy with the gold standard was noted in 12 (6%) cases identified by PMCTA, and in nine (5%) cases identified by autopsy (because of specific findings on PMCTA). The frequency of autopsy and PMCTA discrepancies were not significantly different (p=0·65 for major discrepancies and p=0·21 for minor discrepancies). Cause of death given by PMCTA did not overlook clinically significant trauma, occupational lung disease, or reportable disease, and did not significantly affect the overall population data for cause of death (p≥0·31). PMCTA was better at identifying trauma and haemorrhage (p=0·008), whereas autopsy was better at identifying pulmonary thromboembolism (p=0·004)., Interpretation: For most sudden natural adult deaths investigated by HM Coroners, PMCTA could be used to avoid invasive autopsy. The gold standard of post-mortem investigations should include both PMCT and invasive autopsy., Funding: National Institute for Health Research., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licence. Published by Elsevier Ltd.. All rights reserved.)

CD4 + T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4 + T cells, and demonstrate seemingly non-monotonic alterations in IFN-γ production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naïve CD4 + T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-γ protein production was observed in effector/memory CD4 + T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naïve CD4 + T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naïve, CD4 + T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naïve CD4 + T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4 + T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Diabetes is associated with increased susceptibility to Klebsiella pneumoniae and poor prognosis with infection. We demonstrate accelerated mortality in mice with streptozotocin-induced diabetes following tracheal instillation of K. pneumoniae. Diabetic mice recruited fewer granulocytes to the alveolar airspace and had reduced early production of CXCL1, CXCL2, IL-1β and TNF-α following tracheal instillation of K. pneumoniae-lipopolysaccharide. Additionally, TLR2 and TIRAP expression following K. pneumoniae-lipopolysaccharide exposure was decreased in hyperglycemic mice. These findings indicate that impaired innate sensing and failure to rapidly recruit granulocytes to the site of infection is a mechanism for diabetic susceptibility to respiratory K. pneumoniae infection., (Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Objective/background: The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level., Methods: Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort., Results: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p < .001). Cathepsin G expression was upregulated in histologically unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p = .03). CCL19 also co-localised with CD3 + T-cell lymphocytes in the core region, around where CCL19 was expressed., Conclusions: CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Previous studies reported an association of diabetes mellitus (DM) with TB susceptibility. Many studies were retrospective, had weak diagnostic criteria for DM, and did not assess other comorbidities. The Effects of Diabetes on Tuberculosis Severity (EDOTS) study is addressing these limitations with a longitudinal comparison of patients with TB who are classified as diabetic or normoglycemic according to World Health Organization criteria. We report interim findings after enrolling 159 of a planned 300 subjects., Methods: A cohort study of patients with TB in South India with DM or normoglycemia defined by oral glucose tolerance test (OGTT) and fasting glucose. Glycohemoglobin (HbA1c), serum creatinine, lipids, and 25-hydroxyvitamin D were measured at enrollment. Patients were monitored monthly during TB treatment, and HbA1c measurement was repeated after 3 months., Results: Of 209 eligible patients, 113 (54.1%) were classified as diabetic, 44 (21.0%) with impaired glucose tolerance, and 52 (24.9%) as normoglycemic. More patients with diabetes were detected by OGTT than by HbA1c. Diabetes was a newly received diagnosis for 37 (32.7%) in the DM group, and their median HbA1c (6.8%) was significantly lower than in those with previously diagnosed DM (HbA1c, 10.4%). Among 129 patients monitored for 3 months, HbA1c declined in all groups, with the greatest difference in patients with a newly received diagnosis of DM., Conclusions: Early EDOTS study results reveal a strikingly high prevalence of glycemic disorders in South Indian patients with pulmonary TB and unexpected heterogeneity within the patient population with diabetes and TB. This glycemic control heterogeneity has implications for the TB-DM interaction and the interpretation of TB studies relying exclusively on HbA1c to define diabetic status., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

We previously determined that burst size necrosis is the chief mode of mononuclear cell death in the lungs of mice with tuberculosis. The present study explored the link between infection-induced necrosis of mononuclear phagocytes and neutrophil accumulation in the lungs of mice challenged with one of four Mycobacterium tuberculosis strains of increasing virulence (RvΔphoPR mutant, H37Ra, H37Rv and Erdman). At all time points studied, Erdman produced the highest bacterial load and the highest proportion and number of M. tuberculosis-infected neutrophils. These parameters, and the proportion of TUNEL-positive cells, tracked with virulence across all strains tested. Differences in neutrophil infection were not reflected by levels of chemoattractant cytokines in bronchoalveolar lavage fluid, while interferon-γ (reported to suppress neutrophil trafficking to the lung in tuberculosis) was highest in Erdman-infected mice. Treating Erdman-infected mice with ethambutol decreased the proportion of mononuclear phagocytes with high bacterial burden and the ratio of infected neutrophils to infected mononuclear cells in a dose-dependent manner. We propose that faster replicating M. tuberculosis strains cause more necrosis which in turn promotes neutrophil recruitment. Neutrophils infected with M. tuberculosis constitute a biomarker for poorly controlled bacterial replication, infection-induced mononuclear cell death, and increased severity of immune pathology in tuberculosis., (Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: In patients with carotid stenosis the risk of stroke is highest in the first few days after onset of symptoms and it is low in asymptomatic patients. The ability to identify patients with a high (or low) probability of having a histologically unstable plaque might become a complimentary method that can refine the indications for surgical intervention., Methods: Two histopathologists, using validated American Heart Association criteria, independently graded plaques harvested during carotid endarterectomy. Preoperative Duplex images were independently assessed for juxtaluminal black area, plaque type, plaque area, and grey-scale median (GSM) following image normalization. Logistic regression analysis was then performed to create a model for predicting predominantly histologically unstable or stable plaques., Results: A total of 126 patients were included in the study. Based on the presence and extent of histological features including haemorrhage, thrombus, fibrous tissue, lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques were graded as predominantly stable, while 87 were predominantly unstable. Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI 1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to 6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression indicated that patients with the first two features had a 90% probability of having a histologically unstable plaque. The model was used to calculate the probability of having an unstable plaque in each patient. The receiver operating characteristic curve using the p value was 0.68 (95% CI 0.59-0.78)., Conclusions: Computerized plaque analysis has the potential to identify patients with histologically unstable carotid plaques. This model requires validation, but offers the potential to influence patient selection for emergency interventions and the monitoring of medical therapy., (Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The aim was to test the hypothesis that histologically unstable carotid plaque features were more prevalent in patients undergoing carotid endarterectomy (CEA) in the acute period after onset of symptoms and that the plaque would assume more stable histological characteristics as the delay from the most recent event increased., Methods: Seven histological features of plaque instability (haemorrhage, large lipid core, chronic plaque inflammation, chronic cap inflammation, marked vascularity, cap rupture and many foam cells) were independently quantified and then correlated with recency of symptoms in patients undergoing CEA., Results: In patients undergoing CEA ≤14 days of their last event, 87/119 (73%) exhibited ≥5/7 unstable histological plaque features, compared with 22/40 (55%) of patients undergoing delayed surgery (P = 0.048). As expected, there was a sustained decline in the prevalence of unstable plaque features in 61 patients undergoing surgery between days 7-28. However, there was then a marked increase in the prevalence of plaque haemorrhage (59% up to 65%), large lipid core (41% up to 78%), chronic plaque inflammation (71% up to 91%), cap rupture (35% up to 39%), many foam cells (24% up to 43%) and marked vascularity (71% up to 91%) in 23 patients undergoing CEA after 29 days had elapsed., Conclusion: Patients undergoing surgery ≤14 days had a significantly higher overall burden of high risk plaque features compared with those undergoing delayed CEA. However, the secondary upsurge across a range of unstable plaque features in patients undergoing CEA after ≥29 days had elapsed suggests that the relationship between recency of symptoms and plaque histology is more complex than had been anticipated in previous studies., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Many studies have evaluated histological and gene expression profiles in TIA/stroke patients after onset of symptoms, but there is limited understanding as to how these plaque related features interact before symptom onset. In particular, no studies have evaluated differential gene expression in histologically unstable (vs stable plaques) in neurologically asymptomatic patients., Methods: Nine asymptomatic patients had their plaques scored blindly by two independent Histopathologists using the AHA plaque scoring system. RNA extracted from the plaques was hybridised onto a whole genome microarray. Analysis was performed using GenomeStudio (v1.0) and the DAVID bioinformatics resource (v6.7)., Results: Three plaques were histologically unstable (Grade 2/3), while six were stable (Grade 0/1). 346 differentially expressed genes (>1.3 fold, P < 0.05) were identified (293 down-regulated and 53 up-regulated) between stable and unstable plaques. Genes related to chemokine and protein signalling (pro-inflammatory/pro-apoptotic) were identified to have high enrichment scores (>1.3) and were significantly up-regulated in unstable (asymptomatic) plaques., Conclusion: The findings confirm the intuitively held belief that changes in chemokine and protein signalling may be associated with acute plaque disruption and precede the onset of symptoms. Once validated, these genes could therefore become targets for innovative medical treatments in the future or could help identify asymptomatic patients with histologically unstable plaques that would benefit from surgical intervention., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Characterization of normal changes in the serum proteome during pregnancy may enhance understanding of maternal physiology and lead to the development of new gestational biomarkers. In 23 Nepalese pregnant women who delivered at term, two-dimensional difference in-gel electrophoresis (DIGE) was used to assess changes in relative protein abundance between paired serum samples collected in the first and third trimesters. One-hundred and forty-five of over 700 protein spots in DIGE gels (pI 4.2-6.8) exhibited nominally significant (p < 0.05) differences in abundance across trimesters. Additional filtering using a Bonferroni correction reduced the number of significant (p < 0.00019) spots to 61. Mass spectrometric analysis detected 38 proteins associated with gestational age, cytoskeletal remodeling, blood pressure regulation, lipid and nutrient transport, and inflammation. One new protein, pregnancy-specific β-glycoprotein 4 was detected. A follow-up isotope tagging for relative and absolute quantitation (iTRAQ) experiment of six mothers from the DIGE study revealed 111 proteins, of which 11 exhibited significant (p < 0.05) differences between trimesters. Four of these proteins: gelsolin, complement C1r subcomponent, α-1-acid glycoprotein, and α-1B-glycoprotein also changed in the DIGE analysis. Although not previously associated with normal pregnancy, gelsolin decreased in abundance by the third trimester (p < 0.01) in DIGE, iTRAQ and Western analyses. Changes in abundance of proteins in serum that are associated with syncytiotrophoblasts (gelsolin, pregnancy-specific β-1 glycoprotein 1 and β-2-glycoprotein I) probably reflect dynamics of a placental proteome shed into maternal circulation during pregnancy. Measurement of changes in the maternal serum proteome, when linked with birth outcomes, may yield biomarkers for tracking reproductive health in resource poor settings in future studies., (Published by Elsevier Ltd.)

Objectives: The aim of the current study was to determine whether computerised ultrasound plaque analysis could identify features predictive of an increased risk of early recurrent events after symptom onset., Methods: Between August 2008 and December 2010, 158 consecutive symptomatic patients undergoing carotid endarterectomy (CEA) had their plaques harvested at CEA and then independently scored for markers of histological plaque instability. Duplex ultrasound images recorded prior to CEA were independently assessed using the Iconsoft software., Results: One hundred and fifty eight recently symptomatic patients underwent CEA with 118 (75%) undergoing their operation within 14 days of their most recent clinical event. Twenty (12.7%) suffered a recurrent cerebral ischaemic event following admission to the vascular unit and before undergoing CEA. Using multivariate stepwise analysis; lipid core (OR 4.00, 95% CI 1.07 to 14.83, P = 0.042) and a low GSM (OR 6.21, 95% CI 1.86 to 20.4, P = 0.003) were independently associated with recurrent cerebrovascular events., Conclusion: Within a cohort of patients presenting with recent onset cerebral ischaemic events undergoing CEA, the plaques of patients with recurrent events following admission to hospital had evidence a large lipid core and a low GSM., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Modular component separation following endovascular aortic repair is recognized as a potential source of late failure. The aim of this study was to establish the extent of component separation occurring in branched and fenestrated endografts and to ascertain any factors that predict its occurrence., Design: An analysis of component relationships following fenestrated and branched endovascular aneurysm repair was conducted on all patients with >1 year of digital imaging data. A mathematical model was developed, and retrospectively applied, to determine the minimum stentgraft overlap required to preclude any risk of component separation., Results: Of the 184 patients treated prior to 2006, data (for patients with greater than 1 year follow-up) were available for 106 patients. Fourteen (13%) had evidence of inter-component movement of which 8 developed component separation (<2 stent overlap). All 8 patients with component separation, in addition to 38% of the total cohort, were identified as being at risk for eventual component separation using the mathematical model., Conclusions: Component movement is commonly observed in modular devices, but clinical consequences are rare. The degree of overlap, aneurysm diameter, aneurysm length, and stentgraft diameter can be used to predict the risk of inter-component movement which may result in component separation.

Purpose: To evaluate a novel approach to preserve pelvic perfusion during endovascular AAA repair in patients with common iliac aneurysms extending to the iliac bifurcation., Materials and Methods: A multicenter prospective analysis of patients undergoing implantation of a branched endograft designed to perfuse the internal iliac artery was conducted. All patients enrolled were considered high risk for open surgical repair and presented with common iliac artery aneurysms greater than 20mm and anatomy amenable to implant the branched device. Preoperative high resolution spiral CT, and follow-up CT studies in addition to abdominal radiographs were obtained at discharge, 1, 6, 12, and 24 months., Results: Between 2003 and 2006, 52 patients (53 internal iliacs) were implanted with an investigational device. Mean common iliac aneurysm maximal diameter was 38 mm. The branch graft was combined with a proximal standard bifurcated component (61%), a fenestrated or a visceral branch component (33%), an aortouni-iliac component (2%), and alone in 2 patients (4%, following prior aortobi-iliac repair). Technical success was achieved in 94% of patients. Within the first month, 6 (11%) internal iliac branches occluded. No occlusions were noted after 1 month. The mean follow-up was 14.2 months. Common iliac aneurysm shrinkage was noted in 42% and 81% of patients at 6 and 12 months. There were no rupture, aneurysm related deaths or conversions, but there were 7 deaths during follow-up., Conclusions: The placement of endovascular prostheses that maintain antegrade perfusion of one or both internal iliac arteries is feasible, and early results provide evidence for optimism with regard to safety and efficacy.

Objectives: To evaluate the use of novel technology to treat complex aortic aneurysms involving branches that provide critical end-organ blood supply., Methods: A prospective study was conducted in patients with thoracoabdominal, suprarenal, or common iliac aneurysms (TAA, SRA, or CIA) at high risk for open surgical repair. An endovascular graft using the Zenith platform was customized to fit patient anatomy (TAA or SRA) and combined with Jomed balloon-expandable stent-grafts. Prefabricated hypogastric branches were used with a Zenith abdominal aortic aneurysm (AAA) or Fluency self-expanding fenestrated device in conjunction with a self-expanding stent-graft. Analyses were conducted in accordance with the endovascular aneurysm reporting standards document. Follow-up studies occurred at discharge, 1, 6, and 12 months, and included computed tomography and duplex ultrasound scans, and flat plate radiography., Results: Fifty patients were treated (9 TAA, 20 SRA, 21 CIA). The mean aneurysm size was 7.6 cm (TAA), 7.2 cm (SRA), and 6.1 cm AAA size associated with a mean CIA size of 3.8 cm. Bilateral CIA aneurysms were present in 86% (18/21) of patients with CIA aneurysms. Perioperative mortality was 2% (1/50) and resulted from a myocardial infarction after a planned conduit and iliac endarterectomy required for device access. Five late deaths occurred (2 TAA, 2 SRA, 1 CIA), three of which (2 TAA, 1 SRA) were aneurysm related. Failure to access internal iliac arteries occurred in three cases, and two late hypogastric branch thromboses occurred. No visceral branches were lost acutely or occluded during follow-up. Sac shrinkage (>5 mm) was noted in 65% of patients at 6 months and in all patients (10/10) by 12 months. There were no ruptures or conversions, but nine patients required secondary interventions., Conclusions: Branch vessel technology has made it technically feasible to preserve critical end-organ perfusion in the setting of CIA, SRA, and TAA aneurysms. The relatively low acute mortality rate and lack of short-term branch vessel loss are encouraging and merit further investigation. These advances have the potential to markedly diminish the complications associated with conventional management of complex aneurysms.

Waist circumference (WC) has been postulated to have stronger associations with biomarkers of coronary heart disease (CHD) than BMI. In this study, we measured the level of activity by determining steps walked per day and select biomarkers for CHD risk in 80 overweight or obese (BMI = 25-37 kg/m(2)) premenopausal women to evaluate whether these biomarkers are associated with WC or BMI. The plasma biomarkers measured, using samples from women who had fasted for 12 h, were lipids, apolipoproteins (apo), LDL peak diameter, LDL susceptibility to oxidation, glucose, leptin, and insulin. We identified subjects with the metabolic syndrome (11%) and insulin resistance (30%) to further distinguish subjects at increased risk for CHD. Both BMI and WC were positively correlated with insulin (r = 0.376 and 0.384, respectively, P < 0.05) and leptin (r = 0.614 and 0.512, respectively, P < 0.01) and negatively correlated with the number of steps taken per day (r = -0.245 and -0.354, respectively, P < 0.05). In addition, WC had positive correlations with diastolic blood pressure (r = 0.250, P < 0.05), plasma triglycerides (TG) (r = 0.270, P < 0.05), and apo C-III (r = 0.240, P < 0.05). Women with BMI > or = 30 kg/m(2) or WC > 88 cm had significantly higher leptin concentrations than women having a BMI < 30 kg/m(2) or a WC < or = 88 cm; women with WC > 88 cm also had higher diastolic pressure (P < 0.05), and higher plasma TG (P < 0.05) and apo C-III (P < 0.05) concentrations than those with WC < or = 88. In addition, subjects with the higher WC walked an average of 1000 fewer steps per day (P < 0.01). These results suggest that WC is a stronger predictor of CHD risk than BMI and is more closely associated with the level of exercise in premenopausal women.

This study used receiver operating characteristic analysis to investigate the properties of area under the concentration-time curve during the first 4h after cyclosporin-microemulsion dosing (AUC0-4) and cyclosporin (CyA) levels immediately before and at 2 and 3h after dosing (C0, C2 and C3) to predict the risk of biopsy-proven acute rejection (AR) at 6 months. Ninety-eight kidney transplant recipients treated with CyA-microemulsion-based triple therapy immunosuppression were studied on post-transplant days 3, 5, and 7, and at increasing intervals thereafter. The most sensitive and specific predictor of AR was AUC0-4. Of the single time-point measurements, the measurement properties of C2 were closest to those of AUC0-4, and superior to those of C3. The relationship between C0 and subsequent AR was weak and did not reach statistical significance. On day 3, CyA AUC0-4 > or = 4,400 ng.h/mL and C2 > or = 1,700 ng/mL were each associated with a 92% negative predictive value for rejection in the first 6months. Pharmacokinetic measurements on or after day 5, and measurements on day 3 in patients with delayed graft function, were not predictive of AR. Adequate exposure within the first 3days post transplantation may be critically important in preventing subsequent rejection.

Land-use changes and associated river discharges in coastal tropical regions present a global threat to coral reef environments. This study investigated the temporal variation in biological oxygen demand (BOD5) and suspended particulate matter (SPM) at the mouths of seven rivers on Okinawa Island (Japan) over 20 years. We report strong positive relationships between human population densities within river catchment areas and both average BOD5 concentration (r2 = 0.968; p < 0.001) and SPM (r2 = 0.659; p < 0.003) at the mouths of the rivers. At the reef adjacent to one river (Hija River, 50.2 km2 catchment area) we applied moving window analysis to assess an optimal sampling strategy for elucidating transitional boundaries in coral composition from the river mouth to a point where the effect of river discharge was minimal. The optimal window width for Okinawan rivers was five 1 m2 quadrats spaced over 5 m intervals. This sampling strategy clearly showed dissimilarity spikes in coral community composition up to 400 m from the Hija River mouth, beyond which no significant differences in coral composition were detected using analysis of similarities (ANOSIM). We developed a simple diffusion model linking the rivers' maximum discharge rate, and the average concentration of BOD5 and SPM with the spatial impact on the coral communities. The diffusion model can aid in predicting negative shifts in coral communities expected to result from detrimental land-use changes and is an important tool for monitoring coral reefs.

Several new families of ARF GTPase activating proteins (ARF GAPs) have been described recently that associate with paxillin and other cytoskeletal and signaling proteins. Important insights have been gained regarding their subcellular distribution, enzymatic specificity and protein scaffold function. Evidence suggests an important role for ARF GAPs in mediating changes in the cell's actin cytoskeleton in response to adhesion and growth factor stimulation.

Background: Zinc deficiency may result in abnormal dark adaptation or night blindness, a symptom primarily of vitamin A deficiency. During a placebo-controlled trial in Nepal, weekly vitamin A supplementation of women reduced but failed to eliminate the incidence of night blindness during pregnancy, suggesting a role for zinc., Objective: The study examined the efficacy of daily zinc supplementation in restoring night vision of pregnant women who developed night blindness while routinely receiving either vitamin A, beta-carotene, or placebo in a field trial., Design: Women (n = 202) who reported to be night blind during pregnancy were randomly assigned in a double-blind manner, stratified on vitamin A, beta-carotene, or placebo receipt, to receive 25 mg Zn or placebo daily for 3 wk. Thus, the 6 groups studied were as follows: beta-carotene + zinc, beta-carotene alone, vitamin A + zinc, vitamin A alone (vitamin A + placebo), zinc alone (zinc + placebo), and placebo (2 placebos: one for the vitamin A or beta-carotene study and one for the zinc study). Women underwent a clinic-based assessment that included pupillary threshold testing and phlebotomy before and after supplementation. Supplement use and daily history of night blindness were obtained at home twice every week., Results: Zinc treatment increased serum zinc concentrations, but alone (zinc alone group), failed to restore night vision or to improve dark adaptation. However, women in the vitamin A + zinc group who had baseline serum zinc concentrations <9.9 micromol/L were 4 times more likely to have their night vision restored (95% CI: 1.1, 17.3) than were women in the placebo group and tended to have a small improvement in pupillary threshold scores (by 0.21 log candela/m2; P = 0.09)., Conclusion: These data suggest that zinc potentiated the effect of vitamin A in restoring night vision among night-blind pregnant women with low initial serum zinc concentrations.

Night blindness occurs commonly among women during pregnancy in rural NEPAL: We examined the relationship between maternal night blindness and the risk of mortality occurring among infants in the first 6 mo of life. Stratified analysis by maternal night blindness status during pregnancy was done for 10,000 women participating in a randomized, placebo-controlled trial of vitamin A and beta-carotene supplementation. Mortality of infants of non-night blind women in all three supplementation groups was similar, and when combined, was 63/1000 live births. Relative to this, mortality was higher by 63% [95% confidence interval (CI): 9-138%) and 50% (95% CI: -3 to 133%) among infants of night blind women receiving placebo and beta-carotene, respectively, but only by 14% (95% CI: -33 to 93%) among those receiving vitamin A. Thus, 6-mo mortality was higher among infants of women who had night blindness during pregnancy. Maternal receipt of vitamin A reduced this risk.

SU5416 and SU6668 are potent antiangiogenic small-molecule inhibitors of receptor tyrosine kinases, including those of the vascular endothelial growth factor and platelet-derived growth factor receptor families. The stem cell factor (SCF) receptor, c-kit, is structurally related to these receptors and, although not expressed on mature peripheral blood cells, is expressed in leukemic blasts derived from 60% to 80% of acute myeloid leukemia (AML) patients. The c-kit kinase inhibitory activity of SU5416 and SU6668 was evaluated in MO7E cells, a human myeloid leukemia cell line. Tyrosine autophosphorylation of the receptor, induced by SCF, was inhibited in these cells by SU5416 and SU6668 in a dose-dependent manner (inhibitory concentration of 50% [IC(50)] 0.1-1 microM). Inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, a signaling event downstream of c-kit activation, was also inhibited in a dose-dependent manner. Both compounds also inhibited SCF-induced proliferation of MO7E cells (IC(50) 0.1 microM for SU5416; 0.29 microM for SU6668). Furthermore, both SU5416 and SU6668 induced apoptosis in a dose- and time-dependent manner as measured by the increase in activated caspase-3 and the enhanced cleavage of its substrate poly(ADP-ribose) polymerase. These findings with MO7E cells were extended to leukemic blasts from c-kit(+) patients. In patient blasts, both SU5416 and SU6668 inhibited SCF-induced phosphorylation of c-kit and ERK1/2 and induced apoptosis. These studies indicate that SU5416 and SU6668 inhibit biologic functions of c-kit in addition to exhibiting antiangiogenic properties and suggest that the combination of these activities may provide a novel therapeutic approach for the treatment of AML.

Objective: This paper compares the accuracy of visual estimations of children's food intake in settings where several children eat together off 1 plate vs individual-plate eating scenarios., Design: Eight trained observers were tested in their ability to estimate food portions consumed by children enacting common eating scenarios. Foods were categorized by food group and according to their presentation by individual-plate and shared-plate. Observed food weight estimates were compared to actual weights., Subjects/setting: The 8 observers visually estimated 69 food portions of children eating alone and 26 portions where children were eating from a shared plate. This study was carried out in Sarlahi District, a rural, central lowland region of Nepal., Statistical Analyses: Pearson's correlation coefficients were calculated to examine associations between estimated and actual weights. A fixed effects model was constructed to compare observers., Results: Analyses revealed that observer estimates of food weights under field conditions were well correlated with actual weights for individual-plate (r = 0.89) and for shared-plate (r = 0.84) scenarios. Observers estimated food weights when children ate together on a shared plate less accurately than they did in settings where children ate alone. With the exception of 1 observer, observers did not differ significantly in their ability to estimate food weights. Accuracy of estimations was influenced by food weight with greater error associated with food quantities of less than 70 g., Conclusions: Visual estimation is a relatively accurate, valid method of assessing child food intake under rural field conditions, and the only method to obtain accurate information on dietary intake in regions where shared-plate eating is frequent.

The contribution of nutritional interventions to the reduction in maternal morbidity rates in developing countries is not well known. We assessed the impact of weekly vitamin A and beta-carotene supplementation on the prevalence of pregnancy and postpartum illness symptoms among 15,832 Nepali women in a placebo-controlled, double-masked, cluster-randomized trial. There was no impact of either supplement on morbidity rates reported up to 28 wk of gestation, inclusive. However, in late pregnancy (>28 wk), symptoms of nausea, faintness and night blindness were reduced with vitamin A, but not beta-carotene, supplementation. Vitamin A supplementation shortened the length of labor by 1.5 h 50 min among nulliparous and multiparous women, respectively. Both interventions reduced the postpartum prevalence of at least four loose stools and night blindness. beta-Carotene supplementation also reduced symptoms of high fever postpartum. The mean number of days of any reported illness symptoms was 3-4 per wk throughout pregnancy. Among women receiving vitamin A, the total number of days of illness symptoms accrued over the last 12 wk of pregnancy was lower by 5 d compared with the placebo recipients. We found the burden of pregnancy-related illness symptoms to be high in this rural area of Nepal where antenatal care is poor and most deliveries occur at home. Maternal vitamin A or beta-carotene supplementation resulted in a reduction in the prevalence of selected illness symptoms during late pregnancy, at the time of birth and during 6 mo postpartum, suggesting that a diet adequate in vitamin A may be important for improving women's reproductive health.

Background: Impaired dark adaptation occurs commonly in vitamin A deficiency., Objective: We sought to examine the responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in Nepali women., Design: The dark-adapted pupillary response was tested in 298 pregnant women aged 15-45 y in a placebo-controlled trial of vitamin A and beta-carotene; 131 of these women were also tested at 3 mo postpartum. Results were compared with those for 100 nonpregnant US women of similar age. The amount of light required for pupillary constriction was recorded after bleaching and dark adaptation., Results: Pregnant women receiving vitamin A had better dark-adaptation thresholds (-1.24 log cd/m(2)) than did those receiving placebo (-1.11 log cd/m(2); P: = 0. 03) or beta-carotene (-1.13 log cd/m(2); P: = 0.05) (t tests with Bonferroni correction). Dark-adaptation threshold was associated with serum retinol concentration in pregnant women receiving placebo (P: = 0.001) and in those receiving beta-carotene (P: = 0.003) but not in those receiving vitamin A. Among women receiving placebo, mean dark-adaptation thresholds were better during the first trimester (-1.23 log cd/m(2)) than during the second and third trimesters (-1.03 log cd/m(2); P: = 0.02, t test). The mean threshold of nonpregnant US women (-1.35 log cd/m(2)) was better than that of all 3 Nepali groups (P: < 0.001, t test, for all 3 groups)., Conclusions: During pregnancy, pupillary dark adaptation was strongly associated with serum retinol concentration and improved significantly in response to vitamin A supplementation. This noninvasive testing technique is a valid indicator of population vitamin A status in women of reproductive age.

Anemia and iron deficiency during pregnancy are prevalent in developing countries, but their causes are not always known. We assessed the prevalence and severity of anemia and iron deficiency and their association with helminths, malaria and vitamin A deficiency in a community-based sample of 336 pregnant women in the plains of Nepal. Hemoglobin, erythrocyte protoporphyrin (EP) and serum ferritin were assessed in venous blood samples. Overall, 72.6% of women were anemic (hemoglobin < 110 g/L), 19.9% had moderate to severe anemia (hemoglobin < 90 g/L) and 80.6% had iron deficiency (EP > 70 micromol/mol heme or serum ferritin < 10 microg/L). Eighty-eight percent of cases of anemia were associated with iron deficiency. More than half of the women (54.2%) had a low serum retinol concentration (<1.05 micromol/L), 74.2% were infected with hookworms and 19.8% had Plasmodium vivax malaria parasitemia. Hemoglobin, EP and serum ferritin concentrations were significantly worse and the prevalence of anemia, elevated EP and low serum ferritin was increased with increasing intensity of hookworm infection. Hookworm infection intensity was the strongest predictor of iron status, especially of depleted iron stores. Low serum retinol was most strongly associated with mild anemia, whereas P. vivax malaria and hookworm infection intensity were stronger predictors of moderate to severe anemia. These findings reinforce the need for programs to consider reducing the prevalence of hookworm, malaria infection and vitamin A deficiency where indicated, in addition to providing iron supplements to effectively control anemia.

Background: Wheat flour is a possible food vehicle for vitamin A fortification., Objective: This study assessed the efficacy of consumption of a vitamin A-fortified wheat-flour bun (pandesal) on the vitamin A status of school-age children., Design: This was a double-masked clinical trial conducted in 396 and 439 children aged 6-13 y attending 4 rural schools in the Philippines. The children were randomly assigned to a vitamin A-fortified (experimental) or nonfortified (control) group. A 60-g vitamin A-fortified pandesal (containing approximately 133 microg retinol equivalents) or a nonfortified pandesal was consumed by the children 5 d/wk for 30 wk. Vitamin A status, hemoglobin concentration, anthropometric status, morbidity, and dietary intake were assessed at baseline and 30 wk later. A modified relative dose response (MRDR) was assessed in a subsample of 20% of the children ( approximately 75/group) with the lowest initial serum retinol concentration at the 30-wk follow-up., Results: Baseline serum retinol significantly modified the effect of the intervention. The fortified group, whose initial serum retinol concentrations were below the median, had a 0.07 +/- 0.03-micromol/L greater improvement in serum retinol at the 30-wk follow-up than did the control group (P: = 0.02). Improved vitamin A status was also evident in the MRDR subsample. End-of-study differences in the MRDR showed that vitamin A- fortified pandesal intake decreased the percentage of children with inadequate liver vitamin A stores by 50% (15.3% compared with 28.6%; P: = 0.05)., Conclusions: Daily consumption of vitamin A-fortified pandesal significantly improved the vitamin A status of Filipino school-age children with marginal-to-low initial serum retinol concentrations.

Background: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear., Objective: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness)., Design: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk., Results: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins., Conclusions: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.

Background: The effect of vitamin A supplementation on the survival of infants aged <6 mo is unclear. Because most infant deaths occur in the first few month of life, maternal supplementation may improve infant survival., Objectives: The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants <6 mo of age., Design: Married women of reproductive age in 270 wards of Sarlahi district, Nepal, were eligible to participate. Wards were randomly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate (vitamin A), 42 mg all-trans-beta-carotene, or placebo. Pregnancies were followed until miscarriage, stillbirth, maternal death, or live birth of one or more infants, who were followed through 24 wk of age., Results: A total of 43559 women were enrolled; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial. The rate of fetal loss was 92.0/1000 pregnancies in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.06 (95% CI: 0.91, 1.25) and 1.03 (95% CI: 0.87, 1.19), respectively. The 24-wk mortality rate was 70.8/1000 live births in the placebo group, comparable with rates in the vitamin A and beta-carotene groups, which had relative risks of 1.05 (95% CI: 0.87, 1.25) and 1.03 (95% CI: 0.86, 1.22), respectively., Conclusions: Small weekly doses of vitamin A or beta-carotene given to women before conception, during pregnancy, and through 24 wk postpartum did not improve fetal or early infant survival in Nepal.