A proposed methodology for uncertainty extraction and verification in priority setting partnerships with the James Lind Alliance: an example from the Common Conditions Affecting the Hand and Wrist Priority Setting Partnership.

BACKGROUND: To report our recommended methodology for extracting and then confirming research uncertainties - areas where research has failed to answer a research question - derived from previously published literature during a broad scope Priority Setting Partnership (PSP) with the James Lind Alliance (JLA). METHODS: This process was completed in the UK as part of the PSP for "Common Conditions Affecting the Hand and Wrist", comprising of health professionals, patients and carers and reports the data (uncertainty) extraction phase of this. The PSP followed the robust methodology dictated by the JLA and sought to identify knowledge gaps, termed "uncertainties" by the JLA. Published Cochrane Systematic Reviews, Guidelines and Protocols, NICE (National Institute for Health and Care Excellence) Guidelines, and SIGN (Scottish Intercollegiate Guidelines Network) Guidelines were screened for documented "uncertainties". A robust method of screening, internally verifying and then checking uncertainties was adopted. This included independent screening and data extraction by multiple researchers and use of a PRISMA flowchart, alongside steering group consensus processes. Selection of research uncertainties was guided by the scope of the Common Conditions Affecting the Hand and Wrist PSP which focused on "common" hand conditions routinely treated by hand specialists, including hand surgeons and hand therapists limited to identifying questions concerning the results of intervention, and not the basic science or epidemiology behind disease. RESULTS: Of the 2358 records identified (after removal of duplicates) which entered the screening process, 186 records were presented to the PSP steering group for eligibility assessment; 79 were deemed within scope and included for the purpose of research uncertainty extraction (45 full Cochrane Reviews, 18 Cochrane Review protocols, 16 Guidelines). These yielded 89 research uncertainties, which were compared to the stakeholder survey, and added to the longlist where necessary; before derived uncertainties were checked against non-Cochrane published systematic reviews. CONCLUSIONS: In carrying out this work, beyond reporting on output of the Common Conditions Affecting the Hand and Wrist PSP, we detail the methodology and processes we hope can inform and facilitate the work of future PSPs and other evidence reviews, especially those with a broader scope beyond a single disease or condition.

Room temperature mid-infrared fiber lasing beyond 5 µm in chalcogenide glass small-core step index fiber.

This Letter, to the best of our knowledge, reports mid-infrared fiber lasing beyond 5 µm at room temperature for the first time, Ce3+-doped, chalcogenide glass, step index fiber employed in-band pumping with a 4.15 µm quantum cascade laser. The lasing fiber is was 64 mm long, with a calculated numerical aperture of 0.48 at the lasing wavelengths. The core glass was Ge15As21Ga1Se63 atomic % (at. %), doped with 500 parts-per-million-by-weight Ce, with a 9 µm core diameter. The cladding glass was Ge21Sb10Se69 at. % with a 190 µm outer diameter. As pump power increases continuous wave lasing corresponding to the 2F7/2→2F5/2, transition in the Ce3+ ion occurs at 5.14 µm, 5.17 µm, and 5.28 µm.

Human model of burn injury that quantifies the benefit of cooling as a first aid measure.

BACKGROUND: Burn injuries are a major cause of morbidity and mortality worldwide. Cooling is widely practised as a first aid measure, but the efficacy of cooling burns in human skin has not been demonstrated. A safe, consistent, ethically acceptable model of burning and cooling in live human skin in vivo was developed, and used to quantify the effects of cooling. METHODS: Novel apparatus was manufactured to create and cool burns in women who were anaesthetized for breast reconstruction surgery using a deep inferior epigastric artery perforator flap. Burns were excised between 1 and 3 h after creation, and analysed using histopathological assessment. RESULTS: All 25 women who were approached agreed to take part in the study. There were no adverse events. Increased duration of contact led to increased burn depth, with a contact time of 7·5 s at 70°C leading to a mid-dermal burn. Burn depth progressed over time following injury, but importantly this was modified by cooling the burn at 16°C for 20 min. On average, cooling salvaged 25·2 per cent of the dermal thickness. CONCLUSION: This study demonstrated the favourable effects of cooling on human burns. Public heath messaging should emphasize cooling as first aid for burns. This model will allow analysis of the molecular effects of cooling burns, and provide a platform for testing novel therapies aimed at reducing the impact of burn injury.

ANTECEDENTES: Las lesiones por quemadura son una causa importante de morbilidad y mortalidad en todo el mundo. El enfriamiento de las quemaduras se practica ampliamente como medida de primeros auxilios, pero no se ha demostrado su eficacia en la piel de los seres humanos. Para cuantificar los efectos del enfriamiento, se desarrolló un modelo de quemadura y enfriamiento en piel humana in vivo, seguro, estable y éticamente aceptable. MÉTODOS: Se construyó un dispositivo nuevo para crear y enfriar quemaduras en pacientes que fueron anestesiadas para una reconstrucción mamaria utilizando un colgajo perforante de la arteria epigástrica inferior profunda. Las quemaduras se extirparon entre una y tres horas después de su producción y se analizaron por evaluación histopatológica. Para determinar la significación estadística entre grupos se utilizó las pruebas de ANOVA o de t pareadas, según correspondiera. RESULTADOS: Aceptaron participar en el estudio las 25 pacientes a las que se propuso. No hubo efectos adversos. La mayor duración del contacto conllevó un aumento en la profundidad de la quemadura: con un tiempo de contacto de 7,5 segundos a 70°C se obtuvo una quemadura dérmica de segundo grado. La profundidad de la quemadura aumentó con el tiempo de exposición, pero mejoró de forma sustancial al enfriar la quemadura a 16°C durante 20 minutos. El enfriamiento salvó el 25% del espesor dérmico como promedio. CONCLUSIÓN: Este es el primer estudio que demuestra los efectos favorables del enfriamiento sobre las quemaduras humanas. Los consejos de salud deberían hacer más énfasis en el enfriamiento como forma de primeros auxilios en las quemaduras. Este modelo permitirá identificar los efectos moleculares del enfriamiento en las quemaduras y proporcionará una plataforma para probar nuevos tratamientos encaminados a reducir el impacto de las lesiones por quemadura.

Modeling of resonantly pumped mid-infrared Pr3+-doped chalcogenide fiber amplifier with different pumping schemes.

We propose a model for resonantly pumped Pr3+-doped chalcogenide fiber amplifiers, which includes excited state absorption and the full spectral amplified spontaneous emission spanning from 2 µm to 6 µm. Based on this model, the observed near- and mid-infrared photoluminescence generated from Pr3+-doped chalcogenide fiber is explained. Then the output properties of a 4.1 µm resonantly pumped Pr3+-doped chalcogenide fiber amplifier are simulated in both co- and counter-pumping schemes. Results show that the 4.1 µm counter-pumped fiber amplifier can achieve a power conversion efficiency (PCE) of over 62.8% for signal wavelengths ranging from 4.5 µm to 5.3 µm. This is, to our best knowledge, the highest simulated PCE for a Pr3+-doped chalcogenide fiber amplifier.

Carers' experiences of home enteral feeding: A survey exploring medicines administration challenges and strategies.

WHAT IS KNOWN AND OBJECTIVES: The use of enteral tube feeding at home is becoming more widespread, with patients ranging in age and diseases. Dysphagia and swallowing difficulties can compromise nutritional intake and the administration of oral medications, affecting therapeutic outcomes negatively. Carers' experiences of medicines administration and medicines optimization have not been explored fully. The objectives of this study were to identify issues carers experience in medicines administration; the strategies they have developed to cope; and suggestions to improve the medicines administration process. METHODS: An online survey was promoted nationally; 42 carers completed it. Descriptive statistical analysis was applied, as well as thematic analysis of open-ended responses. Results were compared against the 4 principles of medicines optimization. RESULTS AND DISCUSSION: 93% of respondents administered medications with enteral feeding tubes, but only 62% had received advice from healthcare professionals and only 8% had received written information on how to do so. Responses identified 5 medicines administration issues experienced by carers; 4 strategies they developed to cope; and 3 main areas of suggestions to improve medicines administration via enteral feeding at home. WHAT IS NEW AND CONCLUSION: The 4 principles of medicines optimization have not previously been applied to enteral feeding. We present a novel account of carers' experiences, for example coping with ill-suited formulations and a lack of training and support, which should inform better practice (Principle 1). Carers sometimes experience suboptimal choice of medicines (Principle 2). Carers' practices are not always well-informed and may affect therapeutic outcomes and safety (Principle 3). There is scope for improvement in carer training, education and support to better support medicines optimization (Principle 4).

Randomized feasibility trial of replacing or discarding the nail plate after nail-bed repair in children.

BACKGROUND: Nail-bed injuries are the most common hand injury in children. Surgical dogma is to replace the nail plate after repairing the nail bed. Recent evidence suggests this might increase infection rates and returns to clinic. The aim of this feasibility trial was to inform the design and conduct of a definitive trial comparing replacing or discarding the nail plate after nail-bed repair. METHODS: This study recruited participants from four hand units in the UK between April and July 2015. Participants were children under the age of 16 years with a nail-bed injury requiring surgery. They were randomized to either having the nail plate replaced or discarded after nail-bed repair. The follow-up method was also allocated randomly (postal versus clinic). Information was collected on complications at 2 weeks and 30 days, and on nail-plate appearance at 4 months using the Zook classification. Two possible approaches to follow-up were also piloted and compared. RESULTS: During the recruitment phase, there were 156 potentially eligible children. Sixty were randomized in just over 3 months using remote web-based allocation. By 2 weeks, there were two infections, both in children with replaced nail plates. The nail-replaced group also experienced more complications. There was no evidence of a difference in return rates between postal and clinic follow-up. CONCLUSION: Recruitment was rapid and nail-bed repair appeared to have low complication and infection rates in this pilot trial. The findings have led to revision of the definitive trial protocol, including the mode and timing of follow-up, and modification of the Zook classification.

A feasibility study testing four hypotheses with phase II outcomes in advanced colorectal cancer (MRC FOCUS3): a model for randomised controlled trials in the era of personalised medicine?

BACKGROUND: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies. PATIENTS AND METHODS: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload. RESULTS: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival. CONCLUSIONS: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.

Superior photoluminescence (PL) of Pr³âº-In, compared to Pr³âº-Ga, selenide-chalcogenide bulk glasses and PL of optically-clad fiber.

The photoluminescent-(PL)-properties of Pr³âº-ions in indium-containing selenide-chalcogenide bulk-glasses are found to be superior when compared with gallium-containing analogues. We observe circa doubling of mid-infrared (MIR) PL intensity from 3.5 to 6 µm for bulk glasses, pumped at 1.55 µm wavelength, and an increased excited state lifetime at 4.7 µm. PL is reported in optically-clad fiber. Ga addition is well known to enhance RE³âº solubility and PL behavior, and is believed to form ([RE³âº]-Se-[Ga(III)]) in the glasses. Indium has the same outer electronic-structure as gallium for solvating the RE-ions. Moreover, indium is heavier and promotes lower phonon energy locally around the RE-ion, thereby enhancing the RE-ion PL behavior, as observed here.

Lymphaticovenular anastomosis to prevent cellulitis associated with lymphoedema.

BACKGROUND: One of the complications of lymphoedema is recurrent cellulitis. The aim was to determine whether lymphaticovenous anastomosis (LVA) was effective at reducing cellulitis in patients with lymphoedema. METHODS: This was a retrospective review of patients with arm/leg lymphoedema who underwent LVA. The frequency of cellulitis was compared before and after surgery. The diagnostic criteria for cellulitis were a fever of 38·5°C or higher, and warmth/redness in the affected limb(s). RESULTS: A total of 95 patients were included. The mean number of episodes of cellulitis in the year preceding surgery was 1·46, compared with 0·18 in the year after surgery (P < 0·001). CONCLUSION: LVA reduced the rate of cellulitis in these patients with lymphoedema.

Where are all the surgeons in clinical academia?

INTRODUCTION: High-quality research into surgical disease will benefit surgical patients. Whereas nearly one-fifth of National Health Service (NHS) England consultants are surgeons, less than 5% of the government's health research funding supports surgical research. METHODS: Using an observational study, we identified surgeons in active research fellowships and on selection panels for the three largest pan-specialty medical funding bodies in the UK. We quantified the proportion of editorial board members that are surgeons, and the proportion of surgical research published over a 1-year period in the New England Journal of Medicine, The Lancet and the British Medical Journal. RESULTS: Some 185/1,579 (12%) of research fellowships held by clinicians were awarded to surgeons, with relatively fewer surgeons holding senior fellowships compared with predoctoral fellowships. Across the three research funding bodies, 9/165 (5%) of the clinical panel members were surgeons, whereas for the three pan-specialty journals, 5/84 (6%) of the clinical editorial board members were surgeons. Of the 541 original articles published by the same three journals, only 45 (8%) were classified as surgical. CONCLUSIONS: We show that surgeons were underrepresented across differing domains of clinical academia. The causes of this are likely multifactorial; there are fewer senior surgeons occupying decision-making positions, fewer role models in senior fellowship positions and surgical training may leave less time to engage in research. We propose further qualitative research within the surgical community, funding bodies and journals to understand the origins of the problem and begin to form evidence-based solutions.

T2-weighted MRI defines critical compression in the distal carpal tunnel that is relieved after decompressive surgery.

INTRODUCTION: Despite carpal tunnel syndrome (CTS) being the most common entrapment neuropathy, its pathophysiology remains debated. Sub-synovial connective tissues (SSCT) within the carpal tunnel are thought to play a role but are poorly characterised. MRI analysis offers potentially novel insights into SSCT characteristics. METHODS: A pilot study of T2-weighted MRI was performed in healthy controls (n = 7), and in CTS patients (n = 16) pre- and 6 months post-surgical decompression. Image analysis was performed to quantify SSCT cross-sectional area, SSCT signal intensity ratio, and wrist index (depth/width) at distal, middle, and proximal wrist landmarks. RESULTS: Median SSCT signal intensity was lower in the distal carpal tunnel of CTS patients pre-operatively (0.96) compared to controls (1.13; P = 0.008) and normalised post-operatively (1.13, P = 0.001). Median wrist index was also lower in CTS patients pre-operatively (0.60) than in controls (0.67, P = 0.022), and again normalised post-operatively (0.74, P = 0.001). This was attributed to changes in carpal depth in the anteroposterior axis with decompression surgery. CONCLUSION: This pilot study successfully demonstrated MRI assessment of SSCT in patients with CTS. The decreased SSCT signal intensities suggest predominant changes at the distal tunnel, potentially indicating reduced SSCT perfusion pre-surgery which normalised post-surgery. Our preliminary findings merit further investigation in a larger cohort.

Replication of epidemiological associations of carpal tunnel syndrome in a UK population-based cohort of over 400,000 people.

INTRODUCTION: Several phenotypic factors are associated in the literature with an increased risk of carpal tunnel syndrome (CTS). Along with female sex and older age, certain systemic diseases show an association with CTS, with varying degrees of evidence. METHODS: This study was performed using the UK Biobank resource - a cohort study of over 500,000 participants who have allowed linkage of phenotypic data with their medical records. We calculated the prevalence of CTS and a sex-specific prevalence ratio and compared the body mass index (BMI) between cases and controls. We performed a series of nested case-control studies to compute odds ratios for the association between CTS and three systemic diseases. RESULTS: There were 12,312 CTS cases within the curated UK Biobank dataset of 401,656 (3.1% prevalence), and the female:male ratio was 1.95:1. CTS cases had, on average, a BMI > 2.0 kg/m2 greater than controls. Odds ratios for the association with CTS for three systemic diseases were 2.31 (95% CI 2.17-2.46) for diabetes, 2.70 (95% CI 2.44-2.99) for rheumatoid arthritis, and 1.47 (95% CI 1.38-1.57) for hypothyroidism. Adjusted for BMI, these odds ratios fell to 1.75 (95% CI 1.65-1.86), 2.43 (95% CI 2.20-2.69), and 1.35 (95% CI 1.26-1.43), respectively. DISCUSSION: We harnessed the size and power of UK Biobank to provide robust replication of evidence for the associations between CTS and female sex, raised BMI, and three systemic diseases, which are only mediated in part by raised BMI.

Genetic screening of 202 individuals with congenital limb malformations and requiring reconstructive surgery.

BACKGROUND: Congenital limb malformations (CLMs) are common and present to a variety of specialties, notably plastic and orthopaedic surgeons, and clinical geneticists. The authors aimed to characterise causative mutations in an unselected cohort of patients with CLMs requiring reconstructive surgery. METHODS: 202 patients presenting with CLM were recruited. The authors obtained G-banded karyotypes and screened EN1, GLI3, HAND2, HOXD13, ROR2, SALL1, SALL4, ZRS of SHH, SPRY4, TBX5, TWIST1 and WNT7A for point mutations using denaturing high performance liquid chromatography (DHPLC) and direct sequencing. Multiplex ligation dependent probe amplification (MLPA) kits were developed and used to measure copy number in GLI3, HOXD13, ROR2, SALL1, SALL4, TBX5 and the ZRS of SHH. RESULTS: Within the cohort, causative genetic alterations were identified in 23 patients (11%): mutations in GLI3 (n = 5), HOXD13 (n = 5), the ZRS of SHH (n = 4), and chromosome abnormalities (n = 4) were the most common lesions found. Clinical features that predicted the discovery of a genetic cause included a bilateral malformation, positive family history, and having increasing numbers of limbs affected (all p<0.01). Additionally, specific patterns of malformation predicted mutations in specific genes. CONCLUSIONS: Based on higher mutation prevalence the authors propose that GLI3, HOXD13 and the ZRS of SHH should be prioritised for introduction into molecular genetic testing programmes for CLM. The authors have developed simple criteria that can refine the selection of patients by surgeons for referral to clinical geneticists. The cohort also represents an excellent resource to test for mutations in novel candidate genes.

Nurses as a source of system-level resilience: Secondary analysis of qualitative data from a study of intravenous infusion safety in English hospitals.

BACKGROUND: Deviations from local policy and national recommended best practice are common in the administration of intravenous infusions, but not all result in negative consequences. Some are the result of nurses' clinical judgement. However, little is known about such practices and their effects on the safety of intravenous infusions. Our objective was to explore ways in which nurses contribute to system-level resilience when administering intravenous infusions. METHODS: We conducted a secondary analysis of qualitative data from debriefs and focus groups from a mixed methods study of errors and policy deviations in intravenous infusion administration across 16 English hospitals. Analysis focused on nurses' contributions to system-level resilience, drawing on Larcos's et al. framework of types of resilience. RESULTS: Five types of system-level resilience were identified in nurses' behaviour: anticipatory resilience, responsive resilience, resilience based on past experience, workarounds and nurses performing informal 'risk assessments' in relation to how best to treat individual patients. Examples of practices contributing to infusion safety were found for each of these types of resilience. CONCLUSION: Our findings suggest nurses are a key source of system-level resilience. Some behaviours that may be considered deviations from policy or best practice are the result of reasoned clinical judgement to improve infusion safety in response to the specific situation at hand. Adaptive behaviour is necessary to cope with the complexity of practice. There is a tension between standardisation and supporting flexibility in safety management.

Management of extra-articular fractures of the fifth metacarpal: Operative vs. Non-opeRaTive TrEatment (FORTE) - A systematic review and meta-analysis.

AIMS: Extra-articular fifth metacarpal fractures are treated operatively and non-operatively without consensus. We aim to establish whether there are differences in patient-reported outcome, objective clinical outcome and adverse events for skeletally mature patients with closed extra-articular fractures of the 5th metacarpal that are treated operatively versus non-operatively. PATIENTS: Skeletally mature patients with closed, extra-articular 5th metacarpal fractures. METHODS: A systematic review and meta-analysis of randomised controlled trials using methodology adapted from the Cochrane Handbook for Systematic Review of Interventions and compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. (PROSPERO CRD42018091633). RESULTS: Two trials of 5th metacarpal neck fractures met the inclusion criteria and were included in the final pooled analysis (n = 125). There were no significant differences in patient-reported, objective clinical or radiographic outcomes between the operative and non-operative groups at 12 months. Operatively managed patients reported greater time off work and were more likely to suffer an adverse event. CONCLUSION: Existing trial data is limited and inconclusive in terms of patient-reported outcome measures. Given that there remains wide variation in the treatment of these common injuries around the world, there is a need for further high-quality evidence to guide clinical practice.

Prognostic factors for renal cell carcinoma.

Renal cell carcinoma is a relatively uncommon tumour with a widely varying prognosis depending on several tumour and clinical factors. This review discusses these factors and critically appraises their value both as individual markers and when they are incorporated into scoring systems/models or algorithms. Disease stage (assessed pathologically and/or clinically) and performance status have the strongest evidence as helpful individual prognostic markers but a better discrimination is obtained by combining these and adding in various other indices. Prospective validation of such integrated prognostic models will be essential.

Surgical site infection after hand surgery outside the operating theatre: a systematic review.

We carried out a systematic review to determine the incidence of infection for hand surgery done in settings other than the operating theatre. Databases were searched and a PRISMA chart created by three independent reviewers. From 1200 studies identified, 46 full text articles were reviewed and six were included (two Level 3 studies and four Level 4). In three studies there were no infections after surgery in an office, procedure room or emergency department. Two studies with a combined number of 1962 procedures reviewed carpal tunnel decompressions and reported identical infection rates of 0.4%. Although the current evidence is of poor quality, it suggests that some types of hand surgery may be done outside the operating theatre without increasing the risk of infection. LEVEL OF EVIDENCE: IV.

Cooling of burns: Mechanisms and models.

The role of cooling in the acute management of burns is widely accepted in clinical practice, and is a cornerstone of basic first aid in burns. This has been underlined in a number of animal models. The mechanism by which it delivers its benefit is poorly understood, but there is a reduction in burns progression over the first 48 h, reduced healing time, and some subjective improvements in scarring when cooling is administered after burning. Intradermal temperature normalises within a matter of seconds to a few minutes, yet the benefits of even delayed cooling persist, implying it is not simply the removal of thermal energy from the damaged tissues. Animal models have used oedema formation, preservation of dermal perfusion, healing time and hair retention as indicators of burns severity, and have shown cooling to improve these indices, but pharmacological or immunological blockade of humoural and cellular mediators of inflammation did not reproduce the benefit of cooling. More recently, some studies of tissue from human and animal burns have shown consistent, reproducible, temporal changes in gene expression in burned tissues. Here, we review the experimental evidence of the role and mechanism of cooling in burns management, and suggest future research directions that may eventually lead to improved treatment outcomes.

Theoretical study of population inversion in active doped MIR chalcogenide glass fibre lasers (invited).

We study the mechanism of the population inversion in mid-infrared fibre lasers based on a chalcogenide glass host doped with active lanthanide ions. Three lanthanide dopant ions are considered: terbium, dysprosium and praseodymium. We predict the relevant trivalent ion level populations and gain. The simulation parameters were obtained by fabricating and optically characterising a series of trivalent ion doped chalcogenide glass samples. We also provide simple analytical expressions that aid the design of the cascade lasing process.

Iron fortification of infant cereals: a proposal for the use of ferrous fumarate or ferrous succinate.

Hemoglobin-repletion tests in rats, organoleptic studies, and iron-absorption studies in humans were used to search for Fe sources with high bioavailability that could be added to infant cereals as alternatives to the Fe compounds currently used for fortification. From rat and organoleptic studies on 11 alternative Fe sources, ferrous fumarate, ferrous succinate, and ferric saccharate were selected as the most suitable for infant-cereal fortification and, by use of radioactive labels, absorption of those compounds from fortified cereal was measured in adult human volunteers. There was no difference in absorption between ferrous fumarate and ferrous sulfate whereas the values for ferrous succinate, ferrous saccharate (10% Fe), and ferric pyrophosphate were 92%, 74%, and 39% of the ferrous sulfate values, respectively. We conclude that ferrous fumarate and ferrous succinate are highly available Fe sources in man that can be used to fortify infant cereals without causing fat oxidation or discoloration.