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  1. Wells JC, Strickland SS
    Eur J Clin Nutr, 1996 Oct;50(10):668-71.
    PMID: 8909933
    To evaluate the effect of different methods (plateau or back extrapolation) of calculating total body water (TBW) from deuterium dilution in an environment characterised by high water turnover. The back extrapolation model is assumed to be more accurate when water turnover is high.
  2. Wells JR, Ham JE
    Atmos Environ (1994), 2014 Dec;99:519-526.
    PMID: 30100808 DOI: 10.1016/j.atmosenv.2014.10.015
    A new method for derivatizing carbonyl compounds is presented. The conversion of a series of dicarbonyls to oximes in aqueous solution and from gas-phase sampling was achieved using O-tert-butyl-hydroxylamine hydrochloride (TBOX). Some advantages of using this derivatization agent include: aqueous reactions, lower molecular weight oximes, and shortened oxime-formation reaction time. Additionally, the TBOX derivatization technique was used to investigate the carbonyl reaction products from limonene ozonolysis. With ozone (O3) as the limiting reagent, four carbonyl compounds were detected: 7-hydroxy-6-oxo-3-(prop-1-en-2-yl)heptanal; 3-Isopropenyl-6-oxoheptanal (IPOH), 3-acetyl-6-oxoheptanal (3A6O) and one carbonyl of unknown structure. Using cyclohexane as a hydroxyl (OH•) radical scavenger, the relative yields (peak area) of the unknown carbonyl, IPOH, and 3A6O were reduced indicating the influence secondary OH radicals have on limonene ozonolysis products. The relative yield of the hydroxy-dicarbonyl based on the chromatogram was unchanged suggesting it is only made by the limonene + O3 reaction. The detection of 3A6O using TBOX highlights the advantages of a smaller molecular weight derivatization agent for the detection of multi-carbonyl compounds. The use of TBOX derivatization if combined with other derivatization agents may address a recurring need to simply and accurately detect multi-functional oxygenated species in air.
  3. Mohd Shukri NH, Wells J, Fewtrell M
    Midwifery, 2021 Apr;95:102931.
    PMID: 33540157 DOI: 10.1016/j.midw.2021.102931
    BACKGROUND: The benefits of breastfeeding are well documented, yet substantially below half of all mothers globally meet the recommendation to exclusively breast-feed for 6 months.

    OBJECTIVE: This study aimed to examine whether there were differences in maternal factors, including maternal characteristics and breastfeeding attitudes, between those who were eligible versus non-eligible to be included in a randomised trial, as exclusive breastfeeding was the eligibility criteria for the trial. It also aimed to investigate associations between maternal factors and breastfeeding attitudes.

    METHOD: Primiparous pregnant mothers (n=88) completed questionnaires on demographic factors including maternity care and breastfeeding attitude using self-administered questionnaire and Iowa Infant Feeding Attitude Scale (IIFAS). Two weeks post-birth, mothers were screened for eligibility to be included in a randomised trial including assessing for exclusive breastfeeding (EBF). Findings were compared between inclusion (all EBF mothers) and exclusion groups (non-EBF).

    RESULTS: Inclusion group mothers were significantly younger than those in the exclusion group (26.7±2.8 v 28.5±2.5, p=0.007) and the majority had their husband as the primary maternity care person after birth (X2=12.8, p=0.01). Inclusion group mothers had a more positive perception toward breastfeeding in public and at work on the IIFAS scale (p<0.05). The overall IIFAS score was positively associated with higher breastfeeding confidence (r=0.285, p=0.008), education levels (r=0.31, p=0.003), household income (r=0.32, p=0.003), and age (r=0.28, p=0.008).

    CONCLUSION: EBF mothers (inclusion group) tend to be younger, had husband as primary care, and have more positive perception towards breastfeeding outside home. Overall, maternal characteristics and paternal support could influence breastfeeding practices and should be targeted for future intervention. Maternal attitude and perceptions about breastfeeding in public could be improved to encourage exclusive breastfeeding.

  4. Shukri NHM, Wells J, Mukhtar F, Lee MHS, Fewtrell M
    Int Breastfeed J, 2017;12:33.
    PMID: 28725257 DOI: 10.1186/s13006-017-0124-y
    BACKGROUND: The physiological and psychological signalling between mother and infant during lactation is one of the prominent mother-infant factors that may influence breastfeeding outcomes. The infant can 'signal' his needs through vocalisation, and the mother can respond by allowing or restricting nipple access, which might alter the breast milk composition or volume. This may lead to parent-offspring conflict during the lactation period. Challenging infant behaviour has also been associated with maternal psychological distress, which might affect breastfeeding performance. Most attempts to improve breastfeeding rates focus on providing additional support, yet many aspects of the breastfeeding process are poorly understood. Thus, our objective is to investigate mother-infant signalling during breastfeeding by manipulating maternal psychological state using a relaxation therapy intervention. The study will test the hypothesis that mothers who listen to the therapy will be more relaxed/less stressed and this will favourably alter breast milk composition and/or affect milk volume and hence influence infant outcomes.

    METHODS: A randomised controlled trial will be conducted in first-time breastfeeding mothers and their new-born infants. Pregnant mothers will be recruited at antenatal clinics in Selangor, Malaysia, and four home visits will be carried out at 2, 6, 12 and 14 weeks postnatally. Participants will be randomised into a control and an intervention group in the early post-partum period. Mothers from the intervention group will be asked to listen daily to an audio recording with relaxation therapy during breastfeeding. Maternal psychological state, breastfeeding practices and infant behaviour will be assessed using validated questionnaires. Milk volume will be measured using stable isotopes. Breast milk samples will be collected to measure macronutrient content and hormone levels. Anthropometric measurements (weight, length and head circumference) will be performed during all home visits, including body composition at week 14.

    DISCUSSION: The main outcomes will be the effect of the intervention on maternal psychological state, milk production, cortisol levels, and infant behaviour and growth. Secondary outcomes will be associations between breast milk composition and infant appetite and growth. This study aims to provide a greater understanding of maternal-infant factors which influence breastfeeding outcomes and which may be useful targets for future interventions.

    TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01971216.

  5. Ham JE, Harrison JC, Jackson SR, Wells JR
    Atmos Environ (1994), 2016 May;132:300-308.
    PMID: 27346977
    The reaction products from limonene ozonolysis were investigated using the new carbonyl derivatization agent, O-tert-butylhydroxylamine hydrochloride (TBOX). With ozone (O3) as the limiting reagent, five carbonyl compounds were detected. The yields of the carbonyl compounds are discussed with and without the presence of a hydroxyl radical (OH•) scavenger, giving insight into the influence secondary OH radicals have on limonene ozonolysis products. The observed reaction product yields for limonaketone (LimaKet), 7-hydroxyl-6-oxo-3-(prop-1-en-2-yl)heptanal (7H6O), and 2-acetyl-5-oxohexanal (2A5O) were unchanged suggesting OH• generated by the limonene + O3 reaction does not contribute to their formation. The molar yields of 3-isopropenyl-6-oxo-heptanal (IPOH) and 3-acetyl-6-oxoheptanal (3A6O) decreased by 68% and >95%; respectively, when OH• was removed. This suggests that OH• radicals significantly impact the formation of these products. Nitric oxide (NO) did not significantly affect the molar yields of limonaketone or IPOH. However, NO (20 ppb) considerably decreased the molar reaction product yields of 7H6O (62%), 2A5O (63%), and 3A6O (47%), suggesting NO reacted with peroxyl intermediates, generated during limonene ozonolysis, to form other carbonyls (not detected) or organic nitrates. These studies give insight into the transformation of limonene and its reaction products that can lead to indoor exposures.
  6. Affandi AM, Blumetti TP, Wells J, Hertzberg M, Fernandez-Peñas P
    Australas J Dermatol, 2015 Nov;56(4):294-7.
    PMID: 25496219 DOI: 10.1111/ajd.12270
    Treatment options for advanced stage cutaneous T-cell lymphoma (CTCL) are limited by the their efficacy and side-effects profile. Gemcitabine, a pyrimidine analogue, has been reported to be efficacious in CTCL. Most of the studies published used gemcitabine as a single agent in treating advanced CTCL. Our small case series demonstrated that a combination of gemcitabine and vinorelbine induced partial remission in all four patients with refractory or advanced CTCL, although the effects were not sustained for a long duration (2-6 months). Two patients had neutropenia and one had acute hepatitis, requiring discontinuation of treatment.
  7. Mohd Shukri NH, Wells J, Eaton S, Mukhtar F, Petelin A, Jenko-Pražnikar Z, et al.
    Am J Clin Nutr, 2019 07 01;110(1):121-130.
    PMID: 31161202 DOI: 10.1093/ajcn/nqz033
    BACKGROUND: Biological signaling and communication between mothers and infants during breastfeeding may shape infant behavior and feeding. This signaling is complex and little explored in humans, although it is potentially relevant for initiatives to improve breastfeeding rates.

    OBJECTIVES: The aim of this study was to investigate physiological and psychological aspects of mother-infant signaling during breastfeeding experimentally, testing the effects of a relaxation intervention on maternal psychological state, breast milk intake, milk cortisol levels, and infant behavior and growth.

    METHODS: Primiparous breastfeeding mothers and full-term infants were randomly assigned to receive relaxation therapy [intervention relaxation group; n = 33 (RG)] or to the control group [n = 31 (CG); no relaxation therapy] at 2 wk postpartum. Both groups received standard breastfeeding support. Home visits were conducted at 2 (HV1), 6 (HV2), 12 (HV3) and 14 (HV4) wk to measure maternal stress and anxiety, breast milk intake and milk cortisol, and infant behavior and growth.

    RESULTS: RG mothers had lower stress scores postintervention than the CG (HV3 ∆ = -3.13; 95% CI: -5.9, -0.3) and lower hindmilk cortisol at HV1 (∆ = -44.5%; 95% CI: -76.1%, -12.9%) but not at HV2. RG infants had longer sleep duration (∆ = 82 min/d; 95% CI: 16, 149 min/d) at HV2 and higher gains in weight and body mass index standardized deviation score than the CG infants (∆ = 0.76; 95% CI: 0.3, 1.22; and ∆ = 0.59; 95% CI: 0.09, 1.1, respectively). RG infants had a mean milk intake at HV3 that was 227 g/d higher than that of the CG infants (P = 0.031) after controlling for gender and milk intake at HV1.

    CONCLUSIONS: The trial shows the effectiveness of a simple relaxation intervention for improving maternal and infant outcomes and identifies some potential signaling mechanisms for investigation in future and larger studies, especially in settings where mothers are more stressed, such as those with preterm or low birth weight infants. This trial was registered at clinicaltrials.gov as NCT01971216.

  8. Dodkins J, Hopman WM, Wells JC, Lievens Y, Malik RA, Pramesh CS, et al.
    PMID: 35151802 DOI: 10.1016/j.ijrobp.2022.01.053
    PURPOSE: Randomized control trials (RCTs) are the cornerstone of delivering sustained improvements in cancer outcome. To inform radiotherapy research policy and prioritization, we analyze the radiotherapy RCT landscape including comparison with trials of systemic therapies over the same time period, with a specific focus on funding and disparities across income settings.

    METHODS AND MATERIALS: This retrospective cohort study identified all phase three RCTs evaluating anticancer therapies published from 2014 to 2017. RCTs were classified according to anticancer modality and country of origin. Descriptive statistics were used to compare key characteristics of radiotherapy RCT studies according to study design characteristics, tumor types evaluated, types of intervention appraised, treatment intent and main funding sources.

    RESULTS: The study cohort included 694 RCTs of which 64 were radiotherapy RCTs (9%) compared to 601 (87%) systemic therapy RCTs. 47% of all radiotherapy RCTs focused on two areas of evaluation; combining radiotherapy with systemic agents (25%) and changes in dose fractionation (22%). The most common cancers studied were head and neck (22%), lung (22%) and breast (14%) with cervical cancer trials only representing 3% of the cohort. 33% of radiotherapy RCTs met their primary end point. 62% of radiotherapy RCTs assessed interventions in the curative setting compared to 31% in systemic therapy RCTs. 77% of the radiotherapy RCTs were performed in high-income countries (HIC), 13% in low-and-middle-income countries (LMIC) and 11% in both HIC and LMICs. 17% of radiotherapy RCTs received funding from industry compared to 79% of systemic therapy RCTs.

    CONCLUSION: This study has highlighted the need for greater investment in radiotherapy RCTs and the disparities in conduct of RCTs globally. The study emphases the urgent need for more capacity building for cancer clinical trials in LMICs and more sustainable funding sources.

  9. Santika T, Ancrenaz M, Wilson KA, Spehar S, Abram N, Banes GL, et al.
    Sci Rep, 2017 07 07;7(1):4839.
    PMID: 28687788 DOI: 10.1038/s41598-017-04435-9
    For many threatened species the rate and drivers of population decline are difficult to assess accurately: species' surveys are typically restricted to small geographic areas, are conducted over short time periods, and employ a wide range of survey protocols. We addressed methodological challenges for assessing change in the abundance of an endangered species. We applied novel methods for integrating field and interview survey data for the critically endangered Bornean orangutan (Pongo pygmaeus), allowing a deeper understanding of the species' persistence through time. Our analysis revealed that Bornean orangutan populations have declined at a rate of 25% over the last 10 years. Survival rates of the species are lowest in areas with intermediate rainfall, where complex interrelations between soil fertility, agricultural productivity, and human settlement patterns influence persistence. These areas also have highest threats from human-wildlife conflict. Survival rates are further positively associated with forest extent, but are lower in areas where surrounding forest has been recently converted to industrial agriculture. Our study highlights the urgency of determining specific management interventions needed in different locations to counter the trend of decline and its associated drivers.
  10. Voigt M, Wich SA, Ancrenaz M, Meijaard E, Abram N, Banes GL, et al.
    Curr Biol, 2018 03 05;28(5):761-769.e5.
    PMID: 29456144 DOI: 10.1016/j.cub.2018.01.053
    Unsustainable exploitation of natural resources is increasingly affecting the highly biodiverse tropics [1, 2]. Although rapid developments in remote sensing technology have permitted more precise estimates of land-cover change over large spatial scales [3-5], our knowledge about the effects of these changes on wildlife is much more sparse [6, 7]. Here we use field survey data, predictive density distribution modeling, and remote sensing to investigate the impact of resource use and land-use changes on the density distribution of Bornean orangutans (Pongo pygmaeus). Our models indicate that between 1999 and 2015, half of the orangutan population was affected by logging, deforestation, or industrialized plantations. Although land clearance caused the most dramatic rates of decline, it accounted for only a small proportion of the total loss. A much larger number of orangutans were lost in selectively logged and primary forests, where rates of decline were less precipitous, but where far more orangutans are found. This suggests that further drivers, independent of land-use change, contribute to orangutan loss. This finding is consistent with studies reporting hunting as a major cause in orangutan decline [8-10]. Our predictions of orangutan abundance loss across Borneo suggest that the population decreased by more than 100,000 individuals, corroborating recent estimates of decline [11]. Practical solutions to prevent future orangutan decline can only be realized by addressing its complex causes in a holistic manner across political and societal sectors, such as in land-use planning, resource exploitation, infrastructure development, and education, and by increasing long-term sustainability [12]. VIDEO ABSTRACT.
  11. van Huizen AM, Menting SP, Gyulai R, Iversen L, van der Kraaij GE, Middelkamp-Hup MA, et al.
    JAMA Dermatol, 2022 May 01;158(5):561-572.
    PMID: 35353175 DOI: 10.1001/jamadermatol.2022.0434
    IMPORTANCE: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide.

    OBJECTIVE: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics.

    DESIGN, SETTING, AND PARTICIPANTS: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience).

    MAIN OUTCOMES AND MEASURES: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree.

    RESULTS: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients.

    CONCLUSIONS AND RELEVANCE: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

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