Safety factors as a ‘design’ principle of animal form and function: an historical perspective

ABSTRACT For well over 150 years, factors of safety (also known as safety factors) have been a fundamental engineering concept that expresses how much stronger a system is compared with the intended load. The pioneering work of Robert McNeill Alexander in the early 1980s applied this engineering concept to biomechanics. Over the next decade, evidence from comparative biomechanics supported the idea that safety factors are a fundamental principle of animal form and function. In terms of physiology, Jared Diamond related the maximal capacity of a physiological process to normal functional demands and incorporated evolutionary thinking into the concept of safety factors. It was proposed that evolutionary reasoning is required to understand the magnitudes of biological reserve capacities, an idea called ‘quantitative evolutionary design’. However, the general idea of safety factors as related to organismal form and function is much older. In 1906, Samuel James Meltzer, a physiologist and physician, presented the 5th Harvey Lecture to the New York Academy of Medicine; a lecture entitled ‘The Factors of Safety in Animal Structure and Animal Economy’, which was later published in Science in 1907. The 1907 paper is rarely cited and has never been cited within comparative biomechanics or comparative physiology. The purpose of this Commentary is to highlight Meltzer's historical contribution to the concept of safety factors as a general principle of organismal ‘design’.

His Royal Highness Prince Wongsa Dhiraj Snid and Western Medicine

On the 150th anniversary of the passing of Phra Chao Barommawongse Ther Krom Luang Wongsa Dhiraj Snid (H.R.H. Prince Wongsa Dhiraj Snid) on August 14, 1871, the information about the acceptance of western doctors upon the prince as a corresponding fellow of the New York Academy of Medicine, elected in 1853 is presented along with the information about the 5 generations of doctors in the Snidvongs Royal Family.

Comparing Three Approaches to Salt Intake Assessment Among Lactating Women in Rural Cambodia

Objectives Monitoring population salt intake is a critical component of implementing salt fortification programs. In Cambodia, salt is being considered as a vehicle for thiamine fortification to prevent infantile beriberi among breastfed infants. However, salt intake among lactating mothers is not known. The gold standard for assessing sodium intake is repeat 24-hr urinary sodium concentrations. This method has logistical barriers, especially in low-resource settings, and other methods have not been trialed in this population. Here we compare three methods of assessing salt intake in lactating Cambodian women: repeat 24-hr urinary sodium concentrations (USC), repeat 12-hr observed weighed intake records (OWIR), and household salt disappearance (HSD). Methods Data from trial: NCT03616288. Salt intake was assessed using the three methods in a subsample of lactating women (n = 104) between 8 and 22 weeks postpartum. Women were asked to collect two 24-hour urine samples within 7 days. Repeat 12-hr OWIR were collected from women. Household salt disappearance was recorded fortnightly, and was divided by the number of household members to estimate individual intakes. Descriptive household salt use was also recorded. Differences in estimated salt intake from each method were compared using a Kruskal-Wallis test. Results Mean (95%CI) estimated salt intakes from repeat 24-hr USC, repeat 12-hr OWIR, and HSD were: 9.0 (8.3, 9.8) g/day, 9.1 (7.9, 10.3) g/day, and 10.9 (9.8, 11.9) g/day, respectively. Estimated intakes from HSD were significantly higher than both 24-hr USC (p = 0.009) and 12-hr OWIR (p = 0.002). Estimated intakes from 24-hr USC and 12-hr OWIR were not statistically different (p = 0.6). Salt was being used for purposes other than consumption, such as cleaning fish and vegetables, in 26% of fortnightly visits. Conclusions Repeat 24-hr USC and 12-hr OWIR are both acceptable and logistically feasible methods of salt intake assessment among lactating women in rural Cambodia. While HSD is a less resource-intensive approach, this method over-estimated salt intake. Salt being used for purposes other than consumption may contribute to over-estimation using this method. Funding Sources Bill & Melinda Gates Foundation, New York Academy of Sciences, Canadian Institutes of Health Research, Research Nova Scotia.

Neurocognitive Benefits of Maternal Thiamine Supplementation for Breastfed Cambodian Infants

Objectives Women reliant on rice-heavy diets can have inadequate thiamine intakes, placing breastfed infants at risk of thiamine deficiency and, in turn, neurocognitive impairments. We investigated the impact of maternal thiamine supplementation doses on infants’ cognitive, motor, and language development across the first year. Methods In this double-blind, four-parallel arm, randomized controlled trial, healthy mothers of exclusively breastfed newborn infants were recruited in Kampong Thom, Cambodia. At 2-weeks postnatal, women (n = 335) were randomized to one of four treatment groups to consume one capsule/day with varying amounts of thiamine for 22 weeks: 0 mg, 1.2 mg, 2.4 mg, and 10 mg. At 2-, 12-, 24- and 52-weeks of age, infants were assessed with the Mullen Scales of Early Learning (MSEL). Results Mixed effects modeling suggest that by 6 months of age, the highest maternal thiamine dose (10 mg/day) held significant benefits for infants’ language development, F's (3,659) > 33.2, P's < 0.001, but generally not for motor or visual reception development. Despite having achieved standardized scores on the MSEL that approximated US norms by 6 months, infants showed a significant drop in all cognitive domains following trial completion, indicating that nutritional interventions beyond 6 months may be necessary. Conclusions Findings provide the first experimental evidence that thiamine supplementation among lactating mothers at risk of thiamine deficiency protects their infants’ neurocognitive development, with particular benefit to developing language capacities. Results are consistent with studies that report a widening gap in cognitive test scores over time between children from high vs. low-risk contexts. Important questions remain, particularly with respect to the appropriate duration of thiamine supplementation and/or alternate interventions such as mandatory fortification, with potential to build protective stores of thiamine in preconception or pregnancy. Funding Sources Bill & Melinda Gates Foundation and the New York Academy of Sciences (Opportunity ID OPP1176128).

Maternal Thiamine Supplementation Promotes Infants’ Language Processing at 24 Weeks

Objectives In 2005, researchers observed a link between infants’ access to thiamine (vitamin B1) and their subsequent language functioning: infants fed formula that inadvertently lacked thiamine later displayed significant delays in language and motor development. In the context of a double-blind, randomized, controlled trial, the present research provided the first experimental test of a relationship between early life thiamine exposure and infants’ early language processing. Methods 335 lactating mothers were randomly assigned to receive capsules containing either 0, 1.2, 2.4, or 10 mg of thiamine daily, from 2 weeks postpartum until infants were 24 weeks. We assessed the integrity of 24-week-old infants’ developing system for language processing by measuring the extent to which they displayed attentional enhancement in response to infant-directed speech (IDS) relative to adult-directed speech (ADS). Such IDS-related attentional enhancement implies that infants can differentiate IDS from ADS, which requires underlying skills for analysis of the complex stream of sound that human speech embodies. Of the 335 infants in the study, analyzable data for the IDS preference task were available for 251. Results As predicted, a greater-than-chance percentage of all infants displayed enhanced attention to IDS relative to ADS, replicating prior research (one-sample t(250) = 3.06, P = 0.002). The magnitude of the IDS-elicited attentional-enhancement increased significantly in relation to the thiamine dose that lactating mothers received (beta-weight 0.007, t = 2.57, P = 0.011). Notably, however, when supplementation groups were examined separately, only infants whose mothers received the 10 mg daily supplement displayed a statistically significant IDS-related attentional enhancement (10 mg group: one-sample t(63) = 4.14, P = 0.000; all other groups t’s < 1.41, P’s > 0.16). Conclusions Taken together, these findings confirm a link between infants’ post-natal access to thiamine and their language processing facility at 24 weeks. The findings both showcase the value of the IDS preference task for monitoring the integrity of infants’ language processing, and underscore the importance of adequate thiamine for ensuring infants’ optimal language development. Funding Sources Bill & Melinda Gates Foundation and the New York Academy of Sciences.

Thiamine Status of Supplemented, Lactating Mothers in Rural Cambodia: A Randomized Controlled Trial

Objectives Thiamine deficiency is a cause of infant morbidity and mortality throughout Southeast and South Asia. Maternal intake influences human milk thiamine concentrations, thus mother's intake must be improved to combat infant deficiency. However, the dose of supplemental thiamine required by lactating mothers is unknown. We aimed to estimate the maternal oral thiamine dose required to optimize milk thiamine concentrations, and to investigate the impact of various doses on thiamine status biomarkers. Methods This was a double-blind, four-parallel arm randomized controlled dose-response trial. At 2 weeks postpartum, healthy mothers were randomized to consume one capsule daily for 22 weeks, containing either 0 mg (placebo, n = 83), 1.2 mg (estimated average requirement, n = 86), 2.4 mg (n = 81), or 10 mg (n = 85) thiamine. Human milk total thiamine, whole blood thiamine diphosphate, and erythrocyte transketolase activity coefficient (ETKac) were assessed. An Emax curve, estimated using a non-linear least squares model, was plotted for human milk. Linear mixed-effects models were used to test for differences between treatment groups for milk and blood biomarkers. Results A maternal supplemental dose of 2.35 (95% CI 0.58, 7.01) mg/d was estimated to reach 90% of the maximum average human milk total thiamine concentration of 191 µg/L. The mean (SD) milk thiamine concentration was significantly higher in all intervention groups (183 (91), 190 (105), and 206 (89) µg/L, for 1.2, 2.4, and 10 mg, respectively) compared to placebo (153 (85) µg/L; p < 0.0001), and did not differ from each other. Blood biomarkers followed similar group trends, except for infant ETKac, where only the 10 mg (mean [SD]: 1.18 [0.10]) and placebo (1.12 [0.06]) groups differed significantly (p = 0.003). Conclusions While an estimated maternal dose of 2.35 (0.58, 7.01) mg/d was required to reach a milk thiamine concentration of 191 µg/L in Emax dose analyses, group comparisons suggest a daily dose of 1.2 mg/d is sufficient to improve maternal biomarkers to levels similar to higher doses (2.4 and 10 mg/d) and consistent with thiamine-replete populations. However, a higher maternal dose of 10 mg/d was required to improve infant ETKac status compared to other dose groups. Funding Sources Bill & Melinda Gates Foundation, The New York Academy of Sciences.

Benefits of Maternal Thiamine Supplementation for Enhancing Cambodian Infants’ Social Responsiveness at 24 Weeks

Objectives Infants in Cambodia are at risk for thiamine deficiency, with long-term negative consequences for neuro-cognitive development. We investigated the extent to which maternal thiamine supplementation enhances infants’ responsiveness to social engagement. Such responsiveness is both indicative of neuro-cognitive development and beneficial for subsequent neuro-cognitive progress. Methods 335 lactating Cambodian mothers were randomly assigned to receive a capsule containing 0, 1.2, 2.4, or 10 mg of thiamine daily from 2- until 24-weeks postnatal. We assessed infants’ social responsiveness via a new method – the Primary Engagement Task (PET) – when infants were 2-, 12-, and 24-weeks. In the PET, mothers were asked to elicit and sustain a smile from infants as they added and then removed modalities of engagement (eye-contact/facial expression, voice and touch) across six 30-second “epochs.” Subsequent behavioral coding from video-recordings determined changes in infants’ state across the epochs of the PET. Results Preliminary analyses based on 103 of the 335 infants in the PET at 24 weeks revealed that infants displayed significantly increased alertness as mothers introduced new modalities of engagement in the PET, and a partial decline in alertness as modalities were removed (linear contrast F(1,102) = 24.37, P = 0.000; quadratic contrast F(1,102) = 7.27, P = 0.008). Although maternal thiamine dosage did not influence these patterns overall (F's < 1.56, P's > 0.20), higher maternal thiamine dosage was associated with infants displaying enhanced alertness when mothers first offered eye-contact in the PET (beta-weight = 0.026; t = 2.01, P = 0.047). This pattern of alerting to maternal eye-contact was statistically significant only in the 10 mg group (paired t(25) = 3.14, P = 0.004). Conclusions Infants whose mothers received 10 mg daily thiamine supplementation displayed increased alertness to opportunities to interact socially. These preliminary findings (a) showcase the value of the PET for assessing infants’ responsiveness to caregiver's efforts to engage them socially, and (b) hint that maternal thiamine supplementation promotes infants’ social responsiveness, thereby underscoring the importance of infants’ early access to adequate thiamine for neuro-cognitive thriving. Funding Sources Bill & Melinda Gates Foundation & New York Academy of Sciences.

James Croll and 1876: an exceptional year for a ‘singularly modest man’

ABSTRACT James Croll left school at the age of 13 years, yet while a janitor in Glasgow he published a landmark paper on astronomically-related climate change, claimed as ‘the most important discovery in paleoclimatology’, and which brought him to the attention of Charles Darwin, William Thomson and John Tyndall, amongst others. By 1867 he was persuaded to become Secretary and Accountant of the newly established Geological Survey of Scotland in Edinburgh, and a year after the appearance of his keynote volume Climate and time in 1875, he was lauded with an honorary doctorate from Scotland's oldest university, Fellowship of the Royal Society of London and Honorary Membership of the New York Academy of Sciences. Using a range of archival and published sources, this paper explores aspects of his ‘journey’ and the background to the award of these major accolades. It also discusses why he never became a Fellow of his national academy, the Royal Society of Edinburgh. In the world of 19th-Century science, Croll was not unusual in being both an autodidact and of humble origins, nor was he lacking in support for his endeavours. It is possible that a combination of Croll's modesty and innovative genius fostered advancement, though this did not hinder a willingness to engage in vigorous argument.

Potencial Evocado Auditivo Mismatch Negativity em músicos e não músicos: Revisão sistematica

O potencial evocado de longa latência Mismatch Negativity (MMN) se refere de forma objetiva como método eletrofisiológico às habilidades de discriminação sonora, processamento auditivo, memória auditiva e atenção involuntária em nível central. Tais habilidades são encontradas de maneira distinta entre músicos e não músicos e o MMN é utilizado de forma objetiva para detecta-las. Objetivo: realizar uma revisão sistemática para verificar se existe diferenças de latência e amplitude apresentadas por meio do MMN em músicos e não músicos. Método: A pesquisa foi realizada entre setembro e novembro de 2020, nas bases eletrônicas Pubmed, ScienceDirect, BVS (Lilacs), Scopus, Circumpolar Health Bibliographic Database, SciELO, Embase, Web of science e Cochrane Central Register of Controlled Trials (CENTRAL), bem como as bases de literatura cinzenta OpenGrey.eu, DissOnline, The New York Academy of Medicine, Clinical Evidence e Clinical Trials, utilizando os descritores da seguinte forma Music OR musician OR musicians AND potencial mismatch negavitity OR MMN OR evoked potentials auditory OR Long Latency. Resultados: Foram encontrados 9 artigos , sendo que 7 abordavam que os músicos superavam os não músicos em suas latências e amplitudes de MMN, em contraste 2 artigos não diferenciavam as latências e amplitudes entre músicos e não músicos. Conclusão: Os músicos apresentaram em uma grande maioria dos estudos uma superioridade aos não músicos em amplitude, o que significa que as habilidades neurais de discriminação auditiva e comportamentais dos músicos superam aos de não músicos, os músicos apresentaram menor latência de MMN ainda assim superando os não músicos.

Potencial evocado miogênico vestibular ocular na vertigem posicional paroxística benigna: uma revisão sistemática

O potencial evocado miogênico vestibular ocular possui reflexo a partir de músculos extraoculares, em resposta a sons de elevada intensidade. O VEMP ocular avalia a via vestibular superior e a via contralateral ascendente, através do reflexo vestíbulo-ocular. Caracterizada por breves episódios de vertigem, náuseas e/ou nistagmo de posicionamento à mudança de posição da cabeça, a VPPB é provocada pela presença inapropriada de partículas de estatocônios advindas da mácula utricular flutuantes na endolinfa do(s) canal(is) semicircular(es) ou aglutinados à cúpula do(s) mesmo(s). O presente estudo tem como objetivo verificar se os valores de latência e amplitude dos componentes do oVEMP são diferentes em pacientes com VPPB quando comparados com adultos normais. O estudo trata-se de uma revisão sistemática, onde buscou investigar os valores de latência e amplitude do oVEMP em VPPB e grupo controle, pesquisado nas seguintes bases de dados: PubMed, ScienceDirect, BVS (lilacs), SciELO, Scopus, Circumpolar Health Bibliographic Database, Embase, Web of Science e Cochrane Central Register of Controlled Trials (CENTRAL). Além das bases de literatura cinzenta: OpenGrey, DissOnline, The New York Academy of Medicine, ClinicalEvidence.com e ClinicalTrials.gov. Nos estudos observa-se que as médias de latência n1 e p1 em indivíduos com VPPB e controle saudáveis não mostraram diferenças entre sim, caracterizando como respostas normais. Enquanto, os dados de amplitude n1 e p1 em indivíduos com VPPB foi menor quando comparados com grupo controle. Os achados apontam a relevância do enfoque e validam o estudo, uma vez que os resultados do grau de latência e amplitude podem sugerir alterações desencadeadas pela VPPB. Sendo então o teste oVEMP o mais eficiente para avaliar os casos com VPPB.