Towards algorithm auditing: managing legal, ethical and technological risks of AI, ML and associated algorithms.

-Business reliance on algorithms is becoming ubiquitous, and companies are increasingly concerned about their algorithms causing major financial or reputational damage. High-profile cases include Google's AI algorithm for photo classification mistakenly labelling a black couple as gorillas in 2015 (Gebru 2020 In The Oxford handbook of ethics of AI, pp. 251-269), Microsoft's AI chatbot Tay that spread racist, sexist and antisemitic speech on Twitter (now X) (Wolf et al. 2017 ACM Sigcas Comput. Soc. 47, 54-64 (doi:10.1145/3144592.3144598)), and Amazon's AI recruiting tool being scrapped after showing bias against women. In response, governments are legislating and imposing bans, regulators fining companies and the judiciary discussing potentially making algorithms artificial 'persons' in law. As with financial audits, governments, business and society will require algorithm audits; formal assurance that algorithms are legal, ethical and safe. A new industry is envisaged: Auditing and Assurance of Algorithms (cf. data privacy), with the remit to professionalize and industrialize AI, ML and associated algorithms. The stakeholders range from those working on policy/regulation to industry practitioners and developers. We also anticipate the nature and scope of the auditing levels and framework presented will inform those interested in systems of governance and compliance with regulation/standards. Our goal in this article is to survey the key areas necessary to perform auditing and assurance and instigate the debate in this novel area of research and practice.

Evaluating the impact of engaging older adults and service providers as research partners in the co-design of a community mobility-promoting program: a mixed methods developmental evaluation study.

BACKGROUND: Increasingly researchers are partnering with citizens and communities in research; less is known about research impacts of this engagement. EMBOLDEN is an evidence-informed, mobility-promoting intervention for older adults co-designed by a 26-person Strategic Guiding Council (SGC) of health/social service providers and older adult citizens. This study evaluated research partners' perceptions of engagement strategies, the engagement context, strengths, areas for improvement, as well as the impacts of the guiding council on older-adult identified priority areas. METHODS: This study was guided by developmental evaluation, working in partnership with four older adult SGC members who helped to set evaluation priorities, decide methods, and adapt patient-centred evaluation tools. Data sources included a questionnaire, focus groups and document analysis of meeting notes from 16 SGC meetings that took place between December 2019 and February 2022. A thematic approach to analysis guided the coding of focus group transcripts and SGC meeting notes. Convergent mixed methods guided the integration and presentation of qualitative and quantitative data sources in a joint display of evaluation results. RESULTS: Of 26 SGC members, nine completed the evaluation squestionnaire, and five participated in focus groups. Around two thirds of the SGC commonly attended each meeting. EMBOLDEN's SGC was structured to include a diverse group (across gender, ethnicity and discipline) of older adults and service providers, which was perceived as a strength. Engagement processes were perceived as inclusive and well-facilitated, which stimulated discussion at meetings. Advantages and disadvantages of engaging with the SGC virtually, as compared to in-person (as was the case for the first 3 SGC meetings) were also discussed. Impacts of the SGC were identified across preparatory, execution phase and translational stages of research. Impacts of SGC involvement on members were also described. CONCLUSION: Older adult research partners played an important role designing, implementing, and evaluating co-design approaches in this study. Older adults and service providers can make important contributions to the design, delivery and sharing results of health research through their lived expertise and connections to community. This project contributes to the growing field of citizen and community engagement in research by offering a participatory approach to engagement evaluation that considers diversity, satisfaction, and impact.

It is becoming common for researchers to ask patients and caregivers to become involved with their studies as partners. By partnering with people who have first-hand experience with a condition, researchers hope their studies will be more relevant, run efficiently and have more impact than studies designed by researchers alone. Over the last twenty years, there has been a significant increase in the number of published papers that involve patients and caregivers, but few papers mention what changed because of this involvement. Researchers need to know the best ways to involve patients and caregivers and the impact of doing so.This study aimed to find out how a council of older adults (OAs) and service providers (SPs) impacted a study about collaboratively designing and testing a mobility intervention. This study aimed to find out how council members felt about their involvement in this study, by asking them what went well and what could have been improved.This study used a questionnaire, focus groups and analyzed council meeting notes to inform this study. Four OA council members helped design the study, decide research methods, and adapt wording of questions (focus groups, questionnaire). Between 19% and 35% of council members completed evaluation activities. They felt the study strengths were the diversity of the council, and a welcoming environment for discussion. The council impacted how the study was designed, carried out and how results were shared. Results from this study can improve patient partnership engagement, experiences, and impacts in future studies.

Effectiveness of system navigation programs linking primary care with community-based health and social services: a systematic review.

BACKGROUND: Fragmented delivery of health and social services can impact access to high-quality, person-centred care. The goal of system navigation is to reduce barriers to healthcare access and improve the quality of care. However, the effectiveness of system navigation remains largely unknown. This systematic review aims to identify the effectiveness of system navigation programs linking primary care with community-based health and social services to improve patient, caregiver, and health system outcomes. METHODS: Building on a previous scoping review, PsychInfo, EMBASE, CINAHL, MEDLINE, and Cochrane Clinical Trials Registry were searched for intervention studies published between January 2013 and August 2020. Eligible studies included system navigation or social prescription programs for adults, based in primary care settings. Two independent reviewers completed study selection, critical appraisal, and data extraction. RESULTS: Twenty-one studies were included; studies had generally low to moderate risk of bias. System navigation models were lay person-led (n = 10), health professional-led (n = 4), team-based (n = 6), or self-navigation with lay support as needed (n = 1). Evidence from three studies (low risk of bias) suggests that team-based system navigation may result in slightly more appropriate health service utilization compared to baseline or usual care. Evidence from four studies (moderate risk of bias) suggests that either lay person-led or health professional-led system navigation models may improve patient experiences with quality of care compared to usual care. It is unclear whether system navigation models may improve patient-related outcomes (e.g., health-related quality of life, health behaviours). The evidence is very uncertain about the effect of system navigation programs on caregiver, cost-related, or social care outcomes. CONCLUSIONS: There is variation in findings across system navigation models linking primary care with community-based health and social services. Team-based system navigation may result in slight improvements in health service utilization. Further research is needed to determine the effects on caregiver and cost-related outcomes.

Association of serum folate levels during pregnancy and prenatal depression.

OBJECTIVE: To evaluate the association between serum folate levels during pregnancy and prenatal depression and the extent to which obesity may modify this relationship. METHODS: This secondary data analysis leveraged data from a previous study of pregnant Kaiser Permanente Northern California participants who completed a survey and provided a serum sample between 2011 and 2013. Serum folate was assessed using the Center for Disease Control's Total Folate Serum/Whole Blood Microbiological Assay Method. A score of 15 or greater on the Center for Epidemiologic Studies Depression Scale was defined as prenatal depression. We used Poisson regression to estimate risk of prenatal depression given prenatal serum folate status (low/medium tertiles vs. high tertile) in the full sample and in subsamples of women with pre-pregnancy body mass index in the (a) normal range and (b) overweight/obese range. RESULTS: Of the sample, 13% had prenatal depression. Combined low/medium folate tertiles was associated with prenatal depression (adjusted relative risk [aRR] = 1.97, 95% confidence interval [CI]: 0.93-4.18), although results did not reach statistical significance. This relationship was stronger among women with overweight/obesity than women with normal weight (aRR: 2.61, 95% CI: 1.01-6.71 and aRR: 1.50, 95% CI: 0.34-6.66, respectively). CONCLUSION: Results suggest an association between lower pregnancy folate levels and prenatal depression that may be stronger among women with overweight or obesity. Future studies need to clarify the temporal sequence of these associations.

Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa.

INTRODUCTION: Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania. METHODS: After formal training and certification, local personnel screened children 2-16 years old; those with conditional (170-199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers. RESULTS: Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8-1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children. CONCLUSION: SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.

Main Concept, Sequencing, and Story Grammar Analyses of Cinderella Narratives in a Large Sample of Persons with Aphasia.

Recently, a multilevel analytic approach called Main Concept, Sequencing, and Story Grammar (MSSG) was presented along with preliminary normative information. MSSG analyses leverage the strong psychometrics and rich procedural knowledge of both main concept analysis and story grammar component coding, complementing it with easy-to-obtain sequencing information for a rich understanding of discourse informativeness and macrostructure. This study is the next critical step for demonstrating the clinical usefulness of MSSG's six variables (main concept composite, sequencing, main concept+sequencing, essential story grammar components, total episodic components, and episodic complexity) for persons with aphasia (PWAs). We present descriptive statistical information for MSSG variables for a large sample of PWAs and compare their performance to a large sample of persons not brain injured (PNBIs). We observed significant differences between PWAs and PNBIs for all MSSG variables. These differences occurred at the omnibus group level and for each aphasia subtype, even for PWAs with very mild impairment that is not detected with standardized aphasia assessment. Differences between PWAs and PNBIs were also practically significant, with medium to large effect sizes observed for nearly all aphasia subtypes and MSSG variables. This work deepens our understanding of discourse informativeness and macrostructure in PWAs and further develops an efficient tool for research and clinical use. Future research should investigate ways to expand MSSG analyses and to improve sensitivity and specificity.

Altered Maternal Plasma Fatty Acid Composition by Alcohol Consumption and Smoking during Pregnancy and Associations with Fetal Alcohol Spectrum Disorders.

Objective: Polyunsaturated fatty acids are vital for optimal fetal neuronal development. The relationship between maternal alcohol consumption and smoking with third trimester plasma fatty acids were examined and their association with Fetal Alcohol Spectrum Disorders (FASD).Methods: Moderate to heavy alcohol-using and low/unexposed comparison women were recruited during mid-pregnancy from two prenatal clinics in Ukraine. The participants' infants underwent physical and neurobehavioral exams prior to one-year of age and classified as having FASD by maternal alcohol consumption and neurobehavioral scores. A subset of mother-child pairs was selected representing three groups of cases and controls: Alcohol-Exposed with FASD (AE-FASD, n = 30), Alcohol-Exposed Normally Developing (AE-ND, n = 33), or Controls (n = 46). Third trimester maternal plasma samples were analyzed for fatty acids and levels were compared across groups.Results: The percent of C18:0 (p < 0.001), arachidonic acid (AA, C20:4n-6, p = 0.017) and C22:5n-6 (p = 0.001) were significantly higher in AE-FASD women than controls or AE-ND women. Alcohol-exposed women who smoked had lower C22:5n-3 (p = 0.029) and docosahexaenoic acid (DHA, C22:6n-3, p = 0.005) and higher C22:5n-6 (p = 0.013) than women consuming alcohol alone or abstainers.Conclusion: Alterations in fatty acid profiles were observed in moderate to heavy alcohol-consuming mothers with infants classified with FASD compared to alcohol-exposed normally developing infants or controls.

Mild Jugular Compression Collar Ameliorated Changes in Brain Activation of Working Memory after One Soccer Season in Female High School Athletes.

Recent neuroimaging studies have suggested that repetitive subconcussive head impacts, even after only one sport season, may lead to pre- to post-season structural and functional alterations in male high school football athletes. However, data on female athletes are limited. In the current investigation, we aimed to (1) assess the longitudinal pre- to post-season changes in functional MRI (fMRI) of working memory and working memory performance, (2) quantify the association between the pre- to post-season change in fMRI of working memory and the exposure to head impact and working memory performance, and (3) assess whether wearing a neck collar designed to reduce intracranial slosh via mild compression of the jugular veins can ameliorate the changes in fMRI brain activation observed in the female high school athletes who did not wear collars after a full soccer season. A total of 48 female high school soccer athletes (age range: 14.00-17.97 years) were included in the study. These athletes were assigned to the non-collar group (n = 21) or to the collar group (n = 27). All athletes undewent MRI at both pre-season and post-season. In each session, a fMRI verbal N-Back task was used to engage working memory. A significant pre- to post-season increase in fMRI blood oxygen level dependent (BOLD) signal was demonstrated when performing the N-back working memory task in the non-collar group but not in the collar group, despite the comparable exposure to head impacts during the season between the two groups. The collar group demonstrated significantly smaller pre- to post-season change in fMRI BOLD signal than the non-collar group, suggesting a potential protective effect from the collar device. Significant correlations were also found between the pre- to post-season increase in fMRI brain activation and the decrease in task accuracy in the non-collar group, indicating an association between the compensatory mechanism in underlying neurophysiology and the alteration in the behavioral outcomes.

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status.

OBJECTIVE: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women. METHODS: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations. RESULTS: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability. CONCLUSIONS: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.

The Effects of External Jugular Compression Applied during Head Impact Exposure on Longitudinal Changes in Brain Neuroanatomical and Neurophysiological Biomarkers: A Preliminary Investigation.

OBJECTIVES: Utilize a prospective in vivo clinical trial to evaluate the potential for mild neck compression applied during head impact exposure to reduce anatomical and physiological biomarkers of brain injury. METHODS: This project utilized a prospective randomized controlled trial to evaluate effects of mild jugular vein (neck) compression (collar) relative to controls (no collar) during a competitive hockey season (males; 16.3 ± 1.2 years). The collar was designed to mildly compress the jugular vein bilaterally with the goal to increase intracranial blood volume to reduce risk of brain slosh injury during head impact exposure. Helmet sensors were used to collect daily impact data in excess of 20 g (games and practices) and the primary outcome measures, which included changes in white matter (WM) microstructure, were assessed by diffusion tensor imaging (DTI). Specifically, four DTI measures: fractional anisotropy, mean diffusivity (MD), axial diffusivity, and radial diffusivity (RD) were used in the study. These metrics were analyzed using the tract-based Spatial Statistics (TBSS) approach - a voxel-based analysis. In addition, electroencephalography-derived event-related potentials were used to assess changes in brain network activation (BNA) between study groups. RESULTS: For athletes not wearing the collar, DTI measures corresponding to a disruption of WM microstructure, including MD and RD, increased significantly from pre-season to mid-season (p < 0.05). Athletes wearing the collar did not show a significant change in either MD or RD despite similar accumulated linear accelerations from head impacts (p > 0.05). In addition to these anatomical findings, electrophysiological network analysis of the degree of congruence in the network electrophysiological activation pattern demonstrated concomitant changes in brain network dynamics in the non-collar group only (p < 0.05). Similar to the DTI findings, the increased change in BNA score in the non-collar relative to the collar group was statistically significant (p < 0.01). Changes in DTI outcomes were also directly correlated with altered brain network dynamics (r = 0.76; p < 0.05) as measured by BNA. CONCLUSION: Group differences in the longitudinal changes in both neuroanatomical and electrophysiological measures, as well as the correlation between the measures, provide initial evidence indicating that mild jugular vein compression may have reduced alterations in the WM response to head impacts during a competitive hockey season. The data indicate sport-related alterations in WM microstructure were ameliorated by application of jugular compression during head impact exposure. These results may lead to a novel line of research inquiry to evaluate the effects of protecting the brain from sports-related head impacts via optimized intracranial fluid dynamics.

Analysis of head impact exposure and brain microstructure response in a season-long application of a jugular vein compression collar: a prospective, neuroimaging investigation in American football.

BACKGROUND: Historical approaches to protect the brain from outside the skull (eg, helmets and mouthpieces) have been ineffective in reducing internal injury to the brain that arises from energy absorption during sports-related collisions. We aimed to evaluate the effects of a neck collar, which applies gentle bilateral jugular vein compression, resulting in cerebral venous engorgement to reduce head impact energy absorption during collision. Specifically, we investigated the effect of collar wearing during head impact exposure on brain microstructure integrity following a competitive high school American football season. METHODS: A prospective longitudinal controlled trial was employed to evaluate the effects of collar wearing (n=32) relative to controls (CTRL; n=30) during one competitive football season (age: 17.04±0.67 years). Impact exposure was collected using helmet sensors and white matter (WM) integrity was quantified based on diffusion tensor imaging (DTI) serving as the primary outcome. RESULTS: With similar overall g-forces and total head impact exposure experienced in the two study groups during the season (p>0.05), significant preseason to postseason changes in mean diffusivity, axial diffusivity and radial diffusivity in the WM integrity were noted in the CTRL group (corrected p<0.05) but not in the collar group (p>0.05). The CTRL group demonstrated significantly larger preseason to postseason DTI change in multiple WM regions compared with the collar group (corrected p<0.05). DISCUSSION: Reduced WM diffusivity alteration was noted in participants wearing a neck collar after a season of competitive football. Collar wearing may have provided a protective effect against brain microstructural changes after repetitive head impacts. TRIAL REGISTRATION NUMBER: NCT02696200.

Vitamin D and Reproduction: From Gametes to Childhood.

Vitamin D is well recognized for its essentiality in maintaining skeletal health. Recent research has suggested that vitamin D may exert a broad range of roles throughout the human life cycle starting from reproduction to adult chronic disease risk. Rates of vitamin D deficiency during pregnancy remain high worldwide. Vitamin D deficiency has been associated with an increased risk of fertility problems, preeclampsia, gestational diabetes, and allergic disease in the offspring. Vitamin D is found naturally in only a few foods thus supplementation can provide an accessible and effective way to raise vitamin D status when dietary intakes and sunlight exposure are low. However, the possibility of overconsumption and possible adverse effects is under debate. The effect of vitamin D supplementation during pregnancy and early life on maternal and infant outcomes will be of particular focus in this review.

Vitamin D and maternal and child health: overview and implications for dietary requirements.

The essentiality of vitamin D for normal growth and development has been recognized for over 80 years, and vitamin D fortification programs have been in place in the United States for more than 70 years. Despite the above, vitamin D deficiency continues to be a common finding in certain population groups. Vitamin D deficiency has been suggested as a potential risk factor for the development of preeclampsia, and vitamin D deficiency during infancy and early childhood is associated with an increased risk for numerous skeletal disorders, as well as immunological and vascular abnormalities. Vitamin D deficiency can occur through multiple mechanisms including the consumption of diets low in this vitamin and inadequate exposure to environmental ultraviolet B rays. The potential value of vitamin D supplementation in high-risk pregnancies and during infancy and early childhood is discussed. Currently, there is vigorous debate concerning what constitutes appropriate vitamin D intakes during early development as exemplified by differing recommendations from the Institute of Medicine Dietary Reference Intake report and recent recommendations by the Endocrine Society. As is discussed, a major issue that needs to be resolved is what key biological endpoint should be used when making vitamin D recommendations for the pregnant woman and her offspring.

Pediatric physical therapists' use of support walkers for children with disabilities: a nationwide survey.

PURPOSE: This study investigated pediatric physical therapists' use of support walkers (SWs) for children with disabilities. METHODS: An 8-page survey was mailed to 2500 randomly selected members of the Section on Pediatrics of the American Physical Therapy Association. Respondents to the survey included 513 pediatric physical therapists who were users of SWs. Descriptive statistics were calculated and themes were analyzed. RESULTS: Several SWs were reported as used most often to improve gait, mobility, participation at school, and interaction with peers. Use commonly included a month trial before purchase and 9 sessions of physical therapy to train a child for use in school. Reasons given for the use of SWs were improving impairments, functional limitations, and participation with peers. CONCLUSIONS: Pediatric physical therapists use SWs to increase postural control, mobility, and children's participation in school.

Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development.

A large body of evidence supports the concept that human pregnancy outcome is significantly influenced by the nutritional status of the mother. The consumption of "poor diets" has been associated with an increased risk for pregnancy complications, including gross structural birth defects, prematurity, low birth weight, and an increased risk for neurobehavioral and immunological abnormalities after birth. Forty-four years ago, zinc deficiency in mammals was shown to be teratogenic. Maternal zinc deficiency produces effects ranging from infertility and embryo/fetal death, to intrauterine growth retardation and teratogenesis. Postnatal complications of maternal zinc deficiency can also occur, and include behavioral abnormalities, impaired immunocompetence, and an elevated risk for high blood pressure in the offspring. It has been suggested that developmental zinc deficiency in humans can present a significant challenge to the conceptus, increasing the risk for numerous defects. Developmental zinc deficiency can occur through multiple pathways, and the concept that acute phase response-induced changes in maternal zinc metabolism may be a common cause of embryonic and fetal zinc deficiency is presented. Potential mechanisms underlying the teratogenic effects of zinc deficiency are reviewed. The potential value of maternal zinc supplementation in high risk pregnancies is discussed.

Safety coaches in radiology: decreasing human error and minimizing patient harm.

Successful programs to improve patient safety require a component aimed at improving safety culture and environment, resulting in a reduced number of human errors that could lead to patient harm. Safety coaching provides peer accountability. It involves observing for safety behaviors and use of error prevention techniques and provides immediate feedback. For more than a decade, behavior-based safety coaching has been a successful strategy for reducing error within the context of occupational safety in industry. We describe the use of safety coaches in radiology. Safety coaches are an important component of our comprehensive patient safety program.

A preliminary investigation of four-dimensional ultrasound for evaluation of middle ear ossicles: an in vitro study.

OBJECTIVE: Temporal bone imaging in children has several inherent limitations. Computed tomography has the disadvantage of ionizing radiation, possible sedation, cost and accessibility. Magnetic resonance imaging has most of these disadvantages, with the exception of radiation, and provides bone images of limited resolution. Recent advances in ultrasound have led to its increased application in numerous medical fields. The purpose of this study was to investigate the ability of four-dimensional ultrasound (4DUS) to image middle ear ossicles in vitro and determine if this technology should be adapted for future clinical use. METHODS: Thirty cadaveric ossicles (10 malleus, 10 incus, and 10 stapes) were randomized and measured by two evaluators under a microscope. The ossicles were then immersed in a cold water bath and imaged, randomized, and measured using four-dimensional ultrasound by the same two evaluators. A separate cadaveric temporal bone, modified to allow the ultrasound probe to rest on the tympanic membrane, was imaged to visualize the ossicles in situ and evaluate whether or not the tympanic membrane and malleus would impede visualization of more medial structures. RESULTS: Microscopic measurements were: malleus (h=8.0 mm+/-0.32, w=2.7 mm+/-0.20), incus (h=6.8 mm+/-0.41, w=5.3 mm+/-0.46), stapes (h=3.5 mm+/-0.34, w=2.4 mm+/-0.17). Inter-rater reliability was 0.8. Measurements were in agreement with previously published values. Ultrasound measurements were: malleus (h=8.0 mm+/-0.51, w=2.9 mm+/-0.27), incus (h=6.8 mm+/-0.49, w=5.5 mm+/-0.42), stapes (h=3.6 mm+/-0.41, w=2.5 mm+/-0.19). Inter-rater reliability was 0.7. Mean intra-class correlation coefficient for microscopic and ultrasound measurements was 0.7. Images of the ossicular chain in continuity in the temporal bone specimen were not as clear as images of individual ossicles that were disarticulated and imaged under water. CONCLUSIONS: 4DUS provides reasonable images of ossicles disarticulated and mounted in underwater medium. However, images of the intact ossicular chain in a modified cadaveric temporal bone were not as clear, making interpretation difficult. Further investigation into the development of a thinner ultrasound probe that can pass through the external auditory canal and into overcoming limitations of air in the middle ear cleft are warranted. This could allow for a clinically relevant, faster, lower cost and lower risk alternative to current imaging techniques.

The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: the potential influence of zinc status as an example.

There is increasing evidence that human pregnancy outcome can be significantly compromised by suboptimal maternal nutritional status. Poor diet results in a maternal-fetal environment in which the teratogenicity of other insults such as alcohol might be amplified. As an example, there is evidence that zinc (Zn) can interact with maternal alcohol exposure to influence the risk for fetal alcohol spectrum disorders (FASD). Studies with experimental animals have shown that the teratogenicity of alcohol is increased under conditions of Zn deficiency, whereas its teratogenicity is lessened when animals are given Zn-supplemented diets or Zn injections before the alcohol exposure. Alcohol can precipitate an acute-phase response, resulting in a subsequent increase in maternal liver metallothionein, which can sequester Zn and lead to decreased Zn transfer to the fetus. Importantly, the teratogenicity of acute alcohol exposure is reduced in metallothionein knockout mice, which can have improved Zn transfer to the conceptus relative to wild-type mice. Consistent with the above, Zn status has been reported to be low in alcoholic women at delivery. Preliminary data from two basic science and clinical nutritional studies that are ongoing as part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders support the potential role of Zn, among other nutritional factors, relative to risk for FASD. Importantly, the nutrient levels being examined in these studies are relevant to general clinical populations and represent suboptimal levels rather than severe deficiencies. These data suggest that moderate deficiencies in single nutrients can act as permissive factors for FASD, and that adequate nutritional status or intervention through supplementation may provide protection from some of the adverse effects of prenatal alcohol exposure.

Influence of copper on early development: prenatal and postnatal considerations.

Copper (Cu) is an essential nutrient whose requirement is increased during pregnancy and lactation. These represent times of critical growth and development, and the fetus and neonate are particularly vulnerable to deficiencies of this nutrient. Genetic mutations that predispose the offspring to inadequate stores of Cu can be life threatening as is observed in children with Menkes disease. During the last decade, severe Cu deficiency, once thought to be a rare condition, has been reported in the literature at an increasing frequency. Secondary Cu deficiencies can be induced by a variety of ways such as excessive zinc or iron intake, certain drugs, and bariatric surgery. Premature and low birth weight infants can be born with low Cu stores. A number of mechanisms can contribute to the teratogenicity of Cu including decreased activity of select cuproenzymes, increased oxidative stress, decreased nitric oxide availability, altered iron metabolism, abnormal extracellular matrix protein crosslinking, decreased angiogenesis and altered cell signaling among others. The brain, heart, and vessels as well as tissues such as lung, skin and hair, and systems including the skeletal, immune, and blood systems, are negatively affected by suboptimal Cu during development. Additionally, persistent structural, biochemical, and functional adverse effects in the offspring are noted even when Cu supplementation is initiated after birth, supporting the concept that adequate Cu nutriture during pregnancy and lactation is critical for normal development. Although Cu-containing IUDs are an effective method for increasing intrauterine Cu concentrations and for reducing the risk of pregnancy, high amounts of dietary Cu are not thought to represent a direct developmental risk.

Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial.

BACKGROUND: Epidemiological data shows low dietary magnesium(Mg) may be related to incidence and progression of asthma. OBJECTIVE: To determine if long term(6.5 month) treatment with oral Mg would improve asthma control and increase serum measures of Mg status in men and women with mild-to-moderate asthma. SUBJECTS: 55 males and females aged 21 to 55 years with mild to moderate asthma according to the 2002 National Heart, Lung, and Blood Institute(NHLBI) and Asthma Education and Prevention Program(NAEPP) guidelines and who used only beta-agonists or inhaled corticosteroids(ICS) as asthma medications were enrolled. DESIGN: Subjects were randomly assigned to consume 340 mg(170 mg twice a day) of Mg or a placebo for 6.5 months. MEASUREMENTS: Multiple measures of Mg status including serum, erythrocyte, urine, dietary, ionized and IV Mg were measured. OBJECTIVE: markers of asthma control were: methacholine challenge test(MCCT) and pulmonary function test(PFT) results. Subjective validated questionnaires on asthma quality of life(AQLQ) and control(ACQ) were completed by participants. Markers of inflammation, including c-reactive protein(CRP) and exhaled nitric oxide(eNO) were determined. RESULTS: The concentration of methacholine required to cause a 20% drop in forced expiratory volume in in minute(FEV(1)) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate(PEFR) showed a 5.8% predicted improvement over time(P = 0.03) in those consuming the Mg. There was significant improvement in AQLQ mean score units(P < 0.01) and in overall ACQ score only in the Mg group(P = 0.05) after 6.5 months of supplementation. Despite these improvements, there were no significant changes in any of the markers of Mg status. CONCLUSION: Adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.