A simple rule governs the evolution and development of hominin tooth size.

The variation in molar tooth size in humans and our closest relatives (hominins) has strongly influenced our view of human evolution. The reduction in overall size and disproportionate decrease in third molar size have been noted for over a century, and have been attributed to reduced selection for large dentitions owing to changes in diet or the acquisition of cooking. The systematic pattern of size variation along the tooth row has been described as a 'morphogenetic gradient' in mammal, and more specifically hominin, teeth since Butler and Dahlberg. However, the underlying controls of tooth size have not been well understood, with hypotheses ranging from morphogenetic fields to the clone theory. In this study we address the following question: are there rules that govern how hominin tooth size evolves? Here we propose that the inhibitory cascade, an activator-inhibitor mechanism that affects relative tooth size in mammals, produces the default pattern of tooth sizes for all lower primary postcanine teeth (deciduous premolars and permanent molars) in hominins. This configuration is also equivalent to a morphogenetic gradient, finally pointing to a mechanism that can generate this gradient. The pattern of tooth size remains constant with absolute size in australopiths (including Ardipithecus, Australopithecus and Paranthropus). However, in species of Homo, including modern humans, there is a tight link between tooth proportions and absolute size such that a single developmental parameter can explain both the relative and absolute sizes of primary postcanine teeth. On the basis of the relationship of inhibitory cascade patterning with size, we can use the size at one tooth position to predict the sizes of the remaining four primary postcanine teeth in the row for hominins. Our study provides a development-based expectation to examine the evolution of the unique proportions of human teeth.

Dysfunction of complement receptors CR3 (CD11b/18) and CR4 (CD11c/18) in pre-eclampsia: a genetic and functional study.

OBJECTIVE: To study genetic variants and their function within genes coding for complement receptors in pre-eclampsia. DESIGN: A case-control study. SETTING: Pre-eclampsia is a common vascular disease of pregnancy. The clearance of placenta-derived material is one of the functions of the complement system in pregnancy. POPULATION: We genotyped 500 women with pre-eclamptic pregnancies and 190 pregnant women without pre-eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre-eclamptic pregnancies and 1905 controls from the national FINRISK cohort. METHODS: The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS-1 cells. MAIN OUTCOME MEASURES: Allele frequencies were compared between pre-eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays. RESULTS: The most significantly pre-eclampsia-linked CR3 variant M441K (P = 4.27E-4, OR = 1.401, 95% CI = 1.167-1.682) displayed a trend of increased adhesion to iC3b (P = 0.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b. CONCLUSIONS: Results suggest that changes in complement-facilitated phagocytosis are associated with pre-eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro- and anti-inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre-eclampsia pathogenesis. TWEETABLE ABSTRACT: Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre-eclampsia.

The Neuroanatomy of Autism Spectrum Disorder Symptomatology in 22q11.2 Deletion Syndrome.

22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition associated with a high prevalence of neuropsychiatric conditions that include autism spectrum disorder (ASD). While evidence suggests that clinical phenotypes represent distinct neurodevelopmental outcomes, it remains unknown whether this translates to the level of neurobiology. To fractionate the 22q11.2DS phenotype on the level of neuroanatomy, we examined differences in vertex-wise estimates of cortical volume, surface area, and cortical thickness between 1) individuals with 22q11.2DS (n = 62) and neurotypical controls (n = 57) and 2) 22q11.2DS individuals with ASD symptomatology (n = 30) and those without (n = 25). We firstly observed significant differences in surface anatomy between 22q11.2DS individuals and controls for all 3 neuroanatomical features, predominantly in parietotemporal regions, cingulate and dorsolateral prefrontal cortices. We also established that 22q11.2DS individuals with ASD symptomatology were neuroanatomically distinct from 22q11.2DS individuals without ASD symptoms, particularly in brain regions that have previously been linked to ASD (e.g., dorsolateral prefrontal cortices and the entorhinal cortex). Our findings indicate that different clinical 22q11.2DS phenotypes, including those with ASD symptomatology, may represent different neurobiological subgroups. The spatially distributed patterns of neuroanatomical differences associated with ASD symptomatology in 22q11.2DS may thus provide useful information for patient stratification and the prediction of clinical outcomes.

Attitudes and Uptake of Seasonal Influenza Vaccination for Health Service Executive (HSE) Staff.

Aims Annual seasonal influenza (flu) vaccination is recommended for all healthcare workers (HCW) in the Health Service Executive (HSE) in Ireland. This is to reduce the risk of HCW contracting the flu and onward transmission to their patients. HCW uptake remains less than ideal, despite extensive seasonal influenza campaigns and vaccination promotions. The aim of this study was to investigate the attitudes and uptake to flu vaccination among HCW, and to determine how much these influence their decision to be vaccinated. Methods A survey was sent to HCWs working in three healthcare facilities within HSE North-East following an outbreak of seasonal influenza in a local long-term care facility (LTCF), asking if HCW had been vaccinated for the 2016 to 2017 influenza season; the survey additionally included questions about attitudes and beliefs with respect to vaccination. Results Seventy HSE-employed HCWs in the North-East counties of Ireland responded to survey (93.3% responded to survey; 61.4% were based in long-term care facilties; 80.0% were female; and 35.7% were vaccinated for 2016 to 2017 influenza season). Most respondents reported that HCW flu vaccination was good example for patients (87.1%), while 92.9% acknowledged that it was important in healthcare facilities. The majority of HCW supported annual HCW flu vaccination (68.6%), with 52.9% of respondents reporting that they would be vaccinated for the 2017 to 2018 influenza season. However, only 35.7% agreed with mandatory HCW vaccination. Furthermore, 28.6% of respondents were concerned that flu vaccination was associated with side effects, and 22.9% were not aware that flu vaccination protected their patients. Previous flu vaccination was shown to be the only statistically significant predictor for HCW vaccination (p < 0.001). Discussion These results suggest there is need to address some attitudes and beliefs around HCW vaccination for seasonal influenza, in addition to removing some practical barriers to having vaccination, may help contribute to an improvement in vaccination uptake. It might be useful to focus on specific topics, to create a vaccine promotion culture, like adverse effects of vaccination, and collective benefits for patients in HSE to help improve HCW staff vaccination uptake.

Relationship Between Cortical Gyrification, White Matter Connectivity, and Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, which is accompanied by differences in gray matter neuroanatomy and white matter connectivity. However, it is unknown whether these differences are linked or reflect independent aetiologies. Using a multimodal neuroimaging approach, we therefore examined 51 male adults with ASD and 48 neurotypical controls to investigate the relationship between gray matter local gyrification (lGI) and white matter diffusivity in associated fiber tracts. First, ASD individuals had a significant increase in gyrification around the left pre- and post-central gyrus. Second, white matter fiber tracts originating and/or terminating in the cluster of increased lGI had a significant increase in axial diffusivity. This increase in diffusivity was predominantly observed in tracts in close proximity to the cortical sheet. Last, we demonstrate that the increase in lGI was significantly correlated with increased diffusivity of short tracts. This relationship was not significantly modulated by a main effect of group (i.e., ASD), which was more closely associated with gray matter gyrification than white matter diffusivity. Our findings suggest that differences in gray matter neuroanatomy and white matter connectivity are closely linked, and may reflect common rather than distinct aetiological pathways.

A Dietary Feedback System for the Delivery of Consistent Personalized Dietary Advice in the Web-Based Multicenter Food4Me Study.

BACKGROUND: Despite numerous healthy eating campaigns, the prevalence of diets high in saturated fatty acids, sugar, and salt and low in fiber, fruit, and vegetables remains high. With more people than ever accessing the Internet, Web-based dietary assessment instruments have the potential to promote healthier dietary behaviors via personalized dietary advice. OBJECTIVE: The objectives of this study were to develop a dietary feedback system for the delivery of consistent personalized dietary advice in a multicenter study and to examine the impact of automating the advice system. METHODS: The development of the dietary feedback system included 4 components: (1) designing a system for categorizing nutritional intakes; (2) creating a method for prioritizing 3 nutrient-related goals for subsequent targeted dietary advice; (3) constructing decision tree algorithms linking data on nutritional intake to feedback messages; and (4) developing personal feedback reports. The system was used manually by researchers to provide personalized nutrition advice based on dietary assessment to 369 participants during the Food4Me randomized controlled trial, with an automated version developed on completion of the study. RESULTS: Saturated fatty acid, salt, and dietary fiber were most frequently selected as nutrient-related goals across the 7 centers. Average agreement between the manual and automated systems, in selecting 3 nutrient-related goals for personalized dietary advice across the centers, was highest for nutrient-related goals 1 and 2 and lower for goal 3, averaging at 92%, 87%, and 63%, respectively. Complete agreement between the 2 systems for feedback advice message selection averaged at 87% across the centers. CONCLUSIONS: The dietary feedback system was used to deliver personalized dietary advice within a multi-country study. Overall, there was good agreement between the manual and automated feedback systems, giving promise to the use of automated systems for personalizing dietary advice. TRIAL REGISTRATION: Clinicaltrials.gov NCT01530139; https://clinicaltrials.gov/ct2/show/NCT01530139 (Archived by WebCite at http://www.webcitation.org/6ht5Dgj8I).

White-matter relaxation time and myelin water fraction differences in young adults with autism.

BACKGROUND: Increasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain 'connectivity'. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism. METHOD: We performed a cross-sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T 1 relaxation times (T 1), T 2 relaxation times (T 2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview - Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T 1, T 2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed. RESULTS: Individuals with autism showed widespread WM T 1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T 1. No significant differences or correlations with symptoms were observed with respect to T 2. CONCLUSIONS: Autistic individuals have significantly lower global MWF and higher T 1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions.

Novel database for exposure to fragrance ingredients in cosmetics and personal care products.

Exposure of fragrance ingredients in cosmetics and personal care products to the population can be determined by way of a detailed and robust survey. The frequency and combinations of products used at specific times during the day will allow the estimation of aggregate exposure for an individual consumer, and to the sample population. In the present study, habits and practices of personal care and cosmetic products have been obtained from market research data for 36,446 subjects across European countries and the United States in order to determine the exposure to fragrance ingredients. Each subject logged their product uses, time of day and body application sites in an online diary for seven consecutive days. The survey data did not contain information on the amount of product used per occasion or body measurements, such as weight and skin surface area. Nevertheless, this was found from the literature where the likely amount of product used per occasion or body measurement could be probabilistically chosen from distributions of data based on subject demographics. The daily aggregate applied consumer product exposure was estimated based on each subject's frequency of product use, and Monte Carlo simulations of their likely product amount per use and body measurements. Statistical analyses of the habits and practices and consumer product exposure are presented, which show the robustness of the data and the ability to estimate aggregate consumer product exposure. Consequently, the data and modelling methods presented show potential as a means of performing ingredient safety assessments for personal care and cosmetics products.

Use of an aggregate exposure model to estimate consumer exposure to fragrance ingredients in personal care and cosmetic products.

Ensuring the toxicological safety of fragrance ingredients used in personal care and cosmetic products is essential in product development and design, as well as in the regulatory compliance of the products. This requires an accurate estimation of consumer exposure which, in turn, requires an understanding of consumer habits and use of products. Where ingredients are used in multiple product types, it is important to take account of aggregate exposure in consumers using these products. This publication investigates the use of a newly developed probabilistic model, the Creme RIFM model, to estimate aggregate exposure to fragrance ingredients using the example of 2-phenylethanol (PEA). The output shown demonstrates the utility of the model in determining systemic and dermal exposure to fragrances from individual products, and aggregate exposure. The model provides valuable information not only for risk assessment, but also for risk management. It should be noted that data on the concentrations of PEA in products used in this article were obtained from limited sources and not the standard, industry wide surveys typically employed by the fragrance industry and are thus presented here to illustrate the output and utility of the newly developed model. They should not be considered an accurate representation of actual exposure to PEA.

A structural MRI study of motor conversion disorder: evidence of reduction in thalamic volume.

OBJECTIVE: To investigate potential abnormalities in subcortical brain structures in conversion disorder (CD) compared with controls using a region of interest (ROI) approach. METHODS: Fourteen patients with motor CD were compared with 31 healthy controls using high-resolution MRI scans with an ROI approach focusing on the basal ganglia, thalamus and amygdala. Brain volumes were measured using Freesurfer, a validated segmentation algorithm. RESULTS: Significantly smaller left thalamic volumes were found in patients compared with controls when corrected for intracranial volume. These reductions did not vary with handedness, laterality, duration or severity of symptoms. CONCLUSIONS: These differences may reflect a primary disease process in this area or be secondary effects of the disorder, for example, resulting from limb disuse. Larger, longitudinal structural imaging studies will be required to confirm the findings and explore whether they are primary or secondary to CD.

Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with autism.

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato-thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto-striato-parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto-striato-cerebellar dysregulation in ASD.

The effect of age, diagnosis, and their interaction on vertex-based measures of cortical thickness and surface area in autism spectrum disorder.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is accompanied by an atypical development of brain maturation. So far, brain development has mainly been studied during early childhood in ASD, and using measures of total or lobular brain volume. However, cortical volumetric measures are a product of two distinct biological neuroanatomical features, cortical thickness, and surface area, which most likely also have different neurodevelopmental trajectories in ASD. Here, we therefore examined age-related differences in cortical thickness and surface area in a cross-sectional sample of 77 male individuals with ASD ranging from 7 to 25 years of age, and 77 male neurotypical controls matched for age and FSIQ. Surface-based measures were analyzed using a general linear model (GLM) including linear, quadratic, and cubic age terms, as well as their interactions with the main effect of group. When controlling for the effects of age, individuals with ASD had spatially distributed reductions in cortical thickness relative to controls, particularly in fronto-temporal regions, and also showed significantly reduced surface area in the prefrontal cortex and the anterior temporal lobe. We also observed significant group × age interactions for both measures. However, while cortical thickness was best predicted by a quadratic age term, the neurodevelopmental trajectory for measures of surface area was mostly linear. Our findings suggest that ASD is accompanied by age-related and region-specific reductions in cortical thickness and surface area during childhood and early adulthood. Thus, differences in the neurodevelopmental trajectory of maturation for both measures need to be taken into account when interpreting between-group differences overall.

Zygomatic arch root position in relation to dietary type in haplorhine primates.

The zygomatic root, along with other key craniofacial features, is hypothesized to play a crucial role in strengthening the face in response to stresses and strains related to feeding. As such, it has been cited as indicative of dietary specialization among fossil taxa, although it remains unknown how variable zygomatic arch root position is among living primates, and whether its positioning predicts differences in diet. We test whether primates that consume more mechanically challenging foods possess more anteriorly positioned zygomatic roots compared to those consuming less challenging foods. Zygomatic root position, as defined by the zygomaxillare landmark, was identified and recorded from digital images and physical specimens of adult primate crania. Data were collected from 33 haplorhine species (n = 722). Published data were used to assign species to a dietary type based on patterns of overall consumption along with reliance on especially challenging foods. Pairwise comparisons between mechanically challenging (hard and/or tough) and less mechanically challenging (soft) consumers found significant differences (p < 0.05) in the position of the zygomatic root in 17 of 20 pairs, 11 of which supported the prediction that a more mechanically challenging diet is associated with a more anteriorly placed zygomatic root. PGLS analysis found no significant effect of phylogeny on root position. This suggests that a more anteriorly positioned zygomatic root is useful for identifying dietary specialization in some taxa but is not required for consuming a mechanically challenging diet given that other craniofacial and behavioral factors can facilitate the consumption of such foods.

The impact of alternating drainage and inundation cycles on geochemistry and microbiology of intact peat cores.

The rewetting of degraded peatlands has been adopted as a method to address climate change. Concerns have been raised about the effects of peat inundation and drying cycles, in more extreme climate events, on the potential release of nitrogen (N) species, in particular ammonium (NH4-N), once rewetted, as well as the physico-chemical and biological properties of the peat. This study used intact peat cores to measure the impact of two different cycles of peat inundation and drying (1 month and 2 month) over a total study duration of 56 weeks on the (1) NH4-N, nitrate-N (NO3-N) and dissolved reactive phosphorus (DRP) in the soil pore water; (2) microbial community structure; (3) physico-chemical properties of the peat; and (4) the structure of the peat, and therefore its ability to mitigate flood risks and storm surges. The study found that rewetted cores released NO3-N in the pore water up to a concentration of 6.25 mg L-1, but had no appreciable impact on NH4-N, which remained below 1.7 mg L-1 over the study duration. DRP moved quickly though the upper layers of the cores, but physico-chemical analysis suggested it was adsorbed to more iron-rich soil, which was present at depths below 0.4 m in the cores. Time intervals between inundation produced no significant difference on the forms of inorganic N released, nor did it compact the soil or change the microbial community structure. The depth of the water table, however, had a significant impact on inorganic N release, particularly NO3-N, which indicates that this N species, and not NH4-N, may be problematic in rewetted peatlands.

Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma.

BACKGROUND: Epidemiological studies have linked obesity with many cancers. The insulin-like growth factor (IGF) 1 axis may be an important mediator in obesity-associated cancer. This study examined the relationship between IGF-1 and its receptor (IGF-1R) in oesophageal adenocarcinoma, a cancer strongly linked to obesity. METHODS: Patients with oesophageal adenocarcinoma considered suitable for attempted curative treatment were studied. Visceral adiposity was defined by waist circumference or visceral fat area. Free and total IGF-1 in serum were measured by enzyme-linked immunosorbent assay. Quantitative polymerase chain resection was used to determine mRNA expression of IGF-1 and IGF-1R in resected tumour samples. IGF-1R expression in tissue microarrays (TMAs) was quantified by immunohistochemistry. RESULTS: A total of 220 patients were studied. Total and free IGF-1 levels were significantly increased in the serum of viscerally obese patients. Gene expression analysis revealed a significant association between obesity status and both IGF-1R (P = 0·021) and IGF-1 (P = 0·031) in tumours. TMA analysis demonstrated that IGF-1R expression in resected tumours was significantly higher in viscerally obese patients than in those of normal weight (P = 0·023). Disease-specific survival was longer in patients with negative IGF-1R expression than in those with IGF-1R-positive tumours (median 60·0 versus 23·4 months; P = 0·027). CONCLUSION: This study highlighted the association of the IGF axis with visceral obesity, and a potential impact on the biology of oesophageal adenocarcinoma through its receptor. Targeting the IGF axis may have a rationale in future studies.

Multistate outbreak of Salmonella serotype Typhimurium infections associated with consumption of restaurant tomatoes, USA, 2006: hypothesis generation through case exposures in multiple restaurant clusters.

Multiple salmonellosis outbreaks have been linked to contaminated tomatoes. We investigated a multistate outbreak of Salmonella Typhimurium infections among 190 cases. For hypothesis generation, review of patients' food histories from four restaurant-associated clusters in four states revealed that large tomatoes were the only common food consumed by patients. Two case-control studies were conducted to identify food exposures associated with infections. In a study conducted in nine states illness was significantly associated with eating raw, large, round tomatoes in a restaurant [matched odds ratio (mOR) 3·1, 95% confidence interval (CI) 1·3-7·3]. In a Minnesota study, illness was associated with tomatoes eaten at a restaurant (OR 6·3, mid-P 95% CI 1·05-50·4, P=0·046). State, local and federal regulatory officials traced the source of tomatoes to Ohio tomato fields, a growing area not previously identified in past tomato-associated outbreaks. Because tomatoes are commonly eaten raw, prevention of tomato contamination should include interventions on the farm, during packing, and at restaurants.

Modeling the effects of low-LET cosmic rays on electronic components.

The effects of cosmic radiation in single cells, organic tissues and electronics are a major concern for space exploration and manned missions. Standard heavy ions radiation tests employ ion cocktails with energy of the order of 10 MeV per nucleon and with a linear energy transfer ranging from a few MeV cm(2) mg(-1) to hundreds of MeV cm(2) mg(-1). In space, cosmic rays show significant fluxes at energies up to the order of GeV per nucleon. The present work aims at investigating single event damage due to low-, high- and very-high-energy ions. The European Space Agency reference single event upset monitor data are used to support the discussion. Finally, the effect of ionization induced directly by primary particles and ionization induced by recoils produced in an electronic device is investigated for different types of devices.

What do general practitioners think of the new professional competence scheme?

The Irish Medical Practitioners Act 2007 places a statutory obligation on all registered Medical Practitioners to maintain their professional competence by participating in a recognised Professional Competence Scheme. A questionnaire survey was conducted among 48 GPs attending educational meetings to see if doctors had concerns about the Professional Competence Scheme and to ask if they felt they had the necessary time, skills and knowledge to carry out an audit. Twenty-eight GPs (58%) had concerns regarding their participation in the Professional Competence Scheme; 75% were concerned about the time required, and 67% felt they needed further education about the scheme. Although 73% of doctors reported that they understand how to undertake a clinical audit and 50% reported they have carried out an audit in practice, 60% have never had any teaching on audit and 85% would like teaching in this area. Only 48% of the group surveyed felt that audit was practical in their current practice. Doctors have some concerns about the new Professional Competence Scheme, including the audit component. In particular, they report a requirement for more teaching in this area, and are concerned about the time involved.