Visual complexity of egg patterns predicts egg rejection according to Weber's law.

Visual complexity is ubiquitous in nature. Drivers of complexity include selection in coevolutionary arms races between antagonists. However, the causes and consequences of biological complexity and its perception are largely understudied, partly because complexity is difficult to quantify. Here, we address this by studying egg pattern complexity and its perception in hosts (tawny-flanked prinia Prinia subflava), which visually recognize and reject mimetic eggs of their virulent brood parasite (cuckoo finch Anomalospiza imberbis). Using field data and an optimization algorithm, we compute a complexity metric which predicts rejection of experimentally placed conspecific eggs in prinia nests. Real cuckoo finch eggs exhibit significantly lower pattern complexity than prinia eggs, suggesting that high complexity benefits hosts because it distinguishes host eggs from parasitic eggs. We show that prinias perceive complexity differences according to Weber's law of proportional processing (i.e. relative, rather than absolute, differences between stimuli are processed in discrimination, such that two eggs with simple patterns are more easily discriminable than two with complex patterns). This may influence coevolutionary trajectories of hosts and parasites. The new methods presented for quantifying complexity and its perception can help us to understand selection pressures driving the evolution of complexity and its consequences for species interactions.

Electro-hydrodynamic extraction of DNA from mixtures of DNA and bovine serum albumin.

We report separation of genomic DNA (48 kbp) from bovine serum albumin (BSA) by the electro-hydrodynamic coupling between a pressure-driven flow and a parallel electric field. Electro-hydrodynamic extraction exploits this coupling to trap DNA molecules at the entrance of a microfluidic contraction channel, while allowing proteins and salts to be flushed from the device. Samples (10 µL) containing λ-DNA (1 ng) and BSA (0.3 mg) were injected directly into the device and convected to the contraction channel entrance by a flowing buffer solution. The DNA remains trapped in this region essentially indefinitely, while proteins and salts are eluted. The effectiveness of the concept has been assessed by fluorescence measurements of DNA and BSA concentrations. Electro-hydrodynamic extraction in a single-stage device was found to enhance the concentration of DNA 40-fold, while reducing the BSA concentration by four orders of magnitude. The relative concentrations of DNA to BSA at the contraction channel entrance can be as large as 1.5 : 1, corresponding to an A260/280 ratio of 1.9. The maximum yield of DNA from a salt-free solution is 50%, while salted (150 mM) solutions have a lower yield (38%).

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial.

BACKGROUND: Thymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutritional supplementation. METHODS: The Early Nutrition and Immune Development (ENID) Trial was a randomized 2 × 2 × 2 factorial, partially blinded trial of nutritional supplementation conducted in rural Gambia, West Africa. Pregnant women (N = 875) were randomized to four intervention groups (iron-folate (standard care), multiple micronutrients, protein energy or protein energy + multiple micronutrients at 'booking' (mean gestational age at enrolment = 13.6 weeks, range 8-20 weeks) until delivery. The iron-folate and multiple micronutrient arms were administered in tablet form and the protein energy arms as a lipid-based nutritional supplement. All intervention arms contained 60 mg iron and 400 µg folic acid per daily dose. From 24 to 52 weeks of age, infants from all groups were randomized to receive a daily lipid-based nutritional supplement, with or without additional micronutrients. Thymic size was assessed by ultrasonography at 1, 8, 24 and 52 weeks of infant age, and a volume-related thymic index calculated. Detailed data on infant growth, feeding status and morbidity were collected. RESULTS: A total of 724 (82.7%) mother-infant pairs completed the trial to infant age 52 weeks. Thymic size in infancy was not significantly associated with maternal supplement group at any post-natal time point. Infants who received the daily LNS with additional micronutrients had a significantly larger thymic index at 52 weeks of age (equivalent to an 8.0% increase in thymic index [95% CI 2.89, 13.4], P = 0.002). No interaction was observed between maternal and infant supplement groups. CONCLUSIONS: A micronutrient-fortified lipid-based supplement given in the latter half of infancy increased thymic size, a key mediator of immune function. Improving the micronutrient status of infants from populations with marginal micronutrient status may improve immune development and survival. TRIAL REGISTRATION: ISRCTN registry (controlled-trials.com) Identifier: ISRCTN49285450.

Trapping DNA with a high throughput microfluidic device.

Long strands of DNA can be trapped and concentrated near the inlet of a microfluidic channel by applying a pressure gradient and an opposing electric field. The mechanism for trapping involves a migration of DNA perpendicular to both the fluid flow and the electric field. Migration leads to a highly nonuniform distribution of DNA within a cross section of the channel, with the bulk of the DNA concentrated in a thin (10 µm) layer next to the walls of the channel. This highly concentrated layer generates an electrophoretic flux toward the inlet to the device, despite the much larger fluid flow in the opposite direction. In this paper, the extent to which DNA can be trapped and concentrated by this means has been characterized by fluorescence measurements. At short times (<2 hours) nearly all the incoming DNA remains trapped within the device until the electric field is turned off. The DNA largely accumulates near the inlet, but after 30-60 minutes additional DNA starts to accumulate deeper into the channel. Eventually DNA leaks from the device itself, but ≈80% of the incoming DNA can be retained for up to 5 hours. Optimizing the electric field strength can increase the amount of DNA that can be trapped, but the efficiency is not affected by the channel cross-section.

Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

The prenatal environment can alter an individual's developmental trajectory with long-lasting effects on health. Animal models demonstrate that the impact of the early life environment extends to subsequent generations, but there is a paucity of data from human populations on intergenerational transmission of environmentally induced phenotypes. Here we investigated the association of parental exposure to energy and nutrient restriction in utero on their children's growth in rural Gambia. In a Gambian cohort with infants born between 1972 and 2011, we used multiple regression to test whether parental season of birth predicted offspring birth weight (n = 2097) or length (n = 1172), height-for-age z score (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ) at 2 yr of age (n = 923). We found that maternal exposure to seasonal energy restriction in utero was associated with reduced offspring birth length (crude:-4.2 mm, P = 0.005; adjusted: -4.0 mm, P = 0.02). In contrast, paternal birth season predicted offspring HAZ at 24 mo (crude: -0.21, P = 0.005; adjusted: -0.22, P = 0.004) but had no discernible impact at birth. Our results indicate that periods of nutritional restriction in a parent's fetal life can have intergenerational consequences in human populations. Fetal growth appears to be under matriline influence, and postnatal growth appears to be under patriline intergenerational influences.-Eriksen, K. G., Radford, E. J., Silver, M. J., Fulford, A. J. C., Wegmüller, R., Prentice, A. M. Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

Electro-hydrodynamic concentration of genomic length DNA.

We report a method of concentrating genomic length DNA within a microfluidic device, using a novel mechanism that combines polyelectrolyte migration with electrophoretic recirculation. Suitable combinations of geometry, pressure and voltage will trap long DNA molecules (>10 kbp) within a small volume (approximately 1 nL), amplifying the local concentration at rates in excess of 1000 fold per minute. The rate at which DNA accumulates is length dependent, while charged particles of similar size pass freely through the device. Experimental observations confirm that the rapid accumulation of DNA at the inlet is caused by an outward migration of the polyelectrolyte towards the capillary boundaries, followed by electrophoresis of DNA within the stagnant fluid layer next to the wall.

Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances.

Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with (a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (P=0.0004) and (b) lower probabilities of membership in a class that reported escalating use (P=0.001). These results indicate that: (a) we have identified genetic predictors of smoking cessation success, (b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and (c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts.

Transverse migration of polyelectrolytes in microfluidic channels induced by combined shear and electric fields.

If a dilute solution of a polyelectrolyte such as DNA is forced through a microcapillary by an electric field, while simultaneously driven by a pressure gradient, then the polymer will migrate in directions transverse to the field lines. Here we investigate the sharp increase in concentration in the center of the channel that arises when the flow and electric field drive the polymer in the same direction. We report the first systematic investigation of the effects of flow velocity, electric field, and ionic strength on the degree of migration. Our experiments show that migration increases with increasing shear and electric field as predicted by kinetic theory [Butler et al., Phys. Fluids, 2007, 19, 113101], but eventually saturates as suggested by computer simulations [Kekre et al., Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys., 2010, 82, 050803(R)]. The addition of salt reduces the strength of the migration, consistent with a screening of long-range hydrodynamic flow fields by added salt. However, increasing the ionic strength of a Tris-acetate-EDTA buffer solution has much less effect on the degree of migration.

A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol.

BACKGROUND: Vitamin A supplementation significantly reduces all-cause mortality when given between 6-59 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal vitamin A supplementation conducted across Africa and South Asia have produced conflicting findings. These age-pattern variations might result from immunological interactions between vitamin A supplementation and vaccines. Knowledge on the potential immunological sequelae of human neonatal vitamin A supplementation is so scarce that the foremost aim of this study is to seek indicative data on aspects of immunity likely to be affected by neonatal vitamin A supplementation. The objective of this trial is to test whether human neonatal vitamin A supplementation modulates immune function including improved thymic maturation in infancy and improved systemic immune responses to routine immunization. METHODS/DESIGN: In an area of moderate vitamin A deficiency in a peri-urban area of The Gambia, 200 mother-infant pairs were enrolled in a double-blind randomised controlled trial. Within 48 hours of birth, neonates were randomised with stratification by birth weight and sex to receive either an oral dose of 50,000 IU vitamin A or placebo. Expanded Programme of Immunisation birth vaccinations were administered after supplementation, with subsequent vaccinations administered at 8, 12 and 16 weeks of age. A range of immunological outcomes were examined up to 17 weeks of age, with additional morbidity and anthropometry follow-up carried out throughout the first year of life. The primary endpoint of this trial is the frequency of circulating T regulatory (Treg) cells expressing gut homing receptors in infants at 17 week post-supplementation, with secondary outcomes including thymus maturation and B cell immune responses. DISCUSSION: Indicative immunological data from this trial (and its Bangladeshi counterpart), will complement the larger randomised controlled trials (conducted in India, Tanzania and Ghana), on the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival. Combined these trials, in addition to the existing trials, will inform policy. TRIAL REGISTRATION: clinicaltrials.gov NCT01476358.

Combined food and micronutrient supplements during pregnancy have limited impact on child blood pressure and kidney function in rural Bangladesh.

Observational evidence suggests nutritional exposures during in utero development may have long-lasting consequences for health; data from interventions are scarce. Here, we present a trial follow-up study to assess the association between prenatal food and micronutrient supplementation and childhood blood pressure and kidney function. During the MINIMat Trial in rural Bangladesh, women were randomly assigned early in pregnancy to receive an early or later invitation to attend a food supplementation program and additionally to receive either iron and folate or multiple micronutrient tablets daily. The 3267 singleton birth individuals with measured anthropometry born during the trial were eligible for a follow-up study at 4.5 y old. A total of 77% of eligible individuals were recruited and blood pressure, kidney size by ultrasound, and glomerular filtration rate (GFR; calculated from plasma cystatin c) were assessed. In adjusted analysis, early invitation to food supplementation was associated with a 0.72-mm Hg [(95% CI: 0.16, 1.28); P = 0.01] lower childhood diastolic blood pressure and maternal MMS supplementation was associated with a marginally higher [0.87 mm Hg (95% CI: 0.18, 1.56); P = 0.01] childhood diastolic blood pressure. There was also some evidence that a supplement higher in iron was associated with a higher offspring GFR. No other effects of the food or micronutrient interventions were observed and there was no interaction between the interventions on the outcomes studied. These marginal associations and small effect sizes suggest limited public health importance in early childhood.

Online peer support for mental health problems in the United States: 2004-2010.

BACKGROUND: Help seeking for online peer and other social support in response to depression and other mental health problems offers an electronic technology alternative to traditional mental health care. Here, with nationally representative samples of adult community residents in the USA, we study online peer support help seeking, estimate its occurrence, and investigate depression and other suspected predictors and correlates, some of which might prove to be causal influences. METHOD: The data are from nationally representative probability sample surveys of the non-institutionalized US adult population, with a new independent sample assessed via confidential computerized self-assessment modules each year from 2004 to 2010, yielding estimates about online peer support. A total of 264,431 adults participated in these years. RESULTS: An estimated three per 1000 adults (0.3%) seek online peer support for mental health problems each year (95% confidence interval 0.0022-0.0036). Individuals with depression and/or serious psychological distress are strongly over-represented among these adult online peer support help seekers (odds ratio >7, p < 0.001). Associations with college education, being non-Hispanic white, being female, and age are also noteworthy (p < 0.05). CONCLUSIONS: Online help seeking for mental health social support is becoming frequent enough for study in large sample national surveys, and might well be fostered by active neuropsychiatric ailments such as depression or other serious psychological distress. Open questions remain about whether the result is beneficial, or conditions required for efficacious online peer support, as might be disclosed in definitive evidence from randomized controlled trials.

Embarrassment when illness strikes a close relative: a World Mental Health Survey Consortium Multi-Site Study.

BACKGROUND: In this global study we sought to estimate the degree to which a family member might feel embarrassed when a close relative is suffering from an alcohol, drug, or mental health condition (ADMC) versus a general medical condition (GMC). To date, most studies have considered embarrassment and stigma in society and internalized by the afflicted individual but have not assessed family embarrassment in a large-scale study. METHOD: In 16 sites of the World Mental Health Surveys (WMHS), standardized assessments were completed including items on family embarrassment. Site matching was used to constrain local socially shared determinants of stigma-related feelings, enabling a conditional logistic regression model that estimates the embarrassment close relatives may hold in relation to family members affected by an ADMC, a GMC, or both conditions. RESULTS: There was a statistically robust association such that subgroups with an ADMC-affected relative were more likely to feel embarrassed compared to subgroups with a relative affected by a GMC (p<0.001), even with covariate adjustments for age and sex. CONCLUSIONS: . The pattern of evidence from this research is consistent with conceptual models for interventions that target individual- and family-level stigma-related feelings of embarrassment as possible obstacles to effective early intervention and treatment for an ADMC. Macro-level interventions are under way but micro-level interventions may also be required among family members, along with care for each person with an ADMC.

Chase-away evolution maintains imperfect mimicry in a brood parasite-host system despite rapid evolution of mimics.

We studied a brood parasite-host system (the cuckoo finch Anomalospiza imberbis and its host, the tawny-flanked prinia Prinia subflava) to test (1) the fundamental hypothesis that deceptive mimics evolve to resemble models, selecting in turn for models to evolve away from mimics ('chase-away evolution') and (2) whether such reciprocal evolution maintains imperfect mimicry over time. Over only 50 years, parasites evolved towards hosts and hosts evolved away from parasites, resulting in no detectible increase in mimetic fidelity. Our results reflect rapid adaptive evolution in wild populations of models and mimics and show that chase-away evolution in models can counteract even rapid evolution of mimics, resulting in the persistence of imperfect mimicry.

Intergenerational effects of maternal birth season on offspring size in rural Gambia.

Environmental conditions experienced in early life can influence an individual's growth and long-term health, and potentially also that of their offspring. However, such developmental effects on intergenerational outcomes have rarely been studied. Here we investigate intergenerational effects of early environment in humans using survey- and clinic-based data from rural Gambia, a population experiencing substantial seasonal stress that influences foetal growth and has long-term effects on first-generation survival. Using Fourier regression to model seasonality, we test whether (i) parental birth season has intergenerational consequences for offspring in utero growth (1982 neonates, born 1976-2009) and (ii) whether such effects have been reduced by improvements to population health in recent decades. Contrary to our predictions, we show effects of maternal birth season on offspring birth weight and head circumference only in recent maternal cohorts born after 1975. Offspring birth weight varied according to maternal birth season from 2.85 to 3.03 kg among women born during 1975-1984 and from 2.84 to 3.41 kg among those born after 1984, but the seasonality effect reversed between these cohorts. These results were not mediated by differences in maternal age or parity. Equivalent patterns were observed for offspring head circumference (statistically significant) and length (not significant), but not for ponderal index. No relationships were found between paternal birth season and offspring neonatal anthropometrics. Our results indicate that even in rural populations living under conditions of relative affluence, brief variation in environmental conditions during maternal early life may exert long-term intergenerational effects on offspring.

Twinning propensity and offspring in utero growth covary in rural African women.

In humans and other mammals, some females are more likely to experience twin pregnancies than others, but the reasons behind such individual variation are poorly understood. One hypothesis invokes variation in the dynamics of the insulin-like growth factor (IGF) system, which also regulates foetal growth. Using data from a rural African population living in a highly seasonal environment, we test a novel prediction generated by this hypothesis, that maternal twinning status predicts offspring birthweight. We found that among singleton offspring who experience a favourable in utero environment (born January-June), births before and after twins are, respectively, associated with a 134.07 g and 226.41 g increase in birthweight compared with those born to non-twinning mothers. These results were not mediated by maternal anthropometry. This is consistent with a role for the IGF system in individual variation in twinning propensity, a possibility with implications for understanding mechanisms of life-history variation in humans and other vertebrates.

Lectin microarray profiling of metastatic breast cancers.

Altered protein glycosylation compared with the disease-free state is a universal feature of cancer cells. It has long been established that distinct glycan structures are associated with specific forms of cancer, but far less is known about the complete array of glycans associated with certain tumors. The cancer glycome has great potential as a source of biomarkers, but progress in this field has been hindered by a lack of available techniques for the elucidation of disease-associated glycosylation. In the present study, lectin microarrays consisting of 45 lectins with different binding preferences covering N- and O-linked glycans were coupled with evanescent-field activated fluorescent detection in the glycomic analysis of primary breast tumors and the serum and urine of patients with metastatic breast cancer. A single 50 µm section of a primary breast tumor or <1 µL of breast cancer patient serum or urine was sufficient to detect glycosylation alterations associated with metastatic breast cancer, as inferred from lectin-binding patterns. The high-throughput, sensitive and relatively simple nature of the simultaneous analysis of N- and O-linked glycosylation following minimal sample preparation and without the need for protein deglycosylation makes the lectin microarray analysis described a valuable tool for discovery phase glycomic profiling.

Reactive Flows in Porous Media: Challenges in Theoretical and Numerical Methods.

We review theoretical and computational research, primarily from the past 10 years, addressing the flow of reactive fluids in porous media. The focus is on systems where chemical reactions at the solid-fluid interface cause dissolution of the surrounding porous matrix, creating nonlinear feedback mechanisms that can often lead to greatly enhanced permeability. We discuss insights into the evolution of geological forms that can be inferred from these feedback mechanisms, as well as some geotechnical applications such as enhanced oil recovery, hydraulic fracturing, and carbon sequestration. Until recently, most practical applications of reactive transport have been based on Darcy-scale modeling, where averaged equations for the flow and reactant transport are solved. We summarize the successes and limitations of volume averaging, which leads to Darcy-scale equations, as an introduction to pore-scale modeling. Pore-scale modeling is computationally intensive but offers new insights as well as tests of averaging theories and pore-network models. We include recent research devoted to validation of pore-scale simulations, particularly the use of visual observations from microfluidic experiments.

Mechanics of Vorticella contraction.

Vorticella convallaria is one of a class of fast-moving organisms that can traverse its body size in less than a millisecond by rapidly coiling a slender stalk anchoring it to a nearby surface. The stalk houses a fiber called the spasmoneme, which winds helically within the stalk and rapidly contracts in response to calcium signaling. We have developed a coupled mechanical-chemical model of the coiling process, accounting for the coiling of the elastic stalk and the binding of calcium to the protein spasmin. Simulations of the model describe the contraction and recovery processes quantitatively. The stalk-spasmoneme system is shown to satisfy geometric constraints, which explains why the cell body sometimes rotates during contraction. The shape of the collapsing and recovering stalk bounds its effective bending stiffness. Simulations suggest that recovery from the contracted state is driven by the stalk at a rate controlled by dissociation of calcium from spasmin.

Suspected causal association between cocaine use and occurrence of panic.

AIM: To estimate a suspected causal association between cocaine use and the occurrence of panic. METHODS: Data are from an epidemiologic sample of school-attending youths enrolled in primary school who were traced, rerecruited, and assessed via standardized interviews in young adulthood during 2000-2002. A total of 1,692 young adults comprised the analysis sample. Occurrences of panic and cocaine use were assessed in young adulthood, via standardized item sets from the Diagnostic Interview Schedule. A brief assessment of panic experiences had also been made when the youths were in early adolescence. RESULTS: With statistical adjustment for important covariates, we found a modestly excess occurrence of panic attack-like experiences among those who had used cocaine at least once, relative to occurrence among young people who never had used cocaine (estimated odds ratio, OR = 1.9; p = .014 before exclusion of 288 with early onset panic attack-like experiences; p = .005 after this exclusion). DISCUSSION: The main finding of this study was an association linking cocaine use and panic attack-like experiences, which was more modest than was observed in study samples that included older adults.

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.