Introducing consultant outpatient clinics to community settings to improve access to paediatrics:an observational impact study

Objectives - In line with a national policy to move care ‘closer to home’, a specialist children's hospital in the National Health Service in England introduced consultant-led ‘satellite’ clinics to two community settings for general paediatric outpatient services. Objectives were to reduce non-attendance at appointments by providing care in more accessible locations and to create new physical clinic capacity. This study evaluated these satellite clinics to inform further development and identify lessons for stakeholders. Methods - Impact of the satellite clinics was assessed by comparing community versus hospital-based clinics across the following measures: (1) non-attendance rates and associated factors (including patient characteristics and travel distance) using a logistic regression model; (2) percentage of appointments booked within local catchment area; (3) contribution to total clinic capacity; (4) time allocated to clinics and appointments; and (5) clinic efficiency, defined as the ratio of income to staff-related costs. Results - Satellite clinics did not increase attendance beyond their contribution to shorter travel distance, which was associated with higher attendance. Children living in the most-deprived areas were 1.8 times more likely to miss appointments compared with those from least-deprived areas. The satellite clinics’ contribution to activity in catchment areas and to total capacity was small. However, one of the two satellite clinics was efficient compared with most hospital-based clinics. Conclusions - Outpatient clinics were relocated in pragmatically chosen community settings using a ‘drag and drop’ service model. Such clinics have potential to improve access to specialist paediatric healthcare, but do not provide a panacea. Work is required to improve attendance as part of wider efforts to support vulnerable families. Satellite clinics highlight how improved management could contribute to better use of existing capacity.

Firm-level productivity growth in Northern Ireland:the impact of exporting, innovation and public financial assistance

Motivated by the historically poor productivity performance of Northern Ireland firms and the longstanding productivity gap with the UK, the aim of this thesis is to examine, through the use of firm-level data, how exporting, innovation and public financial assistance impact on firm productivity growth. These particular activities are investigated due to the continued policy focus on their link to productivity growth and the theoretical claims of a direct positive relationship. In order to undertake these analyses a newly constructed dataset is used which links together cross-sectional and longitudinal data over the 1998-2008 period from the Annual Business Survey, the Manufacturing Sales and Export Survey; the Community Innovation Survey and Invest NI Selective Financial Assistance (SFA) payment data. Econometric methodologies are employed to estimate each of the relationships with regards to productivity growth, making use in particular of Heckman selection techniques and propensity score matching to take account of critical issues of endogeneity and selection bias. The results show that more productive firms self-select into exporting but there is no resulting productivity effect from starting to export; contesting the argument for learning-by-exporting. Product innovation is also found to have no impact on productivity growth over a four year period but there is evidence of a negative process innovation impact, likely to reflect temporary learning effects. Finally SFA assistance, including the amount of the payment, is found to have no short term impact on productivity growth suggesting substantial deadweight effects and/or targeting of inefficient firms. The results provide partial evidence as to why Northern Ireland has failed to narrow the productivity gap with the rest of the UK. The analyses further highlight the need for access to comprehensive firm-level data for research purposes, not least to underpin robust evidence-based policymaking.

Impact of a cognitive-behavioral weight control program on body weight, diet quality, and smoking cessation in weight-concerned female smokers

Many people use smoking as a weight control mechanism and do not want to quit because they fear weight gain. These weight-concerned smokers tend to be female, are significantly less likely to stop smoking, are less likely to join smoking cessation programs, and will relapse more often than smokers who are not weight-concerned. Research suggests that a woman’s confidence in her ability to control her weight after quitting relates positively with her intention to quit smoking. Likewise, success in smoking cessation has been associated with increased self-efficacy for weight control. It has been shown that success in changing one negative health behavior may trigger success in changing another, causing a synergistic effect. Recently research has focused on interventions for weight-concerned smokers who are ready to quit smoking. The present study investigated the effect of a cognitive based weight control program on self-efficacy for weight control and the effect on smoking behavior for a group of female weight concerned smokers. Two hundred and sixteen subjects who wanted to lose weight but who were not ready to quit smoking were recruited to participate in a 12-week, cognitive-behavioral weight control program consisting of twelve one-hour sessions. Subjects were randomly assigned to either (1) the weight-control program (intervention group), or (2) the control group. Results of this study demonstrated that subjects in the intervention group increased self-efficacy for weight control, which was associated with improved healthy eating index scores, weight loss, increased self-efficacy for quitting smoking, a decrease in number of cigarettes smoked and triggered positive movement in stage of change towards smoking cessation compared to the control subjects. For these subjects, positive changes in self-efficacy for one behavior (weight control) appeared to have a positive effect on their readiness to change another health behavior (smoking cessation). Further study of the psychological variables that influence weight-concerned female smokers’ decisions to initiate changes in these behaviors and their ability to maintain those changes are warranted.

Herbivore and nutrient impact on primary producer assemblages in a tropical marine environment

Globally, human populations are increasing and coastal ecosystems are becoming increasingly impacted by anthropogenic stressors. As eutrophication and exploitation of coastal resources increases, primary producer response to these drivers becomes a key indicator of ecosystem stability. Despite the importance of monitoring primary producers such as seagrasses and macroalgae, detailed studies on the response of these benthic habitat components to drivers remain relatively sparse. Utilizing a multi-faceted examination of turtle-seagrass and sea urchin-macroalgae consumer and nutrient dynamics, I elucidate the impact of these drivers in Akumal, Quintana Roo, Mexico. In Yal Ku Lagoon, macroalgae bioindicators signified high nutrient availability, which is important for further studies, but did not consistently follow published trends reflecting decreased δ 15N content with distance from suspected source. In Akumal Bay, eutrophication and grazing by turtles and fishes combine to structure patches within the seagrass beds. Grazed seagrass patches had higher structural complexity and productivity than patches continually grazed by turtles and fishes. Results from this study indicate that patch abandonment may follow giving-up density theory, the first to be recorded in the marine environment. As Diadema antillarum populations recover after their massive mortality thirty years ago, the role these echinoids will have in reducing macroalgae cover and altering ecosystem state remains to be clear. Although Diadema antillarum densities within the coral reef ecosystem were comparable to other regions within the Caribbean, the echinoid population in Akumal Bay was an insufficient driver to prevent dominance of a turf-algal-sediment (TAS) state. After a four year study, declining coral cover coupled with increased algal cover suggests that the TAS-dominated state is likely to persist over time despite echinoid recovery. Studies on macroalgal diversity and nutrients within this same region of echinoids indicated diversity and nutrient content of macroalgae increased, which may further increase the persistence of the algal-dominated state. This study provides valuable insight into the variable effects of herbivores and nutrients on primary producers within a tropical coastal ecosystem. Results from this work challenge many of the currently accepted theories on primary producer response to nutrients and herbivory while providing a framework for further studies into these dynamics.

Human Security and Crime in Latin America: The political Capital and Political Impact of Criminal Groups and Belligerents Involved in Illicit Economies

Organized crime and illegal economies generate multiple threats to states and societies. But although the negative effects of high levels of pervasive street and organized crime on human security are clear, the relationships between human security, crime, illicit economies, and law enforcement are highly complex. By sponsoring illicit economies in areas of state weakness where legal economic opportunities and public goods are seriously lacking, both belligerent and criminal groups frequently enhance some elements of human security of the marginalized populations who depend on illicit economies for basic livelihoods. Even criminal groups without a political ideology often have an important political impact on the lives of communities and on their allegiance to the State. Criminal groups also have political agendas. Both belligerent and criminal groups can develop political capital through their sponsorship of illicit economies. The extent of their political capital is dependent on several factors. Efforts to defeat belligerent groups by decreasing their financial flows through suppression of an illicit economy are rarely effective. Such measures, in turn, increase the political capital of anti-State groups. The effectiveness of anti-money laundering measures (AML) also remains low and is often highly contingent on specific vulnerabilities of the target. The design of AML measures has other effects, such as on the size of a country’s informal economy. Multifaceted anti-crime strategies that combine law enforcement approaches with targeted socio-economic policies and efforts to improve public goods provision, including access to justice, are likely to be more effective in suppressing crime than tough nailed-fist approaches. For anti-crime policies to be effective, they often require a substantial, but politically-difficult concentration of resources in target areas. In the absence of effective law enforcement capacity, legalization and decriminalization policies of illicit economies are unlikely on their own to substantially reduce levels of criminality or to eliminate organized crime. Effective police reform, for several decades largely elusive in Latin America, is one of the most urgently needed policy reforms in the region. Such efforts need to be coupled with fundamental judicial and correctional systems reforms. Yet, regional approaches cannot obliterate the so-called balloon effect. If demand persists, even under intense law enforcement pressures, illicit economies will relocate to areas of weakest law enforcement, but they will not be eliminated.

The impact of *experience, industry characteristics, and individual differences on audit risk and the extent of testing decisions: An empirical investigation

The first part of the study examined the effect of industry risk changes on perceived audit risk at the financial statement level and whether these changes depended on individual differences such as experience and tolerance for ambiguity. ^ Forty-eight auditors from two offices of one of the “Big 5” CPA firms participated in this study. The ANOVA results supported the effect of industry risk in the assessment of audit risk at the financial statement level. Higher industry risk was associated with higher perceived audit risk. Tolerance for ambiguity was also significant in explaining the changes in the assessment of audit risk. Auditors with a high tolerance for ambiguity perceived lower audit risk than auditors with a low tolerance for ambiguity. Although ANOVA results did not find experience to be significant, a t-test for experience showed it to be marginally significant and inversely related to audit risk. ^ The second part of this study examined whether differences in perceived audit risk at the financial statement level altered the extent, nature or timing of the planned auditing procedures. The results of the MANOVA suggested an overall audit risk effect at the financial statement level. Perceived audit risk was significant in explaining the variation in the number of hours planned for the total cycle and the number of hours p1anned for the tests of balances and details. Perceived audit risk was not significant in determining the analytical review procedures planned, but assessed inherent risk at the cycle level was significant. The higher the inherent risk the more analytical procedures were planned. Perceived audit risk was not significant in explaining the timing of the procedures, but individual differences were significant. The results showed that experienced auditors and those with a high tolerance for ambiguity were less likely to postpone the performance of the interim procedures or the time at which the majority of audit work would be done. ^

Impact of Vegetable Preparation Method and Taste-Test on Vegetable Preference for First Grade Children in the United States

How children rate vegetables may be influenced by the preparation method. The primary objective of this study was for first grade students to be involved in a cooking demonstration and to taste and rate vegetables raw and cooked. First grade children of two classes (N= 52: 18 boys and 34 girls (approximately half Hispanic) that had assented and had signed parental consent participated in the study. The degree of liking a particular vegetable was recorded by the students using a hedonic scale of five commonly eaten vegetables tasted first raw (pre-demonstration) and then cooked (post-demonstration). A food habit questionnaire was filled out by parents to evaluate their mealtime practices and beliefs about their child’s eating habits. Paired sample t-tests revealed significant differences in preferences for vegetables in their raw and cooked states. Several mealtime characteristics were significantly associated with children’s vegetable preferences. Parents who reported being satisfied with how often the family eats evening meals together were more likely to report that their child eats adequate vegetables for their health (p=0.026). Parents who stated that they were satisfied with their child’s eating habits were more likely to report that their child was trying new foods (p<.001). Cooking demonstrations by nutrition professionals may be an important strategy that can be used by parents and teachers to promote vegetable intake. It is important that nutrition professionals provide guidance to encourage consumption of vegetables for parents so that they can model the behavior of healthy food consumption to their children.

Defining Fluid Restriction in the Management of Infants Following Cardiac Surgery and Understanding the Subsequent Impact on Nutrient Delivery and Growth Outcomes

Adequacy of nutritional intake during the postoperative period, as measured by a change in weight-for-age z-scores from surgery to the time of discharge, was evaluated in infants (n = 58) diagnosed with a congenital heart defect and admitted for surgical intervention at Miami Children’s Hospital using a prospective observational study design. Parental consent was obtained for all infants who participated in the study. Forty patients had a weight available at hospital discharge. The mean preoperative weight-for-age z-score was -1.3 ±1.43 and the mean weight-for-age z-score at hospital discharge was -1.89 ±1.35 with a mean difference of 0.58 ±0.5 (P Nutritional intake during the postoperative period was inadequate based on a decrease in weight-for-age z-scores from the time of surgery until discharged home. Our findings suggested that limited fluid volume for nutrition likely contributes to suboptimal nutritional delivery during the postoperative period; however, inadequate nutrition prescription may also be an important contributing factor. Development of a nutrition protocol for initiation and advancement of nutrition support may reduce the delay in achieving patient’s nutritional goals and may attenuate the observed decrease in z-scores during the postoperative period.

The impact of migration and intergenerational changes on the Cuban family in the United States

This study examines changes in the Cuban family in the United States produced by time, migration, and the rise of new generations. The thesis will use a data set extracted from the 5% Public Use Microdata Series (PUMS) of the U.S. Decennial Census of Population for the years 1970, 1980 and 1990. Contingency table analysis and comparison of means were used to examine various family-related variables. The analysis points to changes in the traditional Cuban family towards less traditional family arrangements. The multigenerational feature of the Cuban household has diminished as the elderly have become independent and are more likely to be living on their own. Although female labor participation remains high, the occupational patterns of the first generation of Cuban women have diversified and a new trend has emerged for the second generation. The second generation of Cuban women demonstrates a strong inclination for white-collar occupations. Fertility rates remain low.

Grabbing Your Attention: The Impact of Finding a First Target in Multiple-Target Search

For over 50 years, the Satisfaction of Search effect, and more recently known as the Subsequent Search Miss (SSM) effect, has plagued the field of radiology. Defined as a decrease in additional target accuracy after detecting a prior target in a visual search, SSM errors are known to underlie both real-world search errors (e.g., a radiologist is more likely to miss a tumor if a different tumor was previously detected) and more simplified, lab-based search errors (e.g., an observer is more likely to miss a target ‘T’ if a different target ‘T’ was previously detected). Unfortunately, little was known about this phenomenon’s cognitive underpinnings and SSM errors have proven difficult to eliminate. However, more recently, experimental research has provided evidence for three different theories of SSM errors: the Satisfaction account, the Perceptual Set account, and the Resource Depletion account. A series of studies examined performance in a multiple-target visual search and aimed to provide support for the Resource Depletion account—a first target consumes cognitive resources leaving less available to process additional targets.

To assess a potential mechanism underlying SSM errors, eye movements were recorded in a multiple-target visual search and were used to explore whether a first target may result in an immediate decrease in second-target accuracy, which is known as an attentional blink. To determine whether other known attentional distractions amplified the effects of finding a first target has on second-target detection, distractors within the immediate vicinity of the targets (i.e., clutter) were measured and compared to accuracy for a second target. To better understand which characteristics of attention were impacted by detecting a first target, individual differences within four characteristics of attention were compared to second-target misses in a multiple-target visual search.

The results demonstrated that an attentional blink underlies SSM errors with a decrease in second-target accuracy from 135ms-405ms after detection or re-fixating a first target. The effects of clutter were exacerbated after finding a first target causing a greater decrease in second-target accuracy as clutter increased around a second-target. The attentional characteristics of modulation and vigilance were correlated with second- target misses and suggest that worse attentional modulation and vigilance are predictive of more second-target misses. Taken together, these result are used as the foundation to support a new theory of SSM errors, the Flux Capacitor theory. The Flux Capacitor theory predicts that once a target is found, it is maintained as an attentional template in working memory, which consumes attentional resources that could otherwise be used to detect additional targets. This theory not only proposes why attentional resources are consumed by a first target, but encompasses the research in support of all three SSM theories in an effort to establish a grand, unified theory of SSM errors.

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.

Impact of ocean acidification and warming on the larval development of the spider crab Hyas araneus from different latitudes (54° vs 79°N), 2010

The combined impacts of future scenarios of ocean acidification and global warming on the larvae of a cold-eurythermal spider crab, Hyas araneus L., were investigated in one of its southernmost populations (living around Helgoland, southern North Sea, 54°N) and one of the northernmost populations (Svalbard, North Atlantic, 79°N). Larvae were exposed at temperatures of 3, 9 and 15°C to present day normocapnia (380 ppm CO2) and to CO2 conditions expected for the near or medium-term future (710 ppm by 2100 and 3000 ppm CO2 by 2300 and beyond). Larval development time and biochemical composition were studied in the larval stages Zoea I, II, and Megalopa. Permanent differences in instar duration between both populations were detected in all stages, likely as a result of evolutionary temperature adaptation. With the exception of Zoea II at 3°C and under all CO2 conditions, development in all instars from Svalbard was delayed compared to those from Helgoland, under all conditions. Most prominently, development was much longer and fewer specimens morphosed to the first crab instar in the Megalopa from Svalbard than from Helgoland. Enhanced CO2 levels (710 and particularly 3000 ppm), caused extended duration of larval development and reduced larval growth (measured as dry mass) and fitness (decreasing C/N ratio, a proxy of the lipid content). Such effects were strongest in the zoeal stages in Svalbard larvae, and during the Megalopa instar in Helgoland larvae.

The differential impact of oxytocin receptor (OXTR) genotypes on the risk of autism spectrum disorder (ASD) and resulting social communication deficits

Background: Autism spectrum disorder (ASD) is multifactorial and is likely the result of complex interactions between multiple environmental and genetic factors. Recently, it has been suggested that each symptom cluster of the disorder, such as poor social communication, may be mediated by different genetic influences. Genes in the oxytocin pathway, which mediates social behaviours in humans, have been studied with single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) being implicated in ASD. This thesis examines the presence of different oxytocin receptor genotypes, and their associations with ASD and resulting social communication deficits. Methods: The relationship between four OXTR variants and ASD was evaluated in 607 ASD simplex (SPX) families. Cases were compared to their unaffected siblings using a conditional logistic approach. Odds ratios and associated 95 percent confidence intervals were obtained. A second sample of 235 individuals with a diagnosis of ASD was examined to evaluate whether these four OXTR variants were associated with social communication scores on the Autism Diagnostic Interview – Revised (ADI-R). Parameter estimates and associated 95 percent confidence intervals were generated using a linear regression approach. Multiple testing issues were addressed using false discovery adjustments. Results: The rs53576 AG genotype was significantly associated with a lower risk of ASD (OR = 0.707, 95% CI: 0.512-0.975). A single genotype (AG) provided by the rs2254298 marker was found to be significantly associated with higher social communication scores (Parameter estimate = 1.833, SE = 0.762, p = 0.0171). This association was also seen in a Caucasian only and mothers as the respondent samples. No association was significant following false discovery rate adjustments. Conclusion: The findings from these studies provide limited support for the role of OXTR SNPs in ASD, especially in social communication skills. The clinical significance of these associations remains unknown, however, it is likely that these associations do not play a role in the severity of symptoms associated with ASD. Rather, they may be important in the appearance of social deficits due to the rs2254298 markers association with enlarged amygdalas.

Molecular docking and geographical information systems as tools to assess the potential impact of veterinary medicines on non-target organisms and the environment

Veterinary medicines (VMs) from agricultural industry can enter the environment in a number of ways. This includes direct exposure through aquaculture, accidental spillage and disposal, and indirect entry by leaching from manure or runoff after treatment. Many compounds used in animal treatments have ecotoxic properties that may have chronic or sometimes lethal effects when they come into contact with non-target organisms. VMs enter the environment in mixtures, potentially having additive effects. Traditional ecotoxicology tests are used to determine the lethal and sometimes reproductive effects on freshwater and terrestrial organisms. However, organisms used in ecotoxicology tests can be unrepresentative of the populations that are likely to be exposed to the compound in the environment. Most often the tests are on single compound toxicity but mixture effects may be significant and should be included in ecotoxicology testing. This work investigates the use, measured environmental concentrations (MECs) and potential impact of sea lice treatments on salmon farms in Scotland. Alternative methods for ecotoxicology testing including mixture toxicity, and the use of in silico techniques to predict the chronic impact of VMs on different species of aquatic organisms were also investigated. The Scottish Environmental Protection Agency (SEPA) provided information on the use of five sea lice treatments from 2008-2011 on Scottish salmon farms. This information was combined with the recently available data on sediment MECs for the years 2009-2012 provided by SEPA using ArcGIS 10.1. In depth analysis of this data showed that from a total of 55 sites, 30 sites had a MEC higher than the maximum allowable concentration (MAC) as set out by SEPA for emamectin benzoate and 7 sites had a higher MEC than MAC for teflubenzuron. A number of sites that were up to 16 km away from the nearest salmon farm reported as using either emamectin benzoate or teflubenzuron measured positive for the two treatments. There was no relationship between current direction and the distribution of the sea lice treatments, nor was there any evidence for alternative sources of the compounds e.g. land treatments. The sites that had MECs higher than the MAC could pose a risk to non-target organisms and disrupt the species dynamics of the area. There was evidence that some marine protected sites might be at risk of exposure to these compounds. To complement this work, effects on acute mixture toxicity of the 5 sea lice treatments, plus one major metabolite 3-phenoxybenzoic acid (3PBA), were measured using an assay using the bioluminescent bacteria Aliivibrio fischeri. When exposed to the 5 sea lice treatments and 3PBA A. fischeri showed a response to 3PBA, emamectin benzoate and azamethiphos as well as combinations of the three. In order to establish any additive effect of the sea lice treatments, the efficacy of two mixture prediction equations, concentration addition (CA) and independent action ii(IA) were tested using the results from single compound dose response curves. In this instance IA was the more effective prediction method with a linear regression confidence interval of 82.6% compared with 22.6% of CA. In silico molecular docking was carried out to predict the chronic effects of 15 VMs (including the five used as sea lice control). Molecular docking has been proposed as an alternative screening method for the chronic effects of large animal treatments on non-target organisms. Oestrogen receptor alpha (ERα) of 7 non-target bony fish and the African clawed frog Xenopus laevis were modelled using SwissModel. These models were then ‘docked’ to oestradiol, the synthetic oestrogen ethinylestradiol, two known xenoestrogens dichlorodiphenyltrichloroethane (DDT) and bisphenol A (BPA), the antioestrogen breast cancer treatment tamoxifen and 15 VMs using Auto Dock 4. Based on the results of this work, four VMs were identified as being possible xenoestrogens or anti-oestrogens; these were cypermethrin, deltamethrin, fenbendazole and teflubenzuron. Further investigation, using in vitro assays, into these four VMs has been suggested as future work. A modified recombinant yeast oestrogen screen (YES) was attempted using the cDNA of the ERα of the zebrafish Danio rerio and the rainbow trout Oncorhynchus mykiss. Due to time and difficulties in cloning protocols this work was unable to be completed. Use of such in vitro assays would allow for further investigation of the highlighted VMs into their oestrogenic potential. In conclusion, VMs used as sea lice treatments, such as teflubenzuron and emamectin benzoate may be more persistent and have a wider range in the environment than previously thought. Mixtures of sea lice treatments have been found to persist together in the environment, and effects of these mixtures on the bacteria A. fischeri can be predicted using the IA equation. Finally, molecular docking may be a suitable tool to predict chronic endocrine disrupting effects and identify varying degrees of impact on the ERα of nine species of aquatic organisms.

Impact of selection and demography on the diffusion of lactase persistence.

The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches. Methodology We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities. Conclusions Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe.