Clinical trial designs of new medicinal products for treating schizophrenia: discussion of EMA's Guideline and a Better Long Term Trial Design

Background and Objectives: Schizophrenia is a severe chronic disease. Endpoint variables lack objectivity and the diagnostic criteria have evolved with time. In order to guide the development of new drugs, European Medicines Agency (EMA) issued a guideline on the clinical investigation of medicinal products for the treatment of schizophrenia. Methods: Authors reviewed and discussed the efficacy trial part of the Guideline. Results: The Guideline divides clinical efficacy trials into short-term trials and long-term trials. The short-term three-arm trial is recommended to replace the short-term two-arm active-controlled non-inferiority trial because the latter has sensitivity issues. The Guideline ultimately makes that three-arm trial a superiority trial. The Guideline discusses four types of long-term trial designs. The randomized withdrawal trial design has some disadvantages. Long-term two-arm active-controlled non-inferiority trial is not recommended due to the sensitivity issue. Extension of the short-term trial is only suitable for extension of the short-term two-arm active-controlled superiority trial. The Guideline suggests that a hybrid design of a randomized withdrawal trial incorporated into a long-term parallel trial might be optimal. However, such a design has some disadvantages and might be too complex to be carried out. Authors suggest instead a three-group long-term trial design, which could provide comparison between test drug and active comparator along with comparison between the test drug and placebo. This alternative could arguably be much easier to carry out compared with the hybrid design. Conclusions: The three-group long-term design merits further discussion and evaluation.

The RGBarrier assay: the parallel study of gene regulatory element performance at defined chromosomal locations

Vertebrate genomes are organised into a variety of nuclear environments and chromatin states that have profound effects on the regulation of gene transcription. This variation presents a major challenge to the expression of transgenes for experimental research, genetic therapies and the production of biopharmaceuticals. The majority of transgenes succumb to transcriptional silencing by their chromosomal environment when they are randomly integrated into the genome, a phenomenon known as chromosomal position effect (CPE). It is not always feasible to target transgene integration to transcriptionally permissive “safe harbour” loci that favour transgene expression, so there remains an unmet need to identify gene regulatory elements that can be added to transgenes which protect them against CPE. Dominant regulatory elements (DREs) with chromatin barrier (or boundary) activity have been shown to protect transgenes from CPE. The HS4 element from the chicken beta-globin locus and the A2UCOE element from a human housekeeping gene locus have been shown to function as DRE barriers in a wide variety of cell types and species. Despite rapid advances in the profiling of transcription factor binding, chromatin states and chromosomal looping interactions, progress towards functionally validating the many candidate barrier elements in vertebrates has been very slow. This is largely due to the lack of a tractable and efficient assay for chromatin barrier activity. In this study, I have developed the RGBarrier assay system to test the chromatin barrier activity of candidate DREs at pre-defined isogenic loci in human cells. The RGBarrier assay consists in a Flp-based RMCE reaction for the integration of an expression construct, carrying candidate DREs, in a pre-characterised chromosomal location. The RGBarrier system involves the tracking of red, green and blue fluorescent proteins by flow cytometry to monitor on-target versus off-target integration and transgene expression. The analysis of the reporter (GFP) expression for several weeks gives a measure of the protective ability of each candidate elements from chromosomal silencing. This assay can be scaled up to test tens of new putative barrier elements in the same chromosomal context in parallel. The defined chromosomal contexts of the RGBarrier assays will allow for detailed mechanistic studies of chromosomal silencing and DRE barrier element action. Understanding these mechanisms will be of paramount importance for the design of specific solutions for overcoming chromosomal silencing in specific transgenic applications.

Improving drug discovery using a neural networks based parallel scoring function

Virtual Screening (VS) methods can considerably aid clinical research, predicting how ligands interact with drug targets. Most VS methods suppose a unique binding site for the target, but it has been demonstrated that diverse ligands interact with unrelated parts of the target and many VS methods do not take into account this relevant fact. This problem is circumvented by a novel VS methodology named BINDSURF that scans the whole protein surface to find new hotspots, where ligands might potentially interact with, and which is implemented in massively parallel Graphics Processing Units, allowing fast processing of large ligand databases. BINDSURF can thus be used in drug discovery, drug design, drug repurposing and therefore helps considerably in clinical research. However, the accuracy of most VS methods is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to solve this problem, we propose a novel approach where neural networks are trained with databases of known active (drugs) and inactive compounds, and later used to improve VS predictions.

The scientific rationale, design and implementation plan for a Biogeochemical-Argo float array

Biogeochemical-Argo is the extension of the Argo array of profiling floats to include floats that are equipped with biogeochemical sensors for pH, oxygen, nitrate, chlorophyll, suspended particles, and downwelling irradiance. Argo is a highly regarded, international program that measures the changing ocean temperature (heat content) and salinity with profiling floats distributed throughout the ocean. Newly developed sensors now allow profiling floats to also observe biogeochemical properties with sufficient accuracy for climate studies. This extension of Argo will enable an observing system that can determine the seasonal to decadal-scale variability in biological productivity, the supply of essential plant nutrients from deep-waters to the sunlit surface layer, ocean acidification, hypoxia, and ocean uptake of CO2. Biogeochemical-Argo will drive a transformative shift in our ability to observe and predict the effects of climate change on ocean metabolism, carbon uptake, and living marine resource management. Presently, vast areas of the open ocean are sampled only once per decade or less, with sampling occurring mainly in summer. Our ability to detect changes in biogeochemical processes that may occur due to the warming and acidification driven by increasing atmospheric CO2, as well as by natural climate variability, is greatly hindered by this undersampling. In close synergy with satellite systems (which are effective at detecting global patterns for a few biogeochemical parameters, but only very close to the sea surface and in the absence of clouds), a global array of biogeochemical sensors would revolutionize our understanding of ocean carbon uptake, productivity, and deoxygenation. The array would reveal the biological, chemical, and physical events that control these processes. Such a system would enable a new generation of global ocean prediction systems in support of carbon cycling, acidification, hypoxia and harmful algal blooms studies, as well as the management of living marine resources. In order to prepare for a global Biogeochemical-Argo array, several prototype profiling float arrays have been developed at the regional scale by various countries and are now operating. Examples include regional arrays in the Southern Ocean (SOCCOM ), the North Atlantic Sub-polar Gyre (remOcean ), the Mediterranean Sea (NAOS ), the Kuroshio region of the North Pacific (INBOX ), and the Indian Ocean (IOBioArgo ). For example, the SOCCOM program is deploying 200 profiling floats with biogeochemical sensors throughout the Southern Ocean, including areas covered seasonally with ice. The resulting data, which are publically available in real time, are being linked with computer models to better understand the role of the Southern Ocean in influencing CO2 uptake, biological productivity, and nutrient supply to distant regions of the world ocean. The success of these regional projects has motivated a planning meeting to discuss the requirements for and applications of a global-scale Biogeochemical-Argo program. The meeting was held 11-13 January 2016 in Villefranche-sur-Mer, France with attendees from eight nations now deploying Argo floats with biogeochemical sensors present to discuss this topic. In preparation, computer simulations and a variety of analyses were conducted to assess the resources required for the transition to a global-scale array. Based on these analyses and simulations, it was concluded that an array of about 1000 biogeochemical profiling floats would provide the needed resolution to greatly improve our understanding of biogeochemical processes and to enable significant improvement in ecosystem models. With an endurance of four years for a Biogeochemical-Argo float, this system would require the procurement and deployment of 250 new floats per year to maintain a 1000 float array. The lifetime cost for a Biogeochemical-Argo float, including capital expense, calibration, data management, and data transmission, is about $100,000. A global Biogeochemical-Argo system would thus cost about $25,000,000 annually. In the present Argo paradigm, the US provides half of the profiling floats in the array, while the EU, Austral/Asia, and Canada share most the remaining half. If this approach is adopted, the US cost for the Biogeochemical-Argo system would be ~$12,500,000 annually and ~$6,250,000 each for the EU, and Austral/Asia and Canada. This includes no direct costs for ship time and presumes that float deployments can be carried out from future research cruises of opportunity, including, for example, the international GO-SHIP program (http://www.go-ship.org). The full-scale implementation of a global Biogeochemical-Argo system with 1000 floats is feasible within a decade. The successful, ongoing pilot projects have provided the foundation and start for such a system.

Are the preference and selection patterns of hermit crabs for gastropod shells species- or site-specific?

Experimental analyses of hermit crabs and their preferences for shells are essential to understand the intrinsic relationship of the crabs' dependence on shells, and may be useful to explain their shell use pattern in nature. The aim of this study was to evaluate the effect of crab species and site on the pattern of shell use, selection, and preference in the south-western Atlantic hermit crabs Pagurus brevidactylus and Pagurus criniticornis, comparing sympatric and allopatric populations. Differently from the traditional approach to evaluate shell preference by simply determining the shell selection pattern (i.e., the number of shells of each type selected), preference was defined (according to [Liszka, D., Underwood, AJ., 1990. An experimental design to determine preferences for gastropod shells by a hermit-crab. J. Exp. Mar. Biol. Ecol., 137(1), 47-62]) by the comparison of the number of crabs changing for a particular shell type when three options were given (Cerithium atratum, Morula nodulosa, and Tegula viridula) with the number of crabs changing for this same type when only this type was offered. The effect of crab species was tested at Cabelo Gordo Beach, where P. brevidacrylus was found occupying shells of C. atratum, M. nodulosa, and T viridula in similar frequencies, whereas P. criniticornis occupied predominantly shells of C atratum. In laboratory experiments the selection patterns of the two hermit-crab species for these three gastropods were different, with P criniticornis selecting mainly shells of C atratum, and R brevidactylus selecting more shells of M. nodulosa. The shell preference was also dependent on crab species, with P. criniticornis showing a clear preference for shells of C atratum, whereas P. brevidactylus did not show a preference for any of the tested shells. The effect of site was tested for the two species comparing data from Cabelo Gordo to Preta (P brevidactylus) and Araca beaches (P. criniticornis). The pattern of shell use, selection, and preference was demonstrated to be dependent on site only for P. brevidactylus. The results also showed that the shell use pattern of P criniticornis can be explained by its preference at both sites, whereas for P. brevidactylus it occurred only at Cabelo Gordo, where the absence of preference was correlated with the similar use of the three gastropod species studied. Finally, the results showed that the shell selection pattern cannot be considered as a measure of shell preference, since it overestimates crab selectivity. (C) 2009 Elsevier B.V. All rights reserved.

Holistic Design In High-Speed Optical Interconnects

Integrated circuit scaling has enabled a huge growth in processing capability, which necessitates a corresponding increase in inter-chip communication bandwidth. As bandwidth requirements for chip-to-chip interconnection scale, deficiencies of electrical channels become more apparent. Optical links present a viable alternative due to their low frequency-dependent loss and higher bandwidth density in the form of wavelength division multiplexing. As integrated photonics and bonding technologies are maturing, commercialization of hybrid-integrated optical links are becoming a reality. Increasing silicon integration leads to better performance in optical links but necessitates a corresponding co-design strategy in both electronics and photonics. In this light, holistic design of high-speed optical links with an in-depth understanding of photonics and state-of-the-art electronics brings their performance to unprecedented levels. This thesis presents developments in high-speed optical links by co-designing and co-integrating the primary elements of an optical link: receiver, transmitter, and clocking.

In the first part of this thesis a 3D-integrated CMOS/Silicon-photonic receiver will be presented. The electronic chip features a novel design that employs a low-bandwidth TIA front-end, double-sampling and equalization through dynamic offset modulation. Measured results show -14.9dBm of sensitivity and energy efficiency of 170fJ/b at 25Gb/s. The same receiver front-end is also used to implement source-synchronous 4-channel WDM-based parallel optical receiver. Quadrature ILO-based clocking is employed for synchronization and a novel frequency-tracking method that exploits the dynamics of IL in a quadrature ring oscillator to increase the effective locking range. An adaptive body-biasing circuit is designed to maintain the per-bit-energy consumption constant across wide data-rates. The prototype measurements indicate a record-low power consumption of 153fJ/b at 32Gb/s. The receiver sensitivity is measured to be -8.8dBm at 32Gb/s.

Next, on the optical transmitter side, three new techniques will be presented. First one is a differential ring modulator that breaks the optical bandwidth/quality factor trade-off known to limit the speed of high-Q ring modulators. This structure maintains a constant energy in the ring to avoid pattern-dependent power droop. As a first proof of concept, a prototype has been fabricated and measured up to 10Gb/s. The second technique is thermal stabilization of micro-ring resonator modulators through direct measurement of temperature using a monolithic PTAT temperature sensor. The measured temperature is used in a feedback loop to adjust the thermal tuner of the ring. A prototype is fabricated and a closed-loop feedback system is demonstrated to operate at 20Gb/s in the presence of temperature fluctuations. The third technique is a switched-capacitor based pre-emphasis technique designed to extend the inherently low bandwidth of carrier injection micro-ring modulators. A measured prototype of the optical transmitter achieves energy efficiency of 342fJ/bit at 10Gb/s and the wavelength stabilization circuit based on the monolithic PTAT sensor consumes 0.29mW.

Lastly, a first-order frequency synthesizer that is suitable for high-speed on-chip clock generation will be discussed. The proposed design features an architecture combining an LC quadrature VCO, two sample-and-holds, a PI, digital coarse-tuning, and rotational frequency detection for fine-tuning. In addition to an electrical reference clock, as an extra feature, the prototype chip is capable of receiving a low jitter optical reference clock generated by a high-repetition-rate mode-locked laser. The output clock at 8GHz has an integrated RMS jitter of 490fs, peak-to-peak periodic jitter of 2.06ps, and total RMS jitter of 680fs. The reference spurs are measured to be –64.3dB below the carrier frequency. At 8GHz the system consumes 2.49mW from a 1V supply.

Morbidity patterns among the underweight, overweight and obese between 2 and 18 years: population-based cross-sectional analyses

CONTEXT: No study has documented how symptomatic morbidity varies across the body mass index (BMI) spectrum (underweight, normal weight, overweight and obese) or across the entire child and adolescent age range. OBJECTIVE: To (1) quantify physical and psychosocial morbidities experienced by 2-18-year-olds according to BMI status and (2) explore morbidity patterns by age. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional data from two Australian population studies (the Longitudinal Study of Australian Children and the Health of Young Victorians Study) were collected during 2000-2006. Participants were grouped into five age bands: 2-3 (n=4606), 4-5 (n=4983), 6-7 (n=4464), 8-12 (n=1541) and 13-18 (n=928) years. MAIN MEASURES: Outcomes-Parent- and self-reported global health; physical, psychosocial and mental health; special health-care needs; wheeze; asthma and sleep problems. Exposure-measured BMI (kg m(-2)) categorised using standard international cutpoints. ANALYSES: The variation in comorbidities across BMI categories within and between age bands was examined using linear and logistic regression models. RESULTS: Comorbidities varied with BMI category for all except sleep problems, generally showing the highest levels for the obese category. However, patterns differed markedly between age groups. In particular, poorer global health and special health-care needs were associated with underweight in young children, but obesity in older children. Prevalence of poorer physical health varied little by BMI in 2-5-year-olds, but from 6 to 7 years was increasingly associated with obesity. Normal-weight children tended to experience the best psychosocial and mental health, with little evidence that the U-shaped associations of these variables with BMI status varied by age. Wheeze and asthma increased slightly with BMI at all ages. CONCLUSIONS: Deviation from normal weight is associated with health differences in children and adolescents that vary by morbidity and age. As well as lowering risks for later disease, promoting normal body weight appears central to improving the health and well-being of the young.

New challenges in making plans: putting design back into the applied science of planning

The origins of the ‘planning’ lie in the regional sciences and attempts to undertake social engineering of land use occupancy.
Over the last 100 years planning, as a discipline, has variously dabbled in design on the margins with urban design and neourbanism, but has stayed staunchly in the applied science and social science realms. This penchant detrimentally affects its graduates abilities to holistically appreciate and envision the consequences of their decisions-making and plan-making, to convey strength of conviction and expertise to the community, but also to establish a solid basis upon which its professional practice applications and decision-making paradigms successfully articulate equity and comprehensiveness of rational land use and development planning and decision-making. While planning re-learnt how to legitimately evaluate design and aesthetics into planning in the 1960s through the emergent McHargian ecological design paradigm, quickly embracing it as a consequence of major environmental land use disasters that occurred ‘on its watch’ that were demonstrable failures of its claimed insight and professional responsibilities, it has struggled as a discipline to embrace design as an integral technology in its daily operations and expressed ‘territory’ of professional responsibility. This paper reviews this legacy and then charts some emergent patterns in the teaching and practice of planning in Australia that are attempting to re-position design as a legitimate and integral part of the knowledge and skills of a professional planners.

Dietary patterns and successful ageing: a systematic review

PURPOSE: Nutrition is a key determinant of chronic disease in later life. A systematic review was conducted of studies examining dietary patterns and quality of life, physical function, cognitive function and mental health among older adults. METHODS: Literature searches in MEDLINE complete, Academic Search Complete, CINAHL Complete, Ageline, Global health, PsycINFO, SCOPUS and EMBASE and hand searching from 1980 up to December 2014 yielded 1236 results. Inclusion criteria included dietary pattern assessment via dietary indices or statistical approaches, a sample of community-dwelling adults aged 45 years and over at baseline and a cross-sectional or longitudinal study design. Exclusion criteria included a single 24-h recall of diet, evaluation of single foods or nutrients, clinical or institutionalised samples and intervention studies. Risk of bias was assessed using the six-item Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies. RESULTS: There were 34 articles (11 cross-sectional and 23 longitudinal) included with 23 studies examining dietary indices and 13 studies using empirical analysis. Most studies examined mental health (n = 10) or cognitive function (n = 18), with fewer studies examining quality of life (n = 6) and physical function (n = 8). Although dietary pattern and outcome assessment methods varied, most studies reported positive associations between a healthier diet and better health outcomes. CONCLUSION: Overall, the number of studies using dietary patterns to investigate diet and successful ageing is small, and further investigation in longitudinal studies is needed, particularly for quality-of-life outcomes. This review provides support for the importance of a healthy diet for the ageing population globally.

Drinking patterns of adolescents who develop alcohol use disorders: results from the Victorian adolescent health cohort study

Objective: We identify drinking styles that place teensat greatest risk of later alcohol use disorders (AUD).Design: Population-based cohort study.Setting: Victoria, Australia.

Participants: A representative sample of 1943adolescents living in Victoria in 1992.Outcome measures: Teen drinking was assessed at6 monthly intervals (5 waves) between mean ages 14.9and 17.4 years and summarised across waves as none,one, or two or more waves of: (1) frequent drinking(3+ days in the past week), (2) loss of control overdrinking (difficulty stopping, amnesia), (3) bingedrinking (5+ standard drinks in a day) and (4) heavybinge drinking (20+ and 11+ standard drinks in a dayfor males and females, respectively). Young AdultAlcohol Use Disorder (AUD) was assessed at 3 yearlyintervals (3 waves) across the 20s (mean ages 20.7through 29.1 years).

Results: We show that patterns of teen drinkingcharacterised by loss of control increase risk for AUDacross young adulthood: loss of control over drinking(one wave OR 1.4, 95% CI 1.1 to 1.8; two or morewaves OR 1.9, CI 1.4 to 2.7); binge drinking (one waveOR 1.7, CI 1.3 to 2.3; two or more waves OR 2.0, CI1.5 to 2.6), and heavy binge drinking (one wave OR2.0, CI 1.4 to 2.8; two or more waves OR 2.3, CI 1.6 to3.4). This is not so for frequent drinking, which wasunrelated to later AUD. Although drinking was morecommon in males, there was no evidence of sexdifferences in risk relationships.

Conclusions: Our results extend previous work byshowing that patterns of drinking that represent loss ofcontrol over alcohol consumption (however expressed)are important targets for intervention. In addition tocurrent policies that may reduce overall consumption,emphasising prevention of more extreme teenagebouts of alcohol consumption appears warranted.

Validation of a body-worn accelerometer to measure activity patterns in octogenarians

OBJECTIVE: To determine the validity of a triaxial body-worn accelerometer for detection of gait and postures in people aged >80 years. DESIGN: Participants performed a range of activities (sitting, lying, walking, standing) in both a controlled and a home setting while wearing the accelerometer. Activities in the controlled setting were performed in a scripted sequence. Activities in the home setting were performed in an unscripted manner. Analyzed accelerometer data were compared against video observation as the reference measure. SETTING: Independent-living and long-term-care retirement village. PARTICIPANTS: Older people (N=22; mean age ± SD, 88.1±5y) residing in long-term-care and independent-living retirement facilities. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The level of agreement between video observation and the accelerometer for the total duration of each activity, and second-by-second correspondence between video observation and the accelerometer for each activity. RESULTS: The median absolute percentage errors between video observation and the accelerometer were <1% for locomotion and lying. The absolute percentage errors were higher for sitting (median, -22.3%; interquartile range [IQR], -62.8% to 10.7%) and standing (median, 24.7%; IQR, -7.3% to 39.6%). A second-by-second analysis between video observation and the accelerometer found an overall agreement of ≥85% for all activities except standing (median, 56.1%; IQR, 34.8%-81.2%). CONCLUSIONS: This single-device accelerometer provides a valid measure of lying and locomotion in people aged >80 years. There is an error of approximately 25% when discriminating sitting from standing postures, which needs to be taken into account when monitoring longer-term habitual activity in this age group.

Design and conduct of a pragmatic randomized controlled trial to enhance smoking-cessation outcomes with exercise: The Fit2Quit study

Background: Most smokers want to stop smoking and many try to quit. However abstinence rates are low and most smokers do not manage to abstain for even a week. Relapse to smoking can be related to the occurrence of tobacco withdrawal symptoms (e.g., sleep disturbance, irritability, and craving) and weight gain. If regular exercise mitigates these effects it could have potential as an aid to smoking cessation. The aim of the Fit2Quit study is to determine the effects of a home and community-based exercise intervention on smoking abstinence at six months when used as an adjunct to usual care (telephone smoking-cessation counseling and nicotine replacement therapy; NRT). Methods/design: A prospective parallel two-arm randomized controlled trial. Participants (n = 1400, 700 per arm) will be randomized to a structured home and community-based exercise program plus usual care (behavioral counseling and NRT) or to usual-care alone. It is targeted that at least 25% of the sample will be of Mori ethnicity (New Zealand indigenous). Outcomes to be measured using intention-to-treat analysis include: seven-day point prevalence of smoking abstinence verified by salivary cotinine (primary outcome); 6 months continuous abstinence; body mass index (BMI); cardio-respiratory fitness; physical activity levels; and cost effectiveness. Discussion: The Fit2Quit study is an example of a large, pragmatic randomized controlled trial in a community setting. Specific components of the exercise intervention are outlined in detail. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12609000637246.

Patterns of time use among regional and rural adolescent girls: associations with correlates of physical activity and health-related quality of life

OBJECTIVES: To describe patterns of time use among regional and rural adolescent girls and compare identified clusters with respect to correlates of physical activity (PA) and health-related quality of life (HRQoL).

DESIGN: Cross-sectional PA and lifestyle survey.

METHODS: Data were from Year 7-9 adolescent girls (aged 12-15 years) from 16 schools involved in a cluster-randomised trial in regional and rural Victoria, Australia (n=494). Time use data were collected using 24-h Previous Day Physical Activity Recall (PDPAR-24) questionnaire, collapsed into 17 categories of time use. Differences between time use clusters with regard to demographics, correlates of PA and HRQoL measured using PedsQL 4.0 Generic Core Scales, were investigated.

RESULTS: Two time use clusters were identified and were associated with correlates of PA and HRQoL. Girls who spent significantly more time in teams sports, non-team sports, school classes, watching TV and sleeping had higher levels of positively aligned PA correlates (e.g. self-efficacy, perceived sports competence) and HRQoL than girls characterised with high levels of computer use and video gaming. CONCLUSIONS: These findings highlight how different activity patterns of regional and rural girls affect HRQoL and can inform future intervention strategies to improve PA levels and HRQoL. Clusters characterised by low levels of PA and high computer use and video gaming require targeted interventions to address barriers to their participation.

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

Use and spatial patterns of newly developed public squares in urban villages in Shenzhen

This paper investigates the use and spatial patterns of newly developed public squares in urban villages in the City of Shenzhen, China. Given the lack of information about how this type of public space has been used by the Chinese, this paper provides insights that enable the development of more user friendly public space in China. The research is based on the fieldwork carried out in 2014 to examine public squares in four urban villages in Shenzhen. Direct observation and activity mapping have been used as major methodology for this research. The focus of this paper will be placed not only the formal aspects such as the design aspiration, scale and provision of public amenity, but also on the usage that includes types of users, there daily activity as well as their location preference.