Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

Dosage form preference consultation study in children and young adults:paving the way for patient-centred and patient-informed dosage form development

Objectives: The current study aims to evaluate dosage form preferences in children and young adults together with identifying the key pragmatic dosage form characteristics that would enable appropriate formulation of orally disintegrating tablets (ODTs). Methods: International, multisite, cross-sectional questionnaire of children and young adults aged from 6 to 18 years. Eligibility was based on age, ability to communicate and previous experience in taking medications. The study was carried out at three locations: the UK, Saudi Arabia and Jordan. The questionnaire instrument was designed for participant self-completion under supervision of the study team.Results 104 questionnaires were completed by the study cohort (n=120, response rate 87%). Results: showed that ODTs were the most preferred oral dosage forms (58%) followed by liquids (20%), tablets (12%) and capsules (11%). The preferred colours were pink or white while the preferred size was small (<8 mm) with a round shape. With regard to flavour, strawberry was the most preferred (30.8%), while orange was the least preferred (5.8%). The results also showed that the most important physical characteristics of ODTs were disintegration time followed by taste, size and flavour, respectively. Conclusions: The results of our study support the WHO's claim for a shift of paradigm from liquid towards ODTs dosage forms for drug administration to young children older than 6 years. Data from this study will also equip formulators to prioritise development of key physical/performance attributes within the delivery system.

Typical performance of gallager-type error-correcting codes

The performance of Gallager's error-correcting code is investigated via methods of statistical physics. In this method, the transmitted codeword comprises products of the original message bits selected by two randomly-constructed sparse matrices; the number of non-zero row/column elements in these matrices constitutes a family of codes. We show that Shannon's channel capacity is saturated for many of the codes while slightly lower performance is obtained for others which may be of higher practical relevance. Decoding aspects are considered by employing the TAP approach which is identical to the commonly used belief-propagation-based decoding.

Managing people and performance:An evidence based framework applied to health service organizations

People and their performance are key to an organization's effectiveness. This review describes an evidence-based framework of the links between some key organizational influences and staff performance, health and well-being. This preliminary framework integrates management and psychological approaches, with the aim of assisting future explanation, prediction and organizational change. Health care is taken as the focus of this review, as there are concerns internationally about health care effectiveness. The framework considers empirical evidence for links between the following organizational levels: 1. Context (organizational culture and inter-group relations; resources, including staffing; physical environment) 2. People management (HRM practices and strategies; job design, workload and teamwork; employee involvement and control over work; leadership and support) 3. Psychological consequences for employees (health and stress; satisfaction and commitment; knowledge, skills and motivation) 4. Employee behaviour (absenteeism and turnover; task and contextual performance; errors and near misses) 5. Organizational performance; patient care. This review contributes to an evidence base for policies and practices of people management and performance management. Its usefulness will depend on future empirical research, using appropriate research designs, sufficient study power and measures that are reliable and valid.

A study of the flow performance of a sodium silicate furnace

The flow characteristics of neutral sodium silicate glass in an open hearth regenerative furnace have been studied using a one tenth scale physical model. The constraints of similarity have been investigated and discussed, and the use of sodium liquor as a cold modelling solution has been developed. Methylene Blue and Sulphacid Brill Pink are used as delineators, and a technique for analysing the concentration of each even in a mixture has been developed. The residence/time distributions from the model have been simulated using a mixed model computer program which identifies the nature and size of the most significant flow streams within the furnace. The results clearly show that the model gives a true representation of the furnace and illustrates a number of alternatives for operating or design changes which will lead to improved production efficiency.

The electron optical limits of performance of single-polepiece magnetic electron lenses

The thesis is concerned with the electron properties of single-polepiece magnetic electron lenses especially under conditions of extreme polepiece saturation. The electron optical properties are first analysed under conditions of high polepiece permeability. From this analysis, a general idea can be obtained of the important parameters that affect ultimate lens performance. In addition, useful information is obtained concerning the design of improved lenses operating under conditions of extreme polepiece saturation, for example at flux densities of the order of 10 Tesla. It is shown that in a single-polepiece lens , the position and shape of the lens exciting coil plays an important role. In particular, the maximum permissible current density in the windings,rather than the properties of the iron, can set a limit to lens performance. This factor was therefore investigated in some detail. The axial field distribution of a single-polepiece lens, unlike that of a conventional lens, is highly asymmetrical. There are therefore two possible physical arrangements of the lens with respect to the incoming electron beam. In general these two orientations will result in different aberration coefficients. This feature has also been investigated in some detail. Single-pole piece lenses are thus considerably more complicated electron- optically than conventional double polepiece lenses. In particular, the absence of the usual second polepiece causes most of the axial magnetic flux density distribution to lie outside the body of the lens. This can have many advantages in electron microscopy but it creates problems in calculating the magnetic field distribution. In particular, presently available computer programs are liable to be considerably in error when applied to such structures. It was therefore necessary to find independent ways of checking the field calculations. Furthermore, if the polepiece is allowed to saturate, much more calculation is involved since the field distribution becomes a non-linear function of the lens excitation. In searching for optimum lens designs, care was therefore taken to ensure that the coil was placed in the optimum position. If this condition is satisfied there seems to be no theoretical limit to the maximum flux density that can be attained at the polepiece tip. However , under iron saturation condition, some broadening of the axial field distribution will take place, thereby changing the lens aberrations . Extensive calculations were therefore made to find the minimum spherical and chromatic aberration coefficients . The focal properties of such lens designs are presented and compared with the best conventional double-polepiece lenses presently available.

Some aspects of performance at a psychokinetic task

Psychokinetic phenomena are currently anomalous with respect to physics. They are not generally accepted as genuine nor are their possible physical mechanisms understood. It is argued here that a certain class of psychokinetic phenomena, termed "directly detectable" psychokinetic effects, are likely to yield possibly important insights into the physical mechanisms mediating psychokinetic phenomena generally. The current use within parapsychological research of randomly behaving psychokinetic target systems is criticised on several grounds. They are of limited scope for use in delineation of physical mechanisms involved in psychokinesis, and their intrinsic characteristics prevent subjects from utilising their possible capacity to learn to produce larger magnitude effects. It is argued that instrumented directly detectable psychokinetic tasks have characteristics which may allow subjects to treat their psychokinetic ability as akin to a normal skill which can be improved with continued practice, using an experimental paradigm similar to that used in the biofeedback training of physiological functions. The task used in this work was a microscopic form of psychokinetic metal-bending, whereby subjects produce pulse-like electrical outputs in a ceramic piezoelectric element used as psychokinetic target. Subjects were not allowed to touch the target and many effects were obtained under witnessed conditions with subjects situated several metres from it. One pilot and three principal longitudinal training studies were performed with a total of seventeen subjects. Six of the seventeen subjects showed significant improvement in their psychokinetic performance in the training studies, one showed a non-significant increase. The other ten failed to show any convincing signs of psychokinetic output. Three of the successful subjects did not show convincing signs of voluntary control over their effects, three did. Large individual differences were found including different rates of learning and levels of initial and final ability. This research was performed by Julian David Isaacs in preparation for the degree of Doctor of Philosophy and was submitted in 1984.

The performance of cement stabilised minestone

This study is concerned with the durability of cement stabilised minestone (CSM). Minestone is dominated by the clay-bearing mudrocks and shales of the Coal Measures. Consequently, engineering problems are often encountered due to the likelihood of these rocks undergoing volume change and degradation when exposed to fluctuations in moisture content. In addition, iron sulphides (chiefly pyrite) are frequently present in minestone as diagenetic minerals which on excavation have the potential to oxidise forming sulphate minerals. The oxidation of sulphides may in itself contribute to volume increase in pyritic rocks and sulphate minerals may combine with the products of cement hydration to produce further expansion. The physical and chemical properties of a wide range of minestones are determined and attempts are made to correlate these with the engineering performance of cement stabilised specimens subjected to short-term immersion in water. Criteria, based on these raw material indices are proposed with a view to eliminating minestones which are unsuitable. A long-term durability study is also described. In this, the geochemical stability of pyrite in CSM was examined together with the role played by the sulphur bearing mineralogy in determining the engineering performance of CSM's exposed to conditions of increased moisture availability. The nature of a number of disrupted CSM pavements which have been examined are also discussed.

Physical and psychophysical analysis of progressive addition lens embodiments

The extent to which the surface parameters of Progressive Addition Lenses (PALs) affect successful patient tolerance was investigated. Several optico-physical evaluation techniques were employed, including a newly constructed surface reflection device which was shown to be of value for assessing semi-finished PAL blanks. Detailed physical analysis was undertaken using a computer-controlled focimeter and from these data, iso-cylindrical and mean spherical plots were produced for each PAL studied. Base curve power was shown to have little impact upon the distribution of PAL astigmatism. A power increase in reading addition primarily caused a lengthening and narrowing of the lens progression channel. Empirical measurements also indicated a marginal steepening of the progression power gradient with an increase in reading addition power. A sample of the PAL wearing population were studied using patient records and questionnaire analysis (90% were returned). This subjective analysis revealed the reading portion to be the most troublesome lens zone and showed that patients with high astigmatism (> 2.00D) adapt more readily to PALs than those with spherical or low cylindrical (2.00D) corrections. The psychophysical features of PALs were then investigated. Both grafting visual acuity (VA) and contrast sensitivity (CS) were shown to be reduced with an increase in eccentricity from the central umbilical line. Two sample populations (N= 20) of successful and unsuccessful PAL wearers were assessed for differences in their visual performance and their adaptation to optically induced distortion. The possibility of dispensing errors being the cause of poor patient tolerance amongst the unsuccessful wearer group was investigated and discounted. The contrast sensitivity of the successful group was significantly greater than that of the unsuccessful group. No differences in adaptation to or detection of curvature distortion were evinced between these presbyopic groups.

Human performance modelling as an aid in the process of manufacturing system design

Manufacturing system design is an ongoing activity within industry. Modelling tools based on Discrete Event Simulation are often used by practitioners during this design cycle. However, such tools do not adequately model the behaviour of 'direct' workers in manufacturing environments. There is an important need to expand the capability of modelling to include the relationships between human centred factors (demography, attitudes, beliefs, etc), their working environment (physical and organizational), and their subsequent performance in terms of productive routines. Therefore, this paper describes research that has formed a pilot modelling methodology that is an important first step in providing such a capability.

Unified model for performance analysis of IEEE 802.11 ad hoc networks in unsaturated conditions

IEEE 802.11 standard has achieved huge success in the past decade and is still under development to provide higher physical data rate and better quality of service (QoS). An important problem for the development and optimization of IEEE 802.11 networks is the modeling of the MAC layer channel access protocol. Although there are already many theoretic analysis for the 802.11 MAC protocol in the literature, most of the models focus on the saturated traffic and assume infinite buffer at the MAC layer. In this paper we develop a unified analytical model for IEEE 802.11 MAC protocol in ad hoc networks. The impacts of channel access parameters, traffic rate and buffer size at the MAC layer are modeled with the assistance of a generalized Markov chain and an M/G/1/K queue model. The performance of throughput, packet delivery delay and dropping probability can be achieved. Extensive simulations show the analytical model is highly accurate. From the analytical model it is shown that for practical buffer configuration (e.g. buffer size larger than one), we can maximize the total throughput and reduce the packet blocking probability (due to limited buffer size) and the average queuing delay to zero by effectively controlling the offered load. The average MAC layer service delay as well as its standard deviation, is also much lower than that in saturated conditions and has an upper bound. It is also observed that the optimal load is very close to the maximum achievable throughput regardless of the number of stations or buffer size. Moreover, the model is scalable for performance analysis of 802.11e in unsaturated conditions and 802.11 ad hoc networks with heterogenous traffic flows. © 2012 KSI.

Performance comparison of OFDM bandwidth request schemes in fixed IEEE 802.16 networks

IEEE 802.16 standard specifies two contention based bandwidth request schemes working with OFDM physical layer specification in point-to-multipoint (PMP) architecture, the mandatory one used in region-full and the optional one used in region-focused. This letter presents a unified analytical model to study the bandwidth efficiency and channel access delay performance of the two schemes. The impacts of access parameters, available bandwidth and subchannelization have been taken into account. The model is validated by simulations. The mandatory scheme is observed to perform closely to the optional one when subchannelization is active for both schemes.

Performance, emission and combustion characteristics of an indirect injection (IDI) multi-cylinder compression ignition (CI) engine operating on neat jatropha and karanj oils preheated by jacket water

Renewable non-edible plant oils such as jatropha and karanj have potential to substitute fossil diesel fuels in CI engines. A multi-cylinder water cooled IDI type CI engine has been tested with jatropha and karanj oils and comparisons made against fossil diesel. The physical and chemical properties of the three fuels were measured to investigate the suitability of jatropha and karanj oils as fuels for CI engines. The engine cooling water circuit and fuel supply systems were modified such that hot jacket water preheated the neat plant oil prior to injection. Between jatropha and karanj there was little difference in the performance, emission and combustion results. Compared to fossil diesel, the brake specific fuel consumption on volume basis was around 3% higher for the plant oils and the brake thermal efficiency was almost similar. Jatropha and karanj operation resulted in higher CO 2 and NO x emissions by 7% and 8% respectively, as compared to diesel. The cylinder gas pressure diagram showed stable engine operation with both plant oils. At full load, the plant oils gave around 3% higher peak cylinder pressure than fossil diesel. With the plant oils, cumulative heat release was smaller at low load and almost similar at full load, compared to diesel. At full load, the plant oils exhibited 5% shorter combustion duration. The study concludes that the IDI type CI engine can be efficiently operated with neat jatropha (or karanj) oil preheated by jacket water, after small modifications of the engine cooling and fuel supply circuits. © 2012 Elsevier Ltd.