Education, preferences for leisure, and the optimal income tax schedule

Recent advances in dynamic Mirrlees economies have incorporated the treatment of human capital investments as an important dimension of government policy. This paper adds to this literature by considering a two period economy where agents are di erentiated by their preferences for leisure and their productivity, both private information. The fact that productivity is only learnt later in an agent's life introduces uncertainty to agent's savings and human capital choices and makes optimal the use of multi-period tie-ins in the mechanism that characterizes the government policy. We show that optimal policies are often interim ine cient and that the introduction of these ine ciencies may take the form of marginal tax rates on labor income of varying sign and educational policies that include the discouragement of human capital acquisition. With regards to implementation, state-dependent linear taxes implement optimal savings, while human capital policies may require labor income taxes that depend directly on agents' schooling.

Carrier momentum relaxation in highly doped polar semiconductors and semiconductor heterostructures

Highly doped polar semiconductors are essential components of today’s semiconductor industry. Most strikingly, transistors in modern electronic devices are polar semiconductor heterostructures. It is important to thoroughly understand carrier transport in such structures. In doped polar semiconductors, collective excitations of the carriers (plasmons) and the atoms (polar phonons) couple. These coupled collective excitations affect the electrical conductivity, here quantified through the carrier mobility. In scattering events, the carriers and the coupled collective modes transfer momentum between each other. Carrier momentum transferred to polar phonons can be lost to other phonons through anharmonic decay, resulting in a finite carrier mobility. The plasmons do not have a decay mechanism which transfers carrier momentum irretrievably. Hence, carrier-plasmon scattering results in infinite carrier mobility. Momentum relaxation due to either carrier–plasmon scattering or carrier–polar-phonon scattering alone are well understood. However, only this thesis manages to treat momentum relaxation due to both scattering mechanisms on an equal footing, enabling us to properly calculate the mobility limited by carrier–coupled plasmon–polar phonon scattering. We achieved this by solving the coupled Boltzmann equations for the carriers and the collective excitations, focusing on the “drag” term and on the anharmonic decay process of the collective modes. Our approach uses dielectric functions to describe both the carrier-collective mode scattering and the decay of the collective modes. We applied our method to bulk polar semiconductors and heterostructures where various polar dielectrics surround a semiconducting monolayer of MoS2, where taking plasmons into account can increase the mobility by up to a factor 15 for certain parameters. This screening effect is up to 85% higher than if calculated with previous methods. To conclude, our approach provides insight into the momentum relaxation mechanism for carrier–coupled collective mode scattering, and better tools for calculating the screened polar phonon and interface polar phonon limited mobility.

Comparison of tendency-oriented perimetry and dynamic strategy in octopus perimetry as a screening tool in a clinical setting: a prospective study

OBJECTIVE: The aim of this study was to compare the results of tendency-oriented perimetry (TOP) and a dynamic strategy in octopus perimetry as screening methods in clinical practice. DESIGN: A prospective single centre observational case series was performed. PARTICIPANTS AND METHODS: In a newly opened general ophthalmologic practice 89 consecutive patients (171 eyes) with a clinical indication for octopus static perimetry testing (ocular hypertension or suspicious optic nerve cupping) were examined prospectively with TOP and a dynamic strategy. The visual fields were graded by 3 masked observers as normal, borderline or abnormal without any further clinical information. RESULTS: 83% eyes showed the same result for both strategies. In 14% there was a small difference (with one visual field being abnormal or normal, the other being borderline). In only 2.9% of the eyes (5 cases) was there a contradictory result. In 4 out of 5 cases the dynamic visual field was abnormal and TOP was normal. 4 of these cases came back for a second examination. In all 4 the follow-up examination showed a normal second dynamic visual field. CONCLUSIONS: Octopus static perimetry using a TOP strategy is a fast, patient-friendly and very reliable screening tool for the general ophthalmological practice. We found no false-negative results in our series.

General unknown screening procedure for the characterization of human drug metabolites: application to loratadine phase I metabolism.

This article describes the application of a recently developed general unknown screening (GUS) strategy based on LC coupled to a hybrid linear IT-triple quadrupole mass spectrometer (LC-MS/MS-LIT) for the simultaneous detection and identification of drug metabolites following in vitro incubation with human liver microsomes. The histamine H1 receptor antagonist loratadine was chosen as a model compound to demonstrate the interest of such approach, because of its previously described complex and extensive metabolism. Detection and mass spectral characterization were based on data-dependent acquisition, switching between a survey scan acquired in the ion-trapping Q3 scan mode with dynamic subtraction of background noise, and a dependent scan in the ion-trapping product ion scan mode of automatically selected parent ions. In addition, the MS(3) mode was used in a second step to confirm the structure of a few fragment ions. The sensitivity of the ion-trapping modes combined with the selectivity of the triple quadrupole modes allowed, with only one injection, the detection and identification of 17 phase I metabolites of loratadine. The GUS procedure used in this study may be applicable as a generic technique for the characterization of drug metabolites after in vitro incubation, as well as probably in vivo experiments.

Dynamic load balancing for the distributed mining of molecular structures

In molecular biology, it is often desirable to find common properties in large numbers of drug candidates. One family of methods stems from the data mining community, where algorithms to find frequent graphs have received increasing attention over the past years. However, the computational complexity of the underlying problem and the large amount of data to be explored essentially render sequential algorithms useless. In this paper, we present a distributed approach to the frequent subgraph mining problem to discover interesting patterns in molecular compounds. This problem is characterized by a highly irregular search tree, whereby no reliable workload prediction is available. We describe the three main aspects of the proposed distributed algorithm, namely, a dynamic partitioning of the search space, a distribution process based on a peer-to-peer communication framework, and a novel receiverinitiated load balancing algorithm. The effectiveness of the distributed method has been evaluated on the well-known National Cancer Institute’s HIV-screening data set, where we were able to show close-to linear speedup in a network of workstations. The proposed approach also allows for dynamic resource aggregation in a non dedicated computational environment. These features make it suitable for large-scale, multi-domain, heterogeneous environments, such as computational grids.

The R2 mobile element of Rhynchosciara americana: Molecular, cytological and dynamic aspects

Ribosomal RNA genes are encoded by large units clustered (18S, 5S, and 28S) in the nucleolar organizer region in several organisms. Sometimes additional insertions are present in the coding region for the 28S rDNA. These insertions are specific non-long terminal repeat retrotransposons that have very restricted integration targets within the genome. The retrotransposon present in the genome of Rhynchosciara americana, RaR2, was isolated by the screening of a genomic library. Sequence analysis showed the presence of conserved regions, such as a reverse transcriptase domain and a zinc finger motif in the amino terminal region. The insertion site was highly conserved in R. americana and a phylogenetic analysis showed that this element belongs to the R2 clade. The chromosomal localization confirmed that the RaR2 mobile element was inserted into a specific site in the rDNA gene. The expression level of RaR2 in salivary glands during larval development was determined by quantitative RT-PCR, and the increase of relative expression in the 3P of the fourth instar larval could be related to intense gene activity characteristic of this stage. 5`-Truncated elements were identified in different DNA samples. Additionally, in three other Rhynchosciara species, the R2 element was present as a full-length element.

Screening of volatile composition from portuguese multifloral honeys using headspace solid-phase microextraction-gas chromatography–quadrupole mass spectrometry

The volatile composition from four types of multifloral Portuguese (produced in Madeira Island) honeys was investigated by a suitable analytical procedure based on dynamic headspace solid-phase microextraction (HS-SPME) followed by thermal desorption gas chromatography–quadrupole mass spectrometry detection (GC–qMS). The performance of five commercially available SPME fibres: 100 μm polydimethylsiloxane, PDMS; 85 μm polyacrylate, PA; 50/30 μm divinylbenzene/carboxen on polydimethylsiloxane, DVB/CAR/PDMS (StableFlex); 75 μm carboxen/polydimethylsiloxane, CAR/PDMS, and 65 μm carbowax/divinylbenzene, CW/DVB; were evaluated and compared. The highest amounts of extract, in terms of the maximum signal obtained for the total volatile composition, were obtained with a DVB/CAR/PDMS coating fibre at 60 °C during an extraction time of 40 min with a constant stirring at 750 rpm, after saturating the sample with NaCl (30%). Using this methodology more than one hundred volatile compounds, belonging to different biosynthetic pathways were identified, including monoterpenols, C13-norisoprenoids, sesquiterpenes, higher alcohols, ethyl esters and fatty acids. The main components of the HS-SPME samples of honey were in average ethanol, hotrienol, benzeneacetaldehyde, furfural, trans-linalool oxide and 1,3-dihydroxy-2-propanone.

Low dynamic muscle strength and its associations with fatigue, functional performance, and quality of life in premenopausal patients with systemic lupus erythematosus and low disease activity: a case–control study

Abstract Background The purpose of the present study was to compare dynamic muscle strength, functional performance, fatigue, and quality of life in premenopausal systemic lupus erythematosus (SLE) patients with low disease activity versus matched-healthy controls and to determine the association of dynamic muscle strength with fatigue, functional performance, and quality of life in SLE patients. Methods We evaluated premenopausal (18–45 years) SLE patients with low disease activity (Systemic lupus erythematosus disease activity index [SLEDAI]: mean 1.5 ± 1.2). The control (n = 25) and patient (n = 25) groups were matched by age, physical characteristics, and the level of physical activities in daily life (International Physical Activity Questionnaire IPAQ). Both groups had not participated in regular exercise programs for at least six months prior to the study. Dynamic muscle strength was assessed by one-repetition maximum (1-RM) tests. Functional performance was assessed by the Timed Up and Go (TUG), in 30-s test a chair stand and arm curl using a 2-kg dumbbell and balance test, handgrip strength and a sit-and-reach flexibility test. Quality of life (SF-36) and fatigue were also measured. Results The SLE patients showed significantly lower dynamic muscle strength in all exercises (leg press 25.63%, leg extension 11.19%, leg curl 15.71%, chest press 18.33%, lat pulldown 13.56%, 1-RM total load 18.12%, P < 0.001-0.02) compared to the controls. The SLE patients also had lower functional performance, greater fatigue and poorer quality of life. In addition, fatigue, SF-36 and functional performance accounted for 52% of the variance in dynamic muscle strength in the SLE patients. Conclusions Premenopausal SLE patients with low disease activity showed lower dynamic muscle strength, along with increased fatigue, reduced functional performance, and poorer quality of life when compared to matched controls.

Computational strategies to include protein flexibility in Ligand Docking and Virtual Screening

The dynamic character of proteins strongly influences biomolecular recognition mechanisms. With the development of the main models of ligand recognition (lock-and-key, induced fit, conformational selection theories), the role of protein plasticity has become increasingly relevant. In particular, major structural changes concerning large deviations of protein backbones, and slight movements such as side chain rotations are now carefully considered in drug discovery and development. It is of great interest to identify multiple protein conformations as preliminary step in a screening campaign. Protein flexibility has been widely investigated, in terms of both local and global motions, in two diverse biological systems. On one side, Replica Exchange Molecular Dynamics has been exploited as enhanced sampling method to collect multiple conformations of Lactate Dehydrogenase A (LDHA), an emerging anticancer target. The aim of this project was the development of an Ensemble-based Virtual Screening protocol, in order to find novel potent inhibitors. On the other side, a preliminary study concerning the local flexibility of Opioid Receptors has been carried out through ALiBERO approach, an iterative method based on Elastic Network-Normal Mode Analysis and Monte Carlo sampling. Comparison of the Virtual Screening performances by using single or multiple conformations confirmed that the inclusion of protein flexibility in screening protocols has a positive effect on the probability to early recognize novel or known active compounds.

Screening for Chlamydia trachomatis: a systematic review of the economic evaluations and modelling

OBJECTIVE: To review systematically and critically, evidence used to derive estimates of costs and cost effectiveness of chlamydia screening. METHODS: Systematic review. A search of 11 electronic bibliographic databases from the earliest date available to August 2004 using keywords including chlamydia, pelvic inflammatory disease, economic evaluation, and cost. We included studies of chlamydia screening in males and/or females over 14 years, including studies of diagnostic tests, contact tracing, and treatment as part of a screening programme. Outcomes included cases of chlamydia identified and major outcomes averted. We assessed methodological quality and the modelling approach used. RESULTS: Of 713 identified papers we included 57 formal economic evaluations and two cost studies. Most studies found chlamydia screening to be cost effective, partner notification to be an effective adjunct, and testing with nucleic acid amplification tests, and treatment with azithromycin to be cost effective. Methodological problems limited the validity of these findings: most studies used static models that are inappropriate for infectious diseases; restricted outcomes were used as a basis for policy recommendations; and high estimates of the probability of chlamydia associated complications might have overestimated cost effectiveness. Two high quality dynamic modelling studies found opportunistic screening to be cost effective but poor reporting or uncertainty about complication rates make interpretation difficult. CONCLUSION: The inappropriate use of static models to study interventions to prevent a communicable disease means that uncertainty remains about whether chlamydia screening programmes are cost effective or not. The results of this review can be used by health service managers in the allocation of resources, and health economists and other researchers who are considering further research in this area.

Cost effectiveness of home based population screening for Chlamydia trachomatis in the UK: economic evaluation of chlamydia screening studies (ClaSS) project

OBJECTIVE: To investigate the cost effectiveness of screening for Chlamydia trachomatis compared with a policy of no organised screening in the United Kingdom. DESIGN: Economic evaluation using a transmission dynamic mathematical model. SETTING: Central and southwest England. PARTICIPANTS: Hypothetical population of 50,000 men and women, in which all those aged 16-24 years were invited to be screened each year. MAIN OUTCOME MEASURES: Cost effectiveness based on major outcomes averted, defined as pelvic inflammatory disease, ectopic pregnancy, infertility, or neonatal complications. RESULTS: The incremental cost per major outcome averted for a programme of screening women only (assuming eight years of screening) was 22,300 pounds (33,000 euros; $45,000) compared with no organised screening. For a programme screening both men and women, the incremental cost effectiveness ratio was approximately 28,900 pounds. Pelvic inflammatory disease leading to hospital admission was the most frequently averted major outcome. The model was highly sensitive to the incidence of major outcomes and to uptake of screening. When both were increased the cost effectiveness ratio fell to 6200 pound per major outcome averted for screening women only. CONCLUSIONS: Proactive register based screening for chlamydia is not cost effective if the uptake of screening and incidence of complications are based on contemporary empirical studies, which show lower rates than commonly assumed. These data are relevant to discussions about the cost effectiveness of the opportunistic model of chlamydia screening being introduced in England.

Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

Predicting the population impact of chlamydia screening programmes: comparative mathematical modelling study

BACKGROUND: Published individual-based, dynamic sexual network modelling studies reach different conclusions about the population impact of screening for Chlamydia trachomatis. The objective of this study was to conduct a direct comparison of the effect of organised chlamydia screening in different models. METHODS: Three models simulating population-level sexual behaviour, chlamydia transmission, screening and partner notification were used. Parameters describing a hypothetical annual opportunistic screening program in 16-24 year olds were standardised, whereas other parameters from the three original studies were retained. Model predictions of the change in chlamydia prevalence were compared under a range of scenarios. RESULTS: Initial overall chlamydia prevalence rates were similar in women but not men and there were age and sex-specific differences between models. The number of screening tests carried out was comparable in all models but there were large differences in the predicted impact of screening. After 10 years of screening, the predicted reduction in chlamydia prevalence in women aged 16-44 years ranged from 4% to 85%. Screening men and women had a greater impact than screening women alone in all models. There were marked differences between models in assumptions about treatment seeking and sexual behaviour before the start of the screening intervention. CONCLUSIONS: Future models of chlamydia transmission should be fitted to both incidence and prevalence data. This meta-modelling study provides essential information for explaining differences between published studies and increasing the utility of individual-based chlamydia transmission models for policy making.

Measurement of intervertebral cervical motion by means of dynamic X-ray image processing and data interpolation

Accurate measurement of intervertebral kinematics of the cervical spine can support the diagnosis of widespread diseases related to neck pain, such as chronic whiplash dysfunction, arthritis, and segmental degeneration. The natural inaccessibility of the spine, its complex anatomy, and the small range of motion only permit concise measurement in vivo. Low dose X-ray fluoroscopy allows time-continuous screening of cervical spine during patient's spontaneous motion. To obtain accurate motion measurements, each vertebra was tracked by means of image processing along a sequence of radiographic images. To obtain a time-continuous representation of motion and to reduce noise in the experimental data, smoothing spline interpolation was used. Estimation of intervertebral motion for cervical segments was obtained by processing patient's fluoroscopic sequence; intervertebral angle and displacement and the instantaneous centre of rotation were computed. The RMS value of fitting errors resulted in about 0.2 degree for rotation and 0.2 mm for displacements. © 2013 Paolo Bifulco et al.

Modelling and analysing cargo screening processes: a project outline

The efficiency of current cargo screening processes at sea and air ports is unknown as no benchmarks exists against which they could be measured. Some manufacturer benchmarks exist for individual sensors but we have not found any benchmarks that take a holistic view of the screening procedures assessing a combination of sensors and also taking operator variability into account. Just adding up resources and manpower used is not an effective way for assessing systems where human decision-making and operator compliance to rules play a vital role. For such systems more advanced assessment methods need to be used, taking into account that the cargo screening process is of a dynamic and stochastic nature. Our project aim is to develop a decision support tool (cargo-screening system simulator) that will map the right technology and manpower to the right commodity-threat combination in order to maximize detection rates. In this paper we present a project outline and highlight the research challenges we have identified so far. In addition we introduce our first case study, where we investigate the cargo screening process at the ferry port in Calais.