The effects of composite laminate stiffness and loading on stress resultant concentration factor around a hole

© 2018, © IMechE 2018. An analytical tool is developed using conformal mapping and the complex variable method for determining the stress resultant concentration factor in an infinite plate with a circular or elliptical hole. This tool is validated against finite element analysis. A population space of 305 laminates is generated by stacking unidirectional carbon fibre reinforced polymer material at various orientations covering a wide spectrum of homogenised stiffness values. The analytical approach is then used to study the effect(s) of loading conditions, stacking sequences and laminate homogenised stiffness values on the stress resultant concentration factor at the edge of a circular hole

Virtual outreach: economic evaluation of joint teleconsultations for patients referred by their general practitioner for a specialist opinion

Objectives To test the hypotheses that, compared with conventional outpatient consultations, joint teleconsultation (virtual outreach) would incur no increased costs to the NHS, reduce costs to patients, and reduce absences from work by patients and their carers.Design Cost consequences study alongside randomised controlled trial.Setting Two hospitals in London and Shrewsbury and 29 general practices in inner London and Wales.Participants 3170 patients identified; 2094 eligible for inclusion and willing to participate. 1051 randomised to virtual outreach and 1043 to standard outpatient appointments.Main outcome measures NHS costs, patient costs, health status (SF-12), time spent attending index consultation, patient satisfaction.Results Overall six month costs were greater for the virtual outreach consultations (pound724 per patient) than for conventional outpatient appointments (pound625): difference in means pound99 ($162; is not an element of138) (95% confidence interval pound10 to pound187, P=0.03). if the analysis is restricted to resource items deemed "attributable" to the index consultation, six month costs were still greater for virtual outreach: difference in means pound108 (pound73 to pound142, P < 0.0001). In both analyses the index consultation accounted for the excess cost. Savings to patients in terms of costs and time occurred in both centres: difference in mean total patient cost 8 pound (5 pound to 10 pound, P < 0.0001). Loss of productive time was less in the virtual outreach group: difference in mean cost pound11 (pound10 to pound12, P < 0.0001).Condusion The main hypothesis that virtual outreach would be cost neutral is rejected, but the hypotheses that costs to patients and losses in productivity would be lower are supported

Solving a novel multi-divisional project portfolio selection and scheduling problem

A common problem faced by organizations is how to select and schedule an optimal portfolio of projects subject to various constraints, such as a limited budget. This problem is known as the project portfolio selection and scheduling problem (PPSSP). Despite the widespread nature of this problem, no existing model adequately addresses a sufficient set of characteristics that arise in real-world problems. One contribution of this article is the proposal of a novel, practical class of PPSSP that consists of multiple groups of projects, proposed by different sections of a major organization. The proposed problem can be considered as a generalized PPSSP given that many specific PPSSPs reported in the literature can be generated by relaxing certain constraints. As this is a novel formulation, existing algorithms cannot ensure high-quality solutions to this problem. Thus, a further contribution of this article is the design of three hybrid meta-heuristic algorithms based on a custom-purpose heuristic and local search operator. A case problem, inspired by future force design (FFD) in the Australian Defence Force (ADF), is presented to exemplify the applicability of this model to a real-world problem. Results indicate that the obtained solutions are of acceptable quality for implementation

Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy

OBJECTIVES: The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. METHODS: The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. RESULTS: The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. SIGNIFICANCE: Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology

Imaging of X-Ray-Excited Emissions from Quantum Dots and Biological Tissue in Whole Mouse

Optical imaging in clinical and preclinical settings can provide a wealth of biological information, particularly when coupled with targetted nanoparticles, but optical scattering and absorption limit the depth and resolution in both animal and human subjects. Two new hybrid approaches are presented, using the penetrating power of X-rays to increase the depth of optical imaging. Foremost, we demonstrate the excitation by X-rays of quantum-dots (QD) emitting in the near-infrared (NIR), using a clinical X-ray system to map the distribution of QDs at depth in whole mouse. We elicit a clear, spatially-resolved NIR signal from deep organs (brain, liver and kidney) with short (1 second) exposures and tolerable radiation doses that will permit future in vivo applications. Furthermore, X-ray-excited endogenous emission is also detected from whole mouse. The use of keV X-rays to excite emission from QDs and tissue represent novel biomedical imaging technologies, and exploit emerging QDs as optical probes for spatial-temporal molecular imaging at greater depth than previously possible

Cryptococcal Meningitis Screening and Community-based Early Adherence Support in People With Advanced Human Immunodeficiency Virus Infection Starting Antiretroviral Therapy in Tanzania and Zambia: A Cost-effectiveness Analysis

BACKGROUND: A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness. METHODS: HIV-infected adults with CD4 count <200 cells/μL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER. RESULTS: Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95$331-$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66-$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/μL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95$43-$211) for all participants with CD4 count up to 200 cells/μL and US$91 (95% CI, $49-$443) among those with CD4 counts <100 cells /μL. Cost-effectveness was most sensitive to mortality estimates. CONCLUSIONS: Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings

Higgs boson enhancement effects on squark-pair production at the LHC

We study the Higgs boson effects on third-generation squark-pair production in proton-proton collision at the CERN Large Hadron Collider (LHC), including \Stop \Stop^*, \Stop\Sbot^*, and \Sbot \Sbot^*. We found that substantial enhancement can be obtained through s-channel exchanges of Higgs bosons at large $\tan\beta$, at which the enhancement mainly comes from $b\bar b$, $b\bar c$, and $c\bar b$ initial states. We compute the complete set of electroweak (EW) contributions to all production channels. This completes previous computations in the literature. We found that the EW contributions can be significant and can reach up to 25% in more general scenarios and at the resonance of the heavy Higgs boson. The size of Higgs enhancement is comparable or even higher than the PDF uncertainties and so must be included in any reliable analysis. A full analytical computation of all the EW contributions is presented.Comment: 23 pages, 7 figures, 1 tabl

ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Background: The H69CIS200 and H69OX400 cell lines are novel models of low-level platinum-drug resistance. Resistance was not associated with increased cellular glutathione or decreased accumulation of platinum, rather the resistant cell lines have a cell cycle alteration allowing them to rapidly proliferate post drug treatment. Results: A decrease in ERCC1 protein expression and an increase in RAD51B foci activity was observed in association with the platinum induced cell cycle arrest but these changes did not correlate with resistance or altered DNA repair capacity. The H69 cells and resistant cell lines have a p53 mutation and consequently decrease expression of p21 in response to platinum drug treatment, promoting progression of the cell cycle instead of increasing p21 to maintain the arrest. Conclusion: Decreased ERCC1 protein and increased RAD51B foci may in part be mediating the maintenance of the cell cycle arrest in the sensitive cells. Resistance in the H69CIS200 and H69OX400 cells may therefore involve the regulation of ERCC1 and RAD51B independent of their roles in DNA repair. The novel mechanism of platinum resistance in the H69CIS200 and H69OX400 cells demonstrates the multifactorial nature of platinum resistance which can occur independently of alterations in DNA repair capacity and changes in ERCC1

Reverse mathematics of matroids

Matroids generalize the familiar notion of linear dependence from linear algebra. Following a brief discussion of founding work in computability and matroids, we use the techniques of reverse mathematics to determine the logical strength of some basis theorems for matroids and enumerated matroids. Next, using Weihrauch reducibility, we relate the basis results to combinatorial choice principles and statements about vector spaces. Finally, we formalize some of the Weihrauch reductions to extract related reverse mathematics results. In particular, we show that the existence of bases for vector spaces of bounded dimension is equivalent to the induction scheme for \Sigma^0_2 formulas

Solution NMR assignment of the C-terminal domain of human chTOG

The microtubule regulatory protein colonic and hepatic tumor overexpressed gene (chTOG), also known as cytoskeleleton associated protein 5 (CKAP5) plays an important role in organizing the cytoskeleton and in particular in the assembly of k-fibres in mitosis. Recently, we dissected the hitherto poorly understood C-terminus of this protein by discovering two new domains—a cryptic TOG domain (TOG6) and a smaller, helical domain at the very C-terminus. It was shown that the C-terminal domain is important for the interaction with the TACC domain in TACC3 during the assembly of k-fibres in a ternary complex that also includes clathrin. Here we now present the solution NMR assignment of the chTOG C-terminal domain which confirms our earlier prediction that it is mainly made of α-helices. However, the appearance of the 1H–15N HSQC spectrum is indicative of the presence of a considerable amount of unstructured and possibly flexible portions of protein in the domain