bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting BRCA1‐BER deficient breast cancer by ATM or DNA‐PKcs blockade either alone or in combination with cisplatin for personalized therapy
Authors: Albarakati Nada , Abdel-Fatah Tarek M.A. , Doherty Rachel , Russell Roslin , Agarwal Devika , Moseley Paul , Perry Christina , Arora Arvind , Alsubhi Nouf , Seedhouse Claire , Rakha Emad A. , Green Andrew , Ball Graham , Chan Stephen , Caldas Carlos , Ellis Ian O. , Madhusudan Srinivasan 
Published: August 2014

BRCA1, a key factor in homologous recombination (HR) repair may also regulate base excision repair (BER). Targeting BRCA1‐BER deficient cells by blockade of ATM and DNA‐PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1 and pol β protein expression in two cohorts (n = 1602 sporadic and n = 50 germ‐line BRCA1 mutated) and mRNA expression in two cohorts (n = 1952 and n = 249). Artificial neural network analysis for BRCA1‐DNA repair interacting genes was conducted in 249 tumours. Pre‐clinically, BRCA1 proficient and deficient cells were DNA repair expression profiled and evaluated for synthetic lethality using ATM and DNA‐PKcs inhibitors either alone or in combination with cisplatin. In human tumours, BRCA1 negativity was strongly associated with low XRCC1, and low pol β at mRNA and protein levels (p < 0.0001). In patients with BRCA1 negative tumours, low XRCC1 or low pol β expression was significantly associated with poor survival in univariate and multivariate analysis compared to high XRCC1 or high pol β expressing BRCA1 negative tumours (ps < 0.05). Pre‐clinically, BRCA1 negative cancer cells exhibit low mRNA and low protein expression of XRCC1 and pol β. BRCA1‐BER deficient cells were sensitive to ATM and DNA‐PKcs inhibitor treatment either alone or in combination with cisplatin and synthetic lethality was evidenced by DNA double strand breaks accumulation, cell cycle arrest and apoptosis. We conclude that XRCC1 and pol β expression status in BRCA1 negative tumours may have prognostic significance. BRCA1‐BER deficient cells could be targeted by ATM or DNA‐PKcs inhibitors for personalized therapy.
SOME ADVANCES ON THE ERLANG(n) DUAL RISK MODEL
Authors: Rodríguez-Martínez Eugenio V. , Cardoso Rui M. R. , Egídio dos Reis Alfredo D. 
Published: August 2014

AbstractThe dual risk model assumes that the surplus of a company decreases at a constant rate over time and grows by means of upward jumps, which occur at random times and sizes. It is said to have applications to companies with economical activities involved in research and development. This model is dual to the well-known Cramér-Lundberg risk model with applications to insurance. Most existing results on the study of the dual model assume that the random waiting times between consecutive gains follow an exponential distribution, as in the classical Cramér-Lundberg risk model. We generalize to other compound renewal risk models where such waiting times are Erlang(n) distributed. Using the roots of the fundamental and the generalized Lundberg's equations, we get expressions for the ruin probability and the Laplace transform of the time of ruin for an arbitrary single gain distribution. Furthermore, we compute expected discounted dividends, as well as higher moments, when the individual common gains follow a Phase-Type, PH(m), distribution. We also perform illustrations working some examples for some particular gain distributions and obtain numerical results.
Smokers’ Treatment Expectancies Predict Smoking Cessation Success
Authors: Fucito Lisa M. , Toll Benjamin A. , Roos Corey R. , King Andrea C. 
Published: August 2014

Introduction: Smokers’ treatment expectancies may influence their choice of a particular medication as well as their medication experience.Aims: This study examined the role of smokers’ treatment expectancies to their smoking cessation outcomes in a completed, randomized, placebo-controlled trial of naltrexone for smoking cessation, controlling for perceptions of treatment assignment.Methods: Treatment-seeking cigarette smokers (N = 315) were randomized to receive either naltrexone (50 mg) or placebo in combination with nicotine patch and behavioural counselling. Expectancies for naltrexone as a smoking cessation aid were assessed at baseline and four weeks after the quit date.Results: More positive baseline medication expectancies predicted higher quit rates at one month in the naltrexone group (OR = 1.45, p = 0.04) but were associated with lower quit rates in the placebo group (OR = 0.66, p = 0.03). Maintaining and/or increasing positive medication expectancies in the first month of treatment was associated with better pill adherence during this interval in the naltrexone group (ps < 0.05). Positive baseline medication expectancies were also associated with the perception of having received naltrexone over placebo among all participants.Conclusions: Positive medication expectancies in smokers may contribute to better treatment response. Assessing treatment expectancies and attempting to maintain or improve them may be important for the delivery, evaluation, and targeting of smoking cessation treatments.
SUCCESSIVE ITERATIONS FOR POSITIVE EXTREMAL SOLUTIONS OF NONLINEAR FRACTIONAL DIFFERENTIAL EQUATIONS ON A HALF-LINE
Authors: ZHANG LIHONG , AHMAD BASHIR , WANG GUOTAO 
Published: August 2014

AbstractIn this paper, positive solutions of fractional differential equations with nonlinear terms depending on lower-order derivatives on a half-line are investigated. The positive extremal solutions and iterative schemes for approximating them are obtained by applying a monotone iterative method. An example is presented to illustrate the main results.
The German Life Assurance Market
Authors: Hawken J. S. , Kilroy R. J. M. 
Published: August 2014

1. The paper sets out a brief description of the life assurance market in the Federal Republic of Germany (including West Berlin). The aim has been to highlight those aspects of the market, in particular the supervision system, which differ significantly from British practice. After a section giving some historical background, the main section outlines the present market and the paper concludes with a brief look at the future.2. The paper is based on the impressions which we obtained in establishing a new branch office of a British proprietary life assurance company in Germany. The views expressed are, however, entirely personal. Our thanks are due to J. A. Langley and R. J. McCurrach, who assembled the statistical material.
More Words and Numbers.
Authors: Redington F. M. 
Published: August 2014

I am always happy to be back where my Institute life started and I am grateful to your Committee for fitting me in at short notice.When you start to write, ideas take on a being of their own. Life is a shy child which hides its face when you stand aloof, but is soon at your elbow to help when you kneel to build with its bricks. Then other bricks begin to appear. As it turns out, my helper is concerned about imagination so ‘imagination’ shall be our subtitle.First, a brief reference to my 1972 paper: the winning themes were—in reverse order, as for beauty queens—third prize to the imminent collapse of our society, second prize to the essential unity of the universe, but an easy winner was double faults at tennis.
Models in Motor Insurance.
Authors: Bennett M. C. 
Published: August 2014

The introduction of high-speed electronic computers has opened the way for analyses of motor insurance risk statistics on a scale not previously possible. We may regard the purpose of the analyses which form the subject of this note as being to test the validity of the existing rating structure by finding out how the claims experience varies from one rating cell to another within that structure; and, more generally, to explore the possibility of devising a more efficient rating structure by defining new levels within the existing factors, or by using new factors in addition to, or in replacement of, those already used.To achieve this purpose it is appropriate to consider on the one hand a detailed investigation of the experience over a limited period, analogous to that carried out when constructing a new standard life table and, on the other hand, a system for keeping the emerging experience under more or less continuous review. For this second aspect it is natural to think in terms of making comparisons between the actual experience and that expected according to the standard table.
Deposit Administration.
Authors: Iqbal M. 
Published: August 2014

An employer contemplating the setting up of a pension scheme might wish to use the investment facilities of a life office for one of two reasons. He might wish to insure the investment risk; he might wish to use the life office's investment expertise in preference to his own or those of, say, an outside adviser. These are two distinct requirements and in analysing the usefulness of an insured pension scheme they have to be considered separately. This paper is concerned primarily with the former.As, except in the case of the managed fund, no part of the life office's assets are allocated to any individual scheme, actuaries have devised various methods of allocating investment return to the scheme. This paper concentrates on the system known as Deposit Administration (DA).
Pension Aspects of Takeovers and Mergers.
Authors: Chapman R. J. , Jagelman R. J. 
Published: August 2014

Over the past few years the Pension Managers of most large groups of companies, and some not so large, have had to grapple with the pension complications which have arisen when their holding company sells or acquires another company. For example, the pension costs of an acquisition may not have been adequately considered, possibly because the Pension Manager had not been one of the limited number of principals who were involved in the negotiations leading up to the acquisition. Even if the Pension Manager has been involved in an advisory capacity during the negotiations, formidable problems may subsequently arise in integrating the previous pension benefits of the new employees with the benefits of existing employees.Detailed consideration of the financial condition of the pension scheme of the company which is taken over has been the exception rather than the rule and many companies have found that a seemingly straightforward undertaking to ‘safeguard’ employees' pension rights involves both higher than anticipated pension costs and problems of comparability between similar grades of employees at different locations within the group.
Erisa.
Authors: Fishman A. S. 
Published: August 2014

In my opinion, the implications of the Employee Retirement Income Security Act of 1974 (ERISA), which was enacted in the U.S. on 2 September 1974, are of vital importance to U.K. pensions' actuaries.Pension schemes which are established in the U.K. by U.K. branch operations of a U.S. parent are subject to the provisions of ERISA. Furthermore, there have recently been suggestions that U.K. subsidiary company operations of a U.S. parent might also be required to prepare ERISA-style reports.Since U.S. enterprises account for some 13% of the U.K.'s total gross product in manufacturing in the private sector, almost every U.K. insurance company, firm of consulting actuaries or pension consultants will have come into contact with some aspect of, or question relating to, ERISA.
The Control Cycle: Financial Control of a Life Assurance Company.
Authors: Goford Jeremy 
Published: August 2014

The intention of this paper is to describe, by way of example, how profit testing is carried on in practice and how by making it central to the company's operation the company may be controlled. The mechanism of control is to test the company's results against the results of profit tests built into a model of the company. We shall also describe how the results of these tests of the company's results are fed back into the profit tests to establish the basis for future tests of the company's results.
The motivation for this paper arose from the need to communicate to shareholders the links between profit testing and the company's actual results. It is all very well to say to shareholders that the products satisfy a certain profitability standard but how does that show itself and how real is that profitability paticularly for a new or expanding company which displays nothing but statutory losses or, at best, break even? This communication also led to the need to explain variations from the original projections and finally to answer the question: what happens to profitability if these variances continue?
Topical Pension Problems (A Personal Overview).
Authors: Kaye Geraldine 
Published: August 2014

Much discussion is taking place currently in the United Kingdom on the subject of pensions. Conferences and symposia have been conducted at various times on many aspects of pensions by such diverse bodies as the Policy Studies Institute (1), the Institute of Fiscal Studies (2), the Trades Union Congress (3), the Pensions Management Institute, the Confederation of British Industry, the National Association of Pension Funds and even our own Institute (4) (in the case of our Institute, on the whole field).
The Government announced an all-embracing enquiry on 16 December 1983. This has been divided into separate parts. Evidence for the first part concerned with ‘portable pensions’ was required by 31 January 1984. Despite the very tight deadline, written evidence was obtained from over 1,500 different sources. This serves to show just how much interest was currently being aroused. The final results of the full Government enquiry are not yet available (September 1984). The unprecedented speed with which the Government has proceeded demonstrates the importance that it attaches to the issues raised, and suggests that any prompted legislation will be given a degree of priority.
Equity from Equities in Bonus Distributions.
Authors: Arbaney A. 
Published: August 2014

Many years ago the question of equitable distributions of surplus would have attracted much discussion. The subject received a full philosophical, financial and mathematical treatment, with the aim of getting it just right.As time passed this subject became less precise. Wider variations in investment conditions and different investment strategies meant that the constraints of the usual bonus methods could only achieve rough justice. Premium rates and valuation bases remained fairly static (often quite rightly so), and the declared results seemed slightly arbitrary and perhaps a little conservative. The work of the traditional actuary seemed a little ‘stodgy’ and the challenge and activity turned to the field of unit linking.Today the picture is different. Just as the introduction of banks to the personal mortgage market seems to have improved the service from Building Societies, so the advent of unit-linking seems to have spurred on the traditional actuary. The expectations of what can be achieved have increased. So, over the period that the methods for valuation, pricing and projection for unit linked contracts have achieved some measure of standardization, the traditional actuary has been pushed more into the role of the pioneer.
A Pension Scheme Wind-up: Legitimate Act or Smash-and-Grab?.
Authors: Southall S. M. , Punter J. D. 
Published: August 2014

The last paper on the winding-up of pension schemes was presented to the Institute by Gilley in March 1972. Since that time it has justifiably been the standard work on the subject and it has only recently been withdrawn from the Institute's examination syllabus. This paper is an attempt to up-date Gilley's work and to describe a complex and practical field of actuarial operation.
Since 1972 there has been a substantial amount of pensions legislation which has inevitably changed the detailed procedures involved in a pension scheme dissolution. Nevertheless, many of the general considerations and ideas expressed in Gilley's paper are still valid today.
The Effects of Solvency Margins on U.K. Life Companies.
Authors: May W. P. , Newbury K. J. 
Published: August 2014

The requirement for a United Kingdom life office to hold solvency margins in addition to its normal actuarial reserves took full effect on 15 March 1984. At the time of writing, solvency margins for U.K. life offices have therefore had an effective life of under two years.
Before the introduction of the regulations, many comments were made within the life insurance industry about the effects which the introduction of the life solvency margins would have on the financial position of U.K. life offices. This therefore seems an appropriate time to reflect on the theoretical financial consequences of solvency margins from the point of view of a U.K. life company, and comment on the practical effects which have been observed to date.
The Effect of Demographic Factors and Indexation on the Long term Financing of the State Earnings-Related Pension Scheme.
Authors: Daykin C. D. , Young A. G. 
Published: August 2014

In September 1974 Barbara Castle published her proposals for a new earnings-related State pension scheme in her White Paper “Better Pensions”. This followed a succession of attempts by previous Secretaries of State for Social Services to change State pension arrangements radically. Unlike the ill-fated Crossman and Joseph schemes, however, the Castle scheme succeeded both in reaching the statute book and in coming into operation. A Bill was introduced in February 1975 and on 7 August 1975 the Social Security Pensions Act 1975 received the Royal Assent.
The State earnings-related pension scheme (SERPS) came into operation on 6 April 1978. It provided State pensions related to earnings, but also offered to employers with good occupational pension schemes the possibility of ‘contracting-out’ and providing equivalent or better earnings-related benefits through their own scheme.
Does imaging of the olfactory tract change the clinical management of patients with olfactory disturbance? A case series of 100 consecutive patients
Authors: Powell J , Elbadawey M Reda , Zammit-Maempel I 
Published: August 2014

AbstractBackground:Isolated olfactory dysfunction is a common complaint; the vast majority of cases are benign and untreatable. A common dilemma is whether to image the olfactory tract of affected patients.Methods:A case review of 100 consecutive patients who underwent magnetic resonance imaging for the primary complaint of olfactory dysfunction was performed. Patients with a diagnosis of chronic rhinosinusitis, with or without nasal polyps, were excluded.Results:Magnetic resonance imaging abnormalities that were considered clinically relevant to the presentation of olfactory dysfunction were found in only seven patients (7 per cent). Of these, only one patient (1 per cent) had an abnormality found that altered their clinical management. A comparison of the findings for children (less than 16 years old,n = 5) with those for adults (equal to or more than 16 years old,n = 95) revealed that 4 per cent of adults scanned had olfactory-related pathology diagnosed, as opposed to 60 per cent of children.Conclusion:Cross-sectional imaging may not be necessary in most patients with olfactory dysfunction. Imaging adds little to the patient history and clinical examination findings.
High jugular bulb in a cohort of patients with definite Ménière's disease
Authors: Redfern R E , Brown M , Benson A G 
Published: August 2014

AbstractObjective:To determine the incidence of high jugular bulb in a group of patients with definite Ménière's disease, and to investigate whether the position or size of the jugular bulb is significantly different in the affected ear than in the unaffected ear.Methods:Retrospective review of patient charts, audiograms, and computed tomography scans to determine the position and size of the jugular bulb in the affected and contralateral ears, as well as other abnormalities.Results:High jugular bulb was found in 57.1 per cent of affected ears. Encroachment of the cochlear and vestibular aqueducts was apparent in 39.3 per cent and 35.7 per cent, respectively, of affected ears. Diverticulum and dehiscence were observed in 28.6 per cent of affected ears. High jugular bulb was significantly associated with encroachment of the cochlear aqueduct (p = 0.003).Conclusion:The mediolateral and anteroposterior position of the jugular bulb determines encroachment of the surrounding structures. An abnormal position is postulated to contribute to the development of Ménière's disease.
Diagnostics for schistosomiasis in Africa and Arabia: a review of present options in control and future needs for elimination
Authors: STOTHARD J. RUSSELL , STANTON MICHELLE C. , BUSTINDUY AMAYA L. , SOUSA-FIGUEIREDO JOSÉ C. , VAN DAM GOVERT J. , BETSON MARTHA , WATERHOUSE DAVID , WARD STEVE , ALLAN FIONA , HASSAN AMIR A. , AL-HELAL MOHAMMAD A. , MEMISH ZIAD A. , ROLLINSON DAVID 
Published: August 2014

SUMMARYWithin the World Health Organization 2012–2020 roadmap for control and elimination of schistosomiasis, the scale-up of mass drug administration with praziquantel is set to change the epidemiological landscape across Africa and Arabia. Central in measuring progress is renewed emphasis upon diagnostics which operate at individual, community and environmental levels by assessing reductions in disease, infections and parasite transmission. However, a fundamental tension is revealed between levels for present diagnostic tools, and methods applied in control settings are not necessarily adequate for application in elimination scenarios. Indeed navigating the transition from control to elimination needs careful consideration and planning. In the present context of control, we review current options for diagnosis of schistosomiasis at different levels, highlighting several strengths and weaknesses therein. Future challenges in elimination are raised and we propose that more cost-effective diagnostics and clinical staging algorithms are needed. Using the Kingdom of Saudi Arabia as a contemporary example, embedding new diagnostic methods within the primary care health system is discussed with reference to both urogenital and intestinal schistosomiasis.
Functional brain-imaging correlates of negative affectivity and the onset of first-episode depression
Authors: Davey C. G. , Whittle S. , Harrison B. J. , Simmons J. G. , Byrne M. L. , Schwartz O. S. , Allen N. B. 
Published: August 2014

Background.The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala–sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression.Method.Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala–sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression.Results.The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala–sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala–sACC connectivity at follow-up.Conclusions.Amygdala–sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological ‘scar’ hypothesis of depression.