Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies.

BACKGROUND: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. METHODS: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. FINDINGS: Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons). INTERPRETATION: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. FUNDING: Cancer Research UK.

Two's company, three's a crowd: experimental evaluation of the evolutionary maintenance of trioecy in Mercurialis annua (Euphorbiaceae).

Trioecy is an uncommon sexual system in which males, females, and hermaphrodites co-occur as three clearly different gender classes. The evolutionary stability of trioecy is unclear, but would depend on factors such as hermaphroditic sex allocation and rates of outcrossing vs. selfing. Here, trioecious populations of Mercurialis annua are described for the first time. We examined the frequencies of females, males and hermaphrodites across ten natural populations and evaluated the association between the frequency of females and plant densities. Previous studies have shown that selfing rates in this species are density-dependent and are reduced in the presence of males, which produce substantially more pollen than hermaphrodites. Accordingly, we examined the evolutionary stability of trioecy using an experiment in which we (a) indirectly manipulated selfing rates by altering plant densities and the frequency of males in a fully factorial manner across 20 experimental plots and (b) examined the effect of these manipulations on the frequency of the three sex phenotypes in the next generation of plants. In the parental generation, we measured the seed and pollen allocations of hermaphrodites and compared them with allocations by unisexual plants. In natural populations, females occurred at higher frequencies in denser patches, a finding consistent with our expectations. Under our experimental conditions, however, no combination of plant densities and male frequencies was associated with increased frequencies of females. Our results suggest that the factors that regulate female frequencies in trioecious populations of M. annua are independent of those regulating male frequencies (density), and that the stable co-existence of all three sex phenotypes within populations is unlikely.

The Expenditure Impacts of Individual Higher Education Institutions (HEIs) and their Students on the Scottish Economy under Devolution: Homogeneity or Heterogeneity?

Comparing each of the twenty Higher Education Institutions (HEIs) in Scotland as separate sectors in an Input-Output table suggests their expenditure patterns are homogenous and that the apparent heterogeneity of their impacts is primarily driven by scale. However, a disaggregation of their income by source reveals a disparity in their dependence upon funding from the devolved Scottish Government and their ability to draw in income/funding from external sources. Acknowledging the binding budget constraint of the Scottish Government and deriving balanced expenditure multipliers reveals large differences in the net-expenditure impact of HEIs upon the Scottish economy, with the source of variation being the origin of income. Applying a novel treatment of student expenditure impacts, identifying the amount of exogenous spending per student, modifies the heterogeneity of the overall expenditure impacts. On balance this suggests that the impacts of impending budget cut-backs will be quite different by institution depending on their sensitivity to public funding. However, predicting the outcome of budget cutbacks at the margin is problematic as we do not know whether public and external incomes are complements or substitutions (and indeed this may vary between individual HEIs).

The Expenditure Impacts of Individual Higher Education Institutions (HEIs) and their Students on the Welsh Economy: Homogeneity or Heterogeneity?

This paper replicates the analysis of Scottish HEIs in Hermannsson et al (2010a) for the case of Wales in order to provide a self-contained analysis that is readily accessible by those whose primary concern is with the regional impacts of Welsh HEIs. When we treat each of the twelve Higher Education Institutions (HEIs) that existed in Wales in 2006 as separate sectors in conventional input-output analysis, their expenditure impacts per unit of final demand appear rather homogenous, with the apparent heterogeneity of their overall impacts being primarily driven by scale. However, a disaggregation of their income by source reveals considerable variation in their dependence upon funding from the devolved Welsh Assembly Government and their ability to draw in income/funding from external sources. Acknowledging the binding budget constraint of the Welsh Assembly Government and deriving balanced expenditure multipliers reveals large differences in the net-expenditure impact of HEIs upon the Welsh economy, with the source of variation being the origin of income. Applying a novel treatment of student expenditure impacts, identifying the amount of exogenous spending per student, modifies the heterogeneity of the overall expenditure impacts. On balance this suggests that the impacts of impending budget cut-backs will be quite different by institution depending on their sensitivity to public funding. However, predicting the outcome of budget cutbacks at the margin is problematic for reasons that we identify.

The Expenditure Impacts of London-based Individual Higher Education Institutions (HEIs) and their Students on the Economy of England: Homogeneity or Heterogeneity?

This paper replicates the analysis of Scottish HEIs in Hermannsson et al (2010a) to identify the impact of London-based HEIs on the English economy in order to provide a self-contained analysis that is readily accessible by those whose primary concern is with the regional impacts of London HEIs. When we treat each of the 38 London-based Higher Education Institutions (HEIs) that existed in England in 2006 as separate sectors in conventional input-output analysis, their expenditure impacts per unit of final demand appear rather homogenous (though less so than HEIs in Wales and Scotland), with the apparent heterogeneity of their overall impacts being primarily driven by scale. However, a disaggregation of their income by source reveals considerable variation in their dependence upon general public funding and their ability to draw in income/funding from external sources. Acknowledging the possible alternative uses of the public funding and deriving balanced expenditure multipliers reveals large differences in the net-expenditure impact of London HEIs upon the English economy, with the source of variation being the origin of income. Applying a novel treatment of student expenditure impacts, identifying the amount of exogenous spending per student, modifies the heterogeneity of the overall expenditure impacts. On balance this suggests that the impacts of impending budget cut-backs will be quite different by institution depending on their sensitivity to public funding. However, predicting the outcome of budget cutbacks at the margin is problematic for reasons that we identify.

The Expenditure Impacts of Individual Higher Education Institutions (HEIs) and their Students on the Northern Irish Economy: Homogeneity or Heterogeneity?

This paper replicates the analysis of Scottish HEIs in Hermannsson et al (2010a) for the case of Northern Ireland in order to provide a self-contained analysis that is readily accessible by those whose primary concern is with the regional impacts of Northern-Irish HEIs. When we treat each of the four Higher Education Institutions (HEIs) that existed in Northern Ireland in 2006 as separate sectors in conventional input-output analysis, their expenditure impacts per unit of final demand appear rather homogenous, with the apparent heterogeneity of their overall impacts being primarily driven by scale. However, a disaggregation of their income by source reveals considerable variation in their dependence upon funding from the devolved Assembly and their ability to draw in income/funding from external sources. Acknowledging the binding budget constraint of the Northern Ireland Assembly and deriving balanced expenditure multipliers reveals large differences in the netexpenditure impact of HEIs upon the Northern Irish economy, with the source of variation being the origin of income. Applying a novel treatment of student expenditure impacts, identifying the amount of exogenous spending per student, modifies the heterogeneity of the overall expenditure impacts. On balance this suggests that the impacts of impending budget cut-backs will be quite different by institution depending on their sensitivity to public funding. However, predicting the outcome of budget cutbacks at the margin is problematic for reasons that we identify.

International Aid to Tanzania – with some comparisons from Ghana and Uganda

This paper has three principal objectives. First, to review the level of Official Development Assistance (ODA) to Tanzania over the last two to three decades, and to place this into an economic context. This review includes some comparisons with the experience of Ghana and Uganda. Second, to discuss three major issues for the Tanzanian aid: the position of ODA as budget support, corruption, and alignment with the principles of the Paris Declaration on Aid Effectiveness. Third, to review the literature on the Tanzanian aid experience, including a range of official evaluation reports produced by the Tanzanian government and by the donor community. The conclusions, broadly, are that ODA has been at a sustained high level for most of the period reviewed, funding a significant amount of government development expenditure, and that economic growth has been strong, with poverty reduction ‘flat-lining’ in Tanzania but being significant in Ghana and Uganda. Experience with budget support in Tanzania has been mixed, corruption continues as a major concern, and improvements to public finance management have been difficult to achieve. In this context governance adjustments come slowly, requiring patience on the part of both recipient governments and the ODA donor community.

Schistosomiasis research funding: the TDR contribution

In spite of the recent decline in financial support on the part of some major donors, the overall international support for schistosomiasis research in current US dollars has been holding steady. However, when adjusted for inflation, a clear decline during the last decade appears and only in a few countries has this decline been balanced by increased national or bilateral funding. The prevailing level of support for schistosomiasis research is barely sufficient to maintain estabilished laboratories and researchers, and highlights the need to attract young investigators. The important goal of brunging a new generation of scientists into the field of schistosomiaisis can only be achieved by a considerable long-term increase in funding, both at the national and the international levels. A break-through in current research emphasizing improved techniques for control is needed to encourage donors and governments to improve the situation.

Trace-element and phosphorus contents in sediment associated with Cretaceous oceanic anoxic events

ABSTRACT : During my SNSF-funded Ph.D. thesis project, I studied the evolution of redox conditions and organic-carbon preservation in the western Tethyan realm during three major positive excursions in the Cretaceous δ13C record, corresponding to the Valanginian, Early Aptian and Late Cenomanian. These periods were characterized by important global environmental and climate change, which was associated with perturbations in the carbon cycle. For the period of the Valanginian δ13C excursion, total organic carbon (TOC) contents and the quality of preserved organic matter are typical of oxic pelagic settings in the western Tethys. This is confirmed by the absence of major excursions in the stratigraphic distribution of RSTE during the δ13C shift. Published TOC data from other parts of the Valanginian oceans indicate that dys- to anaerobic zones were restricted to marginal seas within the Atlantic and Southern Ocean, and to the Pacific. Phosphorus (P) and mineralogical contents suggest a stepwise climatic evolution during the Valanginian, with a humid and warm climate prior to the δ13C shift leading to an increase in continental runoff. During the δ13C shift, a decrease in detrital input and P contents suggests a change in the climate towards more and conditions. During the early Aptian oceanic anoxic event (OAE 1a), a general increase followed by a rapid decrease in P contents suggests enhanced nutrient input at the beginning of OAE 1a. The return to lower values during OAE 1 a, associated with an increase in RSTE contents, may have been related to the weakened capacity to retain P in the sedimentary reservoir due to bottom-water oxygen depletion. In basinal settings, the RSTE distribution indicates well-developed anoxic conditions during OAE la, whereas in the shallower-water environments, conditions were oxic to suboxic, rather than anoxic. Furthermore, in the deeper part of the Tethys, two distinct enrichments have been observed, indicating fluctuations in the intensity of water column anoxia during the δ73C excursion. We also studied the effect of the end-Cenomanian oceanic anoxic event (OAE 2) on an expanded section in the Chrummflueschlucht (E of Euthal, Ct Switzerland). The goal here was to identify paleoceanographic and paleoenvironmental conditions during OAE 2 in this part of the northern Tethyan margin. The results show that this section is one of the most complete sections for the Cenomanian-Turonian boundary interval known from the Helvetic realm, despite a small hiatus between sediments corresponding to peaks 1 and 2 in the δ13C record. The evolution of P contents points to an increase in the input of this nutrient at the onset of OAE 2. The trends in RSTE contents show, however, that this part of the Helvetic realm was not affected by a strong depletion in oxygen conditions during OAE 2, despite its hemipelagic position. A further goal of this project was to submit the samples to a total extraction method (a combined HF/HNO3/HCI acid digestion) and compare the results obtained by the partial HNO3 acid extraction in order to standardize the analytical prócedures in the extraction of RSTE. The obtained results for samples of OAE 1 a suggest that RSTE trends using the partial HNO3 digestion are very comparable to those obtained by the total digestion method and subsequently normalized with regards to AI contents. RÉSUMÉ : Durant ce projet de thèse, financé par le Swiss National Science Funding (SNSF), j'ai étudié l'évolution des conditions redox et de la préservation de carbone organique dans le domnaine ouesttéthysien pendant trois excursions majeures du δ13C au Crétacé correspondant au Valanginien, à l'Aptien inférieur et à la limite Cénomanien-Turonien. Ces périodes sont caractérisées par des changements climatiques et environnementaux globaux associés à des perturbations dans le cylce du carbone. Pour L'excursion positive en δ13C du Valanginien, les analyses du carbone organique total (COT) et les observations palynologiques du domaine téthysien ont présenté des indications d'environnement pélagique relativementbienoxygéné. L'absence d'enrichissements en éléments traces sensibles aux conditions redox (TE) pendant l'excursion positive en δ13C confirme ces interprétations. Les données publiées de COT dans d'autres partie du globe indiquent cependant l'existence de conditions dys- à anaérobiques dans certains bassins restreints de l'Atlantique, l'Océan Austral et du Pacifique. L'évolution du phosphore (P) et la composition minéralogique des sédiments semblent indiquer un climat relativement chaud et humide avant l'excursion en δ13C entraînant une augmentation de l'altération continentale. Pendant le shift isotopique, une diminution des apports détritiques et du P suggèrent une transition vers des conditions plus arides. À l'Aptien Inférieur, le début de l'événement anoxique (OAE 1a) est marqué par une augmentation générale du P dans les sédiments indiquant une augmentation du niveau trophique à la base de l'excursion isotopique. Durant l'événement anoxique, les sédiments sont relativement appauvris en P. Cette diminution rapide associée à des enrichissements en TE est probablement liée à une remobilisation plus importante du P lors de la mise en place de conditions anoxiques dans les eaux de fond. Dans les environnements de bassin, le comportement des TE (enrichissements bien marqués) attestent de conditions réductrices bien marquées alors que dans les environnements moins profonds, les conditions semblent plutôt oxiques à dysoxiques. De plus, deux niveaux d'enrichissement en TE ont été observés dans la partie plus profonde de la Téthys, indiquant des fluctuations assez rapides dans l'intensité de l'anoxie de la colonne d'eau. Nous avons ensuite étudié les effets de l'événement anoxique de la fin du Cenomanien (OAE 2) dans un basin marginal de la marge nord de la Téthys avec la coupe de Chrummflueschlucht (à l'est de Euthal, Ct Schwyz). Les résultats ont montré que cette coupe présente un des enregistrements sédimentaires des plus complets de l'OAE 2 dans le domaine helvétique malgré un hiatus entre le pic 1 et 2 de l'excursion en δ13C. L'évolution du P montre une augmentation au début de l'OAE 2. Cependant, la distribution des TE indique que cette région n'a pas été affectée par des conditions réductrices trop importantes. Un second aspect de ce travail a été l'étude des différentes méthodes sur l'analyse de la distribution des TE. Des échantillons de l'OAE 1a ont été soumis à deux types d'extractions, l'une dite «totale » (attaque combinée d'acides HF/HNO3/HCI) et l'autre dite partielle » (HNO3). Les résultats obtenus suggèrent que les courbes de tendances des TE acquises par extraction partielle sont semblables à celle obtenues par extraction totale et normalisées par l'AI.

Comrades or Culprits? Donor Engagement and Budget Transparency in Aid Dependent Countries

Budget transparency has come to be considered a key aspect of governance. Over the past decade, donors have invested increasing resources in strengthening processes through which budget transparency in developing countries can be enhanced. According to the 2008 Open Budget Index (OBI) Report, however, aid dependency and budget transparency appear to be inversely correlated. This article looks at the role of donor agencies in promoting or preventing budget transparency in aid dependent countries. It analyzes data for a sample of 16 aid-dependent countries included in the OBI, to test some preliminary hypotheses and select six countries for which more detailed findings are then presented. All of these countries have implemented reforms aimed at enhancing budget transparency, with substantial donor support. These, however, often had only limited success, partly because they were not well adapted to the local context, and partly because donors put limited emphasis on improving public access to budget information. Donor efforts were also often offset by other characteristics of donor interventions, namely their fragmentation, lack of transparency, and limited use of program aid modalities such as budget support and pooled sector funding.

Are virtual planning and guided surgery for head and neck reconstruction economically viable?

PURPOSE: Virtual planning and guided surgery with or without prebent or milled plates are becoming more and more common for mandibular reconstruction with fibular free flaps (FFFs). Although this excellent surgical option is being used more widely, the question of the additional cost of planning and cutting-guide production has to be discussed. In capped payment systems such additional costs have to be offset by other savings if there are no special provisions for extra funding. Our study was designed to determine whether using virtual planning and guided surgery resulted in time saved during surgery and whether this time gain resulted in self-funding of such planning through the time saved. MATERIALS AND METHODS: All consecutive cases of FFF surgery were evaluated during a 2-year period. Institutional data were used to determine the price of 1 minute of operative time. The time for fibula molding, plate adaptation, and insetting was recorded. RESULTS: During the defined period, we performed 20 mandibular reconstructions using FFFs, 9 with virtual planning and guided surgery and 11 freehand cases. One minute of operative time was calculated to cost US $47.50. Multiplying this number by the time saved, we found that the additional cost of virtual planning was reduced from US $5,098 to US $1,231.50 with a prebent plate and from US $6,980 to US $3,113.50 for a milled plate. CONCLUSIONS: Even in capped health care systems, virtual planning and guided surgery including prebent or milled plates are financially viable.

Opportunity to shape the prevention and management of obesity

Cooperation and Working Together (CAWT), the cross border health and social care partnership has been working with the Departments of Health to progress a three year cross border obesity prevention and management project aimed at families. They have been successful in securing funding from the EU INTERREG IVA programme. A planning workshop focussing on this will be held on Friday 26 June 2009.

Final Report Review of DHSSPS Training Support Funding For Social Care Voluntary Organisations February 2011 (PDF 368KB)

Review of DHSSPS Training Support Funding Programme For Social Care Voluntary Organisations

Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.

Primary care at Swiss universities--current state and perspective.

BACKGROUND: There is increasing evidence that a strong primary care is a cornerstone of an efficient health care system. But Switzerland is facing a shortage of primary care physicians (PCPs). This pushed the Federal Council of Switzerland to introduce a multifaceted political programme to strengthen the position of primary care, including its academic role. The aim of this paper is to provide a comprehensive overview of the situation of academic primary care at the five Swiss universities by the end of year 2012. RESULTS: Although primary care teaching activities have a long tradition at the five Swiss universities with activities starting in the beginning of the 1980ies; the academic institutes of primary care were only established in recent years (2005 - 2009). Only one of them has an established chair. Human and financial resources vary substantially. At all universities a broad variety of courses and lectures are offered, including teaching in private primary care practices with 1331 PCPs involved. Regarding research, differences among the institutes are tremendous, mainly caused by entirely different human resources and skills. CONCLUSION: So far, the activities of the existing institutes at the Swiss Universities are mainly focused on teaching. However, for a complete academic institutionalization as well as an increased acceptance and attractiveness, more research activities are needed. In addition to an adequate basic funding of research positions, competitive research grants have to be created to establish a specialty-specific research culture.