Using mammographic density to predict breast cancer risk: dense area or percentage dense area.

INTRODUCTION: Mammographic density (MD) is one of the strongest risk factors for breast cancer. It is not clear whether this association is best expressed in terms of absolute dense area or percentage dense area (PDA). METHODS: We measured MD, including nondense area (here a surrogate for weight), in the mediolateral oblique (MLO) mammogram using a computer-assisted thresholding technique for 634 cases and 1,880 age-matched controls from the Cambridge and Norwich Breast Screening programs. Conditional logistic regression was used to estimate the risk of breast cancer, and fits of the models were compared using likelihood ratio tests and the Bayesian information criteria (BIC). All P values were two-sided. RESULTS: Square-root dense area was the best single predictor (for example, χ₁² = 53.2 versus 44.4 for PDA). Addition of PDA and/or square-root nondense area did not improve the fit (both P > 0.3). Addition of nondense area improved the fit of the model with PDA (χ₁² = 11.6; P < 0.001). According to the BIC, the PDA and nondense area model did not provide a better fit than the dense area alone model. The fitted values of the two models were highly correlated (r = 0.97). When a measure of body size is included with PDA, the predicted risk is almost identical to that from fitting dense area alone. CONCLUSIONS: As a single parameter, dense area provides more information than PDA on breast cancer risk

Can Reproductive Health Voucher Programs Improve Quality of Postnatal Care? A Quasi-Experimental Evaluation of Kenya’s Safe Motherhood Voucher Scheme

This study tests the group-level causal relationship between the expansion of Kenya’s Safe Motherhood voucher program and changes in quality of postnatal care (PNC) provided at voucher-contracted facilities. We compare facilities accredited since program inception in 2006 (phase I) and facilities accredited since 2010-2011 (phase II) relative to comparable non-voucher facilities. PNC quality is assessed using observed clinical content processes, as well as client-reported outcome measures. Two-tailed unpaired t-tests are used to identify differences in mean process quality scores and client-reported outcome measures, comparing changes between intervention and comparison groups at the 2010 and 2012 data collection periods. Difference-in-differences analysis is used to estimate the reproductive health (RH) voucher program’s causal effect on quality of care by exploiting group-level differences between voucher-accredited and non-accredited facilities in 2010 and 2012. Participation in the voucher scheme since 2006 significantly improves overall quality of postnatal care by 39% (p=0.02), where quality is defined as the observable processes or components of service provision that occur during a PNC consultation. Program participation since phase I is estimated to improve the quality of observed maternal postnatal care by 86% (p=0.02), with the largest quality improvements in counselling on family planning methods (IRR 5.0; p=0.01) and return to fertility (IRR 2.6; p=0.01). Despite improvements in maternal aspects of PNC, we find a high proportion of mothers who seek PNC are not being checked by any provider after delivery. Additional strategies will be necessary to standardize provision of packaged postnatal interventions to both mother and new-born. This study addresses an important gap in the existing RH literature by using a strong evaluation design to assess RH voucher program effectiveness on quality improvement

Cost of care for cancer patients in England: evidence from population-based patient-level data

background: Health systems are facing the challenge of providing care to an increasing population of patients with cancer. However, evidence on costs is limited due to the lack of large longitudinal databases. methods: We matched cost of care data to population-based, patient-level data on cancer patients in England. We conducted a retrospective cohort study including all patients age 18 and over with a diagnosis of colorectal (275 985 patients), breast (359 771), prostate (286 426) and lung cancer (283 940) in England between 2001 and 2010. Incidence costs, prevalence costs, and phase of care costs were estimated separately for patients age 18–64 and greater than or equal to65. Costs of care were compared by patients staging, before and after diagnosis, and with a comparison population without cancer. results: Incidence costs in the first year of diagnosis are noticeably higher in patients age 18–64 than age greater than or equal to65 across all examined cancers. A lower stage diagnosis is associated with larger cost savings for colorectal and breast cancer in both age groups. The additional costs of care because of the main four cancers amounts to £1.5 billion in 2010, namely 3.0% of the total cost of hospital care. conclusions: Population-based, patient-level data can be used to provide new evidence on the cost of cancer in England. Early diagnosis and cancer prevention have scope for achieving large cost savings for the health system

Background risk of breast cancer and the association between physical activity and mammographic density

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Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

Supertwistor space for 6D maximal super Yang-Mills

6D maximal super Yang-Mills on-shell amplitudes are formulated in superspace using 6 dimensional twistors. The 3,4,5-point tree amplitudes are obtained by supersymmetrizing their bosonic counterparts and confirmed through the BCFW construction. In contrast to 4D this superspace is non-chiral, reflecting the fact that one cannot differentiate MHV from $\bar{{\rm MHV}}$ in 6D. Combined with unitarity methods, this superspace should be useful for the study of multi-loop D dimensional maximal super Yang-Mills and gravity amplitudes. Furthermore, the non-chiral nature gives a natural framework for an off-shell construction. We show this by matching our result with off-shell D=4 N=4 super Yang-Mills amplitudes, expressed in projective superspace.Comment: 6 figures 28 pages. with better sign