The Proportion of Women Who Have a Breast 4 Years after Breast Cancer Surgery: A Population-Based Cohort Study.

BACKGROUND: There are numerous pathways in breast cancer treatment, many of which enable women to retain a breast after treatment. We evaluated the proportion of women who have a breast, either through conserving surgery (BCS) or reconstruction, at 4-years after diagnosis, and how this varied by patient group. METHODS AND FINDINGS: We identified women with breast cancer who underwent initial BCS or mastectomy in English National Health Service (NHS) hospitals between January 2008 and December 2009 using the Hospital Episode Statistics (HES) database. Women were assigned into one of four patient groups depending on their age at diagnosis and presence of comorbidities. The series of breast cancer procedure (BCS, mastectomy, immediate, or delayed reconstruction) undergone by each women was identified over four years, and the proportion of women with a breast calculated. Variation was examined across patient groups, and English Cancer Networks. Between 2008 and 2009, 60,959 women underwent BCS or mastectomy. The proportion with a breast at 4 years was 79.3%, and 64.0%, in women less than 70 years without, and with comorbidities. Whilst in women aged 70 and over without, and with comorbidities, proportions were 52.6%, and 38.2%, respectively. Comorbidities were associated with lower proportions of BCS, but had little effect on reconstruction rates unlike age. Networks variation of 15% or more was found within each patient group, and Cancer Networks tended to have either a high or low proportion across all four patient groups. However, while 14% of women under 70 years had undergone reconstruction, less than 2% of women aged 70 or more had this treatment option. CONCLUSION: The proportion of women diagnosed with breast cancer who retain a breast at 4 years is strongly associated with age, and presence of comorbidities. There was significant variation between Cancer Networks indicating that women's experience in England was dependent on their geographical location of treatment

Superhumps in Cataclysmic Binaries. XXIII. V442 Ophiuchi and RX J1643.7+3402

We report the results of long observing campaigns on two novalike variables: V442 Ophiuchi and RX J1643.7+3402. These stars have high-excitation spectra, complex line profiles signifying mass loss at particular orbital phases, and similar orbital periods (respectively 0.12433 and 0.12056 d). They are well-credentialed members of the SW Sex class of cataclysmic variables. Their light curves are also quite complex. V442 Oph shows periodic signals with periods of 0.12090(8) and 4.37(15) days, and RX J1643.7+3402 shows similar signals at 0.11696(8) d and 4.05(12) d. We interpret these short and long periods respectively as a "negative superhump" and the wobble period of the accretion disk. The superhump could then possibly arise from the heating of the secondary (and structures fixed in the orbital frame) by inner-disk radiation, which reaches the secondary relatively unimpeded since the disk is not coplanar. At higher frequencies, both stars show another type of variability: quasi-periodic oscillations (QPOs) with a period near 1000 seconds. Underlying these strong signals of low stability may be weak signals of higher stability. Similar QPOs, and negative superhumps, are quite common features in SW Sex stars. Both can in principle be explained by ascribing strong magnetism to the white dwarf member of the binary; and we suggest that SW Sex stars are borderline AM Herculis binaries, usually drowned by a high accretion rate. This would provide an ancestor channel for AM Hers, whose origin is still mysterious.Comment: PDF, 41 pages, 4 tables, 16 figures; accepted, in press, to appear December 2002, PASP; more info at http://cba.phys.columbia.edu

Stillbirths:economic and psychosocial consequences

Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity

Epstein-Barr-virus-positive large B-cell lymphoma associated with breast implants: an analysis of eight patients suggesting a possible pathogenetic relationship.

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report eight cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were noninvasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the noninvasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe that this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting

Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer

Background: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging. Methods: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake. Results: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake. Conclusions: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients. Trial registration: ClinicalTrials.gov NCT0058827

Novel Naphthalene-Based Inhibitors of Trypanosoma brucei RNA Editing Ligase 1

African sleeping sickness is a devastating disease that plagues sub-Saharan Africa. Neglected tropical diseases like African sleeping sickness cause significant death and suffering in the world's poorest countries. Current treatments for African sleeping sickness either have high costs, terrible side effects, or limited effectiveness. Consequently, new medicines are urgently needed. RNA editing ligase 1 is an important protein critical for the survival of Trypanosoma brucei, the unicellular parasite that causes African sleeping sickness. In this paper, we describe our recent efforts to use advanced computer techniques to identify chemicals predicted to prevent RNA editing ligase 1 from functioning properly. We subsequently tested our predicted chemicals and confirmed that a number of them inhibited the protein's function. Additionally, one of the chemicals was effective at stopping the growth of the parasite in culture. Although substantial work remains to be done in order to optimize these chemicals so they are effective and safe to use in human patients, the identification of these parasite-killing compounds is nevertheless a valuable step towards finding a better cure for this devastating disease

In vitro nuclear interactome of the HIV-1 Tat protein

<p>Abstract</p> <p>Background</p> <p>One facet of the complexity underlying the biology of HIV-1 resides not only in its limited number of viral proteins, but in the extensive repertoire of cellular proteins they interact with and their higher-order assembly. HIV-1 encodes the regulatory protein Tat (86–101aa), which is essential for HIV-1 replication and primarily orchestrates HIV-1 provirus transcriptional regulation. Previous studies have demonstrated that Tat function is highly dependent on specific interactions with a range of cellular proteins. However they can only partially account for the intricate molecular mechanisms underlying the dynamics of proviral gene expression. To obtain a comprehensive nuclear interaction map of Tat in T-cells, we have designed a proteomic strategy based on affinity chromatography coupled with mass spectrometry.</p> <p>Results</p> <p>Our approach resulted in the identification of a total of 183 candidates as Tat nuclear partners, 90% of which have not been previously characterised. Subsequently we applied <it>in silico </it>analysis, to validate and characterise our dataset which revealed that the Tat nuclear interactome exhibits unique signature(s). First, motif composition analysis highlighted that our dataset is enriched for domains mediating protein, RNA and DNA interactions, and helicase and ATPase activities. Secondly, functional classification and network reconstruction clearly depicted Tat as a polyvalent protein adaptor and positioned Tat at the nexus of a densely interconnected interaction network involved in a range of biological processes which included gene expression regulation, RNA biogenesis, chromatin structure, chromosome organisation, DNA replication and nuclear architecture.</p> <p>Conclusion</p> <p>We have completed the <it>in vitro </it>Tat nuclear interactome and have highlighted its modular network properties and particularly those involved in the coordination of gene expression by Tat. Ultimately, the highly specialised set of molecular interactions identified will provide a framework to further advance our understanding of the mechanisms of HIV-1 proviral gene silencing and activation.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio