SUSY Stops at a Bump

We discuss collider signatures of the "natural supersymmetry" scenario with baryon-number violating R-parity violation. We argue that this is one of the few remaining viable incarnations of weak scale supersymmetry consistent with full electroweak naturalness. We show that this intriguing and challenging scenario contains distinctive LHC signals, resonances of hard jets in conjunction with relatively soft leptons and missing energy, which are easily overlooked by existing LHC searches. We propose novel strategies for distinguishing these signals above background, and estimate their potential reach at the 8 TeV LHC. We show that other multi-lepton signals of this scenario can be seen by currently existing searches with increased statistics, but these opportunities are more spectrum-dependent.Comment: 23 pages, 7 figures, 3 tables. V2: spectrum discussion corrected, most of the changes are in Sec. 2. Benchmarks, analysis and conclusions unchanged. References adde

Study of user-experience of an objective test (QbTest) to aid ADHD assessment and medication management: a multi-methods approach

Background The diagnosis and monitoring of Attention deficit hyperactivity disorder (ADHD) typically relies on subjective reports and observations. Objective continuous performance tests (CPTs) have been incorporated into some services to support clinical decision making. However, the feasibility and acceptability of adding such a test into routine practice is unknown. The study aimed to investigate the feasibility and acceptability of adding an objective computerised test to the routine assessment and monitoring of attention deficit hyperactivity disorder (ADHD). Methods Semi-structured interviews were conducted with clinicians (n = 10) and families (parents/young people, n = 20) who participated in a randomised controlled trial. Additionally, the same clinicians (n = 10) and families (n = 76) completed a survey assessing their experience of the QbTest. The study took place in child and adolescent mental health and community paediatric clinics across the UK. Interview transcripts were thematically analysed. Results Interviewed clinicians and families valued the QbTest for providing an objective, valid assessment of symptoms. The QbTest was noted to facilitate communication between clinicians, families and schools. However, whereas clinicians were more unanimous on the usefulness of the QbTest, survey findings showed that, although the majority of families found the test useful, less than half felt the QbTest helped them understand the clinician’s decision making around diagnosis and medication. The QbTest was seen as a potentially valuable tool to use early in the assessment process to streamline the care pathway. Although clinicians were conscious of the additional costs, these could be offset by reductions in time to diagnosis and the delivery of the test by a Healthcare Assistant. Conclusions The findings indicate the QbTest is an acceptable and feasible tool to implement in routine clinical settings. Clinicians should be mindful to discuss the QbTest results with families to enable their understanding and engagement with the process. Further findings from definitive trials are required to understand the cost/benefit; however, the findings from this study support the feasibility and acceptability of integrating QbTest in the ADHD care pathway

Editorial: Observational studies in ADHD: the effects of switching to modified-release methylphenidate preparations on clinical outcomes and adherence

Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomised controlled trials as these are usually only short-term. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPH-MR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence

XRCC1 gene polymorphisms in a population sample and in women with a family history of breast cancer from Rio de Janeiro (Brazil)

The X-ray repair cross-complementing Group1 (XRCC1) gene has been defined as essential in the base excision repair (BER) and single-strand break repair processes. This gene is highly polymorphic, and the most extensively studied genetic changes are in exon 6 (Arg194Trp) and in exon 10 (Arg399Gln). These changes, in conserved protein sites, may alter the base excision repair capacity, increasing the susceptibility to adverse health conditions, including cancer. In the present study, we estimated the frequencies of the XRCC1 gene polymorphisms Arg194Trp and Arg399Gln in healthy individuals and also in women at risk of breast cancer due to family history from Rio de Janeiro. The common genotypes in both positions (194 and 399) were the most frequent in this Brazilian sample. Although the 194Trp variant was overrepresented in women reporting familial cases of breast cancer, no statistically significant differences concerning genotype distribution or intragenic interactions were found between this group and the controls. Thus, in the population analyzed by us, variants Arg194Trp and Arg399Gln did not appear to have any impact on breast cancer susceptibility

XRCC1 gene polymorphisms in a population sample and in women with a family history of breast cancer from Rio de Janeiro (Brazil)

The X-ray repair cross-complementing Group1 (XRCC1) gene has been defined as essential in the base excision repair (BER) and single-strand break repair processes. This gene is highly polymorphic, and the most extensively studied genetic changes are in exon 6 (Arg194Trp) and in exon 10 (Arg399Gln). These changes, in conserved protein sites, may alter the base excision repair capacity, increasing the susceptibility to adverse health conditions, including cancer. In the present study, we estimated the frequencies of the XRCC1 gene polymorphisms Arg194Trp and Arg399Gln in healthy individuals and also in women at risk of breast cancer due to family history from Rio de Janeiro. The common genotypes in both positions (194 and 399) were the most frequent in this Brazilian sample. Although the 194Trp variant was overrepresented in women reporting familial cases of breast cancer, no statistically significant differences concerning genotype distribution or intragenic interactions were found between this group and the controls. Thus, in the population analyzed by us, variants Arg194Trp and Arg399Gln did not appear to have any impact on breast cancer susceptibility

Retinal repair by transplantation of photoreceptor precursors

Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system repair; photoreceptor degeneration initially leaves the inner retinal circuitry intact and new photoreceptors need only make single, short synaptic connections to contribute to the retinotopic map. So far, brain- and retina-derived stem cells transplanted into adult retina have shown little evidence of being able to integrate into the outer nuclear layer and differentiate into new photoreceptors(1-4). Furthermore, there has been no demonstration that transplanted cells form functional synaptic connections with other neurons in the recipient retina or restore visual function. This might be because the mature mammalian retina lacks the ability to accept and incorporate stem cells or to promote photoreceptor differentiation. We hypothesized that committed progenitor or precursor cells at later ontogenetic stages might have a higher probability of success upon transplantation. Here we show that donor cells can integrate into the adult or degenerating retina if they are taken from the developing retina at a time coincident with the peak of rod genesis(5). These transplanted cells integrate, differentiate into rod photoreceptors, form synaptic connections and improve visual function. Furthermore, we use genetically tagged postmitotic rod precursors expressing the transcription factor Nrl (ref. 6) ( neural retina leucine zipper) to show that successfully integrated rod photoreceptors are derived only from immature post-mitotic rod precursors and not from proliferating progenitor or stem cells. These findings define the ontogenetic stage of donor cells for successful rod photoreceptor transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62596/1/nature05161.pd

p53 Target Gene SMAR1 Is Dysregulated in Breast Cancer: Its Role in Cancer Cell Migration and Invasion

Tumor suppressor SMAR1 interacts and stabilizes p53 through phosphorylation at its serine-15 residue. We show that SMAR1 transcription is regulated by p53 through its response element present in the SMAR1 promoter. Upon Doxorubicin induced DNA damage, acetylated p53 is recruited on SMAR1 promoter that allows activation of its transcription. Once SMAR1 is induced, cell cycle arrest is observed that is correlated to increased phospho-ser-15-p53 and decreased p53 acetylation. Further we demonstrate that SMAR1 expression is drastically reduced during advancement of human breast cancer. This was correlated with defective p53 expression in breast cancer where acetylated p53 is sequestered into the heterochromatin region and become inaccessible to activate SMAR1 promoter. In a recent report we have shown that SMAR1 represses Cyclin D1 transcription through recruitment of HDAC1 dependent repressor complex at the MAR site of Cyclin D1 promoter. Here we show that downmodulation of SMAR1 in high grade breast carcinoma is correlated with upregulated Cyclin D1 expression. We also established that SMAR1 inhibits tumor cell migration and metastases through inhibition of TGFβ signaling and its downstream target genes including cutl1 and various focal adhesion molecules. Thus, we report that SMAR1 plays a central role in coordinating p53 and TGFβ pathways in human breast cancer

Monocyte Scintigraphy in Rheumatoid Arthritis: The Dynamics of Monocyte Migration in Immune-Mediated Inflammatory Disease

Background: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man. Methods/Principal Findings: We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT). We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99m-Tc-HMPAO). Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4x10(-3) (0.95-5.1x10(-3)) % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion. Conclusions/Significance: The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention

Treatment outcomes in HIV-infected adolescents attending a community-based antiretroviral therapy clinic in South Africa

<p>Abstract</p> <p>Background</p> <p>Very few data are available on treatment outcomes of adolescents living with HIV infection (whether perinatally acquired or sexually acquired) in sub-Saharan Africa. The present study therefore compared the treatment outcomes in adolescents with those of young adults at a public sector community-based ART programme in Cape Town, South Africa.</p> <p>Methods</p> <p>Treatment outcomes of adolescents (9-19 years) were compared with those of young adults (20-28 years), enrolled in a prospective cohort between September 2002 and June 2009. Kaplan-Meier estimates and Cox proportional hazard models were used to assess outcomes and determine associations with age, while adjusting for potential confounders. The treatment outcomes were mortality, loss to follow-up (LTFU), immunological response, virological suppression and virological failure.</p> <p>Results</p> <p>883 patients, including 65 adolescents (47 perinatally infected and 17 sexually infected) and 818 young adults, received ART. There was no difference in median baseline CD4 cell count between adolescents and young adults (133.5 vs 116 cells/μL; <it>p </it>= 0.31). Overall mortality rates in adolescents and young adults were 1.2 (0.3-4.8) and 3.1 (2.4-3.9) deaths per 100 person-years, respectively. Adolescents had lower rates of virological suppression (< 400 copies/mL) at 48 weeks (27.3% vs 63.1%; <it>p </it>< 0.001). Despite this, however, the median change in CD4 count from baseline at 48 weeks of ART was significantly greater for adolescents than young adults (373 vs 187 cells/μL; <it>p </it>= 0.0001). Treatment failure rates were 8.2 (4.6-14.4) and 5.0 (4.1-6.1) per 100 person-years in the two groups. In multivariate analyses, there was no significant difference in LTFU and mortality between age groups but increased risk in virological failure [AHR 2.06 (95% CI 1.11-3.81; <it>p </it>= 0.002)] in adolescents.</p> <p>Conclusions</p> <p>Despite lower virological suppression rates and higher rates of virological failure, immunological responses were nevertheless greater in adolescents than young adults whereas rates of mortality and LTFU were similar. Further studies to determine the reasons for poorer virological outcomes are needed.</p