696 research outputs found

    Search for supersymmetry at CMS in events with b-tagged jets and missing transverse energy at 8 TeV

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    This dissertation presents results from a search for physics beyond the Standard Model, using 19.39 pb-1 of data collected by the CMS detector at the Large Hadron Collider, during its 2012 operation at center of mass energy of 8 TeV. It focuses on models of supersymmetry that lead to final states with multiple jets, especially those from b-quark decay, and a large amount of missing transverse momentum. The amounts of background from top-quark, W+jets, Z to invisible, and multi-jet production are determined from data-driven techniques. In particular, this includes a novel estimation of the missing transverse energy spectrum from semi-leptonic top/anti-top decay, which takes advantage of the precise knowledge of the W boson polarization. Predicted yields are consistent with simulated Standard Model processes and the observed data. Since no evidence of new physics is observed, limits are placed on the rate of gluino pair production to a final state with four b-quarks and two neutralinos. This process is excluded at 95% CL for a gluino with mass 1225 GeV and a neutralino with mass up to 350 GeV

    Cardiovascular Pharmacogenomics and Cognitive Function in Patients with Schizophrenia

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138379/1/phar1968_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138379/2/phar1968.pd

    Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.

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    BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is \u3e 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model. RESULTS: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p \u3c 0.0001) and chemotherapy-alone regimens (p \u3c 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment \u3c 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006). CONCLUSION: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients. TRIAL REGISTRATION: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010

    Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.

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    The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice

    The Pseudophosphatase MK-STYX Induces Neurite-Like Outgrowths in PC12 Cells

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    The rat pheochromocytoma PC12 cell line is a widely used system to study neuronal differentiation for which sustained activation of the extracellular signaling related kinase (ERK) pathway is required. Here, we investigate the function of MK-STYX [MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein] in neuronal differentiation. MK-STYX is a member of the MAPK phosphatase (MKP) family, which is generally responsible for dephosphorylating the ERKs. However, MK-STYX lacks catalytic activity due to the absence of the nucleophilic cysteine in the active site signature motif HC(X-5)R that is essential for phosphatase activity. Despite being catalytically inactive, MK-STYX has been shown to play a role in important cellular pathways, including stress responses. Here we show that PC12 cells endogenously express MK-STYX. In addition, MK-STYX, but not its catalytically active mutant, induced neurite-like outgrowths in PC12 cells. Furthermore, MK-STYX dramatically increased the number of cells with neurite extensions in response to nerve growth factor (NGF), whereas the catalytically active mutant did not. MK-STYX continued to induce neurites in the presence of a MEK (MAP kinase kinase) inhibitor suggesting that MK-STYX does not act through the Ras-ERK/MAPK pathway but is involved in another pathway whose inactivation leads to neuronal differentiation. RhoA activity assays indicated that MK-STYX induced extensions through the Rho signaling pathway. MK-STYX decreased RhoA activation, whereas RhoA activation increased when MK-STYX was down-regulated. Furthermore, MK-STYX affected downstream players of RhoA such as the actin binding protein cofilin. The presence of MK-STYX decreased the phosphorylation of cofilin in non NGF stimulated cells, but increased its phosphorylation in NGF stimulated cells, whereas knocking down MK-STYX caused an opposite effect. Taken together our data suggest that MK-STYX may be a regulator of RhoA signaling, and implicate this pseudophosphatase as a regulator of neuronal differentiation

    Healthcare Mistreatment, State-Level Policy Protections, and Healthcare Avoidance Among Gender Minority People

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    Introduction: This study examined whether past experiences of mistreatment in healthcare were associated with greater healthcare avoidance due to anticipated mistreatment among gender minority (GM) people. We evaluated whether state-level healthcare policy protections moderated this relationship. Methods: Data from the 2018 Annual Questionnaire of The PRIDE Study, a national longitudinal study on sexual and gender minority people’s health, were used in these analyses. Logistic regression modeling tested relationships between lifetime healthcare mistreatment due to gender identity or expression and past-year healthcare avoidance due to anticipated mistreatment among GM participants. Interactions between lifetime healthcare mistreatment and state-level healthcare policy protections and their relationship with past-year healthcare avoidance were tested. Results: Participants reporting any lifetime healthcare mistreatment had greater odds of past-year healthcare avoidance due to anticipated mistreatment among gender expansive people (n = 1290, OR = 4.71 [CI]: 3.57–6.20), transfeminine people (n = 263, OR = 10.32 [CI]: 4.72–22.59), and transmasculine people (n = 471, OR = 3.90 [CI]: 2.50–6.13). Presence of state-level healthcare policy protections did not moderate this relationship in any study groups. Conclusions: For GM people, reporting lifetime healthcare mistreatment was associated with healthcare avoidance due to anticipated mistreatment. State-level healthcare policy protections were not a moderating factor in this relationship. Efforts to evaluate the implementation and enforcement of state-level policies are needed. Continued efforts to understand instances of and to diminish healthcare mistreatment of GM people are recommended

    Ekstensifikasi Subjectum Litis Dalam Perselisihan Pemilu Legislatif Dan Pemilihan Kepala Daerah

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    Subjectum litis in The Legislative and Regional Head Election Disputes in Indonesia has been determined in a limited manner in The legislation and The regulation of the Constitutional Court. However along with the election, there is expansion and constriction of subjectum litis. The purpose of this study was to investigate the determinant factors that cause flexibility of subjectum litis in legislative and regional head election dispute. In addition, no previous studies that examine factors associated with the causes flexibility of subjectum litis in the legislative and the regional headselestion.The method used in this research is using qualitative methods with normative juridical approach by collecting data and information of the legislative and head regional election dispute advance in literature. The results obtained in this study that the shift in legislative elections expanded not only to political parties and individuals DPD that can be subjectum litis but also those of individual candidates of political parties can be subjectum litis in the legislative election disputes. The factor that caused it is the choice of electoral system is still used to 2014 electoral system. Meanwhile, the Regional Head election disputes in general as subjectum litis are that couple candidates for Governor and Vice Governor, Regent and Vice Regent and the Mayor and Deputy Mayor. But in its development, the narrowing of the only candidates who met the threshold difference of votes that can act as an applicant. Besides narrowing, there is also an extension where Consitutional court accommodate domestic election observers were registered and accredited by the KPU / KIP can act as subjectum litis and as the applicant would be candidates in the General Election of 2010. Factors that cause the narrowing and expansion in the elections of regional heads are the will of lawmakers and the limited authority of the Consitutional court as well as the presence of a single candidate who is not predictable by lawmakers in drafting electoral laws regional head. Whereas in 2010, the expansion of subjectum litis because the Court did extensive interpretation caused by serious violations of the right to be elected (rights to be a candidate). Suggestions for lawmakers tobe more thoroughly formulate norms by looking at the existing state of society so it can bring justice and legal certainty both for the expectant couple and society

    Search for stop and higgsino production using diphoton Higgs boson decays

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    Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

    Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

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    The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe
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