251 research outputs found
Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset
Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples.
First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls.
Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95-1.00) for schizophrenia detection.
Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals.
The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86-0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71-0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82-0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset
Measurement of the branching ratio of pi^0 -> e^+e^- using K_L -> 3 pi^0 decays in flight
The branching ratio of the rare decay pi^0 -> e^+e^- has been measured in
E799-II, a rare kaon decay experiment using the KTeV detector at Fermilab. The
pi^0's were produced in fully-reconstructed K_L -> 3 pi^0 decays in flight. We
observed 275 candidate pi^0 -> e^+e^- events, with an expected background of
21.4 +- 6.2 events which includes the contribution from Dalitz decays. We
measured BR(pi^0 -> e^+e^-, x>0.95) = (6.09 +- 0.40 +- 0.24) times 10^{-8},
where the first error is statistical and the second systematic. This result is
the first significant observation of the excess rate for this decay above the
unitarity lower bound.Comment: New version shortened to PRL length limit. 5 pages, 4 figures.
Published in Phys. Rev. Let
Measurements of Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Measurements of transverse energy flow are presented for neutral current
deep-inelastic scattering events produced in positron-proton collisions at
HERA. The kinematic range covers squared momentum transfers Q^2 from 3.2 to
2,200 GeV^2, the Bjorken scaling variable x from 8.10^{-5} to 0.11 and the
hadronic mass W from 66 to 233 GeV. The transverse energy flow is measured in
the hadronic centre of mass frame and is studied as a function of Q^2, x, W and
pseudorapidity. A comparison is made with QCD based models. The behaviour of
the mean transverse energy in the central pseudorapidity region and an interval
corresponding to the photon fragmentation region are analysed as a function of
Q^2 and W.Comment: 26 pages, 8 figures, submitted to Eur. Phys.
Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant
Jet event rates in deep inelastic ep scattering at HERA are investigated
applying the modified JADE jet algorithm. The analysis uses data taken with the
H1 detector in 1994 and 1995. The data are corrected for detector and
hadronization effects and then compared with perturbative QCD predictions using
next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2)
is determined evaluating the jet event rates. Values of alpha_S(Q^2) are
extracted in four different bins of the negative squared momentum
transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the
renormalization group equation to these several alpha_S(Q^2) values results in
alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys.
J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4
Differential (2+1) Jet Event Rates and Determination of alpha_s in Deep Inelastic Scattering at HERA
Events with a (2+1) jet topology in deep-inelastic scattering at HERA are
studied in the kinematic range 200 < Q^2< 10,000 GeV^2. The rate of (2+1) jet
events has been determined with the modified JADE jet algorithm as a function
of the jet resolution parameter and is compared with the predictions of Monte
Carlo models. In addition, the event rate is corrected for both hadronization
and detector effects and is compared with next-to-leading order QCD
calculations. A value of the strong coupling constant of alpha_s(M_Z^2)=
0.118+- 0.002 (stat.)^(+0.007)_(-0.008) (syst.)^(+0.007)_(-0.006) (theory) is
extracted. The systematic error includes uncertainties in the calorimeter
energy calibration, in the description of the data by current Monte Carlo
models, and in the knowledge of the parton densities. The theoretical error is
dominated by the renormalization scale ambiguity.Comment: 25 pages, 6 figures, 3 tables, submitted to Eur. Phys.
Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA
The multiplicity structure of the hadronic system X produced in
deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic
system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY
vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant
mass M_X of the system X. Results are presented on multiplicity distributions
and multiplicity moments, rapidity spectra and forward-backward correlations in
the centre-of-mass system of X. The data are compared to results in e+e-
annihilation, fixed-target lepton-nucleon collisions, hadro-produced
diffractive final states and to non-diffractive hadron-hadron collisions. The
comparison suggests a production mechanism of virtual photon dissociation which
involves a mixture of partonic states and a significant gluon content. The data
are well described by a model, based on a QCD-Regge analysis of the diffractive
structure function, which assumes a large hard gluonic component of the
colourless exchange at low Q^2. A model with soft colour interactions is also
successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first
submission - omitted bibliograph
Towards a blood-based diagnostic panel for bipolar disorder
BACKGROUND:
Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.
METHODS AND FINDINGS:
We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies. We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC)?0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.
CONCLUSIONS:
An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.We would like to thank all participants of this study as well as all participating centres for the collaboration and for access to the serum samples. We gratefully acknowledge support by the Stanley Medical Research Institute (no. 07R-1888). The infrastructure for the NESDA study (www.nesda.nl) has been funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and participating universities (VU University Medical Center, Leiden University Medical Center, University Medical Center Groningen). DNC, DWN and NSW efforts were funded by the Stanley Medical Research Institute and the US Department of the Army
Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA
An investigation of the hadronic final state in diffractive and
non--diffractive deep--inelastic electron--proton scattering at HERA is
presented, where diffractive data are selected experimentally by demanding a
large gap in pseudo --rapidity around the proton remnant direction. The
transverse energy flow in the hadronic final state is evaluated using a set of
estimators which quantify topological properties. Using available Monte Carlo
QCD calculations, it is demonstrated that the final state in diffractive DIS
exhibits the features expected if the interaction is interpreted as the
scattering of an electron off a current quark with associated effects of
perturbative QCD. A model in which deep--inelastic diffraction is taken to be
the exchange of a pomeron with partonic structure is found to reproduce the
measurements well. Models for deep--inelastic scattering, in which a
sizeable diffractive contribution is present because of non--perturbative
effects in the production of the hadronic final state, reproduce the general
tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil
A Search for Selectrons and Squarks at HERA
Data from electron-proton collisions at a center-of-mass energy of 300 GeV
are used for a search for selectrons and squarks within the framework of the
minimal supersymmetric model. The decays of selectrons and squarks into the
lightest supersymmetric particle lead to final states with an electron and
hadrons accompanied by large missing energy and transverse momentum. No signal
is found and new bounds on the existence of these particles are derived. At 95%
confidence level the excluded region extends to 65 GeV for selectron and squark
masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure
Low Q^2 Jet Production at HERA and Virtual Photon Structure
The transition between photoproduction and deep-inelastic scattering is
investigated in jet production at the HERA ep collider, using data collected by
the H1 experiment. Measurements of the differential inclusive jet
cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the
transverse energy and the pseudorapidity of the jets in the virtual
photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3
< y < 0.6. The interpretation of the results in terms of the structure of the
virtual photon is discussed. The data are best described by QCD calculations
which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure
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