129 research outputs found
Geminin deficiency enhances survival in a murine medulloblastoma model by inducing apoptosis of preneoplastic granule neuron precursors
Deflections from adolescent trajectories of antisocial behavior: contextual and neural moderators of antisocial behavior stability into emerging adulthood
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146467/1/jcpp12931_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146467/2/jcpp12931.pd
Therapist and computerâbased brief interventions for drug use within a randomized controlled trial: effects on parallel trajectories of alcohol use, cannabis use and anxiety symptoms
Background and AimsDespite their high comorbidity, the effects of brief interventions (BI) to reduce cannabis use, alcohol use and anxiety symptoms have received little empirical attention. The aims of this study were to examine whether a therapistâdelivered BI (TBI) or computerâguided BI (CBI) to address drug use, alcohol consumption (when relevant) and HIV risk behaviors, relative to enhanced usual care (EUC), was associated with reductions in parallel trajectories of alcohol use, cannabis use and anxiety symptoms, and whether demographic characteristics moderated reductions over time.DesignLatent growth curve modeling was used to examine joint trajectories of alcohol use, cannabis use and anxiety symptoms assessed at 3, 6 and 12 months after baseline enrollment.SettingHurley Medical Center Emergency Department (ED) in Flint, MI, USA.ParticipantsThe sample was 780 drugâusing adults (aged 18â60Â years; 44% male; 52% black) randomly assigned to receive either a TBI, CBI or EUC through the HealthiER You study.Interventions and comparatorEDâdelivered TBI and CBIs involved touchscreenâdelivered and audioâassisted content. The TBI was administered by a Masterâsâlevel therapist, whereas the CBI was selfâadministered using a virtual health counselor. EUC included a review of health resources brochures in the ED.MeasurementsAssessments of alcohol use (10âitem Alcohol Use Disorders Identification Test), cannabis use (past 30âday frequency) and anxiety symptoms (Brief Symptom Inventoryâ18) occurred at baseline and 3â, 6â and 12âmonth followâup.FindingsTBI, relative to EUC, was associated with significant reductions in cannabis use [BÂ =Â â0.49, standard error (SE)Â =Â 0.20, PÂ <Â 0.05) and anxiety (BÂ =Â â0.04, SEÂ =Â 0.02, PÂ <Â 0.05), but no main effect for alcohol use. Two of 18 moderation tests were significant: TBI significantly reduced alcohol use among males (BÂ =Â â0.60, SEÂ =Â 0.19, PÂ <Â 0.01) and patients aged 18â25Â years in the TBI condition showed significantly greater reductions in cannabis use relative to older patients (BÂ =Â â0.78, SEÂ =Â 0.31, PÂ <Â 0.05). Results for CBI were nonâsignificant.ConclusionsEmergency departmentâbased therapistâdelivered brief interventions to address drug use, alcohol consumption (when relevant) and HIV risk behaviors may also reduce alcohol use, cannabis use and anxiety over time, accounting for the overlap of these processes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152851/1/add14781.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152851/2/add14781_am.pd
Clinical utility of PKD2 mutation testing in a polycystic kidney disease cohort attending a specialist nephrology out-patient clinic.
BACKGROUND: ADPKD affects approximately 1:1000 of the worldwide population. It is caused by mutations in two genes, PKD1 and PKD2. Although allelic variation has some influence on disease severity, genic effects are strong, with PKD2 mutations predicting later onset of ESRF by up to 20 years. We therefore screened a cohort of ADPKD patients attending a nephrology out-patient clinic for PKD2 mutations, to identify factors that can be used to offer targeted gene testing and to provide patients with improved prognostic information. METHODS: 142 consecutive individuals presenting to a hospital nephrology out-patient service with a diagnosis of ADPKD and CKD stage 4 or less were screened for mutations in PKD2, following clinical evaluation and provision of a detailed family history (FH). RESULTS: PKD2 mutations were identified in one fifth of cases. 12% of non-PKD2 patients progressed to ESRF during this study whilst none with a PKD2 mutation did (median 38.5 months of follow-up, range 16-88 months, pâ<â0.03). A significant difference was found in age at ESRF of affected family members (non-PKD2 vs. PKD2, 54 yrs vs. 65 yrs; pâ<â0.0001). No PKD2 mutations were identified in patients with a FH of ESRF occurring before age 50 yrs, whereas a PKD2 mutation was predicted by a positive FH without ESRF. CONCLUSIONS: PKD2 testing has a clinically significant detection rate in the pre-ESRF population. It did not accurately distinguish those individuals with milder renal disease defined by stage of CKD but did identify a group less likely to progress to ESRF. When used with detailed FH, it offers useful prognostic information for individuals and their families. It can therefore be offered to all but those whose relatives have developed ESRF before age 50
Maternal Exposure to Ambient Levels of Benzene and Neural Tube Defects among Offspring: Texas, 1999â2004
Diabetes and Obesity-Related Genes and the Risk of Neural Tube Defects in the National Birth Defects Prevention Study
Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999â2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy
Molecular characterization of the conoid complex in Toxoplasma reveals its conservation in all apicomplexans, including Plasmodium species
The apical complex is the instrument of invasion used by apicomplexan parasites, and the conoid is a conspicuous feature of this apparatus found throughout this phylum. The conoid, however, is believed to be heavily reduced or missing from Plasmodium species and other members of the class Aconoidasida. Relatively few conoid proteins have previously been identified, making it difficult to address how conserved this feature is throughout the phylum, and whether it is genuinely missing from some major groups. Moreover, parasites such as Plasmodium species cycle through 3 invasive forms, and there is the possibility of differential presence of the conoid between these stages. We have applied spatial proteomics and high-resolution microscopy to develop a more complete molecular inventory and understanding of the organisation of conoid-associated proteins in the model apicomplexan Toxoplasma gondii. These data revealed molecular conservation of all conoid substructures throughout Apicomplexa, including Plasmodium, and even in allied Myzozoa such as Chromera and dinoflagellates. We reporter-tagged and observed the expression and location of several conoid complex proteins in the malaria model P. berghei and revealed equivalent structures in all of its zoite forms, as well as evidence of molecular differentiation between blood-stage merozoites and the ookinetes and sporozoites of the mosquito vector. Collectively, we show that the conoid is a conserved apicomplexan element at the heart of the invasion mechanisms of these highly successful and often devastating parasites
Search for the Standard Model Higgs Boson with the OPAL Detector at LEP
This paper summarises the search for the Standard Model Higgs boson in e+e-
collisions at centre-of-mass energies up to 209 GeV performed by the OPAL
Collaboration at LEP. The consistency of the data with the background
hypothesis and various Higgs boson mass hypotheses is examined. No indication
of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained
on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure
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Molecular characterization of the conoid complex in Toxoplasma reveals its conservation in all apicomplexans, including Plasmodium species
The apical complex is the instrument of invasion used by apicomplexan parasites, and the conoid is a conspicuous feature of this apparatus found throughout this phylum. The conoid, however, is believed to be heavily reduced or missing from Plasmodium species and other members of the class Aconoidasida. Relatively few conoid proteins have previously been identified, making it difficult to address how conserved this feature is throughout the phylum, and whether it is genuinely missing from some major groups. Moreover, parasites such as Plasmodium species cycle through 3 invasive forms, and there is the possibility of differential presence of the conoid between these stages. We have applied spatial proteomics and high-resolution microscopy to develop a more complete molecular inventory and understanding of the organisation of conoid-associated proteins in the model apicomplexan Toxoplasma gondii. These data revealed molecular conservation of all conoid substructures throughout Apicomplexa, including Plasmodium, and even in allied Myzozoa such as Chromera and dinoflagellates. We reporter-tagged and observed the expression and location of several conoid complex proteins in the malaria model P. berghei and revealed equivalent structures in all of its zoite forms, as well as evidence of molecular differentiation between blood-stage merozoites and the ookinetes and sporozoites of the mosquito vector. Collectively, we show that the conoid is a conserved apicomplexan element at the heart of the invasion mechanisms of these highly successful and often devastating parasites
Search for R-Parity Violating Decays of Scalar Fermions at LEP
A search for pair-produced scalar fermions under the assumption that R-parity
is not conserved has been performed using data collected with the OPAL detector
at LEP. The data samples analysed correspond to an integrated luminosity of
about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An
important consequence of R-parity violation is that the lightest supersymmetric
particle is expected to be unstable. Searches of R-parity violating decays of
charged sleptons, sneutrinos and squarks have been performed under the
assumptions that the lightest supersymmetric particle decays promptly and that
only one of the R-parity violating couplings is dominant for each of the decay
modes considered. Such processes would yield final states consisting of
leptons, jets, or both with or without missing energy. No significant
single-like excess of events has been observed with respect to the Standard
Model expectations. Limits on the production cross- section of scalar fermions
in R-parity violating scenarios are obtained. Constraints on the supersymmetric
particle masses are also presented in an R-parity violating framework analogous
to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.
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