MDM2 overexpression is rare in Ovarian Carcinoma irrespective of TP53 mutation status

Somatic mutations in TP53 are seen in many human cancers. In addition, the protein product of the wild-type TP53 can be sequestered by the protein MDM2 (murine double minute 2). This protein is commonly overexpressed in human sarcomas and gliomas, usually as a result of gene amplification. In this study, 43 ovarian carcinomas (OCs) were analysed for aberrations in the TP53 gene by immunohistochemistry (IHC), loss of heterozygosity (LOH) or mutation analysis. The MDM2 gene and its product was studied by Southern blotting and IHC. Over 50% of the OCs studied showed mutations in TP53 by either direct sequencing (19/36, 53%), positive IHC (23,43, 53%) or both, whereas 0/32 had amplification of MDM2 and only 1/37 tumours had positive IHC using the anti-MDM2 antibody IF-2. The solitary example of positive IHC in this series was seen in a mixed müllerian tumour with sarcomatous differentiation and was not accompanied by MDM2 DNA amplification. These results support previous data showing that around 50% of OCs have mutations in TP53 and in addition, suggest that MDM2 is not amplified in OC, but the presence of sarcomatous features in mixed müllerian tumours may result in positive immunohistochemistry with IF-2

Surgical Management of Inguinal Hernias at Bugando Medical Centre in Northwestern Tanzania: Our Experiences in a Resource-Limited Setting.

Inguinal hernia repair remains the commonest operation performed by general surgeons all over the world. There is paucity of published data on surgical management of inguinal hernias in our environment. This study is intended to describe our own experiences in the surgical management of inguinal hernias and compare our results with that reported in literature. A descriptive prospective study was conducted at Bugando Medical Centre in northwestern Tanzania. Ethical approval to conduct the study was obtained from relevant authorities before the commencement of the study. Statistical data analysis was done using SPSS software version 17.0. A total of 452 patients with inguinal hernias were enrolled in the study. The median age of patients was 36 years (range 3 months to 78 years). Males outnumbered females by a ratio of 36.7:1. This gender deference was statistically significant (P=0.003). Most patients (44.7%) presented late (more than five years of onset of hernia). Inguinoscrotal hernia (66.8%) was the commonest presentation. At presentation, 208 (46.0%) patients had reducible hernia, 110 (24.3%) had irreducible hernia, 84 (18.6%) and 50(11.1%) patients had obstructed and strangulated hernias respectively. The majority of patients (53.1%) had right sided inguinal hernia with a right-to-left ratio of 2.1: 1. Ninety-two (20.4%) patients had bilateral inguinal hernias. 296 (65.5%) patients had indirect hernia, 102 (22.6%) had direct hernia and 54 (11.9%) had both indirect and direct types (pantaloon hernia). All patients in this study underwent open herniorrhaphy. The majority of patients (61.5%) underwent elective herniorrhaphy under spinal anaesthesia (69.2%). Local anaesthesia was used in only 1.1% of cases. Bowel resection was required in 15.9% of patients. Modified Bassini's repair (79.9%) was the most common technique of posterior wall repair of the inguinal canal. Lichtenstein mesh repair was used in only one (0.2%) patient. Complication rate was 12.4% and it was significantly higher in emergency herniorrhaphy than in elective herniorrhaphy (P=0.002). The median length of hospital stay was 8 days and it was significantly longer in patients with advanced age, delayed admission, concomitant medical illness, high ASA class, the need for bowel resection and in those with surgical repair performed under general anesthesia (P<0.001). Mortality rate was 9.7%. Longer duration of symptoms, late hospitalization, coexisting disease, high ASA class, delayed operation, the need for bowel resection and presence of complications were found to be predictors of mortality (P<0.001). Inguinal hernias continue to be a source of morbidity and mortality in our centre. Early presentation and elective repair of inguinal hernias is pivotal in order to eliminate the morbidity and mortality associated with this very common problem

Mothers' AdvocateS In the Community (MOSAIC)- non-professional mentor support to reduce intimate partner violence and depression in mothers: a cluster randomised trial in primary care

Background : Effective interventions to increase safety and wellbeing of mothers experiencing intimate partner violence (IPV) are scarce. As much attention is focussed on professional intervention, this study aimed to determine the effectiveness of non-professional mentor support in reducing IPV and depression among pregnant and recent mothers experiencing, or at risk of IPV.Methods : MOSAIC was a cluster randomised trial in 106 primary care (maternal and child health nurse and general practitioner) clinics in Melbourne, Australia. 63/106 clinics referred 215 eligible culturally and linguistically diverse women between January 2006 and December 2007. 167 in the intervention (I) arm, and 91 in the comparison (C) arm. 174 (80.9%) were recruited. 133 (76.4%) women (90 I and 43 C) completed follow-up at 12 months.Intervention: 12 months of weekly home visiting from trained and supervised local mothers, (English &amp; Vietnamese speaking) offering non-professional befriending, advocacy, parenting support and referrals.Main outcome measures: Primary outcomes; IPV (Composite Abuse Scale CAS) and depression (Edinburgh Postnatal Depression Scale EPDS); secondary measures included wellbeing (SF-36), parenting stress (PSI-SF) and social support (MOS-SF) at baseline and follow-up.Analysis: Intention-to-treat using multivariable logistic regression and propensity scoring.Results : There was evidence of a true difference in mean abuse scores at follow-up in the intervention compared with the comparison arm (15.9 vs 21.8, AdjDiff -8.67, CI -16.2 to -1.15). There was weak evidence for other outcomes, but a trend was evident favouring the intervention: proportions of women with CAS scores &ge;7, 51/88 (58.4%) vs 27/42 (64.3%) AdjOR 0.47, CI 0.21 to 1.05); depression (EPDS score &ge;13) (19/85, 22% (I) vs 14/43, 33% (C); AdjOR 0.42, CI 0.17 to 1.06); physical wellbeing mean scores (PCS-SF36: AdjDiff 2.79; CI -0.40 to 5.99); mental wellbeing mean scores (MCS-SF36: AdjDiff 2.26; CI -1.48 to 6.00). There was no observed effect on parenting stress. 82% of women mentored would recommend mentors to friends in similar situations.Conclusion : Non-professional mentor mother support appears promising for improving safety and enhancing physical and mental wellbeing among mothers experiencing intimate partner violence referred from primary care.<br /

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

Ameliorated ConA-Induced Hepatitis in the Absence of PKC-theta

Severe liver injury that occurs when immune cells mistakenly attack an individual's own liver cells leads to autoimmune hepatitis. In mice, acute hepatitis can be induced by concanavalin A (ConA) treatment, which causes rapid activation of CD1d-positive natural killer (NK) T cells. These activated NKT cells produce large amounts of cytokines, which induce strong inflammation that damages liver tissues. Here we show that PKC-θ−/− mice were resistant to ConA-induced hepatitis due to essential function of PKC-θ in NKT cell development and activation. A dosage of ConA (25 mg/kg) that was lethal to wild-type (WT) mice failed to induce death resulting from liver injury in PKC-θ−/− mice. Correspondingly, ConA-induced production of cytokines such as IFNγ, IL-6, and TNFα, which mediate the inflammation responsible for liver injury, were significantly lower in PKC-θ−/− mice. Peripheral NKT cells had developmental defects at early stages in the thymus in PKC-θ−/− mice, and as a result their frequency and number were greatly reduced. Furthermore, PKC-θ−/− bone marrow adoptively transferred to WT mice displayed similar defects in NKT cell development, suggesting an intrinsic requirement for PKC-θ in NKT cell development. In addition, upon stimulation with NKT cell-specific lipid ligand, peripheral PKC-θ−/− NKT cells produced lower levels of inflammatory cytokines than that of WT NKT cells, suggesting that activation of NKT cells also requires PKC-θ. Our results suggest PKC-θ is an essential molecule required for activation of NKT cell to induce hepatitis, and thus, is a potential drug target for prevention of autoimmune hepatitis

The Primary Prevention of PTSD in Firefighters: Preliminary Results of an RCT with 12-Month Follow-Up

AIM: To develop and evaluate an evidence-based and theory driven program for the primary prevention of Post-traumatic Stress Disorder (PTSD). DESIGN: A pre-intervention / post-intervention / follow up control group design with clustered random allocation of participants to groups was used. The "control" group received "Training as Usual" (TAU). METHOD: Participants were 45 career recruits within the recruit school at the Department of Fire and Emergency Services (DFES) in Western Australia. The intervention group received a four-hour resilience training intervention (Mental Agility and Psychological Strength training) as part of their recruit training school curriculum. Data was collected at baseline and at 6- and 12-months post intervention. RESULTS: We found no evidence that the intervention was effective in the primary prevention of mental health issues, nor did we find any significant impact of MAPS training on social support or coping strategies. A significant difference across conditions in trauma knowledge is indicative of some impact of the MAPS program. CONCLUSION: While the key hypotheses were not supported, this study is the first randomised control trial investigating the primary prevention of PTSD. Practical barriers around the implementation of this program, including constraints within the recruit school, may inform the design and implementation of similar programs in the future. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615001362583