Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer

OBJECTIVE: Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-cancer gene therapy, in combination with paclitaxel in patients with platinum resistant ovarian cancer (PROC). METHODS: The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity. RESULTS: The median age of the evaluable patients was 62 years (range 41-82); 97% had high-grade serous cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%. CONCLUSIONS: At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified

A 2017 Horizon Scan of Emerging Issues for Global Conservation and Biological Diversity

We present the results of our eighth annual horizon scan of emerging issues likely to affect global biological diversity, the environment, and conservation efforts in the future. The potential effects of these novel issues might not yet be fully recognized or understood by the global conservation community, and the issues can be regarded as both opportunities and risks. A diverse international team with collective expertise in horizon scanning, science communication, and conservation research, practice, and policy reviewed 100 potential issues and identified 15 that qualified as emerging, with potential substantial global effects. These issues include new developments in energy storage and fuel production, sand extraction, potential solutions to combat coral bleaching and invasive marine species, and blockchain technology.Cambridge Conservation Initiative, funded by the Natural Environment Research Council and the Royal Society for the Protection of Birds, Arcadia, Natural Environment Research Council (Grant ID: NE/N014472/1

Evaluation of Allelic Expression of Imprinted Genes in Adult Human Blood

Imprinted genes are expressed from only one allele in a parent-of-origin dependent manner. Loss of imprinted (LOI) expression can result in a variety of human disorders and is frequently reported in cancer. Biallelic expression of imprinted genes in adult blood has been suggested as a useful biomarker and is currently being investigated in colorectal cancer. In general, the expression profiles of imprinted genes are well characterised during human and mouse fetal development, but not in human adults

Prenatal Stress and Balance of the Child's Cardiac Autonomic Nervous System at Age 5-6 Years

Objective: Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child. Methods: Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12– 20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80 th percentiles). Indicators of cardiac ANS in the offspring at age 5–6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions. Results: 2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p$0.17). Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p$0.07). Conclusion: Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac AN

Mapping medical careers: Questionnaire assessment of career preferences in medical school applicants and final-year students

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the workforce planning of health-care services. However, there is little theoretical understanding of how different medical specialities are perceived or how choices are made, despite there being much work in general on this topic in occupational psychology, which is influenced by Holland's RIASEC (Realistic-Investigative-Artistic-Social-Enterprising-Conventional) typology of careers, and Gottfredson's model of circumscription and compromise. In this study, we use three large-scale cohorts of medical students to produce maps of medical careers. METHODS: Information on between 24 and 28 specialities was collected in three UK cohorts of medical students (1981, 1986 and 1991 entry), in applicants (1981 and 1986 cohorts, N = 1135 and 2032) or entrants (1991 cohort, N = 2973) and in final-year students (N = 330, 376, and 1437). Mapping used Individual Differences Scaling (INDSCAL) on sub-groups broken down by age and sex. The method was validated in a population sample using a full range of careers, and demonstrating that the RIASEC structure could be extracted. RESULTS: Medical specialities in each cohort, at application and in the final-year, were well represented by a two-dimensional space. The representations showed a close similarity to Holland's RIASEC typology, with the main orthogonal dimensions appearing similar to Prediger's derived orthogonal dimensions of 'Things-People' and 'Data-Ideas'. CONCLUSIONS: There are close parallels between Holland's general typology of careers, and the structure we have found in medical careers. Medical specialities typical of Holland's six RIASEC categories are Surgery (Realistic), Hospital Medicine (Investigative), Psychiatry (Artistic), Public Health (Social), Administrative Medicine (Enterprising), and Laboratory Medicine (Conventional). The homology between medical careers and RIASEC may mean that the map can be used as the basis for understanding career choice, and for providing career counselling

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

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

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN