Methods to convert continuous outcomes into odds ratios of treatment response and numbers needed to treat: meta-epidemiological study

Background Clinicians find standardized mean differences (SMDs) calculated from continuous outcomes difficult to interpret. Our objective was to determine the performance of methods in converting SMDs or means to odds ratios of treatment response and numbers needed to treat (NNTs) as more intuitive measures of treatment effect. Methods Meta-epidemiological study of large-scale trials (≥100 patients per group) comparing active treatment with placebo, sham or non-intervention control. Trials had to use pain or global symptoms as continuous outcomes and report both the percentage of patients with treatment response and mean pain or symptom scores per group. For each trial, we calculated odds ratios of observed treatment response and NNTs and approximated these estimates from SMDs or means using all five currently available conversion methods by Hasselblad and Hedges (HH), Cox and Snell (CS), Furukawa (FU), Suissa (SU) and Kraemer and Kupfer (KK). We compared observed and approximated values within trials by deriving pooled ratios of odds ratios (RORs) and differences in NNTs. ROR <1 and positive differences in NNTs imply that approximations are more conservative than estimates calculated from observed treatment response. As measures of agreement, we calculated intraclass correlation coefficients. Results A total of 29 trials in 13 654 patients were included. Four out of five methods were suitable (HH, CS, FU, SU), with RORs between 0.92 for SU [95% confidence interval (95% CI), 0.86-0.99] and 0.97 for HH (95% CI, 0.91-1.04) and differences in NNTs between 0.5 (95% CI, −0.1 to −1.6) and 1.3 (95% CI, 0.4-2.1). Intraclass correlation coefficients were ≥0.90 for these four methods, but ≤0.76 for the fifth method by KK (P for differences ≤0.027). Conclusions The methods by HH, CS, FU and SU are suitable to convert summary treatment effects calculated from continuous outcomes into odds ratios of treatment response and NNTs, whereas the method by KK is unsuitabl

The length-tension diagrams of human oblique muscles in trochlear palsy and strabismus sursoadductorius

We determined the relation between length and tension in detached oblique muscles of 16 strabismus patients that underwent surgery, before and during contraction evoked by intravenous administration of succinylcholine. We frequently found a nonlinear relation between length and tension, unlike our previous findings in recti. In superior oblique palsies, the superior oblique was found, before injection of succinylcholine, to be stiff after elongation, and did not contract after injection of succinylcholine, while the ipsilateral inferior oblique contract after injection of succinylcholine, but with a higher spring constant than did usual. In 3 cases the superior oblique contracted vividly after administration of succinylcholine despite the presence of excyclotropia, stereopsis, torticollis (2 cases) and a hypertropia that increased in adduction, in downgaze, in adduction-and-downgaze and on ipsilateral head-tilt. The finding of a vividly contracting superior oblique is incompatible with the diagnosis of a complete superior oblique palsy. We conclude that some of the cases diagnosed as congenital superior oblique palsy, having a hypertropia increasing in adduction, in downgaze, in adduction-and-downgaze and on ipsilateral head-tilt, are in fact cases of unilateral strabismus sursoadductorius (upshoot in adduction), a non-paretic motility disorder

Pacific origin of the abrupt increase in Indian Ocean heat content during the warming hiatus

Global mean surface warming has stalled since the end of the twentieth century1, 2, but the net radiation imbalance at the top of the atmosphere continues to suggest an increasingly warming planet. This apparent contradiction has been reconciled by an anomalous heat flux into the ocean3, 4, 5, 6, 7, 8, induced by a shift towards a La Niña-like state with cold sea surface temperatures in the eastern tropical Pacific over the past decade or so. A significant portion of the heat missing from the atmosphere is therefore expected to be stored in the Pacific Ocean. However, in situ hydrographic records indicate that Pacific Ocean heat content has been decreasing9. Here, we analyse observations along with simulations from a global ocean–sea ice model to track the pathway of heat. We find that the enhanced heat uptake by the Pacific Ocean has been compensated by an increased heat transport from the Pacific Ocean to the Indian Ocean, carried by the Indonesian throughflow. As a result, Indian Ocean heat content has increased abruptly, which accounts for more than 70% of the global ocean heat gain in the upper 700 m during the past decade. We conclude that the Indian Ocean has become increasingly important in modulating global climate variability

Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections.

Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including β-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts  in vitro. Therapeutic effects have been seen in animal models  in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from  in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections

Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections

Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including β-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections

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

Ontological addiction: classification, etiology, and treatment

Despite the fact that there is increasing integration of Buddhist principles and practices into Western mental health and applied psychological disciplines, there appears to be limited understanding in Western psychology of the assumptions that underlie a Buddhist model of mental illness. The concept of ontological addiction was introduced and formulated in order to narrow some of the disconnect between Buddhist and Western models of mental illness, and to foster effective assimilation of Buddhist practices and principles into mental health research and practice. Ontological addiction refers to the maladaptive condition whereby an individual is addicted to the belief that they inherently exist. The purposes of the present paper are to: (i) classify ontological addiction in terms of its definition, symptoms, prevalence, and functional consequences, (ii) examine the etiology of the condition, and (iii) appraise both the traditional Buddhist and contemporary empirical literature in order to outline effective treatment strategies. An assessment of the extent to which ontological addiction meets the clinical criteria for addiction suggests that ontological addiction is a chronic and valid – albeit functionally distinct (i.e., when compared to chemical and behavioral addictions) – form of addiction. However, despite the protracted and pervasive nature of the condition, recent empirical findings add support to ancient Buddhist teachings and suggest that addiction to selfhood can be overcome by a treatment process involving phases of: (i) becoming aware of the imputed self, (ii) deconstructing the imputed self, and (iii) reconstructing a dynamic and non-dual self

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

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

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV