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

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

Rethinking Serious Games Design in the Age of COVID-19: Setting the Focus on Wicked Problems

We live in a complex world, in which our existence is defined by forces that we cannot fully comprehend, predict, nor control. This is the world of wicked problems, of which the situation triggered by the COVID-19 pandemic is a notable example. Wicked problems are complex scenarios defined by the interplay of multiple environmental, social and economic factors. They are everchanging, and largely unpredictable and uncontrollable. As a consequence, wicked problems cannot be definitively solved through traditional problem-solving approaches. Instead, they should be iteratively managed, recognizing and valuing our connectedness with each other and the environment, and engaging in joint thinking and action to identify and pursue the common good. Serious games can be key to foster wicked problem management abilities. To this end, they should engage players in collective activities set in contexts simulating real-world wicked problem scenarios. These should require the continuous interpretation of changing circumstances to identify and pursue shared goals, promoting the development of knowledge, attitudes and skill sets relevant to tackle real-world situations. In this paper we outline the nature, implications and challenges of wicked problems, highlighting why games should be leveraged to foster wicked problem management abilities. Then, we propose a theory-based framework to support the design of games for this purpose

Controlling the shape of a quantum wavefunction

The ability to control the shape and motion of quantum states(1,2) may lead to methods for bond-selective chemistry and novel quantum technologies, such as quantum computing. The classical coherence of laser light has been used to guide quantum systems into desired target states through interfering pathways(3-5). These experiments used the control of target properties-such as fluorescence from a dye solution(6), the current in a semiconductor(7,8) 8 Or the dissociation fraction of an excited molecule(9)-to infer control over the quantum state. Here we report a direct approach to coherent quantum control that allows us to actively manipulate the shape of an atomic electron's radial wavefunction, We use a computer-controlled laser to excite a coherent state in atomic caesium. The shape of the wavefunction is then measured(10) and the information fed back into the laser control system, which reprograms the optical field. The process is iterated until the measured shape of the wavefunction matches that of a target wavepacket, established at the start of the experiment. We find that, using a variation of quantum holography(11) to reconstruct the measured wavefunction, the quantum state can be reshaped to match the target within two iterations of the feedback loop.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62625/1/397233a0.pd

Improved Outcome Prediction Using CT Angiography in Addition to Standard Ischemic Stroke Assessment: Results from the STOPStroke Study

Purpose: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS.2. Strokes were classified as ‘‘major’ ’ by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was#7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores.10. Results: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p,0.0001). Combining NIHSS with BASIS was highly predictive: 77.6 % (114/147) classified as NIHSS.10/BASIS+ had poor outcomes, versus 21.5 % (77/358) with NIHSS#10/BASIS2 (p,0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95 % CI: 7.9 to 20.0

Targeted Manipulation of Serotonergic Neurotransmission Affects the Escalation of Aggression in Adult Male Drosophila melanogaster

Dopamine (DA) and serotonin (5HT) are reported to serve important roles in aggression in a wide variety of animals. Previous investigations of 5HT function in adult Drosophila behavior have relied on pharmacological manipulations, or on combinations of genetic tools that simultaneously target both DA and 5HT neurons. Here, we generated a transgenic line that allows selective, direct manipulation of serotonergic neurons and asked whether DA and 5HT have separable effects on aggression. Quantitative morphological examination demonstrated that our newly generated tryptophan hydroxylase (TRH)-Gal4 driver line was highly selective for 5HT-containing neurons. This line was used in conjunction with already available Gal4 driver lines that target DA or both DA and 5HT neurons to acutely alter the function of aminergic systems. First, we showed that acute impairment of DA and 5HT neurotransmission using expression of a temperature sensitive form of dynamin completely abolished mid- and high-level aggression. These flies did not escalate fights beyond brief low-intensity interactions and therefore did not yield dominance relationships. We showed next that manipulation of either 5HT or DA neurotransmission failed to duplicate this phenotype. Selective disruption of 5HT neurotransmission yielded flies that fought, but with reduced ability to escalate fights, leading to fewer dominance relationships. Acute activation of 5HT neurons using temperature sensitive dTrpA1 channel expression, in contrast, resulted in flies that escalated fights faster and that fought at higher intensities. Finally, acute disruption of DA neurotransmission produced hyperactive flies that moved faster than controls, and rarely engaged in any social interactions. By separately manipulating 5HT- and DA- neuron systems, we collected evidence demonstrating a direct role for 5HT in the escalation of aggression in Drosophila

Studies of the Decay B+- -> D_CP K+-

We report studies of the decay B+- -> D_CP K+-, where D_CP denotes neutral D mesons that decay to CP eigenstates. The analysis is based on a 29.1/fb data sample of collected at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e+ e- storage ring. Ratios of branching fractions of Cabibbo-suppressed to Cabibbo-favored processes involving D_CP are determined to be B(B- -> D_1 K-)/B(B- -> D_1 pi-)=0.125 +- 0.036 +- 0.010 and B(B- -> D_2 K-)/B(B- -> D_2 pi-)=0.119 +- 0.028 +- 0.006, where indices 1 and 2 represent the CP=+1 and CP=-1 eigenstates of the D0 - anti D0 system, respectively. We also extract the partial rate asymmetries for B+- -> D_CP K+-, finding A_1 = 0.29 +- 0.26 +- 0.05 and A_2 = -0.22 +- 0.24 +- 0.04.Comment: 10 pages, 2 figures, submitted to Physical Review Letter

No cold dust within the supernova remnant Cassiopeia A

A large amount (about three solar masses) of cold (18 K) dust in the prototypical type II supernova remnant Cassiopeia A was recently reported. It was concluded that dust production in type II supernovae can explain how the large quantities (10^8 solar masses) of dust observed in the most distant quasars could have been produced within only 700 million years after the Big Bang. Foreground clouds of interstellar material, however, complicate the interpretation of the earlier submillimetre observations of Cas A. Here we report far-infrared and molecular line observations that demonstrate that most of the detected submillimetre emission originates from interstellar dust in a molecular cloud complex located in the line of sight between the Earth and Cas A, and is therefore not associated with the remnant. The argument that type II supernovae produce copious amounts of dust is not supported by the case of Cas A, which previously appeared to provide the best evidence for this possibility.Comment: 13 pages, 3 figure