A central challenge in neuroscience is how the brain organizes the information necessary to orchestrate behaviour. Arguably, this whole-brain orchestration is carried out by a core subset of integrative brain regions, a 'global workspace', but its constitutive regions remain unclear. We quantified the global workspace as the common regions across seven tasks as well as rest, in a common 'functional rich club'. To identify this functional rich club, we determined the information flow between brain regions by means of a normalized directed transfer entropy framework applied to multimodal neuroimaging data from 1,003 healthy participants and validated in participants with retest data. This revealed a set of regions orchestrating information from perceptual, long-term memory, evaluative and attentional systems. We confirmed the causal significance and robustness of our results by systematically lesioning a generative whole-brain model. Overall, this framework describes a complex choreography of the functional hierarchical organization of the human brain.Interacting pedestrians in a crowd spontaneously adjust their footsteps and align their respective stepping phases. This self-organization phenomenon is known as synchronization. However, it is unclear why and how synchronization forms spontaneously under different density conditions, or what functional benefit synchronization offers for the collective motion of humans. Here, we conducted a single-file crowd motion experiment that directly tracked the alternating movement of both legs of interacting pedestrians. We show that synchronization is most likely to be triggered at the same density at which the flow rate of pedestrians reaches a maximum value. We demonstrate that synchronization is established in response to an insufficient safety distance between pedestrians, and that it enables pedestrians to realize efficient collective stepping motion without the occurrence of inter-person collisions. These findings provide insights into the collective motion behaviour of humans and may have implications for understanding pedestrian synchronization-induced wobbling, for example, of bridges.In strongly correlated materials, quasiparticle excitations can carry fractional quantum numbers. An intriguing possibility is the formation of fractionalized, charge-neutral fermions-for example, spinons1 and fermionic excitons2,3-that result in neutral Fermi surfaces and Landau quantization4,5 in an insulator. Although previous experiments in quantum spin liquids1, topological Kondo insulators6-8 and quantum Hall systems3,9 have hinted at charge-neutral Fermi surfaces, evidence for their existence remains inconclusive. Here we report experimental observation of Landau quantization in a two-dimensional insulator, monolayer tungsten ditelluride (WTe2), a large-gap topological insulator10-13. Using a detection scheme that avoids edge contributions, we find large quantum oscillations in the material's magnetoresistance, with an onset field as small as about 0.5 tesla. Despite the huge resistance, the oscillation profile, which exhibits many periods, mimics the Shubnikov-de Haas oscillations in metals. At ultralow temperatures, the observed oscillations evolve into discrete peaks near 1.6 tesla, above which the Landau quantized regime is fully developed. Such a low onset field of quantization is comparable to the behaviour of high-mobility conventional two-dimensional electron gases. Our experiments call for further investigation of the unusual ground state of the WTe2 monolayer, including the influence of device components and the possible existence of mobile fermions and charge-neutral Fermi surfaces inside its insulating gap.A large proportion of patients with cancer are unresponsive to treatment with immune checkpoint blockade and other immunotherapies. Here, we report a mathematical model of the time course of tumour responses to immune checkpoint inhibitors. The model takes into account intrinsic tumour growth rates, the rates of immune activation and of tumour-immune cell interactions, and the efficacy of immune-mediated tumour killing. For 124 patients, four cancer types and two immunotherapy agents, the model reliably described the immune responses and final tumour burden across all different cancers and drug combinations examined. In validation cohorts from four clinical trials of checkpoint inhibitors (with a total of 177 patients), the model accurately stratified the patients according to reduced or increased long-term tumour burden. We also provide model-derived quantitative measures of treatment sensitivity for specific drug-cancer combinations. The model can be used to predict responses to therapy and to quantify specific drug-cancer sensitivities in individual patients.Therapeutic genome editing requires effective and targeted delivery methods. The delivery of Cas9 mRNA using adeno-associated viruses has led to potent in vivo therapeutic efficacy, but can cause sustained Cas9 expression, anti-Cas9 immune responses and off-target edits. Lentiviral vectors have been engineered to deliver nucleases that are expressed transiently, but in vivo evidence of their biomedical efficacy is lacking. Here, we show that the lentiviral codelivery of Streptococcus pyogenes Cas9 mRNA and expression cassettes that encode a guide RNA that targets vascular endothelial growth factor A (Vegfa) is efficacious in a mouse model of wet age-related macular degeneration induced by Vegfa. A single subretinal injection of engineered lentiviruses knocked out 44% of Vegfa in retinal pigment epithelium and reduced the area of choroidal neovascularization by 63% without inducing off-target edits or anti-Cas9 immune responses. Engineered lentiviruses for the transient expression of nucleases may form the basis of new treatments for retinal neovascular diseases.The prognostic value of electrocardiograms (ECGs) has been reported in predialysis patients but not in incident hemodialysis patients with overhydration and electrolyte disturbances, both of which potentially affect ECG results. We performed a retrospective multicenter cohort study involving incident hemodialysis patients and examined whether ECG parameters immediately before hemodialysis initiation can predict subsequent cardiovascular disease (CVD) using Cox proportional hazards models. read more We explored potential effect modifications by several electrolytes on the predictive power of ECG abnormalities. Among the 618 enrolled patients, 16%, 10%, 46%, and 22% showed a PR interval ≥ 200 ms, QRS interval ≥120 ms, QTc interval ≥ 450/460 ms (male/female), and left ventricular hypertrophy (LVH) by voltage criteria, respectively. Over a median 3-year follow-up, 19% and 16% of the patients developed atherosclerotic and nonatherosclerotic CVD, respectively. The Cox regression model results revealed that the sum of the number of abnormalities in PR, QRS, and QT intervals was a significant risk factor for nonatherosclerotic CVD (hazard ratios (HRs) [95% confidence interval (CI)] 1.