Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. FindingsOf 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1•84, 95% CI 1•53-2•21), male sex (1•63, 1•07-2•48), smoking status (former smoker vs never smoked: 1•60, 1•03-2•47), number of comorbidities (two vs none: 4•50, 1•33-15•28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3•89, 2•11-7•18), active cancer (progressing vs remission: 5•20, 2•77-9•77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2•93, 1•79-4•79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0•24, 0•07-0•84) or the US-Midwest (0•50, 0•28-0•90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.

We demonstrate single-molecule fluorescence imaging beyond the optical diffraction limit in 3 dimensions with a wide-field microscope that exhibits a double-helix point spread function (DH-PSF). The DH-PSF design features high and uniform Fisher information and has 2 dominant lobes in the image plane whose angular orientation rotates with the axial (z) position of the emitter. Single fluorescent molecules in a thick polymer sample are localized in single 500-ms acquisitions with 10-to 20-nm precision over a large depth of field (2 m) by finding the center of the 2 DH-PSF lobes. By using a photoactivatable fluorophore, repeated imaging of sparse subsets with a DH-PSF microscope provides superresolution imaging of high concentrations of molecules in all 3 dimensions. The combination of optical PSF design and digital postprocessing with photoactivatable fluorophores opens up avenues for improving 3D imaging resolution beyond the Rayleigh diffraction limit.microscopy ͉ photoactivation ͉ superresolution ͉ computational imaging ͉ PSF engineering F luorescence microscopy is ubiquitous in biological studies because light can noninvasively probe the interior of a cell with high signal-to-background and remarkable label specificity. Unfortunately, optical diffraction limits the transverse (x-y) resolution of a conventional fluorescence microscope to approximately /(2NA), where is the optical wavelength and NA is the numerical aperture of the objective lens (1). This limitation requires that point sources need to be Ͼ Ϸ200 nm apart in the visible wavelength region to be distinguished with modern high-quality fluorescence microscopes. Diffraction causes the image of a single-point emitter to appear as a blob (i.e., the point-spread function or PSF) with a width given by the diffraction limit. However, if the shape of the PSF is measured, then the center position of the blob can be determined with a far greater precision (termed superlocalization) that scales approximately as the diffraction limit divided by the square root of the number of photons collected, a fact noted as early as Heisenberg in the context of electron localization with photons (2) and later extended to point objects (3, 4) and single-molecule emitters (5-8). Because single-molecule emitters are only a few nanometers in size, they represent particularly useful point sources for imaging, and superlocalization of single molecules at room temperature has been pushed to the 1-nm regime (9) in transverse (2-dimensional) imaging. In the third (z) dimension, diffraction also limits resolution to Ϸ2n /NA 2 with n the index of refraction, corresponding to a depth of field of Ϸ500 nm in the visible wavelength region with modern microscopes. Improvements in 3D localization beyond this limit are also possible by using astigmatism (10, 11), defocusing (12), or simultaneous multiplane viewing (13).Until recently, superlocalization of individual molecules was unable to provide true resolution beyond the diffraction limit (superresolution) because the concentration of emi...

Background Patients with cancer may be at high risk of adverse outcomes from SARS-CoV-2 infection. We analyzed a cohort of patients with cancer and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anti-cancer therapies. Patients and Methods Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between March 17-November 18, 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anti-cancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). Results 4,966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2,872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic Black race, Hispanic ethnicity, worse ECOG performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count, high absolute neutrophil count, low platelet count, abnormal creatinine, troponin, LDH, and CRP were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anti-cancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. Conclusions Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anti-cancer therapies.

The commonly used, monomeric EYFP enabled imaging of intracellular protein structures beyond the optical resolution limit ('super-resolution' imaging) in living cells. By combining photoinduced activation of single EYFP fusions and time-lapse imaging, we obtained sub-40 nm resolution images of the filamentous superstructure of the bacterial actin protein MreB in live Caulobacter crescentus cells. These studies demonstrated that EYFP is a useful emitter for in vivo super-resolution imaging.As is well known, optical fluorescence microscopy is an important tool for cell biology because light can be used to noninvasively probe a sample with relatively small perturbation of the specimen, allowing dynamical observation of the motions of internal structures in living cells but with resolution usually limited to ~250 nm by optical diffraction. Single-molecule widefield fluorescence microscopy achieves nanometer-scale localization accuracy (super-localization) by taking advantage of the fact that the point-spread function (PSF) of an isolated nanoscale emitter can be fit to a precision far greater than the standard diffraction limit 1 . To apply this idea to experiments with high concentrations of label in biologically relevant, roomtemperature studies, a control variable is needed 2 , and photoactivation or photoswitching have been used to maintain the concentration of emitters at the 'single-molecule level', where the PSFs of the individual molecules do not overlap 3-5 . For example, in photoactivated localization microscopy (PALM) 3 , structures labeled by an ensemble of photoactivatable fluorescent proteins too dense to be imaged simultaneously are resolved by repeated cycles in each of which only a sparse subset of the fluorophores is activated. The final, super-resolution image is reconstituted from a superposition of the single-molecule positions.In previous PALM-type imaging, the photoactivatable fluorescent protein has been selected from various sophisticated constructs such as PA-GFP, Dronpa, Kaede, tdEosFP, Dendra2 and rsFastLime 3,6,7 . However, immobilized and apparently bleached single yellow fluorescent proteins (containing mutations S65G,S72A,T203Y or S65G,S72A,T203F) have been shown to reactivate with violet light more than 10 years ago 8 , and the possibility of controllable reactivation suggested that PALM-type imaging should be feasible with the closely related The micrometer-scale size of bacterial cells combined with growing interest in the complex protein localization patterns that control their biology make bacteria important targets for super-resolution imaging. Caulobacter crescentus is a particularly interesting prokaryote because each division is asymmetric, and the progression of the cell cycle requires the dynamic localization of both structural and regulatory proteins 13 . The actin homolog MreB is a bacterial structural protein critical for cell shape, polarity and chromosome segregation in C. crescentus. Low-resolution imaging shows that this protein forms a superstructure that is...

Nanowire fabrication methods can be classified either as 'top down', involving photo- or electron-beam lithography, or 'bottom up', involving the synthesis of nanowires from molecular precursors. Lithographically patterned nanowire electrodeposition (LPNE) combines attributes of photolithography with the versatility of bottom-up electrochemical synthesis. Photolithography defines the position of a sacrificial nickel nanoband electrode, which is recessed into a horizontal trench. This trench acts as a 'nanoform' to define the thickness of an incipient nanowire during its electrodeposition. The electrodeposition duration determines the width of the nanowire. Removal of the photoresist and nickel exposes a polycrystalline nanowire--composed of gold, platinum or palladium--characterized by thickness and width that can be independently controlled down to 18 and 40 nm, respectively. Metal nanowires prepared by LPNE may have applications in chemical sensing and optical signal processing, and as interconnects in nanoelectronic devices.