The Dimorphos ejecta plume properties revealed by LICIACube.

The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.

Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high-risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party-EBMT.

We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.

A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

OBJECTIVE: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. PATIENTS & METHODS: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. RESULTS: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. CONCLUSIONS: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.

High spatial-density, cladding-pumped 6-mode 7-core fiber amplifier for C-band operation.

We present a C-band 6-mode 7-core fiber amplifier in an all-fiberized cladding-pumped configuration for space division multiplexed transmission supporting a record 42 spatial channels. With optimized fiber components (e.g. passively cooled pump laser diode, pump coupler, pump stripper), high power multimode pump light is coupled to the active fiber without any noticeable thermal degradation and an average gain of 18 dB and noise figure of 5.4 dB are obtained with an average differential modal gain of 3.4 dB.

Clinical characteristics and outcome of critically ill COVID-19 patients with acute kidney injury: a single centre cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common manifestation among patients critically ill with SARS-CoV-2 infection (Coronavirus 2019) and is associated with significant morbidity and mortality. The pathophysiology of renal failure in this context is not fully understood, but likely to be multifactorial. The intensive care unit outcomes of patients following COVID-19 acute critical illness with associated AKI have not been fully explored. We conducted a cohort study to investigate the risk factors for acute kidney injury in patients admitted to and intensive care unit with COVID-19, its incidence and associated outcomes. METHODS: We reviewed the medical records of all patients admitted to our adult intensive care unit suffering from SARS-CoV-2 infection from 14th March 2020 until 12th May 2020. Acute kidney injury was defined using the Kidney Disease Improving Global Outcome (KDIGO) criteria. The outcome analysis was assessed up to date as 3rd of September 2020. RESULTS: A total of 81 patients admitted during this period. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. Thirty-six patients (44%) had evidence of AKI (Stage I-33%, Stage II-22%, Renal Replacement Therapy (RRT)-44%). All patients with AKI stage III had RRT. Age, diabetes mellitus, immunosuppression, lymphopenia, high D-Dimer levels, increased APACHE II and SOFA scores, invasive mechanical ventilation and use of inotropic or vasopressor support were significantly associated with AKI. The peak AKI was at day 4 and mean duration of RRT was 12.5 days. The mortality was 25% for the AKI group compared to 6.7% in those without AKI. Among those received RRT and survived their illness, the renal function recovery is complete and back to baseline in all patients. CONCLUSION: Acute kidney injury and renal replacement therapy is common in critically ill patients presenting with COVID-19. It is associated with increased severity of illness on admission to ICU, increased mortality and prolonged ICU and hospital length of stay. Recovery of renal function was complete in all survived patients.

Treatment of dilated cardiomyopathy in a mouse model of Friedreich's ataxia using N-acetylcysteine and identification of alterations in microRNA expression that could be involved in its pathogenesis.

Deficient expression of the mitochondrial protein, frataxin, leads to a deadly cardiomyopathy. Our laboratory reported the master regulator of oxidative stress, nuclear factor erythroid 2-related factor-2 (Nrf2), demonstrates marked down-regulation after frataxin deletion in the heart. This was due, in part, to a pronounced increase in Keap1. To assess if this can be therapeutically targeted, cells were incubated with N-acetylcysteine (NAC), or buthionine sulfoximine (BSO), which increases or decreases glutathione (GSH), respectively, or the NRF2-inducer, sulforaphane (SFN). While SFN significantly (p < 0.05) induced NRF2, KEAP1 and BACH1, NAC attenuated SFN-induced NRF2, KEAP1 and BACH1. The down-regulation of KEAP1 by NAC was of interest, as Keap1 is markedly increased in the MCK conditional frataxin knockout (MCK KO) mouse model and this could lead to the decreased Nrf2 levels. Considering this, MCK KO mice were treated with i.p. NAC (500- or 1500-mg/kg, 5 days/week for 5-weeks) and demonstrated slightly less (p > 0.05) body weight loss versus the vehicle-treated KO. However, NAC did not rescue the cardiomyopathy. To additionally examine the dys-regulation of Nrf2 upon frataxin deletion, studies assessed the role of microRNA (miRNA) in this process. In MCK KO mice, miR-144 was up-regulated, which down-regulates Nrf2. Furthermore, miRNA screening in MCK KO mice demonstrated 23 miRNAs from 756 screened were significantly (p < 0.05) altered in KOs versus WT littermates. Of these, miR-21*, miR-34c*, and miR-200c, demonstrated marked alterations, with functional clustering analysis showing they regulate genes linked to cardiac hypertrophy, cardiomyopathy, and oxidative stress, respectively.

Usability testing of MySkinSelfie: a mobile phone application for skin self-monitoring.

Teledermatology generally involves doctors taking images of patients; however, patients increasingly want to own or have easy access to their health data. MySkinSelfie ( http://myskinselfie.com) is a mobile phone application (app) designed to improve the quality, consistency and accessibility of patient-held photos, and was developed to give patients the ability to generate and hold their own skin images to help guide their skin care. This study assessed the usability of this app in a cohort of patients attending a National Health Service Dermatology clinic. Patients were asked to use the app but were not given specific tasks to achieve. Of the 102 patients recruited, 32 downloaded the app and registered an account, 21 took at least one photo (median 5, range 1-103) and 19 completed the usability questionnaire. The majority of questionnaire respondents found the app easy to use but were more neutral on whether it really helped them to manage their skin problem. MySkinSelfie has been shown to be easy to use. Self-monitoring of skin problems may be useful for a subset of patients, and this is likely to depend on diagnosis, age and other patient factors.

The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

Study on the temperature dependent characteristics of O-band bismuth-doped fiber amplifier.

We report the temperature dependent performance of an O-band bismuth (Bi)-doped fiber amplifier (BDFA) in the temperature range from -60 to +80°C. At room temperature, maximum gains of 27 and 40 dB with noise figures (NFs) of 4.3 and 4.8 dB are measured for -23 dBm signal power in the single and double pass BDFA, respectively. An increment in gain and reduction in NF is observed as the ambient temperature of the BDFA is reduced. In the double pass BDFA, the temperature dependent gain coefficient from -60 to +80°C is found to be around -0.02 and -0.03 dB/°C across the wavelength band of 1300-1360 nm for -10 and -23 dBm signal powers, respectively. We also study the gain and NF characteristics with pump power and signal power at different temperatures, and a maximum gain of 45 dB is obtained at -60°C for -30 dBm signal power.

40 dB gain all fiber bismuth-doped amplifier operating in the O-band.

In this Letter, we investigate and compare the gain and noise figure characteristics of bismuth (Bi)-doped fiber amplifiers configured in both single and double signal pass implementations. A maximum gain of 25 dB and a noise figure of 4 dB is measured at 1360 nm in the single pass configuration for -23 dBm input signal power, whereas in the double pass configuration the gain of the amplifier is improved significantly by 14 dB allowing us to achieve a gain of 39 dB with a noise figure of 5 dB. To the best of our knowledge, this is the highest gain reported to date using Bi-doped fiber as a gain medium. Furthermore, we also study the gain and noise figure dependency on pump power, signal power, and pump wavelength for the double pass amplifier configuration. We observed similar gain and noise figure performance in the double pass configuration to that of the single pass configuration but with the benefit of less pump power and a shorter length of the Bi-doped fiber.

Demonstration of opposing thermal sensitivities in hollow-core fibers with open and sealed ends.

The output phase and propagation time of an optical signal propagating through a hollow-core optical fiber (HCF) drift with changes in environmental temperature significantly less than in conventional optical fibers. In all earlier experimental studies, however, the simplifying assumption was made that the thermo-optic effect of air was negligible. In this Letter, we present, to the best of our knowledge, the first experimental demonstration that the air inside a HCF core can make an appreciable contribution to the fiber's thermal sensitivity with the performance depending on whether the fiber is open to the atmosphere or sealed at both ends (e.g., spliced to solid fiber pigtails). We measure both the sensitivity of the accumulated phase as well as the signal propagation time for both open and sealed HCF and show that these are opposite in sign. Most importantly, we show that the thermal sensitivity contribution from the air inside an open HCF has the sign opposite to the effect of fiber elongation (which is otherwise the dominant effect responsible for the overall thermal sensitivity of HCF). We then go on to show that these two effects can be used to balance each other out in order to achieve zero thermal sensitivity for both accumulated phase and propagation time. We demonstrate this property experimentally over a large spectral range.

Point-by-point femtosecond laser micro-processing of independent core-specific fiber Bragg gratings in a multi-core fiber.

Four 3rd order fiber Bragg gratings were inscribed into separate cores of a 7 core multi-core fiber using the point-by-point inscription technique. A 1030 nm, 206 ± 5 fs laser was used, operating at a frequency of 1 kHz and pulse energy of 2.1 ± 0.2 µJ. Independent Bragg resonances at λB = 1541.01 ± 0.02, 1547.82 ± 0.02, 1532.66 ± 0.02, and 1537.42 ± 0.02 nm and extinction ratios of 13.97 ± 0.4, 16.02 ± 0.4, 10.08 ± 0.4 and 13.40 ± 0.4 dB were recorded. Our data analysis shows that refractive index changes, Δn, of the order 10-3 were induced. Core-specific inscription of fiber Bragg gratings in a multi-core fiber can provide a flexible and versatile platform to address the needs of recent space division multiplexed transmission and optical sensor networks.

FAANG, establishing metadata standards, validation and best practices for the farmed and companion animal community.

The Functional Annotation of ANimal Genomes (FAANG) project aims, through a coordinated international effort, to provide high quality functional annotation of animal genomes with an initial focus on farmed and companion animals. A key goal of the initiative is to ensure high quality and rich supporting metadata to describe the project's animals, specimens, cell cultures and experimental assays. By defining rich sample and experimental metadata standards and promoting best practices in data descriptions, deposition and openness, FAANG champions higher quality and reusability of published datasets. FAANG has established a Data Coordination Centre, which sits at the heart of the Metadata and Data Sharing Committee. It continues to evolve the metadata standards, support submissions and, crucially, create powerful and accessible tools to support deposition and validation of metadata. FAANG conforms to the findable, accessible, interoperable, and reusable (FAIR) data principles, with high quality, open access and functionally interlinked data. In addition to data generated by FAANG members and specific FAANG projects, existing datasets that meet the main-or more permissive legacy-standards are incorporated into a central, focused, functional data resource portal for the entire farmed and companion animal community. Through clear and effective metadata standards, validation and conversion software, combined with promotion of best practices in metadata implementation, FAANG aims to maximise effectiveness and inter-comparability of assay data. This supports the community to create a rich genome-to-phenotype resource and promotes continuing improvements in animal data standards as a whole.

Raman-shifted wavelength-selectable pulsed fiber laser with high repetition rate and high pulse energy in the visible.

A high-pulse-energy, diffraction-limited, wavelength-selectable, visible source, based on Raman frequency shifting of a frequency-doubled Yb-doped fiber laser, has been studied. The relative length-scaling laws of Raman gain and self-phase modulation push the design towards short fiber lengths with large core size. It is experimentally demonstrated that the Raman clean-up effect in a graded-index multi-mode fiber is not sufficient to obtain diffraction-limited beam quality in the short fiber length. Thus, a large-core photonic crystal fiber is used to maintain diffraction-limited performance and output pulse energies of ~1 µJ, at a 1-MHz repetition rate and 1.3-ns pulse-width are successfully achieved. This step-tunable visible source should find applications in photoacoustic microscopy.

Full quadrature regeneration of QPSK signals using sequential phase sensitive amplification and parametric saturation.

We demonstrate all-optical regeneration of both the phase and the amplitude of a 10 GBaud quadrature phase shift keying (QPSK) signal using two nonlinear stages. First we regenerate the phase using a wavelength converting phase sensitive amplifier and then we regenerate the amplitude using a saturated single-pump parametric amplifier, returning the signal to its original wavelength at the same time. We exploit the conjugating nature of the two processing stages to eliminate the intrinsic SPM distortion of the system, further improving performance.

Wavelength conversion of complex modulation formats in a compact SiGe waveguide.

We report a nonlinear signal processing system based on a SiGe waveguide suitable for high spectral efficiency data signals. Four-wave-mixing (FWM)-based wavelength conversion of 10-Gbaud 16-Quadrature amplitude modulated (QAM) and 64-QAM signals is demonstrated with less than -10-dB conversion efficiency (CE), 36-dB idler optical signal-to-noise ratio (OSNR), negligible bit error ratio (BER) penalty and a 3-dB conversion bandwidth exceeding 30nm. The SiGe device was CW-pumped and operated in a passive scheme without giving rise to any two-photon absorption (TPA) effects.

49.6 Gb/s direct detection DMT transmission over 40 km single mode fibre using an electrically packaged silicon photonic modulator.

We present the characterization of a silicon Mach-Zehnder modulator with electrical packaging and show that it exhibits a large third-order intermodulation spurious-free dynamic range (> 100 dB Hz2/3). This characteristic renders the modulator particularly suitable for the generation of high spectral efficiency discrete multi-tone signals and we experimentally demonstrate a single-channel, direct detection transmission system operating at 49.6 Gb/s, exhibiting a baseband spectral efficiency of 5 b/s/Hz. Successful transmission is demonstrated over various lengths of single mode fibre up to 40 km, without the need of any amplification or dispersion compensation.

Thulium-fiber-laser-pumped, high-peak-power, picosecond, mid-infrared orientation-patterned GaAs optical parametric generator and amplifier.

We report a high-peak-power, picosecond, mid-infrared optical parametric generator (OPG) and optical parametric amplifier (OPA) based on orientation-patterned gallium arsenide pumped by a thulium:fiber master-oscillator-power-amplifier employing direct diode-seeded amplification. An OPG tuning range of 2550-2940 nm (signal) and 5800-8300 nm (idler) is demonstrated with peak powers as high as 3 (signal) and 2 kW (idler), and with pulse energies of 0.26 and 0.16 µJ, respectively. When seeded with a 0.6 cm-1 linewidth tunable Cr:ZnSe laser, the OPA idler linewidth is narrowed to 1.4 cm-1 and a small-signal parametric gain of 60 dB is achieved. A maximum peak power of 13.3 (signal) and 3.2 kW (idler) is obtained at an overall conversion efficiency of 36%. The corresponding maximum pulse energies for the signal and idler are 1.07 and 0.26 µJ, respectively.

Radially and azimuthally polarized nanosecond Yb-doped fiber MOPA system incorporating temporal shaping.

We report an Yb-doped fiber master-oscillator power-amplifier (MOPA) system with the capability of selectively generating doughnut-shaped radially and azimuthally polarized beams with user-defined temporal pulse shapes. The desired output polarization was generated with the aid of a nanograting spatially variant half-waveplate (S-waveplate). The latter was used to convert the linearly polarized fundamental (LP01) mode output from the preamplification stages to a doughnut-shaped radially polarized beam prior to the power amplifier stage. A maximum output pulse energy of ∼860 µJ was achieved for ∼100 ns pulses at 25 kHz with user-defined pulse shape for both radial and azimuthal polarization states. The polarization purity and beam propagation factor (M2) were measured to be >12 dB and 2.2, respectively.