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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. Methods We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls.Findings SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. InterpretationThe conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens.

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Diabetes mellitus is associated with extensive morbidity and mortality in any human community. It is well understood that the burden of diabetes is attributed to chronic progressive damage in major end-organs, but it is underappreciated that the most superficial and transparent organ affected by diabetes is the cornea. Different corneal components (epithelium, nerves, immune cells and endothelium) underpin specific systemic complications of diabetes. Just as diabetic retinopathy is a marker of more generalized microvascular disease, corneal nerve changes can predict peripheral and autonomic neuropathy, providing a window of opportunity for early treatment. In addition, alterations of immune cells in corneas suggest an inflammatory component in diabetic complications. Furthermore, impaired corneal epithelial wound healing may also imply more widespread disease. The non-invasiveness and improvement in imaging technology facilitates the emergence of new screening tools. Systemic control of diabetes can improve ocular surface health, possibly aided by anti-inflammatory and vasoprotective agents.

The Daya Bay Reactor Neutrino Experiment is designed to determine precisely the neutrino mixing angle θ 13 with a sensitivity better than 0.01 in the parameter sin 2 2θ 13 at the 90% confidence level. To achieve this goal, the collaboration will build eight functionally identical antineutrino detectors. The first two detectors have been constructed, installed and commissioned in Experimental Hall 1, with steady data-taking beginning September 23, 2011. A comparison of the data collected over the subsequent three months indicates that the detectors are functionally identical, and that detector-related systematic uncertainties exceed requirements.

Citation: You QS, Chan JCH, Ng ALK, et al. Macular vessel density measured with optical coherence tomography angiography and its associations in a large population-based study. Invest Ophthalmol Vis Sci. 2019;60:4830-4837. https://doi.org/10.1167/ iovs.19-28137PURPOSE. We investigate macular perfusion and the systemic and ocular associations in a population-based setting. METHODS.In this cross-sectional study, 2018 adults residing in Hong Kong underwent detailed ophthalmic examinations after consenting to participate. Macular perfusion was measured with optical coherence tomography angiography (OCTA) using the split-spectrum amplitude decorrelation angiography algorithm. The parafoveal flow index and vessel area density were quantified using automated custom-built software. RESULTS.Of the 2018 participants, the OCTA measurements were available for 1940, and 1631 (84.1%) had good quality scans. The right eyes of these 1631 participants (43.1% men) were included for final analysis. Mean age was 49.8 years (range, 18-92 years). Mean global macular vessel density was 47.3% and 55.1% for the superficial and deep retinal layers, respectively. In multivariate analysis, lower superficial vessel density remained significantly associated with lower signal strength index (SSI; P < 0.001, standardized b ¼ 0.607) and male sex (P < 0.001, b ¼ 0.162), and borderline associated with older age (P ¼ 0.09, b ¼ À0.045) and longer axial length (AL; P ¼ 0.09, b ¼ À0.037), while lower deep layer vessel density was significantly associated with lower SSI (P < 0.001, standardized b ¼ 0.667), longer AL (P < 0.001, b ¼ À0.097), and higher creatinine (P < 0.001, b ¼ À0.072).CONCLUSIONS. This large population-based study provided normative OCTA data of macular vessel density and demonstrated that a lower superficial retinal vessel density was significantly associated with lower SSI and male sex, while a lower deep layer retinal vessel density was significantly associated with lower SSI, longer AL, and higher level of creatinine. These associations must be considered when interpreting clinical quantitative OCTA data.

The Daya Bay experiment was the first to report simultaneous measurements of reactor antineutrinos at multiple baselines leading to the discovery ofν e oscillations over km-baselines. Subsequent data has provided the world's most precise measurement of sin 2 2θ 13 and the effective mass splitting ∆m 2 ee . The experiment is located in Daya Bay, China where the cluster of six nuclear reactors is among the world's most prolific sources of electron antineutrinos. Multiple antineutrino detectors are deployed in three underground water pools at different distances from the reactor cores to search for deviations in the antineutrino rate and energy spectrum due to neutrino mixing. Instrumented with photomultiplier tubes, the water pools serve as shielding against natural radioactivity from the surrounding rock and provide efficient muon tagging. Arrays of resistive plate chambers over the top of each pool provide additional muon detection. The antineutrino detectors were specifically designed for measurements of the antineutrino flux with minimal systematic uncertainty. Relative detector efficiencies between the near and far detectors are known to better than 0.2%. With the unblinding of the final two detectors' baselines and target masses, a complete description and comparison of the eight antineutrino detectors can now be presented. This paper describes the Daya Bay detector systems, consisting of eight antineutrino detectors in three instrumented water pools in three underground halls, and their operation through the first year of eight detector data-taking.

Despite advances in artificial intelligence-based diagnostics, ophthalmic clinical skills remain an important acquisition during medical school. Simple ophthalmic examination techniques allow future non-ophthalmic physicians to make timely referrals to ophthalmologists for sight-threatening diseases. Currently, the coronavirus disease 2019 (COVID-19) pandemic poses a serious public health crisis worldwide and an immediate challenge to traditional methods of medical education. With the present threat of disease transmission, face to face small group tutorials are not feasible, especially in the context of ophthalmic clinical skills, which requires close contact between the examiner and the patient.Prior to the outbreak, we introduced ophthalmic clinical skills to second-year pre-clinical undergraduate medical students in the form of face to face demonstrations of techniques by a clinical tutor. A recent published study reported that, video-based materials and written materials were synergistic in enhancing ophthalmic clinical skills and knowledge acquisition in an undergraduate medical programme. 1The objective of our adaption was to introduce video-based and written materials to precede and complement Zoom™ (Zoom Video Communications Inc., San Jose, CA, USA) platform-based small group tutorials. Our aim was to identify advantages and difficulties with this new approach as a necessary replacement for traditional face to face small group clinical demonstrations during the COVID-19 pandemic. | WHAT WA S TRIED?We taught ophthalmic clinical skills to second-year undergraduate medical students, including the visual acuity assessment with near Snellen chart, pupil examination, confrontation test for visual field, extraocular movement examination and direct ophthalmoscope examination. In order to replace face to face 2-hour group tutorials during the COVID-19 outbreak, we devised a three-pronged approach to provide an effective learning experience for our undergraduate medical students. First, for each examination technique, we included written information regarding: (a) technique; (b) physical signs demonstrated; (c) common mistakes by medical students, and (d) clinical relevance. Second, we recorded a video of a clinical teacher demonstrating the techniques on a surrogate patient. We uploaded both written material and videos on the e-learning platform of our medical school. Third, after going through the online materials, the students were split into small groups of 30 students for a single 60-minute tutorial with a clinical teacher on the Zoom cloud-based video conference platform. During the tutorial, the teacher went through each key ophthalmic clinical skill and highlighted important points, pitfalls and clinical knowledge. The last 10 minutes were reserved for questions from students. Using the private message function, students were able to send live questions as they maintained anonymity. Assessment was conducted at the end of the block in the form of objective structured clinical examination (OSCE) stations. | ...