Search

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02–8.39), hair loss (3.99, 3.63–4.39), sneezing (2.77, 1.40–5.50), ejaculation difficulty (2.63, 1.61–4.28) and reduced libido (2.36, 1.61–3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.

Pembrolizumab is licensed for the treatment of pre-treated and PD-L1 positive non-small cell lung cancer (NSCLC), but response is heterogeneous. In this context, the Lung Immune Prognostic Index (LIPI) has been proposed as tool to prognosticate outcome.To investigate the real-world efficacy and safety of pembrolizumab in pre-treated NSCLC patients and the clinical utility of LIPI for patients' selection.Patients with pre-treated NSCLC and PD-L1 ≥ 1% treated with pembrolizumab were included in this retrospective series. The LIPI was used to classify patients in 3 prognostics subgroups according to the pre-treatment dNLR (derived neutrophil to lymphocyte ratio) and LDH in blood. The prognostic impact of the LIPI on progression free survival (PFS) and overall survival (OS) was evaluated with Cox regression. The combined effect of LIPI and other relevant prognostic factors was explored with multivariate regression.In total, 113 consecutive patients were included. Median (mPFS) and mOS was 4.3 (2.6-6.7) and 13.5 (10.3-17.7) months, respectively. Good-, intermediate-, and poor-LIPI was found in 54 (47.8%), 45 (39.8%), and 8 (7.1%) patients, respectively. Median PFS was 5.1 (2.8-9.1), 3.0 (2.5-6.8), and 1.4 (0.5-18.7) months, and mOS was 17.2 (12.0-26.4), 11.8 (8.4-17.1), and 3.7 (0.5-not calculable) months for good-, intermediate-, and poor-LIPI group, respectively. Patients with intermediate-LIPI and poor-LIPI had worse PFS versus good-LIPI, and statistically significant worse OS (p = 0.030 and p = 0.013, respectively). In the multivariate analysis, intermediate- versus good-LIPI (p = 0.190) was not independently associated to PFS or OS. Patients with both good-LIPI and high (≥ 50%) PD-L1 had better OS than all other subgroups defined by LIPI and PD-L1. Immune-related adverse events (irAEs) occurred in 47 (41.6%) patients (12.4% grade ≥ 3). In a time-varying analysis, irAEs were statistically associated with longer OS (HR 0.51, 0.31-0.84; p = 0.008).In our series, the outcome of pembrolizumab in pre-treated NSCLC is consistent with the registration trial. Lung Immune Prognostic Index is a readily available tool able to prognosticate outcome, also in PD-L1-high patients. The positive association between irAEs and OS might aid decision making.

PURPOSE The Christie NHS Foundation Trust launched their electronic patient-reported outcome measures (ePROMs) service in January 2019 in the routine clinical setting. The lung cancer questionnaires consist of 14 symptom items, adapted from the Common Terminology Criteria for Adverse Events (version 5.0) and the EuroQol EQ-5D-5L quality-of-life (QoL) tool. Patients with lung cancer are invited to complete questionnaires assessing their symptoms and QoL using an online platform. METHODS The ePROM responses and clinical, pathologic, and treatment data for patients who completed the questionnaires between January 2019 and December 2020 were extracted from electronic medical records. The symptom and QoL scores of patients who completed baseline pretreatment ePROMs and also those who completed ePROMs pre- and postpalliative lung systemic anticancer therapy (SACT) or radical thoracic radiotherapy were evaluated. Pretreatment questionnaires were analyzed according to age, Eastern Cooperative Oncology Group performance status (ECOG PS), and Adult Comorbidity Evaluation-27 (ACE-27) comorbidity score. RESULTS One thousand four hundred eighty patients with lung cancer were included. There were no statistically significant differences in symptoms and QoL scores between age groups. Cough ( P = .006) and EQ-5D-5L mobility scores ( P = .006) were significantly worse for patients with an ECOG PS of 0-1. Dyspnea ( P = .035), hemoptysis ( P = .023), nausea ( P = .041), mobility ( P = .004), and self-care ( P = .0420) were significantly worse for those with higher ACE-27 scores (2-3 v 0-1). Palliative SACT was associated with a significant improvement in cough ( P < .001) and hemoptysis ( P = .025), but significantly negatively affected mobility ( P = .013). Patients receiving radical thoracic radiotherapy reported a significant improvement in hemoptysis ( P = .042) but worse pain ( P = .002) and fatigue ( P = .01). Other changes in symptom and QoL scores were not significant. CONCLUSION The symptoms and QoL reported at baseline and before and after both palliative SACT and radical thoracic radiotherapy are clinically relevant and meaningful. We have demonstrated that routine implementation of ePROMs into clinical practice is feasible and can inform clinical practice and future research.

WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366$-$959\,nm at $R\sim5000$, or two shorter ranges at $R\sim20\,000$. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for $\sim$3 million stars and detailed abundances for $\sim1.5$ million brighter field and open-cluster stars; (ii) survey $\sim0.4$ million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey $\sim400$ neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in $z1$ million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at $z>2$. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator., 41 pages, 27 figures, accepted for publication by MNRAS

Five graduate students reflect on their experiences in multiple roles to address the question, What does a good teacher do now?—during a pandemic, in a moment of reckoning with white supremacy, in the face of uncounted griefs and challenges. We contend that good teachers craft communities of care for students, colleagues, and themselves. We advance trauma, accessibility, surveillance, and labor as particular sites for that project.

Knowledge about monkeypox transmission risk in congregate settings is limited. In July 2022, the Chicago Department of Public Health (CDPH) confirmed a case of monkeypox in a person detained in Cook County Jail (CCJ) in Chicago, Illinois. This case was the first identified in a correctional setting in the United States and reported to CDC during the 2022 multinational monkeypox outbreak. CDPH collaborated with CCJ, the Illinois Department of Public Health (IDPH), and CDC to evaluate transmission risk within the facility. Fifty-seven residents were classified as having intermediate-risk exposures to the patient with monkeypox during the 7-day interval between the patient's symptom onset and his isolation. (Intermediate-risk exposure was defined as potentially being within 6 ft of the patient with monkeypox for a total of ≥3 hours cumulatively, without wearing a surgical mask or respirator, or potentially having contact between their own intact skin or clothing and the skin lesions or body fluids from the patient or with materials that were in contact with the patient's skin lesions or body fluids.) No secondary cases were identified among a subset of 62% of these potentially exposed residents who received symptom monitoring, serologic testing, or both. Thirteen residents accepted postexposure prophylaxis (PEP), with higher acceptance among those who were offered counseling individually or in small groups than among those who were offered PEP together in a large group. Monkeypox virus (MPXV) DNA, but no viable virus, was detected on one surface in a dormitory where the patient had been housed with other residents before he was isolated. Although monkeypox transmission might be limited in similar congregate settings in the absence of higher-risk exposures, congregate facilities should maintain recommended infection control practices in response to monkeypox cases, including placing the person with monkeypox in medical isolation and promptly and thoroughly cleaning and disinfecting spaces where the person has spent time. In addition, officials should provide information to residents and staff members about monkeypox symptoms and transmission modes, facilitate confidential monkeypox risk and symptom disclosure and prompt medical evaluation for symptoms that are reported, and provide PEP counseling in a private setting.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) infection is frequently associated with a wide range of persistent symptoms, now referred to as post-COVID-19 condition, or Long COVID. The objectives of this study were to assess which symptoms are associated with confirmed SARS CoV-2 beyond 12 weeks post-infection in non-hospitalised individuals, and the risk factors associated with developing persistent symptoms. We undertook a retrospective matched cohort study between 31st January 2020 and 15th April 2021 using data from a large database of UK-based primary care electronic health records, Clinical Practice Research Datalink (CPRD) Aurum. We selected 486,149 adult patients with a confirmed diagnosis of SARS CoV-2 infection that had not been hospitalised within 28 days of the diagnosis (infected cohort). We propensity score matched them to 1,944,580 patients without a coded record of either confirmed or suspected COVID-19 (uninfected cohort). Outcomes were the presence of 115 separate symptoms at ≥12 weeks post-infection, and Long COVID, defined as having at least one of the symptoms included in the World Health Organisation case definition. Separate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) for individual symptoms and Long Covid. 62 symptoms were significantly associated with prior exposure to SARS CoV-2 after 12 weeks. The largest adjusted hazard ratios (aHR) were for anosmia (aHR 6.49, 95% CI 5.02 to 8.39), hair loss (3.99, 3.63 to 4.39), sneezing (2.77, 1.40 to 5.50), difficulties with ejaculation (2.63, 1.61 to 4.28), reduced libido (2.36, 1.61 to 3.47), shortness of breath at rest (2.20, 1.57 to 3.08), fatigue (1.92, 1.81 to 2.03), pleuritic chest pain (1.86, 1.41 to 2.46), hoarse voice (1.78, 1.44 to 2.20), and fever (1.75, 1.54 to 1.98). Among the infected cohort, risk factors for Long COVID included younger age (aHR 0.75, 95% CI 0.70 to 0.81, for those aged ≥70 years compared to those aged 18 to 30 years), female sex (1.52, 1.48 to 1.56), belonging to an ethnic minority group (1.14 [1.07 to 1.22] for mixed race, 1.21 [1.10 to 1.34] for black ethnic groups, and 1.06 [1.03 to 1.10] for other ethnic minority groups, compared to white ethnic groups), socioeconomic deprivation (1.11 [1.07 to 1.16] for the most compared to the least socioeconomically deprived quintile), smoking (1.12, 1.08 to 1.15), obesity (1.10, 1.07 to 1.14), and a wide range of comorbidities such as COPD. SARS CoV-2 in non-hospitalised individuals is associated with a plethora of symptoms being reported at ≥12 weeks post-infection, with a higher risk associated with younger age, female sex, ethnic minority groups, socioeconomic deprivation, smoking, obesity, and several comorbidities.

Children presenting with a suspected seizure are recommended to be seen by a specialist for the diagnosis and management of the epilepsies within 2 weeks of presentation. As part of the Royal College of Pediatrics and Child Health Quality Improvement Project, our project aim was to establish a first afebrile fit telephone clinic in line with The National Institute for Health and Care Excellence guidance. Our results showed safety information was poorly provided and retained at the initial consultation and a follow-up telephone call reinforced safety information and provided a point of contact for patients and families to use. The telephone follow-up also resulted in eight direct referrals into an epilepsy clinic. It is hoped the results from this project will act as a stepping stone to setting up a consultant-led first fit clinic.

In 2010, Haiti and Pakistan experienced immense suffering, death and destruction as these countries faced two of the world’s greatest humanitarian crises. The earthquake in Haiti was very well reported. Celebrities, organizations and individuals recognized the need for help and contributed generously to various relief foundations. Unlike the attention Haiti received, the flood in Pakistan received far less media coverage. The lack of media attention in Pakistan arguably limited the public’s awareness of the flood and reduced the perception of urgency and need for humanitarian support (Winthrop, 2010). This MRP focuses on the news media in the service of reporting on international crises and investigates how the media takes an ideological position when reporting and presenting events to its audience. In this paper, I demonstrate how reporting in a major Canadian newspaper becomes an exercise in ideological power and influences audiences (Fairclough, 2001).

The College Board’s ACCUPLACER Automated Writing Placement Tool is administered more than 8.5 million times each year to place students into college-level or developmental writing courses. ACCUPLACER’s writing assessment consists of a multiple-choice Next-Generation Writing Test and an on-demand essay called WritePlacer. In this review, we offer an overview of ACCUPLACER, considering the test in light of the constructs of writing it emphasizes. We explore the tool’s objectives, its potential affordances, and its limitations and possible futures. We ask whether and how this tool might advance or impede efforts toward racial and gender equity, might promote or resist standard language ideologies, and might carry consequences for course placement.

ObjectiveLeukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in DARS2, encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). DARS2 variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. We noticed highly unusual MRI presentations in 15 cases diagnosed by WES. We examined these cases to determine whether they represent consistent novel LBSL phenotypes.MethodsWe reviewed clinical features, MRI abnormalities, and gene variants and investigated the variants' impact on mtAspRS structure and mitochondrial function.ResultsWe found 2 MRI phenotypes: early severe cerebral hypoplasia/atrophy (9 patients, group 1) and white matter abnormalities without long tract involvement (6 patients, group 2). With antenatal onset, microcephaly, and arrested development, group 1 patients were most severely affected. DARS2 variants were severer than for classic LBSL and severer for group 1 than group 2. All missense variants hit mtAspRS regions involved in tRNAAsp binding, aspartyl-adenosine-5′-monophosphate binding, and/or homodimerization. Missense variants expressed in the yeast DARS2 ortholog showed severely affected mitochondrial function.ConclusionsDARS2 variants are associated with highly heterogeneous phenotypes. New MRI presentations are profound cerebral hypoplasia/atrophy and white matter abnormalities without long tract involvement. Our findings have implications for diagnosis and understanding disease mechanisms, pointing at dominant neuronal/axonal involvement in severe cases. In line with this conclusion, activation of biallelic DARS2 null alleles in conditional transgenic mice leads to massive neuronal apoptosis.

International audience; We present an update on the overall integration progress of the WEAVE next-generation spectroscopy facility for the William Herschel Telescope (WHT), now scheduled for first light in early-2021, with almost all components now arrived at the observatory. We also present a summary of the current planning behind the 5-year initial phase of survey operations, and some detailed end-to-end science simulations that have been implemented to evaluate the final on-sky performance after data processing. WEAVE will provide optical ground-based follow up of ground-based (LOFAR) and space-based (Gaia) surveys. WEAVE is a multi-object and multi-IFU facility utilizing a new 2-degree prime focus field of view at the WHT, with a buffered pick-and-place positioner system hosting 1000 multi-object (MOS) fibres, 20 mini integral field units, or a single large IFU for each observation. The fibres are fed to a single (dual-beam) spectrograph, with total of 16k spectral pixels, located within the WHT GHRIL enclosure on the telescope Nasmyth platform, supporting observations at R~5000 over the full 370-1000nm wavelength range in a single exposure, or a high resolution mode with limited coverage in each arm at R~20000.

WEAVE is the new wide-field spectroscopy facility for the prime focus of the William Herschel Telescope at La Palma, Spain. Its fibre positioner is essential for the accurate placement of the spectrograph's 960 fibre multiplex. We provide an overview of the final assembly and metrology of the fibre positioner, and results of lab commissioning of its robot gantries. A completely new z-gantry for each positioner robot was acquired, with measurements showing a marked improvement in positioning repeatability. We also present the first results of the configuration software testing, and discuss the metrology procedures that must be repeated after the positioner's arrival at the observatory.