Sustaining work ability amongst female professional workers with long COVID.

BACKGROUND: Long COVID (LC) compromises work ability (WA). Female worker WA has been more adversely impacted than WA in men. Exploration of lived experiences could elucidate the WA support required. AIMS: To explore the working conditions and circumstances experienced as affecting sustained WA amongst female workers with LC, to help mitigate worklessness risks. METHODS: Online semi-structured qualitative interviews were conducted with 10 female workers self-reporting or formally diagnosed with LC who had made some attempt to return to work (RTW). Interviews were analysed using template analysis to map themes informing WA enablers and obstacles onto a biopsychosocial model of rehabilitation. RESULTS: All participants were professionals working in an employed or self-employed capacity. Key themes reflecting circumstances that afforded sustained WA included the autonomy over where, when and how to work indicated as facilitated by a professional role, rapid health care access, predominantly sedentary work, competent colleagues able to cover for transient reduced WA, a strong interface between specialist health and management support, and accessible organizational policies that steer health management according to equity rather than equality. Highly flexible, iterative, co-produced RTW planning, tolerant of fluctuating symptom expression appears vital. In return for providing such flexibility, participants felt that employers' workforce diversity and competence would be protected and that workers would need to reciprocate flexibility. CONCLUSIONS: These qualitatively derived findings of workers' lived experiences add to existing guidance on supporting WA for people struggling with LC. Moreover, the same principles seem appropriate for tackling worklessness amongst working-age adults with complex long-term health conditions.

What workers can tell us about post-COVID workability.

BACKGROUND: The apparent functional impact of post-COVID-19 syndrome has workability implications for large segments of the working-age population. AIMS: To understand obstacles and enablers around self-reported workability of workers following COVID-19, to better guide sustainable workplace accommodations. METHODS: An exploratory online survey comprising quantitative and qualitative questions was disseminated via social media and industry networks between December 2020 and February 2021, yielding usable responses from 145 workers. Qualitative data were subjected to content analysis. RESULTS: Over half of the sample (64%) were from the health, social care, and education sectors. Just under 15% had returned to work, and 53% and 50% reported their physical and psychological workability respectively as moderate at best. Leading workability obstacles were multi-level, comprising fatigue, the interaction between symptoms and job, lack of control over job pressures, inappropriate sickness absence management policies, and lack of COVID-aware organizational cultures. Self-management support, modified work, flexible co-developed graded return-to-work planning, and improved line management competency were advocated as key enablers. CONCLUSIONS: Assuming appropriate medical management of any pathophysiological complications of COVID-19, maintaining or regaining post-COVID workability might reasonably follow a typical biopsychosocial framework enhanced to cater to the fluctuating nature of the symptoms. This should entail flexible, regularly reviewed and longer-term return-to-work planning addressing multi-level workability obstacles, co-developed between workers and line managers, with support from human resources, occupational health professionals (OHP's), and a COVID-aware organizational culture.

A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution.

Indo-Pacific Walker circulation drove Pleistocene African aridification.

Today, the eastern African hydroclimate is tightly linked to fluctuations in the zonal atmospheric Walker circulation1,2. A growing body of evidence indicates that this circulation shaped hydroclimatic conditions in the Indian Ocean region also on much longer, glacial-interglacial timescales3-5, following the development of Pacific Walker circulation around 2.2-2.0 million years ago (Ma)6,7. However, continuous long-term records to determine the timing and mechanisms of Pacific-influenced climate transitions in the Indian Ocean have been unavailable. Here we present a seven-million-year-long record of wind-driven circulation of the tropical Indian Ocean, as recorded in Mozambique Channel Throughflow (MCT) flow-speed variations. We show that the MCT flow speed was relatively weak and steady until 2.1 ± 0.1 Ma, when it began to increase, coincident with the intensification of the Pacific Walker circulation6,7. Strong increases during glacial periods, which reached maxima after the Mid-Pleistocene Transition (0.9-0.64 Ma; ref. 8), were punctuated by weak flow speeds during interglacial periods. We provide a mechanism explaining that increasing MCT flow speeds reflect synchronous development of the Indo-Pacific Walker cells that promote aridification in Africa. Our results suggest that after about 2.1 Ma, the increasing aridification is punctuated by pronounced humid interglacial periods. This record will facilitate testing of hypotheses of climate-environmental drivers for hominin evolution and dispersal.

Hepatitis C among vulnerable populations: A seroprevalence study of homeless, people who inject drugs and prisoners in London.

Injecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in the homeless and prisoners. Capturing accurate data on disease prevalence within these groups is challenging but is essential to inform strategies to reduce HCV transmission. The aim of this study was to estimate the prevalence of HCV in these populations. We conducted a cross-sectional study between May 2011 and June 2013 in London and, using convenience sampling, recruited participants from hostels for the homeless, drug treatment services and a prison. A questionnaire was administered and blood samples were tested for hepatitis C. We recruited 491 individuals who were homeless (40.7%), 205 drug users (17%) and 511 prisoners (42.3%). Eight per cent of patients (98/1207, 95% CI: 6.7%-9.8%) had active HCV infection and 3% (38/1207, 95% CI: 2.3%-4.3%) past HCV infection. Overall, one quarter (51/205) of people recruited in drug treatment services, 13% (65/491) of people from homeless residential sites and 4% (20/511) prisoners in this study were anti-HCV positive. Seventy-seven of the 136 (56.6%, 95% CI: 47.9%-65%) of HCV infected participants identified had a history of all three risk factors (homelessness, imprisonment and drug use), 27.3% (95% CI: 20.1%-35.6%) had 2 overlapping risk factors, and 15.4% (95% CI: 10.6%-23.7%) one risk factor. Drug treatment services, prisons and homelessness services provide good opportunities for identifying hepatitis C-infected individuals. Effective models need to be developed to ensure case identification in these settings that can lead to an effective treatment and an efficient HCV prevention.

Evidence for Extending Anomalous Miocene Volcanism at the Edge of the East Antarctic Craton.

Using field observations followed by petrological, geochemical, geochronological, and geophysical data we infer the presence of a previously unknown Miocene subglacial volcanic center ~230 km from the South Pole. Evidence of volcanism is from boulders of olivine-bearing amygdaloidal/vesicular basalt and hyaloclastite deposited in a moraine in the southern Transantarctic Mountains. 40Ar/39Ar ages from five specimens plus U-Pb ages of detrital zircon from glacial till indicate igneous activity 25-17 Ma. The likely source of the volcanism is a circular -735 nT magnetic anomaly 60 km upflow from the sampling site. Subaqueous textures of the volcanics indicate eruption beneath ice or into water at the margin of an ice mass during the early Miocene. These rocks record the southernmost Cenozoic volcanism in Antarctica and expand the known extent of the oldest lavas associated with West Antarctic rift system. They may be an expression of lithospheric foundering beneath the southern Transantarctic Mountains.

RNA polymerase II subunit Rpb9 regulates transcription elongation in vivo.

RNA polymerase II lacking the Rpb9 subunit uses alternate transcription initiation sites in vitro and in vivo and is unable to respond to the transcription elongation factor TFIIS in vitro. Here, we show that RPB9 has a synthetic phenotype with the TFIIS gene. Disruption of RPB9 in yeast also resulted in sensitivity to 6-azauracil, which is a phenotype linked to defects in transcription elongation. Expression of the TFIIS gene on a high-copy plasmid partially suppressed the 6-azauracil sensitivity of Deltarpb9 cells. We set out to determine the relevant cellular role of yeast Rpb9 by assessing the ability of 20 different site-directed and deletion mutants of RPB9 to complement the initiation and elongation defects of Deltarpb9 cells in vivo. Rpb9 is composed of two zinc ribbons. The N-terminal zinc ribbon restored the wild-type pattern of initiation start sites, but was unable to complement the growth defects associated with defects in elongation. Most of the site-directed mutants complemented the elongation-specific growth phenotypes and reconstituted the normal pattern of transcription initiation sites. The anti-correlation between the growth defects of cells disrupted for RPB9 and the selection of transcription start sites suggests that this is not the primary cellular role for Rpb9. Genome-wide transcription profiling of Deltarpb9 cells revealed only a few changes, predominantly in genes related to metabolism.

Yeast RNA polymerase II subunit RPB9. Mapping of domains required for transcription elongation.

The RPB9 subunit of RNA polymerase II regulates transcription elongation activity and is required for the action of the transcription elongation factor, TFIIS. RPB9 comprises two zinc ribbon domains joined by a conserved linker region. The C-terminal zinc ribbon is similar in sequence to that found in TFIIS. To elucidate the relationship between the structure and transcription elongation function of RPB9, we initiated a mutagenesis study on the Saccharomyces cerevisiae homologue. The individual zinc ribbon domains, in isolation or in combination, could not stimulate transcription by a polymerase lacking RPB9, pol IIDelta9. Mutations in the N-terminal zinc ribbon had little effect on transcription activity. By contrast, mutations in the acidic loop that connects the second and third beta-strands of the C-terminal zinc ribbon were completely inactive for transcription. Interestingly, the analogous residues in TFIIS are also critical for elongation activity. A conserved charged stretch in the linker region (residues 89-95, DPTLPR) mediated the interaction with RNA polymerase II.

Transcription elongation through DNA arrest sites. A multistep process involving both RNA polymerase II subunit RPB9 and TFIIS.

The role of yeast RNA polymerase II (pol II) subunit RPB9 in transcript elongation was investigated by examining the biochemical properties of pol II lacking RPB9 (pol IIDelta9). The maximal rate of chain elongation was nearly identical for pol II and pol IIDelta9. By contrast, pol IIDelta9 elongated more efficiently through DNA sequences that signal the elongation complex to pause or arrest. The addition of purified recombinant RPB9 to pol IIDelta9 restored the elongation properties of the mutant polymerase to those of the wild-type enzyme. Arrested pol IIDelta9 complexes were refractory to levels of TFIIS that promoted maximal read-through with pol II. However, both pol II and pol IIDelta9 complexes stimulated with TFIIS undergo transcript cleavage, confirming that transcript cleavage and read-through activities can be uncoupled. Our observations suggest that both TFIIS and RPB9 are required to stimulate the release of RNA polymerase II from the arrested state.

The mechanism of protein crystal growth from lipid layers.

Two-dimensional (2D) crystals of proteins on lipid monolayers can initiate the formation of large three-dimensional (3D) crystals suitable for X-ray diffraction studies. The role of the 2D crystals in this process has not been firmly established. While it is likely that the 2D crystals serve as nuclei for epitaxial crystal growth, other mechanisms, such as non-specific nucleation induced by the high local concentration of the protein at the surface of the lipid layer, cannot be excluded. Using streptavidin as a model system, we have now firmly established that 3D crystal growth from 2D crystals on lipid layers occurs by epitaxy. We show that 2D crystals of streptavidin (space group C222) on biotinated lipid layers nucleate the growth of a 3D crystal form (space group I4I22) that possesses a structural similarity with the 2D crystal, but have no effect on the growth of 3D crystal forms (I222 and P2(1)) that are unrelated to the 2D crystal. At lower pH, a new 3D crystal form (space group P1), unrelated to the previously described 2D crystals, grew from lipid layers. This discovery initially raised concern about the validity of the epitaxial mechanism, but these concerns were alleviated with the subsequent discovery of a structurally related 2D P1 crystal that grew in similar solution conditions. Some parameters affecting epitaxial growth of both the P1 and I4I22 crystals were investigated, revealing several noteworthy features of the epitaxial growth. (1) 2D crystals are very effective nucleating agents; for instance, the P1 2D crystals can direct the growth of P1 3D crystals even under conditions that favour the growth of other crystal forms. (2) The epitaxial 3D crystal grow very rapidly and at amazingly low protein concentrations; P1 3D crystals can be grown from solutions as low as 10 microM streptavidin. (3) There is no obligate requirement for the deposition of pre-formed 2D crystals; lipid layers alone are equally effective at promoting epitaxial crystal growth.

Epitaxial growth of protein crystals on lipid layers.

The growth of three-dimensional protein crystals is seeded by two-dimensional crystals formed on lipid layers. Such crystallization occurs faster and at lower precipitant and protein concentrations than conventional crystal growth. This approach may also allow the crystallization of proteins that resist attempts at crystal growth by other means.