An 11-year validation of wave-surge modelling in the Irish Sea, using a nested POLCOMS-WAM modelling system

In the future it is believed that extreme coastal flooding events will increase (in frequency and intensity) as a result of climate change. We are investigating the flood risks in the eastern Irish Sea posed by extreme storm events. Here, an 11-year simulation (01/01/1996–01/01/2007) including wave–current interaction has been validated. These data can then be used to investigate the potential for coastal flooding in the study area. To accurately model a storm event in the eastern Irish Sea both wave effects and the influence of the external surge need to be considered. To simulate the waves, we have set up a one-way nested approach from a 1° North Atlantic model, to a 1.85 km Irish Sea model, using the state-of-the-art 3rd-generation spectral WAve Model (WAM). This allows the influence of swell to be correctly represented. The Proudman Oceanographic Laboratory Coastal-Ocean Modelling System (POLCOMS) has been used to model the tide–surge interaction. To include the external surge we have set up a one-way nested approach from the 1/9° by 1/6° operational Continental Shelf surge model, to a 1.85 km Irish Sea model. For the high resolution Irish Sea model we use a POLCOMS–WAM coupled model, to allow for the effects of wave–current interaction on the prediction of surges at the coast. Using two classification schemes the coupled model is shown to be good and often very good at predicting the surge, total water elevation and wave conditions. We also find the number of low level surge events has increased in the study area over the past decade. However, this time period is too short to determine any long-term trends in the wave and surge levels

Thumb Base Osteoarthritis: Prevalence, Occupational Risk, and Surgical Outcomes

Osteoarthritis of the carpometacarpal joint at the base of the thumb (CMC1 OA) is common and causes difficulty in grasp, grip, and fine manipulation of the hand. Surgery is recommended after failure of non-operative treatment, andevidence from short and medium-term follow-up studies shows successful relief of pain and return of function. Previous investigations of epidemiology and risk factors were drawn from small case series or radiographic reviews; similarly,surgical outcomes studies have been limited by lack of robust follow-up.The objectives of this thesis were to: 1) evaluate the clinically important prevalence of CMC1 OA by age and sex using physician-assigned diagnoses; 2) study the impact of occupational load on the occurrence of CMC1 OA; and 3) evaluate surgical outcomes including register-based sick leave length as well as long-term follow-up in a tightlycaptured population.Epidemiologic analysis using the Skåne Healthcare Register showed a sex difference in prevalence of CMC1 OA with 2.2% of women compared to 0.6% of men assigned this diagnosis over a 15-year period, with peak prevalence inwomen at age 70-74 years. Occupational load analysis showed that jobs with the heaviest manual work stress conferred the greatest risk of a diagnosis of CMC1 OA, with a monotonic relationship between work load and thumbbase OA in men. Lengthy sick leave periods were noted after both soft tissue and prosthetic implant arthroplasty, but prosthetic implant surgery patients returned to work a mean of 30 days earlier than those treated with soft tissue reconstruction. Finally, in a single-site cohort with 17 years mean follow-up of 96 of 100 (96%) patients after abductor pollicis longus (APL) tendon suspension interposition arthroplasty, we noted good to excellent patient-rated pain and functional outcomes as well as grip and pinch comparable to the non-operated side. These findings confirm long-held beliefs that there is greater female prevalence of CMC1 OA and that heavy labor is associated with increased risk of CMC1 OA. Surgical treatment can relieve pain and improve function, with prosthetic implant arthroplasty associated with earlier return to work

Influenza virus strategies to regulate S1P-metabolizing enzymes and evade host innate immunity for robust viral replication

Viral infection is a complex network of interactions involving the host defending itself against the virus and the virus attempting to subdue host defenses and utilize the cellular machinery to promote its replication. Similar to other viruses, influenza A virus (IAV) manipulates and modulates the host cell to maintain control and optimize the cell for viral replication. One of the central obstacles IAV must overcome to further its replication is the type I IFN innate immune response. We have previously shown that sphingosine 1-phosphate (S1P) lyase (SPL) enhances IKK[epsilon]-mediated type I IFN responses. Here, we show that the nonstructural protein 1 (NS1) of IAV counteracts the SPL-mediated antiviral response by inducing SPL degradation. SPL was ubiquitinated and downregulated upon IAV infection or NS1 expression, and SPL-enhanced IFN production was strikingly inhibited by IAV NS1. Another IAV type I IFN-evasion strategy IAV is viral hemagglutinin (HA) facilitating type I IFN receptor 1 (IFNAR1) degradation. Further defining this, we determined that a cellular protein, poly (ADP-ribose) polymerase 1 (PARP1), plays a critical role in mediating IAV HA-induced degradation of IFNAR1. Knockdown or inhibition of PARP1 rescued IFNAR1 levels during IAV infection or HA expression, and PARP1 was crucial for robust IAV replication, which was associated with regulation of the type I IFN receptor signaling pathway. We have also found that sphingosine kinase 2 (SK2) enhances IAV replication along with multiple host factors. IAV protein synthesis during infection was enhanced by transient overexpression of SK2, and SK2 activity affected p21 expression during IAV infection. IAV infection led to increased SK2 and activated SK2 protein expression, and MEK/ERK activation was found to be important for this increase. Overall, these studies further define IAV-host interactions and reveal novel processes used by IAV to promote its own replication.Includes bibliographical references

Individual and county-level religious participation, corporal punishment, and physical abuse of children: An exploratory study

Parental religiosity has been associated with corporal punishment. However, most of this research has focused exclusively on Christians and has not examined physical abuse. In addition, little is known about how the larger religious environment might be associated with discipline behaviors. In this exploratory study, we examine how individual- and county-level religious attendance are related to corporal punishment and physical abuse. We sampled and surveyed 3,023 parents of children aged 12 and younger from 50 mid-sized California cities. We used weighted Poisson models to calculate the frequency of corporal punishment and physical abuse in the past year. Parents who attend religious groups used corporal punishment more frequently than parents who did not attend religious groups. However, those who lived in counties with greater rates of religious participation used corporal punishment less frequently than those living in counties with lower rates of religious participation. There were no effects for religious participation on physical abuse at the individual or county level. This exploratory study suggests that parents who attend religious groups may be more likely to use some types of physical discipline with children. Religious groups could be imparting parenting norms supporting corporal punishment at the individual level. More research examining specific doctrines and faiths is needed to validate the study findings

RAD54 family translocases counter genotoxic effects of RAD51 in human tumor cells.

The RAD54 family DNA translocases have several biochemical activities. One activity, demonstrated previously for the budding yeast translocases, is ATPase-dependent disruption of RAD51-dsDNA binding. This activity is thought to promote dissociation of RAD51 from heteroduplex DNA following strand exchange during homologous recombination. In addition, previous experiments in budding yeast have shown that the same activity of Rad54 removes Rad51 from undamaged sites on chromosomes; mutants lacking Rad54 accumulate nonrepair-associated complexes that can block growth and lead to chromosome loss. Here, we show that human RAD54 also promotes the dissociation of RAD51 from dsDNA and not ssDNA. We also show that translocase depletion in tumor cell lines leads to the accumulation of RAD51 on chromosomes, forming complexes that are not associated with markers of DNA damage. We further show that combined depletion of RAD54L and RAD54B and/or artificial induction of RAD51 overexpression blocks replication and promotes chromosome segregation defects. These results support a model in which RAD54L and RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to dsDNA in human tumor cells. Thus, in addition to having genome-stabilizing DNA repair activity, human RAD51 has genome-destabilizing activity when expressed at high levels, as is the case in many human tumors

Overexpression of MMPs in Corneas Requiring Penetrating and Deep Anterior Lamellar Keratoplasty.

PurposeMatrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases involved in wound healing processes, including neovascularization and fibrosis. We assessed MMP protein expression levels in diseased corneas of patients requiring penetrating and deep anterior lamellar keratoplasty. The purpose of this study was to test the hypothesis that upregulation of MMPs in diseased corneas is positively associated with clinical levels of corneal neovascularization and fibrosis.MethodsProtein expression levels of nine individual MMPs were quantified simultaneously in human corneal lysates by using the Bio-Plex Pro Human MMP 9-Plex Panel and the MAGPIX technology. Measurements of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13 were performed on diseased specimens from 21 patients undergoing corneal transplantation (17 for penetrating keratoplasty and 4 for deep anterior lamellar keratoplasty) and 6 normal control corneas.ResultsLuminex-based expression analysis revealed a significant overexpression of four of the nine MMPs tested (MMP2, MMP8, MMP12, and MMP13) in patient samples compared to control. Significant overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 was observed in diseased corneas with neovascularization compared with diseased corneas without neovascularization. Overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 also corresponded with the levels of corneal fibrosis. Finally, reduced expression of MMP3 was detected in keratoconus patients.ConclusionsMultiple MMPs are expressed in the corneas of patients with chronic disease requiring keratoplasty even when the pathologic process appears to be clinically inactive. In particular, the expression of several MMPs (MMP2, MMP8, MMP12, and MMP13) is positively associated with increased levels corneal fibrosis and neovascularization

Stress, alcohol use, and punitive parenting during the COVID-19 pandemic

BackgroundEmerging research suggests that parents are experiencing heightened stress during the COVID-19 pandemic. Parental stress is a risk factor for harsh or punitive parenting, and this association may be exacerbated by the use of alcohol. ObjectiveWe examine whether parental stress is associated with use of punitive parenting, as well as whether this association is modified by drinking pattern. Participants & setting We used advertisements and word-of-mouth to recruit 342 parents living in Central Ohio during the initial stay-at-home order for COVID-19. MethodsWe used geographic ecological momentary assessment (gEMA) to measure parental stress and punitive parenting during three time periods (10 a.m., 3 p.m., and 9 p.m.) over a period of fourteen days using an app downloaded to their cellular telephone. Participants also completed a longer baseline survey. We used nested multilevel ordinal regression models, where at-the-moment assessments (Level 1) were nested within individuals (Level 2) to analyze data. ResultsHigher levels of parental stress [OR = 1.149 (95 % CI = 1.123, 1.176)] and later time of day [OR = 1.255 (95 % CI = 1.146, 1.373)] were positively related to odds of punitive parenting. Drinking pattern was not significantly related to punitive parenting in models with demographic covariates. Parents who drank alcohol both monthly and weekly and had higher levels of stress had greater odds of punitive parenting than parents with high levels of stress who abstain from alcohol. ConclusionsAlcohol may be an accelerant in the use of punitive parenting for parents experiencing stress. As alcohol use increases during COVID-19, children may be at higher risk for punitive parenting

Charakterisierung von Verschmutzungsaerosolen bezüglich der mikrophysikalischen Eigenschaften in Europa und Asien während der EMeRGe-Kampagne

Die Prozesse von anthropogenen Aerosolen und ihr Beitrag zur anthropogenen Erwärmung sind immer noch mit großen Unsicherheiten verbunden. Um diese Unsicherheiten zu minimieren, sind gezielte Messungen zur Charakterisierung der Verschmutzungsaerosole nötig, welche dann für die Validierung und Verbesserung der Parametrisierungen in den Modellen herangezogen werden können. Die Abhängigkeit der mikrophysikalischen Aerosoleigenschaften in Bezug auf die Quellregionen, aber auch der Einfluss der Alterung und des Transports auf die Größenverteilungen sind wichtige offene Fragen. Vor allem für die Untersuchung der Transportprozesse sind Messungen auf großen Skalen und auf einer gewissen Höhe nötig, sodass Bodenmessstationen nicht dafür geeignet sind diese Messungen durchzuführen. Dies ist der Grund für die Durchführung der EMeRGe-Kampagne (Effect of Megacities on the Transport and Transformation of Pollutants on the Regional to Global Scales) mit dem Forschungsflugzeug HALO in Europa im Sommer 2017 und in Südostasien im Frühling 2018, bei welcher die Abgasfahnen von Megacitys beprobt wurden. Mit dem „Aerosol Measuring System“ (AMETYST) wurden während dieser Kampagne die Gesamtanzahlkonzentration der Aerosolpartikel im Größenbereich von 10 nm bis 3 µm, die Anzahlkonzentration in verschiedenen Größenkanälen und die Absorptionskoeffizienten für drei verschiedene Wellenlängen gemessen. Da AMETYST bisher nicht vollständig charakterisiert wurde, war es nötig zunächst eine umfassende Charakterisierung und Kalibrierung vor der Datenauswertung durchzuführen, damit mögliche Fehlerquellen berücksichtigt und wenn möglich korrigiert werden können. Für die Beantwortung der Frage, in wie fern sich die mikrophysikalischen Aerosoleigenschaften bei unterschiedlichen Quellregionen unterscheiden, wurden die Messungen in den Abgasfahnen der beiden Megacitys London und Manila herangezogen. Ein Vergleich der Gesamtanzahlkonzentrationen ergab keinen signifikanten Unterschied zwischen den beiden Städten, jedoch waren die Größenverteilungen von der Beprobung der Abgasfahne von Manila signifikant hin zu größeren Partikeldurchmessern verschoben und die Absorptionskoeffizienten waren deutlich höher. Es wurden also durchaus wesentliche Unterschiede zwischen den beiden Quellregionen Europa und Südostasien hinsichtlich der mikrophysikalischen Aerosoleigenschaften gemessen. Wie sich die Transport- und Alterungsprozesse auf die mikrophysikalischen Aerosoleigenschaften auswirken, wurde durch Messungen an der Westküste von Taiwan untersucht. Dort konnten sowohl lokale Emissionen als auch ferntransportierte Emissionen, wie etwa vom asiatischen Festland, vermessen werden. Bei den lokalen Emissionen konnten im Mittel eine höhere Gesamtanzahlkonzentration als bei den transportierten Emissionen gemessen werden, aber beim Vergleich der Größenverteilungen der beiden Emissionstypen gab es keinen signifikanten Unterschied. Dies liegt daran, dass die lokale Verweildauer der Luftmassen länger war als erwartet, sodass die transportierten Emissionen teilweise jünger waren. Eine Unterscheidung nur anhand der Quelle war damit nicht möglich. Aber die Alterungsprozesse, welche meist für ein Anwachsen der Partikel sorgen, konnten beim Vergleich der jungen und alten Emissionen in den Größenverteilungen nachgewiesen werden. Die hier vorgestellten Messungen der mikrophysikalischen Aerosoleigenschaften von Megacitys und an der Westküste von Taiwan helfen anthropogene Emissionsquellen besser zu verstehen und die Transport- und Alterungsprozesse von Aerosolpartikeln zu quantifizieren. Die Datenbasis zur Validierung und Verbesserung der Modellparametrisierungen wird dadurch erhöht.The processes governing the properties of anthropogenic aerosols are still associated with large uncertainties. To minimize these uncertainties, targeted measurements are required to characterize the pollution aerosols, which can then be used to validate and improve the parametrizations in models which assess their climate impact. The dependence of the microphysical aerosol properties in relation to the source regions, but also the influence of aging and transport on the aerosol size distributions are important open questions. Especially for the investigation of the transport processes, measurements on large scales and at a certain height are necessary, therefore ground measurements are not suitable for these measurements. This was the scientific motive for carrying out the EMeRGe campaign (Effect of Megacities on the Transport and Transformation of Pollutants on the Regional to Global Scales) with the research aircraft HALO in Europe in summer 2017 and in Southeast Asia in spring 2018 to measure the pollution plumes from megacities with more than 10 million inhabitants. During this campaign the “Aerosol Measurement System” (AMETYST) measured the total number concentration of aerosol particles in the range from 10 nm to 3 µm, the number concentration in different size channels and the absorption coefficients for three different wavelengths. Since AMETYST has not yet been fully characterized, it was necessary to carry out a comprehensive characterization and calibration before data evaluation so that sources of error can be taken into account and, if possible, corrected. To answer the question to what extent the microphysical aerosol properties differ with regard to different source regions, the measurements of the pollution plumes from the megacities London and Manila were studied in detail. A comparison of the total number concentrations revealed no significant difference between the two cities, however, the size distributions from the Manila pollution plume were significantly shifted towards larger particle diameters and the absorption coefficients were also increased. Thus, clear differences in the microphysical aerosol properties regarding different source regions in Europe and Southeast Asia have been measured. How transport and aging affect the microphysical aerosol properties was investigated by measurements along the west coast of Taiwan. In this measurement area both local emissions and transported emissions from the Asian mainland could be probed. The total aerosol number concentrations from the local emissions were higher on average while the number size distributions were quite similar. This was due to the longer residence time of local emissions, such that the transported emissions were partly younger than the local ones. Because of that a difference based solely on the source of the aerosols could not be determined. But when comparing the number size distributions of young local with old transported emissions, the processes of aging were clearly detected by an increase in the particle diameter. These measurements of the microphysical aerosol properties near megacities and on the west coast of Taiwan help to improve our knowledge of anthropogenic aerosol emission and quantify the processes of transport and aging. Therefore, the database to validate and improve the model parametrizations is increased by this work