Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study

<p>Abstract</p> <p>Background</p> <p>There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU).</p> <p>Methods</p> <p>This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled.</p> <p>Results</p> <p>Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented.</p> <p>Conclusion</p> <p>Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, <it>Candida </it>infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.</p

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

The Lancet Breast Cancer Commission: tackling a global health, gender, and equity challenge

Breast cancer is an increasing global health, gender, socioeconomic, and equity challenge. In 2020, 2·3 million women were diagnosed with breast cancer and there were 685 000 deaths worldwide.1 Not only is breast cancer the highest incident cancer globally, but it is also the most prevalent, causing more disability-adjusted life-years lost than any other malignancy. Tackling breast cancer is a formidable task for health-care systems, policy makers, and other stakeholders. The numbers of people with metastatic breast cancer who go uncounted are concerning. Cancer registries record patients initially presenting with de-novo metastatic breast cancer, but data on those who develop metastases after a diagnosis of early breast cancer are scarce. In a world focused on breast cancer cure, these uncounted people living with metastatic disease face abandonment and stigma

Thy1+ Nk Cells from Vaccinia Virus-Primed Mice Confer Protection against Vaccinia Virus Challenge in the Absence of Adaptive Lymphocytes

While immunological memory has long been considered the province of T- and B- lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for which no cognate germline-encoded receptor has been identified. This immune response results in viral clearance in the absence of classical adaptive T and B lymphocyte populations, and is mediated by a Thy1+ subset of natural killer (NK) cells. We demonstrate that immune protection against infection from a lethal dose of virus can be adoptively transferred with memory hepatic Thy1+ NK cells that were primed with live virus. Our results also indicate that, like classical immunological memory, stronger innate memory responses form in response to priming with live virus than a highly attenuated vector. These results demonstrate that a defined innate memory cell population alone can provide host protection against a lethal systemic infection through viral clearance

Pulmonary Vaccination as a Novel Treatment for Lung Fibrosis

Pulmonary fibrosis is an untreatable, uniformly fatal disease of unclear etiology that is the result of unremitting chronic inflammation. Recent studies have implicated bone marrow derived fibrocytes and M2 macrophages as playing key roles in propagating fibrosis. While the disease process is characterized by the accumulation of lymphocytes in the lung parenchyma and alveolar space, their role remains unclear. In this report we definitively demonstrate the ability of T cells to regulate lung inflammation leading to fibrosis. Specifically we demonstrate the ability of intranasal vaccinia vaccination to inhibit M2 macrophage generation and fibrocyte recruitment and hence the accumulation of collagen and death due to pulmonary failure. Mechanistically, we demonstrate the ability of lung Th1 cells to prevent fibrosis as vaccinia failed to prevent disease in Rag−/− mice or in mice in which the T cells lacked IFN-γ. Furthermore, vaccination 3 months prior to the initiation of fibrosis was able to mitigate the disease. Our findings clearly demonstrate the role of T cells in regulating pulmonary fibrosis as well as suggest that vaccinia-induced immunotherapy in the lung may prove to be a novel treatment approach to this otherwise fatal disease

The impact of atmosphere–ocean–wave coupling on the near-surface wind speed in forecasts of extratropical cyclones

Accurate modelling of air–sea surface exchanges is crucial for reliable extreme surface windspeed forecasts. While atmosphere-only weather forecast models represent ocean and wave effects through sea-state independent parametrizations, coupled multi-model systems capture sea-state dynamics by integrating feedbacks between the atmosphere, ocean and wave model components. Here, we investigate the sensitivity of extreme surface wind speeds to air–sea exchanges at the kilometre scale using coupled and uncoupled configurations of the Met Office’s UK Regional Coupled Environmental Prediction system. The case period includes the passage of extra-tropical cyclones Helen, Ali, and Bronagh, which brought maximum gusts of 36 ms−1 over the UK. Compared with the atmosphere-only results, coupling to the ocean decreases the domain-average sea-surface temperature by up to 0.5 K. Inclusion of coupling to waves reduce the 98th percentile 10-m wind speed by up to 2 ms−1 as young, growing wind waves reduce the wind speed by increasing the sea-surface aerodynamic roughness. Impacts on gusts are more modest, with local reductions of up to 1 ms−1, due to enhanced boundary-layer turbulence which partially offsets air–sea momentum transfer. Using a new drag parametrization based on the Coupled Ocean–Atmosphere Response Experiment 4.0 parametrization, with a cap on the neutral drag coefficient and reduction for wind speeds exceeding 27 ms−1, the atmosphere-only model achieves equivalent impacts on 10-m wind speeds and gusts as from coupling to waves. Overall, the new drag parametrization achieves the same 20% improvement in forecast 10-m wind-speed skill as coupling to waves, with the advantage of saving the computational cost of the ocean and wave models

Genetic differentiation and admixture between sibling allopolyploids in the Dactylorhiza majalis complex

Allopolyploidization often happens recurrently, but the evolutionary significance of its iterative nature is not yet fully understood. Of particular interest are the gene flow dynamics and the mechanisms that allow young sibling polyploids to remain distinct while sharing the same ploidy, heritage and overlapping distribution areas. By using eight highly variable nuclear microsatellites, newly reported here, we investigate the patterns of divergence and gene flow between 386 polyploid and 42 diploid individuals, representing the sibling allopolyploids Dactylorhiza majalis s.s. and D. traunsteineri s.l. and their parents at localities across Europe. We make use in our inference of the distinct distribution ranges of the polyploids, including areas in which they are sympatric (that is, the Alps) or allopatric (for example, Pyrenees with D. majalis only and Britain with D. traunsteineri only). Our results show a phylogeographic signal, but no clear genetic differentiation between the allopolyploids, despite the visible phenotypic divergence between them. The results indicate that gene flow between sibling Dactylorhiza allopolyploids is frequent in sympatry, with potential implications for the genetic patterns across their entire distribution range. Limited interploidal introgression is also evidenced, in particular between D. incarnata and D. traunsteineri. Altogether the allopolyploid genomes appear to be porous for introgression from related diploids and polyploids. We conclude that the observed phenotypic divergence between D. majalis and D. traunsteineri is maintained by strong divergent selection on specific genomic areas with strong penetrance, but which are short enough to remain undetected by genotyping dispersed neutral markers.UE FWF; P22260UE: Y66

Climatic and topographic changes since the Miocene influenced the diversification and biogeography of the tent tortoise (Psammobates tentorius) species complex in Southern Africa

Background: Climatic and topographic changes function as key drivers in shaping genetic structure and cladogenic radiation in many organisms. Southern Africa has an exceptionally diverse tortoise fauna, harbouring one-third of the world’s tortoise genera. The distribution of Psammobates tentorius (Kuhl, 1820) covers two of the 25 biodiversity hotspots in the world, the Succulent Karoo and Cape Floristic Region. The highly diverged P. tentorius represents an excellent model species for exploring biogeographic and radiation patterns of reptiles in Southern Africa. Results: We investigated genetic structure and radiation patterns against temporal and spatial dimensions since the Miocene in the Psammobates tentorius species complex, using multiple types of DNA markers and niche modelling analyses. Cladogenesis in P. tentorius started in the late Miocene (11.63–5.33 Ma) when populations dispersed from north to south to form two geographically isolated groups. The northern group diverged into a clade north of the Orange River (OR), followed by the splitting of the group south of the OR into a western and an interior clade. The latter divergence corresponded to the intensifcation of the cold Benguela current, which caused western aridifcation and rainfall seasonality. In the south, tectonic uplift and subsequent exhumation, together with climatic fuctuations seemed responsible for radiations among the four southern clades since the late Miocene. We found that each clade occurred in a habitat shaped by diferent climatic parameters, and that the niches difered substantially among the clades of the northern group but were similar among clades of the southern group. Conclusion: Climatic shifts, and biome and geographic changes were possibly the three major driving forces shaping cladogenesis and genetic structure in Southern African tortoise species. Our results revealed that the cladogenesis of the P. tentorius species complex was probably shaped by environmental cooling, biome shifts and topographic uplift in Southern Africa since the late Miocene. The Last Glacial Maximum (LGM) may have impacted the distribution of P. tentorius substantially. We found the taxonomic diversify of the P. tentorius species complex to be highest in the Greater Cape Floristic Region. All seven clades discovered warrant conservation attention, particularly Ptt-B–Ptr, Ptt-A and Pv-