Search Results (7)

Anaplastic thyroid cancer (ATC) is considered to be one of the most virulent, treatment-refractory malignancies. Recent molecular insights into the biology of thyroid cancer have transformed ATC management, and BRAF/MEK targeted therapy is now incorporated into guideline-based multidisciplinary care. We report visceral perforation in the setting of an extreme response to such therapy in a patient with ATC. Molecularly targeted therapy afforded a dramatic but life-threatening response to treatment. This report highlights the complexities of care for the patient and treating clinicians. Full article

Aspergillus terreus has attracted interest due to its application in industrial biotechnology, particularly for the production of itaconic acid and bioactive secondary metabolites. As related species also seem to possess a prosperous secondary metabolism, they are of high interest for genome mining and exploitation. Here, we present draft genome sequences for six species from Aspergillus section Terrei and one species from Aspergillus section Nidulantes. Whole-genome phylogeny confirmed that section Terrei is monophyletic. Genome analyses identified between 70 and 108 key secondary metabolism genes in each of the genomes of section Terrei, the highest rate found in the genus Aspergillus so far. The respective enzymes fall into 167 distinct families with most of them corresponding to potentially unique compounds or compound families. Moreover, 53% of the families were only found in a single species, which supports the suitability of species from section Terrei for further genome mining. Intriguingly, this analysis, combined with heterologous gene expression and metabolite identification, suggested that species from section Terrei use a strategy for UV protection different to other species from the genus Aspergillus. Section Terrei contains a complete plant polysaccharide degrading potential and an even higher cellulolytic potential than other Aspergilli, possibly facilitating additional applications for these species in biotechnology. Full article

Australia’s mental health system is failing young people. Calls for accountability, strategic long-term policy planning, and regional leadership have been identified as solutions to guide mental health reform. Developing system dynamics models using a participatory approach (participatory systems modelling (PSM)) is recognized as a useful method that can support decision-making for strategic reform. This paper reports evaluation findings of a youth mental health PSM process conducted in the Australian Capital Territory (ACT). Baseline and follow-up mixed-methods evaluation data were collected in 2022 across diverse stakeholder groups to investigate the feasibility, value, impact, and sustainability of PSM. Although youth mental health system reform was viewed as desirable and a necessity across all stakeholder groups, shared perceptions of disabling powerless was observed regarding their ability to influence current decision-making processes to improve the youth mental health system. This suggests greater accountability is required to support systemic reform in youth mental health. PSM offers promise in improving transparency and accountability of decision-making for youth mental health, as exemplified in the ACT. However, more support and time are required to facilitate transformational change. Future research should investigate empowerment strategies to complement the implementation of findings from dynamic models developed through PSM, as well as the effectiveness of regional youth mental health policy decision-making supported by systems modelling. Full article

Background: In 2015–2016, a large Zika virus (ZIKV) outbreak occurred in the Americas. Although the exact ZIKV antibody kinetics after infection are unknown, recent evidence indicates the rapid waning of ZIKV antibodies in humans. Therefore, we aimed to determine the levels of ZIKV antibodies more than three years after a ZIKV infection. Methods: We performed ZIKV virus neutralization tests (VNT) and a commercial ZIKV non-structural protein 1 (NS1) IgG ELISA in a cohort of 49 participants from Suriname who had a polymerase-chain-reaction-confirmed ZIKV infection more than three years ago. Furthermore, we determined the presence of antibodies against multiple dengue virus (DENV) antigens. Results: The ZIKV seroprevalence in this cohort, assessed with ZIKV VNT and ZIKV NS1 IgG ELISA, was 59.2% and 63.3%, respectively. There was, however, no correlation between these two tests. Furthermore, we did not find evidence of a potential negative influence of DENV immunity on ZIKV antibody titers. Conclusions: ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in this cohort of participants who had a confirmed previous ZIKV infection. This can have implications for future ZIKV seroprevalence studies and possibly for the duration of immunological protection after a ZIKV infection. Full article

In this contribution, the aspects of reptile and amphibian speciation that emerged from research performed over the past decade are reviewed. First, this study assesses how patterns and processes of speciation depend on knowing the taxonomy of the group in question, and discuss how integrative taxonomy has contributed to speciation research in these groups. This study then reviews the research on different aspects of speciation in reptiles and amphibians, including biogeography and climatic niches, ecological speciation, the relationship between speciation rates and phenotypic traits, and genetics and genomics. Further, several case studies of speciation in reptiles and amphibians that exemplify many of these themes are discussed. These include studies of integrative taxonomy and biogeography in South American lizards, ecological speciation in European salamanders, speciation and phenotypic evolution in frogs and lizards. The final case study combines genomics and biogeography in tortoises. The field of amphibian and reptile speciation research has steadily moved forward from the assessment of geographic and ecological aspects, to incorporating other dimensions of speciation, such as genetic mechanisms and evolutionary forces. A higher degree of integration among all these dimensions emerges as a goal for future research. Full article

As Paul Fussell has shown, the First World War was a watershed moment for 20th century British history and culture. While the role of the 36th (Ulster) Division in the Battle of the Somme has become a part of unionist iconography in what is now Northern Ireland, the experience of southern or nationalist Irish soldiers in the war remains underrepresented. Sebastian Barry’s 2005 novel, A Long Long Way is one attempt to correct this historical imbalance. This article will examine how Barry represents the relationship between the First World War and the 1916 Easter Rising through the eyes of his politically-conflicted protagonist, Willie Dunne. While the novel at first seems to present a common war experience as a means of healing political divisions between Ireland and Britain, this solution ultimately proves untenable. By the end of the novel, Willie’s hybrid English–Irish identity makes him an outcast in both places, even as he increasingly begins to identify with the Irish nationalist cause. Unlike some of Barry’s other novels, A Long Long Way does not present a disillusioned version of the early 20th century Irish nationalism. Instead, Willie sympathizes with the rebels, and Barry ultimately argues for a more inclusive Irish national identity. Full article

Menopause is associated with health concerns including vasomotor symptoms, vulvar/vaginal atrophy (VVA), and osteoporosis. Estrogen therapy or combined estrogen-progestin therapy (EPT) are primary treatment options for menopausal symptom relief and osteoporosis prevention. Because EPT has been associated with some safety/tolerability concerns relating to undesirable effects of estrogen and progestin, alternative options are needed. The tissue selective estrogen complex (TSEC) is a novel class of agents pairing a selective estrogen receptor modulator (SERM) with 1 or more estrogens. The TSEC combines the established efficacy of estrogens on menopausal symptoms and bone with the protective effects of a SERM on the reproductive tract. The pairing of bazedoxifene (BZA) with conjugated estrogens (CE) has been evaluated in a series of phase 3 clinical trials. BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg have shown efficacy in reducing the frequency and severity of hot flushes, relieving VVA symptoms, and maintaining bone mass while protecting the endometrium and breast. These BZA/CE doses have been associated with a favorable safety/tolerability profile, with higher rates of cumulative amenorrhea and lower incidences of breast pain than those reported for EPT. Thus, BZA/CE may be a promising alternative to conventional EPT for treating non-hysterectomized, postmenopausal women. Full article