American Studies As a Way of Life

American Studies As a Way of Lif

Optimizing poly (ADP-ribose) polymerase inhibition through combined epigenetic and immunotherapy

Triple‐negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor survival outcomes. Currently, there are no targeted therapies available for TNBCs despite remarkable progress in targeted and immune‐directed therapies for other solid organ malignancies. Poly (ADP‐ribose) polymerase inhibitors (PARPi) are effective anticancer drugs that produce good initial clinical responses, especially in homologous recombination DNA repair‐deficient cancers. However, resistance is the rule rather than the exception, and recurrent tumors tend to have an aggressive phenotype associated with poor survival. Many efforts have been made to overcome PARPi resistance, mostly by targeting genes and effector proteins participating in homologous recombination that are overexpressed during PARPi therapy. Due to many known and unknown compensatory pathways, genes, and effector proteins, overlap and shared resistance are common. Overexpression of programmed cell death‐ligand 1 (PD‐L1) and cancer stem cell (CSC) sparing are novel PARPi resistance hypotheses. Although adding programmed cell death‐1 (PD‐1)/PD‐L1 inhibitors to PARPi might improve immunogenic cell death and be crucial for durable responses, they are less likely to target the CSC population that drives recurrent tumor growth. Lysine‐specific histone demethylase‐1A and histone deacetylase inhibitors have shown promising activity against CSCs. Combining epigenetic drugs such as lysine‐specific histone demethylase‐1A inhibitors or histone deacetylase inhibitors with PARPi/anti‐PD‐1/PD‐L1 is a novel, potentially synergistic strategy for priming tumors and overcoming resistance. Furthermore, such an approach could pave the way for the identification of new upstream epigenetic and genetic signatures.This work was supported by the National Health and Medical Research Council (Grant ID APP1068065) and the UC Deepwater Scholarship (TP)

'Cooking is for everyone?': Exploring the complexity of gendered dynamics in a cookstove intervention study in rural Malawi

BACKGROUND Household air pollution (HAP) resulting from cooking on open fires has been linked to considerable ill-health in women and girls, including chronic respiratory diseases, and has been identified as a contributor to climate change. It has been suggested that cleaner burning cookstoves can mitigate these risks, and that time saved through speedier cooking can lead to the economic empowerment of women. Despite these and other potential advantages of cookstoves, sustained use is difficult to achieve. OBJECTIVE We used qualitative methods (focus groups, interviews, observation) and the participatory methodology Photovoice in order to inform a deeper understanding of gendered social relationships within the Cooking and Pneumonia Study (CAPS) in rural Malawi. METHODS Over five CAPS villages, forty women and ten men were recruited for Photovoice activities, including image collection, village-level focus group discussion and interviews. Data were also collected from interviews with village-based community representatives. RESULTS This study facilitated a rich exploration of context-specific gendered household roles and power relations which found that there was space for contestation in seemingly entrenched and 'traditional' household responsibilities. The results suggest that the introduction of cookstoves through CAPS provided a focus for this contestation. It was evident that men and children also cooked, and that cooking played a central role in the gendered socialisation of children. However, there were no indications that time saved resulted in the empowerment of women. CONCLUSION Our findings suggest that dominant narratives of the links between gender and cookstoves are often reductive and fail to reflect the complexity of gender power relations. The use of qualitative methods incorporating Photovoice helped to facilitate an alternative 'bottom-up' view of cookstove use which demonstrated that while cookstoves may disrupt gendered relationships in target communities, positive impacts for women and girls cannot be assumed

CORPORALIZANDO A DIFERENÇA: QUESTÕES ENTRE DANÇA E ESTUDOS CULTURAIS

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The effect of vitamin K1 supplemention for 12 months on bone mineral density and indices of vitamin K status and bone turnover in adult Crohn s disease patients

peer-reviewedAdult patients with Crohn’s disease (CD), even those in remission, have been shown to have higher circulating under-g-carboxylated osteocalcin (ucOC) concentrations, a sensitive marker of vitamin K nutritional status(1), compared to age- and sex-matched healthy control subjects(2,3). Increased concentrations of ucOC in CD patients in these studies appear to be positively and negatively associated with the rate of bone turnover(3) and bone mineral density (BMD) at some sites(2), respectively. The aim of our study was to investigate whether supplementation with vitamin K1 (1000 mg/d) for 12 months had a positive effect on the rate of bone turnover and BMD in CD patients. We have previously shown that this level of supplementation maximally suppresses the degree of ucOC in CD patients(4).PUBLISHEDpeer-reviewe

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests.

BACKGROUND: We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer. METHODS: 545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing. RESULTS: The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%. CONCLUSION: No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Uptake and adherence to an online intervention for cancer-related distress: older age is not a barrier to adherence but may be a barrier to uptake

Purpose: While online interventions are increasingly explored as an alternative to therapist-based interventions for cancer-related distress, limitations to efficacy potentially include low uptake and adherence. Few predictors of uptake or adherence to online interventions have been consistently identified, particularly in individuals with cancer. This study examined rates and predictors of uptake and adherence to Finding My Way, a RCT of an online intervention versus an information-only online control for cancer-related distress. Methods: Participants were adults with cancer treated with curative intent. Adherence was assessed by login frequency, duration and activity level; analyses examined demographic, medical and psychological predictors of uptake and adherence. Results: The study enrolled 191 adults (aged 26–94 years) undergoing active treatment for cancer of any type. Uptake was highest for females and for individuals with ovarian (80%) and breast cancer (49.8%), and lowest for those with melanoma (26.5%). Adherence was predicted by older age and control-group allocation. Baseline distress levels did not predict adherence. High adherers to the full intervention had better emotion regulation and quality of life than low adherers. Conclusions: Uptake of online intervention varies according to age, gender and cancer type. While uptake was higher amongst younger individuals, once enrolled, older individuals were more likely to adhere to online interventions for cancer-related distressThis work was conducted as part of a larger clinical trial, supported by the National Health and Medical Research Council (grant number 1042942)

Whole Genome Sequencing for Determining the Source of Mycobacterium bovis Infections in Livestock Herds and Wildlife in New Zealand.

The ability to DNA fingerprint Mycobacterium bovis isolates helped to define the role of wildlife in the persistence of bovine tuberculosis in New Zealand. DNA fingerprinting results currently help to guide wildlife control measures and also aid in tracing the source of infections that result from movement of livestock. During the last 5 years we have developed the ability to distinguish New Zealand (NZ) M. bovis isolates by comparing the sequences of whole genome sequenced (WGS) M. bovis samples. WGS provides much higher resolution than our other established typing methods and greatly improves the definition of the regional localization of NZ M. bovis types. Three outbreak investigations are described and results demonstrate how WGS analysis has led to the confirmation of epidemiological sourcing of infection, to better definition of new sources of infection by ruling out other possible sources, and has revealed probable wildlife infection in an area considered to be free of infected wildlife. The routine use of WGS analyses for sourcing new M. bovis infections will be an important component of the strategy employed to eradicate bovine TB from NZ livestock and wildlife