The booster rollout is happening at a time when the NHS is already under huge pressures, and NHS trust leaders are warning of big challenges, particularly workforce shortages, writes Chris Hopson
Mouse syngeneic tumor models are widely used tools to demonstrate activity of novel anti-cancer immunotherapies. Despite their widespread use, a comprehensive view of their tumor-immune compositions ...and their relevance to human tumors has only begun to emerge. We propose each model possesses a unique tumor-immune infiltrate profile that can be probed with immunotherapies to inform on anti-tumor mechanisms and treatment strategies in human tumors with similar profiles. In support of this endeavor, we characterized the tumor microenvironment of four commonly used models and demonstrate they encompass a range of immunogenicities, from highly immune infiltrated RENCA tumors to poorly infiltrated B16F10 tumors. Tumor cell lines for each model exhibit different intrinsic factors in vitro that likely influence immune infiltration upon subcutaneous implantation. Similarly, solid tumors in vivo for each model are unique, each enriched in distinct features ranging from pathogen response elements to antigen presentation machinery. As RENCA tumors progress in size, all major T cell populations diminish while myeloid-derived suppressor cells become more enriched, possibly driving immune suppression and tumor progression. In CT26 tumors, CD8 T cells paradoxically increase in density yet are restrained as tumor volume increases. Finally, immunotherapy treatment across these different tumor-immune landscapes segregate into responders and non-responders based on features partially dependent on pre-existing immune infiltrates. Overall, these studies provide an important resource to enhance our translation of syngeneic models to human tumors. Future mechanistic studies paired with this resource will help identify responsive patient populations and improve strategies where immunotherapies are predicted to be ineffective.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We are not only what we eat, but how. This article examines the 1970s' morality politics of spork usage that accompanied the rollout of rice in school lunches. I argue that these discourses about the ...material culture and etiquette of eating reflect the economic and political context of 1970s Japan and (re)emergent tensions about national identity and the role of children's diet and table manners in determining Japan's future. Japan's national school lunch program is a critical site of "making Japan." Schoolchildren and teachers generally eat identical meals in their classrooms, serving and cleaning up after each other. Revived in 1946 by the Occupation, the program was nearly universal in public elementary and middle schools by the 1960s. Meals were mostly bread, milk, and soup, stew, etc. The spork was the standard utensil. Cheap, multipurpose, and hygienic, it was a rational mass-catering solution. In the mid-1970s, simultaneous to the introduction of rice to the menu, the spork became the villain in a morality play about children's eating habits and the nation's fate. Culturalist pundits warned that sporks hindered development of the special dexterity, cleverness, and sensitivity that made Japan superior among the nations of the world.
You might be saying, “Hold on, I don't even know what I'm passionate about.”
If you're looking to create positive change, see how the lean process can enable your journey of self‐discovery. Start ...small, and Build, Measure, and Learn!
Stage IIIA-N2 non-small cell lung cancer (NSCLC) is a heterogeneous group with different potential therapeutic approaches. Treatment is typically multimodal with either surgical resection after ...neoadjuvant chemotherapy and/or radiation or concurrent chemotherapy and radiation if unresectable. Despite the multimodal treatment and early stage, cure rates have traditionally been low. The introduction of immunotherapy changed the treatment landscape for NSCLC in all stages, and the introduction of immunotherapy in early-stage lung cancer has improved event free survival and overall survival. Tyrosine Kinase inhibitors (TKIs) have also improved outcomes in early-stage mutation-driven NSCLC. Optimal treatment choice and sequence is increasingly becoming based upon personalized factors including clinical characteristics, comorbidities, programmed death-ligand 1 (PD-L1) score, and the presence of targetable mutations. Despite encouraging data from multiple trials, the optimal multimodal sequence of stage IIIA-N2 NSCLC treatment remains unresolved and warrants further investigation. This review article summarizes recent major clinical trials of neoadjuvant and adjuvant treatment including stage IIIA-N2 NSCLC with a focus on immunotherapy and TKIs.
Patients with chronic obstructive pulmonary disease (COPD) often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU) and costs.
To describe the ...comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.
A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted. COPD patients aged 40-89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected. Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis. All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.
Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities. Congestive heart failure (CHF), coronary artery disease, and cerebrovascular disease (CVA) had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively;
<0.0001); other comorbidities examined had moderate associations. CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively;
<0.0001); other comorbidities examined (except chronic kidney disease CKD, obesity, and osteoarthritis) had moderate associations. All comorbidities assessed (except obesity and CKD) were associated with higher all-cause costs (mean ratio range: 1.07-1.54,
<0.0001). CHF, sleep apnea, anxiety, and osteoporosis were associated with higher COPD-related costs (mean ratio range: 1.08-1.67,
<0.0001), while CVA, CKD, obesity, osteoarthritis, and type 2 diabetes were associated with lower COPD-related costs.
This study confirms that specific comorbidities among COPD patients add significant burden with higher HCRU and costs compared to patients without these comorbidities. Payers may use this information to develop tailored therapeutic interventions for improved management of patients with specific comorbidities.
Utilizing the work of Wilfred Bion, Harry Stack Sullivan, and other theorists and practitioners, as well as philosophers and students of race in America, this article argues that racism/white ...supremacy sabotages our work, and yet is fundamental to our way of doing, being, and thinking in our society. As a result of the centrality of racism/white supremacy, the author lays out four challenges which, if met, will aid in overcoming racism/white supremacy: (a) the first challenge of denial, (b) the second challenge of impaired empathy (and the failure to think), (c) the experience of shame, and (d) the denial of death. The article discusses each of these and concludes with a word on the possibility of passion-if we are able to overcome racism/white supremacy.
This article explores the history and politics of American-funded food demonstration buses ("kitchen cars") in postwar Japan. Their express mission was to transform the Japanese national diet. I make ...two primary arguments. First, at least in the short to medium term, the kitchen cars were a win-win for both the United States and Japan. On the one hand, Japan benefited because the kitchen cars taught Japanese women how to cook cheap, nutritious, mostly easy dishes to improve the health of their families and the nation. On the other hand, these menus were planned specifically to increase consumption of American agricultural products, especially wheat, soy, and corn. For US agricultural and political interests, in addition to supporting the economic recovery and political stability of a Cold War ally, the kitchen cars - along with the school lunch program - were instrumental in teaching Japan to accept and consume American produce. My second argument concerns the reasons for the kitchen cars' success. I identify the following two factors: staffing by mostly female professional nutritionists, who combined authority with approachability for the kitchen cars' main audiences of middle-aged, married women; and the kitchen cars' mobility, which allowed them to reach even remote villages and hamlets.
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