Summary Immunotherapy is a promising area of therapy in patients with neuro-oncological malignancies. However, early-phase studies show unique challenges associated with the assessment of ...radiological changes in response to immunotherapy reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumour regression, can still occur after initial disease progression or after the appearance of new lesions. Refinement of the response assessment criteria for patients with neuro-oncological malignancies undergoing immunotherapy is therefore warranted. Herein, a multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describe immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria based on guidance for the determination of tumour progression outlined by the immune-related response criteria and the RANO working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease within 6 months of initiating immunotherapy, including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for the use of corticosteroids. We review the role of advanced imaging techniques and the role of measurement of clinical benefit endpoints including neurological and immunological functions. The iRANO guidelines put forth in this Review will evolve successively to improve their usefulness as further experience from immunotherapy trials in neuro-oncology accumulate.
Clear communication of systematic review findings will help readers and decision makers. We built on previous work to develop an approach that improves the clarity of statements to convey findings ...and that draws on Grading of Recommendations Assessment, Development and Evaluation (GRADE).
We conducted workshops including 80 attendants and a survey of 110 producers and users of systematic reviews. We calculated acceptability of statements and revised the wording of those that were unacceptable to ≥40% of participants.
Most participants agreed statements should be based on size of effect and certainty of evidence. Statements for low, moderate and high certainty evidence were acceptable to >60%. Key guidance, for example, includes statements for high, moderate and low certainty for a large effect on intervention x as: x results in a large reduction…; x likely results in a large reduction…; x may result in a large reduction…, respectively.
Producers and users of systematic reviews found statements to communicate findings combining size and certainty of an effect acceptable. This article provides GRADE guidance and a wording template to formulate statements in systematic reviews and other decision tools.
Infertility is a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. It is estimated to affect between 8 and 12% of ...reproductive-aged couples worldwide. Males are found to be solely responsible for 20–30% of infertility cases but contribute to 50% of cases overall. Secondary infertility is the most common form of female infertility around the globe, often due to reproductive tract infections. The three major factors influencing the spontaneous probability of conception are the time of unwanted non-conception, the age of the female partner and the disease-related infertility. The chance of becoming spontaneously pregnant declines with the duration before conception. The fertility decline in female already starts around 25–30 years of age and the median age at last birth is 40–41 years in most studied populations experiencing natural fertility. The disease-related infertility may affect both genders or be specific to one gender. The factors affecting both genders' fertility are hypogonadotrophic hypogonadism, hyperprolactinemia, disorders of ciliary function, cystic fibrosis, infections, systemic diseases and lifestyle related factors/diseases. Premature ovarian insufficiency, polycystic ovary syndrome, endometriosis, uterine fibroids and endometrial polyps may play a role in female infertility. Male infertility may be due to testicular and post-testicular deficiencies. Semen decline that has been observed over the years, endocrine disrupting chemicals and consanguinity are other factors that may be involved.
•8–12% of reproductive-aged couples worldwide suffer from infertility.•Males contribute to 50% of infertility cases.•The fertility decline in female already starts around 25–30 years.•Some modifiable lifestyle factors can affect fertility.
Pancreatic ductal adenocarcinoma (PDA) is among the most immune-resistant tumor types. Its unique genomic landscape shaped by oncogenic drivers promotes immune suppression from the earliest stages of ...tumor inception to subvert adaptive T cell immunity. Single-agent immune modulators have thus far proven clinically ineffective, and multi-modal therapies targeting mechanisms of immunotherapy resistance are likely needed. Here, we review novel immunotherapy strategies currently under investigation to (1) confer antigen specificity, (2) enhance T cell effector function, and (3) neutralize immunosuppressive elements within the tumor microenvironment that may be rationally combined to untangle the web of immune resistance in PDA and other tumors.
Pancreatic ductal adenocarcinoma (PDA) is among the most immune-resistant tumor types. Its unique genomic landscape shaped by oncogenic drivers promotes immune suppression from the earliest stages of tumor inception to subvert adaptive T cell immunity. Single-agent immune modulators have thus far proven clinically ineffective, and multi-modal therapies targeting mechanisms of immunotherapy resistance are likely needed. Here, we review novel immunotherapy strategies currently under investigation to (1) confer antigen specificity, (2) enhance T cell effector function, and (3) neutralize immunosuppressive elements within the tumor microenvironment that may be rationally combined to untangle the web of immune resistance in PDA and other tumors.
Uniquely bridging theory and practice, this text introduces and overviews the various domains associated with the term critical pedagogy in the field of TESOL/ELT. Critical pedagogy addresses ...concepts, values, curriculum, instructional and associated practices involved in language teaching for social justice. Bringing critical pedagogy to classroom practitioners in a practical and comprehensible way, the text is designed to help teachers get started on critically grounded work in their own teaching. Features• Textbook extracts offer direct and quick illustration of what this perspective might look like in practice• Coverage of feminist and anti-racist pedagogies; sexual identity, oppression and pedagogy; peace and environmental education; and critical English as a foreign language—and their implications for second-language teaching • Historical background• Theoretical background on language and learning• Consideration of applicability of critical/radical educational concepts and traditions to non-Western cultural contexts • A focus on issues of compromise and resistance
This original, timely, and informative text is ideal for any course on methods and approaches in TESOL.
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