Neoadjuvant radiotherapy (RT) is commonly used as standard treatment for rectal cancer. However, response rates are variable and survival outcomes remain poor, highlighting the need to develop new therapeutic strategies. Research is focused on identifying novel methods for sensitising rectal tumours to RT to enhance responses and improve patient outcomes. This can be achieved through harnessing tumour promoting effects of radiation or preventing development of radio-resistance in cancer cells. Many of the approaches being investigated involve targeting the recently published new dimensions of cancer hallmarks. This review article will discuss key radiation and targeted therapy combination strategies being investigated in the rectal cancer setting, with a focus on exploitation of mechanisms which target the hallmarks of cancer.

Democracy is premised on the ability of individuals, often working with others, to influence policies affecting them. However, existing theory cannot always explain why some organized efforts are more influential than others. We introduce the concept of civic feedbacks, arguing that the ways organizations engage individuals in collective action have feedback effects that shape the strategic position of organizations, the options available to leaders, and the likelihood of policy influence. The mechanisms through which civic feedbacks operate include the depth of accountability to the constituency, the network of elite relationships to which leaders subsequently have access, and their ongoing ability to recruit a committed and flexible constituency willing to engage new issues. Analyzing how these feedbacks redound to organizations over time enhances our ability to explain civic organizations’ differential rates of political influence. The concept of civic feedbacks returns organizations and organizational strategy to the center of the study of political influence.

Malnutrition and sarcopenia are prevalent in patients with head and neck squamous cell carcinoma (HNSCC). Pre-treatment sarcopenia and adverse oncological outcomes in this population are well described. The impact of myosteatosis and post-treatment sarcopenia is less well known. Patients with HNSCC (n = 125) undergoing chemoradiotherapy, radiotherapy alone and/or surgery were assessed for sarcopenia and myosteatosis, using cross-sectional computed tomography (CT) imaging at the third lumbar (L3) vertebra, at baseline and 3 months post-treatment. Outcomes were overall survival (OS) at 12 months and 5 years post-treatment. One hundred and one participants had a CT scan evaluable at one or two time points, of which sixty-seven (66 %) participants were sarcopenic on at least one time point. Reduced muscle attenuation affected 93 % (n = 92) pre-treatment compared with 97 % (n = 90) post-treatment. Five-year OS favoured those without post-treatment sarcopenia (hazard ratio, HR 0·37, 95 % CI 0·16, 0·88, P = 0·06) and those without both post-treatment myosteatosis and sarcopenia (HR 0·33, 95 % CI 0·13, 0·83, P = 0·06). Overall, rates of myosteatosis were high at both pre- and post-treatment time points. Post-treatment sarcopenia was associated with worse 5-year OS, as was post-treatment sarcopenia in those who had myosteatosis. Post-treatment sarcopenia should be evaluated as an independent risk factor for decreased long-term survival post-treatment containing radiotherapy (RT) for HNSCC.

Background: Hospital-acquired influenza (HA flu) lacks a consensus definition. However, it is known to be associated with increased inpatient morbidity and mortality. Objective: To describe the clinical course of HA flu in a cohort population. Methods: A retrospective cohort study was conducted at a tertiary-care adult and pediatric teaching hospital. Patients with HA flu during 3 seasons, 2016 through 2019, were identified from medical record information based on timing of the onset of signs and symptoms and positive virologic testing >72 hours after admission. Influenza infection was confirmed by multiplex respiratory PCR, influenza A/B PCR, or direct fluorescent antibody tests. Chart review was performed to abstract patient demographics and comorbidities, length of stay, testing, and timing to antiviral administration as well as diagnosis of pneumonia, coinfections, and 30-day mortality. Escalation of care during hospitalization was defined as a new requirement of supplemental oxygen, invasive or noninvasive ventilation, and transfer to an intensive care unit. Results: During the 3 flu seasons, 132 patients were identified with HA flu; 76 (58%) were women, 6 (4.6%) were aged <18 years, and 126 (95.4%) were adults. Annually, HA-flu patients accounted for 5%–7.8% of all patients hospitalized with laboratory-proven influenza. The median duration between hospitalization and positive flu test was 15 days, and the median length of stay after influenza diagnosis was 6 days. Antiviral treatment was received by 96% of the patients. In total, 41 patients (31%) showed radiographic evidence for pneumonia. Coinfection with either a viral or bacterial pathogen was identified in 25% of the cases. In addition, 26% of the patients experienced an escalation of care, and 20 patients (15%) were transferred to the intensive care unit after HA flu diagnosis. Furthermore, 4 deaths (3%) were attributed to influenza during their hospitalization. Conclusions: HA flu was a frequent cause for escalation in care and was associated with a mortality rate substantially higher than is typically seen in community-based populations with influenza. Coinfection was mostly related to bacteremia and pneumonia, yet not all pneumonias had an associated microbiological diagnosis other than influenza, and there was no significant association between coinfection and mortality. Future work should explore more precise definitions for HA flu as well as its complications.

Funding: None

Disclosures: None

The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.

Intimate ethnography presents a number of challenges: How could I write about my own family in a way that was true to their experience but also an “objective” report? How could I convey telling details without robbing my family of their privacy? How could I rein in my emotions to report their story, and did I pick and choose facts to protect them or to make them more sympathetic? How could I generalize from their experience to that of millions of social assistance recipients? In this Reflections essay, I consider these challenges in light of what other social scientists have said about the issues of close work with individual, sometimes vulnerable, research subjects.

Mental health services are increasingly supporting recovery-oriented practice as a basis for service delivery. There is considerable overlap between the values and approaches associated with recovery-based practice and those already endorsed as good psychiatric practice. However, these agreed principles may not be consistently applied and further steps may be needed if the reorientation of the relationship between psychiatrists and people using psychiatric services is to fully reflect recovery principles. This article describes ways in which psychiatric practice could develop, including conceptualising medication as one of many possible recovery tools that a person can actively use to support their well-being, and a range of practices available to professionals to support people in taking up an active stance in relation to medication. It also identifies recovery-supportive practices for when someone is unable to fully participate in decision-making, owing to crisis, loss of capacity or concerns about safety.