Angela Hill

, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined 'tumour microregions' as spatially distinct cancer cell clusters separated by stromal components. They varied in size and density among cancer types, with the largest microregions observed in metastatic samples. We further grouped microregions with shared genetic alterations into 'spatial subclones'. Thirty five tumour sections exhibited subclonal structures. Spatial subclones with distinct copy number variations and mutations displayed differential oncogenic activities. We identified increased metabolic activity at the centre and increased antigen presentation along the leading edges of microregions. We also observed variable T cell infiltrations within microregions and macrophages predominantly residing at tumour boundaries. We reconstructed 3D tumour structures by co-registering 48 serial ST sections from 16 samples, which provided insights into the spatial organization and heterogeneity of tumours. Additionally, using an unsupervised deep-learning algorithm and integrating ST and CODEX data, we identified both immune hot and cold neighbourhoods and enhanced immune exhaustion markers surrounding the 3D subclones. These findings contribute to the understanding of spatial tumour evolution through interactions with the local microenvironment in 2D and 3D space, providing valuable insights into tumour biology.

Patients experiencing an acute decompensation of schizophrenia or bipolar disorder often present in an agitated state. Agitation presents a barrier to therapy, interrupting the typical physician-patient alliance and creating a disruptive, even hazardous, environment. Rapid assessment and effective treatment are necessary to manage agitation and, potentially, to shorten the time to recovery.One hundred forty-eight acutely agitated patients received either: rapid initial dose escalation (RIDE) in which up to 40 mg of oral olanzapine was allowed on days 1 and 2, up to 30 mg on days 3 and 4, and 5 to 20 mg thereafter; or usual clinical practice (UCP) in which patients received 10 mg/d olanzapine plus up to 4 mg lorazepam on days 1 and 2, up to 2 mg on days 3 and 4, and olanzapine 5 to 20 mg/d thereafter. The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC: poor impulse control, tension, hostility, uncooperativeness, and excitement) measured at 24 hours was the primary measure. Secondary assessments of agitation and safety were also performed.Agitation improved significantly from baseline for both treatment groups; however, improvement with the RIDE strategy was superior to UCP. The RIDE group improvement was superior on the primary efficacy measure (PANSS-Excited) at 24 hours; it was superior on all agitation measures at the end of double-blind treatment. Both treatments were well tolerated, with no clinically significant differences in safety measures. Treatment was not limited by oversedation and attention improved from baseline in both groups.This study demonstrates the value of olanzapine in the treatment of acutely agitated patients. A new approach to olanzapine dosing that expands the initial dose range up to 40 mg/d may offer superior efficacy in rapidly and effectively controlling the symptoms of agitation.

The objective of this study was to determine if the orally disintegrating tablet formulation of olanzapine, Zyprexa Zydis, would facilitate antipsychotic medication compliance in acutely ill, non-compliant patients. Eighty-five acutely ill patients with schizophrenia or schizoaffective disorder who met medication non-compliance criteria received open-label olanzapine orally disintegrating tablets (1020 mgd) for up to 6 wk. Improvement in medication compliance was assessed using various rating scales to measure changes in psychopathology, medication-taking and compliance attitudes, and nursing care burden. Safety variables were also measured. Significant improvement from baseline was demonstrated in the Positive and Negative Syndrome Scale total score at Week 1 and subsequently (p0.001). Significant improvement from baseline was also seen in various scales measuring medication compliance, attitude, and nursing care burden (p0.05). Olanzapine orally disintegrating tablets were well-tolerated. Olanzapine orally disintegrating tablets may benefit acutely ill, non-compliant schizophrenic patients by facilitating acceptance of active antipsychotic drug therapy.

Monitoring homeostasis is an essential aspect of obtaining pathophysiological insights for treating patients. Accurate, timely assessments of homeostatic dysregulation in deep tissues typically require expensive imaging techniques or invasive biopsies. We introduce a bioresorbable shape-adaptive materials structure that enables real-time monitoring of deep-tissue homeostasis using conventional ultrasound instruments. Collections of small bioresorbable metal disks distributed within thin, pH-responsive hydrogels, deployed by surgical implantation or syringe injection, allow ultrasound-based measurements of spatiotemporal changes in pH for early assessments of anastomotic leaks after gastrointestinal surgeries, and their bioresorption after a recovery period eliminates the need for surgical extraction. Demonstrations in small and large animal models illustrate capabilities in monitoring leakage from the small intestine, the stomach, and the pancreas.

BACKGROUND: Depressive symptoms are common in primary care, yet considerable professional controversy exists about appropriate management including the effectiveness of treatments. In addition, avoiding prescribing antidepressants at least initially is recommended. Views of patients themselves should therefore be particularly important in agreeing management strategies. OBJECTIVE: To examine lay beliefs about depressive symptoms in primary care. METHOD: A total of 23 semi-structured interviews were conducted with patients scoring positively for depression on the Hospital Anxiety and Depression Score in a primary care setting. RESULTS: Differentiating 'depression' from understandable reactions to adversity was difficult for patients. The wide range of consequences discussed included adverse effects on others, difficulties coping with feeling out of control and loss of self-identity. Negative images of depression, such as depression being a 20th century phenomenon, were pervasive. Views about medication varied. Various management strategies described included strategies of detachment, engagement in activities and 'blotting out' symptoms. CONCLUSIONS: Patients' views about depressive symptoms are significantly different from conventional medical views. A 'disease management approach' fits uncomfortably with patients' experiences. Acknowledging feelings of loss of control and loss of self-identity in consultations may be useful. The wide employment of techniques patients use to control their disorders, such as support from others, engagement in activities and working at relationships, may be useful to encourage in consultations as alternatives to the use of antidepressant medication.