Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous largescale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.Cancer forms and progresses through a series of critical transitions-from pre-malignant to malignant states, from locally contained to metastatic disease, and from treatment-responsive to treatment-resistant tumors (Figure 1). Although specifics differ across tumor types and patients, all transitions involve complex dynamic interactions between diverse pre-malignant, malignant, and non-malignant cells (e.g., stroma cells and immune cells), often organized in specific patterns within the tumor

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ABSTRACT. Objective. Supine sleep is recommended for infants to decrease the risk of sudden infant death syndrome, but many parents report that their infants seem uncomfortable supine. Many cultures swaddle infants for sleep in the supine position. Swaddled infants are said to "sleep better"; presumably they sleep longer or with fewer arousals. However, there have been no studies of the effect of swaddling on spontaneous arousals during sleep. Arousal is initiated in brainstem centers and manifests as a sequence of reflexes: from sighs to startles and then to thrashing movements. Such "brainstem arousals" may progress to full arousal, but most do not.Methods. Twenty-six healthy infants, aged 80 ؎ 7 days, were studied during normal nap times. Swaddled (cotton spandex swaddle) and unswaddled trials were alternated for each infant. Sleep state (rapid eye move- ment [REM] or quiet sleep [QS]) was determined by behavioral criteria (breathing pattern, eye movements) and electroencephalogram/electrooculogram (10 infants).Respitrace, submental and biceps electromyogram, and video recording were used to detect startles and sighs (augmented breaths). Full arousals were classified by eye opening and/or crying. Frequencies of sighs, startles, and full arousals per hour were calculated. Progression of events was calculated as percentages in each sleep state, as was duration of sleep state.Results. Swaddling decreased startles in QS and REM, full arousal in QS, and progression of startle to arousal in QS. It resulted in shorter arousal duration during REM sleep and more REM sleep.Conclusions. Swaddling has a significant inhibitory effect on progression of arousals from brainstem to full arousals involving the cortex in QS. Swaddling decreases spontaneous arousals in QS and increases the duration of REM sleep, perhaps by helping infants return to sleep spontaneously, which may limit parental intervention. For these reasons, a safe form of swaddling that allows hip flexion/abduction and chest wall excursion may help parents keep their infants in the supine sleep position and thereby prevent the sudden infant death syndrome risks associated with the prone sleep position. Pediatrics 2002;110(6). URL: http://www.pediatrics.org/cgi/content/ full/110/6/e70; sudden infant death syndrome, sighs, startles.ABBREVIATIONS. SIDS, sudden infant death syndrome; REM, rapid eye movement; QS, quiet sleep; EMG, electromyogram; EEG, electroencephalogram; EOG, electrooculogram. S upine sleeping decreases the risk for sudden infant death syndrome (SIDS). 1 However, some parents place their infants in the prone sleep position despite these recommendations. [2][3][4] Many of these parents state that their infants seem more comfortable when prone and sleep better. 4 Studies confirm that the prone position decreases frequency of arousals. [5][6][7][8][9] Swaddled infants placed on their backs are said to "sleep better," presumably meaning that they sleep longer or with fewer arousals. Parents commonly report that infants who are back sleepers "startle ...

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Infants who are inexperienced in prone sleeping have decreased ability to escape from asphyxiating sleep environments when placed prone. These observations potentially explain the increased risk associated with prone sleep in infants who are inexperienced. The increased occurrence of the face-down position in such infants is also potentially explained. These findings suggest that airway protective behaviors may be acquired through the mechanism of operant conditioning (learning).