Knowing how individuals move between places is fundamental to advance our understanding of human mobility (González et al. 2008 Nature 453, 779-782. (doi:10.1038/nature06958)), improve our urban infrastructure (Prato 2009 J. Choice Model. 2, 65-100. (doi:10.1016/S1755-5345(13)70005-8)) and drive the development of transportation systems. Current route-choice models that are used in transportation planning are based on the widely accepted assumption that people follow the minimum cost path (Wardrop 1952 Proc. Inst. Civ. Eng. 1, 325-362. (doi:10.1680/ipeds.1952.11362)), despite little empirical support. Fine-grained location traces collected by smart devices give us today an unprecedented opportunity to learn how citizens organize their travel plans into a set of routes, and how similar behaviour patterns emerge among distinct individual choices. Here we study 92 419 anonymized GPS trajectories describing the movement of personal cars over an 18-month period. We group user trips by origin-destination and we find that most drivers use a small number of routes for their routine journeys, and tend to have a preferred route for frequent trips. In contrast to the cost minimization assumption, we also find that a significant fraction of drivers routes are not optimal. We present a spatial probability distribution that bounds the route selection space within an ellipse, having the origin and the destination as focal points, characterized by high eccentricity independent of the scale. While individual routing choices are not captured by path optimization, their spatial bounds are similar, even for trips performed by distinct individuals and at various scales. These basic discoveries can inform realistic route-choice models that are not based on optimization, having an impact on several applications, such as infrastructure planning, routing recommendation systems and new mobility solutions.

Pilomatricoma is a benign cutaneous tumor originatingfrom hair matrix cells. Anetodermic changes inthe skin overlying pilomatricomas are sometimesreported, although their precise mechanisms remainunknown. We present an unusual case of anetodermicpilomatricoma on the upper extremity of a 17-yearoldboy and report its clinical, histopathologic, andsonographic findings.

Trauma ICU patients may require high and/or prolonged doses of opioids and/or benzodiazepines as part of their treatment. These medications may contribute to drug physical dependence, a response manifested by withdrawal syndrome. We aimed to identify risk factors, symptoms, and clinical variables associated with probable withdrawal syndrome.

Design

Prospective exploratory observational study.

Setting

Trauma ICU in large medical center in Puerto Rico.

Participants

Fifty patients who received opioids and/or benzodiazepines for greater than or equal to 5 days.

Measurements and main results

Using an opioid/benzodiazepine withdrawal syndrome checklist developed from research in adult ICU patients, the Diagnostic and Statistical Manual of Mental Disorders-5, and the International Classification of Diseases, 10th Edition, we evaluated patients at baseline and for 72 hours after drug weaning was initiated. Patients received opioid/benzodiazepine (88%), opioid (10%), or benzodiazepine (2%). Probable withdrawal syndrome occurred in 44%, questionable withdrawal syndrome in 20%, and no withdrawal syndrome in 18 (36%). Signs that were more frequent in the probable withdrawal syndrome group were agitation, diarrhea, fever, tachypnea, lacrimation, and hyperactive delirium. Patients who developed probable withdrawal syndrome spent almost double the amount of time receiving mechanical ventilation, and length of stay was higher in both ICU and hospital when compared with patients in the other two groups. Age, cumulative opioid dose amounts, and previous drug (opioid/benzodiazepine, cannabis, cocaine, or heroin) use were associated with odds of developing withdrawal syndrome. With the addition of Richmond Agitation-Sedation Scale and delirium to the multilevel analysis, older age no longer had its protective effect, whereas increase in Richmond Agitation-Sedation Scale scores, delirium presence, and increased duration of mechanical ventilation were associated with higher odds of withdrawal syndrome.

Conclusions

We identified probable withdrawal syndrome in a sample of trauma ICU patients through observation of several associated symptoms. Significant factors associated with withdrawal syndrome found in this study should be considered when caring for patients being weaned from opioids and/or benzodiazepines. Further validation of the opioid/benzodiazepine withdrawal syndrome checklist is recommended.

BACKGROUND: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. METHODS: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. RESULTS: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. CONCLUSIONS: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.