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Introduction: Healthcare professionals frequently experience work-related fatigue, which may jeopardize their health and put patient safety at risk. In this study, we applied a machine learning (ML) approach based on data collected from a smartwatch to construct prediction models of work-related fatigue for emergency clinicians.Methods: We conducted this prospective study at the emergency department (ED) of a tertiary teaching hospital from March 10–June 20, 2021, where we recruited physicians, nurses, and nurse practitioners. All participants wore a commercially available smartwatch capable of measuring various physiological data during the experiment. Participants completed the Multidimensional Fatigue Inventory (MFI) web form before and after each of their work shifts. Wecalculated and labeled the before-and-after-shift score differences between each pair of scores. Using several tree-based algorithms, we constructed the prediction models based on features collected from the smartwatch. Records were split into training/validation and testing sets at a 70∶30 ratio, and we evaluated the performances using the area under the curve (AUC) measure of receiver operating characteristic on the test set.Results: In total, 110 participants were included in this study, contributing to a set of 1,542 effective records. Of these records, 85 (5.5%) were labeled as having work-related fatigue when setting the MFI difference between two standard deviations as the threshold. The mean age of the participants was 29.6. Most of the records were collected from nurses (87.7%) and females (77.5%). We selected a union of 31 features to construct the models. For total participants, CatBoost classifier achieved the best performances of AUC (0.838, 95% confidence interval [CI] 0.742–0.918) to identify work-related fatigue. By focusing on a subgroup of nurses

The epidermis is the outermost layer of skin. Here, we used targeted lipid profiling to characterize the biogeographic alterations of human epidermal lipids across 12 anatomically distinct body sites, and we used single-cell RNA-Seq to compare keratinocyte gene expression at acral and nonacral sites. We demonstrate that acral skin has low expression of EOS acyl-ceramides and the genes involved in their synthesis, as well as low expression of genes involved in filaggrin and keratin citrullination (PADI1 and PADI3) and corneodesmosome degradation, changes that are consistent with increased corneocyte retention. Several overarching principles governing epidermal lipid expression were also noted. For example, there was a strong negative correlation between the expression of 18-carbon and 22-carbon sphingoid base ceramides. Disease-specific alterations in epidermal lipid gene expression and their corresponding alterations to the epidermal lipidome were characterized. Lipid biomarkers with diagnostic utility for inflammatory and precancerous conditions were identified, and a 2-analyte diagnostic model of psoriasis was constructed using a step-forward algorithm. Finally, gene coexpression analysis revealed a strong connection between lipid and immune gene expression. This work highlights (a) mechanisms by which the epidermis is uniquely adapted for the specific environmental insults encountered at different body surfaces and (b) how inflammation-associated alterations in gene expression affect the epidermal lipidome.

Drawing on a five-ethical principles framework, this study examines how the thirteen recruited doctoral students across disciplines in Hong Kong interpret the idea of and experience "exploitative supervision". Findings reveal that doctoral students' lived experiences of exploitation are expressed in five different themes: autonomy exploitation, justice exploitation, fidelity exploitation, beneficent exploitation, and non-maleficence exploitation. The phenomenon was scaffolded through a Foucauldian perspective on power relations. Varied understandings of academic exploitation among doctoral students point to an urgent need to take reference from the employment and labor law to outline the fundamental rights of doctoral students, set up a probation period for the matching of supervisor-supervisee, and establish a higher-level independent inquiry to handle academic exploitation.

Surgical excision is standard-of-care for primary invasive melanoma, but best care can be unclear for patients who are surgically high-risk or for whom resection may be excessively morbid. Alternatives to surgical excision have emerged for treatment of metastatic melanoma but have not yet been explored for primary invasive melanoma. Two elderly patients with primary invasive melanoma with many medical co-morbidities who were not surgical candidates were determined to be appropriate candidates for an intralesional IL-2 based regimen. Herein we report their clinical and histological outcome. An intralesional-based regimen (intralesional IL-2, topical imiquimod cream 5%, and tretinoin cream 0.1% under occlusion to the treatment site) was administered over the course of six to seven weeks, followed by two weeks of topical-only therapy. A complete response was seen after eight to nine weeks of treating invasive melanomas that were ≥1.85 mm and 5.5 mm thick. For patients with primary invasive melanoma on high morbidity sites and patients who are poor surgical candidates, a neoadjuvant intralesional IL-2-based approach may be a reasonable alternative. The two cases presented here suggest that alternative intralesional-based treatment modalities may minimize the size of the excision site and can be associated with complete histological clearance of invasive melanoma.

The growing complexity of doing a PhD necessarily demands candidates to robustly exercise their agency in navigating the doctoral journey. However, the conceptualisation of how students use their agency across multiple facets of their studies has yet to receive due scholarly attention. Drawing on the subject-centred sociocultural view on agency, this study analysed life story interviews conducted with 16 doctoral students in Hong Kong. Findings show that participants' agency was manifested both in socially and collectively organised enterprises (proactive engagement in a wide array of developmental opportunities, responsiveness to situational research problems, contestation against unsupportive institutional cultures) and as individual-level strategic perspectives and actions (self-management of everyday emotions, imaginative construction of post-graduation prospects). Concurrently, the results shed light on the inextricable and complex linkages between the enactment of agency and the personal, relational, institutional, and broader higher education conditions delimiting students' lived experiences of candidature. Implications for educational practices and future research beneficial to develop doctoral agency are discussed.

Is noun dominance in early lexical acquisition a widespread or a language-specific phenomenon? Thirty Singaporean bilingual English-Mandarin learning toddlers and their mothers were observed in a mother-child play interaction. For both English and Mandarin, toddlers' speech and reported vocabulary contained more nouns than verbs across book reading and toy playing. In contrast, their mothers' speech contained more verbs than nouns in both English and Mandarin but differed depending on the context of the interaction. Although toddlers demonstrated a noun bias for both languages, the noun bias was more pronounced in English than in Mandarin. Together, these findings support early noun dominance as a widespread phenomenon in the lexical acquisition debate but also provide evidence that language specificity also plays a minor role in children's early lexical development.

PurposeResident physician mistreatment and burnout are widespread issues in medical training, but the association between the two remains unclear. This study examines the prevalence and types of mistreatment among resident physicians in core specialties and its association with burnout syndrome as well as feelings of depression/anxiety.MethodsA cross-sectional, survey-based observational study of medical residents was conducted at the University of California, Davis Medical Center in 2014. Current residents (PGY2 or higher) in the internal medicine, family medicine, obstetrics/gynecology, surgery, and pediatrics programs completed anonymous questionnaires addressing topics such as workplace mistreatment, feelings of depression/anxiety, and stress management. Burnout was measured using the Maslach Burnout Inventory.ResultsForty-four out of 105 residents (41.9%) witnessed mistreatment of their co-residents while 26 residents (24.8%) disclosed personal accounts of mistreatment. Seventy-one percent of residents met the criteria for burnout. Residents who had been personally mistreated were almost eight times more likely to report burnout (OR 7.6, 95% CI = 1.7-34.4) and almost four times more likely to report symptoms of anxiety and depression (OR 3.8, 95% CI = 1.6-9.1). Public belittlement or humiliation was the most common type of mistreatment.ConclusionEncountering mistreatment was associated with higher rates of burnout, as well as depression/anxiety. While it is uncertain if mistreatment in the workplace has a causative impact on burnout syndrome, the findings reveal the need to address work-related environmental factors that may contribute to both resident physician mistreatment and burnout.

Drawing on a five-ethical principles framework, this study examines how the thirteen recruited doctoral students across disciplines in Hong Kong interpret the idea of and experience 'exploitative supervision'. Findings reveal that doctoral students' lived experiences of exploitation are expressed in five different themes: autonomy exploitation, justice exploitation, fidelity exploitation, beneficent exploitation, and non-maleficence exploitation. The phenomenon was scaffolded through a Foucauldian perspective on power relations. Varied understandings of academic exploitation among doctoral students point to an urgent need to take reference from the employment and labor law to outline the fundamental rights of doctoral students, set up a probation period for the matching of supervisor-supervisee, and establish a higher-level independent inquiry to handle academic exploitation., Author(s): Michelle W. T. Cheng [sup.1] , Man-Lai Leung [sup.1] Author Affiliations: (1) grid.419993.f, 0000 0004 1799 6254, Graduate School, The Education University of Hong Kong, , B4-G/F-02, 10 Lo [...]

To explore effective growth mindset intervention that is applicable for the higher education setting, study 1 conducted a systematic review to analyze relevant literature published between 2010 and 2021. We identified 13 papers and synthesized the results of these studies to understand how the intervention was designed, conducted, and evaluated, pointing out the lack of attention to visual images as mindset intervention in the existing literature. Accordingly, in study 2, a set of infographic materials was developed and delivered to thirty participants recruited in a university to cultivate a growth mindset. The participants were randomly assigned to an experimental or control group. To measure the effectiveness of the intervention, participants are required to complete a pre-and post-survey. Significant differences were found between the two groups after 6-week intervention, as the experimental group perceived intelligence significantly more malleable. Weekly reflections were analyzed to evaluate the impacts of the designed materials.

Scurvy is a clinical syndrome, resulting from ascorbic acid deficiency. Prevalence of the condition is now extremely low in the Western population and its diagnosis can be challenging without a high index of suspicion. When cases do present, they are often misdiagnosed initially. Therefore, a thorough history, physical exam, and laboratory evaluation are key to showing this now rare but extremely well-known disease. We report a case of scurvy manifesting as persistent non-healing lower-extremity ulcerations, initially mistaken for pyoderma gangrenosum. The patient responded to appropriate replacement therapy, but ulcers were slow to heal. As was the case in our patient, symptom reversal may require additional nutritional replacement. We encourage physicians to consider nutritional deficiencies in their differential diagnoses and highlight the incidence of malnutrition in the proper clinical setting to avoid diagnostic delay.

Actinic keratosis (AK) is a precancerous skin lesion that is common in HIV-positive patients. Without effective treatment, AKs can progress to squamous cell carcinoma. Ingenol mebutate, a PKC agonist, is a US Food and Drug Administration-approved (FDA-approved) topical treatment for AKs. It can induce reactivation of latent HIV transcription in CD4+ T cells both in vitro and ex vivo. Although PKC agonists are known to be potent inducers of HIV expression from latency, their effects in vivo are not known because of the concerns of toxicity. Therefore, we sought to determine the effects of topical ingenol mebutate gel on the HIV transcription profile in HIV-infected individuals with AKs, specifically in the setting of suppressive antiretroviral therapy (ART). We found that AKs cleared following topical application of ingenol mebutate and detected marginal changes in immune activation in the peripheral blood and in skin biopsies. An overall increase in the level of HIV transcription initiation, elongation, and complete transcription was detected only in skin biopsies after the treatment. Our data demonstrate that application of ingenol mebutate to AKs in ART-suppressed HIV-positive patients can effectively cure AKs as well as disrupt HIV latency in the skin tissue microenvironment in vivo without causing massive immune activation.

Eosinophilic fasciitis is a rare connective tissue disorder characterized by inflammation of the fascia that leads to painful, indurated skin. Because of its variable clinical presentation and overlap with conditions, such as morphea, the diagnosis of eosinophilic fasciitis can be challenging and relies on clinical presentation, histopathologic and laboratory analysis, and response to therapy. Herein, we present an unusual, solitary, isolated plaque with pathologic features and response to therapy most consistent with eosinophilic fasciitis.

Past studies revealed that Resident Assistants' (RAs) behavioural patterns are related to experiences and life outcomes of student residents. In this paper, the researchers aimed to investigate the struggles that new RAs encounter in university residential halls in Hong Kong, and to provide practical recommendations based on the findings. Photovoice was adopted to facilitate the participatory approach of the study; and six new RAs were recruited from different residential halls in a university for one semester to co-construct reliable knowledge. Four domains of struggles were identified in the study; difficulties to blend in, levels of involvement, workloads and performance, and role ambiguity. Further research is needed in different contexts to provide more insights to refine policies and approaches for better RAs' residential environment, as it is believed that by improving their residential experiences, it can further enhance students' residential experiences and foster positive residence life outcomes.

A major problem in human cognition is to understand how newly acquired information and long-standing beliefs about the environment combine to make decisions and plan behaviors. Over-dependence on long-standing beliefs may be a significant source of suboptimal decision-making in unusual circumstances. While the contribution of long-standing beliefs about the environment to search in real-world scenes is well-studied, less is known about how new evidence informs search decisions, and it is unclear whether the two sources of information are used together optimally to guide search. The present study expanded on the literature on semantic guidance in visual search by modeling a Bayesian ideal observer's use of long-standing semantic beliefs and recent experience in an active search task. The ability to adjust expectations to the task environment was simulated using the Bayesian ideal observer, and subjects' performance was compared to ideal observers that depended on prior knowledge and recent experience to varying degrees. Target locations were either congruent with scene semantics, incongruent with what would be expected from scene semantics, or random. Half of the subjects were able to learn to search for the target in incongruent locations over repeated experimental sessions when it was optimal to do so. These results suggest that searchers can learn to prioritize recent experience over knowledge of scenes in a near-optimal fashion when it is beneficial to do so, as long as the evidence from recent experience was learnable.

Can residential experiences help undergraduates develop holistic competencies? To answer this question, a study was conducted based on the insights of 211 residents in Hong Kong. Deductive and inductive content analyses were respectively used to examine residence life outcomes, particularly in holistic competencies, and to categorise the types of residential experiences deemed to be effective for these outcomes. Results revealed that participation in hall activities led to the development of residence life outcomes, including justice, humanity, wisdom, courage, transcendence, and wellbeing. Furthermore, planning/organising hall activities greatly improved students' sense of justice while interpersonal dynamics facilitated the improvement of humanity only. The analyses indicated that students without specific engagement in hall activities were also able to develop temperance, particularly in self-regulation. Recommendations are suggested based on the analyses. It is hoped that this study might help inform policy-making processes to provide better residential environment that is beneficial to student holistic development.

ImportanceInnovative, online models of specialty-care delivery are critical to improving patient access and outcomes.ObjectiveTo determine whether an online, collaborative connected-health model results in equivalent clinical improvements in psoriasis compared with in-person care.Design, setting, and participantsThe Patient-Centered Outcomes Research Institute Psoriasis Teledermatology Trial is a 12-month, pragmatic, randomized clinical equivalency trial to evaluate the effect of an online model for psoriasis compared with in-person care. Participant recruitment and study visits took place at multicenter ambulatory clinics from February 2, 2015, to August 18, 2017. Participants were adults with psoriasis in Northern California, Southern California, and Colorado. The eligibility criteria were an age of 18 years or older, having physician-diagnosed psoriasis, access to the internet and a digital camera or mobile phone with a camera, and having a primary care physician. Analyses were on an intention-to-treat basis.InterventionsParticipants were randomized 1:1 to receive online or in-person care (148 randomized to online care and 148 randomized to in-person care). The online model enabled patients and primary care physicians to access dermatologists online asynchronously. The dermatologists provided assessments, recommendations, education, and prescriptions online. The in-person group sought care in person. The frequency of online or in-person visits was determined by medical necessity. All participants were exposed to their respective interventions for 12 months.Main outcomes and measuresThe prespecified primary outcome was the difference in improvement in the self-administered Psoriasis Area and Severity Index (PASI) score between the online and in-person groups. Prespecified secondary outcomes included body surface area (BSA) affected by psoriasis and the patient global assessment score.ResultsOf the 296 randomized participants, 147 were women, 149 were men, 187 were white, and the mean (SD) age was 49 (14) years. The adjusted difference between the online and in-person groups in the mean change in the self-administered PASI score during the 12-month study period was -0.27 (95% CI, -0.85 to 0.31). The difference in the mean change in BSA affected by psoriasis between the 2 groups was -0.05% (95% CI, -1.58% to 1.48%). Between-group differences in the PASI score and BSA were within prespecified equivalence margins, which demonstrated equivalence between the 2 interventions. The difference in the mean change in the patient global assessment score between the 2 groups was -0.11 (95% CI, -0.32 to 0.10), which exceeded the equivalence margin, with the online group displaying greater improvement.Conclusions and relevanceThe online, collaborative connected-health model was as effective as in-person management in improving clinical outcomes among patients with psoriasis. Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic diseases.Trial registrationClinicalTrials.gov Identifier: NCT02358135.

BackgroundPyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood.ObjectiveUse data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology.MethodsTen PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR.ResultsAll PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype.LimitationsSmall sample size was the main limitation.ConclusionWe put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.

BackgroundCathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients.MethodsSerum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development.ResultsSerum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6-18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients.ConclusionCo-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

Despite characteristic features, psoriasis can mimicother dermatologic conditions, such as seborrheicdermatitis, lichen simplex chronicus, and certainnutritional deficiencies such as pellagra. We present apatient with a longstanding history of severe plaquepsoriasis who presented with disfiguring scaly plaquesinvolving greater than 80% body surface area. Thepatient’s disease was minimally responsive to multipletherapies. Repeat punch biopsies demonstratedparakeratosis, psoriasiform hyperplasia, and dilatedblood vessels consistent with psoriasis. Given atypicalclinical features and overall poor treatment responseadditional work up was obtained. A serum nutritionalpanel was consistent with niacin deficiency andthe patient later revealed extensive alcohol intake.A diagnosis of concurrent pellagra was made andthe patient was started on niacin supplementationand instructed to reduce alcohol intake, whilecontinuing adalimumab and high potency topicalsteroids. Within two weeks, his disease had markedlyimproved. Pellagra presents characteristically with aphotosensitivity dermatitis that may appear clinicallyand histologically similar to psoriasis. It is importantto maintain an index suspicion for a secondarypathology in treatment-resistant psoriasis.

This systematic literature review is to find and showcase studies that detail the design of student-centered in-class undergraduate courses that target the development of generic skills in a discipline-specific context. Five studies met the inclusion criteria and were among the 25-year search span. A summary of the selected studies and their findings are presented, alongside an examination of the effectiveness of the various course designs and how generic skills development has been incorporated across different academic disciplines. Challenges and limitations among both selected studies and situation of generic skills development in higher education will also be discussed.

In this expository essay, we introduce some elements of the study of groups by analysing the braid pattern on a knitted blanket. We determine that the blanket features pure braids with a minimal number of crossings. Moreover, we determine polynomial invariants associated to the links obtained by closing the braid patterns of the blanket. [ABSTRACT FROM AUTHOR]

Previous studies have examined Hong Kong's hybrid regime by investigating the interactions among activists, the local government, and the Chinese national government. This article adopts the lens of contentious politics and a multi-level approach to understand regime evolution within the local-national-regional-global nexus. It presents an original dataset that records movement tactics and state responses in four major protests and delineates three phases of state-society contention between 2003 and 2020. It explains regime evolution by highlighting five intertwining factors: activists' tactical learning; organisational ecology in civil society; state repression strategies; regional politics in Greater China; and international political economy. It finds that the first phase (2003–2012) was characterised by an increasing use of disruptive tactics, an emergent call for de-centred mobilisation, and a limited deployment of state security forces. The second phase (2013–2015) exhibited nascent applications of violent tactics, while the state employed more forceful police repression, re-engineered the electoral field, and sponsored counter-mobilisation. The most recent phase (2016–2020) showed activists' intensified use of violent tactics and a strong intention to seek international support. The state responded to local threats and international pressure with violent crackdowns and stricter institutional arrangements, which has resulted in an electoral authoritarian regime that is less-than-competitive. [ABSTRACT FROM AUTHOR]

Tissue clearing methods promise to provide exquisite three-dimensional imaging information; however, there is a need for simplified methods for lower resource settings and for non-fluorescence based phenotyping to enable light microscopic imaging modalities. Here we describe the simplified CLARITY method (SCM) for tissue clearing that preserves epitopes of interest. We imaged the resulting tissues using light sheet microscopy to generate rapid 3D reconstructions of entire tissues and organs. In addition, to enable clearing and 3D tissue imaging with light microscopy methods, we developed a colorimetric, non-fluorescent method for specifically labeling cleared tissues based on horseradish peroxidase conversion of diaminobenzidine to a colored insoluble product. The methods we describe here are portable and can be accomplished at low cost, and can allow light microscopic imaging of cleared tissues, thus enabling tissue clearing and imaging in a wide variety of settings.

Prokineticin 2 (PK2) has been indicated as an output signaling molecule for the suprachiasmatic nucleus (SCN) circadian clock. Most of these studies were performed with nocturnal animals, particularly mice and rats. In the current study, the PK2 and its receptor, PKR2, was cloned from a species of diurnal macaque monkey. The macaque monkey PK2 and PKR2 were found to be highly homologous to that of other mammalian species. The mRNA expression of PK2 and PKR2 in the macaque brain was examined by in situ hybridization. The expression patterns of PK2 and PKR2 in the macaque brain were found to be quite similar to that of the mouse brain. Particularly, PK2 mRNA was shown to oscillate in the SCN of the macaque brain in the same phase and with similar amplitude with that of nocturnal mouse brain. PKR2 expression was also detected in known primary SCN targets, including the midline thalamic and hypothalamic nuclei. In addition, we detected the expression of PKR2 mRNA in the dorsal raphe nucleus (DR) of both macaque and mouse brains. As a likely SCN to dorsal raphe projection has previously been indicated, the expression of PKR2 in the raphe nuclei of both macaque and mouse brain signifies a possible role of DR as a previously unrecognized primary SCN projection target.

The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy.