Biomedical subjects

William Hill

Publications and source records attributed to William Hill.

6 recordsLinked to original sources

PubMed2026

Plasma signals of lung tumor promotion for molecular cancer prevention.

Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8+/claudin4+ alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

Humans↗

PubMed2006

Developing and validating a conceptual model of recurring problems in teaching clinic.

Recurrent problems in medical teaching clinic are common and difficult to address because of complex interpersonal dynamics. To minimize this difficulty, we developed a conceptual model that simplifies problems and identifies the root cause of tension between groups in clinic. We used recursive analysis and modeling of the data from a larger multi-site, multi-method study of problems in teaching clinic. The first dataset from this study consisted of problem lists generated and prioritized by knowledgeable insiders from each site. The second dataset was a cultural consensus analysis independently performed at each site. The final model was checked for face validity and construct validity (using model predictions versus prior data and convergent/discriminant analysis). The study was performed in five Veterans Affairs teaching clinics in the U.S. Our final model, the Perception of Care Map, is a pentagram with five critical perspectives of the clinic visit. These five perspectives are structured care, educational care, relationship-based care, algorithmic care and efficient care. Each group emphasizes one or more of these perspectives, and group locations on the conceptual map explain the observed tensions between groups. Validity of the model is high. The Perception of Care Map may be a useful adjunct for understanding and addressing recurrent problems in teaching clinic.

Ambulatory Care↗

PubMed2005

Testing the exportability of a tool for detecting operational problems in VA teaching clinics.

BACKGROUND: Recurrent operational problems in teaching clinics may be caused by the different medical preferences of patients, residents, faculty, and administrators. These preference differences can be identified by cultural consensus analysis (CCA), a standard anthropologic tool. OBJECTIVE: This study tests the exportability of a unique CCA tool to identify site-specific operational problems at 5 different VA teaching clinics. DESIGN: We used the CCA tool at 5 teaching clinics to identify group preference differences between the above groups. We averaged the CCA results for all 5 sites. We compared each site with the averages in order to isolate each site's most anomalous responses. Major operational problems were independently identified by workgroups at each site. Cultural consensus analysis performance was then evaluated by comparison with workgroup results. PARTICIPANTS: Twenty patients, 10 residents, 10 faculty, members, and 10 administrators at each site completed the CCA. Workgroups included at minimum: a patient, resident, faculty member, nurse, and receptionist or clinic administrator. APPROACH: Cultural consensus analysis was performed at each site. Problems were identified by multidisciplinary workgroups, prioritized by anonymous multivoting, and confirmed by limited field observations and interviews. Cultural consensus analysis results were compared with workgroup results. RESULTS: The CCA detected systematic, group-specific preference differences at each site. These were moderately to strongly associated with the problems independently identified by the workgroups. The CCA proved to be a useful tool for exploring the problems in depth and for detecting previously unrecognized problems. CONCLUSIONS: This CCA worked in multiple VA sites. It may be adapted to work in other settings or to better detect other clinic problems.

Ambulatory Care Facilities↗

PubMed2005

BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury.

BACKGROUND: Mechanisms that affect recovery from fetal and neonatal hypoxic-ischemic (H-I) brain injury have not been fully elucidated. The incidence of intrapartum asphyxia is approximately 2.5%, but the occurrence of adverse clinical outcome is much lower. One of the factors which may account for this relatively good outcome is the process of neurogenesis, which has been described in adult animals. We used a neonatal mouse model to assess new cells in the hippocampus after H-I injury. RESULTS: Neonatal mice underwent permanent unilateral carotid ligation on the seventh postnatal day followed by exposure to 8% hypoxia for 75 minutes. The presence of new cells was determined by bromodeoxyuridine (BrdU) incorporation into cells with sacrifice of the animals at intervals. Brain sections were stained for BrdU in combination with neuronal, glial, endothelial and microglial stains. We found a significant increase in BrdU-positive cells in the neonatal mouse hippocampus in the injured area compared to the non-injured area, most prominent in the dentate gyrus (DG) (154.5 +/- 59.6 v. 92.9 +/- 32.7 at 3 days after injury; 68.9 +/- 23.4 v. 52.4 +/- 17.1 at 35 days after injury, p < 0.0011). Among the cells which showed differentiation, those which were stained as either microglial or endothelial cells showed a peak increase at three days after the injury in the DG, injured versus non-injured side (30.5 +/- 17.8 v. 2.7 +/- 2.6, p < 0.0002). As in the adult animal, neurogenesis was significantly increased in the DG with injury (15.0 +/- 4.6 v. 5.2 +/- 1.6 at 35 days after injury, p < 0.0002), and this increase was subsequent to the appearance of the other dividing cells. Numbers of new oligodendrocytes were significantly higher in the DG on the non-injured side (7.0 +/- 24.2 v. 0.1 +/- 0.3, p < 0.0002), suggesting that oligodendrocyte synthesis was reduced in the injured hippocampus. CONCLUSION: These findings demonstrate that the neonatal animal responds to brain injury with neurogenesis, much like the adult animal. In addition, H-I insult leads to more neurogenesis than hypoxia alone. This process may play a role in the recovery of the neonatal animal from H-I insult, and if so, enhancement of the process may improve recovery.

Animals↗

PubMed2004

A qualitative study of resident learning in ambulatory clinic. The importance of exposure to 'breakdown' in settings that support effective response.

Qualitative analysis of a large ethnographic database from observations of a resident teaching clinic revealed three important findings. The first finding was that breakdown, a situation where an 'actor' (such as a person or the group) is not achieving expected effectiveness, was the most important category because of its frequency and explanatory power. The next finding was that exposure to breakdown was a necessary ingredient for reflective learning. The final finding was that effective response to breakdown (with concomitant reflective learning) requires six factors to be present: the patient is engaged directly; responsibility is matched to authority; tools are matched to tasks; information resources are matched to need; values are matched between co-participants; and expectations are matched with capacity. These findings have implications for planning, improvements and further studies in ambulatory teaching clinics.

Adult↗

PubMed2004

Cultural consensus analysis as a tool for clinic improvements.

Some problems in clinic function recur because of unexpected value differences between patients, faculty, and residents. Cultural consensus analysis (CCA) is a method used by anthropologists to identify groups with shared values. After conducting an ethnographic study and using focus groups, we developed and validated a CCA tool for use in clinics. Using this instrument, we identified distinct groups with 6 important value differences between those groups. An analysis of these value differences suggested specific and pragmatic interventions to improve clinic functioning. The instrument has also performed well in preliminary tests at another clinic.

Anthropology, Cultural↗