Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat.

Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here, we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also down-regulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior.

Clinical risk prediction using language models: benefits and considerations.

OBJECTIVE: The use of electronic health records (EHRs) for clinical risk prediction is on the rise. However, in many practical settings, the limited availability of task-specific EHR data can restrict the application of standard machine learning pipelines. In this study, we investigate the potential of leveraging language models (LMs) as a means to incorporate supplementary domain knowledge for improving the performance of various EHR-based risk prediction tasks. METHODS: We propose two novel LM-based methods, namely "LLaMA2-EHR" and "Sent-e-Med." Our focus is on utilizing the textual descriptions within structured EHRs to make risk predictions about future diagnoses. We conduct a comprehensive comparison with previous approaches across various data types and sizes. RESULTS: Experiments across 6 different methods and 3 separate risk prediction tasks reveal that employing LMs to represent structured EHRs, such as diagnostic histories, results in significant performance improvements when evaluated using standard metrics such as area under the receiver operating characteristic (ROC) curve and precision-recall (PR) curve. Additionally, they offer benefits such as few-shot learning, the ability to handle previously unseen medical concepts, and adaptability to various medical vocabularies. However, it is noteworthy that outcomes may exhibit sensitivity to a specific prompt. CONCLUSION: LMs encompass extensive embedded knowledge, making them valuable for the analysis of EHRs in the context of risk prediction. Nevertheless, it is important to exercise caution in their application, as ongoing safety concerns related to LMs persist and require continuous consideration.

Improving access to breast health services with an interdisciplinary model of care.

This article reports a hospital's experience confronting a community crisis, stemming from local and national breast health access issues, and evaluates the subsequent effectiveness of the initiative to improve breast care service. An interdisciplinary Breast Care Facility was developed adjacent to a Community Hospital. Patients receiving breast cancer screening during the year prior to the Breast Center opening (2002) were compared with patients in subsequent years (2003-2005). Program effectiveness was evaluated by examining screening mammography volume, wait times and cancer detection rates. Screening volume increased by 29.6%. Wait times declined from 30 weeks to 3.5 weeks. Initially, patients with a suspicious screening mammography had a 2-3 week delay for diagnostic mammography and the subsequent evaluation took another 3-4 weeks. Both times improved to an average of 2-5 days. Screening cancer detection rates increased from 3.2 per 1,000, to 6.3 per 1,000. In addition, the number of cancers identified by screening increased from 40% to 58%, p = 0.002. Patient satisfaction measured by survey was over 95%, in areas of courtesy, counseling, and overall care. Our study demonstrates that a comprehensive breast center model can increase access to breast care services, improve patient satisfaction and address focal areas of shortage. Furthermore, in the years after the opening of the breast center the cancer detection rate during screening increased, an important observation that needs to be investigated with future studies.

Decreasing mortality for patients undergoing hip fracture repair surgery.

BACKGROUND: Staten Island University Hospital (Staten Island, New York) undertook an initiative to reduce mortality in a high-risk population on the basis of findings from a root cause analysis (RCA). METHODS: A 78-year-old woman admitted following a fall was diagnosed with a femur fracture. The medical history was significant for chronic obstructive pulmonary disease, hypothyroidism, and laryngeal cancer. A medical consultant classified the patient as grade II (American Society of Anaesthesiologists-Physical Status [ASA] scale), no contra-indication for operating room (OR). An anesthesiologist evaluated the patient as an ASA grade III/IV. The patient went to the OR and died after anesthesia induction. The RCA revealed inadequate communication between providers and preoperative assessment and no framework to privilege providers for high risk preoperative evaluations. Proposed corrective actions included use of a preoperative assessment tool. RESULTS: During the baseline year, 2000, the preimplementation mortality rate for 185 patients undergoing hip fracture repair surgery was 4.9%. For the 644 postimplementation patients, the mortality rate decreased to 2.7% for both 2001 and 2002 and to 1% for 2003. Comparison of the 2000 baseline and 2003 mortalities indicated a statistically significant mortality reduction of 79% (p = .0245). DISCUSSION: Mortality rates can be reduced by systematic application of comprehensive preoperative assessment when implemented by specially trained and privileged staff.