Symposium review: Dairy Brain-Informing decisions on dairy farms using data analytics.

Management decisions can be informed by near-real-time data streams to improve the economics of the farm and to positively benefit the overall health of a dairy herd or the larger environment. Decision support tools can use data management services and analytics to exploit data streams from farm and other economic, health, and agricultural sources. We will describe a decision support tool that couples data analytics tools to underlying cow, herd, and economic data with an application programming interface. This interface allows the user to interact with a collection of dairy applications without fully exposing the intricacies of the underlying system model and understand the effects of different decisions on outputs of interest. The collection of these applications will form the basis of the Dairy Brain decision support system, which will provide management suggestions to farmers at a single animal or farm level. Dairy operations data will be gathered, cleaned, organized, and disseminated through an agricultural data hub, exploiting newly developed ontologies for integration of multiple data sources. Models of feed efficiency, culling, or other dairy operations (such as large capital expenditures, outsourcing opportunities, and interactions with regulators) form the basis of analytical approaches, operationalized via tools that help secure information and control uncertainties. The applications will be independently generated to provide flexibility, and use tools and modeling approaches from the data science, simulation, machine learning, and optimization disciplines to provide specific recommendations to decision makers. The Dairy Brain is a decision support system that couples data analytics tools with a suite of applications that integrate cow, herd, and economic data to inform management, operational, and animal health improving practices. Research challenges that remain include dealing with increased variability as predictions go from herd or pen level down to individual cow level and choosing the appropriate tool or technique to deal with a specific problem.

Medical Scribes, Provider and Patient Experience, and Patient Throughput: a Trial in an Academic General Internal Medicine Practice.

BACKGROUND: Medical scribes have been proposed as a solution to the problems of excessive documentation, work-life balance, and burnout facing general internists. However, their acceptability to patients and effects on provider experience have not been tested in a real-world model of effectiveness. OBJECTIVE: To measure the effect of medical scribes on patient satisfaction, provider satisfaction, and provider productivity. DESIGN: Quasi-experimental difference-in-differences longitudinal design. PARTICIPANTS: Four attending physicians who worked with scribes, 9 control physicians who did not, and their patients in a large, hospital-affiliated academic general internal medicine practice. MAIN MEASURES: Provider experience and patient experience using 5-point Likert scale surveys from the AMA Steps Forward Team Documentation Module, and visits and wRVUs per hour during 4 weeks before and 12 weeks after initiation of a practice model that included use of scribes and a shortened visit template. KEY RESULTS: Participating providers worked a total of 664 clinic sessions and returned 547 (82%) surveys. Average provider experience scores did not differ between providers working with scribes and control providers working without (4.01 vs. 3.40 respectively; p time-by-group interaction = 0.26). Providers with scribes were more likely to agree that work for the encounter would be completed during the visit then controls (3.58 vs. 2.48 respectively; p interaction = 0.04). A total of 6202 visits occurred during the study period. Average patient experience scores did not differ between the experimental and control groups (4.73 vs. 4.75 respectively; p interaction = 0.90). Compared with the control providers, providers with scribes completed more visits per hour (2.29 vs. 1.91; p interaction < 0.001) and generated more wRVUs per hour (3.42 vs. 3.27; p interaction < 0.001). CONCLUSIONS: In this test of a modified practice model, scribes supported greater patient throughput and improved provider perceptions of documentation burden with no decrement in high patient satisfaction.

Procedural Experience With Intubation: Results From a National Emergency Medicine Group.

STUDY OBJECTIVE: Although intubation is a commonly discussed procedure in emergency medicine, the number of opportunities for emergency physicians to perform it is unknown. We determine the frequency of intubation performed by emergency physicians in a national emergency medicine group. METHODS: Using data from a national emergency medicine group (135 emergency departments [EDs] in 19 states, 2010 to 2016), we determined intubation incidence per physician, including intubations per year, intubations per 100 clinical hours, and intubations per 1,000 ED patient visits. We report medians and interquartile ranges (IQRs) for estimated intubation rates among emergency physicians working in general EDs (those treating mixed adult and pediatric populations). RESULTS: We analyzed 53,904 intubations performed by 2,108 emergency physicians in general EDs (53,265 intubations) and pediatric EDs (639 intubations). Intubation incidence varied among general ED emergency physicians (median 10 intubations per year; IQR 5 to 17; minimum 0, maximum 109). Approximately 5% of emergency physicians did not perform any intubations in a given year. During the study, 24.1% of general ED emergency physicians performed fewer than 5 intubations per year (range 21.2% in 2010 to 25.7% in 2016). Emergency physicians working in general EDs performed a median of 0.7 intubations per 100 clinical hours (IQR 0.3 to 1.1) and 2.7 intubations per 1,000 ED patient visits (IQR 1.2 to 4.6). CONCLUSION: These findings provide insights into the frequency with which emergency physicians perform intubations.

The relationship between students' counseling center contact and long-term educational outcomes.

Numerous studies have demonstrated that counseling centers deliver a positive impact on the emotional and social development of college students who receive services. These healthy outcomes, in turn, can lead to increased academic success, such as improved performance, retention, and persistence. While these short-term academic outcomes have been widely investigated, very few studies have explored the relationship between counseling center services and longer-term educational outcomes, such as final grade point average (GPA), time spent at the university, and degree completion. In the current study, counseling center usage, including appointments that were attended, cancelled, and no showed, as well as distal educational variables were examined within 2 cohorts of first-time full-time students over a 6-year period. Findings revealed that both users and nonusers of counseling center services spent a similar amount of time to degree completion and achieved comparable final semester GPAs as well. However, students who utilized counseling services graduated at a significantly lower rate (79.8%) than those who did not use services (86.2%) across the 6-year time span. Post hoc analyses indicated that among students who used counseling services, those who did not graduate scheduled significantly more services than those who graduated, suggesting that students who use the counseling center, and have more chronic and severe mental health problems, may be graduating at a lower rate. Implications are discussed. (PsycINFO Database Record

The Outer Pore and Selectivity Filter of TRPA1.

TRPA1 (transient-receptor-potential-related ion channel with ankyrin domains) is a direct receptor or indirect effector for a wide variety of nociceptive signals, and thus is a compelling target for development of analgesic pharmaceuticals such as channel blockers. Recently, the structure of TRPA1 was reported, providing insights into channel assembly and pore architecture. Here we report whole-cell and single-channel current recordings of wild-type human TRPA1 as well as TRPA1 bearing point mutations of key charged residues in the outer pore. These measurements demonstrate that the glutamate at position 920 plays an important role in collecting cations into the mouth of the pore, by changing the effective surface potential by ~16 mV, while acidic residues further out have little effect on permeation. Electrophysiology experiments also confirm that the aspartate residue at position 915 represents a constriction site of the TRPA1 pore and is critical in controlling ion permeation.

Hippocampal subfield surface deformity in non-semantic primary progressive aphasia.

BACKGROUND: Alzheimer neuropathology (AD) is found in almost half of patients with non-semantic primary progressive aphasia (PPA). This study examined hippocampal abnormalities in PPA to determine similarities to those described in amnestic AD. METHODS: In 37 PPA patients and 32 healthy controls, we generated hippocampal subfield surface maps from structural MRIs and administered a face memory test. We analyzed group and hemisphere differences for surface shape measures and their relationship with test scores and ApoE genotype. RESULTS: The hippocampus in PPA showed inward deformity (CA1 and subiculum subfields) and outward deformity (CA2-4+DG subfield) and smaller left than right volumes. Memory performance was related to hippocampal shape abnormalities in PPA patients, but not controls, even in the absence of memory impairments. CONCLUSIONS: Hippocampal deformity in PPA is related to memory test scores. This may reflect a combination of intrinsic degenerative phenomena with transsynaptic or Wallerian effects of neocortical neuronal loss.

Environmental-scale map use in middle childhood: links to spatial skills, strategies, and gender.

Researchers have shown that young children solve mapping tasks in small spaces, but have rarely tested children's performance in large, unfamiliar environments. In the current research, children (9-10 years; N = 40) explored an unfamiliar campus and marked flags' locations on a map. As hypothesized, better performance was predicted by higher spatial-test scores, greater spontaneous use of map-space coordinating strategies, and participant sex (favoring boys). Data supported some but not all hypotheses about the roles of specific spatial skills for mapping performance. Data patterns were similar on a computer mapping task that displayed environmental-scale videos of walks through a park. Patterns of children's mapping errors suggested both idiosyncratic and common mapping strategies that should be addressed in future research and educational interventions.

Mutant sodium channel for tumor therapy.

Viral vectors have been used to deliver a wide range of therapeutic genes to tumors. In this study, a novel tumor therapy was achieved by the delivery of a mammalian brain sodium channel, ASIC2a, carrying a mutation that renders it constitutively open. This channel was delivered to tumor cells using a herpes simplex virus-1/Epstein-Barr virus (HSV/EBV) hybrid amplicon vector in which gene expression was controlled by a tetracycline regulatory system (tet-on) with silencer elements. Upon infection and doxycycline induction of mutant channel expression in tumor cells, the open channel led to amiloride-sensitive sodium influx as assessed by patch clamp recording and sodium imaging in culture. Within hours, tumor cells swelled and died. In addition to cells expressing the mutant channel, adjacent, noninfected cells connected by gap junctions also died. Intratumoral injection of HSV/EBV amplicon vector encoding the mutant sodium channel and systemic administration of doxycycline led to regression of subcutaneous tumors in nude mice as assessed by in vivo bioluminescence imaging. The advantage of this direct mode of tumor therapy is that all types of tumor cells become susceptible and death is rapid with no time for the tumor cells to become resistant.

Thermodynamics and conformational change governing domain-domain interactions of calmodulin.

Calmodulin (CaM) is a small (148 amino acid), ubiquitously expressed eukaryotic protein essential for Ca(2+) regulation and signaling. This highly acidic polypeptide (pI<4) has two homologous domains (N and C), each consisting of two EF-hand Ca(2+)-binding sites. Despite significant homology, the domains have intrinsic differences in their Ca(2+)-binding properties and separable roles in regulating physiological targets such as kinases and ion channels. In mammalian full-length CaM, sites III and IV in the C-domain bind Ca(2+) cooperatively with ~10-fold higher affinity than sites I and II in the N-domain. However, the difference is only twofold when CaM is severed at residue 75, indicating that anticooperative interactions occur in full-length CaM. The Ca(2+)-binding properties of sites I and II are regulated by several factors including the interplay of interdomain linker residues far from the binding sites. Our prior thermodynamic studies showed that these residues inhibit thermal denaturation and decrease calcium affinity. Based on high-resolution structures and NMR spectra, there appear to be interactions between charged residues in the sequence 75-80 and those near the amino terminus of CaM. To explore electrostatic contributions to interdomain interactions in CaM, KCl was used to perturb the Ca(2+)-binding affinity, thermal stability, and hydrodynamic size of a nested set of recombinant mammalian CaM (rCaM) fragments terminating at residues 75, 80, 85, or 90. Potassium chloride is known to decrease Ca(2+)-binding affinity of full-length CaM. It may act directly by competition with acidic side chains that chelate Ca(2+) in the binding sites, and indirectly elsewhere in the molecule by changing tertiary constraints and conformation. In all proteins studied, KCl decreased Ca(2+)-affinity, decreased Stokes radius, and increased thermal stability, but not monotonically. Crystallographic structures of Ca(2+)-saturated rCaM(1-75) (3B32.pdb) and rCaM(1-90) (3IFK.pdb) were determined, offering cautionary notes about the effect of packing interactions on flexible linkers. This chapter describes an array of methods for characterizing system-specific thermodynamic properties that in concert govern structure and function.

TRP channels in mechanosensation: direct or indirect activation?

Ion channels of the transient receptor potential (TRP) superfamily are involved in a wide variety of neural signalling processes, most prominently in sensory receptor cells. They are essential for mechanosensation in systems ranging from fruitfly hearing, to nematode touch, to mouse mechanical pain. However, it is unclear in many instances whether a TRP channel directly transduces the mechanical stimulus or is part of a downstream signalling pathway. Here, we propose criteria for establishing direct mechanical activation of ion channels and review these criteria in a number of mechanosensory systems in which TRP channels are involved.

TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.

TRPA1, a member of the transient receptor potential (TRP) family of ion channels, is expressed by dorsal root ganglion neurons and by cells of the inner ear, where it has proposed roles in sensing sound, painful cold, and irritating chemicals. To test the in vivo roles of TRPA1, we generated a mouse in which the essential exons required for proper function of the Trpa1 gene were deleted. Knockout mice display behavioral deficits in response to mustard oil, to cold ( approximately 0 degrees C), and to punctate mechanical stimuli. These mice have a normal startle reflex to loud noise, a normal sense of balance, a normal auditory brainstem response, and normal transduction currents in vestibular hair cells. TRPA1 is apparently not essential for hair-cell transduction but contributes to the transduction of mechanical, cold, and chemical stimuli in nociceptor sensory neurons.