Principles for Health Information Collection, Sharing, and Use: A Policy Statement From the American Heart Association.

The evolution of the electronic health record, combined with advances in data curation and analytic technologies, increasingly enables data sharing and harmonization. Advances in the analysis of health-related and health-proxy information have already accelerated research discoveries and improved patient care. This American Heart Association policy statement discusses how broad data sharing can be an enabling driver of progress by providing data to develop, test, and benchmark innovative methods, scalable insights, and potential new paradigms for data storage and workflow. Along with these advances come concerns about the sensitive nature of some health data, equity considerations about the involvement of historically excluded communities, and the complex intersection of laws attempting to govern behavior. Data-sharing principles are therefore necessary across a wide swath of entities, including parties who collect health information, funders, researchers, patients, legislatures, commercial companies, and regulatory departments and agencies. This policy statement outlines some of the key equity and legal background relevant to health data sharing and responsible management. It then articulates principles that will guide the American Heart Association's engagement in public policy related to data collection, sharing, and use to continue to inform its work across the research enterprise, as well as specific examples of how these principles might be applied in the policy landscape. The goal of these principles is to improve policy to support the use or reuse of health information in ways that are respectful of patients and research participants, equitable in impact in terms of both risks and potential benefits, and beneficial across broad and demographically diverse communities in the United States.

Lactational performance effects of supplemental histidine in dairy cows: A meta-analysis.

The objective of this meta-analysis was to examine the effects of supplemental His on lactational performance, plasma His concentration and efficiency of utilization of digestible His (EffHis) in dairy cows. The meta-analysis was performed on data from 17 studies published in peer-reviewed journals between 1999 and 2022. Five publications reported data from 2 separate experiments, which were included in the analyses as separate studies, therefore resulting in a total of 22 studies. In 10 studies, His was supplemented as rumen-protected (RP) His; in 1 study, 2 basal diets with different dHis levels were fed; and in the remaining experiments, free His was infused into the abomasum (4 studies), the jugular vein (3 studies) or deleted from a mixture of postruminally infused AA (4 studies). The main forages in the diets were corn silage in 14 and grass silage in 8 studies. If not reported in the publications, the supplies of dietary CP, metabolizable protein (MP), net energy of lactation, and digestible His (dHis) were estimated using NRC (2001). An initial meta-analysis was performed to test the standard mean difference (SMD; raw mean difference of treatment and control means divided by the pooled standard deviation of the means), that is, effect size, and the corresponding 95% confidence interval (CI) in production parameters between His-supplemented groups versus control. Further, regression analyses were also conducted to examine and compare the relationships between several response variables and dHis supply. Across studies, His supplementation increased plasma His concentration (SMD = 1.39; 95% CI: 1.17-1.61), as well as DMI (SMD = 0.240; 95% CI: 0.051-0.429) and milk yield (MY; SMD = 0.667; 95% CI: 0.468-0.866), respectively. Further, milk true protein concentration (MTP; SMD = 0.236; 95% CI: 0.046-0.425) and milk true protein yield (MTPY; SMD = 0.581; 95% CI: 0.387-0.776) were increased by His supplementation. Notably, the increase in MTP concentration and MTPY were 3.9 and 1.3 times greater for studies with MP-deficient (according to NRC 2001) diets compared with studies with MP-adequate diets. The regression analyses revealed that production parameters (DMI, MY, and MTPY) responded in a nonlinear manner to increasing His supply. Further, we detected a difference in the magnitude of change in MTPY and plasma His concentration with the level of His supply and between His supplementation methods, being greater for infused His compared with RPHis. Lastly, a linear and negative relationship between EffHis and the ratio of total digestible His to net energy for lactation supply was observed, indicating an important interaction between dHis and energy supply and EffHis (i.e., utilization of dHis to support protein export). Overall, these analyses confirm His as an important AA in dairy cattle nutrition.

Codon influence on protein expression in E. coli correlates with mRNA levels.

Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli.

Regulatory oversight, causal inference, and safe and effective health care machine learning.

In recent years, the applications of Machine Learning (ML) in the health care delivery setting have grown to become both abundant and compelling. Regulators have taken notice of these developments and the U.S. Food and Drug Administration (FDA) has been engaging actively in thinking about how best to facilitate safe and effective use. Although the scope of its oversight for software-driven products is limited, if FDA takes the lead in promoting and facilitating appropriate applications of causal inference as a part of ML development, that leadership is likely to have implications well beyond regulated products.

Artificial insemination of cattle: Description and assessment of a training program for veterinary students.

The objective was to assess the effectiveness of a comprehensive artificial insemination (AI) training program designed to facilitate an understanding of the breadth of the AI process, including AI skill acquisition, for preclinical veterinary students. Participants (n = 303) were enrolled at the Ross University School of Veterinary Medicine (Basseterre, St. Kitts, West Indies). The 2-d AI training program (n = 20) consisted of ∼8 h of instruction and ∼8 h of demonstration and hands-on activity. Oral presentations were used to deliver educational content, followed by video clips, discussion, demonstrations, and hands-on activity. Reproductive anatomy and physiology of the estrous cycle, AI sire acquisition, collection, evaluation, cryopreservation and distribution of conventional and sexed semen, storage and handling of frozen semen, use of synchronization protocols, accurate and efficient detection of estrus, and correct AI technique were discussed. True or false pre- and posttests were used to determine the level of knowledge gained by participants during the AI training program. Preclinical veterinary students were required to complete a semen handling and AI technique practical exam to achieve a certificate of completion. Participant program evaluations conducted at the conclusion of the program indicated that veterinary students found the content, structure, discussion, demonstrations, and hands-on activities to be appropriate and useful. No negative comments were offered about the training program, instructor, or activity coinstructors. The AI training program increased the posttest knowledge scores of veterinary students by 22 percentage points. Only 1 participant was unable to achieve a certificate of completion due to failure of the semen handling and AI technique practical exam. These results provide evidence that the AI training program was relevant and effective and that it offered information and skill acquisition with immediate field application.

Emergent postpartum pelvic sonography.

This article describes the variable appearance of the normal postpartum uterus and reviews complications which can occur in the postpartum period, with particular emphasis on the sonographic findings. Postpartum complications are a common presentation to the emergency department. The majority of these patients present with secondary postpartum hemorrhage. Additional symptoms of pain or clinical findings of pyrexia and leukocytosis confound the clinical scenario and necessitate further evaluation with imaging. Ultrasonography is the mainstay in the initial imaging evaluation of the postpartum patient, with occasional progression to CT, MR, or angiography. We sought to provide a brief review of the literature, with pictorial review of key imaging findings, with a focus on ultrasonography. We provide a pictorial and brief literature review, with case examples from our institution, of key postpartum complications. Ultrasonography is an important component of evaluation in postpartum patients, particularly those with hemorrhage or other complication.

Body MRI Subspecialty Reinterpretations at a Tertiary Care Center: Discrepancy Rates and Error Types.

OBJECTIVE. Radiology departments in tertiary care centers are frequently asked to perform secondary interpretations of imaging studies, particularly when a patient is transferred from a community hospital. Discrepancy rates in radiology vary widely, with low rates reported for preliminary resident reports that are overread by attending radiologists (2-6%) and higher rates (up to 56%) for secondary interpretations. Abdominal and pelvic imaging and cross-sectional imaging have the highest discrepancy rates. The purpose of our study was to determine the discrepancy rate and the most common reasons for discrepancies between abdominal and pelvic MRI reports obtained from outside institutions and secondary interpretations of these reports by a fellowship-trained radiologist at a tertiary care center. MATERIALS AND METHODS. We retrospectively identified 395 secondary MRI reports from January 2015 to December 2018 that were labeled as body MRI examinations at a tertiary care center. Thirty-eight cases were excluded for various reasons, including incorrect categorization or lack of outside report. We reviewed the outside reports, compared them with the secondary interpretations, and categorized the cases as discrepancy or no discrepancy. The discrepancies were subdivided into the most likely reason for the error using previously published categories; these categories were also divided into perceptive and cognitive errors. RESULTS. Of the 357 included cases, 246 (68.9%) had at least one discrepancy. The most common reason for error was faulty reasoning (34.3%), which is a cognitive error characterized by misidentifying an abnormality. Satisfaction of search, which is a perceptive error, was the most common reason for second discrepancies (15.0%). CONCLUSION. Secondary interpretations of body MR images at a tertiary care center identify a high rate of discrepancies, with cognitive error types predominating.

Short communication: Reproduction outcomes in dairy heifers following a 14-d progesterone insert presynchronization protocol.

The objectives were to evaluate pregnancy per artificial insemination (AI), days to first AI, and proportion pregnant within 7 d of AI eligibility in dairy heifers subjected to presynchronization compared with dairy heifers not presynchronized. Thirty days before AI eligibility, Holstein heifers were assigned randomly to 1 of 3 groups: 14-d controlled internal drug release (CIDR; containing progesterone) presynchronization, PGF2α presynchronization, or control (no presynchronization). Heifers in the 14-d CIDR presynchronization treatment (n = 119) received a CIDR on d -30, which was removed on d -16, followed by an injection of PGF2α upon entry to the breeding program (d 0). Heifers in the PGF2α presynchronization treatment (n = 118) received an injection of PGF2α on d -11 and d 0. Control heifers (n = 121) were not presynchronized and received an injection of PGF2α on d 0. All heifers received tail paint on d 0 to facilitate once-daily detection of estrus (based on paint removal). Heifers detected in estrus received AI with conventional semen on the same morning as detected estrus. Generalized linear mixed models were used to assess mean treatment differences. Following PGF2α treatment on d 0, more heifers were detected in estrus in the first 7 d after eligibility in the 14-d CIDR group (95.8%) compared with the PGF2α (74.6%) and control (66.9%) groups. Days to first AI differed between treatments (14-d CIDR = 3.6 d vs. PGF2α = 5.0 d vs. control = 6.8 d). Pregnancy per AI for first AI within 7 d of eligibility was 71.9% (14-d CIDR), 58.0% (PGF2α), and 61.7% (control), and differed between 14-d CIDR and PGF2α heifers. Presynchronization with a 14-d CIDR increased the proportion of heifers pregnant in the first 7 d of eligibility (14-d CIDR = 68.9% vs. PGF2α = 43.2% vs. control = 41.3%). Projected days on feed (d 0 to projected calving date) were 295 (14-d CIDR), 302 (PGF2α), and 305 (control), and were different between the 14-d CIDR and control heifers. The potential economic benefit to the producer was $15.85 per heifer presynchronized with a 14-d CIDR protocol compared with the control group. Treatment of dairy heifers with a 14-d CIDR effectively presynchronized estrus, resulting in a greater proportion detected in estrus, reduced days to first AI, and an increased proportion of heifers pregnant within the first 7 d after breeding eligibility compared with heifers presynchronized with a single PGF2α injection and control heifers.

Pregnancy outcomes are not improved by administering gonadotropin-releasing hormone at initiation of a 5-day CIDR-Cosynch resynchronization protocol for lactating dairy cows.

Using a 5-d controlled internal drug-release (CIDR)-Cosynch resynchronization protocol, the objective of this study was to determine the effect of the initial GnRH injection on pregnancy per artificial insemination (P/AI) to the second artificial insemination in lactating Holstein dairy cows. On 37 ± 3 d (mean ± standard deviation) after the first artificial insemination, and upon nonpregnancy diagnosis (d 0 of the experiment), lactating cows eligible for a second artificial insemination (n = 429) were enrolled in a 5-d CIDR-Cosynch protocol. On d 0, all cows received a CIDR insert and were assigned randomly to receive the initial GnRH injection (GnRH; n = 226) of the protocol or no-GnRH (n = 203). Blood samples were collected from a sub-group of cows (n = 184) on d 0 and analyzed for progesterone (P4) concentration. On d 5, CIDR inserts were removed, and all cows received 1 injection of PGF2α. On d 6 and 7, cows were observed once daily by employees for tail-chalk removal, and cows detected in estrus on d 6 or 7 received artificial insemination that day (EDAI), and did not receive the final GnRH injection. The remaining cows not detected in estrus by d 8 received GnRH and timed artificial insemination (TAI). Pregnancy status was confirmed by transrectal palpation of uterine contents at 37 ± 3 d (mean ± standard deviation) after the second artificial insemination. Eliminating the initial GnRH injection had no effect on P/AI compared with cows receiving GnRH (27 vs. 21%), respectively. Similarly, method of insemination (EDAI vs. TAI) and its interaction with treatment had no effect on P/AI. Primiparous cows had greater P/AI than multiparous cows (31 vs. 21%). Mean P4 concentrations (n = 184) at the initiation of the protocol did not differ between treatments (4.51 ± 0.35 ng/mL no-GnRH vs. 3.96 ± 0.34 ng/mL of GnRH). When P4 concentrations were categorized as high (≥1 ng/mL) or low (<1 ng/mL), P/AI tended to be greater for high P4 concentrations (n = 136) compared with low (n = 48) P4 concentrations (26 vs. 16%, respectively). No differences were observed in the proportion of cows with high or low P4 between treatments. Collectively, these results provide evidence that eliminating the initial GnRH in a 5-d CIDR-Cosynch resynchronization protocol for lactating dairy cows did not reduce P/AI in this study.

Sexual selection predicts brain structure in dragon lizards.

Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size.

Regulating Black-Box Medicine.

Data drive modern medicine. And our tools to analyze those data are growing ever more powerful. As health data are collected in greater and greater amounts, sophisticated algorithms based on those data can drive medical innovation, improve the process of care, and increase efficiency. Those algorithms, however, vary widely in quality. Some are accurate and powerful, while others may be riddled with errors or based on faulty science. When an opaque algorithm recommends an insulin dose to a diabetic patient, how do we know that dose is correct? Patients, providers, and insurers face substantial difficulties in identifying high-quality algorithms; they lack both expertise and proprietary information. How should we ensure that medical algorithms are safe and effective? Medical algorithms need regulatory oversight, but that oversight must be appropriately tailored. Unfortunately, the Food and Drug Administration (FDA) has suggested that it will regulate algorithms under its traditional framework, a relatively rigid system that is likely to stifle innovation and to block the development of more flexible, current algorithms. This Article draws upon ideas from the new governance movement to suggest a different path. FDA should pursue a more adaptive regulatory approach with requirements that developers disclose information underlying their algorithms. Disclosure would allow FDA oversight to be supplemented with evaluation by providers, hospitals, and insurers. This collaborative approach would supplement the agency's review with ongoing real-world feedback from sophisticated market actors. Medical algorithms have tremendous potential, but ensuring that such potential is developed in high-quality ways demands a careful balancing between public and private oversight, and a role for FDA that mediates--but does not dominate--the rapidly developing industry.

Short communication: Comparison of the GreenFeed system with the sulfur hexafluoride tracer technique for measuring enteric methane emissions from dairy cows.

The objective of this study was to compare 2 commonly used techniques for measuring methane emissions from ruminant animals: the GreenFeed (GF) system and the sulfur hexafluoride (SF6) technique. The study was part of a larger experiment in which a methane inhibitor, 3-nitrooxypropanol, fed at 4 application rates (0, 40, 60, and 80 mg/kg of feed dry matter) decreased enteric methane emission by an average of 30% (measured by both GF and SF6) in a 12-wk experiment with 48 lactating Holstein cows fed a total mixed ration. The larger experiment used a randomized block design and was conducted in 2 phases (February to May, phase 1, and June to August, phase 2), with 2 sets of 24 cows in each phase. Using both GF and SF6 techniques, methane emission data were collected simultaneously during experimental wk 2, 6, and 12 (phase 1) and 2, 9, and 12 (phase 2), which corresponded to a total of 6 sampling periods. During each sampling period, 8 spot samples of gas emissions (staggered over a 3-d period) were collected from each cow using GF, as well as 3×24-h collections using the SF6 technique. Methane emission data were averaged per cow for the statistical analysis. The mean methane emission was 373 (standard deviation=96.3) and 405 (standard deviation=156) g/cow per day for GF and SF6, respectively. Coefficients of variation for the 2 methods were 25.8 and 38.6%, respectively; correlation and concordance between the 2 methods were 0.40 and 0.34, respectively. The difference in methane emission between the 2 methods (SF6 - GF) within treatment was from 46 to 144 and 24 to 27 g/d for phases 1 and 2, respectively. In the conditions of this experiment, the SF6 technique produced larger variability in methane emissions than the GF method. The overall difference between the 2 methods was on average about 8%, but was not consistent over time, likely influenced by barn ventilation and background methane and SF6 concentrations.

Informed consent for return of incidental findings in genomic research.

PURPOSE: Researchers face the dilemma of how to obtain consent for return of incidental findings from genomic research. We surveyed and interviewed investigators and study participants, with the goal of providing suggestions for how to shape the consent process. METHODS: We performed an online survey of 254 US genetic researchers identified through the NIH RePORTER database, abstracts from the 2011 American Society of Human Genetics meeting, and qualitative semi-structured interviews with 28 genomic researchers and 20 research participants. RESULTS: Most researchers and participants endorsed disclosure of a wide range of information about return of incidental findings, including risks, benefits, impact on family members, data security, and procedures, for return of results in the event of death or incapacity and for recontact. However, most researchers were willing to devote 30 min or less to this process and expressed concerns that disclosed information would overwhelm participants, a concern shared by many participants themselves. CONCLUSION: There is a disjunction between the views of investigators and participants about the amount of information that should be disclosed and the practical realities of the research setting, including the time available for consent discussions. This strongly suggests the need for innovative approaches to the informed consent process.

Models of consent to return of incidental findings in genomic research.

Genomic research-including whole genome sequencing and whole exome sequencing-has a growing presence in contemporary biomedical investigation. The capacity of sequencing techniques to generate results that go beyond the primary aims of the research-historically referred to as "incidental findings"-has generated considerable discussion as to how this information should be handled-that is, whether incidental results should be returned, and if so, which ones.Federal regulations governing most human subjects research in the United States require the disclosure of "the procedures to be followed" in the research as part of the informed consent process. It seems reasonable to assume-and indeed, many commentators have concluded-that genomic investigators will be expected to inform participants about, among other procedures, the prospect that incidental findings will become available and the mechanisms for dealing with them. Investigators, most of whom will not have dealt with these issues before, will face considerable challenges in framing meaningful disclosures for research participants.To help in this task, we undertook to identify the elements that should be included in the informed consent process related to incidental findings. We did this by surveying a large number of genomic researchers (n = 241) and by conducting in-depth interviews with a smaller number of researchers (n = 28) and genomic research participants (n = 20). Based on these findings, it seems clear to us that routine approaches to informed consent are not likely to be effective in genomic research in which the prospect of incidental findings exists. Ensuring that participants' decisions are informed and meaningful will require innovative approaches to dealing with the consent issue. We have identified four prototypical models of a consent process for return of incidental findings.

Mysidopsis jenseni n. sp. from the Pacific coast of Washington, with first description of female M. intii Holmquist, 1957 (Crustacea: Mysida: Mysidae).

Mysidopsis jenseni n. sp. is described from the Puget Sound area, Washington, USA from sand/rocky bottoms in depths of 8 to 15 m. This new species increases the number of American Pacific species of Mysidopsis to eight. Based on a collection of M. intii Holmquist, 1957 from coastal waters of Chile, a supplementary description of the male is presented and the female is described for the first time. The presence of a mid-dorsal lappet near the posterior margin of the carapace of females only distinguishes the new species from all other Mysidopsis species except M. velifera Brattegard, 1973 from the Caribbean. M. jenseni is further separated from its American Pacific congeners by the following combination of characters: antennal scale 34 times as long as wide with a rounded apex and distal suture; uropodal endopod with 89 spiniform setae along ventromedial margin; telson with 4654 spiniform setae along all margins. The presence of lobe-like protuberances on the basis and dactylus of thoracic endopods 38 was documented for the new species, M. intii and other species of Mysidopsis as well as species belonging to the other four genera within the Tribe Mysidopsini. A key to the species of Mysidopsis of the Pacific coasts of the Americas is given.

Systematic enhancement of protein crystallization efficiency by bulk lysine-to-arginine (KR) substitution.

Structural genomics consortia established that protein crystallization is the primary obstacle to structure determination using x-ray crystallography. We previously demonstrated that crystallization propensity is systematically related to primary sequence, and we subsequently performed computational analyses showing that arginine is the most overrepresented amino acid in crystal-packing interfaces in the Protein Data Bank. Given the similar physicochemical characteristics of arginine and lysine, we hypothesized that multiple lysine-to-arginine (KR) substitutions should improve crystallization. To test this hypothesis, we developed software that ranks lysine sites in a target protein based on the redundancy-corrected KR substitution frequency in homologs. This software can be run interactively on the worldwide web at https://www.pxengineering.org/. We demonstrate that three unrelated single-domain proteins can tolerate 5-11 KR substitutions with at most minor destabilization, and, for two of these three proteins, the construct with the largest number of KR substitutions exhibits significantly enhanced crystallization propensity. This approach rapidly produced a 1.9 Å crystal structure of a human protein domain refractory to crystallization with its native sequence. Structures from Bulk KR-substituted domains show the engineered arginine residues frequently make hydrogen-bonds across crystal-packing interfaces. We thus demonstrate that Bulk KR substitution represents a rational and efficient method for probabilistic engineering of protein surface properties to improve crystallization.

The lophogastrids (Crustacea: Peracarida: Lophogastrida) of Indonesia and its adjacent waters. An updated checklist.

The zoogeographic distribution of lophogastrid species (Crustacea: Peracarida: Lophogastrida) occurring in the Indonesian waters is presented. For each species, data on general distribution, bathymetric ranges, habitat and localities reported on published data are provided. A total of 20 lophogastrid species belonging to three families and seven genera occur in Indonesian waters (about 38% of all known lophogastrids species worldwide), a number greater than other areas of Southeast Asia. Also, based on current information, the number of species or species richness is greater than other regions, such as Madagascar, North Pacific off Japan, Mediterranean, Canary Island, northern mid-Atlantic ridge, Iberian Peninsula, Mexico, and Angola Basin (SE Atlantic). Most of the Indonesian species are distributed worldwide, but one species, Lophogaster inermis appears to be endemic to Indonesia. Previous listings of Paralophogaster intermedius occurring in Southeast Asian waters is not verified in any collections, and has therefore been removed from our updated list.