Vulnerability to climate change of United States marine mammal stocks in the western North Atlantic, Gulf of Mexico, and Caribbean.

Climate change and climate variability are affecting marine mammal species and these impacts are projected to continue in the coming decades. Vulnerability assessments provide a framework for evaluating climate impacts over a broad range of species using currently available information. We conducted a trait-based climate vulnerability assessment using expert elicitation for 108 marine mammal stocks and stock groups in the western North Atlantic, Gulf of Mexico, and Caribbean Sea. Our approach combined the exposure (projected change in environmental conditions) and sensitivity (ability to tolerate and adapt to changing conditions) of marine mammal stocks to estimate vulnerability to climate change, and categorize stocks with a vulnerability index. The climate vulnerability score was very high for 44% (n = 47) of these stocks, high for 29% (n = 31), moderate for 20% (n = 22), and low for 7% (n = 8). The majority of stocks (n = 78; 72%) scored very high exposure, whereas 24% (n = 26) scored high, and 4% (n = 4) scored moderate. The sensitivity score was very high for 33% (n = 36) of these stocks, high for 18% (n = 19), moderate for 34% (n = 37), and low for 15% (n = 16). Vulnerability results were summarized for stocks in five taxonomic groups: pinnipeds (n = 4; 25% high, 75% moderate), mysticetes (n = 7; 29% very high, 57% high, 14% moderate), ziphiids (n = 8; 13% very high, 50% high, 38% moderate), delphinids (n = 84; 52% very high, 23% high, 15% moderate, 10% low), and other odontocetes (n = 5; 60% high, 40% moderate). Factors including temperature, ocean pH, and dissolved oxygen were the primary drivers of high climate exposure, with effects mediated through prey and habitat parameters. We quantified sources of uncertainty by bootstrapping vulnerability scores, conducting leave-one-out analyses of individual attributes and individual scorers, and through scoring data quality for each attribute. These results provide information for researchers, managers, and the public on marine mammal responses to climate change to enhance the development of more effective marine mammal management, restoration, and conservation activities that address current and future environmental variation and biological responses due to climate change.

Colon and Rectal Surgery Robotic Training Programs: An Evaluation of Gender Disparities.

BACKGROUND: Female surgeons are subjected to implicit bias throughout their careers. The evaluation of gender bias in training is warranted with increasing numbers of female trainees in colon and rectal surgery. OBJECTIVE: This study aimed to evaluate gender bias in colon and rectal surgery training program operative experience. DESIGN: This is a retrospective cohort study. SETTING: The Association of Program Directors for Colon and Rectal Surgery robotic case log database contains operative details (procedure, attending surgeon, case percentage, and operative segments) completed by trainees as console surgeon for 2 academic years (2016-2017, 2017-2018). MAIN OUTCOME MEASURE: The primary outcomes measured are the percentage of trainee console participation and the completion of total mesorectal excision. Resident and attending surgeon gender was recorded retrospectively. The cohort was separated into 4 groups based on resident and attending surgeon gender combination. Case volume, average console participation per case, and completion of total mesorectal excisions were compared for each group by using interaction regression analysis. RESULTS: Fifty-two training programs participated, including 120 trainees and 190 attending surgeons. Forty-five (37.5%) trainees and 36 (18.9%) attending surgeons were women. The average number of cases per trainee was 23.27 per year for women and 28.15 per year for men (p = 0.19). Average console participation was 53.5% for women and 61.7% for men (p < 0.001). Male attending surgeons provided female trainees less console participation than male counterparts (52.1% vs 59.7%, p < 0.001). Female attending surgeons provided the same amount of console participation to female and male trainees (63.3% vs 61.8%, p = 0.62). Male trainees performed significantly more complete total mesorectal excision console cases than female trainees (57.16% vs 42.38%, p < 0.0001). LIMITATIONS: The data are subject to self-reporting bias. CONCLUSIONS: There is gender disparity in robotic operative experience in colon and rectal surgery training programs with less opportunity for console participation and less opportunity to complete total mesorectal excisions for female trainees. This trend should be highlighted and further evaluated to resolve this disparity. See Video Abstract at http://links.lww.com/DCR/B224. PROGRAMAS DE CAPACITACIÓN ROBÓTICA SOBRE CIRUGÍA DE COLON Y RECTO: UNA EVALUACIÓN DE LAS DISPARIDADES DE GÉNERO: Cirujanos mujeres están sujetas a sesgos implícitos a lo largo de sus carreras. La evaluación del sesgo de género en el entrenamiento se amerita por un número cada vez mayor de aprendices femeniles en cirugía de colon y recto.Evaluar el sesgo de género en la experiencia operativa en programas de entrenamiento de cirugía de colon y recto.Estudio de cohorte retrospectivo.La base de datos de registro de casos robóticos de la Asociación de Directores de Programas para Cirugía de Colon y Rectal contiene detalles operativos (procedimiento, cirujano asistente, porcentaje de casos y segmentos operativos) completados por los alumnos como cirujanos de consola durante dos años académicos (2016-17, 2017-18).Porcentaje de participación de la consola de entrenamiento y finalización de la escisión mesorrectal total. Se registraron retrospectivamente el sexo de los médicos residentes y asistentes. La cohorte se separó en cuatro grupos según la combinación de género residente y asistente. El volumen de casos, la participación promedio de la consola por caso y la finalización de las extirpaciones mesorrectales totales se compararon para cada grupo mediante el análisis de regresión de interacción.Participaron 52 programas de capacitación, incluidos 120 aprendices y 190 cirujanos asistentes. Cuarenta y cinco (37.5%) aprendices y 36 (18.9%) cirujanos asistentes eran mujeres. El número promedio de casos por aprendiz fue de 23.27 / año para mujeres y 28.15 / año para hombres (p = 0.19). La participación promedio de la consola fue del 53.5% para las mujeres y del 61.7% para los hombres (p <0.001). Los cirujanos asistentes masculinos proporcionaron a las mujeres aprendices menos participación en la consola en comparación con sus compañeros masculinos (52.1% vs 59.7%, p <0.001). Los cirujanos asistentes femeninos proporcionaron la misma cantidad de participación en la consola a los aprendices femeninos y masculinos (63.3% vs 61.8%, p = 0.62). Los aprendices masculinos realizaron casos de consola TME significativamente más completos que las aprendices femeninas (57.16% vs 42.38%, p <0.0001).Los datos están sujetos a sesgos de autoinforme.Existe una disparidad de género en la experiencia quirúrgica robótica en los programas de entrenamiento de cirugía de colon y recto con menos oportunidades para la participación de la consola y menos oportunidades para completar las extirpaciones mesorrectales totales para las mujeres en formación. Esta tendencia debe destacarse y evaluarse para resolver esta disparidad. Consulte Video Resumen en http://links.lww.com/DCR/B224. (Traducción-Dr. Adrián Ortega).

Comprehensive enhanced recovery pathway significantly reduces postoperative length of stay and opioid usage in elective laparoscopic colectomy.

BACKGROUND: A comprehensive enhanced recovery pathway (ERP) was implemented in patients undergoing laparoscopic colectomy in an attempt to reduce postoperative opioid consumption. We hypothesized that improved local analgesia and increased use of non-opioid pain medication, combined with earlier feeding and ambulation, would allow for earlier return of bowel function and shorter postoperative length of stay (LOS). METHODS: We retrospectively reviewed 89 patients who underwent elective partial laparoscopic colectomy with our ERP fully integrated compared to a historical control group of 162 patients. Differences between the ERP and control groups average return of bowel function, postoperative LOS, opioid medication usage, and complications were compared statistically using the student's t-test and Fisher exact test. Pain was controlled with the laparoscope-guided transversus abdominis plane (TAP), scheduled doses of non-narcotic medications, and reserved use of opioids. Patient, nursing and resident education regarding all aspects of the ERP was emphasized. RESULTS: Patients in the ERP group had a significant decrease of opioid usage, earlier return of bowel function, and shorter postoperative hospital LOS. Opioid use was reduced from 75 to 19 mg I.V. morphine (p = 0.0001). Patients had an average return of bowel function of 0.66 days earlier from postoperative day (POD) 2.99 to POD 2.33 (p = 0.0001) and were discharged from the hospital 1 day sooner on POD 2.7 compared with POD 3.7 (p = 0.0013). There was no statistically significant difference in postoperative complications between the control and ERP groups. CONCLUSION: The new ERP, including TAP block and postoperative pain medication protocol limiting I.V. narcotics, is effective in controlling pain in elective partial laparoscopic colectomy. Pain control management together with regimented early feeding and ambulation allow for significantly earlier return of bowel function and shorter postoperative LOS.

Identification, production, and use of polyol-responsive monoclonal antibodies for immunoaffinity chromatography.

Immunoaffinity chromatography is a powerful tool for purification of proteins and protein complexes. The availability of monoclonal antibodies (mAbs) has revolutionized the field of immunoaffinity chromatography by providing a continuous supply of highly uniform antibody. Before the availability of mAbs, the recovery of the target protein from immobilized polyclonal antibodies usually required very harsh, often denaturing conditions. Although harsh conditions are often still used to disrupt the antigen-antibody interaction when using a mAb, various methods have been developed to exploit the uniformity of the antigen-antibody reaction in order to identify agents or conditions that gently disrupt this interaction and thus result in higher recovery of active protein from immunoaffinity chromatography. We discuss here the use of a specific type of monoclonal antibody that we have designated "polyol-responsive monoclonal antibodies" (PR-mAbs). These are naturally occurring mAbs that have high affinity for the antigen under binding conditions, but have low affinity in the presence of a combination of low molecular weight hydroxylated compounds (polyols) and nonchaotropic salts. Therefore, these PR-mAbs can be used for gentle immunoaffinity chromatography. PR-mAbs can be easily identified and adapted to a powerful protein purification method for a target protein.

Minimal promoter systems reveal the importance of conserved residues in the B-finger of human transcription factor IIB.

The "B-finger" of transcription factor IIB (TFIIB) is highly conserved and believed to play a role in the initiation process. We performed alanine substitutions across the B-finger of human TFIIB, made change-of-charge mutations in selected residues, and substituted the B-finger sequence from other organisms. Mutant proteins were examined in two minimal promoter systems (containing only RNA polymerase II, TATA-binding protein, and TFIIB) and in a complex system, using TFIIB-immunodepleted HeLa cell nuclear extract (NE). Mutations in conserved residues located on the sides of the B-finger had the greatest effect on activity in both minimal promoter systems, with mutations in residues Glu-51 and Arg-66 eliminating activity. The double change-of-charge mutant (E51R:R66E) did not show activity in either minimal promoter system. Mutations in the nonconserved residues at the tip of the B-finger did not significantly affect activity. However, all of the mutations in the B-finger showed at least 25% activity in the HeLa cell NE. Chimeric proteins, containing B-finger sequences from species with conserved residues on the side of the B-finger, showed wild-type activity in a minimal promoter system and in the HeLa cell NE. However, chimeric proteins whose sequence showed divergence on the sides of the B-finger had reduced activity. Transcription factor IIF (TFIIF) partially restored activity of the inactive mutants in the minimal promoter system, suggesting that TFIIF in HeLa cell NE helps to rescue the inactive mutations by interacting with either the B-finger or another component of the initiation complex that is influenced by the B-finger.

The sigma-1 antagonist BMY-14802 inhibits L-DOPA-induced abnormal involuntary movements by a WAY-100635-sensitive mechanism.

RATIONALE: Levodopa (L-DOPA), the gold standard treatment for Parkinson's disease (PD), eventually causes L-DOPA-induced dyskinesia (LID) in up to 80% of patients. In the 6-hydroxydopamine (6-OHDA) rat model of PD, L-DOPA induces a similar phenomenon, which has been termed abnormal involuntary movement (AIM). We previously demonstrated that BMY-14802 suppresses AIM expression in this model. OBJECTIVES: Although BMY-14802 is widely used as a sigma-1 antagonist, it is also an agonist at serotonin (5-HT) 1A and adrenergic alpha-1 receptors. The current study was conducted to determine which of these mechanisms underlies BMY-14802's AIM-suppressing effect. This characterization included testing the 5-HT1A agonist buspirone and multiple sigma agents. When these studies implicated a 5-HT1A mechanism, we subsequently undertook a pharmacological reversal study, evaluating whether the 5-HT1A antagonist WAY-100635 counteracted BMY-14802's AIM-suppressing effects. RESULTS: Buspirone dose-dependently suppressed AIM, supporting past findings. However, no AIM-suppressing effects were produced by drugs with effects at sigma receptors, including BD-1047, finasteride, SM-21, DTG, trans-dehydroandrosterone (DHEA), carbetapentane, and opipramol. Finally, we show for the first time that the AIM-suppressing effect of BMY-14802 was dose-dependently prevented by WAY-100635 but not by the alpha-1 antagonist prazosin. CONCLUSIONS: BMY-14802 exerts its AIM-suppressing effects via a 5-HT1A agonist mechanism, similar to buspirone. Other 5-HT1A agonists have failed clinical trials, possibly due to submicromolar affinity at other receptors, including D2, which may exacerbate PD symptoms. BMY-14802 is a promising candidate for clinical trials due to its extremely low affinity for the D2 receptor and lack of extrapyramidal effects during prior clinical trials for schizophrenia.

Antigen-binding properties of monoclonal antibodies reactive with human TATA-binding protein and use in immunoaffinity chromatography.

The TATA-binding protein (TBP) plays a central role in the assembly of most eukaryotic transcription initiation complexes. We have characterized 3 monoclonal antibodies (mAbs) that react in the far amino-terminal (N-terminal) domain of the human TBP molecule (residues 1-99). One of these mAbs (designated 1TBP22) is a polyol-responsive monoclonal antibody (PR-mAb) and was adapted to an immunoaffinity chromatography procedure for purifying bacterially expressed, recombinant human TBP. The epitope for mAb 1TBP22 maps to residues 55-99, which includes the polyglutamine region. However, mAb 1TBP22 does not react with poly-l-glutamine. Human TBP, contained on the pET11a plasmid, was expressed in Escherichia coli Rosetta (DE3)pLysS. The cell lysate from 330 ml of induced culture was treated with polyethyleneimine (PEI) at 0.5 M NaCl to precipitate the nucleic acids. After centrifugation, the supernatant fluid was applied to an immunoadsorbent containing mAb 1TBP22. After extensive washing, the TBP was eluted with buffer containing 0.75 M ammonium sulfate and 40% propylene glycol. Human TPB purified by the immunoaffinity chromatography method was found to be active in gel-shift assays and transcription assays. Preliminary data indicate that this mAb might be useful for purifying protein complexes containing TBP from HeLa cell extracts.

Constraints on definite article alternation in speech production: to "thee" or not to "thee"?

A recent study showed that the pronunciation of the definite article in English (as either a reduced "thuh" or an unreduced "thee") depends on a number of different factors, including the pronunciation, spelling, and stress assignment of the following word (Raymond, Fisher, & Healy, 2002). However, it is not clear from previous research whether these factors influenced performance implicitly in normal speech production or whether explicit knowledge of the object of the experiment was relied on. In Experiment 1, we examined implicit performance on pronunciation of the definite article and found more systematic behavior than had previously been observed but, again, an influence of the pronunciation, spelling, and stress assignment of the following word. In Experiment 2, we tested the influence of the following word on definite article production during language development for two groups of children 8 and 10 years of age. This experiment showed increasing use of the unreduced form during development and a further influence of orthography. We interpret these results in terms of an interaction between perception and production in which the production system makes use of generalizations on the basis of both phonological and orthographic representations generated in perception.