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Outcomes: 1. Learn about the Massachusetts Medical Schools' Collaborative's toolbox of educational competencies and curriculum mapping in serious illness communication, with examples on using the tools to improve curricula at each school 2. Generate ideas and strategies for developing educational activities at your own institution that promote learners' acquisition of palliative care skills, regardless of their future discipline All clinicians require a sophisticated set of serious illness communication (SIC) skills to ensure high-quality, humanistic care for patients and families from diverse communities as they face life-changing medical decisions at vulnerable times in their lives. However, most clinicians are not trained in SIC and, as former students, learned these concepts "on the fly" or in electives. The Massachusetts Medical Schools' Collaborative was created to change this paradigm and ensure all students receive foundational SIC training. The collaborative includes faculty, administrators, and students from four schools (Boston University School of Medicine, Harvard Medical School, Tufts University School of Medicine, and UMass Chan Medical School) and is convened by the Massachusetts Coalition for Serious Illness Care, a group of over 125 member organizations focused on equity in serious illness care. Our collaborative seeks to develop longitudinal, developmentally based curricula in SIC. We first developed and published five educational SIC competencies. We then created a standardized curriculum mapping process to understand existing educational activities across schools and opportunities to fill gaps defined by the competencies. The collaborative also conducted focus groups with 50 fourth-year medical students; among key themes, students viewed SIC as essential, yet described their exposure as based mostly on "luck" if they were included in family meetings or coached on SIC. Armed with the competencies, curricular mapping, and focus group data, leaders at each school are expanding curricula in SIC and palliative care based on local needs and resources. Presenters will use most of the session to share concrete examples of curriculum design and implementation based on the collaborative's toolbox, which will be available for participants to bring to their own institutions. As a field, we can make this critical investment in the next generation of clinicians and create educational best practices to help build more trustworthy, equitable healthcare systems. [ABSTRACT FROM AUTHOR]

Marine alginates are well established in wound management. Compared with different modern wound dressings, marine alginates cannot prove superior effects on wound healing. Alginates from bacteria have never been studied for medical applications so far, although the microbial polymer raises expectations for improved binding of wound factors because of its unique O-acetylation. Due to its possible positive effects on wound healing, alginates from bacteria might be a superior future medical product for clinical use. To prove the binding capacity of microbial alginates to pathophysiological factors in chronic wounds, we processed microbial alginate fibres, produced from fermentation of the soil bacterium Azotobacter vinelandii ATCC 9046, into needle web dressings and compared them with commercial dressings made of marine alginate. Four dressings were assessed: Marine alginate dressings containing either ionic silver or zinc/manganese/calcium, and microbial alginate dressings with and without nanosilver. All dressings were tested in an in vitro approach for influence on chronic wound parameters such as elastase, matrix metalloproteases-2, tumour necrosis factor-α, interleukin-8, and free radical formation. Despite the alginate origin or addition of antimicrobials, all dressings were able to reduce the concentration of the proinflammatory cytokines TNF-α and IL-8. However, microbial alginate was found to bind considerable larger amounts of elastase and matrix metalloproteases-2 in contrast to the marine alginate dressings. The incorporation of zinc, silver or nanosilver into alginate fibres did not improve their binding capacity for proteases or cytokines. The addition of nanosilver slightly enhanced the antioxidant capacity of microbial alginate dressings, whereas the marine alginate dressing containing zinc/manganese/calcium was unable to inhibit the formation of free radicals. The enhanced binding affinity by microbial alginate of Azotobacter vinelandii to pathophysiological factors may be interesting to support optimal conditions for wound healing. [ABSTRACT FROM AUTHOR]

The discovery of JAK2V617F a decade ago led to optimism for a rapidly developing treatment revolution in Ph- myeloproliferative neoplasms. Unlike BCR-ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF), post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS)/ myeloproliferative neoplasm (MPN) syndromes. JAK-STAT inhibitors have changed this, drastically ameliorating symptoms and ultimately beginning to show evidence of impact on survival. Now, the genetic foundations of myelofibrosis and MDS/MPN are rapidly being elucidated and contributing to targeted therapy development. This has been empowered through updated response criteria for MDS/MPN and refined prognostic scoring systems in these diseases. The aim of this article is to summarize concisely the current and rationally designed investigational therapeutics directed at JAK-STAT, hedgehog, PI3K-Akt, bone marrow fibrosis, telomerase, and rogue epigenetic signaling. The revolution in immunotherapy and novel treatments aimed at previously untargeted signaling pathways provides hope for considerable advancement in therapy options for those with chronic myeloid disease. [ABSTRACT FROM AUTHOR]

In 2003,Laricobius nigrinusFender was introduced into the eastern United States as a biological control agent of the hemlock woolly adelgid (Adelges tsugaeAnnand). Following its release, it was discovered thatL. nigrinuswas hybridising and producing viable progeny withLaricobius rubidusLeConte, a species native to eastern North America. Recently,Laricobius osakensisMontgomery and Shiyake was imported from Japan into the USA as a potential biological control agent of hemlock woolly adelgid. Hybridisation betweenL. nigrinusandL. rubidusled to interest in the outcome of interactions betweenL. osakensisand the other twoLaricobiusspp. The purpose of this study was to determine ifL. osakensiscould mate withL. nigrinus, if they could produce hybrid progeny, and whether mating interferes with reproductive output.Laricobiusspp. were observed mating directly following emergence and found to be capable of producing sterile eggs in the absence of a mating event. Laboratory and confined field studies found no evidence thatL. osakensisandL. nigrinuscould produce hybrid progeny and the interaction between the two species did not result in a lower reproduction associated with interspecific mating attempts. Interbreeding should therefore not have an impact on biological control using these species. Fecundity experiments showed thatL. osakensisproduced eggs earlier in the season and at a higher rate thanL. nigrinus, suggesting thatL. osakensismay have the potential to be an even more successful biological control agent thanL. nigrinus. [ABSTRACT FROM AUTHOR]

Two adelgid predators, Laricobius nigrinus Fender and Laricobius rubidus LeConte, were recently discovered to produce hybrid progeny in the eastern United States. L. rubidus is native to eastern North America where it feeds on pine bark adelgid ( Pineus strobi Hartig) and L. nigrinus is native to western North America and was introduced to the eastern United States in 2003 for biological control of hemlock woolly adelgid ( Adelges tsugae Annand). Currently, L. nigrinus and L. rubidus form a mosaic of hybrid zones throughout the eastern United States. It is not known whether these zones will be maintained over time and whether hybridization will impact the efficacy of biological control or result in displacement of L. rubidus . Sampling from 2007 to 2012 on eastern hemlock ( Tsuga canadensis Carrière) showed a clear increase in L. nigrinus , a decrease in L. rubidus , and a steady proportion of hybrids. Sampling from 2010 to 2012 on both eastern hemlock and white pine ( Pinus strobus L.) at ten sites showed that L. nigrinus was more dominant on hemlock and L. rubidus was more dominant on white pine, which may demonstrate habitat preference and promote segregation between the two species. Site factors were tested for a relationship with the proportion of hybrids. The number of years L. nigrinus had been present at the site was the only factor that showed a relationship. The results suggest that L. nigrinus may displace L. rubidus on hemlock, but not on white pine at sites where they are both present. [ABSTRACT FROM AUTHOR]

Laricobius osakensis (Coleoptera: Derodontidae) was imported from Japan to the United States in 2006 for study in quarantine facilities as a potential biological control of Hemlock Woolly Adelgid. Laricobius osakensis was released from quarantine in 2010, but it was soon discovered that the colony also contained a cryptic species, Laricobius naganoensis. This led to the placement of L. osakensis back into quarantine and development of a method to purify the colony. To distinguish the two species, we designed a restriction fragment length polymorphism (RFLP) assay using mitochondrial DNA sequences and developed a non-lethal testing method. Twenty-one diagnostic nucleotide sites separated the two species, and they both exhibited extraordinary intra-specific haplotype diversity. Sequencing the ITS2 nuclear region did not produce evidence of hybridization between the species in the field or in the lab colony. Splitting the colony into small groups and testing their species composition was successful in isolating L. osakensis. Efforts should be made to maintain high genetic diversity in L. osakensis colonies. Continued genotyping of new colony stock will be necessary to fully characterize the diversity within both species. [ABSTRACT FROM AUTHOR]

Histone deacetylase 3 (HDAC3) contributes to the regulation of gene expression, chromatin structure, and genomic stability. Because HDAC3 associates with oncoproteins that drive leukemia and lymphoma, we engineered a conditional deletion allele in mice to explore the physiological roles of Hdac3 in hematopoiesis. We used the Vav-Cre transgenic allele to trigger recombination, which yielded a dramatic loss of lymphoid cells, hypocellular bone marrow, and mild anemia. Phenotypic and functional analysis suggested that Hdac3 was required for the formation of the earliest lymphoid progenitor cells in the marrow, but that the marrow contained 3-5 times more multipotent progenitor cells. Hdac3–/– stem cells were severely compromised in competitive bone marrow transplantation. In vitro, Hdac3–/– stem and progenitor cells failed to proliferate, and most cells remained undifferentiated. Moreover, one-third of the Hdac3–/– stem and progenitor cells were in S phase 2 hours after BrdU labeling in vivo, suggesting that these cells were impaired in transit through the S phase. DNA fiber-labeling experiments indicated that Hdac3 was required for efficient DNA replication in hematopoietic stem and progenitor cells. Thus, Hdac3 is required for the passage of hematopoietic stem/progenitor cells through the S phase, for stem cell functions, and for lymphopoiesis. [ABSTRACT FROM AUTHOR]

The t(8;21) and t(16;21) that are associated with acute myeloid leukaemia disrupt two closely related genes termed Myeloid Translocation Genes 8 (MTG8) and 16 (MTG16), respectively. Many of the transcription factors that recruit Mtg16 regulate haematopoietic stem and progenitor cell functions and are required to maintain stem cell self-renewal potential. Accordingly, we found that Mtg16-null bone marrow (BM) failed in BM transplant assays. Moreover, when removed from the animal, Mtg16-deficient stem cells continued to show defects in stem cell self-renewal assays, suggesting a requirement for Mtg16 in this process. Gene expression analysis indicated that Mtg16 was required to suppress the expression of several key cell-cycle regulators including E2F2, and chromatin immunoprecipitation assays detected Mtg16 near an E2A binding site within the first intron of E2F2. BrdU incorporation assays indicated that in the absence of Mtg16 more long-term stem cells were in the S phase, even after competitive BM transplantation where normal stem and progenitor cells are present, suggesting that Mtg16 plays a role in the maintenance of stem cell quiescence. [ABSTRACT FROM AUTHOR]

Medical Education 2011: : 166-175 Academic medical centres may adopt new learning technologies with little data on their effectiveness or on how they compare with traditional methodologies. We conducted a comparative study of student reflective writings produced using either an electronic (blog) format or a traditional written (essay) format to assess differences in content, depth of reflection and student preference. Students in internal medicine clerkships at two US medical schools during the 2008-2009 academic year were quasi-randomly assigned to one of two study arms according to which they were asked to either write a traditional reflective essay and subsequently join in faculty-moderated, small-group discussion ( n = 45), or post two writings to a faculty-moderated group blog and provide at least one comment on a peer's posts ( n = 50). Examples from a pilot block were used to refine coding methods and determine inter-rater reliability. Writings were coded for theme and level of reflection by two blinded authors; these coding processes reached inter-rater reliabilities of 91% and 80%, respectively. Anonymous pre- and post-clerkship surveys assessed student perceptions and preferences. Student writing addressed seven main themes: (i) being humanistic; (ii) professional behaviour; (iii) understanding caregiving relationships; (iv) being a student; (v) clinical learning; (vi) dealing with death and dying, and (vii) the health care system, quality, safety and public health. The distribution of themes was similar across institutions and study arms. The level of reflection did not differ between study arms. Post-clerkship surveys showed that student preferences for blogging or essay writing were predicted by experience, with the majority favouring the method they had used. Our study suggests there is no significant difference in themes addressed or levels of reflection achieved when students complete a similar assignment via online blogging or traditional essay writing. Given this, faculty staff should feel comfortable in utilising the blog format for reflective exercises. Faculty members could consider the option of using either format to address different learning styles of students. [ABSTRACT FROM AUTHOR]

Context: Research suggests that pharmaceutical marketing influences prescribing and may cause cognitive dissonance for prescribers. This work has primarily been with physicians and physician-trainees. Questions remain regarding why prescribers continue to meet with pharmaceutical representatives (PRs).Objective: To describe the reasons that prescribers from various health professions continue to interact with PRs despite growing evidence of the influence of these interactions.Design, Setting, and Participants: Multi-disciplinary focus groups with 61 participants held in practice settings and at society meetings.Results: Most prescribers participating in our focus groups believe that overall PR interactions are beneficial to patient care and practice health. They either trust the information from PRs or feel that they are equipped to evaluate it independently. Despite acknowledgement of study findings to the contrary, prescribers state that they are able to effectively manage PR interactions such that their own prescribing is not adversely impacted. Prescribers describe few specific strategies or policies for these interactions, and report that policies are not consistently implemented with all members of a clinic or institution. Some prescribers perceive an inherent contradiction between academic centers and national societies receiving money from pharmaceutical companies, and then recommending restriction at the level of the individual prescriber. Prescribers with different training backgrounds present a few novel reasons for these meetings.Conclusions: Despite evidence that PR detailing influences prescribing, providers from several health professions continue to believe that PR interactions improve patient care, and that they can adequately evaluate and filter information presented to them by PRs. Focus group comments suggest that cultural change is necessary to break the norms that exist in many settings. Applying policies consistently, considering non-physician members of the healthcare team, working with trainees, restructuring the current primary care model and offering convenient, individualized, non-biased educational options may aid success. [ABSTRACT FROM AUTHOR]

Background: Recent changes in healthcare system and training mandates have altered the clinical learning environment. We incorporated reflective writing into Internal Medicine clerkships (IMcs) in multiple institutions so students could consider the impact of clerkship experiences on their personal and professional development. We analyzed student reflections to inform curricula and support learning.Methods: We qualitatively analyzed the reflections of students at 3 US medical schools during IMcs (N = 292) to identify themes, tone, and reflective quality using an iterative approach. Chi-square tests assessed differences between these factors and across institutions.Findings: Students openly described powerful experiences. Major themes focused on 4 categories: personal issues (PI), professional development (PD), relational issues (RI), and medical care (MC). Each major theme was represented at each institution, although with significant variability between institutions in many of the subcategories including student role (PI), development-as-a-physician (PD), professionalism (PD) (p < 0.001). Students used positive tones to describe student role, development-as-a-physician and physician-patient relationship (PD) (p < 0.01-0.001), and negative tones for quality and safety (MC) (p < 0.05). Only 4% of writings coded as professionalism had a positive tone. Students employed a "reporting" voice in writing about clinical problem-solving, healthcare systems, and quality/safety (MC).Discussion: Reflection is considered important to professional development. Our analysis suggests that students at 3 institutions reflect on similar experiences. Theme variability across institutions implies curricula should be tailored to local culture. Reflective quality analysis suggests students are better equipped to reflect on certain experiences over others, which may impact learning. Student reflections can function as a mirror for our organizations, offer institutional feedback for support and improvement, and inform curricula for learners and faculty. [ABSTRACT FROM AUTHOR]

Uncontrolled hypertension is a significant health problem, due in part to patients' under-use of antihypertensive medications. This study explored what factors influence patients' decisions to accept or resist initiation of pharmacologic therapy for hypertension. A total of 210 subjects reviewed a clinical vignette and a hypothetical physician-patient dialogue. They then self-reported their likelihood of accepting the physician's recommendation to initiate therapy with an antihypertensive. Additional measures included trust in the physician, satisfaction, beliefs about medication effectiveness, safety and side-effects, and beliefs about hypertension. Analyses included bivariate correlations and multivariate linear regression. Findings suggest that the strongest correlates of intent to begin therapy were trust in the physician (r = 0.65, p< 0.01), satisfaction with communication (r= 0.53, p< 0.01), and belief that medications can effectively treat hypertension (r = 0.45, p< 0.01). Three other beliefs were also correlated with acceptance of treatment: the belief that physicians do not prescribe unsafe medications (r=0.25, p<0.01), worry about having hypertension (r = 0.18, p<0.01) and belief that hypertension is a very serious disease (r= 0.26, p<0.01). Acceptance of treatment was not correlated with worry about medication side-effects or belief that medications cause problems (p> 0.01). The tone of the dialogue (positive versus negative) did not result in statistically significant differences in subjects' responses on any measures. The study concludes that attention to patients' perceptions and beliefs about hypertension and medication efficacy may help patients accept pharmacologic treatment. [ABSTRACT FROM AUTHOR]

CONTEXT: Trainees are exposed to medical errors throughout medical school and residency. Little is known about what facilitates and limits learning from these experiences. OBJ'ECT/VE: To identify major factors and areas of tension in trainees' learning from medical errors. DESIGN, SETTING, AND PARTICIPANTS: Structured telephone interviews with 59 trainees (medical students and residents) from 1 academic medical center. Five authors reviewed transcripts of audiotaped interviews using content analysis. RESULTS: Trainees were aware that medical errors occur from early in medical school. Many had an intense emotional response to the idea of committing errors in patient care. Students and residents noted variation and conflict in institutional recommendations and individual actions. Many expressed role confusion regarding whether and how to initiate discussion after errors occurred. Some noted the conflict between reporting errors to seniors who were responsible for their evaluation. Learners requested more open discussion of actual errors and faculty disclosure. No students or residents felt that they learned better from near misses than from actual errors, and many believed that they learned the most when harm was caused. CONCLUSIONS: Trainees are aware of medical errors, but remaining tensions may limit learning, institutions can immediately address variability in faculty response and local culture by disseminating clear, accessible algorithms to guide behavior when errors occur. Educators should develop longitudinal curricula that integrate actual cases and faculty disclosure. Future multi-institutional work should focus on identified themes such as teaching and learning in emotionally charged situations, learning from errors and near misses and balance between individual and systems responsibility. [ABSTRACT FROM AUTHOR]

Purpose To assess primary care preceptors' perceptions of the issues involved in teaching when medical errors occur. In particular, we examined preceptors' responses to trainees involved in medical errors, factors influencing their response, and their perceptions of barriers to teaching from medical errors. Methods A total of 38 primary care preceptors participated in 7 focus groups on teaching and medical errors. Participants were drawn from medical schools throughout the northeastern USA. Content analysis of transcripts identified major themes. Results We developed a framework describing how preceptors and learners respond to medical errors, the factors that influence these responses, and the relationships between these. We also identified barriers to teaching from medical errors. Preceptors are especially sensitive to learners' distress as a result of errors. Emotional distress and self-doubt are seen as inimical to learning, possibly causing more attention to be directed to emotional support than to correction and instruction. At the same time, accepting responsibility for errors was seen as prerequisite to learning. For many preceptors, vivid recollections of their own errors during training were influential in determining how they in turn responded as preceptors; none reported having received training in this area. Conclusion This study describes preceptors' experiences of responding to trainees' medical errors, and identifies barriers to teaching from errors. The intersection of patient safety and medical education is a critical area for future research. We propose a framework that may help guide future research efforts, which should focus on identifying factors that promote faculty development to optimise learning and reduce the likelihood of future errors. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about how well clinicians are aware of their own adherence to clinical guidelines, an important indicator of quality. We compared clinicians’ beliefs about their adherence to hypertension guidelines with data on their actual performance. Methods: We surveyed 139 primary care clinicians at three Veterans Affairs medical centers, asking them to assess their own adherence to hypertension guidelines. We then extracted data from the centers’ clinical databases on guideline-concordant medication use and blood pressure control for patients cared for by these providers during a 6-month period. Data were collected for patients with hypertension and diabetes, hypertension and coronary disease, or hypertension with neither of these comorbid conditions. Results: Eighty-six clinicians (62%) completed the survey. Each clinician saw a median of 94 patients with hypertension (mean age, 65 years). Patients were treated with an average of 1.6 antihypertensive medications. Overall, clinicians overestimated the proportion of their patients who were prescribed guideline-concordant medications (75% perceived vs. 67% actual, P <0.001) and who had blood pressure levels <140/90 mm Hg on their last visit (68% perceived vs. 43% actual, P <0.001). Among individual clinicians, there were no significant correlations between perceived and actual guideline adherence (r = 0.18 for medications, r = 0.14 for blood pressure control; P ≥0.10 for both). Clinicians with relatively low actual guideline performance were most likely to overestimate their adherence to medication recommendations and blood pressure targets. Conclusion: Clinicians appear to overestimate their adherence to hypertension guidelines, particularly with regards to the proportion of their patients with controlled blood pressure. This limited awareness may represent a barrier to successful implementation of guidelines, and could be addressed through the use of provider profiles and point-of-service feedback to clinicians. [Copyright &y& Elsevier]

Context: Morbidity and mortality conferences in residency programs are intended to discuss adverse events and errors with a goal to improve patient care. Little is known about whether residency training programs are accomplishing this goal. Objective: To determine the frequency at which morbidity and mortality conference case presentations include adverse events and errors and whether the errors are discussed and attributed to a particular cause. Design, Setting, and Participants: Prospective survey conducted by trained physician observers from July 2000 through April 2001 on 332 morbidity and mortality conference case presentations and discussions in internal medicine (n = 100) and surgery (n = 232) at 4 US academic hospitals. Main Outcome Measures: Frequencies of presentation of adverse events and errors, discussion of errors, and attribution of errors. Results: In internal medicine morbidity and mortality conferences, case presentations and discussions were 3 times longer than in surgery conferences (34.1 minutes vs 11.7 minutes; P = .001), more time was spent listening to invited speakers (43.1% vs 0%; P<.001), and less time was spent in audience discussion (15.2% vs 36.6%; P<.001). Fewer internal medicine case presentations included adverse events (37 [37%] vs 166 surgery case presentations [72%]; P<.001) or errors causing an adverse event (18 [18%] vs 98 [42%], respectively; P = .001). When an error caused an adverse event, the error was discussed as an error less often in internal medicine (10 errors [48%] vs 85 errors in surgery [77%]; P = .02). Errors were attributed to a particular cause less often in medicine than in surgery conferences (8 [38%] of 21 medicine errors vs 88 [79%] of 112 surgery errors; P<.001). In discussions of cases with errors, conference leaders in both internal medicine and surgery infrequently used explicit language to signal that an error was being discussed and infrequently acknowledged having made an error. Conclusions: Our findings call into question whether adverse events and errors are routinely discussed in internal medicine training programs. Although adverse events and errors were discussed frequently in surgery cases, teachers in both surgery and internal medicine missed opportunities to model recognition of error and to use explicit language in error discussion by acknowledging their personal experiences with error. [ABSTRACT FROM AUTHOR]

Human telomerase reverse transcriptase (hTERT) is the catalytic component of a functional telomerase complex, which is important in maintaining cell immortality. In most normal human adult cells, the expression of telomerase is very low and/or transient. In contrast, almost 90% of human tumors express a relatively high level of telomerase implying the possibility of using hTERT as a universal candidate tumor antigen. In this study, we show that human monocyte-derived dendritic cells (DCs) lack telomerase activity. Similar to other normal somatic cells, DCs express the RNA (hTR) component but not the catalytic component, hTERT. We also show that telomerase activity could be reconstituted using either lipid-mediated transfection of the hTERT plasmid DNA or transduction with an E1-, E3-deleted adenoviral vector containing the hTERT gene. However, relative to plasmid transfection, adenoviral gene transfer produced higher levels of hTERT expression. Nine of 10 Adh TERT-transduced DCs were able to generate CTL responses, while only three of nine plasmid-transfected DCs did. CTLs primed against hTERT exhibited killing of telomerase positive but not telomerase negative tumor lines of diverse tissue origins. Antigenic specificity of these T cells to telomerase was further determined by introducing hTERT gene into a telomerase negative cell line, U2OS, by adenoviral transduction. Although some antigenic specificity was directed against adenoviral epitopes, the majority of CTLs were targeted against telomerase-derived antigen(s). Thus, the hTERT gene, particularly as delivered via the recombinant adenovirus, may be useful as vaccine to induce specific T-cell-mediated tumor immunity in cancer patients. In addition, our results suggest that telomerase activity and/or telomerase expression after hTERT gene transfer have a predictive value in the success of hTERT/DC-based cancer vaccination. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare maternity leave satisfaction between physicians and nonphysicians. Currently, paid maternal leave is not guaranteed in the United States, resulting in palpable dissatisfaction among parents. Previous studies have shown associations between length of paid leave and career satisfaction and maternal happiness. Materials and Methods: A Qualtrics® electronic survey was distributed to female professionals through email and social media from April 2019 to March 2020. Inclusion criterion was ≥1 child by birth or adoption, or active pregnancy. Continuous and categorical data were analyzed using two-sample t-test and chi-square, respectively. Results: Of 808 respondents, 77% were physicians. Mean age at birth/adoption of first child was higher in physicians versus nonphysicians (32.1 years vs. 29.7 years; p < 0.001). Physicians took shorter maternity leave than nonphysicians (10.9 weeks vs. 12.0 weeks, p = 0.017) with half of that time paid by employers (5.4 weeks vs. 5.9 weeks, p = 0.2). Dissatisfaction was high among physicians (85.1%) and nonphysicians (92.4%) that correlates with maternity leave compensation dissatisfaction (49% vs. 71.3%, p < 0.001). Thirty-four percent of physicians versus 41% of nonphysicians stated that their health was negatively impacted by maternity leave length. Physicians and nonphysicians reported similar incidences of depression, and breastfeeding, delivery, and other postpartum complications. When queried, 38.8% of physicians and 57% of nonphysicians said they would desire >16 weeks of paid maternity leave (p < 0.001). Conclusions: In conclusion, dissatisfaction among professional women on maternity leave duration and compensation is high in the United States. Given health implications for both mother and child, this should invite further discussion and changes. [ABSTRACT FROM AUTHOR]

The article presents a study which describes the contribution of myeloid translocation gene 16/Eto2, a transcriptional corepressor that is disrupted in acute myeloid leukemia, to murine T-cell development.

Abstract: Objective: To report how patient viewpoints on caring inform curriculum development for teaching sessions on delivering bad news, making the transition to palliative care, and communicating about a medical error. Methods: We conducted focus groups that used patients recruited from the surrounding community to view videotapes of physicians delivering bad news, talking with a patient about palliative care, and communicating about a medical error. We used focus group results, combined with evidence from the medical literature to inform curriculum content for workshops conducted with Internal Medicine and Family Medicine residents at the University of Massachusetts Medical School. Results: Patient perspectives on caring gathered through focus groups differed in significant ways from the existing medical literature on caring when providers are communicating in the challenging situations that were depicted. Our data pointed out that individual reactions were unique and sometimes contradictory in that one person saw behavior as caring that others thought was uncaring. Participants often used qualifiers in their comments like “appropriate” amounts of information, “measured” empathy, chooses words carefully to reflect the relative nature of caring. “Arranges to meet healthcare needs,” an issue that extends beyond the encounter, was seen as a new component of caring not previously described. Applying these concepts to curriculum required that we not only focus on the behavioral skills involved in these tasks, but also the processes of assessing patient''s informational and emotional needs, and then taking steps to meet them, while adjusting behavior in real time to meet patients needs for caring. Workshops delivered were highly evaluated by residents. Conclusion: Patient perspectives on caring when providers deliver bad news, discuss transitions to palliative care, and communicate about a medical error reinforce that patient expectations for caring are highly contextualized and physician behavior needs to be individualized. We taught residents not only behavioral skills, but also the process skills of anticipating patient reactions, recognizing patient clues, planning and choosing effective strategies on the fly, and assessing one''s own performance characteristic of communication expertise. Practice implications: Teaching caring attitudes with challenging communication tasks requires that learners appreciate and value not only caring behaviors but also learn the process by which they must adjust and titrate their actions to meet patient needs. [Copyright &y& Elsevier]

Objective: To provide a detailed description of the steps involved in a laparoscopic radical prostatectomy in relation to the complex neurovascular anatomy of the male pelvis.Aim and hypothesis: We aimed at delineating the neurovascular anatomy to assist in nerve preservation during laparoscopic and robotic radical prostatectomies.Methods: A team of urologists and an anatomist performed anatomic dissections of 12 male cadavers using a combination of laparoscopic equipment, magnification, and open surgical dissection. Each step involved in laparoscopic prostatectomy was reviewed in relation to the possible impact the step could have on the neurovascular bundles.Results: Dissections were performed systematically to mimic various steps of laparoscopic and robotic prostatectomy. The neurovascular bundles were identified and correlated with video images of actual surgery. This enabled us to construct computer simulations and show the actual nerves on the operative pictures. We specially unraveled the relationship between neurovascular bundles and lateral pelvic and Denonvillier’s fascias, both of which enclose and hide these important structures. The course of the bundles was traced from its origin at pelvic plexus to its distal course along the urethra.We also showed the important relationship between pelvic plexus ganglions and seminal vesicles to illustrate the vulnerability of these nerves to thermal, electrical and/or crush injury during seminal vesicle and prostatic pedicle dissections. The importance of additional fine neural plexus along the posterior and antero-lateral surface of the prostate was shown by both gross anatomical and microscopic images. The distal precarious location of the bundles was illustrated by dissections showing anteriorly lifted prostate.These anatomico-operative correlations have not been published for laparoscopic and robotic prostatectomies, which differ significantly in its visual angles, magnifications and sometimes three-dimensional (3D) visualization from its open counter part.Conclusion: Laparoscopic and robotic radical prostatectomy provides exposure and visualization of male pelvis not previously appreciated. It is only through a careful reexamination of the anatomy of the male pelvis, in the context of this new procedure, that the improvements in visualization and exposure benefit the surgeon. Our work provides a detailed map relating to operative steps to aid the surgeon in the performance of a nerve sparing robotic and laparoscopic radical prostatectomy. [Copyright &y& Elsevier]

COE, CHRISTOPHER L, BOSENBERG, LEON T, FISCHER, MELISSA, and LEVINE, SEYMOUR Psychological Factors Capable of Preventing the inhibition of Antibody Responses in Separated Infant Monkeys CHILD DEVELOPMENT, 1987, 58, 1420-1430 The capacity of infant squirrel monkeys to mount an antibody response to viral challenge was evaluated after removal from their mothers m several social and physical environments Control and separated infants were rejected with a benign virus, the bacteriophage X174, and levels of neutralizing antibody were assessed for 3 weeks Infants separated alone m an unfamiliar environment showed a significant reduction m antibody levels as compared to control infants Allowing infants to remain in the home environment, either alone or with peers, prevented this inhibition of antibody responses from occurring Similarly, providing familiar peers in the novel environment facilitated the normal expression of antibody responses These results indicate that the trauma of maternal separation is significantly reduced when infants are familiar with the separation environment or familiar social companions are available The reduced antibody response was associated with the highest level of adrenal activation induced by the unfamiliar separation condition, but antibody titers and plasma cortisol levels could not be specifically correlated in individual infants. [ABSTRACT FROM AUTHOR]

Penile strangulation is an infrequent clinical condition that has widely been reported. It usually results following placement of a constriction device to enhance sexual stimulation. Early treatment is essential to avoid potential complications, including ischemic necrosis and autoamputation. We describe the use of a Large Orthopedic Pin Cutter to remove a metal penile constriction device in the Emergency Department (ED). This case report describes the relatively safe technique of using an instrument available in many hospitals that can be added to the physician's arsenal in the removal of metal constriction devices. [ABSTRACT FROM AUTHOR]

Objective: To discuss the study design and data analysis for three‐phase interrupted time series (ITS) studies to evaluate the impact of health policy, systems, or environmental interventions. Simulation methods are used to conduct power and sample size calculation for these studies. Methods: We consider the design and analysis of three‐phase ITS studies using a study funded by National Institutes of Health as an exemplar. The design and analysis of both one‐arm and two‐arm three‐phase ITS studies are introduced. Results: A simulation‐based approach, with ready‐to‐use computer programs, was developed to determine the power for two types of three‐phase ITS studies. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from −0.9 to 0.9 with various effect sizes. The power increased as the sample size or the effect size increased. The power to detect the same effect sizes varied largely, depending on testing level change, trend changes, or both. Conclusion: This article provides a convenient tool for investigators to generate sample sizes to ensure sufficient statistical power when three‐phase ITS study design is implemented. [ABSTRACT FROM AUTHOR]

Myeloid cell leukemia 1 ( Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade, poor survival, and resistance to chemotherapy. Mcl-1 is amplified in many human cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is a promising cancer target. Here, we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation, mitochondrial depolarization, and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors. PDB ID codes Comp. 2: ; Comp. 5: . [ABSTRACT FROM AUTHOR]

Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was -7.5 SDs with a very delayed bone age of-13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (-5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: We compared the operative and immediate postoperative experience of the trocar-based Prolift® and non-trocar-based Elevate® techniques used to repair vaginal prolapse. Methods: A retrospective review of Prolift and Elevate repairs was performed. Baseline characteristics and operative and postoperative variables evaluated included compartment(s) repaired, adjacent organ injury, operative time (OT), change in hemoglobin (ΔH), pain score, narcotic use, length of stay (LOS), and short-term complications. Categorical variables were assessed as counts and percent frequency. Data were compared using chi-squared analysis and paired t test. Results: Prolift ( n = 143) and Elevate ( n = 77) patients were similar in age ( p = 0.19). Concurrent hysterectomy was done in 22 (15.4 %) and 24 (31.2 %), respectively, and concurrent midurethral sling placed in 100 (70 %) and 50 (65 %), respectively. LOS (median, 25th,75th) after anterior/apical compartment repairs was shorter with Elevate, whether with (1.0; 1.0,1.5 vs. 2.0 days;1.0, 2.0; p = 0.003) or without (2.0; 1.0, 2.0 vs. 2.0 days; 2.0, 3.0; p = 0.024) hysterectomy, but no differences in OT, ΔH, pain score, or narcotic use occurred. Posterior compartment mean pain scores were lower with Prolift (3.6 ± 2.2 vs. 1.7 ± 1.5, p = 0.035), and three-compartment-repair pain scores were lower with Elevate (0.6 ± 1.3 vs 2.5 ± 1.9; p = 0.013). Three bladder injuries occurred with Prolift but none with Elevate. Conclusions: Operative and postoperative experiences were similar between groups; however, Elevate anterior/apical repairs had shorter LOS, which might reflect more aggressive discharge planning. There were no bowel or major vascular injuries, and the Prolift trocar bladder injuries did not alter the surgical procedure. [ABSTRACT FROM AUTHOR]

Abstract: Hybridization between introduced biological control agents and native species has the potential to impact native biodiversity and pest control efforts. This study reports progress towards predicting the outcome of hybridization between two beetle species, the introduced Laricobius nigrinus Fender and the native L. rubidus LeConte. L. nigrinus is a predator from western North America introduced to hemlock stands in the eastern United States as a biological control of the hemlock woolly adelgid [Adelges tsugae Annand (Hemiptera: Adelgidae)]. Laricobius rubidus is a closely related eastern species that also feeds on A. tsugae but prefers pine adelgids (Pineus strobi Hartig) on white pine (Pinus strobus L.). Six microsatellite markers plus mitochondrial COI haplotypes were used to examine genetic structure of these two Laricobius species across North America. In their native ranges, major geographic features have impacted gene flow: the intermountain region in the West, and the Appalachian Mountains in the East. Analysis of 1229 individuals from adelgid-infested hemlock trees in release sites in the eastern United States found widespread hybridization with asymmetrical introgression towards L. nigrinus on hemlock. The ultimate outcome of hybridization could therefore be a complex mosaic of genetic introgression across the landscape, depending on the distribution of hemlock and pine. This study confirms the importance of evaluating the potential for introduced biological control agents to hybridize with their native relatives. This system also provides an excellent opportunity to improve our understanding of emerging hybrid zones by tracking its progress over time. [Copyright &y& Elsevier]

The article reviews several articles related to medicine including "Undergraduate Medical Education," in the "Journal of General Internal Medicine" in 2008, "Continuing Medical Education," in the journal "Annals of Internal Medicine" in 2007, and "Undergraduate Medical Education," in the "Journal of Urology" in 2008.

This journal watch is sponsored by the Alliance for Clinical Education (ACE). The purpose of this article is to summarize medical education manuscripts from specialty journals that are important and relevant to educators across specialties. Specialties included in our review were cardiology, gastroenterology, general internal medicine, pulmonology, nephrology, hematology and oncology, endocrinology, rheumatology, infectious disease, and neurology. We are grateful to Teaching and Learning in Medicine and ACE for giving us the opportunity to publish this review. The Clerkship Directors in Internal Medicine Research Committee conducted this review. Included are English articles published from September 2006 through September 2007. PubMed was searched for peer-reviewed research publications reporting primary data on medical education. Medical subject heading terms included combinations of medical education, medical student, residency training, practice, undergraduate medical education, graduate medical education, internship and residency, and continuing medical education. We also reviewed the bibliographies of all articles found though our PubMed search to identify additional articles that may not have been included in PubMed's search engine. Furthermore, we discussed identified articles with content experts in each specialty to ensure that appropriate journals and articles were included from each subspecialty. The journals that we selected for review are not often read by the typical medical educator. We included articles from general and subspecialty journals of internal medicine excluding the following, which have a focus on medical education or cross-specialties: Academic Medicine, Advances in Health Science Education, Medical Education, Medical Teacher, Teaching and Learning in Medicine, Journal of the American Medical Association, and New England Journal of Medicine. Specialties included in our review were cardiology, gastroenterology, general internal medicine, pulmonology, nephrology, hematology and oncology, endocrinology, rheumatology, infectious disease, and neurology. We also reviewed the bibliographies of all articles found though our PubMed search to identify additional articles. Furthermore, we discussed identified articles with content experts in each specialty to ensure that appropriate journals and articles were included from each subspecialty. Authors rated each article based on relevance, rigor, importance, and generalizibility of findings. We also sought to include articles from each phase in the continuum of medical education: undergraduate, graduate, and continuing medical education as well as qualitative and quantitative studies. Articles were ranked by each author. We then held conference calls and had e-mail discussions to establish consensus on the articles included in this review. The following is a summary of each selected article grouped by theme. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Caring is closely associated with reduced malpractice litigation, adherence to treatment and even symptom relief. Caring also is included in pay for performance formulas as well as widely utilized for quality improvement purposes. Our objective in this prospective qualitative study was to define caring behaviors associated with three challenging encounters: discussing the transition from curative to palliative care, delivering bad news (cancer), and discussing a medical error (misplaced test result). The purpose was to lay the groundwork for the creation of a ‘patient-centered’ caring attitude checklist that could help the healthcare provider understand and ultimately enhance the patient''s experience of care. Methods: Groups of randomly selected lay people, henceforth referred to as patients: (1) engaged in ‘think aloud’ exercises to help create a 15-item caring behavior checklist; (2) used the checklist to rate videotapes of simulated challenging encounters conducted by twenty primary care physicians (total of 600 ratings sets); and (3) participated in 12 separate 1.5h focus groups discussing the caring (and non-caring) behaviors exhibited in videotapes of the highest and lowest rated encounters. Results: Thirteen behaviors emerged as focal for describing a doctor''s caring attitude but with disagreement as to whether specific examples of these behaviors were ‘caring’ or ‘uncaring.’ For example, although the concept of empathic inquiry was considered important by most patients, the physician question, “Is there someone you can call or talk with” (about a cancer diagnosis) was interpreted by one patient as ‘very caring’ while another was ‘impressed with how uncaring’ the statement appeared. Conclusion: At the conceptual level there is a set of behaviors that represent caring, however, the manifestation of these behaviors is ‘in the eye of the beholder.’ The most important element of caring may not be the set of behaviors but a set of underlying abilities that include taking the patient''s perspective and reflecting on the patient''s responses. Practice implications: Medical education must focus on the underlying abilities of caring. [Copyright &y& Elsevier]

Background: The 4th-year internal medicine subinternship (subI), with its strong emphasis on experience-based learning and increased patient responsibilities, is an important component of undergraduate medical education. Discussions have begun amongst educational leaders on the importance of standardizing curriculum and evaluation tools utilized during the subinternship. Purpose: The objective of this survey was to describe the current state of educational practices regarding the subI curriculum, use of Clerkship Directors in Internal Medicine (CDIM) curricular guidelines, evaluation methodologies, and subintern call frequency and duty hours. Methods: The survey was a part of the CDIM annual survey sent to 109 institutional members in 2005. The subinternship survey included 17 questions that addressed the prevalence of formal curricula in the subinternship, use of CDIM curricular guidelines and resources, and the evaluation tools utilized for assessment of the subinternship. Two questions examined the call frequency and duty hours of the subinterns. Results: Eighty-eight members responded (81%). Of the respondents, 37% have a formal curriculum and 35% used CDIM curricular guidelines for the subinternship. More than half of the respondents agreed that the curricular guide helped organize their subI rotations (53%), and 48% agreed that it enhanced the quality of subI education. A global rating summative evaluation form (56%) was the most commonly used evaluation tool in the subinternship. Objective Structured Clinical Examinations1-3 (1%) and Mini-Clinical Evaluation Exercise (mini-CEX)4(2%) were much less utilized during the subinternship. The respondents expressed an interest in the development of a standardized exam (47%) and clinical assessment tools such as the mini-CEX (59%). The vast majority of IM subinterns participate in 3 to 9 calls per rotation and spend less than 80 hr in the hospital per week. Conclusions: A formal curriculum is offered in slightly more than one third of subIs. Clerkship directors expressed interest in developing standardized evaluation tools to assess subintern competencies. The majority of IM subinterns spend less than 80 hr in the hospital per week. Further studies are needed to assess barriers to incorporating a formal curriculum and develop standardized tools to assess subintern competencies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Disclosure of medical errors is encouraged, but research on how patients respond to specific practices is limited. OBJECTIVE: This study sought to determine whether full disclosure, an existing positive physician-patient relationship, an offer to waive associated costs, and the severity of the clinical outcome influenced patients' responses to medical errors. PARTICIPANTS: Four hundred and seven health plan members participated in a randomized experiment in which they viewed video depictions of medical error and disclosure. DESIGN: Subjects were randomly assigned to experimental condition. Conditions varied in type of medication error, level of disclosure, reference to a prior positive physician-patient relationship, an offer to waive costs, and clinical outcome. MEASURES: Self-reported likelihood of changing physicians and of seeking legal advice: satisfaction, trust, and emotional response. RESULTS: Nondisclosure increased the likelihood of changing physicians, and reduced satisfaction and trust in both error conditions. Nondisclosure increased the likelihood of seeking legal advice and was associated with a more negative emotional response In the missed allergy error condition, but did not have a statistically significant impact on seeking legal advice or emotional response in the monitoring error condition. Neither the existence of a positive relationship nor an offer to waive costs had a statistically significant impact. CONCLUSIONS: This study provides evidence that full disclosure is likely to have a positive effect or no effect on how patients respond to medical errors. The clinical outcome also influences patients' responses. The impact of an existing positive physician-patient relationship, or of waiving costs associated with the error remains uncertain. [ABSTRACT FROM AUTHOR]

• PI3k-δ is the most abundant PI3K subunit among monocytic leukemia samples. • CMML patient samples are uniquely sensitive to PI3K-δ inhibition by umbralisib. • Ruxolitinib and umbralisib synergistically decrease growth in CMML patient samples. • This combination can simultaneously suppress STAT5, ERK, S6, and AKT signaling. Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome characterized by monocytic proliferation in the presence of dysplastic bone marrow changes, inflammatory symptoms, and propensity for transformation to acute myeloid leukemia (AML), with a poor prognosis and limited treatment options. Unlike the α and β isoforms, the phosphatidylinositol-3-kinase (PI3K)–δ signaling protein is predominantly expressed by hematopoietic cells and therefore has garnered interest as a potential target for the treatment of lymphomas and leukemias. We revealed a pattern of increased PIK3CD:PIK3CA ratio in monocytic M5 AML patients and cell lines, and this ratio correlated with responsiveness to pharmacological PI3K-δ inhibition in vitro. Because CMML is a disease defined by monocytic clonal proliferation, we tested the PI3K-δ inhibitor umbralisib as a single agent and in combination with the JAK1/2 inhibitor ruxolitinib, in CMML. Our ex vivo experiments with primary CMML patient samples revealed synergistic inhibition of viability and clonogenicity with this combination. Phospho-specific flow cytometry revealed that dual inhibition had the unique ability to decrease STAT5, ERK, AKT, and S6 phosphorylation simultaneously, which offers a mechanistic hypothesis for the enhanced efficacy of the combination treatment. These preclinical data indicate promising activity by co-inhibition of PI3K-δ and JAK1/2 and support the use of ruxolitinib + umbralisib combination therapy in CMML under active clinical investigation. [ABSTRACT FROM AUTHOR]