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It has been my great good fortune in this life to work, in different ways and at different times, with two extraordinary educators. I have known Pedro Noguera, now Dean of the Rossier School of Education at USC, for upwards of 30 years, since he was my undergraduate professor at UC Berkeley. I have known Michael Matsuda, Superintendent of the Anaheim Union High School District (AUHSD), since we initiatied a robust partnership for leadership preparation between our two institutions in 2018. In Hebrew, a shadchan is a matchmaker. When I read the call for this special issue of VUE, with its focus on schools as community institutions, I thought of them both. My role was mainly that of shadchan; I proposed the Conversations in Urban Educationersation to the two of them, and edited the published version into something comprehensible for a reader outside of the California context. Dean Noguera and Superintendent Matsuda had met before; on December 16, 2021, Noguera interviewed Matsuda via Zoom, and the district produced a transcript. That interview, edited for comprehension as well as flow, is provided below.Matsuda has served as the superintendent of AUHSD for eight years. It is a large, urban school district located in Orange County, not far from Disneyland. AUHSD is a majority minority school district that covers five cities, including Anaheim. The district enrolls over 29,000 students, and about 45 different languages are spoken by the families it serves. It is a gateway community that serves large numbers of refugee immigrants. Demographically, the district is predominantly Latin-X, (65%), with another 20% of its students from Asian and Pacific Islander backgrounds. The overwhelming majority of students are from low-income households, with a substantial number (approximately 4,000) who lack stable housing.

The dilemma of how to categorize and classify diseases has been debated for centuries. The field of medical genetics has historically approached nosology based on clinical phenotypes observed in patients and families. Advances in genomic sequencing and understanding of genetic contributions to disease often provoke a need to reassess these classifications. The Clinical Genome Resource (ClinGen) has developed frameworks to classify the strength of evidence underlying monogenic gene-disease relationships, variant pathogenicity, and clinical actionability. It is therefore necessary to define the disease entity being evaluated, which can be challenging for genes associated with multiple conditions and/or a broad phenotypic spectrum. We therefore developed criteria to guide "lumping and splitting" decisions and improve consistency in defining monogenic gene-disease relationships. Here, we outline the precuration process, the lumping and splitting guidelines with examples, and describe the implications for clinical diagnosis, informatics, and care management.

PURPOSESeveral groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease, and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed.METHODSThe GenCC drafted harmonized definitions for differing levels of gene-disease validity based on existing resources, and performed a modified Delphi survey with three rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members.RESULTSBased on 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contains 15,241 gene-disease assertions on 4,569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%.CONCLUSIONTerminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.

The discovery of BRCA1 and BRCA2 in the 1990s revolutionized the way we research and treat breast, ovarian, and pancreatic cancers. In the case of pancreatic cancers, germline mutations occur in about 10–20% of patients, with mutations in BRCA1 and BRCA2 being the most common. BRCA genes are critical in DNA repair pathways, particularly in homologous recombination, which has a serious impact on genomic stability and can contribute to cancerous cell proliferation. However, BRCA1 also plays a fundamental role in cell cycle checkpoint control, ubiquitination, control of gene expression, and chromatin remodeling, while BRCA2 also plays a role in transcription and immune system response. Therefore, mutations in these genes lead to multiple defects in cells that may be utilized when treating cancer. BRCA mutations seem to confer a prognostic benefit with an improved overall survival due to differing underlying biology. These mutations also appear to be a predictive marker, with patients showing increased sensitivity to certain treatments, such as platinum chemotherapy and PARP inhibitors. Olaparib is currently indicated for maintenance therapy in metastatic PDAC after induction with platinum-based chemotherapy. Resistance has been found to these therapies, and with a 10.8% five-year OS, novel therapies are desperately needed.

Vandetanib is a once-daily oral multikinase inhibitor that targets the rearranged during transfection (RET) tyrosine kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor. Among its observed toxicity profile is QT prolongation, diarrhea, and rash, including photosensitivity. This article presents 3 patients with photoinduced cutaneous side effects of vandetanib, including both photoallergic and phototoxic reactions. We review the spectrum of cutaneous photosensitivity reactions and the necessity of histopathologic evaluation to distinguish photoallergic and phototoxic reactions. Given its high prevalence of specifically photoinduced side effects and the variety of the histologic and clinical presentations, reinforcing attentive sun protection could potentially prevent dose reduction or drug cessation in patients treated with vandetanib.

Globally, seafood is an important protein source because it is a nutritious food source produced with relative efficiency compared to other proteins. Because of problems related to overfishing and deleterious environmental impacts, over the last decade, non-governmental organizations (NGOs) have increased their focus on seafood sustainability while businesses have incorporated this issue into their corporate social responsibility (CSR) reporting. Sustainability is a concept that can be addressed in terms of scale of issues considered (narrow vs. broad) as well as the scope of how they are measured (undemanding or demanding). Currently, the message of seafood sustainability is becoming complicated in that the journey toward sustainability is being referred to as having achieved a state of sustainability. In addition, companies making a “sustainable” declaration are often at different points in the “scale/scope” arena. As a result, buyers, retailers and consumers have difficulty differentiating between these products. Furthermore, they often assume that a “sustainable” product has no further need for improvement, when in fact this is rarely the case. This change in reference from a continual process (a journey) to a static point (it is sustainable) limits further advances in seafood sustainability and the drive for continual improvement. Herein, the “Law of the Minimum”, growth toward an end goal will occur until one factor becomes limiting, is adopted as an analogy for sustainability. By refocusing the sustainability discussion on a progressive series of challenges to be met, the discussion will return to the journey as the central point. Doing so will help refresh the dialogue around seafood, and to create new opportunities for improvement.

Background/Context Peer Assistance and Review (PAR), or peer review as it has historically been called, has existed in a handful of school districts since the early 1980s. In 1999, California became the first state to pass PAR legislation; at that time, a major district had not implemented the policy in over a decade. Setting This is an in-depth study of one urban district in California, given the pseudonym Rosemont, as it implemented PAR following California's legislation. Program With PAR, designated “PAR coaches”—teachers identified for excellence and released from teaching duties full-time for 2–3 years—provide mentoring to teachers new to the district or the profession, intervention for identified veteran teachers experiencing difficulty, and the formal personnel evaluations of both groups. These PAR coaches are not school based but rather report to an oversight panel composed of teachers and administrators from across the district. Research Questions A companion study previously found that the rate of dismissals increased dramatically after the implementation of PAR in Rosemont. This study examines one aspect of Rosemont's PAR program, its oversight panel. The study examines three questions that in turn address the design, process, and outcomes of PAR and the PAR panel in Rosemont: (1) How did the PAR panel work? (2) How, if at all, did the presence of an oversight panel affect the teacher evaluation process? (3) How, if at all, did the presence of an oversight panel affect personnel outcomes? Participants The study involved all PAR coaches (10) and all members of the PAR panel (9) for the first year of program implementation. Research Design The study employed an embedded single-case design in Rosemont over 1 1/2 years. Data Collection and Analysis The study relied on observations (311 hours of meetings) and semistructured interviews (39). I used QSR NVivo data management. I coded observation scripts and interview transcripts were coded to a schema developed from the progressive coding patterns that I observed, and analyzed them in response to the research questions. Findings The Rosemont data demonstrate that the PAR panel both supported the coaches to do their jobs and held them accountable. The community of educators created by PAR and the PAR panel appears to have proved a more rigorous, evidence-based check on classroom teaching performance. I also present data demonstrating the shortcomings of the PAR panel structure in the face of enduring norms against accountability in education. Conclusions Significant shifts in organizational structure occurred to support the PAR coaches in their role as evaluators. Making the typically solitary practice of teacher evaluation transparent to colleagues fundamentally altered the nature of educational accountability.

Districts play a key and relatively unexamined role in distributed leadership research. This article explores how leadership was distributed through a district structure designed to improve the quality of teaching by improving the quality of teacher evaluation. It examines peer assistance and review, a policy designed to address the key problems of traditional teacher evaluation by allowing administrators and teacher leaders to share accountability for evaluation processes and decisions. The article presents data from a peer assistance and review program in one urban district, detailing how the program distributed accountability for teacher quality across the district organization. The article extends previous work on distributed leadership by showing how the design of shared tasks can effectively distribute accountability. The article also extends previous work on distributed leadership by elucidating the democratic effects of that distribution. As such, the article addresses questions of instrumentality (i.e., how can district leaders design and implement a better teacher evaluation system?) and agency (i.e., what are the political implications of distributing formal authority for teacher evaluation out of the hands of administrators and into the hands of teachers?).

Scholars and practitioners have long criticized teacher evaluation as ineffective. Peer assistance and review (PAR) alters traditional teacher evaluation, as master teachers conduct summative as well as formative assessment of beginning teachers and veteran teachers in need of intervention. Relying on data from a longitudinal case study of one urban district, this article describes key components of teacher evaluation with PAR, in particular how it differs from teacher evaluation as typically conducted by principals. Findings are reported across six key factors: time, professional development, transparency, labor relations, decision making, and accountability. Notably, a substantially higher level of accountability appeared present with PAR than prior to program implementation. In contrast to popular opinion, this study provides an example of teachers willing and able to engage in the summative evaluation of their peers, a key component of professionalism and professionalization. Implementation challenges...

The reproductive status and body condition of 195 (≥185 cm curved fork length, CFL; assigned age 7 and above) Atlantic bluefin tuna were assessed in the Gulf of Maine during the commercial fishing season of June–October, 2000–2002. Given the distance between known spawning and feeding grounds, the prevailing paradigm for Atlantic bluefin tuna (Thunnus thynnus thynnus, L.) suggests that the most likely histological state for females arriving in the Gulf of Maine after spawning would be a resting or quiescent state with little or no perigonadal fat. Alternatively, the presence of mature or mature-inactive histological states in some females supports a more varied or individualistic model for bluefin reproduction. No relationship was found between body condition and reproductive status. Males were found in all reproductive stages, but were more likely to be in spawning condition (stages 4 and 5) or a mature-inactive state (stage 6) in June and July. Female bluefin tuna were found in stage 1 (immature or non-spawning) and stage 6 (mature-inactive). Stage 6 females were only present in June and July and smaller females ( 235 cm CFL) sampled during those same months. The presence of smaller females in stage 6 arriving at the same time as larger females in stage 1 indicates that Western Atlantic bluefin tuna may have an asynchronous reproductive schedule and may mature at a smaller size than the currently accepted paradigm suggests.

Scholars have argued that combining supervision and evaluation is a conflict of interest that will damage the coaching process. Peer assistance and review (PAR) is an approach to the supervision and evaluation of teachers that runs counter to this argument, as the coach charged with providing professional support to a new or struggling veteran teacher also plays a formal role in that teacher’s summative personnel evaluation. This article presents data from a study of one urban school district in California as it implemented a PAR program, asking: (1) To what degree do PAR mentees trust their coaches, who conduct both formative and summative assessments? (2) How do PAR mentees who do not trust their coaches differ from those who do? Mentees’ trust in their coaches was a point and a half higher than their lack of trust in their coaches, as self-reported on a 4-point Likert scale. Those mentees who did not report a high degree of trust in their coaches were low-performing mentees.

This article explores a case of shifting leadership responsibility for teacher evaluation. Peer Assistance and Review (PAR) formally involves teachers in the summative evaluation of other teachers—although the boundaries of the involvement are often vague. Since teacher evaluation has traditionally been the domain of school principals, involving teachers in teacher evaluation raises questions about how those faced with the new role make sense of it and enact it. The article draws on theories of professions, organizations, and institutions to examine the implementation of PAR in one large urban school district. Findings suggest that, despite positive sentiments about the policy across stakeholder groups, those involved wanted principals to remain a central figure in the evaluation of teachers in PAR. Education’s hierarchical norms, the difficulty of conducting evaluations, district leadership, and program ambiguity are identified as challenges to distributing leadership.

Most gastrointestinal stromal tumors (GISTs) carry activating mutations of the KIT gene encoding the receptor tyrosine kinase KIT. In a previous study we were able to show an association between the lack of KIT mutations (wild-type GISTs) and the presence of a significant epithelioid tumor component. A very recent study described the occurrence of PDGFRalpha mutations in KIT wt GISTS. Therefore, we studied a panel of 87 GISTs for mutations in the hot spot regions of the PDGFRalpha gene with single strand conformation polymorphism analysis and sequencing and correlated the PDGFRalpha status with pathomorphological data. We detected 20 cases with exon 18 mutations but none with exon 12 mutations. The mutations were located in the second kinase domain of PDGFRalpha with 16 point mutations, and four larger deletions of 9 to 12 bp. All cases with mutations in the PDGFRalpha gene revealed wild-type KIT in common regions of mutation, ie, exons 9 and 11. Most interestingly, the occurrence of PDGFRalpha mutations was significantly associated with a higher frequency of epithelioid or mixed morphology (18 of 20 cases, P0.0001) and gastric location (all cases, P = 0.0008). Our data indicate that GISTs represent distinctive entities, differing in genetic, biological, and morphological features.

PURPOSE: N-(4-hydroxyphenyl) retinamide ([4-HPR], Fenretinide; R.W. Johnson Pharmaceutical Research Institute, Springhouse, PA) and tamoxifen (TAM) have synergistic antitumor and chemopreventive activity against mammary cancer in preclinical studies. We performed a pilot study of this combination in women at high risk for developing breast cancer. PATIENTS AND METHODS: Thirty-two women were treated with four cycles of 4-HPR, 200 mg orally (PO) for 25 days of each 28-day cycle, and TAM, 20 mg PO once daily for 23 months beginning after 1 month of 4-HPR alone. Tolerability, dark adaptometry, tissue biopsies, and retinoid plasma concentrations (Cp) were evaluated. RESULTS: Symptomatic reversible nyctalopia developed in two patients (6%) on 4-HPR, but 16 (73%) of 22 patients had reversible changes in dark adaptation, which correlated with relative decrease in Cp retinol (P ≤ .01). Four patients stopped treatment for side effects, and 84% of patients had hot flashes. Other commonly reported (grade ≤ 2) reversible toxicities included skin and ocular dryness, fatigue, and mood changes. Serum high-density lipoprotein increased and cholesterol decreased from baseline to month 4. Baseline mean ± SD Cp retinol was 708 ± 280 ng/mL. Mean ± SD Cp of 4-HPR, N-(4-methoxyphenyl) retinamide (4-MPR), and retinol after 1 month of 4-HPR were 0.34 ± 0.21 μmol/L, 0.28 ± 0.21 μmol/L, and 282 ± 127 ng/mL, respectively. Mean retinoid Cps did not change after 3 months of 4-HPR + TAM. CONCLUSIONS: TAM administration did not affect Cp 4-HPR or 4-MPR. Reversible nyctalopia correlated with relative decrease in Cp retinol but was not symptomatic for most patients. TAM + 4-HPR has acceptable tolerability for this high-risk cohort.