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The article focuses on writers of American fiction. Some writers of fiction, such as Charles Dickens and William Dean Howells, begun to publish early in their twenties. Washington Irving had shown his genius in "Salmagundi." "Voices of the Night" was published by Henry Wadsworth Longfellow when he was thirty-two.

The article pays tribute to U.S. statesmen Samuel Adams and Alexander Hamilton. Adams was the father of the grand moment which uttered its convictions in the Declaration of Independence. He created a public sentiment in favor of independence. Meanwhile, Hamilton had nothing to recommend him but talent, integrity and manliness. He was of the opinion that no man exceeded him in probity and sterling virtue.

The article discusses the significance of speed in doing any literary works. It stresses that writers as well as authors should develop this skill to succeed in their profession. It mentions poet James Russell Lowell and author J. G. Holland for being fast writers who created great works in literature. Furthermore, it acknowledges writers who produce not just great quantity but good quality of literary works as well.

Presents the poem "On Laying Aside a Text-Book I Loved," by C. M. Barrows. First Line: Farewell, friend of happy years! Last Line: Thou hast done thy best for me.

Emphasizes the importance for teachers to teach their students how to read fast. Consequence of giving students the impression that reading fast is a fault; Overview of the practical use of reading fast; Benefits of learning to read fast.

Background: Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is often not specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants., Methods: Using dedicated pipelines to address the technical challenges posed by the mtDNA - circular genome, variant heteroplasmy, and nuclear misalignment - single nucleotide variants, small indels, and large mtDNA deletions were called from exome and genome sequencing data, in addition to RNA-sequencing when available. A cohort of 6,660 rare disease families were analyzed (5,625 genetically undiagnosed, 84%) from the Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) Consortium as well as other rare disease cohorts., Results: Diagnostic mtDNA variants were identified in 10 previously genetically undiagnosed families (one large deletion, eight reported pathogenic variants, one novel pathogenic variant). In one additional undiagnosed proband, the detection of >900 heteroplasmic variants provided functional evidence of pathogenicity to a novel de novo variant in the nuclear gene POLG (DNA polymerase gamma), responsible for mtDNA replication and repair., Conclusion: mtDNA variant calling from data generated by exome and genome sequencing for nuclear variant analysis resulted in a genetic diagnosis or detection of a candidate variant for 0.4% of undiagnosed families affected by a broad range of rare diseases., Competing Interests: A.O’D-L was a paid consultant to Tome Biosciences, Ono Pharma USA, Addition Therapeutics, Congenica, receives research funding from Pacific Biosciences, and is on the American Journal of Human Genetics Editorial Board (unpaid). H.L.R has received rare-disease research funding from Microsoft. V.G.S. serves as an advisor to Ensoma. All other authors declare no competing interests.

Although a rare medical condition, gastric ischemia is a medical emergency and requires prompt recognition. Current literature review is scarce, with a primary focus on iatrogenic, surgical, and vascular etiologies. The cases discussed focus on hypoperfusion secondary to refractory shock as the etiology of gastric ischemia and, unfortunately, death. Our cases add to the current literature by highlighting an alternative, less common etiology, thus broadening a clinician's suspicion of gastric ischemia complications in critically ill patients., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Verma et al.)

Context: Children are a uniquely vulnerable patient population with restricted abilities for self-advocacy and autonomy, risking infringement upon their dignity. Yet the concept of dignity in pediatrics remains underexplored relative to the adult literature and other outcome measures., Objectives: To characterize how dignity is defined, evaluated, and/or measured in pediatrics., Methods: We conducted a systematic review following PRISMA guidelines across the following databases: MEDLINE, Embase, Cumulative Index of Nursing and Allied Health, PsycINFO, Global Health, Social Science Premium Collection, and Dissertation and Theses. We included publications from database inception through April 2023, in English, involving children aged 0-18 years, and prioritizing dignity as a central theme with a focus on defining, evaluating, or measuring dignity. Study descriptions and pertinent characteristics were extracted and synthesized using a predefined form., Results: Forty-four articles met inclusion criteria; fewer than half comprised original research (20/44, 45%). Most studies (38/44, 86%) included description of the meaning of dignity, with emergence of salient themes around respect, communication, agency/autonomy, and privacy. Less than half (19/44, 43%) included a measurement or evaluation of dignity; approximately one-third described dignity therapy. More than one-third of publications focused on dignity at end of life (17/44, 39%) and included discussions of palliative medicine and hospice (15/44, 34%)., Conclusion: Relatively few published studies describe dignity in pediatrics. Opportunities exist to broaden scholarship on this topic in partnership with patients, families, and clinicians, with the goal of assessing and strengthening dignity-centered care across the illness course and at the end of life., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Cardiac arrest in pregnancy is a rare but serious complication, occurring at a rate of 1 in every 9,000 patients hospitalized for delivery. This review article provides a comprehensive overview of maternal cardiac arrest for critical care transport providers. This article discusses the pertinent physiologic changes in pregnancy, common contributing factors, and special circumstances that can develop during a maternal cardiac arrest. We also provide current approaches to managing this population and special considerations for transport providers., Competing Interests: Declaration of Competing Interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2024 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia.

Objective: To understand shift-level determinants of emergency physician (EP) burnout, relationships were tested between EP shift demands, stress, and fatigue., Method: EP ( n = 16) were assessed over 114 shifts that occurred before and during the COVID-19 pandemic. Salivary cortisol (an indicator of stress) and self-reported fatigue were collected prior to and following each shift. An objective crowding score (National Emergency Department Overcrowding Scale) per shift was calculated. Shift demands were assessed at the end of each shift., Results: Multilevel models revealed that shift demands, National Emergency Department Overcrowding Scale, and the pandemic were related to higher levels of end-of-shift cortisol, but not fatigue. Cortisol levels were higher for shifts with a higher number of demands, greater crowding, and during the pandemic., Conclusions: Shift demands predicted objective indicators of stress, but not self-reported fatigue. Interventions are needed to decrease stress and shift demands to reduce EP burnout., Competing Interests: Conflicts of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl , one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

Debate remains around the anatomical origins of specific brain cell subtypes and lineage relationships within the human forebrain 1-7 . Thus, direct observation in the mature human brain is critical for a complete understanding of its structural organization and cellular origins. Here we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific mosaic variant barcode analysis. From four hemispheres and two different human neurotypical donors, we identified 287 and 780 mosaic variants, respectively, that were used to deconvolve clonal dynamics. Clonal spread and allele fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted than resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome transcriptome analysis at both a cell-type-specific and a single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1 + inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of mosaic variants across 17 locations within one parietal lobe reveals that restriction of clonal spread in the anterior-posterior axis precedes restriction in the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus, cell-type-resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal neurologic activity. We report six individuals from three unrelated families harboring biallelic deleterious variants in CAPN15 with phenotypes overlapping those previously described for this disorder. Of the individuals affected, four demonstrate radiographic evidence of the classical triad of Dandy-Walker malformation including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation. Cerebellar anomalies have not been previously reported in association with CAPN15-related disease. Here, we present three unrelated families with findings consistent with oculogastrointestinal neurodevelopmental syndrome and cerebellar pathology including Dandy-Walker malformation. To corroborate these novel clinical findings, we present supporting data from the mouse model suggesting an important role for this protein in normal cerebellar development. Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy-Walker malformation with biallelic CAPN15 variants, thereby expanding the neurologic spectrum among patients affected by CAPN15-related disease., (© 2023 Wiley Periodicals LLC.)

Debate remains around anatomic origins of specific brain cell subtypes and lineage relationships within the human forebrain. Thus, direct observation in the mature human brain is critical for a complete understanding of the structural organization and cellular origins. Here, we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific Mosaic Variant Barcode Analysis. From four hemispheres from two different human neurotypical donors, we identified 287 and 780 mosaic variants (MVs), respectively that were used to deconvolve clonal dynamics. Clonal spread and allelic fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted compared with resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome-transcriptome analysis at both a cell-type-specific and single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1 + inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of MVs across 17 locations within one parietal lobe reveals restrictions of clonal spread in the anterior-posterior axis precedes that of the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus cell-type resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain., Competing Interests: Competing interests K.K. is a senior scientist at Bioskryb Genomics Inc. All other authors declare no competing interests.

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass transmembrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG and intellectual disability. Tmem161b knockout mice fail to develop midline hemispheric cleavage, whereas knock-in of patient mutations and patient-derived brain organoids show defects in apical cell polarity and radial glial scaffolding. We found that TMEM161B modulates actin filopodia, functioning upstream of the Rho-GTPase CDC42. Our data link TMEM161B with human PMG, likely regulating radial glia apical polarity during neocortical development.

Current treatments for xerostomia/dry mouth are palliative and largely ineffective. A permanent clinical resolution is being developed to correct hyposalivation using implanted hydrogel-encapsulated salivary human stem/progenitor cells (hS/PCs) to restore functional salivary components and increase salivary flow. Pluripotent epithelial cell populations derived from hS/PCs, representing a basal stem cell population in tissue, can differentiate along either secretory acinar or fluid-transporting ductal lineages. To develop tissue-engineered salivary gland replacement tissues, it is critical to reliably identify cells in tissue and as they enter these alternative lineages. The secreted protein α-amylase, the transcription factor MIST1, and aquaporin-5 are typical markers for acinar cells, and K19 is the classical ductal marker in salivary tissue. We found that early ductal progenitors derived from hS/PCs do not express K19, and thus earlier markers were needed to distinguish these cells from acinar progenitors. Salivary ductal cells express distinct polarity complex proteins that we hypothesized could serve as lineage biomarkers to distinguish ductal cells from acinar cells in differentiating hS/PC populations. Based on our studies of primary salivary tissue, both parotid and submandibular glands, and differentiating hS/PCs, we conclude that the apical marker MUC1 along with the polarity markers INADL/PATJ and SCRIB reliably can identify ductal cells in salivary glands and in ductal progenitor populations of hS/PCs being used for salivary tissue engineering. Other markers of epithelial maturation, including E-cadherin, ZO-1, and partition complex component PAR3, are present in both ductal and acinar cells, where they can serve as general markers of differentiation but not lineage markers.

Background: Limited English proficiency has been shown to negatively affect health outcomes. However, as of now, little is known about survival rates of patients with limited English proficiency (LEP) and pancreatic ductal adenocarcinoma (PDAC) when compared to patients with English proficiency (EP) in an urban, non-safety net setting. We aimed to compare survival rates between patients with LEP and those with EP who had a diagnosis of PDAC., Methods: A single-institution retrospective propensity-matched cohort study of patients with biopsy-proven PDAC was undertaken. Demographics, clinical characteristics, and language information were collected for all participants. Patients were classified as having LEP or EP based on their preferred speaking language at the time of admission and matched on baseline characteristics using propensity scores. Survival analysis methods were used to study survival rates in patients with PDAC based on their EP status., Results: Of 739 included patients, 71 (9.48%) had LEP, mean age was 68.4 ± 10.9, and 51.8% were female. Both groups of patients were comparable for age, gender, marital status, and time to treatment. LEP status was associated with higher odds of death in both unmatched (HR 1.65, 95% CI 1.22-2.22) and matched (HR 1.60, 95% CI 1.03-2.47) analyses. Additionally, patients with LEP had significantly decreased odds of receiving cancer-directed treatment and increased odds of advanced stage cancer at presentation., Conclusions: In this cohort of patients with PDAC, LEP predicted worse survival. The results of this study suggest that, after accounting for interpreter use, other factors contribute to this disparity. Such factors, as yet unmeasured, may include health literacy and cultural expectations, for which further investigation is warranted to better understand and limit this survival disparity., (© 2021. The Society for Surgery of the Alimentary Tract.)

In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients' prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo . The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases - two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer., Competing Interests: A patent (application number:13/320,635, compositions for the treatment of metastatic cancer and methods of use thereof) was filed by BZ, IC, and CB, and was published on Mar 15th, 2012 (publication number: 20120064008) based on data shown in this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chung, Zhou, Barrows, Banyard, Wilson, Rummel, Mizokami, Basu, Sengupta, Shaikh, Sengupta, Bielenberg and Zetter.)

Abstract: This article in MRS Bulletin and the framework set out in the introductory article articulate a scenario of renewable electrons and electrification of end use appliances and industrial processes as a plausible paradigm to realize a carbon-free energy economy. The subsequent articles cover specific sectoral or chemical applications of those renewable electrons (e.g., for hydrogen, transportation, building use, electrochemical storage, and within the chemical industry). This article addresses the intersections among and across those sectors. We describe the importance of considering integrated systems and systems of systems as we consider pathways to a decarbonized energy economy. Further, we review and summarize key insights into the innovation challenges that reside at the particular integration interfaces among sectors, and highlight the opportunity for advances in materials and processes that will be critical to successful achievement of economy-wide, low-carbon energy systems., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive License to the Materials Research Society 2022.)

Introduction: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC., Materials and Methods: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score., Results: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival., Conclusion: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com., Competing Interests: Declaration of competing interest The authors of the abovementioned manuscript have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Multiple efforts have sought to improve teaching effectiveness and the learning environment (LE), but prior research has not focused on attending physicians' perceptions of mistreatment or contribution to the LE. The purpose of this study was to assess the perception and role of surgical faculty in the medical student LE., Design: A semistructured interview guide was developed using a comprehensive approach including extensive literature search and focus groups. Data were audio-recorded and transcribed verbatim. Content analysis was used to identify emergent themes., Setting: Beth Israel Deaconess Medical Center, an academic tertiary care facility located in Boston, Massachusetts., Participants: Fifteen faculty in the Department of Surgery underwent detailed interviews. Participants were selected using purposive-stratified criterion-based sampling., Results: Multiple themes emerged: (1) The competing demands on medical student's time are a negative factor in the LE; (2) Faculty expectations conflict with the existing curriculum; (3) Faculty are concerned with the possibility of being reported for providing negative feedback; (4) Faculty remain unfamiliar with policies regarding the LE/mistreatment; (5) A motivated medical student makes the educational interaction more productive independent of specialty of choice., Conclusions: Faculty identified that the most important factors contributing to a negative LE were a mismatch between expectations of medical students and faculty, and the conflict between the current curriculum and the faculty member's perceived ideal educational framework. Importantly, faculties were largely unfamiliar with LE/mistreatment policies and standards. These findings suggest a need for targeted curricula for faculty to raise awareness of components of a positive LE and tools to teach effectively within the contemporary medical school curriculum., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague-Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (&lt;1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.

Current healthcare economic evaluations are based only on the perspective of a single stakeholder to the healthcare delivery process. A true value-based decision incorporates all of the outcomes that could be impacted by a single episode of surgical care. We define the value proposition for robotic surgery using a stakeholder model incorporating the interests of all groups participating in the provision of healthcare services: patients, surgeons, hospitals and payers. One of the developing and expanding fields that could benefit the most from a complete value-based analysis is robotic hepatopancreaticobiliary (HPB) surgery. While initial robot purchasing costs are high, the benefits over laparoscopic surgery are considerable. Performing a literature search we found a total of 18 economic evaluations for robotic HPB surgery. We found a lack of evaluations that were carried out from a perspective that incorporates all of the impacts of a single episode of surgical care and that included a comprehensive hospital cost assessment. For distal pancreatectomies, the two most thorough examinations came to conflicting results regarding total cost savings compared to laparoscopic approaches. The most thorough pancreaticoduodenectomy evaluation found non-significant savings for total hospital costs. Robotic hepatectomies showed no cost savings over laparoscopic and only modest savings over open techniques. Lastly, robotic cholecystectomies were found to be more expensive than the gold-standard laparoscopic approach. Existing cost accounting data associated with robotic HPB surgery is incomplete and unlikely to reflect the state of this field in the future. Current data combines the learning curves for new surgical procedures being undertaken by HPB surgeons with costs derived from a market dominated by a single supplier of robotic instruments. As a result, the value proposition for stakeholders in this process cannot be defined. In order to solve this problem, future studies must incorporate (I) quality of life, survival, and return to independent function alongside data such as (II) intent-to-treat analysis of minimally-invasive surgery accounting for conversions to open, (III) surgeon and institution experience and operative time as surrogates for the learning curve; and (IV) amortization and maintenance costs as well as direct costs of disposables and instruments., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

We recently identified an additional isoform of human thymosin beta 15 (also known as NB-thymosin beta, gene name TMSB15A) transcribed from an independent gene, and designated TMSB15B. The purpose of this study was to investigate whether these isoforms were differentially expressed and functional. Our data show that the TMSB15A and TMSB15B isoforms have distinct expression patterns in different tumor cell lines and tissues. TMSB15A was expressed at higher levels in HCT116, DU145, LNCaP, and LNCaP-LN3 cancer cells. In MCF-7, SKOV-3, HT1080, and PC-3MLN4 cells, TMSB15A and TMSB15B showed approximately equivalent levels of expression, while TMSB15B was the predominant isoform expressed in PC-3, MDA-MB-231, NCI-H322, and Caco-2 cancer cells. In normal human prostate and prostate cancer tissues, TMSB15A was the predominant isoform expressed. In contrast, normal colon and colon cancer tissue expressed predominantly TMSB15B. The two gene isoforms are also subject to different transcriptional regulation. Treatment of MCF-7 breast cancer cells with transforming growth factor beta 1 repressed TMSB15A expression but had no effect on TMSB15B. siRNA specific to the TMSB15B isoform suppressed cell migration of prostate cancer cells to epidermal growth factor, suggesting a functional role for this second isoform. In summary, our data reveal different expression patterns and regulation of a new thymosin beta 15 gene paralog. This may have important consequences in both tumor and neuronal cell motility.

Histone posttranslational modifications that accompany DNA replication, nucleosome assembly, and H2A/H2B exchange were examined in human tissue culture cells. Through microsequencing analysis and chromatin immunoprecipitation, it was found that a subset of newly synthesized H3.2/H3.3 is modified by acetylation and methylation at sites that correlate with transcriptional competence. Immunoprecipitation experiments suggest that cytosolic predeposition complexes purified from cells expressing FLAG-H4 contain H3/H4 dimers, not tetramers. Studies of the deposition of newly synthesized H2A/H2B onto replicating and nonreplicating chromatin demonstrated that H2A/H2B exchange takes place in chromatin regions that contain acetylated H4; however, there is no single pattern of H4 acetylation that accompanies exchange. H2A/H2B exchange is also largely independent of the deposition of replacement histone variant, H3.3. Finally, immunoprecipitation of nucleosomes replicated in the absence of de novo nucleosome assembly showed that histone modifications do not prevent the transfer of parental histones to newly replicated DNA and thus have the potential to serve as means of epigenetic inheritance. Our experiments provide an in-depth analysis of the "histone code" associated with chromatin replication and dynamic histone exchange in human cells.

Adult females of Leptoconops (Brachyconops) californiensis Wirth & Atchley and 1 female of Leptoconops (Holoconops) sp. near knowltoni were collected from 5 species of lizards in desert sand dune habitats in San Bernardino and Riverside counties, California, and northern Sonora, Mexico. Feeding by L. californiensis was observed on the dorsum (usually the heads) of the lizards, with up to 6 L. californiensis on a host at 1 time. The L. sp. near knowltoni appeared to be trying to feed but did not contain blood. Midges fed during calm, warm daylight periods from March through October. Reptile feeding by Ceratopogonidae is reviewed.

To test the hypothesis that reduced protein synthesis may increase life span by retarding genetic informational transfer during early life and reducing the use of the genetic code and thereby minimizing genetic imperfections as they may occur during late life, two approaches were used. In the first protein synthesis was depressed by the administration of cycloheximide, in the second by reducing the dietary protein level. One-day-old chick embryos were injected with either 0.8 gamma or 1.0 gamma of cycloheximide. On the second and third day of incubation both stage of development and heart rate were lower in the treated embryos. Growth was retarded throughout the 17 days of incubation as measured by size and DNA contents. As estimated by the activities of various enzymes per unit DNA, cells of the treated embryos were the same as normal ones of the same age. Sixteen-month-old female Wistar rats which had been previously maintained on a commercial diet (23.4% protein) were fed diets which contained either 24, 12, 8 or 4% casein throughout their remaining life span. Except for a lowering of the body weights of the animals fed the 4% casein diet, the body weights of the remaining animals were unchanged. Reducing the dietary protein level from 24% to 12% increased the life span (25%) of the animals.

The intestinal absorption of doses of vitamin B12 and of niacin was examined in 6, 12, and 24 months old female Wistar rats. Rats were dosed via stomach tube with radioactive forms of the vitamins and were killed 16 hours later. Percent of the dose remaining in the stomach and gastrointestinal tract and in the collected feces was determined. Absorption of the two vitamins was not influenced by the age of the animals.

Twenty-one day old and seventeen month old female mice were fed the following three dietary regimes for one or six months: 1) 24% protein ad libitum; 2) 4% protein ad libitum; or 3) 24% protein intermittently fed (diet offered for twenty-four hours on Monday and Wednesday, and for eight hours on Friday). The activities of succinoxidase, malic dehydrogenase and cholinesterase as well as the concentrations of protein and DNA were determined in livers and kidneys. Calculated on the basis of DNA, the activities of these three enzymes as well as protein content were decreased in the 4% and intermittent-fasted animals and increased in the intermittent-fed animals. The mean values of the enzymes as well as the protein content per mg. of DNA of the intermittent-fed and intermittent-fasted animals were essentially the same as that of the 24% ad libitum controls. These findings were obtained on both young-growing and adult animals. INDEX WORDS: Dietary restriction, enzymes, age, mouse, protein synthesis, genetic code use.

The absorption of vitamins A and D was examined in 6, 12, and 24 months old female Wistar rats. Animals were dosed by stomach tube with radioactive forms of vitamins A and D and killed 18 hours later. Isotope in feces collected during this time and isotope remaining in the gastrointestinal tract were determined and subtracted from total dose to determine percentage of absorption. Under the conditions of this study, age had no significant effect on the absorption of vitamins A and D.