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As in many cancers, genetic analysis of thyroid cancers has identified subgroups that differ in their pathogenesis and has defined targets that make the cancer susceptible to particular therapies. Recent progress leading to new treatments is reviewed. Advances in the understanding of the genetic and biologic characteristics of thyroid cancer, coupled with the development of new molecular targeted therapeutics, have led to the improved diagnosis and treatment of patients with this cancer. In this review, we focus on the effect of these discoveries on all types of thyroid cancer and particularly on how they are transforming clinical care. Spectrum of Thyroid Cancers The transformation of endodermal-derived thyroid follicular cells or neural crest–derived thyroid C cells leads to distinct types of cancer (Figure 1). Follicular cells give rise to two main forms of differentiated thyroid cancer: papillary thyroid . . .

Background Jeffrey A. Norton could have been a professional football player but instead he chose to pursue a career in medicine and in the process became an outstanding academic surgeon. This story recounts his ascent from a small town in Massachusetts to the pinnacle of academic surgery. Methods After graduating from high school in Albany, New York, Jeff continued his education at Dartmouth University, the State University of New York Upstate Medical University at Syracuse (SUNY Upstate Medical University), and the Department of Surgery at the Duke University School of Medicine. When he completed the surgical residency, he spent 10 years at the National Cancer Institute (NCI) where he and his colleagues made significant contributions to the diagnosis and treatment of patients with endocrine tumors. After leaving the NCI, he had highly productive years as a Professor in Departments of Surgery at Washington University, the University of California at San Francisco, and Stanford University. He became a member of every major academic surgical society and won numerous awards for his accomplishments in research. His expertise in educating medical students and surgical residents is legendary. Results In addition to his academic accomplishments, Jeff trained legions of young surgeons who subsequently made significant contributions in surgical investigation and clinical surgery. Conclusion It is most fitting that the Stanford University School of Medicine has assembled a group of Jeffrey Norton’s colleagues in academic medicine and surgery to pay tribute to his achievements as a surgical scientist.

Medullary thyroid carcinoma is so common among patients with multiple endocrine neoplasia and familial medullary thyroid carcinoma that prophylactic thyroidectomy is often performed. This study involved 50 patients who had undergone prophylactic thyroidectomy after identification of the RET mutation that is characteristically associated with this lesion. Five to 10 years later, 88 percent had no evidence of persistent or recurrent medullary thyroid carcinoma. This study involved 50 patients who had undergone prophylactic thyroidectomy. Five to 10 years later, 88 percent had no evidence of persistent or recurrent medullary thyroid carcinoma. Medullary thyroid carcinoma, a cancer of the parafollicular (C) cells, develops in virtually all patients with multiple endocrine neoplasia (MEN) type 2A (MEN-2A) or type 2B (MEN-2B) and in those with familial medullary thyroid carcinoma. 1 – 3 Medullary thyroid carcinoma is the most common cause of death in patients with these endocrinopathies, and total thyroidectomy that is performed before medullary thyroid carcinoma develops or spreads beyond the gland is currently the only curative treatment. Over time, patients with MEN-2A, MEN-2B, or familial medullary thyroid carcinoma develop a spectrum of C-cell disorders, beginning with C-cell hyperplasia and progressing to intrathyroidal medullary thyroid . . .

Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post‐vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP‐IPV‐Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post‐vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G‐CSF, IL‐1RA and IL‐6. Post‐vaccination fever was associated with increased expression of SELL , involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin‐3, ‐5 and GM‐CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine. SYNOPSIS A randomised clinical trial evaluates transcriptomic and proteomic profiles following infant concomitant 4CMenB vaccination, compared with control vaccines alone. A novel framework is provided for both understanding and predicting vaccine immunogenicity and reactogenicity. 4CMenB vaccination is associated with a distinct gene expression and plasma protein signature. Post‐vaccination fever is associated with increased expression of SELL, involved in neutrophil recruitment. Transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine are presented. Graphical Abstract A randomised clinical trial evaluates transcriptomic and proteomic profiles following infant concomitant 4CMenB vaccination, compared with control vaccines alone. A novel framework is provided for both understanding and predicting vaccine immunogenicity and reactogenicity.

Welsh's milkweed (Asclepias welshii) is an endemic species in the dogbane family (Apocynaceae) with primary distribution in Coral Pink Sand Dunes State Park in Kane County, Utah, and with a few small populations in adjacent areas of Utah and Arizona. The insects known to occur on Welsh's milkweed include the monarch butterfly (Danaus plexippus), a milkweed beetle (Tetraopes annulatus), the western small milkweed bug (Lygaeus kalmii kalmii), the oleander aphid (Aphis nerii), and a few bee species. The obligate association of milkweeds with the monarch butterfly implies that Welsh's milkweed may be an important resource for the group of Mexican overwintering monarch butterflies that migrate northwest in the spring and possibly interbreed with monarchs overwintering along the Pacific coast. The endemic Coral Pink Sand Dunes tiger beetle (Cicindela albissima) is also a narrowly endemic species that occurs in the same dune system as Welsh's milkweed.

A Nazareth Manifesto is an eloquent and impassioned ecumenical proposal for re-envisioning Christianity's approach to social engagement away from working \"for\" the people to being \"with\" them. * Questions the effectiveness of the current trend of intervention as a means of fixing the problems of people in distressed and disadvantaged circumstances * Argues that Jesus spent 90% of his life simply being among the people of Nazareth, sharing their hopes and struggles, therefore Christians should place a similar emphasis on being alongside people in need rather than hastening to impose solutions * Written by a respected priest and broadcaster and renowned Christian ethicist and preacher * Supported by historical, contemporary, exegetical and anecdotal illustrations

Children face specific risks from antimicrobial resistance, yet UK policy has failed to recognise them as a distinct group, say Samuel Channon-Wells and Sanjay Patel

Background Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression. Methods We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment. We included a novel 3-transcript signature for childhood tuberculosis, and four published signatures which differentiate bacterial infection, viral infection, or Kawasaki disease from other febrile illnesses. Signature performance was assessed using receiver operating characteristic curve statistics. We also explored conceptual frameworks for multiclass diagnostic signatures, including additional transcripts found to be significantly differentially expressed in previous studies. Relaxed, regularised logistic regression models were used to derive two novel multiclass signatures: a mixed One-vs-All model (MOVA), running multiple binomial models in parallel, and a full-multiclass model. In-sample performance of these models was compared using radar-plots and confusion matrix statistics. Results Samples from 91 children were included in the study: 23 bacterial infections (DB), 20 viral infections (DV), 14 Kawasaki disease (KD), 18 tuberculosis disease (TB), and 16 healthy controls. The five signatures tested demonstrated cross-platform performance similar to their primary discovery-validation cohorts. The signatures could differentiate: KD from other diseases with area under ROC curve (AUC) of 0.897 [95% confidence interval: 0.822–0.972]; DB from DV with AUC of 0.825 [0.691–0.959] (signature-1) and 0.867 [0.753–0.982] (signature-2); TB from other diseases with AUC of 0.882 [0.787–0.977] (novel signature); TB from healthy children with AUC of 0.910 [0.808–1.000]. Application of signatures outside of their designed context reduced performance. In-sample error rates for the multiclass models were 13.3% for the MOVA model and 0.0% for the full-multiclass model. The MOVA model misclassified DB cases most frequently (18.7%) and TB cases least (2.7%). Conclusions Our study demonstrates the feasibility of NanoString technology for cross-platform validation of multiple transcriptomic signatures in parallel. This external cohort validated performance of all five signatures, including a novel sparse TB signature. Two exploratory multi-class models showed high potential accuracy across four distinct diagnostic groups.

Depression is an umbrella term used to describe a mood disorder with a broad spectrum of symptoms including a persistent feeling of sadness, loss of interest, and deficits in social behavior. Epigenetic research bridges the environmental and genetic landscape and has the potential to exponentially improve our understanding of such a complex disorder. Depression is also a sexually dimorphic disorder and variations exist within epigenetic modification sites between sexes. These sex-specific mediators may impact behavioral symptomology and could serve as therapeutic targets for treatments to improve behavioral deficits. This mini review will focus on the social behavior perspective of depression and specifically explore the sexually different epigenetic modifications on depression.

Featuring updates, revisions, and new essays from various scholars within the Christian tradition, The Blackwell Companion to Christian Ethics, Second Edition reveals how Christian worship is the force that shapes the moral life of Christians. * Features new essays on class, race, disability, gender, peace, and the virtues * Includes a number of revised essays and a range of new authors * The innovative and influential approach organizes ethical themes around the shape of Christian worship * The original edition is the most successful to-date in the Companions to Religion series