Spon1+ inflammatory monocytes promote collagen remodeling and lung cancer metastasis through lipoprotein receptor 8 signaling.

Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung cancer (NSCLC) is the most common subset. We previously found that infiltration of tumor inflammatory monocytes (TIMs) into lung squamous carcinoma (LUSC) tumors is associated with increased metastases and poor survival. To further understand how TIMs promote metastases, we compared RNA-Seq profiles of TIMs from several LUSC metastatic models with inflammatory monocytes (IMs) of non-tumor-bearing controls.

War and disaster are forcing a major rethink around mass casualty management.

Mass casualty events (MASCAL) do not follow the same rules as typical major incidents. In the West at least, the latter often occur in stable, networked trauma systems, whereas MASCAL are characterised by overwhelming numbers of patients, compounded by protracted scene and transport times, decompensated response systems and significant disruption to infrastructure, command and control.This paper describes the 8Ds approach being taken by the UK Defence Medical Services and the North Atlantic Treaty Organization Emergency Medicine Panel framework to approach MASCAL.

Contact lens-related complications in austere conditions among military personnel: a systematic review.

Introduction: Military service personnel are required to deploy to austere environments where they are exposed to harsh conditions. Many service personnel continue to wear contact lenses when deployed as they are an effective alternative to spectacles by affording superior ergonomic functionality, although they are associated with significant complications. We aimed to explore the prevalence and type of contact lens-related complications among deployed service personnel worldwide.

Comprehensive Viral Genotyping Reveals Prognostic Viral Phylogenetic Groups in HPV16-Associated Squamous Cell Carcinoma of the Oropharynx.

Unlabelled: Human papillomavirus-positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV-associated malignancy in the United States and is primarily caused by HPV subtype 16 (HPV16). Favorable treatment outcomes have led to increasing interest in treatment deescalation to reduce treatment-related morbidity. Prognostic biomarkers are needed to identify appropriately low-risk patients for reduced treatment intensity.

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036.

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes.

Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors.

Transcriptional silencing of HIV in CD4 T cells generates a reservoir of latently infected cells that can reseed infection after interruption of therapy. As such, these cells represent the principal barrier to curing HIV infection, but little is known about their characteristics. To further our understanding of the molecular mechanisms of latency, we characterized a primary cell model of HIV latency in which infected cells adopt heterogeneous transcriptional fates.

Temporal controls on crown nonstructural carbohydrates in southwestern US tree species.

In trees, large uncertainties remain in how nonstructural carbohydrates (NSCs) respond to variation in water availability in natural, intact ecosystems. Variation in NSC pools reflects temporal fluctuations in supply and demand, as well as physiological coordination across tree organs in ways that differ across species and NSC fractions (e.g.

Subcutaneous Lidocaine for Cancer-Related Pain.

Intravenous lidocaine infusions have been shown to be effective for cancer related pain, but access is restricted to acute care settings. If able to be shown to be safe and effective, the subcutaneous route could expand access to residential hospices or patients' homes. This randomized, double-blind, placebo controlled, 2 × 2 crossover trial evaluated the effectiveness, safety, toxicity, and impact on quality of life of a limited duration subcutaneous lidocaine infusion (SCLI) for chronic cancer pain.

Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer.

Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits.

The Prognostic Significance of Low-Frequency Somatic Mutations in Metastatic Cutaneous Melanoma.

Little is known about the prognostic significance of somatically mutated genes in metastatic melanoma (MM). We have employed a combined clinical and bioinformatics approach on tumor samples from cutaneous melanoma (SKCM) as part of The Cancer Genome Atlas project (TCGA) to identify mutated genes with potential clinical relevance. After limiting our DNA sequencing analysis to MM samples ( = 356) and to the CANCER CENSUS gene list, we filtered out mutations with low functional significance (snpEFF).

Use of supplemental oxygen in emergency patients: a systematic review and recommendations for military clinical practice.

Introduction: Supplemental oxygen is a key element of emergency treatment algorithms. However, in the operational environment, oxygen supply poses a challenge. The lack of high-quality evidence alongside emerging technologies provides the opportunity to challenge current guidelines.

Epidemiological study of emergency ambulance activation in the British Eastern Sovereign Base Area of Cyprus, September 2013 to August 2016.

Objectives: To record the activation and use of the Eastern Sovereign Base Area (ESBA) emergency ambulance service of British Forces Cyprus between 1 September 2013 and 31 August 2016. To reflect on these findings in light of data from 1995 to 1998 to identify current treads and areas of development.

Method: Retrospective epidemiological study of all activations of the ESBA emergency ambulance service within the study period.

Military Prehospital Emergency Care: defining and professionalising the levels of care provided along the Operational Patient Care Pathway.

The Defence Medical Services aims to provide gold standard care to ill and injured personnel in the deployed environment and its prehospital emergency care (PHEC) systems have been proven to save lives. The authors have set out to demonstrate, using existing literature, consensus and doctrine that the NHS Skills for Health framework can be reflected in military prehospital care and provides an existing model for defining the levels of care our providers can offer. In addition, we have demonstrated how these levels of care support the Operational Patient Care Pathway and add to the body of evidence for the use of specialist PHEC teams to allow the right patient to be transported on the right platform, with the right medical team, to the right place.

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes.

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist.

Methods: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.

General Duties Medical Officer Role 1 remote supervision in the era of Army Contingency Operations.

The return to contingency after Operation HERRICK (2002-2014 Afghanistan conflict) has seen an emerging trend for small-scale rapidly developing expeditionary operations. The associated small, remote medical footprint for such operations, often within a coalition construct, reliant on host nation support is in direct conflict with the General Medical Council (GMC) guidelines for junior doctor supervision in an 'approved practice setting'. If a General Duties Medical Officer (GDMO) is nominated to support future operations, the provision of assured patient care and supervision within GMC guidelines, while ensuring career progression and ongoing education, may prove a challenge.

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

Background: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis.

Patient Satisfaction: Receiving a copy of the GP letter following fracture or elective orthopaedic clinic.

Following orthopaedic/fracture clinics at our hospital, patients now receive a copy of the letter summarizing an outpatient consultation that is sent to their General Practitioner. We undertook a patient satisfaction questionnaire to determine if patients found this change in practice beneficial. Of the 83 patients who had received this letter, most patients had read the letter (96%) and understood the content (90%).

Baking a mass-spectrometry data PIE with McMC and simulated annealing: predicting protein post-translational modifications from integrated top-down and bottom-up data.

Motivation: Post-translational modifications are vital to the function of proteins, but are hard to study, especially since several modified isoforms of a protein may be present simultaneously. Mass spectrometers are a great tool for investigating modified proteins, but the data they provide is often incomplete, ambiguous and difficult to interpret. Combining data from multiple experimental techniques-especially bottom-up and top-down mass spectrometry-provides complementary information.

Automated data integration and determination of posttranslational modifications with the protein inference engine.

This chapter describes using the Protein Inference Engine (PIE) to integrate various types of data--especially top down and bottom up mass spectrometer (MS) data--to describe a protein's posttranslational modifications (PTMs). PTMs include cleavage events such as the n-terminal loss of methionine and residue modifications like phosphorylation. Modifications are key elements in many biological processes, but are difficult to study as no single, general method adequately characterizes a protein's PTMs; manually integrating data from several MS experiments is usually required.

Supervising junior doctors and "on-call" responsibilities: Brus v Australian Capital Territory; Greater Southern Area Health Service v Angus.

The recent decisions of Brus v Australian Capital Territory [2007] ACTSC 83 and Greater Southern Area Health Service v Angus [2007] NSWSC 1211 highlight different aspects of the difficulties associated with supervision of junior doctors in the present public-funded Australian public hospital system. Their facts reveal how difficult it is for senior staff to achieve the fine balance required to assist trainees by according adequate experience and responsibility on the one hand, and to ensure patient safety, on the other. In addition, these cases highlight problems with the supervision process that are likely to be exacerbated in a privatised health care setting where senior staff may have less inclination to supervise struggling juniors unless adequately remunerated for such teaching, an issue of considerable controversy given the focus on profit of those institutions.

Carney v Newton: expert evidence about the standard of clinical notes.

In Carney v Newton [2006] TASSC 4 the Tasmanian Supreme Court heard a claim that the defendant breached his duty of care by failing to properly diagnose and treat a node positive carcinoma in the plaintiff's breast tissue. At trial, argument turned on the actual dialogue that took place during the initial consultation, with significant reliance on the clinical notes of the defendant. The court gave considerable weight to "expert" witnesses in ascertaining the acceptability of the defendant's conduct concerning the maintenance and interpretation of his clinical notes.

Whistleblowing and scientific misconduct: renewing legal and virtue ethics foundations.

Whistleblowing in relation to scientific research misconduct, despite the benefits of increased transparency and accountability it often has brought to society and the discipline of science itself, remains generally regarded as a pariah activity by many of the most influential relevant organizations. The motivations of whistleblowers and those supporting them continued to be questioned and their actions criticised by colleagues and management, despite statutory protections for reasonable disclosures appropriately made in good faith and for the public interest. One reason for this paradoxical position, explored here, is that whistle blowing concerning scientific misconduct lacks the policy support customarily derived from firm bioethical and jurisprudential foundations.

The Carhart case and late-term abortions -- what's next in Australia?

A recent case in the United States Supreme Court has indicated a change in course on the issue of abortion rights. In Gonzales v Carhart 127 S Ct 1610 (2007), the Supreme Court, in April 2007, upheld federal legislation banning a particular late-term abortion procedure with no exceptions (even to preserve the mother's life). This column examines the case in the context of recent Australian cases involving abortion issues.