Clinical and testing protocols for the analysis of epidermal growth factor receptor mutations in East Asian patients with non-small cell lung cancer:a combined clinical-molecular pathological approach

Several randomized phase III studies in advanced stage non-small cell lung cancer (NSCLC) confirmed the superior response rate and progression-free survival of using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor as first-line therapy compared with chemotherapy in patients with activating EGFR mutations. Despite the need for EGFR mutation tests to guide first-line therapy in East Asian NSCLC, there are no current standard clinical and testing protocols.

The anatomy of Last Glacial Maximum climate variations in south Westland, New Zealand, derived from pollen records

We present pollen records from three sites in south Westland, New Zealand, that document past vegetation and inferred climate change between approximately 30,000 and 15,000 cal. yr BP. Detailed radiocarbon dating of the enclosing sediments at one of those sites, Galway tarn, provides a more robust chronology for the structure and timing of climate-induced vegetation change than has previously been possible in this region. The Kawakawa/Oruanui tephra, a key isochronous marker, affords a precise stratigraphic link across all three pollen records, while other tie points are provided by key pollen-stratigraphic changes which appear to be synchronous across all three sites. Collectively, the records show three episodes in which grassland, interpreted as indicating mostly cold subalpine to alpine conditions, was prevalent in lowland south Westland, separated by phases dominated by subalpine shrubs and montane-lowland trees, indicating milder interstadial conditions. Dating, expressed as a Bayesian-estimated single 'best' age followed in parentheses by younger/older bounds of the 95% confidence modelled age range, indicates that a cold stadial episode, whose onset was marked by replacement of woodland by grassland, occurred between 28,730 (29,390-28,500) and 25,470 (26,090-25,270) cal. yr BP (years before AD, 1950), prior to the deposition of the Kawakawa/Oruanui tephra. Milder interstadial conditions prevailed between 25,470 (26,090-25,270) and 24,400 (24,840-24,120) cal. yr BP and between 22,630 (22,930-22,340) and 21,980 (22,210-21,580) cal. yr BP, separated by a return to cold stadial conditions between 24,400 and 22,630 cal. yr BP. A final episode of grass-dominated vegetation, indicating cold stadial conditions, occurred from 21,980 (22,210-21,580) to 18,490 (18,670-17,950) cal. yr BP. The decline in grass pollen, indicating progressive climate amelioration, was well advanced by 17,370 (17,730-17,110) cal. yr BP, indicating that the onset of the termination in south Westland occurred sometime between ca 18,490 and ca 17,370 cal. yr BP. A similar general pattern of stadials and interstadials is seen, to varying degrees of resolution but generally with lesser chronological control, in many other paleoclimate proxy records from the New Zealand region. This highly resolved chronology of vegetation changes from southwestern New Zealand contributes to the examination of past climate variations in the southwest Pacific region. The stadial and interstadial episodes defined by south Westland pollen records represent notable climate variability during the latter part of the Last Glaciation. Similar climatic patterns recorded farther afield, for example from Antarctica and the Southern Ocean, imply that climate variations during the latter part of the Last Glaciation and the transition to the Holocene interglacial were inter-regionally extensive in the Southern Hemisphere and thus important to understand in detail and to place into a global context. © 2013 Elsevier Ltd. All rights reserved.

Prostate stereotactic ablative body radiotherapy using a standard linear accelerator:toxicity, biochemical, and pathological outcomes

Biological dose escalation through stereotactic ablative radiotherapy (SABR) holds promise of improved patient convenience, system capacity and tumor control with decreased cost and side effects. The objectives are to report the toxicities, biochemical and pathologic outcomes of this prospective study.

Book review of Atlas of Anatomy by Patrick W. Tank and Thomas R. Gest:Book review of Atlas of Anatomy

Book review of Atlas of Anatomy by Patrick W. Tank and Thomas R. Gest

Picture Quiz: Know your anatomy.

A 25 year old man was brought into the emergency
department by ambulance. He was involved in a road
traffic incident and had an obvious site of blood loss from
a fracture of an upper limb. On his arrival at the
emergency department, you are told that the ambulance
paramedic was unable to gain intravenous access and
are asked by the person in charge of resuscitation to try
to gain access. You are unable to find any peripheral
veins because he is hypovolemic. You attempt to put in a
central line via the femoral vein (fig 1).

Anatomy and Neurophysiology of Coughing: CHEST Guideline and Expert Panel Report

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera as well as somatosensory nerves innervating the chest wall, diaphragm and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychological methods for treatment of dystussia, is high and modern imaging methods have revealed potential neural substrates for some features of cough in the human.

Cultivating creative learners in higher education: Engaging students in anatomy through art

Introduction
Nursing and midwifery students often struggle to engage with bioscience modules because they lack confidence in their ability to study science (Fell et al., 2012). Consequently many have difficulty applying anatomical and physiological information, essential to providing safe and effective patient care (Rogers, 2014; Rogers and Sterling, 2012); therefore a need exists for nurse educators to explore different methods of delivery of these important topics to enhance current curricula (Johnston, 2010). Inspired by the reported success of creative methods to enhance the teaching and learning of anatomy in medical education (Noel, 2013; Finn and McLachlan, 2010), this pilot study engaged nursing students in anatomy through the art of felt. The project was underpinned by the principles of good practice in undergraduate education, staff-student engagement, cooperation among students, active learning, prompt feedback, time on task, high expectations and respect for diverse learning styles (Chickering and Gamson, 1987).

Method
Undergraduate student nurses from Queen’s University, Belfast, enrolled in the year one ‘Health and Wellbeing’ model were invited to participate in the project. Over a six week period the student volunteers worked in partnership with teaching staff to construct individual, unique, three dimensional felt models of the upper body. Students researched the agreed topic for each week in terms of anatomical structure, location, tissue composition and vascular access. Creativity was encouraged in relation to the colour and texture of materials used. The evaluation of the project was based on the four level model detailed by Kirkpatrick and Kirkpatrick (2006) and included both quantitative and qualitative analysis:• pre and post knowledge scores• self-rated confidence• student reflections on the application of learning to practice.

Results
At the end of the project students had created felt pieces reflective of their learning throughout the project and ‘memorable’ three dimensional mental maps of the human anatomy. Evaluation revealed not only acquisition of anatomical knowledge, but the wider benefits of actively engaging in creative learning with other students and faculty teaching staff.

The project has enabled nurse educators to assess the impact of innovative methods for delivery of these important topics.

Evaluation of Video Presentation to Deliver Surgical Anatomy Teaching

Title Evaluation of Video Presentation to Deliver Surgical Anatomy Teaching

Authors Walsh I.K., Boohan M., Dorman A.

Objectives To evaluate the efficacy of newly introduced video presentation to deliver Surgical Anatomy teaching to undergraduate medical students.

Design and Setting Qualitative and quantitative study using questionnaires and focus groups, employing students undertaking the perioperative medicine module of the phase 4 undergraduate medical curriculum at Queen’s University Belfast.

Outcome Measures To determine:
(1) if video presentation is effective in delivering surgical anatomy teaching,
(2) student’s learning preferences regarding this teaching method.
Results The questionnaire response rate was 89% (216 of 244 students; female: male ratio 1.25) and 42 students participated in 6 focus groups. Mean questionnaire responses indicated a favourable opinion on quality assurance items, with a mixed response to video presentation as a learning method. 71% of students preferred to receive a lecture in person, rather than via video presentation. There were no statistically significant differences between genders regarding learning preferences in general and regarding video versus live presentation in particular. Exploratory factor analysis demonstrated that favourable responses to video presentation were strongly associated with perceived audiovisual quality and learning preferences (Cronbach’s alpha coefficient 0.77), with 72% of students considering video presentation worthwhile. Positive perception of overall quality was strongly associated with learning preferences as well as more generic quality assurance issues (80% students; alpha coefficient 0.83).
The results were supported by triangulation of the above quantitative data with qualitative data generated by the focus groups. Students further articulated the view that video presentation may be more appropriate and effective in a mixed method setting.

Reference Basu Roy R, McMahon GT. Video-based cases disrupt deep critical thinking in problem-based learning. Med Educ 2012 Apr;46(4):426-435.

Evaluation of Multidisciplinary Delivery of Surgical Anatomy Teaching

Title Evaluation of Multidisciplinary Delivery of Surgical Anatomy Teaching

Authors Walsh I.K., Taylor S.J., Dorman A, Boohan M.

Objectives To evaluate the efficacy of newly introduced multidisciplinary methods to deliver Surgical Anatomy teaching to undergraduate medical students.

Design and Setting Qualitative and quantitative study using questionnaires and focus groups, employing students of the perioperative and emergency medicine (POEM) module of the phase 4 undergraduate medical curriculum at Queen’s University Belfast.

Outcome Measures To determine:
(1) if multidisciplinary teaching is effective in delivering surgical anatomy teaching,
(2) student’s learning preferences regarding this teaching method.
Results The questionnaire response rate was 89% (216 of 244 students; female: male ratio 1.25) and 42 students participated in 6 focus groups. Mean questionnaire responses indicated a favourable opinion on quality assurance items and multidisciplinary teaching. 81% of students agreed that multidisciplinary teaching enhanced learning and 86% felt that this did not adversely affect interaction. A positive contribution towards POEM learning was reported for Radiology (95% of students), Anatomy (93%) and Surgery (78%). The benefits of multidisciplinary teaching were congruent for Anatomy, Radiology and Surgery with 78% of students indicating a perceived favourable association with learning. Multidisciplinary teaching was not associated with diluted interaction, with 62% of students describing interaction as sufficient. 88% of students positively ranked tutor characteristics of enthusiasm and encouragement as being strongly associated with teacher quality. Positive perception of overall quality was strongly associated with learning preferences as well as more generic quality assurance issues (80% students; alpha coefficient 0.83).
The results were supported by triangulation of the above quantitative data with qualitative data generated by the focus groups. Whilst students frequently misunderstood the meaning of “multidisciplinary teaching”, there was an appreciation of the method’s worth; students recognised and valued the relevance of Anatomy, Radiology and Surgery teaching to POEM learning. The importance of vertically integrating Anatomy into all stages of the undergraduate curriculum was especially recognised.

Reference Aarnio M, Nieminen J, Pyorala E, Lindbolm-Ylanne S. Motivating medical students to learn. 2010 Med Teach;32(4):199-204.

FKBPL Is a Critical Antiangiogenic Regulator of Developmental and Pathological Angiogenesis

OBJECTIVE: The antitumor effects of FK506-binding protein like (FKBPL) and its extracellular role in angiogenesis are well characterized; however, its role in physiological/developmental angiogenesis and the effect of FKBPL ablation has not been evaluated. This is important as effects of some angiogenic proteins are dosage dependent. Here we evaluate the regulation of FKBPL secretion under angiogenic stimuli, as well as the effect of FKBPL ablation in angiogenesis using mouse and zebrafish models.

APPROACH AND RESULTS: FKBPL is secreted maximally by human microvascular endothelial cells and fibroblasts, and this was specifically downregulated by proangiogenic hypoxic signals, but not by the angiogenic cytokines, VEGF or IL8. FKBPL's critical role in angiogenesis was supported by our inability to generate an Fkbpl knockout mouse, with embryonic lethality occurring before E8.5. However, whilst Fkbpl heterozygotic embryos showed some vasculature irregularities, the mice developed normally. In murine angiogenesis models, including the ex vivo aortic ring assay, in vivo sponge assay, and tumor growth assay, Fkbpl(+/-) mice exhibited increased sprouting, enhanced vessel recruitment, and faster tumor growth, respectively, supporting the antiangiogenic function of FKBPL. In zebrafish, knockdown of zFkbpl using morpholinos disrupted the vasculature, and the phenotype was rescued with hFKBPL. Interestingly, this vessel disruption was ineffective when zcd44 was knocked-down, supporting the dependency of zFkbpl on zCd44 in zebrafish.

CONCLUSIONS: FKBPL is an important regulator of angiogenesis, having an essential role in murine and zebrafish blood vessel development. Mouse models of angiogenesis demonstrated a proangiogenic phenotype in Fkbpl heterozygotes.